Idiopathic pulmonary fibrosis (IPF) presents limited therapeutic options that often involve severe side effects, making the development of innovative treatments essential. While tracheloside (TCL) demonstrates various medicinal properties, its mechanism of action remains incompletely understood. This study examines TCL’s effects and mechanisms on bleomycin (BLM)-induced pulmonary fibrosis in mice. A BLM-induced pulmonary fibrosis model was established in vivo to assess TCL’s anti-fibrotic and anti-oxidative properties. In vitro studies utilized transforming growth factor-β (TGF-β) and matrix stiffness-induced myofibroblast differentiation models to investigate TCL’s mechanism. The results demonstrated that TCL inhibited BLM-induced pulmonary fibrosis. In vitro experiments revealed that TCL activated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), suppressed TGF-β or matrix stiffness-induced myofibroblast differentiation, decreased nicotinamide adenine dinucleotide phosphate oxidase isoform 4 (NOX4) expression, enhanced antioxidant enzyme expression, and mitigated oxidative stress. Additionally, activated AMPK inhibited NOX4 expression and, notably, reduced NOX4 activation through competitive binding to p22 phox. The findings indicate that TCL alleviates TGF-β or matrix stiffness-induced myofibroblast differentiation and oxidative stress via the AMPK/NOX4 signaling pathway, thereby exhibiting anti-fibrotic and anti-oxidative effects. This research presents novel insights into AMPK’s regulation of NOX4.

Marine terpenoids are a structurally diverse class of natural products produced by marine organisms, characterized by unique molecular architectures and notable biological activities. They play essential roles in ecological interactions and chemical defense, while also exhibiting promising therapeutic properties, including anti-inflammatory and anti-tumor effects. In this review, we compile 13 132 reported marine terpenoids, of which 2066 have documented biological activities, and provide a concise summary of their organismal origins, molecular scaffolds, and associated activities. Cheminformatics approaches are further applied to compare the chemical space of marine versus terrestrial terpenoids, highlighting their structural distinctiveness. Finally, we discuss promising directions for the discovery, utilization, and synthesis of marine terpenoids, with the goal of promoting comprehensive and sustainable exploration of these valuable marine resources.

Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1’s effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg⁻¹) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21−25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 μmol·L⁻¹), a specific TLR4 blocker, against S1 (10 μmol·L⁻¹) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 μg·mL⁻¹) to elucidate the TLR4 pathway’s mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1’s positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1’s therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

Hypertension represents a significant chronic non-infectious disease in China, where Qingda Granule (QDG) has traditionally been employed for its management. However, the mechanisms underlying QDG’s kidney protective effects remain incompletely understood. This study investigates QDG’s role in ameliorating hypertensive kidney injury (KI) and elucidates the associated mechanisms. Network analysis identified potential therapeutic targets related to mitochondrial function and the extracellular signal-regulated kinase (ERK) cascade. Ribonucleic acid (RNA) sequencing revealed differentially expressed genes (DEGs) in hypertensive mouse kidneys, which were enriched in mitochondrial-related functions and normalized by QDG treatment. QDG attenuated angiotensin II (Ang II)-induced blood pressure elevation and enhanced renal artery flow. Both cellular and animal experiments demonstrated that QDG inhibits the ERK/ribosomal S6 kinase 1 (RSK1) signaling axis, thereby preventing Ang II-induced mitochondrial damage and renal cell apoptosis. ERK pathway inhibitors confirmed QDG’s mechanism of action through the ERK/RSK1 pathway. These findings indicate that QDG ameliorates hypertensive KI by preserving mitochondrial function through modulation of the ERK/RSK1 network, presenting a novel therapeutic approach for managing hypertensive KI in clinical practice.

