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Positive effect of Haritaki

Terminalia Chebula: Diabetes

Scientific experiments and studies on the positive effect of Haritaki in diabetes.

In numerous studies, it was found that Haritaki could significantly reduce blood glucose levels. Haritaki is suggested in them several times for the treatment of type 2 diabetes and in general as a useful tool for diabetics.

Anti-hyperglycemic effect of chebulagic acid from the fruits of Terminalia chebula Retz

International Journal of Molecular Sciences 2012;13(5):6320-33. doi: 10.3390/ijms13056320. Epub 2012 May 22.

In the present study, we firstly compared rat intestinal a-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. 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.

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.

[Link to the scientific study]

The role of mTOR and oral intervention of combined Zingiber officinale-Terminalia chebula extract in type 2 diabetes rat models

Journal of Food Biochemistry 2020 Jul;44(7):e13250. doi: 10.1111/jfbc.13250. Epub 2020 May 27.

The present study examined the potential of Zingiber officinale-Terminalia chebula extract alone (ZO and TC) and in combination (ZOTC) against type 2 diabetes via downregulation of mechanistic target of rapamycin (mTOR). The 1:4 (ZOTC) ratio showed high cell survival percentage against the rat insulinoma cell line (RIN-5F) when compared to other possible ratios of ZOTC. Oral administration of ZO alone, TC alone, combined ZOTC (1:4), and the positive control metformin (Met) in fructose-streptozotocin (STZ) -induced diabetic rats showed reduced blood glucose levels, reduced insulin resistance (HOMA-IR), increased insulin levels, and increased pancreatic beta cell function (HOMA-ß). ZOTC treatment in diabetic rats ameliorated the antioxidant status without affecting liver and serum parameters. Histological evaluation of the pancreas was performed to find pathological changes; the transcriptional and immunohistochemistry results showed reduced mTOR expression in the pancreas during ZOTC treatment. Conclusively, the results obtained suggest that ZOTC treatment against fructose-STZ-induced type 2 diabetes rat models can help regulate blood glucose, insulin levels, and normalize pancreatic ß cell damage. PRACTICAL APPLICATIONS: Type 2 diabetes is a chronic metabolic disorder that affects a large number of populations worldwide. Zingiber officinale (ZO) and Terminalia chebula (TC) has been used in traditional medicine since ancient times against various ailments, including diabetes. In this study, we reported the effect of the combined ZOTC that showed significant blood glucose reduction and increased insulin levels via mTOR when compared to individual treatments. This finding is valuable for food technologists and alternative medicine practitioners to know the antidiabetic effect of the ZOTC combination.

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Effect of an aqueous extract of Terminalia chebula on endothelial dysfunction, systemic inflammation, and lipid profile in type 2 diabetes mellitus: A randomized double-blind, placebo-controlled clinical study

Phytotherapy Research 2020 Dec;34(12):3226-3235. doi: 10.1002/ptr.6771. Epub 2020 Jul 2.

Endothelial dysfunction is a crucial complication in type 2 diabetic patients, related to cardiovascular risk. Terminalia chebula (TC), a traditional ayurvedic herb, is known for its antioxidant and antihyperlipidemic activity. A prospective, randomized, double-blind, placebo-controlled clinical study was undertaken to evaluate the effects of an aqueous extract of T. chebula 250 and 500 mg versus placebo on endothelial dysfunction and biomarkers of oxidative stress in type 2 diabetic patients. A total of 60 eligible patients were randomized to receive either T. chebula 250 mg, T. chebula 500 mg, or placebo twice daily for 12 weeks. The subjects were assessed based on the endothelial function, the levels of nitric oxide, malondialdehyde, glutathione, high sensitivity C-reactive protein, glycosylated hemoglobin, and lipid profile at baseline and after 12 weeks of treatment. Treatment with T. chebula 250 mg and T. chebula 500 mg for 12 weeks significantly improved the endothelial function (reflection index) compared to placebo (absolute changes: - T. chebula 250: -2.55 ± 1.82% vs. T. chebula 500: -5.21 ± 2.41% vs. placebo: 1.40 ± 2.11%). Other cardiovascular risk indicators were also significantly ameliorated in the treatment groups compared to placebo. In conclusion, T. chebula (especially, 500 mg BID dose) significantly minimized the cardiovascular risk factors in patients with type 2 diabetes compared to placebo.

