Luteolin (3′,4′,5,7-tetrahydroxyflavone) is a naturally occurring flavonoid found in diverse plant families, including Apiaceae, Brassicaceae and Lamiaceae, and is a major bioactive component of Chinese medicines such as Chrysanthemum morifolium and Perilla frutescens. It possesses antidepressant, anti-inflammatory, antioxidant and neuroprotective activities, and has shown therapeutic potential in depression, Alzheimer’s disease (AD) and Parkinson’s disease (PD). Based on a comprehensive PubMed search, this review examines the shared pathological features-neuroinflammation, oxidative stress and synaptic dysfunction-across these three disorders and elucidates the pharmacological actions of luteolin. Clinical trial data were retrieved from NIH and ICTRP registries. We critically analyze current research limitations, including the lack of validated direct targets beyond PPARγ, the predominance of pathway-based evidence without orthogonal validation, and significant pharmacokinetic defects (low oral bioavailability, rapid glucuronidation, poor BBB penetration). While luteolin holds promise for central nervous system (CNS) disorders, its clinical translation requires advanced drug delivery systems (e.g., nano-formulations, brain-region-specific prodrugs), combination therapies or structural modification, and future cohort studies for prophylactic use. Addressing these priorities will be essential for its therapeutic development.

Ephedra decoction, Mahuangtang (MHT), is a traditional herbal formula comprising Ephedrae sinica (ES), Prunus armeniaca (PA), Cinnamomum cassia(CC), and Glycyrrhiza uralensis (GU). MHT is used to treat colds, influenza, and other respiratory conditions. This study investigates the anticoronaviral effect of MHT and elucidates its mode of action and the active antiviral components of MHT. UHPLC-MS/MS analysis showed the holistic quality and equivalency between MHT and a mixture of four herbal components and identified nine representative compounds in MHT. The inhibitory activity of MHT and its components was examined with HCoV-OC43, SARS-CoV-2, its omicron variants, and pseudotyped lentiviruses. Time-of-addition assay, viral attachment assay, viral penetration assay, virucidal assay, and SARS-CoV-2 Mpro, PLpro, and RdRp activity assay were performed. MHT and its components, ES, CC, and GU, except PA, inhibited coronavirus infection. While MHT, and its components ES, and CC exhibited the suppression of virus entry with a virucidal activity, GU demonstrated inhibition of viral infection in the late stage. PA and its compound, amygdalin, did not inhibit coronavirus infection. Furthermore, Cinnamic aldehyde in CC and liquiritin, liquiritigenin, glycyrrhizin, and glabridin in GU were the active compounds of MHT but not ephedrine alkaloids in ES. MHT and its components inhibited the activity of Mpro and PLpro proteases and RdRp. Molecular docking analysis showed the binding affinity between RdRp and glabridin and between RBD-ACE2 and cinnamic aldehyde. Additionally, we showed that MHT induced the expression of IFN-related antiviral genes by activating the STAT1 pathway. MHT exhibited the potential to function as a multifaceted therapeutic candidate for treating broad-spectrum coronavirus infection by targeting multiple stages of viral infection.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which microglia-mediated neuroinflammation contributes to disease progression. Icariin (ICA), a major bioactive flavonoid from Epimedium, has neuroprotective activity, but how it regulates mitochondrial quality control and inflammatory injury in microglia remains unclear. In the present study, APP/PS1 transgenic mice and Aβ_1-42-stimulated BV-2 microglia were used to examine the effects of ICA on mitophagy, mitochondrial stress, NLRP3/GSDMD-related pyroptotic changes, and neuroinflammation. Behavioral testing, histological analysis, transcriptomic profiling, immunofluorescence, Western blotting, ELISA, molecular docking, molecular dynamics simulation, cellular thermal shift assay, Mdivi-1 co-treatment, and siRNA-mediated Pink1 knockdown were performed. ICA improved cognitive deficits in APP/PS1 mice and reduced microglial inflammatory activation. Transcriptomic and experimental analyses showed that ICA enhanced mitophagy-related responses, restored mitochondrial membrane potential, and reduced excessive mitochondrial reactive oxygen species accumulation. Molecular docking, molecular dynamics simulation, and cellular thermal shift assay supported potential engagement of ICA with PINK1. ICA also reduced NLRP3 inflammasome-associated inflammatory injury, GSDMD-related pyroptotic changes, and IL-1β and IL-18 release. In APP/PS1 mice, Mdivi-1 co-treatment weakened the anti-inflammatory effects of ICA. In Aβ_1-42-stimulated BV-2 microglia, Pink1 knockdown reduced ICA-induced LC3/TOM20 colocalization and partially reversed the inhibitory effects of ICA on NLRP3 inflammasome-associated inflammatory markers. Overall, ICA enhances PINK1-associated mitophagy, alleviates mitochondrial stress, and attenuates NLRP3/GSDMD-related microglial pyroptotic injury in AD-related models. These findings suggest that PINK1-associated mitochondrial quality control contributes to the neuroprotective effects of ICA.

