Introduction: This study comparatively evaluated the chemical profiles and antiinflammatory activities of Radix Tetrastigmae extracts originating from Zhejiang and Guangxi. Methods: Chemical constituents were characterized by HPLC-ESI-HRMS/MS combined with GNPS-based molecular networking, and anti-inflammatory effects were assessed in RAW 264.7 macrophages and in a zebrafish model. Results: Both extracts were predominantly composed of flavonoids and their glycosides, yet exhibited clear geographic differences in molecular networking features. Neither extract exhibited cytotoxicity, and both significantly reduced LPS-induced nitric oxide release In Vitro; moreover, at 100 μg/mL, both extracts attenuated neutrophil accumulation in zebrafish to a degree comparable to that of dexamethasone. Discussion: Geographic origin was associated with differences in the profiles of the predominant, putatively annotated flavonoids and their glycosides, as well as in anti-inflammatory activity, suggesting that these metabolites may contribute to the observed effects, although their individual contributions require further confirmation. Conclusion: Overall, both extracts exhibited anti-inflammatory activity In Vitro and in vivo, supporting further isolation of active constituents and development of quality markers for Radix Tetrastigmae.
Introduction/Objective: Endocrine therapy is the cornerstone of treatment for Hormone Receptor-positive (HR+) breast cancer, but its long-term administration is frequently accompanied by multiple adverse effects. Gynostemma pentaphyllum (GP), a traditional Chinese herbal medicine with a long history of ethnomedical application, has been widely used for "tonifying qi, nourishing yin, clearing heat, and resolving dampness." This narrative review aims to synthesize preclinical evidence evaluating the potential and underlying mechanisms of GP as an adjunctive therapy for breast cancer endocrine therapy, integrating its ethnopharmacological basis with modern mechanistic data. Methods: Preclinical studies investigating GP extracts or their bioactive components were systematically collected from PubMed, Web of Science, Scopus, and CNKI (January 2010– December 2025) and narratively synthesized to summarize their multi-target mechanisms in enhancing efficacy and reducing toxicity during endocrine therapy. As a narrative review, a quantitative meta-analysis and a formal risk-of-bias assessment were not performed; however, study characteristics and quality indicators were tabulated for transparency. Results: Preclinical evidence suggests that GP exhibits pleiotropic pharmacological activities that align with its ethnopharmacological properties. For enhanced efficacy, GP potentiates the effects of endocrine drugs and may help overcome drug resistance by modulating key signaling pathways including ERα, PI3K/AKT/mTOR, and STAT3. For toxicity mitigation, GP has been shown in preclinical models to improve lipid and glucose metabolism via activation of AMPK/PPARα pathways, alleviate anxiety, insomnia, and vasomotor symptoms by regulating GABA/5-HT and neurokinin B signaling, reduce systemic inflammation by inhibiting NF- κB/NLRP3 pathways, and exert antioxidant and immunoprotective effects through Nrf2 pathway activation and potential gut microbiota modulation. These effects collectively address the metabolic, neurological, immune, and organ-related challenges associated with long-term endocrine therapy, though primarily based on in vitro and animal studies. Discussion: Based on its ethnopharmacological background and multi-target network, GP shows preclinical promise as a potential integrative strategy for "enhancing efficacy and reducing toxicity" in breast cancer endocrine therapy. These findings should be interpreted within a broader translational context: the multi-target pharmacology of GP is conceptually consistent with the complex, systemic nature of endocrine therapy-related adverse effects, suggesting that a single botanical agent could simultaneously address metabolic, neurological, immune, and organ-related sequelae. However, current evidence is primarily derived from preclinical studies with substantial variability in extract composition and characterization, limiting direct clinical extrapolation. Conclusion: GP exhibits pleiotropic preclinical activities supporting its potential as an adjunctive agent in breast cancer endocrine therapy. High-quality clinical trials are urgently needed to validate its clinical efficacy, safety, optimal dosage, pharmacokinetic profile, herb-drug interaction potential, and potential combinations with emerging therapies.
Natural products play a crucial role in drug discovery, whether as drugs, lead compounds, or cytotoxic payloads of antibody-drug conjugates. Cyclohexadepsipeptides, a class of microbial secondary metabolites, are primarily synthesized by nonribosomal peptide synthetases. They consist of a six-moiety macrocycle with alternating amide and ester bonds between amino acid and hydroxy acid moieties. Notably, compared to their bacterial counterparts, cyclohexadepsipeptides exhibit greater diversity in non-proteinogenic amino acids and more complex post-translational modifications, resulting in richer chemical structures and bioactivities. This review adopts a structure-based classification system, categorizing known fungal-derived cyclohexadepsipeptides into three types according to the number of hydroxy acid moieties (one to three). This study summarizes the source organisms, extraction conditions, and bioactivities of these natural compounds. Analysis reveals that cyclohexadepsipeptides with five amino acids and one hydroxy acid are primarily isolated from marine fungi and most commonly exhibit insecticidal activity, while those cyclohexadepsipeptides with three amino acids and three hydroxy acids are primarily isolated from entomopathogenic or plant endophytic fungi and mainly display anticancer properties. Ethyl acetate, ethanol, and methanol is the most frequently employed extraction solvents. Furthermore, the study attempts to analyze the structure-activity relationships of these natural products. It is not difficult to find that the quantity and arrangement of hydroxy acid moieties in cyclohexadepsipeptides directly affect the bioactivities of these compounds, and the length and type of side chains outside the ring also have an impact on the maintenance of their bioactivities. It is hoped that this work will provide a valuable reference for the application of this type of natural compound in drug discovery.
