Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis.

Ning Qu,Kaori Suyama,Miyuki Kuramasu,Yoshie Hirayanagi,Shogo Hayashi,Masahiro Itoh,Kou Sakabe,Hayato Terayama,Kenta Nagahori,Yuki Ogawa

doi:10.3390/ijms21051716

Abstract

Busulfan is used as a chemotherapeutic drug to treat childhood and adult chronic myelogenous leukemia, and as an immunosuppressive agent before bone marrow transplantation. A key side effect of busulfan is the alteration of male reproductive function. Infertility caused by anti-cancer treatments has become a significant concern, but there are currently limited treatments for this condition. Recently, we demonstrated that Gosha-jinki-gan, a traditional Japanese medicine, completely reversed the spermatogenesis defects caused by cancer treatment in mice. Hochu-ekki-to and Hachimi-jio-gan are commonly used to treat male infertility, and Hachimi-jio-gan shares herbal ingredients with Gosha-jinki-gan. Therefore, in the present study, we administered Hachimi-jio-gan and Hochu-ekki-to alone or in combination to mice with severe aspermatogenesis caused by busulfan treatment. We performed testis weight measurements, quantitative histological assessments of the testes and the epididymis, and evaluated sperm counts and morphology. We also assessed the expression of immune mediators and macrophage markers. Treatment with a combination of both the medicines significantly reduced busulfan-induced testicular toxicity when compared to the lone treatment with either medicine. We demonstrated that treatment efficacy was related to a differential impact on testicular inflammation, and that the synergistic effect of co-administration completely reversed the busulfan-induced damage to the reproductive functions.

Highlights

Male infertility and abnormalities in sperm production can be caused by a variety of disorders, including anatomical problems, hormonal imbalances, genetic defects, and psychological problems or behavioral problems [1]
We further examined the immunological factors that are involved in spermatogenesis after anti-cancer treatment
There were no significant differences in the body weights of the BSF-treated mice compared to mice in the control group on day 60 after a single intraperitoneal administration of the drugs (Figure 1A)

Summary

Introduction

Male infertility and abnormalities in sperm production can be caused by a variety of disorders, including anatomical problems, hormonal imbalances, genetic defects, and psychological problems or behavioral problems [1]. Oriental herbal medicines have been reported to improve total sperm count and motility These include the Hachimi-jio-gan and Hochu-ekki-to Japanese traditional medicines, which are clinically used to treat male infertility. Hachimi-jio-gan, which is called BaWei DiHuang Wan in Chinese, is a herbal mixture containing eight ingredients (Table 1). It was discovered more than 1800 years ago by the notable Dr Zhongjing Zhang [2] and was used in traditional medicine to treat diabetes and urinary disorders [3,4]. Hochu-ekki-to, known as BuZhong YiQi Wan in Chinese, is a herbal mixture containing ten ingredients (Table 1) and is clinically used to treat idiopathic male infertility. Treatment with Hochu-ekki-to before an influenza infection in mice significantly increased the expression of interferon-alpha (IFN-α), several Toll-like receptors (TLRs), and defensins [11,12]

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Discussion

Conclusion