In conclusion, Terminalia chebula (especially, 500 mg BID dose) significantly minimized the cardiovascular risk factors in patients with type 2 diabetes compared to placebo.

[Link to the scientific study]

The anti-diabetic and antioxidant effects of a combination of Commiphora mukul, Commiphora myrrha and Terminalia chebula in diabetic rats

Avicenna Journal of Phytomedicine Sep-Oct 2019;9(5):454-464.

Male Wistar rats (n=48) were randomly assigned into: control; diabetic; diabetic+metformin (300 mg/kg); diabetic+dose 1 of herbal combination (438 mg/kg of C. mukul+214 mg/kg of C. myrrha+857 mg/kg of T. chebula); diabetic+dose 2 (642 mg/kg of C. mukul+214 mg/kg of C. myrrha+642 mg/kg of T. chebula); and diabetic+dose 3 (857 mg/kg of C. mukul+438 mg/kg of C. myrrha+1714 mg/kg t of T. chebula). All treatments were given orally by gavage. Diabetes was induced by STZ (60 mg/kg, i.p.). At the end of study (day 28), blood glucose, insulin and lipid profile; as well as hepatic malondialdehyde (MDA) and thiol content, and superoxide dismutase (SOD) and catalase (CAT) activities were determined. Results: In diabetic rats, plasma glucose, triglycerides (TG), total cholesterol (TC), and LDL-C, as well as hepatic MDA levels were elevated but plasma HDL-C and insulin, and hepatic thiol content and SOD and CAT activities were reduced compared to control (p<0.01-p<0.001). In diabetic+dose 3, plasma TC, TG, and LDL-C and hepatic MDA level decreased (p<0.001), while plasma HDL-C and insulin, and hepatic thiol content, and SOD and CAT activities increased compared to diabetic (p<0.01-p<0.001). Treatment with dose 1 and 2 improved such abnormalities in diabetic rats except for insulin level (p<0.05-p<0.001). The herbal combination effects were comparable to those of metformin. Metformin did not significantly change serum insulin and HDL-C levels, and hepatic SOD activity; however, serum levels of TC, TG, and LDL-C, as well as hepatic MDA levels, thiol content and CAT activity were improved compared to diabetic (p<0.05-p<0.001). Conclusion: These results indicate that this herbal combination acts as an anti-diabetic, antioxidant and hypolipidemic agent and it may be suggested as a beneficial remedy for diabetic patients.

[Link to the scientific study]

Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats

BMC Complementary and Alternative Medicine 2006 May 7;6:17.

[Link to the scientific study]

Long-term effects of Terminalia chebula Retz. on hyperglycemia and associated hyperlipidemia, tissue glycogen content and in vitro release of insulin in streptozotocin induced diabetic rats

Experimantal and Clinical Endocrinology & Diabetes 2007 Nov;115(10):641-6.

The aqueous extract of the fruits of Terminalia chebula Retz. has been evaluated for its antidiabetic activity in streptozotocin (STZ) induced mild diabetic rats and compared with a known drug, tolbutamide. The oral effective dose (ED) of the extract was observed to be 200 mg/kg body weight, which produced a fall of 55.6% (p<0.01) in the oral glucose tolerance test. Oral administration of ED of aqueous extract of T.chebula (AETC) daily once for two months reduced the elevated blood glucose by 43.2% (p<0.01) and significantly reduced the increase in glycosylated hemoglobin (HbA1c) (p<0.01). The same dose also showed a marked improvement in controlling the elevated blood lipids as well as decreased serum insulin levels in contrast to the untreated diabetic animals. Hepatic and skeletal muscle glycogen content decreased by 75% and 62.9% respectively in diabetic controls, these alterations were partly prevented (34.9% and 21.17%) in AETC treated group when compared to the healthy controls. The in vitro studies with pancreatic islets showed that the insulin release was nearly two times more than that in untreated diabetic animals. The treatment did not have any unfavorable effect on other blood parameters of liver and kidney function tests. LD 50 was found to be above 3 g/kg bw i.e. 15 times of ED, because there were no deaths of animals even at this dose indicating high margin of safety. These findings suggest further investigations for the possible use of the aqueous extract of fruits of T.chebula for the treatment of diabetes.

