The phytochemical investigation of Veratrum mengtzeanum Loes. roots resulted in the isolation and characterization of two novel, namely Mengtzeanines A (1), Mengtzeanines B (2), and eight known steroidal alkaloids (3–10). Their structural properties were assessed though extensive spectroscopic techniques. All constituents 1–10 were analyzed for suppression of NO formation in LPS-induced RAW264.7 macrophages. Among them, constituent 6 (Verazine) showed inhibition against LPS-induced NO production (IC₅₀ = 20.41 μM). Additionally, compound 6 could inhibit the secretion of IL1β, IL6, and TNFα, and downregulate the productions of iNOS and COX2 in LPS-induced RAW264.7 macrophages. Further experiments revealed that 6 exhibited a potent anti-inflammatory level in LPS-stimulated RAW264.7 macrophages via inhibiting NF-κB, and triggering of Keap1/Nrf2/HO-1 axis, implying that compound 6 may be a promising candidate for treating inflammatory disorders.

The tetrahydro-β-carboline heterocycle is a privileged scaffold found in numerous natural products and bioactive drugs, demonstrating significant potential for cancer therapy. In this study, we designed and synthesized 33 novel tetrahydro-β-carboline derivatives (2–34) based on this core structure and evaluated their anticancer activity against human lung cancer (A549). Among them, compounds 8 and 16 exhibited potent cytotoxicity against A549 cells, effectively suppressing cell migration and colony formation. Mechanistic studies revealed that these compounds promoted apoptosis by upregulating pro-apoptotic Bax, downregulating anti-apoptotic Bcl-2, and activating caspase proteins. Molecular docking and dynamics simulations demonstrated that compounds 8 and 16 form stable complexes with the Eg5 protein through multiple hydrogen bonds, which was further validated by thermal shift assays. Collectively, these findings indicate that compounds 8 and 16 induce apoptosis in A549 cells by selectively targeting and stabilizing Eg5, highlighting their potential as lead candidates for lung cancer therapy.

As a traditional Tibetan medicine and health food, the fleshy roots of Sphallerocarpus gracilis were adopted to extract polyphenol powder(PP) in this research. Using a DSS-induced colitis mouse model combined with multi-omics analysis and experimental validation, we explored the protective effects and molecular mechanisms of PP against intestinal inflammation. PP mitigated colitis-related symptoms in a dose-dependent manner, inhibited pro-inflammatory cytokines and dose-dependently reversed elevated IL-10 levels to BC group. Multi-omics data revealed that PP intervention was associated with gut microbiota remodeling, enrichment of Akkermansia muciniphila, restoration of bacterial–fungal homeostasis, and improvement of tryptophan and biotin metabolism. By suppressing HMGB1 and RAGE expression, PP blocked the AGE-RAGE-mediated inflammatory cascade. In addition, PP maintained intestinal mucosal integrity through goblet cell protection, MDA reduction, and the regulation of BAX/Bcl-2, MMP3 and MMP9. Overall, PP relieves UC by regulating gut microecology, host metabolism and the AGE-RAGE pathway, which supports the translational potential of natural polyphenols for inflammatory bowel disease treatment as a gut microecological modulator.

Background: Solar dermatitis (SD) is an inflammatory skin disease caused by excessive exposure to ultraviolet (UV) radiation. Gastrodia elata (GE) is a medicinal and edible plant with broad pharmacological activities; however, the polarity distribution of its active components and their specific mechanisms of action in SD remain incompletely understood. Methods: Different polarity fractions of GE-petroleum ether extract (PEE), ethyl acetate extract (EAE), and n-butanol extract (NBAE) were prepared and evaluated in a UVB-induced SD mouse model. We integrated metabolomics, network pharmacology, molecular docking, molecular dynamics simulations, and molecular biology techniques to identify key active ingredients and regulatory mechanisms. Results: The EAE group significantly ameliorated epidermal thickening and collagen damage in SD mice. Mechanistically, EAE and its active component luteolin (LUT) likely suppressed abnormal activation of the JUN pathway (binding energy: −9.1 kcal/mol), leading to downregulation of the pro-inflammatory cytokines tumour necrosis factor-alpha and inerleukin-1 beta. Conclusions: The EAE fraction alleviates SD through multi-component, multitarget synergistic effects, with LUT as a core bioactive component that inhibits the JUN pathway to mitigate skin inflammation and oxidative damage. EAE also accelerated SD recovery by modulating critical metabolic pathways, including arginine biosynthesis and terpenoid backbone biosynthesis. These findings identify EAE and LUT as promising candidate therapeutics for SD.