The global rise in aging populations has made healthy longevity a critical priority in medical research. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), the primary bioactive component of Polygonum multiflorum Thunb. (commonly known as Fallopia multiflora Thunb., He shou wu, Fo-ti, or Polygoni multiflori radix), has emerged as a promising agent for combating aging and age-related diseases. This systematic review evaluates the anti-aging properties of TSG and its protective effects against age-related pathologies. The current evidence demonstrates that TSG exhibits comprehensive anti-aging effects, including lifespan extension, neuroprotection (e.g., ameliorating Alzheimer’s and Parkinson’s diseases), cardiovascular protection (e.g., reducing atherosclerosis and hypertension), delay of gonadal aging, reduction in bone loss (e.g., mitigating osteoporosis), and promotion of hair regrowth. Mechanistically, TSG alleviates oxidative stress, inflammation, and apoptosis while enhancing mitophagy, mitochondrial function telomerase activity, and epigenetic regulation. These multi-target actions align with the holistic principles of traditional Chinese medicine, highlighting TSG’s potential as a multifaceted anti-aging agent. However, further research is required to establish standardized quantitative systems for evaluating TSG’s efficacy, paving the way for its broader clinical application in promoting healthy aging.

Polygoni Multiflori Radix Praeparata (PMRP), a processed root of Polygonum multiflorum Thunb. (known as Zhiheshouwu in Chinese medicine), exhibits anti-aging properties and is used to improve ovarian aging. However, its therapeutic mechanism against premature ovarian insufficiency (POI) remains unclear. This study investigates whether PMRP alleviates POI by inhibiting PANoptosis—a cell death pathway characterized by the concurrent occurrence and interplay of pyroptosis, apoptosis, and necroptosis. POI was induced in rats using tripterygium glycosides. We evaluated the estrous cycle, serum hormone levels (follicle-stimulating hormone [FSH], estrogen [E₂], anti-Müllerian hormone [AMH]), follicular development, and the ultrastructure of granulosa cells. PANoptosome assembly (apoptosis-associated speck-like protein containing a CARD [ASC]/caspase-8/receptor-interacting protein kinase 3 [RIPK3] co-localization) and key effectors of PANoptosis (caspase 3, cleaved caspase 3, gasdermin D [GSDMD], cleaved GSDMD, GSDME, RIPK1, mixed-lineage kinase domain-like protein [MLKL], and p-MLKL) were analyzed. PMRP restored the estrous cycle, lowered FSH levels, and increased E₂ and AMH levels in POI rats. It reduced follicular atresia, preserved primordial follicles, and suppressed PANoptosis-like death in granulosa cells. Mechanistically, PMRP disrupted PANoptosome assembly and downregulated key effectors of PANoptosis. PMRP alleviates POI by inhibiting PANoptosis in granulosa cells, overcoming the previous limitations of targeting single death pathways and providing novel insights into the pathogenesis and treatment strategies for POI.

This study aims to elucidate the active components and underlying molecular mechanisms by which the ethanol-water extract of Cinnamomum migao H.W. Li (MG-EWE) inhibits cardiac fibroblast (CF) transdifferentiation and IL-6 production, providing insights into its anti-myocardial fibrosis effects. The chemical composition of MG-EWE was characterized using UPLC-Q-TOF-MS. Network pharmacology analysis identified active constituents and their mechanisms in inhibiting IL-6 production in CFs. An isoproterenol (ISO)-induced rat CF model was established to evaluate the effects of MG-EWE and its main monomers, Laurolitsine and Hecogenin, on cell proliferation, migration, collagen metabolism, IL-6 production, and key proteins in the ADRB2/JNK signaling pathway. A total of 173 compounds were identified in MG-EWE, with 14 core constituents regulating IL-6 synthesis via 16 key targets, including ADRB2 and MAPK9. Gene Ontology enrichment indicated that MG-EWE affects phosphorylation and the JNK signaling cascade. Molecular docking showed strong binding affinities between Laurolitsine, Hecogenin, and their targets ADRB2 and JNK. Experimentally, MG-EWE, Laurolitsine, and Hecogenin significantly inhibited ISO-induced CF proliferation, migration, and hydroxyproline synthesis, as well as the expression of p-ADRB2, p-JNK, p-c-Jun, and IL-6. MG-EWE inhibits CF transdifferentiation and IL-6 production via the ADRB2/JNK/c-Jun signaling axis, mediated by its constituents Laurolitsine and Hecogenin, highlighting its potential for drug development targeting myocardial fibrosis.

Polygonum multiflorum Thunb. is a widely consumed functional food and dietary supplement in East Asia. However, whether its bioactive component, 2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐D‐glucoside (TSG), can alleviate premature ovarian insufficiency (POI) remains unknown. This study aimed to investigate whether TSG administration alleviates POI in association with suppression of ZBP1/PANoptosis signaling. A tripterygium glycoside‐induced POI rat model was treated with TSG via intraperitoneal injection. Ovarian function was assessed via estrous cycles, hormone assays (FSH, E ₂ , AMH), and histopathology. The formation of the ZBP1/PANoptosome and key executioners of PANoptosis were analyzed by immunofluorescence and Western blot. In triptolide‐injured KGN granulosa cells, TSG's effects were measured by assessing cell viability, apoptosis, lactate dehydrogenase (LDH) release, and PANoptosis activation with or without ZBP1 overexpression. TSG significantly restored estrous cyclicity, improved hormone profiles, and preserved follicular reserve in POI rats. At the molecular level, TSG was associated with reduced ZBP1/PANoptosome formation and downstream executioners (e.g., cleaved Caspase‐3, N‐GSDMD, p‐MLKL). In cells, TSG mitigated cellular injury . Crucially, while ZBP1 overexpression aggravated damage and amplified PANoptosis signaling, TSG co‐treatment significantly reversed these effects, indicating that ZBP1/PANoptosis signaling may be associated with the protective effects of TSG against POI. In conclusion, TSG mitigates POI in association with the suppression of ZBP1/PANoptosis, thereby enhancing the mechanistic understanding of POI pathogenesis and positioning TSG as a candidate for further investigation.