Anti-type 2 diabetes mellitus compounds and pharmacological mechanism of Dendrobium officinale

Abstract Objectives This study aimed to explore the effective compounds and pharmacological mechanisms of Dendrobium officinale for the treatment of T2DM. Methods A qualitative analysis of effective compounds of D. officinale was performed by UPLC-ESI-Q-Orbitrap, network pharmacology analysis was used to preliminarily predict anti-T2DM mechanisms of D. officinale , virtual screening of effective compounds of D. officinale and validation of core protein targets were subsequently implemented through molecular docking technique. 3T3-L1 mouse preadipocytes was to validate the anti-T2DM therapeutic effect and pharmacological mechanism of D. officinale , relevant biochemical indexes and proteins were detected by biochemical assay kits and western blot method. Results There were 27 chemical compounds identified in D. officinale , anti-T2DM compounds of D. officinale were α-linolenic acid, naringenin, n-trans-feruloyltyramine, paprazine, et al. D. officinale extract could promote glucose uptake of 3T3-L1 cells in a dose-dependent manner and increase TG content in the cells, anti-T2DM mechanisms of D. officinale may involve PI3K/Akt, insulin resistance and insulin signaling pathways, core compounds of D. officinale were α-linolenic acid, naringenin, n-trans-feruloyltyramine, paprazine, isobutyl 4-hydroxybenzoate, pinellic acid, azelaic acid, acuminoside, rac-1-monopalmitoylglycerol and atractyloside A according to degree value of the network, anti-T2DM core targets of D. officinale were also screened out, including PIK3CA, AKT1, AKT2, MAPK1, MAPK3, MAP2K1, HRAS, PRKCA, MAPK8 and EGFR. Acuminoside, naringenin, n-trans-feruloyltyramine, et al. exhibited better affinity effects with PIK3CA, AKT1 and AKT2 while their docking scores were below −7.2 kcal mol −1 . The expressions of p-PI3K, p-AKT and GLUT4 in 3T3-L1 cells were significantly upregulated by D. officinale extract which indicated PI3K/Akt pathway was activated in insulin resistance and insulin signaling pathways of 3T3-L1 adipocytes under the therapeutic effect of D. officinale . Conclusions D. officinale could improve insulin resistance in T2DM by modulating PI3K/Akt, insulin resistance and insulin signaling pathways, acuminoside, naringenin, n-trans-feruloyltyramine, et al. from D. officinale could be used as anti-T2DM lead compounds with PI3K, AKT and GLUT4 as protein targets.