Abstract

Traditional Chinese medicine (TCM) has been practiced in the treatment of bone diseases and alcoholism. Chronic excessive alcohol use results in alcohol-induced bone diseases, including osteopenia and osteoporosis, which increases fracture risk, deficient bone repair, and osteonecrosis. This preclinical study investigated the therapeutic effects of TCM herbal extracts in animal models of chronic excessive alcohol consumption-induced osteopenia. TCM herbal extracts (Jing extracts) were prepared from nine Chinese herbal medicines, a combinative herbal formula for antifatigue and immune regulation, including Astragalus, Cistanche deserticola, Dioscorea polystachya, Lycium barbarum, Epimedium, Cinnamomum cassia, Syzygium aromaticum, Angelica sinensis, and Curculigo orchioides. In this study, Balb/c male mice were orally administrated alcohol (3.2 g/kg/day) with/without TCM herbal extracts (0.125 g/kg, 0.25 g/kg, or 0.5 g/kg) by gavage. Our results showed that after 50 days of oral administration, TCM herbal extracts prevented alcohol-induced osteopenia demonstrated by μ-CT bone morphological analysis in young adults and middle-aged/old Balb/c male mice. Biochemical analysis demonstrated that chronic alcohol consumption inhibits bone formation and has a neutral impact on bone resorption, suggesting that TCM herbal extracts (Jing extracts) mitigate the alcohol-induced abnormal bone metabolism in middle-aged/old male mice. Protocatechuic acid, a natural phenolic acid in Jing extracts, mitigates in vivo alcohol-induced decline of alkaline phosphatase (ALP) gene expression in the bone marrow of Balb/c male mice and in vitro ALP activity in pre-osteoblast MC3T3-E1 cells. Our study suggests that TCM herbal extracts prevent chronic excessive alcohol consumption-induced osteopenia in male mice, implying that traditional medicinal plants have the therapeutic potential of preventing alcohol-induced bone diseases.

Highlights

  • Traditional Chinese medicine has treated various diseases, including bone diseases and alcoholism

  • We used the dose of 3.2 g/kg of alcohol administered by gavage for 50 days, which induced significant bone loss in young adult male Balb/c mice, as shown in Figure 2, for the effects of herbal extracts on alcohol-induced osteopenia

  • Our data showed that 3.2 g/kg alcohol induced significant bone loss in young adult male Balb/c mice after 50 days of oral administration by gavage (Figure 3); the low, middle, and high doses of Chinese herbal extracts alleviate the chronic alcohol consumption-induced trabecular bone damage; all three doses of Chinese herbal extracts mitigate the alcoholinduced decreases of bone mineral density and relative bone volume or bone volume fraction (Figures 3B,C); the Chinese herbal extracts alleviate alcohol-reduced trabecular number decrease (Figure 3D) and the corresponding increase of trabecular separation (Figure 3E), but no effects were observed for trabecular thickness (Figure 3F)

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Summary

Introduction

Traditional Chinese medicine has treated various diseases, including bone diseases and alcoholism. The effects of alcohol on human health are complex It is debatable about the benefits of moderate drinking, epidemiological studies suggest that lightmoderate alcohol consumption benefits the heart and circulatory system, protects against diabetes, and is associated with lower risks for mortality and cancer in older adults (Howard et al, 2004; Karlamangla et al, 2009; Mostofsky et al, 2016; Kunzmann et al, 2018). Light to moderate alcohol consumption is generally reported to be beneficial or have a neutral impact on bone health in old adults, while chronic excessive drinking induces bone mass loss and osteoporosis, which increases fracture risk, deficient bone repair and causes alcohol-induced osteonecrosis (Turner, 2000; Chakkalakal, 2005; Maurel et al, 2012; Sommer et al, 2013; Mikosch 2014; Gaddini et al, 2016)

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