Throughout history, biopharmaceuticals have been essential in addressing health crises and enhancing human well-being. With advancements in genetic engineering, biotechnology, and bioinformatics, the development and approval rates of new biopharmaceuticals have surged, placing them at the forefront of the pharmaceutical field. Modern manufacturing processes and streamlined regulatory pathways have further expedited approval timelines, providing hope for previously untreatable conditions and significantly improving patients’ quality of life worldwide. However, despite these advancements, ambiguity persists regarding the definition of biopharmaceuticals due to the use of varied terms and a lack of standardized definitions. This article addresses this confusion by proposing a clear and comprehensive definition of biopharmaceuticals. Additionally, we present a reclassification of biopharmaceuticals into seven distinct verticals based on their functions. We assert that biopharmaceuticals not only offer superior therapeutic benefits for human health but also contribute to environmental sustainability, promoting a healthier planet. Thus, this article aims to clarify the scope of biopharmaceuticals and advocate for their broader adoption in the pursuit of global health and environmental integrity.

Sirtuins are a family of NAD⁺-dependent class III histone deacetylases that regulate histones and other proteins. The mammalian sirtuins comprise seven members that have a role in energy metabolism, DNA repair, inflammation, cell survival, apoptosis, cellular senescence, oxidative stress, and mitochondrial production. Sirtuin modulation may have beneficial effects on aging and age-related diseases; thus, attracting a growing interest in discovering small molecules modifying their activity. A class of compounds both natural and chemically synthesized has emerged as sirtuin activators. This review discusses mammalian sirtuins in aging, the small molecules that activate sirtuins, modulation of sirtuin activity, and its impact in alleviating the effects of aging.

Aim: To expand the understanding of the structure-activity relationship within a family of amino acid-derived β-lactam TRPM8 (transient receptor potential melastatin channel, subtype 8) antagonists, this work investigated both the configuration-dependence of potency and selectivity, and explored strategies for increasing total polar surface area (TPSA).

Methods: Diastereoisomeric compounds derived from H-Phe-O^tBu, and analogues incorporating differently substituted benzoyl groups, were synthesized by stereoselective solution pathways. Ca²⁺ microfluorometry assays were used for TRPM8 antagonist activity assessment, and then confirmed through electrophysiology (patch-clamp assay). The pharmacological activity in vivo was studied on a mice model of oxaliplatin-induced peripheral neuropathy.

Results: For O^tBu derivatives, a 3S,4S-configuration was preferred, while compounds with 2'R chiral centers show higher selectivity for TRPM8 versus transient receptor potential vanilloid, subtype 1 (TRPV1) than their 2'S-counterparts. N-terminal benzoyl derivatives, which increased TPSA values, resulted in equipotent compounds as previous prototypes, but also showed activity in other pain-related targets [TRPV1 and cannabinoid receptor, subtype 2 (CB₂R)]. A selectedN-benzoyl derivative displays antinociceptive activity in vivo.

Conclusions: The potency and selectivity of these β-lactam TRPM8 antagonists developed from amino acid derivatives depend not only on the configuration but also on the substituents at the 4-carboxy and at theN-benzoyl groups. Dual and multitarget compounds were discovered within this family of TRPM8 antagonists.

The integration between the tumor-suppressive and oncogenic signaling pathways controls various cellular activities of cancer cells, including cell growth and apoptosis. While the activation of oncogenes fuels cancer progression and escape mechanisms, tumor suppressors regulate and counterbalance the negative effects of oncogenic signaling. Notably, phosphatase and tensin homolog (PTEN) constitute one of the important family members of tumor suppressor genes, which play critical roles in regulating the activities of tumor cells. Thus, an impaired, mutated, or loss of PTEN is associated with low survival or high tumor recurrence rates in cancer patients. Importantly, high tumor expression of a G-protein coupled platelet-activating factor-receptor (PAFR) is associated with increased tumor progression as well as decreased overall survival and poor prognosis in malignancies such as non-small cell lung cancer (NSCLC). Along similar lines, overactivation or mutations in epidermal growth factor receptor (EGFR) signaling are detected in various human malignancies and associated with poor prognosis. The goal of the current minireview was to highlight the significance of the mechanistic insights between the PTEN and PAFR as well as the PAFR and EGFR pathways in impacting cancer growth and/or efficacy of therapeutic agents in experimental model systems.

Microbial biotransformations are valuable tools from “green chemistry” and involve converting parental molecules into new daughter ones with unique physical, chemical, or pharmacological properties. These reactions are often carried out by cells grown under a planktonic phenotype. However, microbial cells grown under a phenotype of biofilm can improve biotransformation bioprocesses once they form more biomass per volume, are more resistant to extreme conditions (pH, temperature, and toxic substances), remain active for extended periods, are less prone to cell washouts, and reduce re-inoculation demands, leading to increased production rates due to their unique physiological features. In addition, experience has shown that biofilms may furnish a broader array of new daughter molecules. This review highlighted the benefits of using biofilms in microbial biotransformations to obtain a variety of bioactives.

Lutein, a natural dihydroxy carotenoid and a member of the non-vitamin A carotenoids family, is abundant in yellow-colored fruits and green leafy vegetables such as spinach and lettuce. As the second most common type of carotenoid found in human serum, lutein offers a plethora of medicinal benefits, including anti-cancer, anti-inflammatory, and anti-oxidative properties. It is well-absorbed and systemically localized to the liver, lung, and retina, where it can cross the blood-retina barrier and accumulate in the macular pigment. Due to its anti-oxidative and singlet oxygen quenching properties, lutein is reported to reduce the risk of age-related macular degeneration (AMD). Higher concentrations of fasting plasma carotenoids and enhanced skin yellowing after lutein consumption indicate its presence in various regions of the human body, including the skin, breast, brain, and cervix. Lutein has remarkable benefits for neurodegenerative diseases, cardiovascular health, liver protection, and bone disease prevention. In the central nervous system (CNS), lutein supports brain homeostasis through its antioxidant and anti-inflammatory properties, increasing interleukin-10 (IL-10) and reducing tumor necrosis factor-α (TNF-α). It reduces the risk of coronary artery disease and exerts anti-inflammatory effects on peripheral blood mononuclear cells (PBMCs). Lutein protects against alcohol-induced liver damage by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Additionally, lutein promotes bone health by enhancing mineralized bone nodule development and inhibiting osteoclast production, reducing bone resorption, and suppressing soluble receptor activator of nuclear factor kappa B ligand (RANKL). These multifaceted benefits make lutein a valuable agent in disease prevention and health promotion. This review discusses the comprehensive profile of lutein as a phytochemical activity, including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neurological, and cardioprotective effects. Additionally, it discusses lutein’s beneficial impact on macular degeneration and eye diseases, showcasing its potential as a natural, plant-based therapeutic agent.

Aim: The aim of this study was to examine the effectiveness and safety of lysozyme-based spray in the treatment of oral mucositis in patients undergoing head and neck radiotherapy.

Methods: A prospective, open-label study was conducted on patients with ulcerative inflammation of the oral cavity and pharynx mucous membranes clinically assessed for oral mucositis according to the World Health Organization (WHO) Oral Toxicity Scale. Patients were randomly divided into a lysozyme group (using a spray containing lysozyme + cetylpyridinium + lidocaine) and a control group (using a compounded preparation containing gentamicin + dexamethasone + lidocaine). The efficacy and safety of therapy were evaluated on the baseline and three follow-up visits (7, 14, and 21 days after the baseline visit).

Results: The total number of participants was 56, of which 26 were in lysozyme and 30 in the control group. The efficacy parameters were similar between the groups and there was no deterioration of symptoms during the follow-up period of 21 days. A significantly lower pain intensity when eating solid food was observed after 21 days in lysozyme compared to the control group. No adverse reactions were observed.

Conclusions: This study showed the efficacy and safety of lysozyme-based spray for treating radiotherapy-induced oral mucositis. The availability of new treatment options based on lysozyme, a natural enzybiotic present in the saliva of healthy subjects, could bring added value to the treatment of oral mucositis and the prevention of its complications. However, a larger randomized, blinded study is needed to confirm our results [the study was registered at the Agency for Medicinal Products and Medical Devices of Bosnia and Herzegovina (https://klinicka.almbih.gov.ba/pages/klinicka-registar-javni) under the protocol number LCS-OM-01].

Antibiotic resistance is a significant threat to public health and drug development, driven largely by the overuse and misuse of antibiotics in medical and agricultural settings. As bacteria adapt to evade current drugs, managing bacterial infections has become increasingly challenging, leading to prolonged illnesses, higher healthcare costs, and increased mortality. This review explores the critical role of antibiotics in fighting infections and the mechanisms that enable bacteria to resist them. Key antibiotics discussed include carvacrol, dalbavancin, quinolones, fluoroquinolones, and zoliflodacin, each with unique actions against bacterial pathogens. Bacteria have evolved complex resistance strategies, such as enzyme production to neutralize drugs, modifying drug targets, and using efflux pumps to remove antibiotics, significantly reducing drug efficacy. Additionally, the review examines the challenges in antibiotic development, including a declining discovery rate of novel drugs due to high costs and regulatory complexities. Innovative approaches, such as structure-based drug design, combination therapies, and new delivery systems, are highlighted for their potential to create compounds with enhanced action against resistant strains. This review provides valuable insights for researchers and developers aiming to combat antibiotic resistance and advance the development of robust antibacterial therapies for future health security.

