Black Raspberry and Phlomis Umbrosa Turcz. Extract Mixture (BLB301) Alleviates Dexamethasone-Induced Muscle Atrophy by Modulating Oxidative Stress and Protein Turnover Pathways

Abstract

This study aimed to evaluate the protective effects of black raspberry (Rubus occidentalis L. L.), shady Jerusalem sage (Phlomis umbrosa Turcz.), and their combination (BLB301) on dexamethasone-induced muscle atrophy using both cellular and animal models. In the former, the cytotoxicity and mRNA expression of key anabolic and catabolic markers were evaluated in C2C12 cells subjected to hydrogen peroxide (H₂O₂)-induced oxidative stress and treated with the extracts. In the latter, male ICR mice were assigned to the following groups: control (CON), dexamethasone injection (DEX), and DEX receiving 100 mg/kg, 200 mg/kg, or 400 mg/kg BLB301. C2C12 cells treated with BLB301 exhibited higher scavenging activity and mTOR expression than the CON and DEX cells. The mice in the DEX group exhibited significantly lower body weight (b.w.), grip strength, and muscle-to-b.w. ratios and higher oxidative stress and catabolic marker (myostatin, atrogin-1, and MuRF1) expression levels than those in the other groups. BLB301 mitigated the foregoing effects in a dose-dependent manner by increasing the antioxidant enzyme activity and decreasing the malondialdehyde levels. It also upregulated key anabolic pathways (PI3K/Akt/mTOR/S6K1) and muscle-specific transcription factors (Myf5, MyoD, and myogenin). BLB301 also downregulated the catabolic markers and restored the balance between protein synthesis and degradation. Therefore, BLB301 alleviates dexamethasone-induced muscle atrophy by modulating oxidative stress and by promoting and inhibiting anabolic and catabolic pathways, respectively. The findings of this study demonstrate the potential of BLB301 as a therapeutic agent for muscle-wasting conditions.