The Shenqi Fuzheng (SQ) formula, made from Codonopsis Radix (Dangshen, DS) and Astragali Radix (Huangqi, HQ), has been used in Traditional Chinese Medicine (TCM) and exhibits cardio-protective effects against acute myocardial infarction (AMI). However, the molecular basis of DS-HQ synergy remains unclear. Here, we combined RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) to explore their synergistic mechanisms. Transcriptomic analyses showed that SQ influenced the AMI network more effectively than either herb alone. ScRNA-seq analysis revealed that these synergistic effects involve both direct and indirect pro-angiogenic pathways. The combination treatment enhanced pro-angiogenic responses in microvascular endothelial subpopulations and promoted angiogenesis in the border zone. It also enhanced the anti-inflammatory role of a specific reparative macrophage subset and stimulated vascular endothelial growth factor A (VEGFA) secretion from these cells, supporting the VEGFA-VEGFR signaling between macrophages and microvascular endothelial cells. This coordinated regulation provides a plausible mechanistic explanation for the reduced infarct size and improved cardiac outcomes seenin vivo, highlighting the therapeutic value of TCM.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease closely associated with aging, yet the contribution of cellular senescence to fibrotic remodeling and its therapeutic implications remain incompletely understood. Syringin, a phenylpropanoid glycoside derived from Acanthopanax senticosus, has been reported to possess anti-inflammatory and antioxidant activities, but its role in IPF has not been elucidated. In this study, bulk lung transcriptomic data from the GTEx project and nine IPF cohorts were integrated with IPF scRNA-seq data to characterize senescence-associated fibrotic programs. A systems-level compound prioritization strategy incorporating reversed gene expression scoring, network proximity analysis, drug-likeness and toxicity evaluation was applied to identify candidate molecules. The results revealed a pronounced aging-associated transcriptomic profile in IPF lungs, with strong concordance between age-related and IPF-related gene programs. Single-cell analyses further identified senescent fibroblast populations as key cellular hubs characterized by elevated expression of SASP factors. Syringin was subsequently validated in TGFβ1–stimulated fibroblasts, and a murine model of bleomycin-induced pulmonary fibrosis. Syringin consistently attenuated fibroblast activation, cellular senescence markers, and pulmonary fibrosis in vivo and in vitro. Mechanistically, syringin markedly reversed the activation of replication stress–associated signaling pathways. Molecular docking and CETSA suggested a potential interaction between syringin and CHK1. Furthermore, CHK1 knockdown partially abrogated the regulatory effects of syringin on the ATR/CHK1–p53 signaling cascade, supporting CHK1 as a functional mediator of syringin activity. Collectively, these findings identify syringin as a natural small molecule with anti-senescent and anti-fibrotic properties, and may represent a potential therapeutic strategy for IPF.

Alzheimer’s disease (AD) is a severely debilitating condition that significantly hampers independent living, with no effective treatments currently available. Traditional Chinese medicine (TCM) has shown substantial promise in both preventing and alleviating AD symptoms. The medicinal properties-specifically hot, warm, cool, and cold-serve as a critical link between TCM theory and clinical application. However, the majority of research has concentrated on individual herbs for AD, with relatively few comprehensive studies exploring the biological mechanisms through which these herbs exert their medicinal properties. In this context, data mining, network pharmacology, and multi-omics approaches, including metabolomics, gut microbiota analysis, and proteomics, were employed to elucidate the effects and mechanisms of action of three hot/warm property herbs (THPH) and three cold/cool property herbs (TCPH) in the treatment of AD. Findings indicated that the herbs effective against AD primarily possess warm properties. THPH demonstrated a significant enhancement in cognitive, learning, and memory functions in AD rat models when compared to TCPH, potentially achieving therapeutic effects by boosting the synthesis of the neurotransmitter acetylcholine. Furthermore, THPH modulated energy metabolism, corrected metabolic imbalances in both brain and serum within AD rat models, inhibited oxidative stress, restored synaptic plasticity-related proteins and signaling pathways, and maintained intestinal microbiota homeostasis. Consequently, this study offers valuable insights into the therapeutic implications of the hot (warm) and cold (cool) properties of TCM in the management of Alzheimer’s disease.