Over the last 60 years, only four new classes of antibiotics have been introduced, while the prevalence of antibiotic-resistant Gram-positive and Gram-negative bacteria has risen. This underscores the urgent need for new antibacterial therapeutics. This commentary leverages the recent exploration of γ-substituted-N-acylated-N-aminoethyl amino acid peptides (γ-AApeptides) to mimic the structures and function of natural antimicrobial peptides (AMPs), highlighting the promise and limitations for developing a new, effective treatment for antibiotic-resistant bacteria.

Aim: This research utilizes the ethanolic extract from seeds of Monodora myristica and its biosynthesized selenium nanoparticles (SeNPs) for the treatment of diabetic nephropathy (DN) in male Wistar rats.

Methods: Biosynthesis of crystalline, quasi-spherical shape 5.0 ± 0.25 nm SeNPs was achieved using M. myristica seed extract as a reducing agent, followed by surface plasmon resonance measurement by ultraviolet-visible (UV-Vis) spectrophotometer, Fourier transformed infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HR-TEM), and selected area electron diffraction (SAED) for confirmation of nanoparticle biosynthesis. Male Wistar rats were induced with diabetes using a 3-weeks high-fat diet and a single intraperitoneal injection of streptozotocin (STZ). Experimental groups included normal control group, untreated diabetic controls and those treated with either metformin (a standard drug), ethanolic extract or biosynthesized SeNPs ofM. myristica seed extract. Biochemical analyses assessed renal function via serum creatinine and urea levels. Histological evaluations of kidney tissues were performed to assess structural changes.

Results: Treatment with M. myristica seed extract and its biosynthesized SeNPs significantly improved renal function, evidenced by reduced serum creatinine and urea levels. Histopathological studies showed preserved renal architecture and reduced inflammatory damage, particularly in the combination therapy group, indicating a synergistic effect.

Conclusions: This study highlights the potential of M. myristica and its biosynthesized SeNPs in mitigating DN through nephroprotective mechanisms. These findings advocate for the exploration of nanotechnology combined with bioactive plant compounds as effective strategies for managing DN.

Ischemic stroke (IS) is a leading cause of death globally. IS occurs due to a blockage of cerebral arteries, leading to neuronal injury, tissue death, and brain infarcts. This induces lack of oxygenation to the brain which induces neuroinflammation, characterised by interactions involving molecules which can exacerbate brain damage but also aid recovery through processes like microglial phagocytosis. Post-stroke depression (PSD) affects 30–33% of stroke survivors, complicating recovery with various symptoms. The pathophysiology of PSD involves disruptions in the glutamatergic and monoaminergic systems, the gut-brain axis, and neuroinflammation. Agomelatine, an atypical antidepressant, can potentially treat both IS and PSD. It acts as a melatonin receptor agonist and a serotonin receptor antagonist, enhancing dopamine and norepinephrine availability in the prefrontal cortex. Agomelatine’s neuroprotective, anti-inflammatory, antioxidative, and antiapoptotic properties have been demonstrated in research, where it reduces reactive oxygen species (ROS) levels and activates the Nrf2 pathway, promoting antioxidative enzyme expression. Additionally, it prevents microglial activation by inhibiting the toll-like receptor 4 (TLR4)/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) pathway, thus reducing inflammation. This review examines the pathophysiology of IS and PSD, highlighting agomelatine’s multifaceted therapeutic potential. Agomelatine’s distinct pharmacological profile and minimal side effects make it a compelling candidate for IS and PSD treatment, necessitating further exploration to optimise stroke management and improve patient outcomes.

Aim: To identify peptides derived from bovine lactoferricin (LfcinB) as potential therapeutics for colon cancer treatment. We systematically modified dimeric peptides to enhance their selectivity against colon cancer cells and reduce toxicity. We examined the effects of specific changes, such as substituting L-arginine (Arg) with L-ornithine (Orn) and/or D-Arg, on cytotoxic activity in colon cancer cells, as well as activity in prostate and cervical cancer cell lines. Additionally, we assessed the type of cell death induced and the in vivo toxicity of the dimeric peptides.

Methods: The peptides were synthesized by manual solid-phase peptide synthesis, purified by reverse phase-solid phase extraction (RP-SPE), and characterized by RP-high performance liquid chromatography (RP-HPLC), and mass spectrometry (MS). Their cytotoxic effect on cancer and non-cancerous cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The most promising dimeric peptide underwent scale-up synthesis to yield approximately 1 g. The type of induced cell death was analyzed through cytometry assays, while preliminarily toxicity studies were conducted inGalleria mellonella, zebrafish, and CD1 mice.

Results: Our findings demonstrated that dimeric peptides containing L-Orn or D-Arg residues exhibited potent and selective cytotoxic effects against colon cancer cells (Caco-2 and HT-29), prostate cancer cells (DU-145), and cervical adenocarcinoma (HeLa). Notably, these modified peptides showed minimal toxicity in human erythrocytes, HEK 293 cells or fibroblasts, and Galleria mellonella larvae. Peptide 3: (R-Orn-WQWRFKKLG)₂-K-Ahx, emerged as particularly promising, preserving its integrity and anticancer activity during scaled-up synthesis. Furthermore, peptide 3 induced behavioral changes and sedation in CD1 mice and showed significantly lower toxicity in zebrafish.

Conclusions: The results suggested that specific modifications of Arg/Orn residues in dimeric peptides enhance their cytotoxicity against colon cancer cells and reduce in vivo toxicity. These modified peptides hold promise as safe and effective therapeutic candidates, potentially expanding the treatment options available for cancer.

Protein phosphorylation is a fundamental regulatory mechanism governing a broad spectrum of cellular processes. In the nervous system, it is critical for modulating neurotransmitter release, synaptic plasticity, neuronal excitability, and cell survival. Dysregulation of protein kinase activity is closely linked to the pathogenesis of various neurological and psychiatric disorders, positioning several kinases as promising therapeutic targets. Although protein kinase inhibitors (PKIs), a major class of compounds that modulate kinase activity, have shown considerable therapeutic success in oncology, their application in neurological diseases remains in the early stages of exploration. Of the 82 PKIs approved by the Food and Drug Administration (FDA), 37 are now in various preclinical and clinical trials for neurological conditions, primarily targeting signaling pathways mediated by key protein kinases implicated in these diseases. This review examines the roles of critical protein kinases and the therapeutic effects of their inhibitors in neurodegenerative, psychiatric, and selected neurological disorders, such as autism spectrum disorders (ASD) and epilepsy. We focus on Abelson kinase I (ABL1), calmodulin-dependent kinase II (CaMKII), casein kinase 1δ (CK1δ), c-Jun N-terminal kinase (JNK), cyclin-dependent kinase 5 (CDK5), dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A), leucine-rich repeat kinase 2 (LRRK2), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase, and protein kinase C (PKC) in neurodegenerative diseases. Additionally, we discuss CaMKII, CDK5, ERK1/2, PI3K/AKT/GSK3, protein kinase A (PKA), and PKC in psychiatric disorders, focusing on schizophrenia and mood disorders, and analyze GSK3β, ERK1/2, and mTOR in ASD and epilepsy. This review underscores the therapeutic potential of PKIs in neurological disorders while highlighting ongoing challenges and the need for further research to refine kinase-targeted therapies.

Bunium persicum Boiss. Fedtsch., a highly valued spice crop from the Apiaceae family, is renowned for its rich phytochemical profile, including compounds such as cuminaldehyde, α-terpinene-7-al, γ-terpinene-7-al, γ-terpinene, p-cymene, and β-pinene. These bioactive constituents contribute to its diverse therapeutic properties, including antioxidant, antimicrobial, anti-inflammatory, lipid and glucose-lowering, and anti-carcinogenic activities. Due to its limited growth in specific wild regions and over-exploitation,B. persicum faces significant conservation challenges, both in vitro and in situ. In India, its primary hotspots are in Jammu and Kashmir, Himachal Pradesh, and Uttarakhand. This review provides a comprehensive examination ofB. persicum’s functional properties, with a focus on its traditional uses, phytochemistry, and pharmacological activities, highlighting the need for its conservation and sustainable use.

Aim: The objective of this study was to develop a minimal physiologically based pharmacokinetic (mPBPK) model to predict area under the curve (AUC) and maximum plasma concentration (C_max) of drugs in subjects with varying degrees of hepatic impairment and compare this mPBPK model with the whole body PBPK model.

Methods: Hepatic impairment classification system, which is based on Child-Pugh score was used. In this mPBPK model, 4 physiological parameters [portal and renal blood flow, glomerular filtration rate (GFR), and liver size] and 2 biochemical parameters (albumin and bilirubin) were used. Total number of drugs analyzed in this study was 52, and the predicted C_max and AUC values were compared with dedicated clinical trials. Out of 52 drugs, the predictive performance of mPBPK was compared with the whole body PBPK model for 27 drugs, and the remaining 25 drugs were used to further test the robustness of the mPBPK model.

Results: The results of the study indicated that the predictive performance of the mPBPK model was comparable with the whole body PBPK model, both in terms of C_max and AUC. For 52 drugs, there were 120 data points for AUC (37, 47, and 36 for mild, moderate, and severe hepatic impairment, respectively), and from mPBPK model, 92%, 94%, and 89% data points were within 0.5–2-fold prediction error, respectively.

Conclusions: Overall, the results of the study indicated that the proposed mPBPK model, in its predictive performance, is as robust and accurate as whole body PBPK model.

