Yindan Pinggan Capsules alleviates acetaminophen-induced liver injury by modulating ferroptosis via the system Xc−/GSH/GPX4 axis and the LPCAT3–ACSL4 pathway

Yinchenhao Decoction Alleviates Liver Injury in CYP2D6-Induced Autoimmune Hepatitis Mice: An Integrated Transcriptomic and Proteomic Analysis.

Mangiferin mitigates mercuric chloride-induced hepatotoxicity: targeting Nrf2, NF-κB, NLRP3, and ER stress.

Man could be considered as a potential protective agent against HgCl2-induced liver injury through controlling oxidative stress, inflammation, and apoptosis.

Dendrobium nobile Lindl. alleviates acute alcoholic liver injury in mice by modulating bile acid metabolism via the enterohepatic circulation.

ETHNOPHARMACOLOGICAL RELEVANCE Dendrobium nobile Lindl. (DNL), a traditional Chinese medicine used for over two millennia, is attached for nourishing Yin, clearing heat, and promote fluid production. Despite its hepatoprotective potential, the underlying mechanisms need to be further explored. AIM OF THE STUDY This study aimed to investigate the protective effects and further elucidate the mechanisms of Dendrobium nobile Lindl. aqueous extract (DNAE) from two different geographical origins (Chishui and Haikou) against acute alcoholic liver injury (AALI) using an integrated approach, with a particular focus on the modulation of bile acid metabolism via the enterohepatic FXR signaling pathway. MATERIALS AND METHODS In this study, an acute alcoholic liver injury (AALI) mouse model was established by a single intragastric administration of 53% alcohol, following 14 consecutive days of pretreatment with DNAE from Chishui or Haikou. Physiological and pathological changes were evaluated, and the hepatic BA profiles were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chemical compositional differences between DNL from Chishui and Haikou were characterized by UPLC-Q/TOF-MS and GC. The expression levels of genes involved in BA synthesis and metabolism were measured in both liver and intestine by quantitative real-time PCR (qRT-PCR). Additionally, Fxr-knockout mice were employed to verify the role of FXR in the observed effects. RESULTS DNAE from both Chishui and Haikou origins significantly ameliorated alcohol-induced physiological and pathological alterations. The chemical composition of DNL, particularly the profile of secondary metabolites and the content of dendrobine, remains largely consistent between Chishui and Haikou origins. DNAE restored the metabolic balance of hepatic BAs by reducing primary BAs (CA, CDCA, βMCA, αMCA) and secondary BAs (DCA, LCA). Notably, DNAE derived from Chishui exhibited a more pronounced regulatory effect, specifically in enhancing the abundance of taurine-conjugated BAs. Consistently, DNAE pretreatment upregulated the hepatic BA synthase genes Cyp8b1 and Cyp7a1, downregulated the BA metabolism-associated genes Fxr and Shp. In Fxr-knockout mice, DNAE treatment did not attenuate alcohol-induced liver injury. Interestingly, DNAE increased the expression of intestinal BA metabolism genes Fxr and Fgf15, triggered extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) signaling to downregulate Cyp7a1 expression and inhibits BA synthesis. CONCLUSION DNAE from both Chishui and Haikou origins alleviates acute alcoholic liver injury in mice by modulating bile acid metabolism via the enterohepatic FXR signal pathway, with the Chishui origin showing a more potent regulatory effect on taurine-conjugated BA abundance.

Xuebijing alleviates acute hydrogen sulfide-induced pyroptosis in rat spleen via suppression of the caspase-1/NLRP3 pathway

Hydrogen sulfide (H2S) is a pervasive environmental toxicant with well-established immunotoxic effects. However, its action on lymphoid organs—particularly whether it triggers splenic pyroptosis—remains elusive. This study explored the effect of acute H2S exposure on rat spleen and the therapeutic potential of Xuebijing (XBJ), a traditional Chinese medicine for sepsis. Rats were exposed to 300 ppm H2S for 3 h, with or without 7-day XBJ pretreatment (4 mg/kg, i.p.). Splenic injury was evaluated by histopathology, ultrastructure, oxidative stress parameters, immunofluorescence, and immunoblotting. H2S exposure alone caused marked splenic damage, evidenced by increased organ coefficient, disrupted tissue architecture, mitochondrial swelling, and redox imbalance [depleted glutathione (GSH), superoxide dismutase (SOD), catalase (CAT); elevated malondialdehyde (MDA)]. Mechanistically, H2S activated the NF-κB/NLRP3/caspase-1 axis, upregulating NLRP3, ASC, cleaved caspase-1, and GSDMD-N, along with elevated interleukin-1β (IL-1β) and interleukin-18 (IL-18). XBJ pretreatment reversed these alterations, suppressing NF-κB phosphorylation, inflammasome assembly, and pyroptotic cell death. These findings demonstrate that H2S induces splenic pyroptosis via the NF-κB/NLRP3/caspase-1 pathway, and that XBJ confers protection by interrupting this cascade, offering a mechanism-based candidate for the treatment of acute H2S poisoning.

