Yimeng Fan

Pulmonary fibrosis (PF) is a chronic pulmonary disease characterized by excessive extracellular matrix (ECM) deposition, with cigarette smoking being a major risk factor and no effective treatment at present. Transforming growth factor beta 1 (TGF-β1) plays a key role in PF and regulating oxidative stress. This study investigated the effects and mechanisms of Artemisia rupestris L. ethanol extract (ER) on cigarette smoke (CS)-induced PF. We used pull-down and LC–MS analyses to screen and identify compounds that bind to TGF-β1 in ER. We demonstrated that ER inhibits CS-induced PF, lung inflammation, and oxidative stress, thereby improving pulmonary structural injury. The ER inhibits fibroblast activation and fibroblast-to-myofibroblast transition (FMT), reducing collagen deposition for the treatment of PF. We identified the active ingredient in ER that binds to TGF-β1, namely, Luteolin 7-glucuronide (LG). LG inhibits the TGF-β1 signaling pathway through targeted binding to TGF-β1, downregulates the expression of downstream proteins (including collagen I, α-SMA, MMP-2, and MMP-9), and inhibits fibronectin expression. It also inhibits fibroblast activation and FMT, enhances E-cadherin expression to promote fibroblast adhesion, and suppresses collagen deposition, alleviating PF. Based on these findings, we propose that LG might be a promising therapeutic drug candidate for treating PF.

Inflammatory bowel disease (IBD) represents a highly recurrent gastrointestinal disorder and global public health issue. However, it lacks effective and safe strategies for its control. Although Ginkgo biloba extract (GBE) has been suggested to exhibit preventive and therapeutic activity for the control of IBD, whether its activity is associated with its ability to modulate intestinal microbiota remains to be addressed. To investigate the effect of GBE on controlling IBD, a Citrobacter Rodentium (CR)-induced mouse colitis model was used, and then histopathological examinations, biochemical assays, immunohistochemistry, and immunoblotting were performed to detect histological changes, cytokines, and tight junction (TJ) proteins in the intestine samples. We also studied 16s rRNA to detect changes in intestinal microbiota and used GC-MS to determine the microbiota-related metabolites short chain fatty acids (SCFAs). The results of our studies revealed that pre-treatment with GBE was sufficient for protecting the animals from CR-induced colitis. As a mechanism for GBE activity, GBE treatment was able to modulate the intestinal microbiota and increase the SCFAs capable of decreasing the pro-inflammatory factors and up-regulating the anti-inflammatory factors while elevating the intestinal-barrier-associated proteins to maintain the integrity of the intestines. Accordingly, our results led to a strong suggestion that GBE should be seriously considered in the preventive control of CR-induced colitis and in the development of effective and safe therapeutic strategies for controlling IBD.