Exploring the mechanism of Madetuliayate Formula on denervated muscle weakness and atrophy based network pharmacology and validation analysis

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Background The Madetuliayate Formula (MDTF) is a traditional Chinese medicine that shows promise in treating nerve injury (NI) and its complications, including muscle weakness (MW) and muscle atrophy (MA). However, the specific bioactive compounds and pharmacological mechanisms underlying its therapeutic effects remain unclear. Methods We employed network pharmacology analysis, molecular docking, molecular dynamics simulations, and in vivo validation experiments to investigate the potential mechanisms of MDTF in the treatment of NI, MW, and MA. Results Through network pharmacology analysis, we identified 112 active ingredients, including quercetin, (+)-catechin, apigenin, oleic acid, and luteolin, along with 7903 corresponding targets of MDTF. By intersecting these targets with those associated with NI, MW, and MA, we identified 302 common targets. We constructed a PPI network to illustrate the MDTF-component-target-disease interactions and screened five target genes: SRC, STAT3, TP53, EGFR, and PIK3CA. Gene ontology (GO) terms and KEGG pathway enrichment analyses indicated that MDTF may influence the signaling pathways PiC, CCRI, LAA, PGC, CMC, and Mir-CA. Molecular docking studies demonstrated that the primary active ingredients exhibit strong binding activity with the target genes. Molecular dynamics simulations confirmed the stability of the docking results between the main active ingredients and the 3D structures of the target genes. Animal experiments indicated that MDTF treatment significantly improved NI, MW, and MA, as evidenced by enhanced conduction function in a nerve model ( P < 0.05), increased maximum muscle strength, and greater muscle thickness of the biceps femoris (All P < 0.05), as well as changes in weight ( P < 0.05). Mechanistically, the potential mechanism of action appears to involve the inhibition of SRC, STAT3, TP53, and EGFR, while activating PIK3CA. Conclusions MDTF may enhance NI and its complications, MW and MA, by inhibiting SRC, STAT3, TP53, and EGFR, while activating PIK3CA.

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