Heat stress (HS), a pervasive environmental stressor, significantly disrupts systemic physiological homeostasis, posing substantial threats to human and animal health. Sheng Mai San (SMS), a classic Traditional Chinese Medicine (TCM) formula, exerts its therapeutic effects by replenishing qi (the vital energy governing physiological functions) and nourishing yin (the material basis responsible for moistening and cooling actions). This formula demonstrates significant efficacy in astringing sweating and preventing collapse. However, its precise molecular mechanisms against HS-induced myocardial injury remain incompletely elucidated. This study initially employed physicochemical analytical methods to determine the contents of total polysaccharides, saponins, and flavonoids in SMS and evaluated its antioxidant activity. Subsequently, both in vitro and in vivo rat models of HS were established to systematically assess the alterations in reactive oxygen species (ROS), antioxidant enzymes (GSH, SOD, CAT), and heat shock proteins (HSP70, HSP90) following SMS intervention, thereby investigating HS-induced myocardial injury and the protective effects of SMS. Furthermore, Western blot, immunofluorescence, and qRT-PCR techniques were utilized to quantitatively analyze key molecules in the Keap1-Nrf2-HO-1 and Stub1-HSF1 signaling pathways. The results demonstrated that total polysaccharides were the most concentrated in SMS, followed by total saponins. This formula exhibited potent free radical scavenging capacity against DPPH, ABTS, and OH⁻, along with significant reducing activity. HS-induced myocardial injury reached its peak severity at 6-12 h post-stress exposure. SMS intervention effectively suppressed excessive ROS generation, enhanced the activities of antioxidant enzymes (GSH, SOD, and CAT), and downregulated HSP70 and HSP90 mRNA expression levels, thereby significantly mitigating cardiomyocyte damage. Mechanistic investigations revealed that SMS conferred cardioprotection through dual modulation of the Keap1-Nrf2-HO-1 and Stub1-HSF1 signaling pathways. This study not only provides a novel TCM-based therapeutic strategy for preventing and treating HS-related cardiovascular disorders but also establishes a crucial theoretical foundation for further exploration of SMS’s pharmacological mechanisms and clinical applications.

Pyrrolizidine alkaloids (PAs), a category of naturally occurring secondary metabolites, are commonly found in various botanical sources. Accumulating evidence indicates that PAs and their biologically active metabolites can interact with cellular components and trigger a variety of toxic effects in animals and humans. Notably, PAs exhibit significant hepatotoxic potential via nutritional supplements, environmental dissemination, food chain contamination, and broader ecological pollution. In this review, we summarize PA-induced hepatotoxicity in humans and animals and the underlying molecular mechanisms. It involves oxidative stress, mitochondrial dysfunction, apoptosis, ER stress, inflammation, autophagy, and ferroptosis. Several key signaling pathways, such as nuclear factor-erythroid 2 related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), protein kinase RNA-like endoplasmic reticulum kinase (PERK), toll like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), transforming growth factor beta (TGF-β), p53, farnesoid X receptor (FXR), and pregnane X receptor (PXR), are also implicated. Furthermore, this review discusses diagnostic approaches, metabolic activation pathways, and detoxification strategies targeting PA-induced liver injury. Collectively, this review provides a comprehensive understanding of the molecular basis of PA hepatotoxicity and underscores the urgent need for improved risk assessment, early diagnosis, and effective detoxification interventions to mitigate PA-related liver diseases in humans and animals.

Background/Objectives: Calf diarrhea is a serious health problem in dairy farming, which seriously affects their production performance in adulthood. Diarrhea in calves is usually treated with antibiotics, which may lead to issues of antibiotic residue and resistance. Therefore, finding antibiotic alternatives is of critical importance. Yigong San (YGS) is a traditional Chinese medicine formula traditionally indicated for inflammatory gastrointestinal disorders. This study aimed to investigate whether YGS can be used as an alternative to antibiotics for the effective treatment of calf diarrhea and the underlying mechanisms. Methods: Ten healthy Holstein calves served as the control (Ctrl) group, while twenty diarrheic calves were randomly assigned to either a natural diarrhea (ND) group or a YGS treatment (YGS) group, which received YGS for seven days. Serum samples were collected post-treatment and analyzed for biochemical parameters, oxidative stress indicators, cytokine levels, and metabolomic profiles. Results: The results showed that YGS effectively alleviated diarrhea and improved abnormal biochemical indicators. YGS significantly increased serum levels of CAT, GSH-PX, and SOD, while reducing MDA levels. In addition, YGS also suppressed the expression of multiple proinflammatory cytokines, including IL-1α, TNF-α, IL-1β, IL-17A, IL-18, IL-21, IFN-γ, as well as chemokines CXCL9 and CXCL10. Metabolomic analysis revealed that YGS treatment significantly improved metabolic disorders and enriched the Arginine and Proline Metabolism pathways. The metabolites 1-methylhydantoin and ornithine were significantly and negatively correlated with pro-inflammatory cytokine levels. Conclusions: YGS effectively treats calf diarrhea by enhancing antioxidant capacity, reducing inflammatory factor levels, regulating immune function, and modulating serum metabolites. It provided valuable insights for the development of safe and effective antibiotic alternatives for preventing and treating calf diarrhea.