The brain is the most stringently safeguarded organ in the human body. The 7-mm-thick cra- nial vault shields the central nervous system (CNS) from external damage, while the blood- brain barrier (BBB) functions as a specific physiological barrier, successfully safeguarding it from circulating toxins and pathogens. BBB disruption is closely linked to the emergence and development of various CNS disorders, and the strong constraints of BBB on substance ex- change present a considerable obstacle to medicine administration for the treatment of neur- ological diseases. Aromatic orifice-opening agents (AOOAs), a specific class of traditional Chinese medicine (TCM), exhibit a unique bidirectional interaction with BBB. Such agents can loosen the BBB junctions, transiently enhance its permeability, and ease the passage of medic- ations into the brain, a phenomenon referred to as the “permeability-promoting” effect on BBB. In contrast, under pathological conditions, AOOAs can preserve BBB integrity and exert a “permeability-restricting” effect by reducing inflammatory responses and alleviating oxidat- ive stress. This review systematically analyzes the regulatory factors affecting BBB permeabil- ity, investigates the dual mechanisms by which AOOAs protect and penetrate the BBB, and highlights the innovative opportunities and significant potential these agents present for treating CNS disorders.

Atherosclerosis (AS) is widely recognized as the principal pathological substrate underlying chronic cardiovascular diseases (CVDs). It is a chronic, progressive, and inflammatory disease characterized by excessive lipid deposition, oxidative stress, inflammatory response, plaque formation and rupture, thrombosis and vascular calcification (VC). Vascular smooth muscle cells (VSMCs) are essential for maintaining the normal structure of blood vessels and play a pivotal role in the pathological process of AS. Their proliferation, migration, differentiation, senescence and death processes critically influence the progression of AS. The specific mechanism of VSMCs participating in AS remains a central focus of research in the cardiovascular field. In recent years, natural products have garnered considerable attention in the field of AS prevention and treatment, primarily due to their multi-target effects, low toxicity and side effects. However, there is still a lack of systematic review of natural compounds that alleviate AS by regulating the function of VSMCs. This article focuses on the core role of VSMCs in the progression of AS, and systematically reviews the natural compounds targeting VSMCs metabolism and their molecular regulatory mechanisms. By combing the relevant pharmacological activities and potential targets, the pathological function of VSMCs in AS is further elucidated, thereby providing an important theoretical basis for the development of novel and efficient AS treatment strategies.

As a globally known medicinal and aromatic herb, Artemisia argyi (A. argyi) has excellent health benefit and economic value, especially in the field of anti-pathogenic microorganisms. At present, pathogens such as parasites, fungi, bacteria, and viruses, pose a serious threat to human health and environmentally friendly, becoming a substantial global medical burden. Researchers worldwide are focusing on developing natural antibacterial drugs. Thereinto, we collected data on the pharmacological effects of A. argyi on pathogenic microorganisms from ancient Chinese herbal texts and medical books, and the publications referring to the effects of A. argyi on bacteria, fungi, viruses, and other pathogenic microorganisms from 2005 to 2025. Simultaneously, patent searches were conducted to explore the development and utilization of the anti-pathogenic activity of A. argyi in various fields over the past 20 years. We found that A. argyi has excellent efficacy and extensive practical applications against pathogenic microorganisms. Modern studies have confirmed its inhibitory effects on common bacteria such as Escherichia coli and Staphylococcus aureus; human and crop pathogenic fungi such as Candida albicans and Aspergillus niger; and viruses such as herpes zoster virus, respiratory syncytial virus, and hepatitis B virus. Moreover, the development and application of anti-pathogenic activity of A. argyi are broad. In brief, this study provides perspectives for fully utilizing the advantages of A. argyi in anti-pathogenic effect, and supporting its potential for functional product development and applications in the fields of daily health products, agriculture and the pharmaceutical industry.

