Deciphering the myth of icariin and synthetic derivatives in improving erectile function from a molecular biology perspective: a narrative review

Yuanjie Niu; Guiting Lin; Jiancheng Pan; Jihong Liu; Yongde Xu; Qiliang Cai; Tao Wang; Yang Luan; Yegang Chen; Yuhong Feng; Xiaoqing Yang; Wenjie Tian; Wong Jin Bae; Ruili Guan; Zhongcheng Xin

doi:10.21037/tau-22-232

Deciphering the myth of icariin and synthetic derivatives in improving erectile function from a molecular biology perspective: a narrative review

Transl Androl Urol. 2022 Jul;11(7):1007-1022. doi: 10.21037/tau-22-232.

Authors

Yuanjie Niu^#^{1

2}, Guiting Lin^#³, Jiancheng Pan^#^{1

2}, Jihong Liu^{4

5}, Yongde Xu⁶, Qiliang Cai^{1

2}, Tao Wang^{4

5}, Yang Luan^{4

5}, Yegang Chen^{1

2}, Yuhong Feng^{1

2}, Xiaoqing Yang², Wenjie Tian⁷, Wong Jin Bae⁷, Ruili Guan⁸, Zhongcheng Xin^{1

2

8}

Affiliations

¹ Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
² China-Korea Joint Research Center for Male Reproductive and Sexual Medicine, Institute of Urology, Tianjin, China.
³ Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
⁴ Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁶ Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
⁷ Department of Urology, Seoul St. Mary's Hospital, the Catholic University of Korea, Seoul, Korea.
⁸ Andrology Center, Peking University First Hospital, Peking University, Beijing, China.

^# Contributed equally.

Abstract

Background and objective: Although epimedium herb (EH) has been widely used in ancient Chinese medicine to enhance sexual activity, its pharmacological mechanism is not clear. Modern studies have shown that epimedium herb is rich in icariin (ICA, a flavonoid compound), and 91.2% of icariin is converted to icariside II (ICA II) by hydrolytic enzymes in intestinal bacteria after oral administration. YS-10 is a synthetic derivative of icariside II. The aim of this review was to summarize the contemporary evidence regarding the pharmacokinetics, therapeutic properties, and molecular biological mechanisms of ICA and some ICA derivatives for erectile dysfunction therapy.

Methods: A detailed search was conducted in the PubMed database using keywords and phrases, such as "icariin" AND "erectile dysfunction", "icariside II" AND "erectile dysfunction". The publication time is limited to last 20 years. Articles had to be published in peer reviewed journals.

Key content and findings: ICA and its some derivatives showed the specific inhibition on phosphodiesterase type 5 (PDE5) and the promotion of testosterone synthesis. In addition, by regulating various reliable evidence of signaling pathways such as PI3K/AKT, TGFβ1/Smad2, p38/MAPK, Wnt and secretion of various cytokines, ICA and ICA derivatives can activate endogenous stem cells (ESCs) leading to endothelial cell and smooth muscle cell proliferation, nerve regeneration and fibrosis inhibition, repair pathological changes in penile tissue and improve erectile function.

Conclusions: ICA and some of its derivatives could be a potential treatment for restoring spontaneous erections. In addition ICA and his derivatives may also be valuable as a regenerative medicine approach for other diseases, but more clinical and basic researches with high quality and large samples are recommended.

Keywords: Epimedium herb (EH); endogenous stem cells; erectile dysfunction; icariin; molecular mechanism.

Publication types

Review