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

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

Shunyu Lu,* Hongliang Zhang,* Xiaojie Wei, Xiang Huang, Lixiu Chen, Luhui Jiang, Xingchun Wu, Xing Zhou, Luhui Qin, Yuchun Li, Xing Lin, Renbin HuangPharmaceutical College, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this wo...

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Autores principales: Lu S, Zhang H, Wei X, Huang X, Chen L, Jiang L, Wu X, Zhou X, Qin L, Li Y, Lin X, Huang R
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2019
Materias:
2-Dodecyl-6-methoxycyclohexa-2
5-diene-1
4-dione
diabetic nephropathy
TLR4 /MyD88/NF-?B signalling pathway
Specialties of internal medicine
RC581-951
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spelling oai:doaj.org-article:a2a3b02f601049a585814b1e4438290d2021-12-02T07:11:33Z2-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 pathway1178-7007https://doaj.org/article/a2a3b02f601049a585814b1e4438290d2019-08-01T00:00:00Zhttps://www.dovepress.com/2-dodecyl-6-methoxycyclohexa-25-diene-14-dione-isolated-from-averrhoa--peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Shunyu Lu,* Hongliang Zhang,* Xiaojie Wei, Xiang Huang, Lixiu Chen, Luhui Jiang, Xingchun Wu, Xing Zhou, Luhui Qin, Yuchun Li, Xing Lin, Renbin HuangPharmaceutical College, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workBackground: 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 pathwayLu SZhang HWei XHuang XChen LJiang LWu XZhou XQin LLi YLin XHuang RDove Medical Pressarticle2-Dodecyl-6-methoxycyclohexa-25-diene-14-dionediabetic nephropathyTLR4 /MyD88/NF-?B signalling pathwaySpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 1355-1363 (2019)
institution DOAJ
collection DOAJ
language EN
topic 2-Dodecyl-6-methoxycyclohexa-2
5-diene-1
4-dione
diabetic nephropathy
TLR4 /MyD88/NF-?B signalling pathway
Specialties of internal medicine
RC581-951
spellingShingle 2-Dodecyl-6-methoxycyclohexa-2
5-diene-1
4-dione
diabetic nephropathy
TLR4 /MyD88/NF-?B signalling pathway
Specialties of internal medicine
RC581-951
Lu S
Zhang H
Wei X
Huang X
Chen L
Jiang L
Wu X
Zhou X
Qin L
Li Y
Lin X
Huang R
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
description Shunyu Lu,* Hongliang Zhang,* Xiaojie Wei, Xiang Huang, Lixiu Chen, Luhui Jiang, Xingchun Wu, Xing Zhou, Luhui Qin, Yuchun Li, Xing Lin, Renbin HuangPharmaceutical College, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workBackground: 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
format article
author Lu S
Zhang H
Wei X
Huang X
Chen L
Jiang L
Wu X
Zhou X
Qin L
Li Y
Lin X
Huang R
author_facet Lu S
Zhang H
Wei X
Huang X
Chen L
Jiang L
Wu X
Zhou X
Qin L
Li Y
Lin X
Huang R
author_sort Lu S
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/a2a3b02f601049a585814b1e4438290d
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