Consun Pharmaceutical Group Ltd.

Acetaminophen (APAP) overdose has long been recognized as the main cause of drug-induced liver injury (DILI), characterized by glutathione (GSH) depletion and reactive oxygen species (ROS) accumulation, leading to ferroptosis and inflammatory responses. There is an urgent need for liver-protective agents to combat ferroptosis, modulate oxidative stress, and ameliorate inflammation. Catechin, a well-known polyphenol compound, has been shown to have antioxidant potential. However, its protective role on APAP-induced liver injury (AILI) has not been elucidated. In this study, we evaluated the modulating effects of catechin on AILI and observed that catechin attenuated liver injury by reducing inflammation. Mechanistically, catechin alleviated hepatic oxidative stress by inhibiting ROS accumulation, malondialdehyde (MDA) production, and GSH depletion. Furthermore, catechin, as a hepatic injury reparative agent, could counteract APAP-induced hepatocyte ferroptosis by activating the xCT/GPX4 pathway, and is expected to be a novel natural inhibitor of ferroptosis. Additionally, the transcriptomic results indicated that the inhibition of Stat1 by catechin is important for the management of AILI. Inhibition of signal transducer and activator of transcription 1 (STAT1) expression, achieved through the use of the STAT1 inhibitor fludarabine in vivo and small interfering RNA (siRNA) in vitro, was confirmed to attenuate APAP-induced ferroptosis. In conclusion, the present study identified a novel natural drug inhibitor of ferroptosis and revealed its mechanism of action to inhibit ferroptosis, regulate oxidative stress, and ameliorate inflammation in AILI. This further provides new insights into the novel natural ferroptosis inhibitors for the treatment of ROS-related inflammatory diseases.

Type 17 T helper (Th17) cells, which are a subtype of CD4⁺ T helper cells, secrete pro-inflammatory cytokines such as IL-17A, IL-17F, IL-21, IL-22, and GM-CSF, which play crucial roles in immune defence and protection against fungal and extracellular pathogen invasion. However, dysfunction of Th17 cell immunity mediates inflammatory responses and exacerbates tissue damage. This pathological process initiated by Th17 cells is common in kidney diseases associated with renal injury, such as glomerulonephritis, lupus nephritis, IgA nephropathy, hypertensive nephropathy, diabetic kidney disease and acute kidney injury. Therefore, targeting Th17 cells to treat kidney diseases has been a hot topic in recent years. This article reviews the mechanisms of Th17 cell-mediated inflammation and autoimmune responses in kidney diseases and discusses the related clinical drugs that modulate Th17 cell fate in kidney disease treatment.

Yi-Shen-Hua-Shi (YSHS) granule is a modern Chinese patent drug for treating chronic glomerulonephritis (CGN). It is derived from a traditional Chinese medicine formula Sheng-Yang-Yi-Wei decoction that is used to treat CGN in ancient China. Pharmacological activities of YSHS granule have not been reported. In this work, we investigated the anti-CGN effects and TGFβ signaling-related mechanism of action of this herbal drug.

The rat model of CGN was established by injection of cationization-bovine serum albumin (C-BSA) for five weeks. After finishing C-BSA injection, drugs were intragastrically administered to the rats once daily for four weeks. Clinical signs were recorded daily. Serum and urine biochemical parameters were analyzed by respective kits. Protein levels were examined by Western blotting. Pathological changes of renal tissues were evaluated by HE and Masson's trichrome staining.

No significant differences in clinical signs and body weights were found among normal, model and drug treatment groups. Proteinuria; albuminuria; increased urine volume; elevated urea nitrogen, creatinine, total cholesterol and triglyceride levels in sera; decreased serum total protein and albumin; as well as renal pathological damage and fibrosis were observed in CGN model rats. YSHS granule ameliorated all the abnormal behavioral and biochemical changes in the model rats. Mechanical investigations showed that YSHS granule down-regulated proteins levels of TGFβ1, phospho-Smad2/3 (Thr 8) and Smad4 in rat renal tissues. In conclusion, YSHS granule demonstrates therapeutic effects in a rat model of CGN, and inhibition of the TGFβ/Smad signaling pathway is involved in the mechanism of action of the granule. This study provides a pharmacological basis for the use of modern YSHS granule and ancient Sheng-Yang-Yi-Wei decoction in treating CGN.