Integration of Metabolomics with Network Pharmacology Deciphers the Anti‐Fatigue Activity Mechanisms of the Extract of Mirabilis himalaica Root

Abstract Fatigue, a common symptom in both diseased and healthy individuals, is a biological phenomenon characterized by a sense of extreme physical or mental exhaustion. To explore novel drugs and food sources of anti‐fatigue, the hydroalcoholic extract of the root of Mirabilis himalaica (MH extract) is evaluated as anti‐fatigue agents in this work, and clarifies that the mechanism of MH intervention in fatigue symptoms, and distribution of the anti‐fatigue constituents in the plant of Mirabilis himalaica is examined. The results show that the MH extract have a significantly anti‐fatigue effect via the pharmacological experiment and biochemical indicators. The network pharmacology, metabolomics, molecular docking, and pharmacology are integrated to determine that boeravinone A, B, and E are the pharmacoperones of anti‐fatigue. Moreover, the compounds of boeravinone are present only in the root and not in the leaf and stem of the Mirabilis himalaica , which validates that root of Mirabilis himalaica is historically and officially utilized medicinal parts.