Abstract

Muscle atrophy is an abnormal condition characterized by loss of skeletal muscle mass and function and is primarily caused by injury, malnutrition, various diseases, and aging. Leaf of lotus (Nelumbo nucifera Gaertn), which has been used for medicinal purposes, contains various active ingredients, including polyphenols, and is reported to exert an antioxidant effect. In this study, we investigated the effect of water extract of lotus leaf (LL) on muscle atrophy and the underlying molecular mechanisms of action. Amounts of 100, 200, or 300 mg/kg/day LL were administered to dexamethasone (DEX)-induced muscle atrophy mice for 4 weeks. Micro-computed tomography (CT) analysis revealed that the intake of LL significantly increased calf muscle volume, surface area, and density in DEX-induced muscle atrophy mice. Administration of LL recovered moving distance, grip strength, ATP production, and body weight, which were decreased by DEX. In addition, muscle damage caused by DEX was also improved by LL. LL reduced the protein catabolic pathway by suppressing gene expression of muscle atrophy F-Box (MAFbx; atrogin-1), muscle RING finger 1 (MuRF1), and forkhead box O (FoxO)3a, as well as phosphorylation of AMP-activated kinase (AMPK). The AKT-mammalian target of the rapamycin (mTOR) signal pathway, which is important for muscle protein synthesis, was increased in LL-administered groups. The HPLC analysis and pharmacological test revealed that quercetin 3-O-beta-glucuronide (Q3G) is a major active component in LL. Thus, Q3G decreased the gene expression of atrogin-1 and MuRF1 and phosphorylation of AMPK. This compound also increased phosphorylation levels of mTOR and its upstream enzyme AKT in DEX-treated C2C12 cells. We identified that LL improves muscle wasting through regulation of muscle protein metabolism in DEX-induced muscle atrophy mice. Q3G is predicted to be one of the major active phenolic components in LL. Therefore, we propose LL as a supplement or therapeutic agent to prevent or treat muscle wasting, such as sarcopenia.

Highlights

  • Muscle atrophy, known as muscle wasting, refers to a condition in which skeletal muscle mass is lost and is mainly accompanied by impairment of physical activity due to abnormal weakness in muscle strength and function [1]

  • Muscle atrophy can be caused by various diseases or conditions, such as disuse from illness or injury, malnutrition, diabetes, cachexia associated with certain systemic diseases, side effects from pharmaceutical therapy, and aging [2,3]

  • lotus leaf (LL) Administration Has a Positive Effect on Calf Muscle Volume, Surface Area, and Density in

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Summary

Introduction

Known as muscle wasting, refers to a condition in which skeletal muscle mass is lost and is mainly accompanied by impairment of physical activity due to abnormal weakness in muscle strength and function [1]. Muscle atrophy can be caused by various diseases or conditions, such as disuse from illness or injury, malnutrition, diabetes, cachexia associated with certain systemic diseases (e.g., cancer, congestive heart failure, and chronic obstructive pulmonary disease), side effects from pharmaceutical therapy, and aging [2,3]. Reduced muscle mass and function from muscle atrophy increase morbidity and mortality. Loss of muscle mass is clinically related to poor prognosis and resistance to pharmaceutical treatment in cancer patients [4]. Loss of muscle mass can result in frequent falls and decreased ability to walk, thereby reducing the quality of life [2]. An effective treatment for muscle atrophy is lacking [5]

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