Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺–K⁺ ATP content in renal medulla. After treatment with cis-DG and trans-DG, expression of calcineurin (CAN) and Ca/calmodulin-dependent protein kinase II (CaMK II) was decreased in renal tissue and Ca²⁺ influx was inhibited, thereby reducing the secretion of transforming growth factor-β (TGFβ), reversing the increase in adhesion and inflammatory factor E-selectin and monocyte chemotactic protein 1 (MCP-1) induced by high NaCl, while reducing oxidative stress status and decreasing the expression of cyclooxygenase-2 (COX2). Furthermore, inhibition of protein kinase C (PKC) expression also contributed to these improvements. The cis-DG and trans-DG reduced the expression of p-p44/42 MAPK, p-JNK and p-p38, inhibited the phosphorylation of the MAPK signaling pathway in NRN52e cells induced by high salt, decreased the overexpression of p-p38 and p-HSP27, and inhibited the overactivation of the p38-MAPK signaling pathway, suggesting that the p38-MAPK pathway may play a vital role in the hypertonic-induced adhesion and inflammatory response. From the results of this study, it can be concluded that the mechanism of cis-DG and trans-DG may mainly be through inhibiting the p38-MAPK signaling pathway, inhibiting the excessive activation of the RAAS system, and thereby reducing adhesion and inflammatory factors.

Background. Duzhong Butiansu (DZBTS) prescription contains many traditional Chinese medicines and has been shown to have a curative effect on male fertility. However, the efficacy and mechanism of DZBTS in the treatment of male infertility induced by heat stress have not been reported. The aim of the present study is to elucidate the effect and mechanism of DZBTS on spermatogenic function of a heat stress model in rats. Methods. Male Wistar rats (280–320 g) were given different doses of DZBTS (0.4853 g/kg/d or 0.9707 g/kg/d), Shengjing capsule (0.56 g/kg/d), or double distilled water for 15 days. A 43°C hot water bath for 30 minutes was used to stimulate the testis of rats. Sperm count, sperm motility, the organ index of kidney and gonadal organs, serum sex hormone levels, and serum oxidising reaction index were measured. Haematoxylin and eosin (HE) staining was used to observe the morphology of the testis and kidney. The expression of Hsp70 in testes was observed by immunofluorescence. The changes in heat stress, reproductive‐related protein, and mRNA were measured by western blot assay and RT‐qPCR. Results. Heat stress downregulated the levels of sex hormone (P < 0.05 or P < 0.01) and its receptor androgen receptor (AR) protein expression and mRNA (P < 0.01) in rats. Meanwhile, heat stress downregulated the levels of CAMP‐responsive element‐binding (CREB1) protein and mRNA (P < 0.01), which are involved with spermatogenesis. Heat stress also decreased the oxidative damage index. Furthermore, Hsp70 and the heat shock transcription factor 1 (HSF1) protein pathway and mRNA level were overactivated (P < 0.05 or P < 0.01). Finally, the organ coefficients of the kidney and gonadal organs of rats were decreased. The sperm concentration and motility also decreased significantly (P < 0.01). DZBTS could recover these changes induced by heat stress. Conclusions. Our results for the first time have found that DZBTS can improve spermatogenesis disorder in a heat stress model in rats, which may be mainly by regulating AR, sperm regulatory protein CREB1, and the HSF/Hsp70 signaling pathway to decrease oxidative stress.

Purpose: Doxorubicin (DOX) precipitates cell apoptosis in testicular tissues, and it is imperative to develop drugs to alleviate the spermatogenic disorders it causes. Eugenia caryophyllata Thunb is often used to treat male sexual disorders. Eugenol, a major component of Eugenia caryophyllata Thunb. has inadequate stability and low solubility, which limits its pharmacological effects. Eugenol nanoparticles (NPs) (ENPs) are expected to overcome these limitations. The protective effects of ENPs against DOX-induced reproductive toxicity were studied in mice. Methods: Eugenol was encapsulated in Methoxy-Poly(ethylene glycol)-Poly(lactide-co-glycolide) nanoparticles (mPEG-PLGA-NPs), and their role in ameliorating spermatogenic dysfunction was verified in vivo and in vitro. Results: We present a promising delivery system that encapsulates eugenol into mPEG-PLGA-NPs and forms them into nanocomposites. In vitro, ENPs significantly reduced doxorubicin-induced ROS and inflammatory factors in GC-1 cells and regulated the expression of the mitochondrial autophagy protein PINK1 and meiosis-related protein SCP3. In vivo, ENPs significantly increased sperm motility in mice, reduced apoptosis and oxidative stress in the testes, inhibited the testicular PINK1/Parkin and BNIP3/NIX signaling pathways, and enhanced the expression of factors associated with meiosis. Conclusion: Given their safety and efficacy, these ENPs have potential application prospects in mitigating doxorubicin-induced spermatogenic dysfunction.