Anggriani, Rista (2014) Study On The Mechanism Underlying The Hypoglycemic And Anti-Inflammatory Activity Of 5β, 19-Epoxy-25-Methoxy-Cucurbita-6,23-Diene-3β,19-Diol, A Triterpene Isolated From Momordica Charantia. Magister thesis, Universitas Brawijaya.
Abstract
English Abstract
Insulin resistance is a physiological condition in which cells fail to respond to the hormone insulin. Insulin resistance is associated with hyperglycemia and can contribute to a diagnosis of Type II diabetes. Therefore, the treatment of insulin resistance is a key strategy to prevent this illness. In a previous study of this laboratory, a triterpene, 5β, 19-epoxy-25- methoxy cucurbita-6, 23-diene-3β,19-diol (EMCD), purified from Momordica charantia L. wild variant was identified as a likely as an insulin sensitizer due to its effects in increasing glucose uptake in TNF-α-treated FL83B cells under insulin stimulation. The potential of EMCD was investigated and found to be comparable to that of insulin. EMCD has been demonstrated to have an insulin-like activity on glucose uptake in normal FL83B cells. The mechanism by which EMCD increases glucose uptake both as an insulin sensitizer and through insulin-like activity was further investigated. The results revealed that the presence of insulin is necessary in EMCD-activated tyrosine phosphorylation of IRS-1, Akt, and phosphorylation of AS160 in TNF-α-induced insulin resistant FL83B cells. This effect is likely, at least in part, related to its inhibiting effect on PTP-1B. Meanwhile, on normal cells EMCD had no effect on tyrosine phosphorylation of IRS-1 and Akt activation, but EMCD activated phosphorylation of AS160. The underlying mechanism possibly involves factors other than AMPK. The anti-diabetic potential of EMCD was also evaluated via PTP-1B inhibitory assay. EMCD showed potent inhibitory activity against PTP-1B with IC50 value of 94.70 μM and exhibited uncompetitive type inhibition. Meanwhile, molecular modelling between EMCD and PTP-1B with or without pNPP showed that EMCD has tendency acting partially as competitive and uncompetitive inhibition againts PTP-1B. In vivo its anti-diabetic activity did not reach statistical significance but it still suppressed blood glucose concentration in normal mice. However, EMCD acted in reducing TPA-induced ear edema. Therefore, these result suggest that EMCD possesses multiple action as insulin sensitizer and also as insulin-like effect in increasing glucose uptake that could be considered as a novel natural medicine for treating diabetes as well as inflammatory-related
| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | TES/615.323 63/ANG/s/041401587 |
| Subjects: | 600 Technology (Applied sciences) > 615 Pharmacology and therapeutics > 615.3 Organics drugs |
| Divisions: | S2/S3 > Magister Bioteknologi Perikanan dan Kelautan, Fakultas Perikanan dan Ilmu Kelautan |
| Depositing User: | Budi Wahyono Wahyono |
| Date Deposited: | 03 Jun 2014 14:56 |
| Last Modified: | 03 Jun 2014 14:56 |
| URI: | http://repository.ub.ac.id/id/eprint/158056 |
Actions (login required)
 |
View Item |