EMCD, a hypoglycemic triterpene isolated from Momordica charantia wild variant, attenuates TNF-α-induced inflammation in FL83B cells in an AMP-activated protein kinase-independent manner.
Insulin resistance is a causative factor for type 2 diabetes, whereas the development of insulin resistance is closely related to chronic inflammation induced by factors such as tumor necrosis factor-α (TNF-α). Momordica charantia, also known as bitter melon, has been used as an herbal medicine and reported to ameliorate inflammation and hyperglycemia. Previously, a triterpene 5β,19-epoxy-25-methoxy-cucurbita-6,23-diene-3β,19-diol (EMCD), purified from M. charantia L. wild variant WB24, was found to activate AMP-activated protein kinase (AMPK) and have a hypoglycaemic effect in TNF-α-treated FL83B cells. AMPK has been a target for developing anti-diabetic medicine and suggested to play a role in anti-inflammation. The current study aims to investigate if EMCD might repress TNF-α-induced inflammation via AMPK. TNF-α-induced inflammation in FL83B cells was characterized using Western blotting and reverse transcriptase-polymerase chain reaction. Consequently, the expression of inflammatory markers including inducible nitric oxide synthase (iNOS), the p65 subunit of nuclear factor-κB (NF-κB), protein-tyrosine phosphatase-1B, TNF-α and interleukin-1β were significantly elevated by TNF-α in the cell, and EMCD obviously suppressed the TNF-α-induced expression of these markers. When the effect of EMCD was tested simultaneously with epigallocatechin-3-gallate (EGCG), a catechin from green tea reported to be anti-inflammatory, EMCD showed a more obvious anti-inflammatory activity than EGCG did. Investigation of the underlying mechanism suggested that EMCD inhibited the activation of the IκB kinase (IKK) complex and the NF-κB pathway, and the effect was likely independent of AMPK. Collectively, the multiple functions of EMCD suggest it to be a potential agent in treating diabetic complications and other inflammation-related disorders.
Department of Biological Science and Technology, National Pingtung University of Science and Technology, Room BT212, Biotechnology Hall, No. 1, Shuehfu Rd., Neipu, Pingtung 91201, Taiwan. hlcheng@mail.npust.edu.tw
Hsueh-Ling
HL
Cheng
Ching-Yi
CY
Kuo
Yun-Wen
YW
Liao
Chen-Chen
CC
Lin
D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D029777:Momordica charantia; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000633:toxicity*
D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D010936:Plant Extracts; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D055372:AMP-Activated Protein Kinases