Aim: This study evaluates the efficacy of amino-functionalized mesoporous silica nanoparticles (MSNs) in the controlled release of dexamethasone phosphate (DexaP), aiming to enhance therapeutic outcomes and minimize systemic toxicity.

Methods: In this study, amino-functionalized MSNs were synthesized using a modified Stöber process and characterized their chemical and physical properties through various analytical techniques. The study focused on the adsorption and release kinetics of DexaP, employing multiple kinetic models to explore the interaction dynamics.

Results: The amino-functionalized MSNs demonstrated effective DexaP loading and controlled release profiles. The kinetic analysis revealed a predominance of chemisorptive interactions, supporting sustained drug release. Enhanced biocompatibility was confirmed through cytotoxicity assays.

Conclusions: Amino-functionalized MSNs offer a promising platform for the targeted and controlled delivery of anti-inflammatory drugs, with significant potential to improve patient adherence and reduce adverse effects. The findings advocate for further development of MSNs as a versatile tool in advanced drug delivery systems.

Multiple drug-resistantStaphylococcus aureus bacterial pathogens are causative agents of serious infectious disease and are responsible for significant morbidity and mortality rates. Of particular concern in the public health domain are strains of methicillin-resistant S. aureus (MRSA), a member of the Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Escherichia coli (ESKAPEE) group of bacterial pathogens, many of which are recalcitrant to effective chemotherapy in the clinical setting due to their resistance to multiple antimicrobial agents. An important mechanism that confers multi-drug resistance in MRSA involves the active efflux of structurally different antimicrobial agents by members of the major facilitator superfamily (MFS) of proteins. The multidrug efflux pumps of the MFS share similar amino acid sequences, protein structures, and a common evolutionary origin. As such, the multidrug efflux pumps of the MFS are thought to operate by a similar solute transport mechanism and, thus, represent suitable targets for modulating their transport activities. This review article addresses MRSA as a serious pathogen, the mechanisms of antimicrobial resistance, and the functional and structural roles of the multidrug efflux pumps of the MFS in conferring pathogenicity.

4-Aminobenzoic acid (PABA, para-aminobenzoic acid) exhibits multifaceted therapeutic potential in neuropsychiatric disorders through its roles in neurotransmitter modulation, anti-inflammatory action, and antioxidant defense. Experimental and clinical evidence demonstrates that PABA enhances serotonin and dopamine synthesis by activating key enzymes (e.g., tryptophan hydroxylase and tyrosine hydroxylase), thereby stabilizing mood and improving cognitive function. Mechanistically, PABA suppresses neuroinflammation by inhibiting NF-κB signaling and cytokine production (e.g., IL-1β, TNF-α) while scavenging reactive oxygen species (ROS) to mitigate oxidative stress and protect neuronal integrity. Clinical studies indicate that PABA may synergize with traditional antidepressants by targeting serotonin reuptake transporters (SERT) and monoamine oxidase (MAO), offering improved outcomes in major depressive disorder. Despite promising results, further research is needed to optimize dosing regimens, validate long-term safety, and explore pharmacogenomic interactions. Crucially, experimental validation through cellular and animal models is required to substantiate PABA’s proposed mechanisms, particularly its regulation of NF-κB signaling and enzyme activity in neurotransmitter synthesis. This review underscores PABA’s potential as a neuroprotective agent and calls for integrated strategies to translate mechanistic insights into clinical applications for complex neurological conditions.

Aim: To evaluate the efficacy of experimental propolis varnish containing 15% green propolis in reducing Streptococcus mutans (SM) from saliva and dental biofilms.

Methods: Patients aged 8–11 years were recruited from a preventive program. After prophylaxis, propolis varnish was applied to collect saliva and biofilm samples at regular times (baseline/T0, 2nd day/T1, 3rd day/T2, 4th day/T3, 5th day/T4, 10th day/T5, 15th day/T6, and 30th day/T7). After each sampling, stimulated whole saliva was homogenized for 30 s, and tenfold serial dilutions in saline were plated on mitis-salivarius-bacitracin (MSB) agar and incubated at 37°C for 48 h. Colonies with typical morphology were counted, and the number of colony-forming units (CFU)/mL was compared via an independent sample t test. For quantitative real-time PCR (qPCR), the data were statistically analysed via one-way ANOVA with the Holm‒Sidak post hoc test.

Results: There was a significant difference in salivary SM levels between T0/T1 (baseline/2nd day) and T1/T7 (2nd day/30th day), but no difference was observed from the 3rd day onwards. The qPCR results also revealed a decrease in the number of SMs in the biofilm in the first days after varnish application.

Conclusions: A single application of green propolis varnish reduced SM in saliva and biofilms for three days. Whether these findings affect the incidence of caries needs to be confirmed through studies, which may improve the original formulation (International Clinical Trials Registry Platform registration code: NCT02052973).

Proteins from the neurotrophin family perform trophic and regulatory functions in the nervous and other body systems. Understanding the mechanisms of neurotrophin action is crucial not only for the evolution of fundamental scientific knowledge but also for developing new treatment strategies targeting neurotrophin signaling regulation. At our center, dimeric dipeptide mimetics of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have been obtained based on the structure of neurotrophins’ individual loops β-turns. These mimetics activated tyrosine kinase (Trk) receptors TrkA, TrkB, or TrkC specific to their respective neurotrophins, but exhibited varied activation patterns in the main post-receptor signaling cascades. Thus, some dipeptides activated all three main phosphoinositide 3-kinase (PI3K)/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phospholipase C-gamma (PLC-γ) pathways, while others triggered only PI3K/Akt and PLC-γ or MAPK/ERK and PLC-γ. Herewith, dipeptides exhibited a specific set of effects (neuroprotective, differentiating, antidepressant-like, anxiolytic, memory-enhancing, analgesic, antidiabetic) within the spectrum of biological activities of their corresponding native neurotrophin. It was revealed that these effects are influenced by both the patterns of post-receptor signaling activation and the nature of progenitor neurotrophin, uncovering significant correlations. This article is dedicated to reviewing the data that has been collected.

Folic acid (FA) residue is a well-known and widely spread targeting ligand, or biovector, used as a component in engineering artificial nanosized and submicron particles (NSPs) to target various cells and treat a variety of diseases that are associated with FA (or folate) receptors (FR) overexpression. A particular place in the list of these diseases is held by various cancer types, for which overexpression of FR on the cell surface is often accompanied by a more severe disease course, increased resistance to the conventional chemotherapy, and poorer prognosis. The incorporation of albumin into NSPs has been shown to enhance their biocompatibility, give high compatibility with drug molecules, prolong their circulation, reduce thrombogenic activity, and improve their colloidal stability. Nowadays albumin-based NSPs with FA residue as a targeting agent are used for chemotherapy, photothermal and photodynamic therapy, combined therapy, visualization, and theranostics (also known as theragnostics) for various types of cancer: breast, cervical, ovarian, prostate, nasopharyngeal, gastric, colorectal, liver cancer, and brain tumors. A limited number of studies have also focused on the use of NSPs in rheumatoid arthritis treatment. In this review, we discuss the ways of FA-albumin conjugation and conjugation of FA to albumin-modified NSPs systems. An application of nanosized and submicron delivery systems on the base of serum albumin and FA for therapy and diagnostics is discussed.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes a global epidemic named COVID-19. It still continues to plague humans with severe complications and unique sequelae, causing huge economic losses in the world. Pathophysiological studies showed that important life organs, such as the lungs, brain, kidneys, heart, liver, and immune system, and even reproductive ones are affected directly or indirectly in patients with COVID-19. Classically and newly discovered drugs, concerning antiviral replication, anti-inflammation, blockage of pathogenic processes, alleviation of symptoms, and especially distinctive multi-actions of Traditional Chinese Medicine, were screened out and tested, presenting promising therapeutic effects on the virus before or even though abundant effective vaccines come out. Moreover, other strategies are underway, including the use of plasma therapy, monoclonal neutralizing antibodies, vaccine trials, and emerging drugs with distinct interference mechanisms. This review features the novel progress on the latest-discovered antiviral drugs and the effective Traditional Chinese Medicine, and highlights the advantages and shortages of different therapeutic strategies and the predicted potential targets of the used Traditional Chinese Medicine components, which provides a valuable reference for clinical treatment continuously to combat COVID-19.

Epstein-Barr virus (EBV), human papillomavirus (HPV), and hepatitis C virus (HCV) are significant human pathogens associated with various diseases, employing complex molecular mechanisms for cellular entry and immune evasion. Peptide-based research, using more than 700 synthetic peptides, has deciphered some of the molecular interactions between viral proteins and host cell receptors, offering promising diagnostics and therapeutic strategies. In EBV, binding peptides have been identified: 11382, 11389, and 11416 derived from gp350/220; 11435, 11436, and 11438 from gp85 [glycoprotein H (gH)]; and 11521 from BNRF1/p140. Most of these peptide sequences are surface-exposed and are part of the contact regions with human cell receptors, making them promising candidates for strategies aimed at inhibiting EBV invasion of human cells. Peptide 11382 is the target of the neutralizing antibody 72A1; peptides 11382 and 11416 induce interleukin-6 production; peptide 11435 binds to integrin αvβ6, and peptide 11438 triggers a cytokine storm. In the HPV L1 protein, a major component of the viral capsid, peptides 18283 and 18294 have been identified as epithelial cell-binding peptides located on the virus surface. Parts of the sequences are recognized by anti-HPV neutralizing antibodies. These two peptides, along with peptide 18301, have been identified as potential biomarkers for HPV infection because they are recognized by antibodies elicited during natural HPV infection, making them suitable targets for serological detection. In the envelope proteins E1 and E2 from HCV, five hepatocyte- and CD81-positive cell-binding peptides have been identified. The sequences of these peptides contain linear B-cell epitopes recognized by neutralizing antibodies, and some of them have been used to develop serological tests for determining HCV infection. Peptide-based approaches can lead to innovative strategies for the prevention, diagnosis, and treatment of these viral diseases. Additionally, these peptides and their sequences can be used to modulate the immune response and generate tools for cancer theragnostic.

