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Antioxidative effects of Haritaki

Terminalia Chebula: Antioxidative

Scientific experiments and studies that underline the antioxidative effects of Haritaki.

Science has proven in multiple studies, that Haritaki protects cells from the damage caused by free radicals. Free radicals may play a part in cancer, heart disease, stroke, and other diseases of aging.

Oxidative stress, caused by the overproduction of free radicals, leads to the development of many chronic diseases including cancer. Free radicals are known to damage cellular biomolecules like lipids, proteins, and DNA that results in activation of multiple signaling pathways, growth factors, transcription factors, kinases, inflammatory and cell cycle regulatory molecules. Antioxidants, which are classified as exogenous and endogenous, are responsible for the removal of free radicals and consequently the reduction in oxidative stress-mediated diseases.

The following scientific experiments and studies confirm the antioxidant effect of Haritaki (Terminalia Chebula). The list represents some of the scientific studies, that have been made on this subject and has no claim to completeness.

Terminalia Chebula Attenuates DMBA/Croton Oil-Induced Oxidative Stress and Inflammation in Swiss albino Mouse Skin

Toxicology International Jan-Apr 2015;22(1):21-9. doi: 10.4103/0971-6580.172252.

Objective

The present study was designed to investigate underlying molecular mechanism for antitumorigenic potential of Terminalia chebula (TC) against chemically-induced skin tumorigenesis in Swiss albino mice. It is used as herbal medicine because it exhibits antioxidant, anti-inflammatory, and anticarcinogenic activity. However, the précised underlying mechanism remains to be elucidated.

Materials and methods

In light of the important role of nuclear factor-kappaB (NF-?B), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (i-NOS), ornithine decarboxylase (ODC), proinflammatory cytokines, oxidative stress in carcinogenesis, chemopreventive efficacy of TC against 7,12-dimethylbenz[a] anthracene (DMBA), and croton oil-induced 2-stage skin carcinogenesis was studied in terms of cytoprotective antioxidant enzymes activity, lipid peroxidation (LPO), inflammatory responses, and expression of various molecular markers in skin tissues.

Results

We found that topical application of TC at dose of 30 mg/kg b. wt. mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Histological findings further supported the protective effects of TC against DMBA/croton oil-induced cutaneous damage.

Conclusion

The findings of the present study suggest that the chemopreventive effect of TC is associated with upregulation of endogenous cytoprotective machinery and downregulation of inflammatory mediators (interleukin (IL)-6, COX-2, i-NOS, ODC, and NF-?B).

We found that topical application of TC at dose of 30 mg/kg b. wt. mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Histological findings further supported the protective effects of TC against DMBA/croton oil-induced cutaneous damage.

[Link to the scientific study]

Effect of Terminalia chebula aqueous extract on oxidative stress and antioxidant status in the liver and kidney of young and aged rats

Cell Biochemistry & Function 2009 Aug;27(6):358-63. doi: 10.1002/cbf.1581.

We evaluated the preventive effects of Terminalia chebula (T. chebula) aqueous extract on oxidative and antioxidative status in liver and kidney of aged rats compared to young albino rats. The concentrations of malondialdehyde (MDA), lipofuscin (LF), protein carbonyls (PCO), activities of xantione oxidase (XO), manganese-superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PDH), levels of glutathione (GSH), vitamin C and vitamin E were used as biomarkers. In the liver and kidney of aged animals, enhanced oxidative stress was accompanied by compromised antioxidant defences. Administration of aqueous extract of T. cheubla effectively modulated oxidative stress and enhanced antioxidant status in the liver and kidney of aged rats. The results of the present study demonstrate that aqueous extract of T. cheubla inhibits the development of age-induced damages by protecting against oxidative stress.

Administration of aqueous extract of T. cheubla effectively modulated oxidative stress and enhanced antioxidant status in the liver and kidney of aged rats. The results of the present study demonstrate that aqueous extract of T. cheubla inhibits the development of age-induced damages by protecting against oxidative stress.

[Link to the scientific study]

Protective effects of chebulic acid from Terminalia chebula Retz. against t-BHP-induced oxidative stress by modulations of Nrf2 and its related enzymes in HepG2 cells

Food Science and Biotechnology 2018 Sep 27;28(2):555-562. doi: 10.1007/s10068-018-0477-z. eCollection 2019 Apr.

