Icariin promotes mouse Leydig cell testosterone synthesis via the Esr1/Src/Akt/Creb/Sf-1 pathway.

Icariin (ICA), extracted from Epimedium, is a flavonoid used in traditional Chinese medicine. Di(2-ethylhexyl) phthalate (DEHP) is a phthalate used in commercial products as a plasticizer that can influence the human endocrine and reproduction system. We previously found that ICA reversed DEHP-induced damage through the prevention of reactive oxygen species accumulation and promotion of testosterone secretion. Here we investigated the mechanisms of ICA in promoting testosterone secretion from murine Leydig cells. We used ICA, DEHP, the Akt agonist SC-79, the Akt inhibitor MK2206, and the Creb inhibitor KG501 to determine the effect of these treatments on the expression levels of the steroidogenic enzymes, Cyp11a1 and Hsd3b, which play critical roles in androgen production, in Leydig cells. Bioinformatic analysis was used to search for ICA-targeted proteins and their associated pathways. We found that icariin interacted with estrogen receptor on the cell membrane, leading to increased phosphorylation levels of Akt and Creb proteins and enhanced transcription of genes encoding steroidogenic enzymes and testosterone synthesis. We further investigated ICA activity in vivo using male mice pretreated with 100 mg/kg ICA and then treated with 750 mg/kg DEHP. ICA pretreatment reversed the reduced protein expression levels of Cyp11a1 and Hsd3b induced by DEHP in Leydig cells in vivo. Furthermore, while the phosphorylation levels of Akt and Creb were decreased in testes of mice exposed to DEHP alone, these effects were reversed by ICA pretreatment. These findings indicate that ICA promotes testosterone synthesis via the Esr1/Src/Akt/Creb/Sf-1 signaling pathway.

Semaglutide attenuates excessive exercise-induced myocardial injury through inhibiting oxidative stress and inflammation in rats.

AIMS: To investigate the protective effects and mechanism of semaglutide on exercise-induced myocardial injury. MAIN METHODS: Effects of semaglutide on lipopolysaccharide (LPS)-induced oxidative stress injuries and inflammatory response were assessed in H9c2 cell via MTT assay and Western blot. Quiet control group, over training group and three doses of semaglutide treated overtraining groups were subjected to the swimming training with increasing load for consecutive 10 weeks. Immediately after the last training, the body weight, myocardial morphological changes, injury markers and inflammatory response related proteins of the model rats were analyzed. KEY FINDINGS: Semaglutide at three concentrations in LPS treated H9c2 cells significantly increased the survival rate and inhibited the apoptosis of cardiomyocytes. Moreover, semaglutide activated AMPK pathway, improve autophagy and inhibited reactive oxygen species production in LPS treated H9C2 cells. In vivo results further revealed that chronic treatment of semaglutide induced significant increase in myocardial injury markers. The pathological histology analysis results showed that semaglutide ameliorated myocardial morphological changes, reduced area of lipid accumulation and significantly decreased the expression levels of NF-κB, TNF-α and IL-1ß. SIGNIFICANCE: Semaglutide exert the protective effects on exercise-induced cardiomyopathy by activating AMPK pathway, increasing autophagy, reducing the production of ROS and inflammation-related proteins.