[Link to the scientific study]

Inhibitory effect of Terminalia chebula Retz. fruit extracts on digestive enzyme related to diabetes and oxidative stress

Journal of Enzyme Inhibtion Medicinal Chemistry 2012 Aug;27(4):578-86. doi: 10.3109/14756366.2011.603130. Epub 2012 Apr 18.

Terminalia chebula fruit extracts were prepared sequentially with hexane, ethyl acetate, methanol and methanol-water (70:30) and tested for their a-glucosidase inhibitory and antioxidant potential. The study resulted in the formulation of an extract with high a-glucosidase inhibitory potential (IC(50) 0.19 ± 0.03 µg mL(-1)) enriched with hydrolysable tannins. Also, each of the extract was chemically characterized by reversed-phase high-performance liquid chromatography on the basis of their marker compounds chebulagic acid, chebulinic acid and corilagin in order to give explanation to the significant activity shown by the extracts. The antioxidant potential of the highly active extract was evaluated in the cellular level also using superoxide dismutase, glutathione S-transferase and induced oxidative stress assays. The results indicated the possibility of using the extract as a nutraceutical health supplement in the management of type 2 diabetes.

[Link to the scientific study]

In vitro antioxidant and inhibitory potential of Terminalia bellerica and Emblica officinalis fruits against LDL oxidation and key enzymes linked to type 2 diabetes

Food and Chemical Toxicology 2011 Jan;49(1):125-31. doi: 10.1016/j.fct.2010.10.006. Epub 2010 Oct 14.

[Link to the scientific study]

Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats

BMC Complementary Alternative Medicine 2006; 6: 17. Published online 2006 May 7. doi: 10.1186/1472-6882-6-17

[Link to the scientific study]

Anti hyperglycemic evalutation of Terminalia Chebula Leaves

International Journal of Pharmacy and Pharmaceutical Sciences, Vol 10, Issue 11, 43-48

Objective

The antihyperglycaemic potentiality of Terminalia chebula leaves has not yet been investigated thoroughly compared to its fruit counterpart. Therefore, the purpose of this study was to assess the hypoglycaemic potentiality of Terminalia chebula Retz leaves both in vitro and in vivo.

Methods

Fresh leaves of T. chebula were collected, authenticated and grounded to a fine powder. The powdered material was extracted in methanol. The hypoglycaemic potentiality of the extract was accessed in vitro using enzyme alpha-amylase and alpha-glucosidase. The antihyperglycaemic activity of the methanol extract active fraction was accessed in vitro and in vivo. The active fraction thus obtained was partially characterized using Fourier transform infrared spectroscopy (FTIR) and High-performance liquid chromatography (HPLC) analysis.

Results

The crude leave methanol extract of Terminalia chebula demonstrated 100% a glucosidase inhibition with IC50–0.956±0.342 mg/ml compared to standard drug acarbose. Oral administration of the active fraction to diabetic rats loaded with maltose significantly (P<0.05) retarded the postprandial spike of blood glucose level compared to standard drug acarbose. Partial characterization of the fraction reveals the presence of hydrosoluble tannin gallic acid.

Conclusion

The study provides an in vitro and in vivo rationale evidence of Terminalia chebula leaves to retard postprandial hyperglycemia.

[Link to the scientific study]

Hypoglycemic Effect of Terminalia Chebula Retz. Fruit on Alloxan-Induced Diabetic Rats

Siriraj Medical Journal, Volume 69, No.2: 2017

Objective

To evaluate the hypoglycemic effect of ethanolic extract of terminalia chebula Retz. fruits on alloxan-induced diabetic rats compared with standard oral hypoglycemic drug, metformin. Methods: A randomized controlled experimental animal study was done. 30 Wistar albino rats were induced diabetes by alloxan (100 mg/kg). 80%-ethanolic extraction of fruits of terminalia chebula Retz. was performed by using Soxhlet extraction method. Group 1 was normal control. Group 2 was alloxan-induced diabetic control, group 3 was metformin 100 mg/kg standard group, groups 4, 5 and 6 were extracts 100, 200 and 400 mg/kg orally administered fruit extract for 28-days, respectively. Fasting blood glucose (FBG) levels were measured at the end of the first, second, third and fourth weeks by using standardized glucometer.