Aim: This study aimed to computationally identify and optimize 4-hydroxy isoleucine (4HILe) derivatives from fenugreek as multitarget antidiabetic agents against α-glucosidase, α-amylase, and aldose reductase [PDB (protein data bank) IDs: 5NN8, 4GQR, 4QX4].

Methods: A multi-step computational workflow was employed to identify and optimize 4HILe derivatives as antidiabetic agents. Molecular docking using the Schrödinger Suite screened 23 ligands against three enzyme targets to evaluate binding affinities and interactions. Molecular dynamic (MD) simulations conducted with GROMACS (Groningen machine chemical simulations) over 100 ns assessed conformational stability through RMSD (root mean square deviation) and RMSF (root mean square fluctuation) analysis. Binding free energy calculations [MM-GBSA (molecular mechanics-generalized Born surface area)] and free energy landscape (FEL) studies are performed to validate the thermodynamics of protein-ligand interactions. Additionally, generative AI modeling using LigDream generated 100 novel compounds derived from 4HILe, subsequently validated through docking studies to identify promising inhibitors.

Results: The study identified 4HILe-4, 2R-3S-4R-4HILe, and 4HILe-Amide-2 as potent derivatives with superior binding affinities [ΔG (Gibbs free energy): −49.3 to −42.3 kcal/mol] compared to co-crystal ligands (−45.3 kcal/mol), as determined by docking and MM-GBSA calculations. MD revealed stable protein-ligand complexes, evidenced by low RMSD values (0.2–0.4 nm) and minimal residue fluctuations (RMSF), confirming their structural integrity. The generative AI approach using LigDream also generated 100 novel 4HILe derivatives, with top candidates exhibiting strong docking scores and key molecular interactions against α-glucosidase, α-amylase, and aldose reductase. Notably, compound 10 (−9.424 kcal/mol), compound 4 (−8.167 kcal/mol), and compound 28 (−13.760 kcal/mol) emerged as promising inhibitors for further investigation.

Conclusions: The study highlights 4HILe derivatives as promising inhibitors for diabetes-associated enzymes, demonstrating robust binding and dynamic stability. Integrating molecular dynamics, free energy calculations, and AI-driven generative modeling provides a strong framework for accelerating antidiabetic drug discovery. These findings pave the way for experimental validation and the development of next-generation therapeutics targeting insulin resistance and hyperglycemia.

Metabolic syndrome is a complex, multifactorial disorder, with emerging research emphasizing the significant role of gut health in its prevention and management. Recent studies suggest that dietary strategies promoting a healthy gut microbiome, including the incorporation of fiber, fermented foods, and healthy fats, are crucial for regulating metabolism. Additionally, the use of postbiotics and supplements, such as probiotics, omega-3 fatty acids, and polyphenols, provides promising avenues for enhancing metabolic health. This holistic approach to managing metabolic syndrome not only supports gut health but also offers the potential for improving long-term health outcomes. This review examines the influence of the gut microbiome on metabolism, highlighting the increasing significance of dietary strategies and supplements in managing metabolic syndrome.

Cancer remains the second leading cause of death globally, posing an ongoing threat to public health. A hallmark of cancer cells is their capacity to invade adjacent tissues and evolve into malignant forms, often resulting in aggressive tumors resistant to conventional treatments. At the heart of this therapeutic challenge are cancer stem cells (CSCs), which possess distinctive capabilities for self-renewal, differentiation, and generation of diverse tumor cell populations. These CSCs have been identified across multiple tissue types, including lung, colon, breast, pancreas, and ovary. Research has demonstrated that CSC subpopulations contribute significantly to therapeutic resistance, tumor recurrence, and metastasis by regulating multiple signaling pathways, making them compelling targets for cancer therapy. Notably, emerging evidence suggests that natural products may offer protective benefits against cancer development while potentially targeting CSCs. This review synthesizes current knowledge of CSCs, examining their identifying markers, isolation techniques, study methods, and associated signaling pathways. Additionally, we explore various natural products that specifically target CSCs across different cancer types, presenting potential strategies to address the persistent challenges of drug resistance and cancer relapse.

Aim: The development of selective and potent antitumor agents remains a significant challenge. This study aimed to synthesize and evaluate biaryl hydroxy-1,2,3-triazoles and 9H-fluorene-1,2,3-triazole hybrids, inspired by previously identified bioactive 1,2,3-triazoles, for their cytotoxic potential against human cancer cell lines.

Methods: A library of 13 biaryl hydroxy-1,2,3-triazoles and 11 fluorene-1,2,3-triazoles was synthesized using optimized Suzuki and telescopic one-pot reactions, with yields ranging from 16% to 97%. The cytotoxicity of these compounds was tested against HCT-116 (colorectal cancer), SNB-19 (astrocytoma), MDA-MB-231 (triple-negative breast cancer), and MOLM-13 (acute myeloid leukemia, FLT3-ITD mutant) cell lines.

Results: Two fluorene-triazoles, 1-(2-bromophenyl)-4-(9H-fluoren-9-yl)-1H-1,2,3-triazole (LSO258) and 1-(4-bromophenyl)-4-(2-fluoro-9H-fluoren-9-yl)-1H-1,2,3-triazole (LSO272), both containing bromine substituents, exhibited selective cytotoxicity against MOLM-13, with half-maximal inhibitory concentration (IC₅₀) values of 25.5 μM and 12.5 μM, respectively. Furthermore, LSO258 and LS0272 showed a selectivity index ≥ 2 towards the MOLM-13 cell line. Biaryl hydroxy-1,2,3-triazoles displayed broader activity, with [1,1’-biphenyl]-2-yl(1-(2,5-dibromophenyl)-1H-1,2,3-triazol-4-yl)methanol (LSO278), featuring two bromine groups, demonstrating potency across HCT-116, MDA-MB-231, and MOLM-13 (IC₅₀: 23.4 μM, 34.3 μM, and 18.7 μM, respectively). However, structural rigidity did not consistently predict activity, as 1-(2,5-dibromophenyl)-4-(9H-fluoren-9-yl)-1H-1,2,3-triazole (LSO275), a rigid fluorene-triazole, was inactive. MOLM-13 was the most sensitive cell line, with compounds such as 4-(9H-fluoren-9-yl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazole (LSO259) and (1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)(4’-fluoro-[1,1’-biphenyl]-2-yl)methanol (LSO280), achieving maximum growth inhibition (MGI > 55%) despite not reaching IC₅₀ values.

Conclusions: The results highlight the critical role of bromine substitution on the aryl azide-derived ring in modulating cytotoxic activity. The study reinforces the potential of rigid fluorene-based scaffolds as promising leads for the development of targeted therapies against FLT3-mutant leukemia, aligning with previous reports on 1,2,3-triazole hybrids antiproliferative activity in leukemia models.

Aim: The PI3K (phosphoinositide 3-kinase)-alpha isoform is found upregulated in 30–40% of breast cancer. Currently, there are limited selective and specific drugs that target PI3K-alpha, and no natural therapeutic option is available. This study aims to develop natural hybrid antagonists of PI3K-alpha for breast cancer therapeutics.

Methods: 25 pan-PI3K and PI3K-alpha targeting drugs were obtained from various sources, including the COCONUT (Collection of Open Natural Products) database. On the parent dataset, high throughput virtual screening (HTVS), standard precision (SP) docking, and extra precision (XP) docking were performed to produce Murcko scaffolds and heterogenous fragments. Murcko scaffolds are hybridized with fragments of natural compounds (Category 1) and drugs (Category 2), respectively. Hybrids are docked with HTVS, SP, and XP, followed by induced fit docking and ADME (absorption, distribution, metabolism, and excretion) prediction. MM/GBSA (molecular mechanics/generalized Born and surface area) was performed on the docked poses.

Results: Highest docking scores of –13.354 kcal/mol and –12.670 kcal/mol were achieved by hybrids in Category 1 and Category 2, respectively. MM/GBSA free energy ranged from –51.14 kcal/mol to –72.66 kcal/mol. In terms of binding docking, pharmacological properties, and Lipinski’s rule of five, the natural hybrids outperformed the parent drugs.

Conclusions: PI3K-alpha kinase proteins can be targeted with natural-drug hybrid antagonists for breast cancer treatment. Hybrid molecules, such as NH-01 and NH-06, show better binding with promising ADME properties. Thus, in vivo and in vitro testing is necessary to prove the value of such hybrids.

Aim: This paper investigates two possible treatment targets for neuroblastoma (NB) stage 4 (NBS4), c-Src kinase (Csk) and retinoic acid (RA) signalling pathways as potential candidates for a multi-target drug. Research has demonstrated that many cancer cells overexpress and/or hyperactivate c-Src, a tyrosine that is a member of the Src-family kinases. In the case of NBS4, there are indications that successful inhibition of c-Src could inhibit disease progression. Research into the altered signalling of RA, which preserves the differentiated state of adult neurons, neural stem cells, and NB cells (SH-SY5Y), is also investigated as a potential multi-target drug.

