Protective effect of Echinacoside, Cistanche and Cordyceps militaris extract on reproductive damage in rats

[Speaker] Xiaoying Zhang:1
[Co-author] Zhihui Jiang:1,2
1:College of Veterinary Medicine, Northwest Agriculture and Forestry University, China, 2:Research Center of Modern Biotechnology, School of Biotechnology and Food Engineering, Anyang Institute of Technology, Anyang, Henan 455000, China

Background: Male infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Our early work demonstrated that Cistanche extracts and Cordyceps militaris extract protect against sperm damage in mice and that echinacoside (ECH) is one of the major active components. Here we report an essential role for ECH, a natural product that reverses or protects against oligoasthenospermia in rat.
Methods: The distribution of ECH was assayed by HPLC, the quantity and quality of sperm was evaluated and hormone levels were determined by radioimmunosorbent assay. The levels of androgen receptor (AR) and key steroidogenic-related genes were reduced as determined by Western blot and qPCR analysis. The interaction between ECH and AR were evaluated by fluorescence localization assay, indirect ELISA and molecular docking. To investigate the protective effect of C. militaris extract against bisphenol A induced reproductive damage, the level of oxidative damage, sperm parameters, hormone levels, and histopathological changes were examined.
Results: ECH significantly increased the quantity of sperm and secretions of luteinizing hormone and testosterone. ECH was distributed to the hypothalamus but not the testes. ECH combined with hypothalamic AR in the pocket of Met-894 and Val-713 to inhibit transfer of AR from the cytoplasm to nuclei in the hypothalamus. While negative feedback of sex hormone regulation was inhibited, positive feedback was stimulated to increase the secretion of luteinizing hormone and testosterone subsequently enhancing the quantity of sperm. C. militaris significantly alleviated the BPA-induced reproductive damage by increasing testicular superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione (GSH); as well as by reducing serum malondialdehyde (MDA). C. militaris not only obviously enhanced the levels of serum LH and T, but it also improved the sperm count and motility compared to the BPA-treated group.
Conclusions: All data demonstrate that ECH blocks AR activity in the hypothalamus to increase the quantity of sperm and protect against oligoasthenospermia in rats. The C. militaris through the antioxidant pathway to protect the BPA induced reproductive damage.
Keywords: echinacoside - Cordyceps militaris - sperm

Figure 1. Mechanism by which ECH enhances the sperm counts.

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