Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway

Abstract

Background/Aims: Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD), isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Methods: Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA)-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. Conclusions: DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway.

Hyperbaric oxygen protects against myocardial reperfusion injury via the inhibition of inflammation and the modulation of autophagy

“…The parallel amplification of rat β-Actin and GAPDH were performed for references. The levels of mRNA expression were determined using the 7300 Real Time PCR system SDS software according to the 2 -ΔΔCt method [ 54 ].…”

<p>2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione isolated from <em>Averrhoa carambola L</em>. root ameliorates diabetic nephropathy by inhibiting the TLR4/MyD88/NF-κB pathway</p>

“…Recently, we used a high-sugar and high-fat diet integrated with low-dosage STZ to generate a diabetic nephropathy mouse model and found that DMDD significantly relieved renal pathological damage, blood urea nitrogen, serum creatinine, blood urea and urine protein levels. Experiments showed that DMDD significantly attenuated the apoptosis of MIN6 cells which induced by Palmitic Acid through inhibiting the TLR4/MyD88/NF-κB signalling pathway 5,28,29. Now, we intend to investigate TLR4 as a target to explore the mechanism of DMDD-mediated protection in diabetic nephropathy, providing experimental basis and theoretical support for DMDD treatment of DN.…”

<p>Anti-Breast Cancer Effect of 2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione in vivo and in vitro Through MAPK Signaling Pathway</p>

“…7 Previous studies have confirmed that its pharmacological effects mainly include antihyperglycemic, regulation of blood lipids, and lessening of inflammation. [8][9][10][11] Recent studies have found that DMDD can inhibit the proliferation of various cancer cells 12 and inhibit breast tumor growth in mice. 13 However, its antitumor mechanism is still unclear, and further research is needed.…”