Methods: Using computer-aided technology, including OpenEye Scientific suite, Molegro Virtual docking, Samson suite, and Discovery Studio Visualiser, the results revealed that the receptors for both targets, Csk and RA, share similar amino acid sequencing that ranges from 80–100%, offering the possibility of further testing for multi-target drug use. Work was done to explore possible synthesis routes for each of the four compounds using the retrosynthesis program Spaya. Predictive toxicology was done using the Toxicity Estimation Software Tool (T.E.S.T.).

Results: Four compounds (inhibitors) targeting the Csk tyrosine kinase and RA pathways were identified as potential inhibitors.

Conclusions: Currently, no effective therapeutic agents for NBS4 exist. Immunotherapy which has proven effective in treating various cancers, is currently used to treat NBS4 and has a 40% to 50% survival rate. This paper investigates two possible treatment targets for NBS4, Csk and RA signalling pathways as possible candidates for a multi-target drug. Four potential inhibitors have been identified.

Microbial pathogens with antibiotic resistance have become challenging to manage in the last few decades. The situation is alarming and a threat to humankind. Despite emerging new drug candidates, there are numerous strategies for efficient antibiotic delivery for treating such infections; antibiotic-resistant bacteria are still not eradicated adequately from the infected hosts. Recently, antimicrobial peptides (AMPs) have emerged as saviors in overcoming antibiotic resistance against bacteria. AMPs are being produced naturally as well as synthetically. Irrespective of the source of production, AMPs have shown higher specificity and lower toxicity to the host. Such functions have been attributed to distinct structures, functions, and varied mechanisms of action. This review highlights sources, structural and physiological characteristics, action mechanisms, and biological potency towards clinical applications. Most recently, AMPs have also been explored in treating cancers and tumors. Despite the entry of a few AMPs into clinical trials, there are limitations associated with their usage, like shorter half-life, protease cleavage, and toxicity. There is an urgent need to produce AMPs with intensified activity, biocompatibility, and lesser toxicity. This review sheds light on these aspects and the future of AMPs for the betterment of the human race.

Aim: This study aimed to elucidate the structural basis for the interaction of five natural anti-arthritic compounds, diacerein, rhein, glucosamines [glucosamine 3-sulfate (G3S), and glucosamine 6-sulfate (G6S)], and chondroitin disaccharide Δdi-4S (C4S) with cytochrome P450 2C9 (CYP2C9).

Methods: The investigated compounds were docked individually to the defined binding site in CYP2C9 based on the published crystal structure (PDB code: 1R9O).

Results: All investigated ligands bound deep in the active site pocket in close proximity to the heme. Except for chondroitin, all ligands are bonded to residues found in critical secondary structures that form the boundary of the active site cavity, including B-C loop, F helix, F-G loop, and I helix. A total of 12 amino acids were involved in the binding, and all were critical residues located in four out of six substrate recognition sites (SRSs) that have been identified as important substrate binding and catalysis regions in other CYP isoforms. The relatively more potent binding (lower CDOCKER interaction energy) observed for diacerein and rhein compared to glucosamines and C4S are likely due to two main factors: a higher number of bonds between the ligand molecule and CYP2C9 active site residues (14 versus 0–4), and direct interaction with the heme moiety. The binding residues identified in both diacerein and rhein were the residues that also bonded with sulfaphenazole, the specific and potent CYP2C9 inhibitor.

Conclusions: Collectively, this study has provided insights into structural features of CYP2C9 critical for inhibition and formed a basis for further exploration of structural determinants for potency and specificity of therapeutic compounds as CYP2C9 inhibitors.

Pentafuranosylnucleos(t)ides represent a class of natural compounds regulating diverse cell functions being preferably components of biopolymers and also participating as cyclic regulatory low-molecular ligands. Disaccharide nucleosides and related analogs are considered as therapeutically potent compounds for the treatment of cancer, viral diseases, and a variety of metabolic disorders by mimicking a structure of biochemically occurring molecules participating in nicotinamide adenine dinucleotide (NAD⁺) transformation. Several approaches have been developed on the way to the chemical synthesis of poly(adenosine diphosphate ribose) (PAR), a unique biopolymer taking part in DNA repair and associated functions, that would allow extensive studies of molecular mechanisms of a variety of diseases. The present review consists of the following main parts, the first one including structural characterization, biochemical roles, and chemical synthesis of disaccharide nucleosides from different sources and biopolymers on their basis, the second one describing therapeutic applications of disaccharide nucleosides and their analogs. General conclusion and perspectives are summarized in the last part.

Aim: The immunosuppressive drug brequinar (BQR) is a potent inhibitor of dihydroorotate dehydrogenase (DHODH) active against autoimmune diseases and viral infections. This oral drug is currently evaluated for the treatment of cancers, notably acute myeloid leukemia to limit the suppressive function of myeloid cells. A combination of BQR and an anti-PD-1 (programmed death-1) antibody has revealed potent antitumor and antimetastatic activities. BQR induced a marked down-regulation of PD-L1 (programmed death-ligand 1) gene expression and a large decrease of PD-L1 protein expression in implanted tumors in mice.

Methods: The present study evaluated the capacity of BQR to interact directly with the PD-L1 protein dimer using molecular modeling.

Results: Molecular docking experiments revealed a modest capacity of BQR to stabilize PD-L1 dimers. The PD-L1 binding capacities of four known BQR analogs were compared to establish structure-binding relationships. The protein binding was significantly enhanced when the acid function of BQR was replaced with a trifluoroethanol substituent. The interaction was further reinforced when BQR was coupled to a mitochondria-targeted triphenylphosphine (TPP) unit. Among three BQR-TPP hybrids, compound B2 with a short alkyl linker revealed a prominent capacity to interact with PD-L1, superior to that of the reference biphenyl ligand BMS-202.

Conclusions: Two PD-L1 binders derived from BQR have been identified and the protein interaction modeled. Our study underlines the possibility of designing novel small molecule ligands targeted to the PD-L1 dimer interface based on the BQR scaffold.

Merozoite invasion of erythrocytes relies on molecular interactions between parasite and host proteins, making these proteins potential therapeutic targets. This review summarizes research on Plasmodium falciparum merozoite invasion conducted at the Instituto de Inmunología, San Juan de Dios Hospital, between 1990 and 2000. Erythrocyte-binding analyses of P. falciparum proteins merozoite surface protein 1 (MSP-1), MSP-2, acid basic repeat antigen (ABRA) (MSP-9), apical membrane antigen-1 (AMA-1), rhoptry-associated protein 1 (RAP-1), glycophorin-binding protein 130 (GBP-130), serine repeat antigen 5 (SERA-5), erythrocyte-binding antigen 140 (EBA-140), and EBA-175 identified 50 high-activity binding peptides (HABPs) with nanomolar-range dissociation constants. Most of these peptides inhibit merozoite invasion and belong to erythrocyte-binding regions of their respective proteins. Several HABPs overlap with epitopes recognized by inhibitory monoclonal antibodies (mAbs). MSP-1 HABP-5501 contains epitopes for mAbs 12.8, 12.10, MaliM03 fragment antigen binding (Fab), and 42D6 Fab, all of which block invasion. MSP-2 HABPs include epitopes targeted by opsonizing antibodies, while MSP-9 HABPs (2148–2153) interact with Band 3 during invasion. AMA-1 HABPs (4315, 4316, and 4325) contribute to the 1F9 epitope, a key target of immune recognition. RAP-1 HABP-26188 elicits inhibitory antibodies, including cross-reactive mAbs SP5.2 and SP8.18, the latter displaying parasite growth inhibition. GBP-130 HABP-2220 binds glycophorin and induces invasion-blocking antibodies. SERA-5 HABP-6725 contains sequences targeted by native SERA-5 antibodies, while HABPs 6727 and 6733 are recognized by antibodies from natural infection and vaccination. EBA-140 HABPs (26135, 26144, and 26147) are located in Region II (RII) and are recognized by mAbs with moderate to strong neutralizing activity. EBA-175 HABPs (1779, 1783, 1814, 1815, and 1818) are in recombinant fragments recognized by antibodies eluted from immune complexes. HABPs 1779 and 1783, located in RII, bind erythrocytes independently of sialic acid, inhibit rRII-EBA binding, and interact with α(2,3)-sialyllactose. HABP-1783 also contains the target site of mAb R217, which potently blocks EBA-175 binding to glycophorin A and inhibits invasion.

Aim: The objective of this study was to develop a simple quantitative model (SQM) to predict maximum plasma concentration (C_max) and the area under the curve (AUC) of renally excreted drugs (n = 16) in pregnant women from non-pregnant women.

Methods: The SQM was developed using 6 physiological parameters and the fraction unbound protein in plasma (f_up) as the product characteristic. The six physiological parameters used in this study were total body water, blood volume, cardiac output, glomerular filtration rate (GFR), volume of the fetoplacental unit and blood flow of the fetoplacental unit. A factor was derived based on the average values of the physiological parameters and f_up for different gestational ages to predict C_max and AUC values in pregnant women from non-pregnant women. The predicted values from SQM were then compared with the dedicated clinical studies as well as predicted values by a physiologically-based pharmacokinetic (PBPK) model.

