Background: Diabetes mellitus involves complex pathogenesis requiring multi-target interventions. Citrus reticulata ‘Dahongpao’ from Chongqing exhibits anti-diabetic potential, but its mechanisms remain elusive. Methods: We employed an integrative strategy: GC-MS identified 82 compounds (96.61% coverage), dominated by D -limonene (62.48%). Network pharmacology revealed 36 diabetes-related targets. Molecular docking prioritized ligands (thymol: −6.8 kcal/mol with FABP1; n-hexadecanoic acid: −6.7 kcal/mol with PTGS2). Critical validation was achieved via 100-ns molecular dynamics (MD) simulations and MM-GBSA binding free energy calculations. Results: MD simulations demonstrated structural stability (RMSD < 2.5 Å) for core complexes (e.g., CYP19A1/thymol). MM-GBSA quantified robust binding for FABP1/dodecanoic acid (−43.26 kcal/mol) and PTGS2/n-hexadecanoic acid (−43.93 kcal/mol), driven by van der Waals forces. Hydrogen bond dynamics revealed persistent interactions (e.g., thymol–THR102 in FABP1), while RMSF highlighted ligand-induced flexibility in fatty acids. Pathway analysis implicated PPAR signaling and insulin resistance. Conclusion: Citrus reticulata ‘Dahongpao’ essential oil combats diabetes through synergistic multi-target modulation, validated by dynamic ligand–protein stability and energetics. This study presents an in silico framework that integrates phytochemical profiling and computational analyses to facilitate natural product drug discovery.

Citron (Citrus medica L.) peel essential oil is rich in terpenoids, but their composition and formation mechanisms remain unclear. We analyzed volatile compounds and gene expression in citron peel across three developmental stages using GC-MS and RNA-seq. GC-MS identified 91 volatiles, with γ-Terpinene and D-Limonene the most abundant; terpenes dominated (95.60–87.72%) but decreased with maturation, with 19 differential terpenoid metabolites. Differential expression analysis identified 10,238 genes with significant changes across three stages, including 256 TPS genes and 656 transcription factors. Via WGCNA and correlation analysis, 10 gene–metabolite pairs were identified, including 5 key genes and 2 transcription factors linked to nerol synthesis. These findings provide a framework for future research on citron genetics, terpenoid identification, and regulatory mechanisms of terpenoid biosynthesis.

The antioxidant properties and characteristic metabolites of Phlomoides rotata (P. rotata) essential oils (EOs) remain largely unexplored. To address this gap, we combined metabolomic profiling with in vitro antioxidant assays to systematically characterize EOs from P. rotata. Cryoprecipitation of EOs yielded two fractions: crystals (Crs) and crystal-free EOs (CEs). GC-MS identified 125 components (84.41-94.86%), including 94 novel reports in P. rotata. Dominant constituents were long-chain fatty acids (LCFAs, 42.33-75.73%) and their esters (3.44-15.21%), notably palmitic acid (14.49-63.13%), myristic acid, linoleic acid, oleic acid, and methyl palmitate. Eleven norisoprenoids, including trans-β-damascenone, were discovered—a fivefold increase from previously reported diversity—with their biosynthetic pathways elucidated. Eleven chemical markers were established, encompassing geraniol, linalool, trans-β-damascenone, hexahydrofarnesyl acetone, palmitic acid, α-terpineol, myristic acid, phytol, linoleic acid, oleic acid, and methyl palmitate. Palmitic acid, myristic acid, methyl palmitate, and hexahydrofarnesyl acetone showed negligible or pro-oxidative activity. Linoleic acid, oleic acid, trans-β-damascenone, and phytol exhibited concentration-dependent antioxidant effects. Phytol demonstrated exceptional potency, surpassing quercetin in cellular antioxidant activity at 80 μmol/L. CEs exhibited significantly stronger antioxidant capacity in both DPPH and ABTS assays compared to EOs and Crs. Palmitic acid depletion in CEs was identified as a critical factor driving enhanced antioxidant performance. This study not only establishes P. rotata EOs as a rich source of phytol-based antioxidants but also deciphers the dual roles of LCFAs, providing a foundation for developing natural antioxidants.