Table 2.
Experimental model | Mechanism of action |
---|---|
T2DM Chinese hamsters | Changed the expression of hepatic peroxisome proliferator-activated receptors and its target genes [15] |
3T3-L1 cells | Increased glucose uptake in fat cells and inhibited the differentiation of preadipocytes [16] |
Sprague Dawley rats | Reduced plasma FFA and triglyceride levels and inhibited the expression of liver TNF-α [17] |
Sprague Dawley rats | Increased HNF-4α expression [18] |
Wistar rats | Regulated the expression of endoplasmic reticulum chaperone ORP150 and reduced ER stress [19] |
HepG2 cells | Regulated AMPK activity to decrease its downstream gluconeogenesis protein expression [20] |
Wistar rats | Inhibited pancreatic β-cell apoptosis by inhibiting ASK1 protein expression [21] |
Wistar rats | Increased PI-3K p85 and GLUT4 protein expression in skeletal muscles of T2DM rats [22] |
Insulin resistant rat models | Inhibited TNF-α secretion and reduced serum free fatty acid level [23] |
Wistar rats | Increased mRNA expression of adiponectin gene and decreased IRI in T2DM rats [24] |
T2DM Chinese hamsters | Inhibited the expression of PEPCK, 6Pase, and PGC-1α by enhancing CYP7A1 and Gck expression induced by the upregulation of LXRα expression [25] |
L6 myotubes | Inhibited fatty acid uptake at least in part by reducing PPAR gamma and FAT/CD36 expression [26] |
L6 rat skeletal muscle cells | Induced InsR gene expression through a protein kinase C (PKC) dependent activation of its promoter. Inhibited PKC abolished BBR-caused InsR promoter activation and InsR mRNA transcription [27] |
Nonalcoholic fatty liver disease rat liver |
Upregulated the mRNA and protein levels of IRS-2 [28] |
3T3-L1 adipocytes | Reversed free fatty acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ [29] |
Cultured HepG2 cells | Attenuated ER stress and improved insulin signal transduction [30] |
Rat skeletal muscle cells | Modulated key molecules in the insulin signaling pathway, leading to increased glucose uptake in insulin-resistant cells [31] |
Insulin resistant rat models | Stimulated AMPK activity [32] |
T2DM hamsters | Altered the transcriptional programs of the visceral white adipose tissue LXRs, PPARs, and SREBPs [33] |
Diabetic hamsters | Altered the transcriptional programs of hepatic SREBPs, LXRα, and PPARα [34] |
Mouse primary hepatocyte | Upregulated HNF4α expression to induce hepatic glucokinase activity [35] |
Mouse primary hepatocyte | Upregulated HNF6 mRNA expression and induced hepatic glucokinase activity [36] |
HepG2 cells | Increased hepatic glucose consumption [37] |
Wistar rats | Elevated IRS-1, IRS-2, and p85 mRNA expression in the peripheral tissues [38] |
Sprague Dawley rats | Increased the content of GLU4 mRNA in skeletal muscles, increased the content of GLUT4 protein in cells, and enhanced insulin activity in the peripheral tissues [39] |
Kunming mice | Inhibited gluconeogenesis and/or stimulated glycolysis [40] |
Diabetic rat model | Stimulated GLP-1 release [41] |
Wistar rats | Regulated INS and GH levels by enhancing SS levels through the hypothalamus-pituitary-pancreatic axis system [42] |
HepG2 cells | Increased InsR mRNA transcription and protein expression [43] |
Alloxan-induced diabetic mice | Upregulated the activity of Akt [44] |
Wistar rats | Stimulated GK activity and expression [45] |
3T3-L1 adipocytes and L6 myocytes | Inhibited PTP 1B activity and increased phosphorylation of IR, IRS1, and Akt in 3T3-L1 adipocytes [46] |
Streptozotocin-induced diabetic rats |
Enhanced GLP-1-(7-36) amide secretion [47] |
Mammalian cells | Functioned as an agonist of the fatty acid receptor GPR40 [48] |
T2DM rat models | Lowered serum RBP4 levels and upregulated the expression of tissue GLUT4 protein [49] |
Streptozotocin-induced diabetic rats |
Exhibited inhibitory effects on intestinal disaccharidases and β-glucuronidase [50] |
L6 rat skeletal muscles | Stimulated glucose uptake through the AMP-AMPK-p38 MAPK pathway [51] |
3T3-L1 adipocytes | Enhanced GLUT1 expression and stimulated the GLUT1-mediated glucose uptake by activating GLUT1 [52] |
Alloxan-induced diabetic C57BL/6 mice |
Upregulated Akt activity via insulin signaling pathways [53] |
Molecular model | Inhibited H-PTP 1B [54] |
Streptozotocin-induced diabetic rats |
Involved PKA-dependent pathways [55] |
Normal animals (dogs and rats) |
Acutely inhibited α-glucosidase [56] |
Molecular model | Inhibited DPP IV [57] |
L929 fibroblast cells | Significantly activated GLUT1 transport [58] |
Diabetic rats | Directly inhibited gluconeogenesis in the liver [59] |
Rat model | Inhibition of glucose oxidation in mitochondria may contribute to increased AMP/ATP ratio and AMPK activation [60] |
Caco-2 cell line | Inhibited α-glucosidase activity and decreased glucose transport across the intestinal epithelium [61] |
T2DM: type 2 diabetes mellitus; TNF: tumor necrosis factor; FFA: free fatty acid; HNF: hepatocyte nuclear factor; ER: endoplasmic reticulum; ORP: oxygen-regulated protein; AMPK: AMP-activated protein kinase; ASK: apoptosis signal-regulating kinase; mRNA: messenger RNA; IRI: insulin resistant index; PEPCK: phosphoenolpyruvate carboxylase kinase; PGC-1α: peroxisome proliferator-activated receptor-γ coactivator 1α; CYP7A1: cholesterol 7 α-hydroxylase; GCK: glucokinase; PI-3K: phosphatidylinositol 3-kinase; GLUT4: glucose transporter type 4; PPAR: peroxisome proliferator-activated receptor; FAT/CD36: fatty acid translocase; PKC: protein kinase C; BBR: berberine; IKKβ: inhibitor kappa B kinase β; LXRs: liver X receptors; SREBPs: sterol regulatory element binding proteins; IRS: insulin receptor substrates; GLP: glucagon-like peptide; INS: insulin; GH: growth hormone; SS: somatostatin; Akt: protein kinase B; PTP1B: protein tyrosine phosphatase 1B; IR: insulin resistance; GPR40: G protein-coupled receptor 40; RBP4: retinol-binding protein 4; H-PTP 1B: human protein tyrosine phosphatase 1B; DPP IV: dipeptidyl peptidase IV; AMP: adenosine monophosphate; ATP: adenosine triphosphate.