Results

At the end of first, second, third and fourth weeks, the FBG levels of diabetic control were 325.7±28.2, 308.5±69.8, 322.7±65.8 and 369.2±57.4 mg/dL, those of metformin (100 mg/kg) were 76.2±9.5, 92.5±14.9, 94.5±17.9 and 90.8±9.9 mg/dL, those of the terminalia chebula Retz. extract 100 mg/kg were 232.5±78.6, 122.8±41.4, 109.2±33.6 and 132.3±41.1 mg/dL, extract 200 mg/kg were 82.7±8.2, 82.7±8.2, 89.7±9.8 and 89±15.2 mg/dL, and extract 400 mg/kg were 80.2±9, 83.5±7.1, 91±11.5 and 82.7±5.9 mg/dL, respectively. When all treatment groups were compared with diabetic control, the FBG levels were significantly reduced ( p <0.001). There was no significant difference in FBG levels between standard group and extract (200 and 400 mg/kg) groups. Conclusion: The 80%-ethanolic extract of terminalia chebula Retz. has significant hypoglycemic effect on alloxan-induced diabetic rats and it was comparable with standard drug, metformin. The effective dose was 200 to 400 mg/kg.

[Link to the scientific study]

Potent anti-inflammatory Terminalia chebula fruit showed in vitro anticancer activity on lung and breast carcinoma cells through the regulation of Bax/Bcl-2 and caspase-cascade pathways

Journal of Food Biochemistry 2020 Dec;44(12):e13521. doi: 10.1111/jfbc.13521. Epub 2020 Oct 11.

The present study was aimed to investigate the anticancer and anti-inflammatory activities of Terminalia chebula fruit (TCME). The TCME was evaluated for in vitro anticancer activity on A549 and MCF-7 cells. TCME showed cytotoxicity toward A549 (IC50 - 359.06 ± 20.04 µg/ml), and MCF-7 (IC50 - 61.02 ± 5.55 µg/ml) cells. The flow-cytometer analysis revealed increase in sub G1 population and apoptotic population, which were observed through cell cycle analysis and annexin-V-FLUOS staining. Confocal microscopy showed DNA fragmentation in both the cell lines upon TCME treatment. Moreover, TCME treatment induces activation of apoptosis-related caspase-cascade pathways in both the cell lines. TCME treatment on RAW 264.7 cells revealed the anti-inflammatory properties by regulating nitrite and TNF-a production; iNOS, COX-2 levels, and translocation of NF-?B protein. Finally, HPLC analysis revealed the bioactive phytocompounds present in TCME. In conclusion, the combined results showed the potent anticancer and anti-inflammatory properties of T. chebula fruit. PRACTICAL APPLICATIONS: Lung cancer is a leading cause of death in men with 35.5% incidences and 30.8% mortality rate worldwide. On the contrary, breast cancer possesses 55.2% incidences and 16.6% mortality rate among the female worldwide. The present findings revealed the anti-lung and -breast cancer activity along with the potent anti-inflammatory potentials of Terminalia chebula fruit. These findings will helpful to isolate the active drug molecules from the Terminalia chebula fruit and mark them as an anticancer and anti-inflammatory agent.

Confocal microscopy showed DNA fragmentation in both the cell lines upon erminalia chebula fruit (TCME) treatment. Moreover, TCME treatment induces activation of apoptosis-related caspase-cascade pathways in both the cell lines. TCME treatment on RAW 264.7 cells revealed the anti-inflammatory properties by regulating nitrite and TNF-a production; iNOS, COX-2 levels, and translocation of NF-?B protein. Finally, HPLC analysis revealed the bioactive phytocompounds present in TCME. In conclusion, the combined results showed the potent anticancer and anti-inflammatory properties of T. chebula fruit.

[Link to the scientific study]

Gallic acid from Terminalia chebula inhibited the growth of esophageal carcinoma cells by suppressing the Hippo signal pathway

Iran Journal Basic Medicine Sciences 2020 Nov;23(11):1401-1408. doi: 10.22038/ijbms.2020.42283.9982.