Traditional Chinese medicine (TCM) establishes that the kidney serves vital systemic functions and its deficiency represents a fundamental factor influencing various diseases, including asthma. The kidney-tonifying method represents a widely implemented clinical approach in TCM to address kidney deficiency. This study hypothesized that bone marrow mesenchymal stem cells (BMSCs) function as key contributors to the kidney-tonifying method. An ovalbumin (OVA)-induced asthma mouse model received treatment with the traditional kidney-tonifying formula, Qi-Xian decoction (QXD). QXD demonstrated significant therapeutic efficacy, enhanced BMSC proliferation in mouse bone marrow, and facilitated their migration to lung tissues. Inhibition of the CXCL12/CXCR4 axis diminished the QXD-induced migration of endogenous BMSCs and reduced QXD’s efficacy in asthma treatment. QXD-containing serum enhanced BMSC proliferation and promoted CXCL12-induced BMSC migration in vitro. These findings indicate that endogenous BMSCs may serve as a crucial mediator in the therapeutic effects of the kidney-tonifying method. Furthermore, the mild and sustained stimulation of production and enhanced homing of endogenous BMSCs presents a potential novel approach for effective asthma treatment.

Atractylodimers A−D (1−4), sesquiterpenoid dimers (SDs) featuring a unique cage-like structure, were isolated from the rhizomes of Atractylodes macrocephala. The most distinctive characteristic of these isolates was the highly twisted “cap” structure based on highly twisted five-membered oxygen heterocyclic rings. Notably, compound 1 contained a furo[2,3b]furan ring, a caged 3,10-oxa-tricyclo[5.2.1.0^4,9]decane moiety, and 6/6/5/5/5/5/6/6 octocyclic skeleton. Compounds 2−3 exhibited a spiro-tetrahydrofuran ring, while compound 4 incorporated a caged spiro-2,5,9-oxa-tricyclo[5.2.1.0^4,10]decane scaffold for unit linkage. Their structures were definitively established through spectroscopic methods and X-ray diffraction experiments. Plausible biosynthetic pathways of compounds 1−4 were proposed. Compounds 1 and 2 demonstrated significant neuroprotective effects against serum deprivation-induced PC12 cell damage.

Cartilage injuries remain a significant therapeutic challenge due to cartilage’s limited capacity for self-repair. Traditional treatment approaches for cartilage injuries, including surgical interventions, microfracture and autologous chondrocyte implantation, may alleviate symptoms but frequently present limitations such as surgical trauma, uncertain efficacy, and adverse effects. Active ingredients derived from traditional Chinese medicine (TCM), which possess anti-inflammatory, anti-apoptotic, proliferation-promoting, and differentiation-inducing properties, have emerged as a promising research focus for treating cartilage damage. However, clinical applications of TCM have been constrained by factors including low bioavailability, insufficient stability, and limited targeting capabilities. The integration of TCM active ingredients with biomaterials offers novel solutions to these challenges. This article examines the pathological foundations of cartilage injury, the mechanisms through which TCM active ingredients such as polysaccharides, flavonoids, terpenoids, aldehydes, polyphenols, and saponins address cartilage injury, and the therapeutic applications of TCM active ingredients combined with biomaterials. These biomaterial delivery systems encompass gels, nanomaterials, microspheres, and tissue scaffolds. Additionally, this article analyzes the challenges and potential development trajectories for combining TCM active ingredients with biomaterials in cartilage injury treatment, offering new perspectives for therapeutic intervention.

Ten previously undescribed rearranged 4,9-friedodrimane merosesquiterpenoids, designated ircinrimanes A−J (1−10), were isolated from the marine sponge Ircinia sp., collected from the South China Sea. Their structures and absolute configurations were definitively elucidated through a combination of spectroscopic data analysis, DP4+ probability assessments, electronic circular dichroism (ECD) calculations, and Mo₂(OAc)₄ experiment. Compounds 1−4 contained benzene rings, with compound 1 featuring an unusual 2-carbonyl morpholin ring, while compound 2 possessed a benzoxazole ring. Compounds 5−9 comprised sesquiterpenoid quinones with distinct amino side chains at C-20, and compound 10 incorporated an ethoxy side chain. Notably, compounds 1−10 demonstrated an unusual rearrangement of 4,9-friedodrimane sesquiterpenes. Compounds 2, 5−8 and 10 demonstrated cytotoxic activity, while compound 2 exhibited anti-inflammatory activity in zebrafish.