Although chebulic acid isolated from Terminalia chebular has diverse biological effects, its effects on the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of downstream genes have not been elucidated. The purpose of this research is to investigate the hepatoprotective mechanism of chebulic acid against oxidative stress produced by tert-butyl hydroperoxide (t-BHP) in liver cells. The treatment with chebulic acid attenuated cell death in t-BHP-induced HepG2 liver cells and increased intracellular glutathione content, upregulated the activity of heme oxygenase-1, and also increased the translocation of Nrf2 into the nucleus and Nrf2 target gene expression in a dose-dependent manner. The exposure of chebulic acid activated the phosphorylation of mitogen-activated protein kinases. The overall result is that chebulic acid has cytoprotective effect on t-BHP-induced hepatotoxicity in HepG2 cells through Nrf2-mediated antioxidant enzymes.

The treatment with chebulic acid attenuated cell death in t-BHP-induced HepG2 liver cells and increased intracellular glutathione content, upregulated the activity of heme oxygenase-1, and also increased the translocation of Nrf2 into the nucleus and Nrf2 target gene expression in a dose-dependent manner.

[Link to the scientific study]

Isolation of chebulic acid from Terminalia chebula Retz. and its antioxidant effect in isolated rat hepatocytes

Archives of Toxicology 2007 Mar;81(3):211-8. doi: 10.1007/s00204-006-0139-4. Epub 2006 Aug 24.

A hepatoprotective compound was isolated from the ethanolic extract of the fruits of Terminalia chebula Retz. by consecutive solvent partitioning, followed by silica gel and Sephadex LH-20 column chromatographies. The purified compound was identified as a mixture of chebulic acid and its minor isomer, neochebulic acid, with a ratio of 2:1 by spectroscopic analysis including 1D and 2D NMR and MS spectroscopy. To our knowledge, this is the first report on the protection of rat hepatocytes against oxidative toxicity by chebulic acid obtained from T. chebula Retz. This compound exhibited in vitro a free radical-scavenging activity and ferric-reducing antioxidant activity. Also, the specific ESR spectrum for the (*)OOH radical signals consisting of three-line ESR spectra was within the field of 0.27 mT, whereas 2.5 and 0.25 mg/ml of chebulic acid significantly reduced the signal intensity of the ESR spectra to 0.06 mT and 0.11 mT, respectively. Using isolated rat hepatocyte experiment, we demonstrated that the treatment of hepatocytes with chebulic acid significantly reduced the tert-butyl hydroperoxide (t-BHP)-induced cell cytotoxicity, intracellular reactive oxygen species level, and the ratio of GSSH, oxidized form of glutathione (GSH) to the over total GSH (GSH + GSSG) (4.42%) as compared to that with t-BHP alone (8.33%).

Using isolated rat hepatocyte experiment, we demonstrated that the treatment of hepatocytes with chebulic acid significantly reduced the tert-butyl hydroperoxide (t-BHP)-induced cell cytotoxicity, intracellular reactive oxygen species level, and the ratio of GSSH, oxidized form of glutathione (GSH) to the over total GSH (GSH + GSSG) (4.42%) as compared to that with t-BHP alone (8.33%).

[Link to the scientific study]

Effect of Terminalia arjuna stem bark on antioxidant status in liver and kidney of alloxan diabetic rats

Veterinary Medicine and Science 2021 Sep;7(5):1778-1785. doi: 10.1002/vms3.580. Epub 2021 Jul 20.

Free radicals and associated oxidative stress induced by alloxan are implicated in eliciting pathological changes in diabetes mellitus. Terminalia arjuna bark, an indigenous plant used in ayurvedic medicine in India, primarily as a cardiotonic is also used in treating diabetes, anemia, tumors and hypertension. The present study examined the effect of ethanolic extract (250 and 500 mg/kg body weight) of Terminalia arjuna stem bark in alloxan induced diabetic rats and its lipid peroxidation, enzymatic and nonenzymatic activity was investigated in the liver and kidney tissues. The extract produced significant (P<0.05) reduction in lipid peroxidation (LPO). The effect of oral T. arjuna at the dose of 500 mg/kg body weight was more than the 250 mg/kg body weight. The extract also causes a significant (P<0.05) increase in superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase glutathione reductase and glucose-6-phosphate dehydrogenase, reduced glutathione, vitamin A, vitamin C, vitamin E, total sulfhydryl groups (TSH) and non protein sulfhydryl groups (NPSH) in liver and kidney of alloxan induced diabetic rats, which clearly shows, the antioxidant property of T. arjuna bark. The result indicates that the extract exhibit the antioxidant activity through correction of oxidative stress and validates the traditional use of this plant in diabetic animals.

