Wang Kai, Li Juntao, Zheng Xinyu, Xu Jian, Wang Zhe, Li Senjie, Yang Qiang, Wu Yue, Yang Dong-Hua, Yao Shen, Zheng Xiangwei
Science and Technology Experiment Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2023 Jul 14;14:1233468. doi: 10.3389/fphar.2023.1233468. eCollection 2023.
Kidney-Yang deficiency syndrome (KDS) is a group of diseases related to hypothalamic-pituitary-adrenal (HPA) axis and sexual dysfunction. The folium of Maxim. (FEB) includes raw and prepared slices, named RFEB and PFEB, respectively. PFEB is traditionally believed to be good for tonifying kidney-Yang and improving sexual dysfunction. However, there are few studies comparing the pharmacological effects of RFEB and PFEB, and their underlying mechanisms. In this study, we aimed to compare the effects and safety of RFEB and PFEB on the HPA axis and sexual function. Additionally, the mechanisms of their roles in relation to the neuroendocrine-immune (NEI) network in the KDS model mice were explored. Male adult C57BL/6 mice were treated with corticosterone to establish a KDS mouse model, and RFEB and PFEB were administered intragastrically. Corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), testosterone levels and oxidative damage indexes were measured. The mRNA and protein levels of and in hypothalamus and pituitary, endothelial nitric oxide synthase (eNOS) and phosphodiesterase 5 (PDE5) in corpus cavernosum were examined. TNFα, IL-6, NF-κB, eNOS and PDE5 were investigated in mouse corpus cavernosum. Our results showed that PFEB was more effective than RFEB in increasing corticosterone-suppressed levels, enhancing levels and cAMP/cGMP ratio, and reducing oxidative damage. , PFEB significantly increased eNOS and inhibited PDE5 expression in corpus cavernosum. PFEB showed stronger protective effect on normal spleen lymphocytes from apoptosis both and . Additionally, it noticeably inhibited the levels of inflammatory cytokines in corpus cavernosum. Both RFEB and PFEB were safe and did not cause any clinical signs of toxicity in mice at the dosage of 20 times dosages of that in the Chinese Pharmacopeia. We demonstrated that PFEB was better than RFEB at tonifying the kidney-Yang by comparing their effects on improving the NEI network, which includes the HPA axis, immune system and corpus cavernosum. This study revealed that PFEB could significantly improve the sexual function of KDS mice by regulating the HPA axis and activating the immune system through the NEI network.
肾阳虚证（KDS）是一组与下丘脑 - 垂体 - 肾上腺（HPA）轴及性功能障碍相关的疾病。淫羊藿叶（FEB）包括生品和炮制品，分别命名为RFEB和PFEB。传统上认为PFEB有益肾阳、改善性功能。然而，比较RFEB和PFEB药理作用及其潜在机制的研究较少。本研究旨在比较RFEB和PFEB对HPA轴及性功能的作用和安全性。此外，还探讨了它们在KDS模型小鼠中与神经内分泌 - 免疫（NEI）网络相关的作用机制。雄性成年C57BL/6小鼠用皮质酮处理以建立KDS小鼠模型，并通过灌胃给予RFEB和PFEB。检测促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）、环磷酸腺苷（cAMP）、环磷酸鸟苷（cGMP）、睾酮水平及氧化损伤指标。检测下丘脑和垂体中相关基因的mRNA和蛋白水平，以及阴茎海绵体中内皮型一氧化氮合酶（eNOS）和磷酸二酯酶5（PDE5）。检测小鼠阴茎海绵体中的TNFα、IL - 6、NF - κB、eNOS和PDE5。我们的结果表明，在增加皮质酮抑制的相关水平、提高相关水平及cAMP/cGMP比值、减少氧化损伤方面，PFEB比RFEB更有效。此外，PFEB显著增加阴茎海绵体中eNOS表达并抑制PDE5表达。在体内和体外实验中，PFEB对正常脾淋巴细胞凋亡均表现出更强的保护作用。此外，它显著抑制阴茎海绵体中炎性细胞因子水平。在相当于《中国药典》规定剂量20倍的剂量下，RFEB和PFEB对小鼠均安全，未引起任何毒性临床症状。通过比较RFEB和PFEB对改善包括HPA轴、免疫系统和阴茎海绵体在内的NEI网络的作用，我们证明PFEB在补肾阳方面优于RFEB。本研究表明，PFEB可通过调节HPA轴并通过NEI网络激活免疫系统，显著改善KDS小鼠的性功能。