Desaminotyrosine Alleviates Hepatic Ischemia-Reperfusion Injury via the MAPK/Ferroptosis Axis and Bifidobacterium pseudolongum Modulation.

Ischemia-reperfusion (I/R) is a common and unavoidable phenomenon during surgeries such as hepatectomy and liver transplantation, severely affecting patient prognosis. However, clinically intervention and treatment measures remain very limited. Using human hepatocyte organoid hypoxia-reoxygenation (H/R) and murine hepatic ischemia-reperfusion (I/R) models, we demonstrate that the microbiota-derived flavonoid desaminotyrosine (DAT) attenuates I/R-induced hepatic injury by suppressing inflammation and apoptosis while promoting the abundance of probiotic Bifidobacterium in the gut. Through integrated spatial transcriptomics and metabolomics, we identified that DAT specifically alters the MAPK signaling pathway/ ferroptosis gene transcriptome in the portal vein (PV) zones, promotes the production of antioxidants (taurine) in the central vein (CV) zones, reduces the level of pro-ferritinosis substrates (arachidonic acid), thereby enhancing the expression of GPX4 and Nrf2, inhibiting ferroptosis, then ameliorate hepatic I/R injury. Meanwhile, the pseudo-germ-free mouse model confirmed that DAT alleviated hepatic I/R injury in a gut microbiota dependent manner. DAT reduces hepatic I/R injury by increasing the abundance of gut Bifidobacterium pseudolongum (Bif). Our research results reveal a novel microbial metabolite that improves hepatic I/R injury, clarify the inhibitory effect of DAT on ferroptosis, discover new therapeutic uses of DAT, and identify Bif as a potential novel probiotic for preventing liver I/R injury, providing new options for the preventive treatment of liver I/R injury.

"Radiation-Synthesized Gallotannin Hydrogel Attenuates Trisenox-Induced Nephrotoxicity in Rats: miR-223/TXNIP Axis Modulation of Oxidative Stress and Inflammation".

Arsenic trioxide (ATO) is a potent therapeutic agent against acute promyelocytic leukemia; nevertheless, its clinical utility is severely restricted by dose-limiting nephrotoxicity. This study investigated the protective potential of a radiation-synthesized gallotannin hydrogel (GTH) against ATO-induced kidney injury in rats. Forty male Wistar rats were randomized into four experimental groups: Control, ATO (4 mg/kg, i.p., for 4 weeks), GTH (2 mg/kg, i.p.), and ATO + GTH. GTH treatment was initiated during the third week of ATO administration, with GTH being administrated one hour prior to ATO injection. Following the experimental period, animals were sacrificed, tissue histology was examined, and renal function was assessed by serum urea and creatinine levels. Oxidative stress was evaluated via MDA, SOD, GSH, and GPx markers. Additionally, miR-223 and TXNIP expression levels were quantified using qRT-PCR. Inflammatory mediators (NF-κB, NLRP3, Caspase-1, IL-1β, and IL-18), endoplasmic reticulum (ER) stress markers (PERK, eIF2α, and CHOP), and the apoptotic marker caspase-3 were analyzed by ELISA. Our results revealed that GTH noticeably ameliorated kidney dysfunction, as evidenced by reduced serum urea and creatinine levels. Furthermore, GTH attenuated oxidative stress by decreasing MDA levels and restoring antioxidant enzyme activities (SOD, GSH, and GPx). Histological analysis confirmed that GTH mitigated structural renal damage. Molecularly, GTH administration suppressed the ATO-induced upregulation of miR-223 and TXNIP. This downregulation correlated with a reduction in inflammatory mediators, attenuation of ER stress markers, and decreased apoptosis. These findings demonstrate that radiation-synthesized gallotannin hydrogel (GTH) exerts nephroprotective effects against ATO-induced nephrotoxicity. These benefits are driven by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms mediated via modulation of the miR-223/TXNIP axis.