Killari Kishore Naidu, Polimati Haritha, Prasanth D S N B K, Singh Gagandeep, Panda Siva Prasad, Vedula Girija Sastry, Tatipamula Vinay Bharadwaj
Department of Pharmaceutical Sciences, AU College of Pharmaceutical Sciences, Andhra University Visakhapatnam-530 003 India.
Department of Pharmacognosy, KVSR Siddhartha College of Pharmaceutical Sciences Vijayawada AP 520010 India.
RSC Adv. 2023 Apr 26;13(19):12991-13005. doi: 10.1039/d3ra01542d. eCollection 2023 Apr 24.
Male sexual dysfunctions such as infertility and impotence are recognized as the consequences of diabetes. Salazinic acid (Sa) is a depsidone found in lichen genera of , , and , which has prominent free radical and α-glucosidase inhibitory actions. The present study establishes the beneficial role of salazinic acid (Sa) to combat the deleterious effects of streptozotocin-induced diabetes on the male reproductive system of rats. In a dose-dependent manner, Sa significantly restored the reproductive organs weight, sperm characteristics, and testicular histoarchitecture in diabetic rats. Further, a significant recovery of insulin, follicle-stimulating hormone, luteinizing hormone and testosterone levels in serum was recorded in Sa-treated diabetic rats. The malondialdehyde levels were significantly lowered, and the activities of glutathione, superoxide dismutase, glutathione peroxidase and catalase, markedly elevated in the blood serum, as well as testicular tissue after Sa-supplementation. Sa also suppressed the protein expression levels of tumor necrosis factor-α in serum. The high dose of Sa showed significant improvement in glycemia and testicular protection, similar to sildenafil citrate. Moreover, the docking results showed that both Sa and sildenafil have a high affinity toward the target protein, PDE5 with binding affinity values found to be -9.5 and -9.2 kcal mol, respectively. Molecularly, both Sa and sildenafil share similar hydrogen bonding patterns with PDE5. Hence, our study clearly showed the protective role of Sa against diabetic-induced spermatogenic dysfunction in rats, possibly by competing with cGMP to bind to the catalytic domain of PDE5 and thereby controlling the oxidative impairment of testes.
男性性功能障碍如不育和阳痿被认为是糖尿病的后果。柳珊瑚酸(Sa)是一种在地衣属、、和中发现的缩酚酸环醚,具有显著的自由基和α-葡萄糖苷酶抑制作用。本研究确定了柳珊瑚酸(Sa)在对抗链脲佐菌素诱导的糖尿病对大鼠雄性生殖系统的有害影响方面的有益作用。Sa以剂量依赖的方式显著恢复了糖尿病大鼠的生殖器官重量、精子特征和睾丸组织结构。此外,在接受Sa治疗的糖尿病大鼠中,血清中胰岛素、促卵泡激素、促黄体生成素和睾酮水平显著恢复。补充Sa后,血清以及睾丸组织中的丙二醛水平显著降低,谷胱甘肽、超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶的活性显著升高。Sa还抑制了血清中肿瘤坏死因子-α的蛋白表达水平。高剂量的Sa在血糖控制和睾丸保护方面显示出显著改善,类似于枸橼酸西地那非。此外,对接结果表明,Sa和西地那非对靶蛋白磷酸二酯酶5(PDE5)都具有高亲和力,结合亲和力值分别为-9.5和-9.2 kcal/mol。在分子水平上,Sa和西地那非与PDE5具有相似的氢键模式。因此,我们的研究清楚地表明了Sa对糖尿病诱导的大鼠生精功能障碍具有保护作用,可能是通过与环磷酸鸟苷(cGMP)竞争结合到PDE5的催化结构域,从而控制睾丸的氧化损伤。