Results: Out of 17 C_max data points, 15 (88.2%), 15 (88.2%), and 12 (70.6%) data points were within 0.5–2.0-fold, 0.5–1.5-fold and 0.7–1.30-fold prediction error, respectively, by SQM, whereas, 17 (100%), 15 (88.2%), and 13 (76.5%) data points were within 0.5–2.0-fold, 0.5–1.5-fold and 0.7–1.30 fold prediction error, respectively, by PBPK. Out of 36 AUC data points, 36 (100%), 34 (94.4%), and 30 (83.3%) data points were within 0.5–2.0-fold, 0.5–1.5-fold and 0.7–1.30-fold prediction error, respectively, by SQM, whereas, 35 (97.2%), 33 (91.7%), and 27 (75%) data points were within 0.5–2.0-fold, 0.5–1.5-fold and 0.7–1.30-fold prediction error, respectively, by PBPK. The results of the study indicated that the predictive power of both models was very good.

Conclusions: The results of the study indicate that the SQM in its predictive performance is as robust and accurate as whole body PBPK.

Since our previous summary of the 74 FDA-approved kinase inhibitors in clinical and preclinical trials for non-cancerous neurological treatment, the US FDA has approved 13 additional kinase inhibitors since early 2022. This update incorporates new evidence for the now 87 FDA-approved kinase inhibitors in clinical and preclinical trials for the treatment of non-cancerous neurological disorders. By the end of October 2024, nearly all 87 FDA-approved kinase inhibitors have been tested in various animal models of non-cancerous neurological disorders, with twenty entered into clinical trials and six used for off-label treatments of neurological conditions in humans. Considering the challenges posed by intellectual property (IP), legal considerations, and limited blood-brain barrier (BBB) permeability, which may restrict some FDA-approved kinase inhibitors from effectively targeting the central nervous system (CNS), we further discuss the feasibility of designing novel proprietary analogs with enhanced BBB penetration to improve their therapeutic potential in neurological disorders. The new drugs typically retain full IP rights and remain costly; while repurposing kinase inhibitors may provide effective and affordable treatments for non-cancerous neurological disorders.

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is becoming a major public health concern in Africa, particularly in cities, due to urbanization, dietary changes, and improved diagnostic tools. The present study discusses the benefits, disadvantages, and practical limitations of the pharmacological treatments for IBD patients that are currently accessible in Africa. Given the limits of conventional treatments, such as their potential for considerable side effects, high cost, and often limited accessibility, this review explores emerging new treatment approaches such as nanomedicine, personalized medicine, and the use of traditional African medicines. Highlighting the urgency for potential alternative treatments, this review explores new and developing therapeutic innovations to enhance IBD management and improve the quality of life for African patients.

The tropics are abundant in both animals and plants, but also in pathogenic agents. There, the world’s greatest burden of diseases and mortality is concentrated. Co-infections are the rule, making laboratory diagnosis complex. Simultaneous multidiagnostic methods are desirable; however, they are mostly expensive and inaccessible to the populations of the region. The aim of our research was to produce synthetic peptides of the most important pathogens that can be used in a simultaneous multidiagnostic technique. Thus, we designed a low-cost method to detect antibodies, the multiple antigen blot assay (MABA), using synthetic peptides as the main source of antigens from endemic tropical diseases. This method allows the simultaneous detection of antibodies against 26 different agents with only a few microliters of sera, plasma, or saliva. The development of this system is the result of a long process, and the pipeline of our approach from then to nowadays is presented. Specific epitopes with the greatest antigenic potential using immunoinformatic algorithms have been selected from worldwide and tropical pathogens and then assayed by a successive chain of immunological techniques [PEPSCAN^®, enzyme-linked immunosorbent assay (ELISA), and MABA] to evaluate the sensitivity and specificity of those synthetic peptides for their usefulness in diagnosis. Years of work have been required for this complex process, with the recent incorporation of new immunoinformatic predictive tools, methodologies, and cost advantages. It can be concluded that synthetic peptides are a promising approach for diagnostic processes based either on the detection of antigens or antibodies.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of cellular redox balance and detoxification, critical for maintaining hepatocyte homeostasis. However, its dysregulation has emerged as a key driver in hepatocellular carcinoma (HCC), the most prevalent form of liver cancer. This review synthesizes recent advancements (2023–2025) to elucidate Nrf2’s context-dependent dual functions: tumor suppressive roles during early carcinogenesis through oxidative stress mitigation, versus oncogenic effects in advanced stages via promoting proliferation, survival, and treatment resistance. We systematically analyze molecular mechanisms of Nrf2 activation, including Kelch-like ECH-associated protein 1 (KEAP1)-dependent/independent pathways and epigenetic regulation, supported by clinical data linking Nrf2 expression to patient prognosis. Preclinical and translational research on Nrf2-targeted therapies is evaluated, with a focus on combinatorial strategies overcoming resistance. Despite challenges in developing selective modulators, integrating multi-omics biomarkers and context-specific interventions offers promise for precision medicine in HCC.

Aim: Depression is one of the most important mental diseases. Different pharmacological and non-pharmacological methods are used to treat depression. Traditional and complementary medicine also have a special role in the treatment of depression. Among the specific medicinal formulations mentioned in Traditional Persian Medicine (TPM), an important and widely used form is “Mufarrah” (exhilarating), which indirectly refers to the mood-stabilizing group. In this work, a related traditional formulation has been reformulated and standardized as a conventional tablet.

Methods: A simple and famous example among this group is “Mufarrah-e-Bared-e-Saghir”, containing Rosa × damascena Herrm., Coriandrum sativum L., Melissa Officinalis L. Following tablet preparation of the mentioned remedy, total phenolic and flavonoid content was determined using the spectrophotometric method. Volatile constituent analysis and quantification of linalool as the main component were carried out via gas chromatography (GC) [GC/MS (mass spectrometry) and GC/FID (flame ionization detector)].

Results: According to the results, the main compound of the final product was linalool (54.6%). Linalool, total phenol, and total flavonoid amounts have been calculated, respectively, 2,379.65 ± 262.13 µg/mL of the extracted essential oil, 163.23 ± 0.61, and 41.41 ± 2.3 mg/g extract.

Conclusions: Prepared tablets as a reformulated traditional medicine product with rich total phenols and flavonoids, as well as the presence of linalool as a considerable icon with antidepressant activities, can be introduced to the Persian medicinal plants market to control depression.

Aim: The objective of this study is to ascertain the antimicrobial and anticancer properties of dry Morinda citrifolia L. (noni) pulp hydroalcoholic extracts.

Methods: In this study, dry noni samples were immersed in hydro-alcoholic solvents, ethanol (EtOH) and methanol (MeOH). Using the intelligent-flash extractor (KBE-I5) and freeze-vacuum dryer, noni ethanol (NE) and noni methanol (NM) extracts were obtained for antimicrobial testing against bacterial and fungal strains via disc diffusion assay. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, acridine orange (AO) staining, and western blotting to evaluate anticancer effects on human cancer cells. Novel phytoconstituents were identified using dual-mode ultra-performance liquid chromatography quadrupole exactive orbitrap-tandem mass spectrometer (UPLC-Q-exactive orbitrap-MS/MS) analysis.

Results: Extraction yielded 16.8% for NE and 25.8% for NM. NE minimum inhibitory concentrations (MICs) against Escherichia coli (EC), Saccharomyces cerevisiae (SC), Staphylococcus aureus (SA), and Streptococcus thermophilus (ST) being 177, 52, 388, and 283 mg/mL. NM MICs values were 105, 47, 312, and 135 mg/mL, respectively. Anticancer half inhibitory concentrations (IC₅₀s) for NE against human colon adenocarcinoma cell (HT-29) and human bladder cancer cell lines (UMUC-3) were 758 and 899 µg/mL. For NM, IC₅₀s were 1,231 (HT-29) and 1,173 (UMUC-3) µg/mL. Cell death indicators include organelle deformities, AO fluorescence, and autophagy protein expression. In dual ion-scan mode UPLC analysis, 17 distinct phytoconstituents were identified, including 2-Hydroxycinnamic acid, 4-Hydroxycinnamic acid, and riboflavin, known for treating cancer, metabolic dysfunctions, and COVID-19. The 14 constituents were discovered in noni fruit for the first time.

Conclusions: Noni fruit extracts show antimicrobial/anticancer activity and therapeutic potential, establishing noni fruit as a promising food and medicinal source based on composition.

Aim: This study evaluates the in vitro and in vivo antiplasmodial, hemolytic, and antioxidant activities of a combined extract of Ageratum conyzoides (A. conyzoides) and Bidens pilosa (B. pilosa), a traditionally used but scientifically unvalidated combination.

Methods: Plant leaves were extracted via aqueous decoction and cold maceration, combining equal parts to mimic traditional preparation. In vitro antiplasmodial activity against the chloroquine-sensitive Plasmodium falciparum 3D7 (Pf3D7) strain was assessed using the SYBR Green I assay. Cytotoxicity was evaluated via hemolysis test, and antioxidant potential using DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], and FRAP (ferric ion reducing antioxidant potential) assays. The most potent combination was tested for acute toxicity and curative antimalarial activity in a rodent model.

Results: Extract yields ranged from 6.6% (cold maceration extract of B. pilosa) to 29.2% [aqueous decoction extract of combination (Cd)]. Extracts showed moderate to mild in vitro antiplasmodial activity [IC₅₀ (median inhibitory concentration): 24.8–96.6 µg/mL], with the aqueous Cd showing potential synergism [CI (combination index) < 1]. No significant cytotoxicity was observed (< 10% hemolysis). Moderate to good antioxidant activity was found in DPPH [SC₅₀ (median scavenging concentration): 134.65–307.55 µg/mL] and ABTS assays (SC₅₀: 92.23–183.45 µg/mL), with Cd showing the highest activity. FRAP values were low. The Cd extract demonstrated no significant acute toxicity up to 5,000 mg/kg and significant in vivo antimalarial activity, achieving 65% parasite inhibition at 200 mg/kg/day. It also prolonged survival time, with a maximum survival of 28 days at 200 mg/kg/day.