The effect of oral T. arjuna at the dose of 500 mg/kg body weight was more than the 250 mg/kg body weight. The extract also causes a significant (P<0.05) increase in superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase glutathione reductase and glucose-6-phosphate dehydrogenase, reduced glutathione, vitamin A, vitamin C, vitamin E, total sulfhydryl groups (TSH) and non protein sulfhydryl groups (NPSH) in liver and kidney of alloxan induced diabetic rats, which clearly shows, the antioxidant property of T. arjuna bark. The result indicates that the extract exhibit the antioxidant activity through correction of oxidative stress and validates the traditional use of this plant in diabetic animals.

[Link to the scientific study]

Protective effect of Terminalia arjuna against alcohol induced oxidative damage of rat erythrocyte membranes

Journal of Ayurveda and Integrative Medicine Apr-Jun 2021;12(2):330-339. doi: 10.1016/j.jaim.2021.02.001. Epub 2021 Mar 14.

Background

Alcohol is a widely abused drug with many health implications, mainly caused by the oxidative and nitrosative stress on different body parts. Ayurvedic herbalism authenticates the multiple therapeutic applications of Terminalia arjuna bark due to its rich phytochemical repertoire.

Objective

To observe the extent of oxidative damage caused to erythrocytes by alcohol and assess the protective ability of T. arjuna bark powder aqueous extract (AETA) against the damage.

Materials and methods

Wister albino rats were categorized into four groups of eight rats per group; first group (control) was fed with glucose, second group was given alcohol at a dose of 20% v/v; 5g alcohol/kg b. wt/day, third group was co-administered with AETA (0.5 g/kg b. wt/day) and alcohol and the fourth group was kept on bark extract alone. Blood samples were collected and evaluated for different biochemical parameters after the completion of the treatment period.

Results

Alcohol significantly increased the erythrocyte membrane protein carbonyl and malondialdehyde (MDA) contents, along with a concomitant decrease in the membrane antioxidant status, when compared to the control group. Chromatographic analysis of the alcohol-treated rat erythrocyte membranes revealed altered membrane individual phospholipid contents and fluidity properties. Alcohol-induced morphological changes in the erythrocytes and its effect on decreasing the resistance of hypotonic shock induced by NaCl are evident from the hemolysis curves. However, AETA administration to alcoholic rats beneficially modulated the membrane properties anvd protected erythrocytes from damage.

Conclusion

Results suggest that AETA protects erythrocytes from alcohol-induced oxidative stress, biophysical, and biochemical changes very effectively.

Alcohol significantly increased the erythrocyte membrane protein carbonyl and malondialdehyde (MDA) contents, along with a concomitant decrease in the membrane antioxidant status, when compared to the control group. Chromatographic analysis of the alcohol-treated rat erythrocyte membranes revealed altered membrane individual phospholipid contents and fluidity properties. Alcohol-induced morphological changes in the erythrocytes and its effect on decreasing the resistance of hypotonic shock induced by NaCl are evident from the hemolysis curves. However, Terminalia arjuna bark powder aqueous extract administration to alcoholic rats beneficially modulated the membrane properties anvd protected erythrocytes from damage.

[Link to the scientific study]

Protective Effect of Aqueous Extract of Terminalia arjuna against Dehydrating Induced Oxidative Stress and Uremia in Male Rat

Iranian Journal of Pharmaceutical Research Spring 2010;9(2):153-61

The present study has been designed to find out the protective effect of aqueus extract of Terminalia arjuna against dehydration induced oxidative stress and uremia, protection by plant extract in male Wister strain albino rats, and therefore to find out the scientific basis of local use of Terminalia arjuna bark extract by village ayurved doctors to protect the progressive kidney disorder (renal failure) relating to dehydration and other related problems. Water withdrawing for 15 days in male Wister strain albino rats resulted in a significant elevation in the level of blood nitrogenous products (i.e. urea and creatinine). On the other hand, it increased the levels of free radicals, melondialdehyde (MDA) and conjugated dienes (CD) along with a significant diminution in the activities of superoxide dismutse (SOD) and catalase in blood. All these water markers were significantly prevented after administration of aqueous extract of Terminalia arjuna bark. These results suggest that dehydration induced oxidative stress and uremia in male rats may be protected by using the above mentioned medicinal plants extract. This herbal extract showed no toxic effect on blood and kidney, based on the measurements of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities (data not shown).