Insulin resistance is a hallmark of type 2 diabetes (T2DM) and can increase the risk of cognit- ive impairment, including Alzheimer’s disease. Nuciferine, an alkaloid derived from lotus leaves, shows neuroprotective effects. This study investigated nuciferine’s protective role in T2DM-induced cognitive impairment (T2DM-CI) and its mechanisms. Mouse models were cre- ated using high-fat diets and streptozotocin, along with high glucose-induced HT-22 cells. Nu- ciferine reduced blood glucose, improved cognitive function, and mitigated glial cell activa- tion, neuron and synapse loss in T2DM mice. It enhanced insulin signaling by increasing pro- tein levels of IR, IRS1, and IGF-1R, reversing PI3K and AKT phosphorylation, inhibiting GSK3β activity, and reducing hyperphosphorylated Tau in HT-22 cells and T2DM mice. mRNA levels of these molecules matched their protein levels. Further studies revealed that nuciferine dir- ectly interacts with IR, knocking out IR abolished its effects on the PI3K/AKT pathway. Thus, nuciferine activates the PI3K/AKT pathway via IR, improving insulin resistance and slowing T2DM-CI progression.

Psoriasis is a chronic skin disease driven by skin inflammation and abnormal subcutaneous blood vessels. Yinxie Granules (YXKL) is a clinically effective traditional Chinese medicine (TCM) formula that has shown promise in psoriasis treatment, but its pharmacological mechanisms and material basis remain unclear, limiting its clinical application and co-administration with other drugs. In this study, we explored the mechanism and active components of YXKL in the treatment of psoriasis using patient samples, IMQ-induced psoriatic mice, zebrafish, and in vitro assays. We discovered that YXKL alleviated skin inflammation and restored the skin barrier by reducing M1 macrophage/Th17 infiltration, lowering pro-inflammatory cytokines (IL-6, IFN-β, IL-23, IL-17), and increasing loricrin expression. Mechanistically, we identified a dynamic transition in STING signaling during psoriasis progression. Both the STING/IRF3 and STING/NF-κB pathways were activated in moderate psoriasis, while only the STING/NF-κB pathway was hyperactivated in severe disease. YXKL specifically targeted the STING/NF-κB pathway to mitigate inflammation and vasculopathy but had no significant impact on the upstream regulators, including TRAF6, LKB1, AMPK, and ULK1. Quercetin and kaempferol were identified as the primary STING-modulating components in YXKL, binding to STING proteins and inhibiting downstream pathway activation. These flavonoid components mediate the anti-psoriatic effects of YXKL by simultaneously suppressing skin inflammation and angiogenesis while enhancing vascular integrity through STING inhibition in both keratinocytes and endothelial cells. Our results elucidated the molecular basis of YXKL for psoriasis treatment, highlighting STING/NF-κB as a pivotal therapeutic target in mitigating psoriasis development and providing natural candidate compounds as potential STING inhibitors.

Pinoresinol diglucoside (PDG), an active component derived from Eucommia ulmoides, exhibits therapeutic effects against apoptosis, inflammation, and hypertrophy, etc. However, whether PDG plays a protective role in diabetic cardiomyopathy (DCM) is not fully elucidated. This study aimed to investigate the role and potential mechanism of PDG in DCM. The possible mechanism of PDG targeting DCM was identified by network pharmacology, bioinformatics, machine learning and molecular docking methods. The heart function of mice was evaluated using echocardiography. The pathological changes in the heart of mice were detected using H&E staining. Changes of Ca²⁺ fluorescence intensity values in H9c2 cells were assessed by confocal microscopy. Apoptosis was evaluated by TUNEL staining and flow cytometry. The expression of DCM-related genes and proteins, both in vivo and in vitro, was examined by qRT-PCR and Western blot. The results showed that PDG effectively improved the cardiac function and suppressed cardiac hypertrophy, inflammation, and cardiomyocyte apoptosis caused by DCM. Intriguingly, molecular docking results revealed that the therapeutic effect of PDG on DCM was associated with stromal interaction molecule 1 (STIM1), calcium release-activated calcium channel protein 1 (Orai1), and nuclear factor of activated T-cells 3 (NFAT3) signaling. Consistently, animal experiments results indicated that PDG significantly downregulated the expression of STIM1, Orai1, NFAT3 at the protein level, as well as the associated store-operated calcium entry (SOCE). Therefore, our findings revealed that PDG can alleviate cardiac hypertrophy, inflammation and apoptosis in DCM by downregulating the STIM1, Orai1, and NFAT3 signaling molecules. Thus, PDG may be a promising therapeutic candidate for treating DCM.