Gypensapogenin I (GI) is a new dammarane type triterpenoid saponin extracted from Gynostemma pentaphyllum. This study explored the therapeutic potential and mechanism of GI on liver fibrosis (LF). LF is a key pathological stage of chronic liver disease, and the current treatment is limited. In the mouse LF model induced by carbon tetrachloride (CCl₄) and the LX-2 hepatic stellate cell model activated by transforming growth factor-β1 (TGF-β1), GI showed significant antifibrotic effects in vitro and in vivo, and could reduce liver injury, inflammation, collagen deposition and cell activation. Mechanistic studies have shown that GI exerts its effect by directly targeting MST1 protein. The direct and specific interaction between GI and MST1 was confirmed by surface plasmon resonance (SPR), drug affinity reaction target stability (DARTS) and cell thermal transition analysis (CETSA). Site directed mutagenesis further identified Arg181 as a key residue necessary for the stable binding of GI to MST1. This binding activated the Hippo signaling pathway, promoted the phosphorylation of MST1, LATS1/2 and YAP, resulting in the retention and inactivation of YAP in the cytoplasm. More importantly, after knockdown ofSTK4 gene encoding Mst1 by siRNA, the antifibrotic effect of GI was completely abolished, thus establishing MST1 as its essential functional target. In summary, this study found that GI is a novel MST1 agonist, which alleviates LF by targeting Arg181 residue, restoring Hippo/YAP pathway homeostasis and inhibiting hepatic stellate cell activation, which makes GI a promising candidate drug in the treatment of LF.

Chemical research on the fungus Bipolaris sp. led to the identification of seven ent-kaurane diterpenoids, kaurepenoids A–G (1–7), marking the first isolation of such diterpenoids from this genus. Kaurepenoids A–F (1–6) represent the first 2-nor-ent-kaurane diterpenoids with a fused 5/6/6/5 tetracyclic ring system. Kaurepenoid G (7) bears a rare 2,3-epoxy-ent-kaurane skeleton. Their structures and absolute configurations were elucidated by NMR, ECD calculations, and single-crystal X-ray diffraction analyses. Putative biosynthetic pathways for kaurepenoids A–F were proposed. Furthermore, the derivatization of both kaurepenoids B and C as starting materials afforded five derivatives (8–12). Among these compounds, kaurepenoid A could increase the efficacy of anticancer drug paclitaxel (PTX) by 204-fold at 20 μmol·L⁻¹. Mechanistic investigation demonstrated that kaurepenoid A could inhibit the transport function of P-glycoprotein (P-gp) rather than affecting its expression, and the possible recognition mechanism was predicted by molecular docking.

Two unprecedented rearranged fusicoccane diterpenoids, hyperperins A (1) and B (2), and twenty-two new fusicoccane diterpenoids, hyperperins C–X (3–24), were isolated from the aerial parts of Hypoestes purpurea, as well as one known analog (25). The structures and absolute configurations of all newly isolated compounds were determined through comprehensive analyses, including NMR spectroscopy, HR-ESI-MS, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Structurally, compounds 1 and 2 were characterized by a previously unreported carbon skeleton featuring a 5/7/5/3 tetracyclic ring system. Compounds 19 and 20 represent the first examples of fusicoccane diterpenoids with epoxy groups at C-2/C-6 and C-6/C-7, respectively. A plausible biosynthesis pathway for compounds 1 and 2 was proposed. Additionally, compounds 1, 2, 3, 7, and 25 exhibited potent inhibitory activity against the Ca_v3.1 calcium channel with IC₅₀ values of 15.06 ± 1.19, 9.00 ± 1.04, 6.04 ± 0.67, 14.00 ± 1.20, and 6.26 ± 0.82 μmol·L⁻¹, respectively. These findings enrich the structural diversity of fusicoccane diterpenoids and provide promising lead compounds for the development of Ca_v3.1 calcium channel inhibitors.