[Link to the scientific study]

Antioxidant activities of leaf galls extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae)

Acta Scientiarum Polonorum Technologia Alimentaria Apr-Jun 2015;14(2). doi: 10.17306/J.AFS.2015.2.11.

Background

Free radicals are implicated in several metabolic diseases and the antioxidant therapy has gained an utmost importance in the treatment. The medicinal properties of plants have been investigated and explored for their potent antioxidant activities to counteract metabolic disorders. In this study, the chemical composition and free radical scavenging potential of leaf gall extracts (ethanol, petroleum ether, chloroform and aqueous) of Terminelia chebula is evaluated, which is extensively used in the preparation of traditiona medications to treat various metabolic diseases.

Methods

The presences of phenolics, flavonoids, triterpens, saponins, glycosides, phytosterols, reducing sugars were identified in the extracts according to standard procedures. The free radical scavenging activities of the extract were also analysed by standard procedures.

Results

The methanol extract had the highest total phenolic and flavonoid content. The antioxidant activities of leaf gall extracts were examined using diphenylpicrylhydrazyl (DPPH), Super oxide radical scavenging, Hydroxyl scavenging and ferric reducing power (FRAP) methods. In all the methods, the ethanolic extract showed higher free radical scavenging potential than all the other extracts.

Conclusions

As the higher content of both total phenolics and flavonoids were found in the ethanolic extract, so the significantly high antioxidant activity can be positively correlated to the high content of total polyphenols/flavonoids of the ethanol extract. The results of this study confirm the folklore use of T. chebula leaves gall extracts as a natural antioxidant and justify its ethnobotanical use. Further, the results of antioxidant properties encourage the use of T. chebula leave gall extracts for medicinal health, functional food and nutraceutical applications.

[Link to the scientific study]

Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats

Journal of Ethnopharmacology 2018 Apr 6;215:124-131. doi: 10.1016/j.jep.2017.12.008. Epub 2017 Dec 14.

Ethnopharmacological relevance

Teminalia chebula (TC) has been traditionally used in the Ayurvedic system of medicine primarily for gastrointestinal disorders. Its fruit extract has also been used to treat epilepsy and other CNS disorders.

Aim of the study

To evaluate the effect of hydroalcoholic fruit extract of Terminalia chebula (HETC) on experimental models of seizures, seizure-induced cognitive impairment and oxidative stress in rats.

Materials and methods

In vitro antioxidant activity of HETC was evaluated by using ABTS, NO and DPPH radical scavenging assay. For in-vivo study, seizures were induced in Wistar rats (200-225g) by pentylenetetrazole (PTZ) and maximal-electroshock. (MES). The anticonvulsant effect of the HETC (250, 500, and 1000mg/kg, orally) was evaluated in seizure models. The therapeutic and sub-therapeutic dose of valproate and phenytoin were also assayed. The potential effect of co-administration of HETC (500mg/kg) with sub-therapeutic dose of valproate and phenytoin were also evaluated in PTZ and MES seizures model respectively. Effect on cognition was assessed using elevated plus maze (EPM) and passive avoidance test (PA). The in- vivo oxidative stress parameters (malondialdehyde and glutathione) were assessed in the cerebral cortex and hippocampus part of rat brain.

Results

The IC50 value of HETC in in vitro antioxidant assays i.e. ABTS, DPPH and NO radical scavenging assay was found to be 2.27µg/ml, 6.04µg/ml and 4.37µg/ml respectively. In experimental study, PTZ and MES treated groups exhibited 100% seizures with increased oxidative stress (p < 0.001) and cognitive deficits (p < 0.01) as compared to control group. HETC at highest dose (1000mg/kg) showed 83.33% (5/6) protection in MES induced seizures while 66.66% (4/6) protection in PTZ induced seizures. However, HETC (1000mg/kg) and co-administration of sub-therapeutic dose of HETC with valproate and phenytoin showed complete protection. In addition, it also attenuated the seizure induced oxidative stress and cognitive impairment as indicated by significant (p < 0.01) improvement in the transfer latencies in EPM and PA as compared to PTZ and MES treated group.

