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

Authors Lu S, Zhang H, Wei X, Huang X, Chen L, Jiang L, Wu X, Zhou X, Qin L, Li Y, Lin X, Huang R

Received 20 March 2019

Accepted for publication 16 May 2019

Published 7 August 2019 Volume 2019:12 Pages 1355—1363

DOI https://doi.org/10.2147/DMSO.S209436

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Melinda Thomas

Peer reviewer comments 2

Editor who approved publication: Dr Konstantinos Tziomalos


Shunyu Lu,* Hongliang Zhang,* Xiaojie Wei, Xiang Huang, Lixiu Chen, Luhui Jiang, Xingchun Wu, Xing Zhou, Luhui Qin, Yuchun Li, Xing Lin, Renbin Huang

Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China

*These authors contributed equally to this work

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.

Keywords: 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione, diabetic nephropathy, TLR4/MyD88/NF-κB signalling pathway

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