The pharmacological effects and safety of the raw and prepared folium of Epimedium brevicornu Maxim. on improving kidney-yang deficiency syndrome and sexual dysfunction

Abstract

Background: Kidney-Yang deficiency syndrome (KDS) is a group of diseases related to hypothalamic-pituitary-adrenal (HPA) axis and sexual dysfunction. The folium of Epimedium brevicornu 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.Methods: 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 CRH and ACTH 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.Results: Our results showed that PFEB was more effective than RFEB in increasing corticosterone-suppressed ACTH levels, enhancing CRH levels and cAMP/cGMP ratio, and reducing oxidative damage. In vivo, PFEB significantly increased eNOS and inhibited PDE5 expression in corpus cavernosum. PFEB showed stronger protective effect on normal spleen lymphocytes from apoptosis both in vitro and in vivo. 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.Conclusion: 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.

WITHDRAWN: Exploring Pathogenesis and Biomarkers Through Establishment of a Rat Model of Male Infertility with Liver Depression and Kidney Deficiency

“…For instance, in rats with Kidney De ciency, SOD activity in serum shows a signi cant reduction, while MDA content experiences a marked elevation [37] .…”

“…In this context, intracellular proin ammatory cytokines are prone to generating excessive in ammatory responses, exacerbating the prevailing in ammatory state. As integral reproductive organs, the testes are subject to regulatory control by the immune system and concurrently exhibit interactive in uences with LD & KD, which are commonly accompanied by elevated levels of proin ammatory cytokines [37][38] .…”

“…Among these cytokines, IL-6, IL-1β, and TNF-α play a pivotal role in provoking testicular impairment [37,39] . Notably, IL-1β assumes a central role within the cascade of in ammatory responses [40] , while TNF-α originating from germ cells facilitates testicular detriment through the in ammatory pathways, concurrently dictating the modulation of germ cell apoptosis [41] .…”

Exploring pathogenesis and biomarkers through establishment of a rat model of male infertility with liver depression and kidney deficiency

“…Similarly, oxidative stress has been implicated in Kidney Deficiency. For instance, in rats with Kidney Deficiency, SOD activity in serum shows a significant reduction, while MDA content experiences a marked elevation [ 53 ].…”

“…In this context, intracellular proinflammatory cytokines are prone to generating excessive inflammatory responses, exacerbating the prevailing inflammatory state. As integral reproductive organs, the testes are subject to regulatory control by the immune system and concurrently exhibit interactive influences with LD & KD, which are commonly accompanied by elevated levels of proinflammatory cytokines [ 53 , 60 ]. Among these cytokines, IL-6, IL-1β, and TNF-α play a pivotal role in provoking testicular impairment [ 53 , 61 ].…”