Halogen substituents play a crucial role in the structural diversity and biological activity of natural products, and the synthesis of halogenated molecules remains an area of significant research interest. This study describes the generation of 15 new halogenated angucyclinones through the incorporation of halogen-containing phenylamines into a biosynthetic C-ring-cleaved angucyclinone under mild conditions. The newly synthesized compounds feature halogen substituents encompassing all four halogen atoms (F, Cl, Br, I), with some compounds containing multiple halogen types. Structural elucidation was accomplished through ultraviolet (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopic analyses, expanding the structural diversity of angucyclinone-type polyketides. Cytotoxicity evaluations revealed that eight compounds demonstrated moderate cytotoxic activities against four human tumor cell lines, with half maximal inhibitory concentration (IC₅₀) values ranging from 3.35 ± 0.37 to 16.02 ± 6.60 μmol·L⁻¹. These findings highlight the significant potential of combining biosynthetic and chemical approaches in generating bioactive halogenated molecules.

Necroptosis, a necrotic form of regulated cell death, plays a crucial role in various tissues and disorders, including sepsis. This process occurs primarily through a caspase-independent mechanism mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL). Necroptosis-related diseases frequently manifest with excessive inflammatory responses. Corilagin, a gallotannin exhibiting potent anti-inflammatory and anti-oxidant properties, has received increasing attention. However, its effects on necroptosis and associated disorders remain unexplored. In this study, we utilize a surface plasmon resonance-liquid chromatography-tandem mass spectrometry (SPR-LCMS/MS) screening approach to identify corilagin’s target proteins and demonstrate its binding to necroptosis-related proteins. In vitro, corilagin inhibits necroptosis induced by either tuberculosis, tumor necrosis factor-α (TNF-α), LCL-161, and inhibitor (IDN-6556) (TSI) (tumor necrosis TNF-α combined with LCL-161 (a Smac mimic) and pan-caspase inhibitor IDN-6556), or lipopolysaccharide (LPS) with IDN-6556. Additionally, it suppresses the phosphorylation of MLKL, RIPK1, and RIPK3, while preventing necrosome formation during necroptotic induction. Corilagin also mitigates the TSI-induced reduction in mitochondrial membrane potential, a characteristic of necroptosis-associated mitochondrial dysfunction and the generation of mitochondrial reactive oxygen species (mtROS). In a mouse model of sepsis associated with necroptosis, corilagin administration reduces the severity of LPS-induced acute lung injury, correlating with decreased MLKL phosphorylation in lung tissues. These results indicate that corilagin attenuates RIPK1/RIPK3/MLKL signaling, potentially through reducing mtROS production, thereby inhibiting necroptosis and offering protection against LPS-induced acute lung injury.

Epimedium Herba (EH) demonstrates significant therapeutic potential against prostate cancer (PC), though its mechanisms of action remain incompletely understood. This study investigates the pharmacological mechanisms of EH in treating PC through network pharmacology analysis and experimental validation. Active components and potential targets of EH were identified using network pharmacology from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The STRING database facilitated the construction of a protein-protein interaction (PPI) network for shared targets and the identification of core anti-PC targets. Messenger ribonucleic acid (mRNA) and protein expression of core target genes in normal prostate and PC tissues, along with their correlation to overall PC survival, were analyzed using The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the potential targets. Molecular docking of quercetin with key targets (TP53, TNF, heat shock protein 90 alpha family class A member 1 (HSP90AA1), AKT1, CASP3, and ESR1) was conducted, with results visualized using PyMOL. In vitro experiments validated the network pharmacology predictions. Twenty-three active ingredients of EH were identified, and the intersection of potential targets with PC targets yielded 183 potential targets. PPI network analysis revealed six key genes: targets (TP53), TNF, HSP90AA1, AKT1, CASP3, and ESR1. GO enrichment analysis identified 2369 biological processes (BP), 77 cellular components (CC), and 215 molecular functions (MF). KEGG pathway enrichment analysis demonstrated that EH's anti-cancer effects were mediated through interleukin-17 (IL-17), TNF, phosphatidylinositol 3-kinase (PI3K)-AKT, apoptosis, p53, HIF-1, mitogen-activated protein kinase (MAPK), nuclear factor κB (NF-κB), and EGFR tyrosine kinase inhibitor resistance pathways. Core target validation confirmed consistency with the study’s findings. Molecular docking indicated stable binding between the six core targets and quercetin. In vitro experiments confirmed quercetin’s inhibition of proliferation and induction of apoptosis in ACT-1 cells. This investigation identifies potential therapeutic targets for PC through network pharmacology and experimental validation.