Conclusions: This preliminary investigation suggests that combined extracts of A. conyzoides and B. pilosa exhibit noteworthy in vitro and in vivo antiplasmodial activity against the tested strains. Further studies are warranted to validate these findings and develop optimized formulations as potential antimalarials.

Aim: The science of manipulating matter at almost atomic scales to create new structures and devices that function at nanoscale dimensions is known as nanotechnology, which is essential to many sciences, such as medicine and environment. This field of study has been reported to investigate better alternatives for the advancement of medicine; one such alternative is the use of plants, which contain substantial amounts of essential phytochemicals. This study aims to utilize such a plant species, Canna indica (C. indica) leaves, known as traditional medicinal plants or commonly grown plants, to synthesize silver nanoparticles (AgNPs) and evaluate their potential in green medicine.

Methods: The synthesis was carried out using five varieties of leaf water extracts: Pink red, Yellow, Pink, Yellow red, and Red, under different conditions, to which scanning electron microscopy was performed. The antioxidant capacity was evaluated by total flavonoid content, total phenolic content, total antioxidant capacity, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. The antibacterial activity of AgNPs and water extracts was evaluated againstStaphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Finally, the cytotoxicity of AgNP is evaluated using the brine shrimp lethality assay.

Results: The optimum condition for AgNP synthesis was determined to be room temperature, and Pink_AgNPs were observed as spherical with a size of 27–48 nm in scanning electron microscopy. The antioxidant assays concluded that AgNPs show significantly higher antioxidant capacity and exhibit higher scavenging activity. This study’s findings showed the efficiency of AgNPs against both strains, and higher efficiency againstS. aureus. It was observed that with 240 ppm of AgNPs, 100% viability is obtained.

Conclusions: These novel findings emphasize the significance of C. indica AgNPs, their promise in the medical field, and their application in manufacturing green medicine for environmentally friendly healthcare.

Gene-based medicine is transforming modern healthcare by offering precise, personalized interventions that target the genetic causes of disease. Breakthroughs in gene editing technologies, including clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) nuclease technologies (CRISPR-Cas9), base editing, and prime editing, are enabling promising therapeutic applications for rare inherited disorders and complex conditions like cancer. Furthermore, improvements in both viral and non-viral delivery methods are expanding clinical possibilities and enhancing safety measures. Despite these advancements, challenges such as off-target effects, ethical considerations, production complexities, and high costs continue to hinder widespread adoption. This review explores current innovations in gene-based medicine, addresses remaining obstacles, and outlines future directions, emphasizing the transformative potential of genomic-driven therapies for patients worldwide.

Cholecystokinin (CCK) is the most prevalent neuropeptide in the brain, where it affects satiety, pain modulation, memory, and anxiety. Its effects are mediated by GPCRs known as the “alimentary (gastrointestinal)” CCK₁r (CCK 1 receptor) and the brain-specific CCK₂r (CCK 2 receptor). While stress causes CCK to be released and full CCK₂r agonists are potent panicogenic agents, specific CCK₂r antagonists are ineffective at lowering human anxiety. As a result, the therapeutic potential of CCK as a target in psychiatry has been questioned. By compiling relevant new and historical scientific data retrieved from Scopus and PubMed, the aim of this review was to suggest a new function of CCK neurotransmission, the regulation of neuronal homeostasis during stress. Four lines of evidence were discussed that support the hypothesis of a CCK-driven neuronal homoestasis: (1) Homeostatic plasticity including synaptic scaling and intrinsic excitability; (2) its interaction with retrograde endocannabinoid signaling; (3) neuroprotective role; and (4) dynamic neuromodulation of CCK release. CCK functions as a crucial and essential molecular switch of neural circuits and neuroplasticity through its remarkable cell-specific modulation of glutamate and GABA release via CCK₂r. CCKergic neurons are downstream of the activation of cannabinoid type-1 (CB1) receptors in order to generate and stabilize rhythmic synchronous network activity in the hippocampus. CCK is also released to modulate other neurotransmitters like dopamine and opioids when neuronal firing is intense during the processing of anxiety/fear, memory, and pain. CCK likely functions to restore baseline neuronal function and protect neurons from harm under these conditions. Anxiety, depression, and schizophrenia could result from compensatory plastic changes of the CCKergic system that go awry during neuronal homeostasis. This review concludes by examining the benefits of putative compounds that exhibit a combination of CCK agonist and antagonist activity at multiple locations within the CCKergic system, as well as off-targets in managing mental conditions.

Nanotechnology is a relatively young field of science that has found wide application in medicine, especially in oncology. It focuses on studying molecules at the atomic, molecular, and supramolecular levels, enabling the development of innovative therapeutic solutions. Thanks to research in this field, it has become possible to introduce nanoparticles (NPs) into therapy, specially designed molecules that release the drug in a precisely defined place. This approach allows for maintaining the appropriate therapeutic concentration of the drug substance in the body for a longer period of time. The use of NPs in the treatment of cancer diseases helps to overcome the limitations of traditional chemotherapy, such as systemic, toxic effects of drugs, lack of specificity towards cancer cells, and limited bioavailability. NPs can be used not only as drug carriers, but also as contrast agents enabling imaging at the molecular level. More accurate visualization of diseased tissues is possible thanks to the small size of NPs, optical properties, and the ability to accumulate in the tumor area. Additionally, the use of specific ligands allows detection of pathological changes at the cellular level, allowing for earlier detection of changes, which in turn increases the probability of complete recovery of the patient.

Aim: Menopausal women are suffering from stress-related disorders, and in the previous studies, Khaya anthotheca (K. anthotheca) decoction exhibited estrogenic and anxiolytic properties. Taken together, the aim of this study was to evaluate the effects of K. anthotheca decoction on behavioral disorders and oxidative stress induced by repeated variable stress in ovariectomized Wistar rats.

Methods: Forty-two female Wistar rats (10–12 weeks old; 145 ± 10 g) were used. They were ovariectomized (except those from the sham operated group). Fourteen days after ovariectomy, animals were randomly distributed into 7 groups (n = 6): sham operated and negative control groups receiving distilled water; two positive control groups receiving estradiol valerate and diazepam (1 mg/kg each), and three other groups receiving the tested doses of K. anthotheca extract (125, 250, and 500 mg/kg each). The treatment was applied every week. Anxiety, depression, and motor coordination were assessed throughout the experimental procedure. The anti-oxidative potential of the extract was evaluated in rat brain homogenate.

Results: It was noted that K. anthotheca extract induced anxiolytic effects marked by an increase in the locomotory activity during open field, light/dark, and elevated plus maze tests. Besides, its anti-depressive effects were shown by a significant (p < 0.05) decrease in the immobilization time during the forced swimming test. By improving the suspension time during grid and wire grip tests, the distance covered, and the number of switch directions during the beam walking test, the extract increased motor coordination. The antioxidant potential of the extract was marked by a significant decrease ( p < 0.01) in malondialdehyde level and an increase ( p < 0.05) in reduced glutathione level.

Conclusions: These results provide valuable insights into the potential therapeutic application of the K. anthotheca extract; however, more studies are needed to elucidate mechanisms of action.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more rapidly progressive variant steatohepatitis (MASH) are widespread chronic liver conditions linked to obesity and other common metabolic disorders. The emergence of tirzepatide, a dual incretin receptor agonist targeting both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, presents major therapeutic potential for MASLD. This review article explores the mechanisms of action of tirzepatide, highlighting its ability to improve glycemic control, promote weight loss, and potentially ameliorate hepatic steatosis and fibrosis. Recent studies suggest that tirzepatide may offer significant benefits in managing MASLD/MASH by modulating metabolic pathways and enhancing liver health. However, further research is needed to fully understand its long-term impact on MASLD/MASH progression and outcomes across diverse patient populations.

Probiotics, originating at birth, play a crucial role in the development and maintenance of a healthy and disease-free environment within the gut of both humans and animals. These beneficial microorganisms from fermented, processed, and non-dairy foods provide numerous health benefits, such as stress reduction, disease prevention, immune stimulation, gut microbiota control, nutritional supplementation, diarrheal disease relief, vitamin production, weight management, and anticancer activities. With more health problems on the rise and the negative side effects of conventional medication and antibiotics prevailing, natural supplements such as probiotics are a relief. Probiotics, such asLactobacillus, Bifidobacterium, and Saccharomyces, have been identified as safe and effective candidates for gut health applications. This review addresses the current understanding of the mechanism of action of probiotics, their functions in human health, and their therapeutic potential for various diseases. We emphasize the importance of prioritizing probiotic administration along with conventional medicinal drugs for their wide benefits and fewer side effects. Our findings aim to direct future studies on the modes of action of probiotics against emerging health challenges.