Gallic acid (GA) decreased cell viability and colony formation of EC9706 and KYSE450 cells, which was more obvious as the concentration increased. In addition, GA promoted cell apoptosis in a concentration-dependent manner with the up-regulation of pro-apoptotic proteins (Bax, cleaved caspase-3, and cleaved caspase-9) and nuclear YAP/TAZ, as well as the down-regulation of anti-apoptotic protein Bcl-2 and the levels of p-YAP and p-TAZ. Moreover, GA decreased the growth of xenograft tumor in vivo, with the reduction in the tumor volume and the reduction of YAP and TAZ expressions in the tumor tissues. In addition, Ki-67 expression in GA groups was lower than those in the Model group, with the increase in caspase-3 expression in the tumor tissues. Changes aforementioned were obviously shown in the 0.3% GA group. Conclusion: GA blocked the activity of the Hippo pathway to suppress cell proliferation of esophageal carcinoma (EC) and facilitate cell apoptosis, which is expected to be a novel strategy for treatment of EC.

[Link to the scientific study]

Tannins from Terminalia chebula fruits attenuates GABA antagonist-induced anxiety-like behaviour via modulation of neurotransmitters

The Journal of Pharmacy and Pharmacology 2018 Dec;70(12):1662-1674. doi: 10.1111/jphp.13007. Epub 2018 Sep 10.

Terminalia chebula tannin-rich extract (TCHE) supplementation increased locomotion in mice towards open arm (EPM), time spent in illuminated area (LDT), rearing frequency (OFT) and number of shocks (VCT) compared to PTX (P < 0.05). Furthermore, TCHE down-regulated serum cortisol levels and showed increased levels of 5-HT, DA and NE. Gene expressions such as BDNF, CREB, GABAA and 5-HT1A were up-regulated by TCHE treatment compared to PTX. Conclusions: Terminalia chebula tannin-rich extract showed significant anxiolytic activity against picrotoxin and could be used as natural therapy in neurodegenerative disorders.

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Evaluating the Anticancer Potential of Ethanolic Gall Extract of Terminalia chebula (Gaertn.) Retz. (Combretaceae)

Pharmacognosy Research Jul-Sep 2016;8(3):209-12. doi: 10.4103/0974-8490.182919.

The ethanolic leaf gall extract of T. chebula showed effective cytotoxic activities; which might be attributed to the phenolics/flavonoids present in higher concentration. Future work will be interesting to know the chemical composition of the extract and also better understand the mechanism of action of the constituents present in the extract to develop it as drug for therapeutic application. Summary: The present investigation establishes the anticancer activities of T. chebula leaf gall extracts on BRL3A, MCF-7, and A-549 cells. Presumably, these activities could be attributed in part to the phenolics/flavanoids features of the extract that has been demonstrated to act as cytotoxic agents. The experimental evidence obtained in the laboratory model could provide a rationale for the traditional use of plant as a source of easily available effective anticancer agents to the people, particularly in developing countries.

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The Role of Monocarboxylate Transporters and Their Chaperone CD147 in Lactate Efflux Inhibition and the Anticancer Effects of Terminalia chebula in Neuroblastoma Cell Line N2-A

European Journal Medicinal Plants 2016;12(4):EJMP.23992. doi: 10.9734/EJMP/2016/23992. Epub 2016 Feb 22.

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Proteomic analysis of Terminalia chebula extract-dependent changes in human lymphoblastic T cell protein expression

Journal of Medical Foods 2012 Jul;15(7):651-7. doi: 10.1089/jmf.2011.1998. Epub 2012 Apr 3.

Terminalia chebula is a native plant from southern Asia to southwestern China that is used in traditional medicine for the treatment of malignant tumors and diabetes. This plant also has antibacterial and immunomodulatory properties. The present study assessed T. chebula extract-dependent protein expression changes in Jurkat cells. Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry and Ingenuity Pathways Analysis (IPA) were performed to assess protein expression and networks, respectively. A comparative proteomic profile was determined in T. chebula extract (50 µg/mL)-treated and control cells; the expressions of ß-tubulin, ring finger and CHY zinc finger domain containing 1, and insulin-like growth factor 1 receptor kinase were significantly down-regulated in T. chebula extract-treated Jurkat cells. Moreover, the molecular basis for the T. chebula extract-dependent protein expression changes in Jurkat cells was determined by IPA. Treatment with the T. chebula extract significantly inhibited nuclear factor-?B activity and affected the proteomic profile of Jurkat cells. The molecular network signatures and functional proteomics obtained in this study may facilitate the evaluation of potential antitumor therapeutic targets and elucidate the molecular mechanism of T. chebula extract-dependent effects in Jurkat cells.

[Link to the scientific study]


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