Combined treatment with extracorporeal shockwaves therapy and an herbal formulation for activation of penile progenitor cells and antioxidant activity in diabetic erectile dysfunction

Seung Hwan Jeon; Woong Jin Bae; Guan Qun Zhu; Wenjie Tian; Eun Bi Kwon; Ga Eun Kim; Sung Yeoun Hwang; Kyu Won Lee; Hyuk Jin Cho; U-Syn Ha; Sung-Hoo Hong; Ji Youl Lee; Sae Woong Kim

doi:10.21037/tau.2020.01.23

Combined treatment with extracorporeal shockwaves therapy and an herbal formulation for activation of penile progenitor cells and antioxidant activity in diabetic erectile dysfunction

Transl Androl Urol. 2020 Apr;9(2):416-427. doi: 10.21037/tau.2020.01.23.

Authors

Seung Hwan Jeon^{1

2}, Woong Jin Bae^{1

2}, Guan Qun Zhu^{1

2}, Wenjie Tian^{1

2}, Eun Bi Kwon^{1

2}, Ga Eun Kim^{1

2}, Sung Yeoun Hwang³, Kyu Won Lee^{1

2}, Hyuk Jin Cho¹, U-Syn Ha¹, Sung-Hoo Hong¹, Ji Youl Lee¹, Sae Woong Kim^{1

2}

Affiliations

¹ Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
² Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
³ KEMIMEDI, Seoul, Korea.

Abstract

Background: A Korean herbal formulation named KH-204 was reported to have an antioxidant effect in our previous study. We hypothesized that Low-intensity extracorporeal shockwave therapy (Li-ESWT) combined with KH-204 would accelerate the treatment of erectile dysfunction (ED) by enhancing antioxidant. We investigated the synergistic effect of Li-ESWT and KH-204 for ED and explored the mechanism.

Methods: Human umbilical vein endothelial cells (HUVEC) were treated with KH-204 and LI-ESWT in vitro. Fifty 5-week-old male Sprague Dawley rats received an intraperitoneal injection of 5-ethynyl-20-deoxyuridine (EdU) which can label live cells, and were randomly divided into five groups: (I) normal; (II) diabetes mellitus-associated erectile dysfunction (DMED); (III) DMED + KH-204; (IV) DMED + Li-ESWT; and (V) DMED + KH-204/Li-ESWT. Li-ESWT treatment was repeated three times a week every other day for four weeks in group 4 and 5. Meanwhile, rats in group 3 and 5 were orally fed 400 mg/kg of KH-204 daily for 1 month. Following a 1-week washout period, penile tissues were evaluated by immunostaining and Western blotting.

Results: KH-204 combined with Li-ESWT improved intracavernosal pressure (ICP) in DMED rats. Li-ESWT/KH-204 stimulated HUVEC tube formation and promoted proliferation. Li-ESWT drove progenitor cells to migrate to penile tissue and KH-204 protected penile progenitor cells in the corpus cavernosum. Oxidative stress was relieved by KH-204/Li-ESWT. Treatment with KH-204/Li-ESWT protected penile progenitor cells, which were recruited to the corpus cavernosum by Li-ESWT, from apoptosis via its antioxidant activity. KH-204/Li-ESWT protected penile tissue from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), increasing superoxide dismutase (SOD), decreasing 8-hydroxy-20-deoxyguanosine (8-OHdG), and reducing apoptosis. KH-204/Li-ESWT promoted stromal derived factor-1 (SDF-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in DMED rats.

Conclusions: KH-204 protected penile progenitor cells, which were recruited to the corpus cavernosum by Li-ESWT, from apoptosis via its antioxidant activity. The combination of Li-ESWT and KH-204 as a synergy therapy could be a potential and effective treatment for DMED.

Keywords: Low-intensity extracorporeal shockwave therapy; antioxidant; diabetes mellitus; erectile dysfunction (ED); herbal formulation; progenitor cells.