Introduction: Paracetamol is the most common cause of drug- induced liver injury, which is associated with oxidative stress, cytokine release, and apoptosis. Boswellic acid (BA), with anti- inflammatory and antioxidant effects, can ameliorate liver injury but has poor solubility and bioavailability. The objective of this study was to design boswellic acid nanoparticles (BA-NPs) and test their protective effect against paracetamol-induced liver injury in mice. Methods: BA-NPs were prepared by a surfactant-assisted emulsion method and characterized by UV-Vis spectroscopy, FT-IR analysis, dynamic light scattering (DLS), zeta potential measurements, and transmission electron microscopy (TEM). Acute oral toxicity (LD₂⁽) was assessed in healthy mice. Liver- intoxicated mice were treated with paracetamol (1 g/kg, po) and pretreated for 14 days with BA- NPs (75 mg/kg, po) or silymarin (50 mg/kg). Measurements included serum liver enzymes (ALT, AST, and ALP), lipid profile markers (TC, TG, and HDL), oxidative stress indicators (GSH, CAT, GPx, SOD, and MDA), inflammatory cytokines and their markers (IL- 6 and TNF–α), the apoptotic marker p 53, caspase- 8 and STAT 3 mRNA expression measured by qPCR, and molecular docking simulations to predict boswellic acid's binding affinity to target proteins. Results: The formulated BA- NPs were spherical and monodisperse (54. 54.54 ± 2. 76 nm) with colloidal stability (zeta potential:- 18. 84 mV; PDI: 0. 26). The LD50 was estimated to be 1500 mg/kg, indicating relatively low acute toxicity. BA-NP pretreatment alleviated paracetamolinduced increases in ALT, AST, and ALP; normalized dyslipidemia; restored antioxidant activity; and decreased MDA levels. We observed that the levels of pro- inflammatory cytokines (IL- 6, TNF- α) and p 53 were strongly downregulated. The expression of both caspase-8 and STAT3 was also downregulated by BA-NPs. Molecular docking data showed that boswellic acid bound significantly to caspase-8 (ΔG = -7.97 kcal/mol) and STAT3 (ΔG = -7.95 kcal/mol), supporting its mechanism of hepatoprotection. Discussion: Our results indicate that BA- NPs prepared by Span 60/Tween 80 emulsification provide potent hepatoprotection against paracetamol- induced liver injury through synergistic, multi- mechanistic action, significantly protecting against hepatic injury by concurrently suppressing oxidative stress, inflammatory signaling pathways, and apoptosis, three interconnected molecular events critical to the pathogenesis of paracetamol hepatotoxicity. Conclusion: BA-NPs prepared via emulsification of Span 60/Tween 80 offer potent hepatoprotection against paracetamol-induced liver injury by primarily modulating oxidative stress, inflammation, and apoptosis. This approach not only highlights a potentially novel therapeutic for drug- induced hepatotoxicity but also overcomes the pharmacokinetic barriers of the native boswellic acid agent and provides an improved alternative to currently available drugs.
Background: Curculigo latifolia is a valuable natural resource in Brunei Darussalam with high phytochemical potential and ethnobotanical importance. Methods: The present study investigates the antioxidant activity of C. latifolia Leaves (CL) and C. latifolia Roots (CR) ethanolic extracts using the Oxygen Radical Absorbance Capacity (ORAC) chemical assay and on hydrogen peroxide (H2O2)-induced human keratinocyte (Ha- CaT) cells. The anticancer activity was tested against human colon (HT-29/CD63_nluc) and Pancreatic (PANC-1) cancer cell lines. Gas Chromatography-Mass Spectrometry (GC-MS) was used to identify chemical compounds. Results and Discussion: The GC-MS analysis identified phytol, γ-Tocopherol, vitamin E, and stigmasterol in the extracts. Antioxidant activity of CL and CR extracts evaluated using the ORAC assay was minimal, with values at 28.80 μmol Trolox Equivalent (TE)/L and 25.84 μmol TE/L, respectively, compared to the positive control, ascorbic acid, which reached 97.1 μmol TE/L. Additionally, in H2O2-induced HaCaT cells, pre-treatment with the extracts did not provide significant cellular protection. Moreover, the CL and CR extracts did not exhibit anticancer activities against HT-29/CD63_nluc and PANC-1 cancer cell lines under the conditions tested. Conclusion: CL and CR extracts exhibited promising antioxidant activity via electron donation, but showed limited cytoprotective and anticancer effects, with CR showing a potential response to anti-austerity conditions.
