Panax quinquefolius saponins promote remyelination via orchestrating HMGCS1-NPC1-MAL-mediated lipid metabolism and rebalancing JAK-STAT signaling in a cuprizone-induced demyelination model.

Combined clemastine fumarate and selenomethionine promote remyelination via PI3K/Akt/mTOR signaling in experimental multiple sclerosis.

Forsythoside A Alleviates Hypertensive Nephropathy by Promoting Mitophagy and Inhibiting Ferroptosis via ASCL1-CCNB1/mTOR Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE Forsythiae Fructus, a classic heat-clearing and detoxifying herb in traditional Chinese medicine (TCM), is widely used for inflammatory conditions. Its primary bioactive component, Forsythoside A (FTA), exhibits potent anti-inflammatory and antioxidant activities. Given that hypertensive nephropathy is characterized by chronic inflammation, oxidative stress, and fibrosis-hallmarks that correspond to "heat" and "toxin" pathologies in TCM theory-Forsythiae Fructus represents a rational candidate for HN therapy. However, the precise mechanisms by which FTA inhibits HN progression remain incompletely elucidated. AIM OF THE STUDY This study aims to investigate the protective effects of FTA against Ang II-induced HN and to elucidate the underlying signaling mechanisms. MATERIALS AND METHODS We established HN models in C57BL/6 mice and NRK-52E cells using Ang II. The effects of FTA on renal injury were investigated through renal dysfunction indicators and tissue staining. RNA sequencing, molecular docking, CETSA and SPR technologies were employed to explore potential target sites and mechanisms of FTA in renal injury. RESULTS FTA mitigated Ang II-induced renal injury by reducing renal dysfunction markers (Cr, BUN and Alb/Cr), restoring renal tissue architecture, and decreasing inflammatory markers (Ilb, Il6, Tnf), without exerting antihypertensive effects. RNA sequencing revealed associations with mTOR and ASCL1.Taken together, our in vivo and in vitro data reveal that FTA binds to ASCL1 and inhibits its activity, subsequently blocking the downstream CCNB1/mTOR pathway to confer renal protection. This inhibition promotes mitophagy and inhibits ferroptosis, ultimately alleviating renal injury. CONCLUSIONS This study confirmed that FTA can bind to ASCL1, targeting the ASCL1-CCNB1/mTOR pathway to protect the kidney from Ang II-induced injury, offering broad therapeutic prospects for the treatment of HN.

Panax notoginseng saponins (PNS)alleviates rheumatoid arthritis by regulating HIF-1α/PKM2-mediated glycolysis to inhibit Th17 differentiation

Polydatin improves mitochondrial dynamics dysrhythmia by regulating BMAL1 to prevent and treat metabolic dysfunction-associated fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE Polygonum cuspidatum, a traditional Chinese medicine indicated for "blood stasis" and "damp-heat" disorders (e.g., arthralgia, jaundice, amenorrhea), has modern relevance as these conditions correlate with dyslipidemia, inflammation, and microcirculatory issues. Its main constituent, polydatin (PD), exhibits multiple bioactivities, yet its role in metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. AIM OF THE STUDY To elucidate the mechanisms by which PD alleviates MAFLD through BMAL1-mediated mitochondrial dynamics. MATERIALS AND METHODS FFA-induced HepG2 cells and HFD-induced MAFLD rats were used to evaluate the effects of PD on hepatic lipid accumulation, mitochondrial function, and oxidative stress immune imbalance via histological staining and biochemical assays. Additionally, molecular docking, molecular dynamics simulations, and BMAL1 knockdown experiments were conducted to identify potential upstream regulators. RESULTS PD significantly suppressed lipid accumulation, reduced levels of ROS, MDA, NLRP3, TNF-α, and IL-1β, while enhancing SOD activity, thereby alleviating oxidative stress-immune imbalance. PD increased mitochondrial membrane potential (MMP), ATP content, and mtDNA copy number, reversing mitochondrial dysfunction. Notably, PD improved expression rhythms of BMAL1 and mitochondrial dynamics-related genes (DRP1, OPA1, MFN1, MFN2, FIS1), normalizing their amplitude and phase. Concurrently, PD activated the mitochondrial autophagy pathway by upregulating PINK1 and PARKIN expression, thereby facilitating timely clearance of impaired mitochondria. Most importantly, all the aforementioned therapeutic benefits of PD were abolished upon BMAL1 knockdown, establishing BMAL1 as an essential target for PD's action. CONCLUSION This is the first study to demonstrate that PD alleviates MAFLD by mediating BMAL1-regulated circadian rhythms of mitochondrial dynamics, positioning PD as a potential therapeutic candidate for MAFLD.

Treatment with Biaoxu Ganmao Granules ameliorates cyclophosphamide-induced immunosuppression in mice: Paeoniflorin-associated modulation of the TLR4/NF-κB pathway.

BXGG partially reversed CTX-associated reductions in body weight, thymus and spleen indices and partially restored serum interleukin-2, interleukin-4 (IL-4), and interferon-gamma (IFN-γ) levels, and white blood cell, lymphocyte, platelet, and reticulocyte counts.

Atractylodes macrocephala Koidz. Polysaccharides Alleviate Liver Fibrosis in Association With Suppression of cGAS-STING Signaling and Mitochondrial Apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE Atractylodes macrocephala Koidz. is a premier tonic herb in East Asian medicine, traditionally used to strengthen the spleen, resolve dampness, and treat digestive ailments. While its clinical efficacy in metabolic and immune disorders is well-recognized, the specific therapeutic potential and molecular mechanisms of Atractylodes macrocephala Koidz. polysaccharides (AMPs) against liver fibrosis remain to be fully elucidated. AIM OF THE STUDY This study aimed to evaluate the hepatoprotective and anti-fibrotic effects of AMPs and to examine the associated mechanisms, with emphasis on mitochondrial injury-related indicators and cGAS-STING/NLRP3 inflammatory activation. METHODS Liver fibrosis was induced in C57BL/6 mice using three etiologically distinct and complementary models: a methionine-choline-deficient (MCD) diet, carbon tetrachloride (CCl4) injections, and bile duct ligation (BDL). AMPs (100 and 200 mg/kg) were administered daily by oral gavage. Liver injury, fibrosis severity, and macrophage infiltration were assessed using histopathology, immunohistochemistry, and biochemical analyses. Transcriptomic profiling was used to identify differentially expressed genes, and the association of AMPs with mitochondrial DNA (mtDNA)-related danger signaling and cGAS-STING inflammatory activation was examined by qPCR, immunofluorescence, and Western blotting. RESULTS AMPs consistently attenuated liver injury and fibrosis across all three models, accompanied by reduced STING activation predominantly localized to F4/80+ macrophages and decreased CD68+ macrophage infiltration. These improvements were associated with suppression of the cGAS-STING-NLRP3 inflammatory cascade and downregulation of macrophage-related transcriptional programs, concordant with improved biochemical indices and fibrosis severity. CONCLUSION Collectively, these findings suggest that AMPs exert antifibrotic activity in experimental liver fibrosis. This activity was associated with reduced cGAS-STING/NLRP3 inflammatory activation and modulation of mitochondria-associated apoptotic signaling, supporting further focused mechanistic evaluation of AMPs in fibrotic liver disease.