Conclusions

The findings suggest that HETC exhibited significant anticonvulsant activity and also potentiated the subtherapeutic dose of phenytoin and valproate indicate its usefulness as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.

The IC50 value of the fruit extract of Terminalia chebula (HETC) in in vitro antioxidant assays i.e. ABTS, DPPH and NO radical scavenging assay was found to be 2.27µg/ml, 6.04µg/ml and 4.37µg/ml respectively. In experimental study, pentylenetetrazole (PTZ) and maximal-electroshock (MES) treated groups exhibited 100% seizures with increased oxidative stress (p < 0.001) and cognitive deficits (p < 0.01) as compared to control group. HETC at highest dose (1000mg/kg) showed 83.33% (5/6) protection in MES induced seizures while 66.66% (4/6) protection in PTZ induced seizures. However, HETC (1000mg/kg) and co-administration of sub-therapeutic dose of HETC with valproate and phenytoin showed complete protection. In addition, it also attenuated the seizure induced oxidative stress and cognitive impairment as indicated by significant (p < 0.01) improvement in the transfer latencies in elevated plus maze (EPM) and avoidance test (PA) as compared to PTZ and MES treated group. Conclusions: The findings suggest that HETC exhibited significant anticonvulsant activity and also potentiated the subtherapeutic dose of phenytoin and valproate indicate its usefulness as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.

[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.

Objective

Effects of Commiphora mukul and Commiphora myrrha ethanolic extracts and Terminalia chebula hydro-ethanolic extract combination were evaluated in streptozotocin (STZ)-induced diabetic rats.

Materials and methods

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]

Ellagic acid derivatives from Terminalia chebula Retz. increase the susceptibility of Pseudomonas aeruginosa to stress by inhibiting polyphosphate kinase

Journal of Applied Microbiology 2015 Apr;118(4):817-25. doi: 10.1111/jam.12733. Epub 2015 Feb 3.

Aim

Polyphosphate kinase 1 (PPK1) plays an important role in virulence, antibiotic resistance and survival under stress conditions and, therefore, is an attractive therapeutic target to control infections caused by multiple drug resistant Pseudomonas aeruginosa. This study explores the PPK1 inhibiting activity of ellagic acid derivatives (EADs) from Terminalia chebula Retz. that could increase the susceptibility of Ps. aeruginosa to in vitro stress conditions.

Methods and results

EADs reduced ppk1 gene expression by 93% (P < 0·05) and completely inhibited its activity (P < 0·01) at 0·5 mg ml(-1) . EADs-treated Ps. aeruginosa showed marked reduction in polyphosphate granules in cytosol. Expression of rpoS, the downstream master stress response regulator, was reduced by 94% (P < 0·05) and the sensitivity of Ps. aeruginosa increased many fold to desiccation, oxidative (H2 O2 ) and antibiotic (piperacillin) stresses. PPK-regulated swimming, swarming and twitching motilities and biofilm formation were also reduced significantly (P = 0·05) in MPAO1 and the clinical strains of Ps. aeruginosa.

Conclusion

EADs from T. chebula inhibited PPK1 expression and its activity and increased the sensitivity of Ps. aeruginosa to desiccation and oxidative stress while reducing tolerance to piperacillin.

Significance and impact of the study

The study underlines the potential of EADs as therapeutic agent against Ps. aeruginosa.

[Link to the scientific study]

Antioxidant activity of ethanolic extract of Terminalia chebula fruit against isoproterenol-induced oxidative stress in rats

Indian Journal of Biochemistry and Biophysics 2005 Aug;42(4):246-9.