Cedarwood essential oil (CWO), obtained from Cedrus and related species, has a long history in traditional medicine but remains relatively underexplored in modern pharmacology. This review consolidates current evidence on its phytochemical composition and pharmacological activities. Literature was retrieved from PubMed, Web of Science, and Scopus up to July 2025, including in vitro, in vivo, and limited clinical studies. Findings suggest antimicrobial, anti-inflammatory, sedative, and dermatological properties, primarily attributed to sesquiterpenes such as cedrol and α-cedrene. However, most data derive from small-scale or preclinical studies, with limited standardization of dosage and formulations. Safety aspects and toxicological gaps are also highlighted as essential considerations for future clinical translation. We conclude that CWO shows therapeutic potential, but rigorous clinical trials, standardized protocols, and comprehensive toxicological evaluations are essential before its safe and effective integration into evidence-based practice.

Metabolic dysfunction-associated steatohepatitis (MASH) is emerging as a leading cause of cirrhosis, hepatocellular carcinoma, and liver-related mortality worldwide. Among the most advanced pharmacologic candidates are resmetirom, a highly liver-selective thyroid hormone receptor-β (THR-β) agonist, and semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) already approved for diabetes and obesity. Although both agents improve hepatic steatosis, their mechanisms of action, extra-hepatic benefits, and safety signatures diverge markedly. Resmetirom, which was approved by the Food and Drug Administration (FDA) in March 2024, acts hepatocentrically to accelerate β-oxidation, lower atherogenic lipoproteins, and deliver early signals necessary for fibrosis regression, all while largely avoiding systemic thyrotoxic effects. Semaglutide acts systemically by reducing caloric load through pronounced weight loss and glycemic control, producing the highest rates of histologic MASH resolution reported to date, albeit with less direct antifibrotic efficacy and characteristic gastrointestinal tolerability issues. This comparative perspective juxtaposes the two compounds with respect to molecular pharmacology, clinical efficacy, safety, and potential clinical positioning, and proposes that, because resmetirom primarily targets hepatic lipid disposal whereas semaglutide unloads systemic caloric pressure, their complementary actions could be harnessed sequentially or in combination to achieve broader, more durable disease modification across the heterogeneous spectrum of patients with MASH.

The escalating threat of antibiotic resistance and its advancing mechanisms for resistance development underscore the imperative need for alternative approaches to treat life-threatening infections. Consideration of bacteriophages, as well as antimicrobial peptides (AMPs) that can specifically target and eliminate particular bacteria, is gaining prominence for the improved treatment of infections. The effectiveness of bacteriophages and AMPs has been known for a long time, and their combined use is being investigated recently. Studies have shown that the use of phages or phage-derived enzymes (endolysins) in combination with AMPs has shown promising results in combating multidrug resistant bacteria. Bacteriophages lyse bacteria by hijacking the bacterial cell’s metabolic machinery, leading to the production of phage virus inside it and finally bursting the bacteria, while AMPs act by disrupting the bacterial cell membrane or affecting intracellular targets after penetration. In this review, we discuss previous studies on the combined use of both phages or phage-derived enzymes and AMPs, demonstrating their synergistic effects for combating multidrug resistant pathogens. Their mechanisms of action, and possible mechanisms of synergy and development of bacterial resistance to these, are discussed. Approaches, including genetic engineering, for improving their efficacy have been discussed. Safety and ethical issues regarding their use in human subjects are discussed. In summary, this review emphasizes the need for further research on the combined use of AMPs and bacteriophages to tap their potential effectiveness for treating antimicrobial-resistant infections.

Buarque et al. (Explor Drug Sci. 2025;3:1008107. DOI: 10.37349/eds.2025.1008107) reported the synthesis of 13 biaryl hydroxy-1,2,3-triazoles and 11 fluorene-1,2,3-triazole hybrids via optimized Suzuki and telescopic one-pot reactions. Cytotoxicity evaluations against colorectal cancer (HCT-116), astrocytoma (SNB-19), triple-negative breast cancer (MDA-MB-231), and acute myeloid leukemia, FLT3-ITD mutant (MOLM-13) cell lines revealed promising antitumor activity. 1-(2-bromophenyl)-4-(9H-filoren-9-yl)-1H-1,2,3-triazole (LSO258) and 1-(4-bromophenyl)-4-(2-fluoro-9H-fluron-9-yl)-1H-1,2,3-triazole (LSO272), both being fluorene-1,2,3-triazole hybrids with bromine substituents, could selectively inhibit the activity of MOLM-13 cells, while the biaryl hydroxy-1,2,3-triazoles compounds exhibited broader antitumor activity. It is worth noting that an inevitable phenomenon is observed: The above compounds have significant aromatic structural characteristics, and their large aromatic systems lead to increased molecular hydrophobicity, resulting in poor water solubility. This critical druggability limitation will directly restrict the development of formulations. To tackle this issue, this paper proposes micelles as the optimal solution. As a carrier structure formed by the self-assembly of amphiphilic surfactants, micelles possess a unique “hydrophobic core-hydrophilic shell” configuration. Their hydrophobic core layer can efficiently encapsulate triazole compounds containing aromatic structures. Compared to other nanomedicine formulations such as solid dispersions and nanoencapsulation technology, micelles demonstrate significant advantages in terms of stability, process simplicity, and biocompatibility.

Antimicrobial peptides (AMPs) are a heterogeneous group of small, naturally occurring molecules that are an integral part of the innate immunity of nearly all life forms. Their amphiphilic nature, cationic character, and small size distinguish AMPs, which have a wide spectrum antimicrobial activity against bacteria, fungi, parasites, and viruses. Their specific ability to selectively destroy microbial membranes, without harming host cells, makes them promising contenders to treat the growing threat of antimicrobial resistance (AMR), which has undermined the effectiveness of traditional antibiotics. The action mechanisms of AMPs are multifaceted, involving both membrane-disruptive mechanisms, like barrel stave pore formation, toroidal pore induction, and carpet-like membrane degradation, and non-membrane targeting mechanisms, like inhibition of nucleic acid synthesis, protein translation, and cell wall biosynthesis. AMPs are structurally diverse, from α-helices and β-sheets to cyclic and unstructured peptides, and are distributed abundantly in nature, being derived from mammals, amphibians, insects, plants, and microorganisms. Apart from antimicrobial activity, AMPs have immunomodulatory and regenerative activities, enabling their use in many therapeutic and industrial applications. These are for the construction of new anti-infective agents, wound healing compounds, medical device coatings to inhibit biofilm growth, natural food preservatives, adjuvants for vaccines, and possible anti-cancer drugs. Although they hold great promise, stability, toxicity, and production scale issues continue to hinder translation to the clinic. This review highlights the structural variability, modes of action, and novel uses of AMPs, with a focus on their status as next-generation therapeutics against multidrug-resistant microbes and for promoting biomedical innovation.

Aim: Diabetes mellitus is a serious public health problem, and the condition is managed using herbal medicine by many African traditional healers. This study aimed to provide scientific evidence on the effects of aqueous and ethanol extracts of Xymalos monospora (X. monospora) leaves on some biochemical parameters in diabetic rats.

Methods: This experiment included 63 male Wistar rats. Diabetes was induced for 10 days by intraperitoneal injection of dexamethasone (16 mg/kg) in overnight fasted rats. The diabetic rats were treated with aqueous (100 and 200 mg/kg) and ethanol (100 and 200 mg/kg) extracts of X. monospora leaves and metformin (40 mg/kg) for 15 days. Fasting blood glucose, serum lipid profile, atherogenicity indices (Castelli’s Risk Index, Atherogenic Coefficient, Atherogenic Index of Plasma), tumor necrosis factor alpha, and hepatic glycogen were evaluated.

Results: Treatment with the aqueous extracts at 100 and 200 mg/kg significantly reduced fasting blood glucose by 29.2% (p = 0.016) and 35.9% (p = 0.009), respectively. Also, the ethanol extracts at 100 and 200 mg/kg significantly reduced fasting blood glucose by 20.7% (p = 0.038) and 31.2% (p = 0.027), respectively. The aqueous extract (200 mg/kg) significantly reduced total cholesterol and triglyceride concentrations by 31.5% (p = 0.017) and 30.7% (p = 0.023), respectively. There was a significant reduction in atherogenicity indices (p < 0.05), and liver glycogen levels improved. The extracts reduced the levels of tumor necrosis factor alpha, but this was not significant ( p > 0.05). However, histopathological studies were not carried out, and the above findings may not directly translate to clinical efficacy.

Conclusions: These findings demonstrate that the oral administration of aqueous and ethanol extracts of X. monospora leaves has significant antidiabetic effects, including a decrease in fasting blood glucose, improvement of serum lipid profile, and increased glycogen storage.

Aim: One of the causes of Alzheimer’s disease (AD) is the structural change and aggregation of target proteins due to the binding of metal ions. In this study, we investigated where copper(II) ions bound to the protein egg white lysozyme crystals in a hydrophilic buffer solution after ions were synthesized from an amino acid Schiff base copper(II) complex with a hydrophobic azobenzene group.

Methods: X-ray crystallographic studies of the complexes and egg white lysozyme were then studied. Molecular docking studies for the binding of copper(II) ion with egg white lysozyme were also carried out.

Results: The results suggest that the hydrophobicity of the introduced complex affected how deeply the resultant copper(II) ion penetrated into the protein. It has been revealed that when metal complexes are soaked into protein crystals, the metal complexes act as carriers, and metal ions tend to dissociate and bind to appropriate functional groups on certain specific residues of the protein. His15 and Glu35 were the more common binding residues of the protein that bound to the metal ion.

Conclusions: An anti-Irving-Williams behaviour was observed for the interaction of the copper(II) complex with the lysozyme. Docking studies revealed various potential binding sites of copper(II) ion with the lysozyme.