Modulation of Fatigue and Oxidative Stress by Lactobacillus plantarum CQPC02 in a Murine Model of Exercise-Induced Exhaustion

Sichuan pickle, a traditional Chinese fermented food, harbours a diverse microbial community. Microorganisms represent a promising source for the development of novel and potent therapeutic agents against human diseases. Herein, we investigated the anti-fatigue and antioxidant effects of Lactobacillus plantarum CQPC02 (LP-CQPC02), a strain isolated from Sichuan pickle, in a mouse model of exercise-induced exhaustion. ICR mice were orally administered LP-CQPC02 for four weeks. A fatigue model was established using a forced swim test. Subsequently, hepatic glycogen, skeletal muscle glycogen, lactic acid (LA), blood urea nitrogen (BUN), and free fatty acid (FFA) levels were measured via physicochemical methods. Serum levels of creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were determined using commercial assay kits. Histopathological alterations in liver tissue were examined by hematoxylin and eosin (H&E) staining, and mRNA expression changes in the liver and skeletal muscle were analysed via quantitative real-time PCR (qPCR). The results demonstrated that both vitamin C (positive control) and LP-CQPC02 significantly prolonged the exhaustive swimming time of mice, with a positive correlation observed between the LP-CQPC02 dose and the exhaustion time. LP-CQPC02 administration increased liver glycogen, muscle glycogen, and FFA levels in a dose-dependent manner, while concurrently reducing LA and BUN concentrations. Serum activities of CK, AST, and ALT were gradually decreased with increasing doses of LP-CQPC02. Furthermore, LP-CQPC02 treatment elevated SOD and CAT activities and reduced MDA content dose-dependently. At the molecular level, LP-CQPC02 upregulated the mRNA expression of copper/zinc-SOD (Cu/Zn-SOD), manganese-SOD (Mn-SOD), and CAT in the liver tissue of exhausted mice. In skeletal muscle, LP-CQPC02 enhanced the expression of the alanine/serine/cysteine/threonine transporter 1 (ASCT1) and suppressed the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumour necrosis factor-alpha (TNF-α). In summary, LP-CQPC02 exhibits pronounced anti-fatigue and antioxidant activities, suggesting its potential as a microbial-derived therapeutic agent. The novelty of this work lies in the first systematic demonstration that a specific Lactobacillus plantarum strain from traditional Sichuan pickle alleviates exercise-induced fatigue through multi-pathway synergism. The innovation extends beyond exploring the therapeutic value of traditional food-borne microbes to elucidating the comprehensive molecular mechanisms underlying their effects in vivo. These mechanisms encompass the regulation of energy metabolism (e.g., enhancing glycogen storage), mitigation of oxidative stress (e.g., boosting antioxidant enzyme activities and reducing lipid peroxidation), and modulation of key genes related to antioxidant defence and inflammation in hepatic and muscular tissues (e.g., Cu/Zn-SOD, Mn-SOD, CAT, ASCT1, iNOS, TNF-α). The implications of this research are twofold. Firstly, it provides robust experimental evidence supporting the development of LP-CQPC02 as a novel probiotic-based anti-fatigue agent, facilitating the translational application of functional foods or microecological therapeutics. Secondly, it identifies promising directions for future research, including the clarification of its active components, precise molecular targets, and potential gut microbiota-mediated mechanisms, as well as the exploration of its clinical applicability for chronic fatigue and related metabolic disorders.