Antioxidant activity of ethanolic extract of fruits of Terminalia chebula (500 mg/kg body wt, orally for 30 days) against isoproterenol-induced oxidative stress was investigated in rats. The levels of serum lipid peroxides, iron, ascorbic acid, vitamin E, plasma iron-binding capacity, and the activities of ceruloplasmin and glutathione were assayed, in addition to the activities of the antioxidant enzymes--glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase in the heart tissue. Administration of isoproterenol increased the levels of lipid peroxides and iron, with corresponding decrease in the activities of the enzymic and non-enzymic antioxidants. The pre-treatment with ethanolic extract of fruits significantly prevented the alterations induced by isoproterenol, and maintained a near normal antioxidant status. Results suggest that the cardioprotective effect of T. chebula fruit may partly be attributed to its antioxidant properties.

[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.

The present study evaluated the free radical scavenging capacity and antioxidant potential of different solvent extracts (Hexane (HE), ethyl acetate (EA), methanol (ME), 70% methanol (MW) and Water (WA)) of Terminalia bellerica (TB) and Emblica officinalis (EB) fruits. Methanol extract (ME) of TB and EB fruits exhibited maximum scavenging activity against DPPH, superoxide, hydroxyl and nitric oxide radicals. Cell based antioxidant activity was assayed by flow cytometry using DCFH-DA as probe. Methanol extracts were also screened for their antidiabetic activity via inhibition of α-amylase, α-glucosidase and antiglycation assays. Results showed that ME of TB and EB can act as potent α-amylase and α-glucosidase inhibitor. Significant antiglycation activity also confirms the therapeutic potential of these extracts against diabetes. Both the extracts significantly inhibited the oxidation of LDL under in vitro conditions. Liquid chromatography-mass spectroscopy (LC-MS) analysis revealed that methanol extract of TB and EB contains ellagic acid and ascorbic acid as the major compound respectively.

[Link to the scientific study]

Mutagenicity and oral toxicity studies of Terminalia chebula

Phytotherapy Research 2012 Jan;26(1):39-47. doi: 10.1002/ptr.3504. Epub 2011 May 2.

The fruit of Terminalia chebula Retz. (T. chebula), which is a member of the Combfreetaceae family, is used widely in Asian countries as a traditional folk medicine, and its extract has been reported to be an anticancer, antidiabetic and anticaries agent. In our previous study, chebulic acid isolated from T. chebula extract was confirmed to show antioxidant activity and protective action against endothelial cell dysfunction. In order to support the safety-in-use of the ethyl acetate (EtOAc)-soluble portion of a T. chebula ethanol extract containing 29.4% chebulic acid content, the prepared portion was tested in an in vitro mutagenicity assay, and a single- and 14-day repeated dose oral toxicity study. In the bacterial mutation assay, up to 5000 µg/mL concentration of the EtOAc-soluble portion, the numbers of colonies did not increase whether with or without metabolic activation. In the oral toxicity study, the single oral dose of the extract at 2000 mg/kg did not produce mortality or abnormal lesions in the internal organs of rats. The results of a 14-day orally repeated dose showed that the EtOAc-soluble portion of T. chebula ethanol extracts gave no adverse effects at dosages of 2000 mg/kg in rats in the study.

[Link to the scientific study]

Structure analysis and antioxidant activities of an amylopectin-type polysaccharide isolated from dried fruits of Terminalia chebula

Carbohydrate Polymers 2019 May 1;211:100-108. doi: 10.1016/j.carbpol.2019.01.097. Epub 2019 Feb 1.

Dried fruits of Terminalia chebula (TF) are used as herbal medicine for diverse symptoms, and their bioactivities are known to involve antioxidant activities. The aim of this study was to elucidate the structure and antioxidant effects of an active TF polysaccharide (TFP). The neutral polysaccharide (named as TFP-a) isolated by ion-exchange chromatography was a homogenous α-Glc-rich polysaccharide (over 70% α-Glc, 534.9 kDa, PDI 1.36) with a porous and flake-like morphology. Linkage and NMR data comprehensively showed that TFP-a was an amylopectin-type polysaccharide with (1→4)-α-Glc(p) backbone branched at C6/C2. Side chains were composed of (1→4)-β-Gal(p) substituted with α-Ara(f), β-GalUA(p), β-GalUA(p)-Me, and α-Rham(p). In antioxidant activity assays, TFP-a exhibited potent and concentration-dependent antioxidant effects, including DPPH and superoxide radical scavenging and reducing power. We concluded that TFP-a is an amylopectin-type polysaccharide that may be used as a potential natural antioxidant.

