A Combination of Cuscuta chinensis and Lycium barbarum Ameliorates Spermatogenic Impairment in Mice and Is Associated With Modulation of the miR-21/PTEN/PI3

SC-FL is a traditional Chinese herbal formula that has been used for kidney tonification and the clinical treatment of oligospermia and asthenospermia. This medicinal compound comprises dodder seed ( Cuscuta chinensis Lam .) and wolfberry fruit ( Lycium barbarum L .). However, the precise mechanisms of SC-FL remain undetermined. Therefore, this study aimed to identify potential therapeutic targets of SC-FL in oligoasthenozoospermia and validate these targets in vivo . To establish a spermatogenic dysfunction model, male BALB/c mice were administered glucosides of Tripterygium wilfordii Hook. f. (GTW) and then treated with SC-FL. Furthermore, the expression of microRNA-21 (miR-21), key PI3K/AKT/mTOR signaling pathway-related proteins and mRNAs, as well as molecular markers of cell proliferation and apoptosis, was evaluated. The results indicated that the mouse body weight did not significantly differ across SC-FL-treated groups compared to the GTW group (non-treated model group); however, the high-dose SC-FL mice showed significantly higher testicular weight ( p < 0.05 ). Both medium- and high-dose SC-FL mice showed significantly increased sperm concentration and motility relative to the GTW group ( p < 0.01 ). Histological analysis by hematoxylin and eosin staining revealed that SC-FL treatment alleviated GTW-induced testicular tissue damage and preserved testicular structure. SC-FL treatment reduced serum IL-6 and TNF-α levels and decreased PTEN mRNA and protein expression. It also increased miR-21, PI3K, AKT, and mTOR mRNA expression and increased the phosphorylated protein levels of PI3K, AKT, and mTOR, whereas total PI3K, AKT, and mTOR protein abundance remained relatively unchanged. In conclusion, SC-FL increased sperm concentration and motility and reduced serum inflammatory cytokine levels in mice. These beneficial effects were accompanied by increased miR-21 expression, decreased PTEN expression, and increased phosphorylation of PI3K, AKT, and mTOR. These findings indicate an association between the protective effects of SC-FL and alterations in the miR-21/PTEN/PI3K/AKT/mTOR signaling axis, but do not establish causal mediation by this pathway.