Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway

Abstract

Background: Diabetes mellitus (DM) induces impairment of male reproductive system and is considered as a key factor that could partially provide an explanation for male infertility. Thus, understanding the mechanism underlying DM-induced infertility will aid in the identification of novel therapeutic stratagems. Objectives: To delineate the role of ROS/JAK2/NFκB pathway in DM-induced low reproductive function and impaired spermatogenesis. Additionally, to investigate the protective effect of monomeric Berberine (BB) that inhibits ROS/JAK2/NFκB pathway, in the pathogenesis of DM-induced infertility.Methods: 12-week-old male Sprague-Dawley rats were divided into four groups: control group, DM group, control plus BB group, and DM plus BB group. Streptozotocin was used to induce DM. After treating the rats with BB for 4 weeks, fertility tests were conducted to investigate the reproductive function, and testis weight along with sperm motility was assessed through microscope. Oxidative stress was evaluated by DHE staining. TUNEL staining was utilized to detect the state of apoptosis. Cell experiments were carried out to define the role of BB in vitro. Immunohistochemistry, immunofluorescence, and Western blotting were employed to measure the protein expression. Results:Our results indicate that the reproductive function of DM rats was low, accompanied by decreased testis weight and sperm motility in addition to the impairment of the seminiferous tubules. However, there was a significant improvement in the reproductive function parameters in the BB-treated DM rats. Subsequently, our data revealed that DM rats produce an increased level of ROS in the testis, which activates JAK2 further activating the NFκB pathway, leading to increased apoptosis and impaired cells in the testicles. However, BB could attenuate the ROS production and abrogate activation of JAK2/NFκB pathway, thus inhibiting the apoptosis in the testicular cells of DM rats.Conclusion: ROS/JAK2/NFκB pathway is involved in the DM-induced low reproductive function and impaired spermatogenesis. BB can play a protective role in

JAK Inhibition Prevents DNA Damage and Apoptosis in Testicular Ischemia-Reperfusion Injury via Modulation of the ATM/ATR/Chk Pathway

“…Excessive generation of ROS is a key trigger of JAK/STAT signaling [4]. Increased ROS levels activate the JAK2/NFκB pathway in the testis, which triggers apoptosis and results in dysfunctional testicles, while JAK2 inhibition reduces oxidative damage and cell apoptosis in the testis [21,22]. In vitro, JAK/STAT phosphorylation was increased in high glucose, and quercetin treated Sertoli cells, implicating JAK's role in diabetes-induced testicular damage [23].…”

Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats

“…Treatment with BBR and finasteride significantly restored the GSH, CAT, SOD, (GPx by finasteride, only) and approved the antioxidant properties of the test ingredients. Previous studies have shown that BBR (as an anti-oxidant agent) can prevent damage to testicular tissue, reproductive function, and disruption of spermatogenesis through inhibiting the ROS/JAK2/NFκB pathway and reducing oxidative stress [ 32 , 67 ].…”

Berberine is sufficient to restore the destroyed seminiferous tubule structure and hypospermatogenesis in diabetes mellitus

“…After the adaption for a month, 60 six‐week age male wild‐type Sprague–Dawley rats were used to build a type 1 diabetes rat model, and the induction process was based on previous study 3 . After a 12‐week duration of diabetes, intragastric administration was used for a 4‐week treatment of BB (Figure 1).…”