[Link to the scientific study]

Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): characterization, quantitation and determination of antioxidant capacities

Phytochemistry 2010 Jul;71(10):1132-48. doi: 10.1016/j.phytochem.2010.03.018. Epub 2010 May 6.

Thirty-four polyphenolic substances in methanol extracts of the fruits of Terminalia bellerica, Terminalia chebula and Terminalia horrida, three plants used in Egyptian folk medicine, were initially identified by HPLC-ESI-MS and quantitated by analytical HPLC after column chromatography on Sephadex LH-20. After purification by semi-preparative HPLC the compounds were identified by their mass and fragmentation patterns using ESI-MS-MS. For several compounds detailed 1H/13C NMR analysis at 600 MHz was performed. Two polyphenolics, namely 4-O-(4''-O-galloyl-alpha-L-rhamnopyranosyl)ellagic acid and 4-O-(3'',4''-di-O-galloyl-alpha-L-rhamnopyranosyl)ellagic acid were identified by NMR. Antioxidant capacities of the raw fruit extracts and the major isolated substances were determined using the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), oxygen radical absorbance capacity (ORAC) and ferric reducing ability of plasma (FRAP) in vitro assays and indicated that chebulic ellagitannins have high activity which may correlate with high potential as cancer chemopreventive agents. Therefore, further studies (metabolism, bioavailability and toxicity) of the polyphenolics in Terminalia species using preclinical models and in vivo human intervention trials are warranted.

[Link to the scientific study]

Antioxidant activity of polyphenolic extract of Terminalia chebula Retzius fruits

Journal of Taibah University for Science Volume 10, Issue 6, November 2016, Pages 805-812

The objective of this study was to investigate the in vitro antioxidant activities of polyphenolic extract of Terminalia chebula Retzius (Combretaceae) fruits. The polyphenolic extract of T. chebula fruits was evaluated for antioxidant activity by determining the reducing power, total antioxidant capacity, DPPH radical concentration (IC50 14 μg/mL), nitric oxide radical concentration (IC50 30.51 μg/mL) and hydrogen peroxide scavenging activity (IC50 265.53 μg/mL) under in vitro conditions. Moreover, the phytochemical characterisation of the extract was also measured by determining the total phenolic, flavonoid, tannin and ascorbic acid contents. Characterisation of the extract was also performed by HPLC profiling with the standard gallic acid. The present study demonstrated that the extract has significant reducing capacity and nitric oxide scavenging activity. It also scavenges hydrogen peroxide-induced radicals. The activity of the extract may be due to the total polyphenolic content. The antioxidant activity of the extract is significantly higher than the standard ascorbic acid, and its activity is concentration-dependent. It is concluded that a polyphenolic-rich fraction of T. chebula fruits is a potential source of natural antioxidants.

[Link to the scientific study]

Development of antioxidant activity and pattern recognition of terminalia chebula retzius extracts and its fermented products

Chia-Lin Chang, Che-San Lin in Research Institute of Biotechnology, Hungkuang University, October 2010

This study was to determine the difference of antioxidant activities between unfermented extracts and fermented products for Terminalia chebula Retzius, and to recognize antioxidative patterns. The methanol extract, water extract, 95 % ethanol extract, fermented product of dried powder at 25 °C and fermented product of residues after 95 % ethanol extraction at 37 °C showed good antioxidant activities based the scavenging effect on 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the horseradish peroxidase (HRP)-luminol-hydrogen peroxide (H2O2) assay, respectively. The methanol extract, water extract, 95 % ethanol extract, fermented product of dried powder at 15 °C and fermented product of water extract at 25 °C exhibited a good value of antioxidant activity based on the pyrogallol-luminol assay. The antioxidative pattern plots revealed valuable information and showed good correlation between scavenging effect on DPPH radical assay and HRP-luminol-H2O2 assay. These results may represent promising plant-sources of medicine in the future.