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic metabolic disease that severely affects human health. Quzhou Fructus Aurantii ethyl acetate extract (QFAEE) is a mixture rich in diverse natural flavonoids that exhibits multiple pharmacological properties, including significant anti-inflammatory and antioxidant activities. However, the anti-MASH effects of QFAEE and the underlying mechanisms remain unknown. This study aimed to investigate the therapeutic effects of QFAEE on MASH and the related mechanisms. The therapeutic effects of QFAEE on hepatic steatosis, inflammatory responses, oxidative stress and apoptotic activity were systematically evaluated in both in vivo and in vitro models of metabolic stress. QFAEE administration significantly reduced hepatic lipid accumulation, inflammatory cell infiltration and liver injury in HFHC diet-fed mice. Combined RNA sequencing and network pharmacology analyses revealed that QFAEE exerted its anti-MASH effects through modulation of the PPAR signaling pathway. QFAEE ameliorated MASH by activating PPARα and subsequently upregulating CPT1A, which promoted mitochondrial and peroxisomal β-oxidation. Notably, PPARα inhibition promoted hepatic lipid accumulation, inflammation and oxidative stress in hepatocytes, all of which were significantly attenuated by QFAEE treatment. These findings suggest that QFAEE prevents metabolic stress-induced MASH progression by activating PPARα signaling.

Eleven new highly oxygenated cembrane-type diterpenoids (1−7 and 10−13) and two known analogues (8−9) were isolated from the South China Sea soft coral Sinularia pedunculata. Their structures were determined through extensive spectroscopic analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) approach and X-ray diffraction analysis. Notably, compounds 3 and 4 were rare cembrane diterpenoids featuring a tetrahydropyran moiety with 5,8-ether and 4,8-ether linkages, respectively, while compounds 4 and 9 inhibited HBV DNA replication with IC₅₀ values of 0.87 and 1.15 μmol·L⁻¹ in HepAD38 cells, respectively. Mechanism investigation suggested that compound 9 accelerated capsid formation without affecting the levels of HBV cccDNA, total RNA, or pgRNA.

Pneumonia is a highly prevalent acute respiratory infection worldwide, and Inula britannica displayed an anti-pneumonia effect. Herein, twenty compounds were isolated from I. britannica, including seven newly discovered compounds—six terpenoids named inulabritanoids P−U (1−6) and one novel lignan, inulabritanoid V (7)—along with thirteen known compounds (8−20). Their structural frameworks were clarified through 1D and 2D NMR, and HR-MS data. Effects of all the elucidated compounds for anti-pneumonia activities were assessed using the lipopolysaccharide (LPS)-induced pneumonia model in MH-S alveolar macrophages. Compounds 3, 5, 6,12, and 18 showed potent anti-pneumonia activities in LPS-exposed MH-S cells. Notably, compound 6 exhibited the most potent bioactivity: it significantly inhibited nitric oxide (NO) production and downregulated the expression levels of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-6, and chemokine (C-C motif) ligand 5 (CCL5). Further investigations revealed that the anti-pneumonia effect of compound 6 depended on inhibiting the NF-κB and MAPK/AP-1 signaling pathways. These results indicate that compound 6 represents a viable lead molecule for combating pneumonia, laying a foundation for future studies.