Jerang Miti, Gurusubramanian Guruswami, Singh Ved Prakash, Roy Vikas Kumar
Department of Zoology, Mizoram University, Aizawl, Mizoram 796 004, India.
Department of Industrial Chemistry, Mizoram University, Aizawl, Mizoram 796 004, India.
J Steroid Biochem Mol Biol. 2025 Jul;251:106748. doi: 10.1016/j.jsbmb.2025.106748. Epub 2025 Apr 4.
Zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone) is a phytochemical with potent anti-inflammatory and antioxidant properties. It has been shown that zingerone protects testis under pathological conditions by its antioxidant and anti-inflammatory effects. However, there is no direct evidence that zingerone specifically affects the testicular steroidogenesis in normal conditions. Therefore, in this study, we have investigated the effects of zingerone on testicular steroidogenesis by using in vivo and silico approaches. The mice were divided into four groups: Control, 10, 25, and 50 mg/kg dosages of zingerone, which were administered orally for 35 days. It was observed that zingerone treatment modulates both circulating hormone levels and the expression of steroidogenic protein markers. Specifically, the higher doses of zingerone resulted in an increase in the circulating estrogen and androstenedione levels, while progesterone, testosterone, and follicle-stimulating hormone levels were reduced. Further, no significant change was observed in the circulating LH level. The higher doses of zingerone resulted in an increased expression and localisation of 3βHSD, CYP19A1, LHR and decreased expression and localisation of StAR, CYP11A1, and 17βHSD protein. Our silico studies showed that the steroidogenic proteins (CYP11A1, 3βHSD, 17βHSD) when double docked with zingerone alongside its native ligands (cholesterol, pregnenolone, androstenedione) showed an increase in the binding affinity. In contrast, StAR, CYP19A1 when double docked with zingerone and its native ligands exhibited a lesser binding affinity compared to when these proteins were single docked with their native ligand and zingerone. In conclusion, in vivo study showed zingerone stimulates androstenedione, estrogen secretion and up-regulates the expression of CYP19A1, LHR and 3βHSD proteins, whereas it down-regulates the expression of StAR, CYP11A1 and 17βHSD proteins and circulating testosterone, progesterone, follicle-stimulating hormone levels. Furthermore, in silico study has also shown the binding affinities of zingerone with the steroidogenic markers. Thus, zingerone has modulatory effects on testicular steroid biosynthesis in normal mice.
姜辣素（4-(4-羟基-3-甲氧基苯基)-2-丁酮）是一种具有强大抗炎和抗氧化特性的植物化学物质。研究表明，姜辣素在病理条件下通过其抗氧化和抗炎作用保护睾丸。然而，尚无直接证据表明姜辣素在正常条件下会特异性影响睾丸类固醇生成。因此，在本研究中，我们采用体内和计算机模拟方法研究了姜辣素对睾丸类固醇生成的影响。将小鼠分为四组：对照组、10、25和50mg/kg剂量的姜辣素组，口服给药35天。观察到姜辣素处理可调节循环激素水平和类固醇生成蛋白标志物的表达。具体而言，较高剂量的姜辣素导致循环雌激素和雄烯二酮水平升高，而孕酮、睾酮和促卵泡激素水平降低。此外，循环促黄体生成素水平未观察到显著变化。较高剂量的姜辣素导致3βHSD、CYP19A1、LHR的表达和定位增加，而StAR、CYP11A1和17βHSD蛋白的表达和定位降低。我们的计算机模拟研究表明，类固醇生成蛋白（CYP11A1、3βHSD、17βHSD）与姜辣素及其天然配体（胆固醇、孕烯醇酮、雄烯二酮）进行双重对接时，结合亲和力增加。相比之下，StAR、CYP19A1与姜辣素及其天然配体进行双重对接时，与这些蛋白仅与天然配体进行单一对接相比，结合亲和力较低。总之，体内研究表明姜辣素刺激雄烯二酮、雌激素分泌，并上调CYP19A1、LHR和3βHSD蛋白的表达，而它下调StAR、CYP11A1和17βHSD蛋白的表达以及循环睾酮、孕酮、促卵泡激素水平。此外，计算机模拟研究还显示了姜辣素与类固醇生成标志物的结合亲和力。因此，姜辣素对正常小鼠睾丸类固醇生物合成具有调节作用。