[Link to the scientific study]

Antioxidant activity of polyphenolic extract of Terminalia chebula Retzius fruits

Journal of Taibah University for Science, 2018, Volume 10, Issue 4, Extent;: 805-812

The objective of this study was to investigate the in vitro antioxidant activities of polyphenolic extract of Terminalia chebula Retzius (Combretaceae) fruits. The polyphenolic extract of T. chebula fruits was evaluated for antioxidant activity by determining the reducing power, total antioxidant capacity, DPPH radical concentration (IC50 14μg/mL), nitric oxide radical concentration (IC50 30.51μg/mL) and hydrogen peroxide scavenging activity (IC50 265.53μg/mL) under in vitro conditions. Moreover, the phytochemical characterisation of the extract was also measured by determining the total phenolic, flavonoid, tannin and ascorbic acid contents. Characterisation of the extract was also performed by HPLC profiling with the standard gallic acid. The present study demonstrated that the extract has significant reducing capacity and nitric oxide scavenging activity. It also scavenges hydrogen peroxide-induced radicals. The activity of the extract may be due to the total polyphenolic content. The antioxidant activity of the extract is significantly higher than the standard ascorbic acid, and its activity is concentration-dependent. It is concluded that a polyphenolic-rich fraction of T. chebula fruits is a potential source of natural antioxidants.

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Antioxidant and Free Radical Scavenging Activities of Terminalia chebula

Biological and Pharmaceutical Bulletin, Volume 26 (2003) Issue 9

Free radicals react with biological molecules and destroy the structure of cells, which eventually causes free-radical induced disease such as cancer, renal failure, aging, etc. In this study, 6 extracts and 4 pure compounds of Terminalia chebula RETZ. were investigated for anti-lipid peroxidation, anti-superoxide radical formation and free radical scavenging activities. The superoxide radical scavenging of the 4 pure compounds was further evaluated using electron spin resonance (ESR) spectrometry. The results showed that all tested extracts and pure compounds of T. chebula exhibited antioxidant activity at different magnitudes of potency. The antioxidant activity of each pure compound was derived from different pathways and was suggested to be specific.

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In-Vitro antioxidant, anti-lipid peroxidative activities and In-Silico study of Terminalia chebula bioactive compounds

International Journal of Phytomedicine and Phytotherapy, Article number: 83 (2020)

Zielsetzung

Bewertung der antioxidativen Aktivitäten und Identifizierung der bioaktiven Verbindungen in Heißwasserextrakten der Terminalia chebula Frucht.

Methoden

Die antioxidativen Aktivitäten wurden mittels DPPH-Assay, Lipidperoxidationstest, Eisenchelation und Gesamtantioxidationstest bestimmt. Die phenolische Zusammensetzung wurde mittels HPLC-DAD bestimmt. Humanes Rab8b-Protein wurde für die Validierung der entzündungshemmenden Wirkung der Verbindungen verwendet. Die String-Analyse für Proteinsynergismus wurde verwendet.

Ergebnisse

Die Analyse der Phenole von Terminalia chebula Retzius (Combretaceae) zeigte eine entzündungshemmende Wirkung. Die spezifischen phenolischen Zusammensetzungen wurden mittels Hochleistungsflüssigkeitschromatographie (HPLC) bestimmt und führten zur Identifizierung von Rutin, Catechin, Kaffeesäure, Gallussäure, Ellagsäure, Epicatechin und Quercetin als antioxidative Verbindungen. Das menschliche Rab8b-Protein wurde für das Protein-Docking ausgewählt und alle Verbindungen außer Rutin zeigten gute Ergebnisse. Die ADMET-Eigenschaften wurden mit Hilfe von AdmetSar überprüft und alle sieben Verbindungen zeigten eine Validierung der AMET-Eigenschaften. Die Synergismen der Verbindungen wurden mit Hilfe der STRING-Analyse analysiert, und unsere Liganden zeigten eine starke Bindung mit menschlichen Rab8b-Proteinen. Der wässrige Extrakt war in der Lage, die Lipidperoxidation in Eigelb-Phospholipid-Homogenat zu hemmen. Der Extrakt fängt das 2,2-Diphenyl-1-Picrylhydrazyl-Radikal (DPPH) ab (IC50, 71,5 ± 2,1 μg/ml). Der Extrakt zeigte hohe Metallchelatbildungsaktivitäten und reduzierende Fähigkeiten im Phosphomolybdän-Assay.

Schlussfolgerungen

Es wird geschlussfolgert, dass Extrakte aus T. chebula eine gute antioxidative und entzündungshemmende Wirkung haben und reich an Phenolen sind.

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