<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>

Abstract

Background Averrhoa carambola L. is a traditional medicinal herb that has long been used to treat diabetes. Our previous studies found that 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) isolated from A. carambola L . roots could ameliorate diabetic nephropathy (DN), but its exact mechanism remains unclear. Methods A DN model was established by streptozotocin (STZ, 100 mg/kg body weight) in TLR4 knockout (TLR4-/-, KO) mice and wild-type (WT) mice. Body weight and blood glucose were evaluated after oral administration of DMDD (12.5, 25, 50 mg/kg body weight/d) in diabetic mice. The levels of serum lipids, including TC, TG, HDL, and LDL and kidney function indexes Scr and BUN, were detected by biochemical equipment. The levels of inflammatory cytokines including IL-6 and TNF-α, were determined by ELISA kits. Furthermore, changes in renal ultrastructure were observed by electron microscopy. Western blot analysis and RT-PCR were used to assess the protein expression and mRNA levels of TLR4, MyD88 and NF-κB. Results DMDD treatment attenuated diabetic nephropathy, as a result of a decline in blood glucose, serum creatinine, and blood urine nitrogen levels and an increase in the quantity and density of podocytes, combined with improved dyslipidaemia. DMDD treatment inhibited the inflammatory response and downregulated the expression of the TLR4/MyD88/NF-κB pathway in diabetic mice, and these changes were significantly different in TLR4-/- mice. Conclusion DMDD alleviates diabetic nephropathy by mitigating kidney damage and inflammation via the inhibition of the TLR4/MyD88/NF-κB signalling pathway.

Antihyperlipidemic and Antioxidant Effects of Averrhoa Carambola Extract in High-Fat Diet-Fed Rats

“…Accordingly, consumption of A. carambola has been demonstrated to boost immunity and help remove toxins from the body. In addition, A. carambola extracts exhibit anti-inflammatory and antiulcerogenic properties [13] and ameliorate nonalcoholic hepatic steatosis [14] and diabetic nephropathy [15]. Our previous study indicated that methanolic extract of A. carambola leaf (MEACL) demonstrated antihyperlipidemic and antioxidant effects in poloxamer-407-induced hyperlipidemic rat model that were comparable to that of atorvastatin [16].…”

Emerging Exotic Fruits: New Functional Foods in the European Market

“…Studies on A. cherimola have identified a-glucosidase inhibitor phenolamides from leaves [44], acetylcholinesterase inhibitor alkaloids from the fruit peel [48], anticancer acetogenins and cyclic peptides from seeds [33,41], and tyrosinase inhibitor proanthocyanidins from the fruit pericarp [52]. Studies on A. carambola have suggested versatile therapeutic uses of the compound DMDD from the root, including the treatment of diabetic kidney disease [113], metabolic syndrome [114], Alzheimer's disease [122], and breast cancer cells [125], and in addition an antihyperglycemic effect of apigenin-6-C-b-fucopyranoside from the leaves [115]. Concern for possible adverse effects point to nephrotoxic oxalic acid and neurotoxic caramboxin of A. carambola fruit [128,130], but these problems are uncommon and linked to high intake and kidney comorbidity, while no warning is issued for regular consumption by healthy people.…”

“…The cyclohexanedione 2-Dodecyl-6methoxycyclohexa-2,5-diene-1,4-dione (DMDD) isolated from the root has been proved to lessen the hyperglycemia-stimulated, epithelial-mesenchymal transition, an initiating step of diabetic kidney disease, in a proximal tubule epithelial cell line [112]. In a streptozotocin-induced, diabetic nephropathy mouse model, DMDD has mitigated kidney damage and inflammation by inhibiting NF-kB activation induced by the TLR4/Myeloid Differentiation factor (Myd88) signaling pathway [113]. DMDD has also contrasted the obesity and insulin resistance induced in mice by a high-fat diet, by decreasing body and adipose tissue weights, glucose and lipid serum levels, as well as TLR4 and Myd88 expression in adipose tissue, and increasing insulin sensitivity [114].…”

<p>Protective Effect of Benzoquinone Isolated from the Roots of <em>Averrhoa carambola</em> L. on Streptozotocin-Induced Diabetic Mice by Inhibiting the TLR4/NF-κB Signaling Pathway</p>

“…12 Our previous works have revealed that the extract of Averrhoa carambola L. root had a high hypoglycemic activity on streptozotocin-induced diabetic mice. 13,14 The present research was projected to increase the hypoglycemic activity of BACR in diabetic animals. Figure 6 Pancreatic histological changes by HE staining (400×) (n=10).…”