Rhodiola crenulata (RC) is a traditional herb and functional food that has demonstrated beneficial effects in improving physical function, enhancing work capacity, alleviating fatigue, and preventing altitude sickness. Additionally, RC has shown promising effects in the treatment of non-alcoholic fatty liver disease (NAFLD), although its specific bioactive components and underlying mechanisms remain unclear. In this study, ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS) combined with network pharmacology was employed to identify six potential bioactive compounds from the serum of rats treated with RC—Salidroside, Tyrosol, Crenulatin, Catechin gallate, Eriodictyol, and Rhodiooctanoside—that may contribute to its therapeutic effects on NAFLD. The efficacy of these compounds in improving NAFLD was assessed in vitro using HepG2 cells exposed to Palmitic acid (PA), and it was found that Catechin gallate exhibited a significant effect in reducing lipid accumulation in HepG2 cells. Furthermore, based on network pharmacology predictions, molecular docking studies suggested that the primary targets of Catechin gallate in alleviating fatty liver might include ABCB1, DYRK1A, PGD, and FUT4. Molecular dynamics simulations revealed stable binding interactions between Catechin gallate and these four target proteins. This study clarifies the material basis of RC in the treatment of NAFLD and provides a theoretical foundation for the application of RC and Catechin gallate as functional additives for the management of NAFLD.

Background: Finger citron (Citrus medica L. var. sarcodactylis Swingle, CM) is an important edible and medicinal plant. Owing to its diverse pharmacological properties, its fruit has long served as a traditional Chinese medicine and has increasingly been developed for functional food applications. However, its non-fruit parts, including leaves, branches, and roots, remain underutilized. Methods: In this study, CM fruit (CMF), leaves (CML), roots (CMR), and branches (CMB) were selected to systematically compare their small-molecule metabolic profiles and antioxidant and anti-inflammatory activities. Untargeted metabolomics was conducted based on ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Meanwhile, antioxidant capacity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, and anti-inflammatory activity was assessed using a lipopolysaccharide (LPS)-induced RAW 264.7 macrophage inflammation model. Results: Metabolomic analysis revealed 826 differential metabolites across the four CM parts (CMs), reflecting pronounced organ-specific metabolic features. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the variations in metabolite profiles across the four CMs were primarily linked to amino acid metabolism, phenylalanine metabolism, and unsaturated fatty acid metabolism. In the antioxidant assays, the DPPH radical scavenging activity at 2 mg/mL followed the order CML (78.37 ± 7.29%), CMR (73.30 ± 2.68%), CMB (40.71 ± 0.16%), and CMF (36.67 ± 1.67%), whereas ABTS radical scavenging activity followed the order CMR (51.36 ± 2.17%), CML (48.30 ± 1.64%), CMB (45.23 ± 1.72%), and CMF (18.48 ± 0.22%). In the LPS-stimulated RAW 264.7 macrophage model, at 0.4 mg/mL, inhibition of nitric oxide (NO) production followed the order CML (88.18 ± 4.02%), CMB (87.21 ± 3.02%), CMF (68.05 ± 2.54%), and CMR (67.21 ± 9.12%). Correlation analysis further suggested that features putatively annotated as minecoside, maltotetraose, and (+)-catechin may be associated with antioxidant or anti-inflammatory activities. Conclusions: The study revealed differences in metabolite composition and bioactivities among different CMs, providing an experimental basis for the development and utilization of non-fruit parts, especially leaves, and for further investigation of their bioactive constituents.