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Effects of phenolic-rich extracts of Clinacanthus nutans on high fat and high cholesterol diet-induced insulin resistance.

ABSTRACT: Clinacanthus nutans is used traditionally in many parts of Asia to improve well-being, but there are limited studies on its efficacy. We explored the potential use of C. nutans for prevention of high fat and high cholesterol diet-(HFHC-) induced insulin resistance in rats.The leaf of C. nutans was extracted using water (AL extract) and methanol (AML extract), and the extracts were fed to rats alongside the HFHC diet for 7 weeks, and compared with simvastatin. Oral glucose tolerance test, and serum insulin, retinol binding protein 4 (RBP4), adiponectin and leptin were measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was computed, while transcriptional regulation of hepatic insulin signaling genes was also assessed.Glycemic response was higher in the HFHC group compared with the AL and AML groups, which also had lower serum RBP4, fasting glucose, insulin and HOMA-IR. Serum adiponectin levels were higher, while leptin levels were lower in the AML and AL groups compared to the HFHC group. There was upregulation of the Insulin receptor substrate, phosphotidyl inositol-3-phosphate, adiponectin receptor and leptin recetor genes, in comparison with the HFHC group.Overall, the results showed that the HFHC diet worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. C.nutans, on the other hand, attenuated the metabolic effects and transcriptional changes induced by the HFHC diet. The results suggested that C.nutans may be a good source of functional ingredient for the prevention of insulin resistance.

SUBMITTER: Sarega N

PROVIDER: S-EPMC4770701 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Project description:This project studied the effect of vermicompost application on the composition of bioactive anthocyanin and phenolic compounds, and the antioxidant activity of Clinacanthus nutans. The correlation between the bioactive constituents and antioxidant capacity was also evaluated. In this project, a field study was conducted using a randomized complete block design (RCBD) with four treatment groups, including control plants (CC), plants supplied with chemical fertilizer (CF), plants supplied with vermicompost (VC), and plants supplied with mixed fertilizer (MF). The leaves of C. nutans from all treatment groups were harvested, subjected to solvent extraction, and used for quantification of total anthocyanin content (TAC), total phenolic content (TPC), and total flavonoid content (TFC). The initial antioxidant activity of the extracts was evaluated using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, as well as after two and four weeks of storage at -20 °C and 4 °C. Data analysis showed that CC plants contained the highest TAC (2180.14 ± 338.43 µg/g dry weight) and TFC (276.25 ± 3.09 mg QE/g dry weight). On the other hand, CF plants showed the highest TPC (181.53 ± 35.58 mg GAE/g dry weight). Moreover, we found that CC plants had the highest antioxidant potential against DPPH radicals whereas MF plants showed the lowest antioxidant potential. After four weeks of extract storage at -20 °C and 4 °C, the TPC, TFC, TAC, and antioxidant potential of the extracts decreased. Extracts from VC showed the lowest percentage of total phenolic and total flavonoid loss after extract storage at -20 °C and 4 °C compared with other plant extracts. At this juncture, it could be deduced that the application of vermicompost had little effect on the expression of phenolics, flavonoids, or anthocyanin in C. nutans. However, the extract from plants treated with vermicompost (VC and MF) showed better stability compared with CC and CF after extract storage at different temperatures.

Project description:BackgroundClinacanthus nutans extracts have been consumed by the cancer patients with the hope that the extracts can kill cancers more effectively than conventional chemotherapies. Our previous study reported its anti-inflammatory effects were caused by inhibiting Toll-like Receptor-4 (TLR-4) activation. However, we are unsure of its anticancer effect, and its interaction with existing chemotherapy.MethodsWe investigated the anti-proliferative efficacy of polar leaf extracts (LP), non-polar leaf extracts (LN), polar stem extract (SP) and non-polar stem extracts (SN) in human breast, colorectal, lung, endometrial, nasopharyngeal, and pancreatic cancer cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT assay. The most potent extracts was tested along with gemcitabine using our established drug combination analysis. The effect of the combinatory treatment in apoptosis were quantified using enzyme-linked immunosorbent assay (ELISA), Annexin V assay, antibody array and immunoblotting. Statistical significance was analysed using one-way analysis of variance (ANOVA) and post hoc Dunnett's test. A p-value of less than 0.05 (p < 0.05) was considered statistical significance.ResultsAll extracts tested were not able to induce potent anti-proliferative effects. However, it was found that pancreatic ductal adenocarcinoma, PDAC (AsPC1, BxPC3 and SW1990) were the cell lines most sensitive cell lines to SN extracts. This is the first report of C. nutans SN extracts acting in synergy with gemcitabine, the first line chemotherapy for pancreatic cancer, as compared to conventional monotherapy. In the presence of SN extracts, we can reduce the dose of gemcitabine 2.38-5.28 folds but still maintain the effects of gemcitabine in PDAC. SN extracts potentiated the killing of gemcitabine in PDAC by apoptosis. Bax was upregulated while bcl-2, cIAP-2, and XIAP levels were downregulated in SW1990 and BxPC3 cells treated with gemcitabine and SN extracts. The synergism was independent of TLR-4 expression in pancreatic cancer cells.ConclusionThese results provide strong evidence of C. nutans extracts being inefficacious as monotherapy for cancer. Hence, it should not be used as a total substitution for any chemotherapy agents. However, SN extracts may synergise with gemcitabine in the anti-tumor mechanism.

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Effects of phenolic-rich extracts of Clinacanthus nutans on high fat and high cholesterol diet-induced insulin resistance.

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