Four sesquiterpene glycosides from loquat (Eriobotrya japonica) leaf ameliorates palmitic acid-induced insulin resistance and lipid accumulation in HepG2 Cells via AMPK signaling pathway

Abstract

Insulin resistance (IR), caused by impaired insulin signal and decreased insulin sensitivity, is generally responsible for the pathophysiology of type 2 diabetes mellitus (T2DM). Sesquiterpene glycosides (SGs), the exclusive natural products from loquat leaf, have been regarded as potential lead compounds owing to their high efficacy in hypoglycemia and hypolipidemia. Here, we evaluated the beneficial effects of four single SGs isolated from loquat leaf, including SG1, SG2, SG3 and one novel compound SG4 against palmitic acid-induced insulin resistance in HepG2 cells. SG1, SG3 and SG4 could significantly enhance glucose uptake of insulin-resistant HepG2 cells at non-cytotoxic concentration. Meanwhile, Oil Red O staining showed the decrease of both total cholesterol and triglyceride content, suggesting the amelioration of lipid accumulation by SGs in insulin-resistant HepG2 cells. Further investigations found that the expression levels of phosphorylated AMPK, ACC, IRS-1, and Akt were significantly up-regulated after SGs treatment, on the contrary, the expression levels of SREBP-1 and FAS were significantly down-regulated. Notably, AMPK inhibitor Compound C (CC) blocked the regulative effects, while AMPK activator AICAR mimicked the effects of SGs in PA-treated insulin-resistant HepG2 cells. In conclusion, SGs (SG4>SG1≈SG3>SG2) improved lipid accumulation in insulin-resistant HepG2 cells through the AMPK signaling pathway.

Total Sesquiterpene Glycosides from Loquat Leaves Ameliorate HFD‐Induced Insulin Resistance by Modulating IRS‐1/GLUT4, TRPV1, and SIRT6/Nrf2 Signaling Pathways

“…For quantification, nerolidol-3- O - α - l -rhamnopyranosyl-(1→4)- α - l -rhamnopyranosyl-(1→2)-[ α - l -rhamnopyranosyl-(1→6)]- β -D-glucopyranoside (SG1), nerolidol-3- O - α - l -rhamnopyranosyl-(1→4)- α - l -rhamnopyranosyl-(1→2)- β -D-glucopyranoside (SG2), nerolidol-3- O - α - l -rhamnopyranosyl-(1→2)-[ α - l -rhamnopyranosyl-(1→6)]- β -D-glucopyranoside (SG3), and nerolidol-3-O- α - l -arabinopyranosyl-(1→4)- α - l -rhamnopyranosyl-(1→2)-[ α - l -rhamnopyranosyl-(1→6)]- β -D-glucopyranoside (SG4) were purified as standard compounds, and the same conditions were applied to HPLC. The chemical structure of SG1-4 is shown in Figures 1(b) and 1(c) and was consistent with the reported literatures [ 35 , 37 – 39 ].…”

“…According to earlier studies, extracts of loquat leaves reduced TC and promoted glucose uptake in HFD-induced IR condition, which was instrumental in treating IR [ 43 , 44 ]. Our previous investigation indicated that sesquiterpene glycosides from loquat leaves exhibited the bioactivity of reducing lipid accumulation and enhancing glucose uptake in insulin-resistant HepG2 cells via AMPK pathway [ 37 ].…”

“…Total sesquiterpene glycosides from loquat leaves were prepared in our lab following the method that we reported earlier [ 36 , 37 ]. In brief, the powder of dried loquat leaves was percolated with 80% ethanol solution twice.…”

miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells

“…A high insulin-induced insulin-resistant HepG2 cells model was established according the related references. [21][22][23] HepG2 cells were cultured in DMEM containing 10% FBS, 100 U/mL penicillin and 100 mg/mL streptomycin in 5% CO 2 in a humidified atmosphere. After the cells achieved about 80% confluence, the medium was changed and high concentration of insulin (30 μM) was supplemented to induce insulin-resistant model.…”

A draft genome at chromosome level and metabolomes of leave, root and flowers provide insights into the molecular basis of medicinal ingredients of loquat (Eriobotrya japonica (Thunb.) Lindl)

“…More than fourth metabolites incldung ursolic acid, ursolic acid methyl ester, acetyl ursolic acid, and oleanolic acid, chlorogenic acid, neochlorogenic acid, caffeic acid with potential medicinal value have been detected in different organs of loquat by classical instrumental analyses [51,52] . However, Traditional phytochemistry methods are very time-consuming, and labor intensive and low-throughput.…”