Therapeutic Effects of Xianlu Oral Solution on Rats with Oligoasthenozoospermia through Alleviating Apoptosis and Oxidative Stress.

Idiopathic oligoasthenozoospermia (iOAZS) is one of the major causes of male infertility, and the ideal therapies for iOAZS have not been established yet. Traditional Chinese medicine (TCM), including Xianlu oral solution (XL), has been widely used as an adjunct treatment for male infertility in the clinic. However, the underlying mechanisms of XL treatment on iOAZS are still not known. Here, we found that XL treatment has therapeutic effects on ornidazole (ORN)-induced OAZS model rats through the amelioration of testis tissues spermatogenesis and the improvement of sperm concentration and motility. Moreover, XL treatment ameliorated the serum hormone levels, mitochondrial membrane potential, apoptosis status, and oxidative stress status in the testis tissues of iOAZS model rats. These findings identify a potential mechanism underlying the therapeutic effects of Xianlu oral solution on iOAZS, and Xianlu oral solution may be used as a traditional Chinese medicine (TCM) therapy for male infertility caused by iOAZS in clinical practice.

Celastrol inhibits ezrin-mediated migration of hepatocellular carcinoma cells.

Progression of hepatocellular carcinoma involves multiple genetic and epigenetic alterations that promote cancer invasion and metastasis. Our recent study revealed that hyperphosphorylation of ezrin promotes intrahepatic metastasis in vivo and cell migration in vitro. Celastrol is a natural product from traditional Chinese medicine which has been used in treating liver cancer. However, the mechanism of action underlying celastrol treatment was less clear. Here we show that ROCK2 is a novel target of celastrol and inhibition of ROCK2 suppresses elicited ezrin activation and liver cancer cell migration. Using cell monolayer wound healing, we carried out a phenotype-based screen of natural products and discovered the efficacy of celastrol in inhibiting cell migration. The molecular target of celastrol was identified as ROCK2 using celastrol affinity pull-down assay. Our molecular docking analyses indicated celastrol binds to the active site of ROCK2 kinase. Mechanistically, celastrol inhibits the ROCK2-mediated phosphorylation of ezrin at Thr567 which harnesses liver cancer cell migration. Our findings suggest that targeting ROCK2-ezrin signaling is a potential therapeutic niche for celastrol-based intervention of cancer progression in hepatocellular carcinoma.