| Description: |
Chebulagic acid is a potent DNA topoisomerase inhibitor, and is also COX-2 and 5-LOX dual inhibitor. Chebulagic acid may be of value as broad-spectrum antivirals for limiting emerging/ recurring viruses known to engage host cell glycosaminoglycans for entry. Chebulagic acid can be used to control blood glucose and manage type 2 diabetes, although clinical trials are needed.
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| Targets: |
COX | LOX | Topoisomerase | HIV | AMPK | Autophagy | mTOR | ATPase | PPAR | GLUT | Bcl-2/Bax | Caspase | P450 (e.g. CYP17) | CDK | NF-kB | MMP(e.g.TIMP) | VEGFR | IkB | IKK |
| In vitro: |
| BMC Complement Altern Med. 2014 Aug 29;14:319. | | Chebulagic acid from Terminalia chebula causes G1 arrest, inhibits NFκB and induces apoptosis in retinoblastoma cells.[Pubmed: 25169718] | Plants are the valuable source of natural products with important medicinal properties. Most of the approved anti cancer drugs have a natural product origin or are natural products. Retinoblastoma is the most common ocular cancer of children. Although chemotherapy is the preferred mode of therapy, a successful treatment for retinoblastoma requires enucleation. Chebulagic acid (CA) from Terminalia chebula was shown to have anti-proliferative properties in the studies on cancerous cell lines. Due to anti cancer properties of CA and due to limitation in treatment options for retinoblastoma, the present study is undertaken to understand the role of CA on the proliferation of retinoblastoma cells.
METHODS AND RESULTS:
Anti proliferative potential of CA was determined by MTT assay. The expression levels of various cell death mediators in retinoblastoma cells with CA treatment were assessed by Western blotting. Flowcytometer analysis was used to estimate the mitochondrial membrane potential (MMP) and to determine the percentage of cells undergoing apoptosis.
The present study showed CA inhibited the proliferation of retinoblastoma cells in a dose dependent manner. CA modulated MMP, induced release of Cytochrome c, activated caspase 3 and shifted the ratio of BAX and Bcl2 towards cell death. G1 arrest, noticed in CA treated cells, is mediated by the increase in the expression of CDK inhibitor p27. CA treatment also decreased the levels of NFκB in the nucleus. This decrease is mediated by suppression in degradation of IκBα.
CONCLUSIONS:
CA has shown significant anti proliferative potential on retinoblastoma cells. Our findings clearly demonstrate that CA induces G1 arrest, inhibits NFκB and induces apoptosis of retinoblastoma cells. | | Sci Rep. 2015 Apr 10;5:9642. | | The natural compound chebulagic acid inhibits vascular endothelial growth factor A mediated regulation of endothelial cell functions.[Pubmed: 25859636] | Vascular endothelial growth factor A (VEGFA) plays an important role in tumour angiogenesis and its angiogenic action is mainly mediated through its VEGF receptor 2 (VEGFR-2). Therefore drugs targeting VEGFA/VEGFR-2 are being presently used in the clinics for treatment of several types of solid malignant tumours.
METHODS AND RESULTS:
We here in report that low dose of chebulagic acid (CA), a hydrolysable tannin found in myrobalan fruits can inhibit VEGFA induced vascular permeability, endothelial cell proliferation, migration, tube formation and thereby, angiogenesis by suppressing VEGFR-2 phosphorylation.
CONCLUSIONS:
CA may thus be an effective and useful natural inhibitor of VEGFA mediated angiogenesis. |
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| In vivo: |
| Int J Mol Sci. 2012;13(5):6320-33. | | Anti-hyperglycemic effect of chebulagic acid from the fruits of Terminalia chebula Retz.[Pubmed: 22754367] |
METHODS AND RESULTS:
In the present study, we firstly compared rat intestinal α-glucosidase inhibitory activity by different ethanol-aqueous extractions from the dried fruits of Terminalia chebula Retz. The enzymatic assay showed that the 80% ethanol extract was more potent against maltase activity than both 50% and 100% ethanol extracts. By HPLC analysis, it was determined that the 80% ethanol extract had a higher content of chebulagic acid than each of 50% or 100% ethanol extract. Next, we investigated how efficiently chebulagic acid could inhibit sugar digestion by determining the glucose level on the apical side of the Caco-2 cell monolayer. The result showed that the maltose-hydrolysis activity was down-regulated by chebulagic acid, which proved to be a reversible inhibitor of maltase in Caco-2 cells. On the other hand, chebulagic acid showed a weak inhibition of sucrose-hydrolysis activity. Meanwhile, chebulagic acid did not have an obvious influence on intestinal glucose uptake and was not effective on glucose transporters. Further animal studies revealed that the oral administration of chebulagic acid (100 mg/kg body weight) significantly reduced postprandial blood glucose levels by 11.1% in maltose-loaded Sprague-Dawley (SD) rats compared with the control group, whereas the oral administration of chebulagic acid did not show a suppressive effect on postprandial hyperglycemia in sucrose- or glucose-loaded SD-rats.
CONCLUSIONS:
The results presented here suggest that chebulagic acid from T. chebula can be used to control blood glucose and manage type 2 diabetes, although clinical trials are needed. |
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