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Antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica and its bioactive component ellagic acid against diclofenac induced oxidative stress and hepatotoxicity.

ABSTRACT: Long term usage and overdose of diclofenac (DCF), an anti-inflammatory drug is known to cause oxidative stress and liver injury. The present study reports the antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica (Tb) fruit aqueous and ethyl acetate extracts and its bioactive compound ellagic acid (EA) against DCF-induced toxicity. in vitro antioxidant activities were measured by ABTS and FRAP assays while anti-inflammatory activity was assessed by the albumin denaturation method. The adverse effects of DCF and hepatoprotective potential of Tb extracts and EA were assessed in serum and liver tissue of rats after oral administration for 21 days. Silymarin was used as standard hepatoprptective agent for comparison. Hepatic markers analyzed in serum included ALP, GPT, GOT, LDH, ?-glutamyl transferase, total protein, creatinine, and uric acid while superoxide dismutase (SOD) and catalase (CAT) were analyzed in liver tissue. The EA exhibited superior ABTS radical scavenging, FRAP, and anti-inflammatory activities as compared to fruit extracts. DCF treatment led to rise in the levels of most of the serum hepatic markers with decline in total serum protein as well as SOD and CAT in liver tissue. The supplementation of extracts, EA and silymarin in DCF treated rats significantly reduced the adverse effects of DCF on serum and tissue markers. Histopathology of the liver indicated that extracts and EA significantly decreased the degree of liver fibrosis. The hepatoprotective ability of EA was comparable to the silymarin but activity of Tb fruit extracts was little lower. Among fruit extracts ethyl acetate extract exhibited better activity than aqueous extract. The results revealed that ellagic acid and T. bellirica fruit extracts have potential to mitigate oxidative stress and hepatotoxicity produced by long term use of diclofenac.

SUBMITTER: Gupta A

PROVIDER: S-EPMC7772792 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica and its bioactive component ellagic acid against diclofenac induced oxidative stress and hepatotoxicity.

Gupta Ashutosh A Kumar Ramesh R Ganguly Risha R Singh Amit Kumar AK Rana Harvesh Kumar HK Pandey Abhay Kumar AK

Toxicology reports 20201224

Long term usage and overdose of diclofenac (DCF), an anti-inflammatory drug is known to cause oxidative stress and liver injury. The present study reports the antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica (Tb) fruit aqueous and ethyl acetate extracts and its bioactive compound ellagic acid (EA) against DCF-induced toxicity. in vitro antioxidant activities were measured by ABTS and FRAP assays while anti-inflammatory activity was assessed by ...[more]

PMID: 33391996

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Project description:BackgroundPlants belonging to the genus Terminalia such as Terminalia bellirica and Terminalia sericea are used traditionally to treat several diseases and health disorders. Up to this date, the roots of Terminalia sericea and the fruits of Terminalia bellirica are the mostly studied plant parts. The phytochemical composition and the biological activities of the leaves of both species are not well identified so far.MethodsThe secondary metabolites of Terminalia bellirica and Terminalia sericea leaves were identified using HPLC-PDA-MS/MS. The antioxidant activities of the leaves extracts were determined by DPPH and FRAP assays. The hepatoprotective potential was evaluated in rats with D-galactosamine induced liver damage. The effect of the extracts on the expression of the anti-apoptotic marker Bcl-2 was measured in an immunohistochemical study. The most abundant compounds identified in the studied extracts were docked into Bcl-2: Bim (BH3) interaction surface using molecular operating environment software.ResultsA total of 85 secondary metabolites were identified in the leaf extracts of both species. Ellagitannins such as corilagin, chebulagic acid, galloylpunicalagin, and digalloyl-hexahydroxydiphenoyl-hexoside were found to be the major components in Terminalia bellirica whereas flavonoid glycosides including quercetin rutinoside and quercetin galloyl-glucoside were highly abundant in Terminalia sericea. The studied extracts exhibited pronounced antioxidant activities, moderate anti-apoptotic and hepatoprotective potential. In silico docking experiments revealed that the compounds abundant in the extracts were able to bind to Bcl-2: Bim (BH3) interaction surface with an appreciable binding free energy.DiscussionThe antioxidant and hepatoprotective activities exhibited by the studied extracts might be attributed to the high content of the polyphenols. The anti-apoptotic activity could be due to the interference with the apoptotic pathway mediated by Bcl-2: Bim interaction. These findings support the medicinal relevance of Terminalia bellirica and Terminalia sericea and provide a rational base for their utilization in folk medicine.

Project description:Phyllodiumpulchellum has been traditionally used as a medicinal herb because of its health-promoting effects, such as its hepatoprotective and antioxidant activities. In the present study, the petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, and aqueous fraction were successively obtained from the ethanol extract of P. pulchellum. Two fractions, ethyl acetate fraction and n-butanol fraction, were found to display hepatoprotective and antioxidant activities. Further chemical investigation of the active fractions led to the isolation of its main constituents, including 11 flavonoids (1⁻11) and 8 indole alkaloids (12⁻19). There were 9 flavonoids (1⁻9) that were obtained from the ethyl acetate fraction, and 2 flavonoids (10 and 11) and 8 alkaloids (12⁻19) from the n-butanol fraction. Compounds 1⁻11 and 16⁻19 were isolated for the first time from P. pulchellum, and 1, 2, 8, 11, and 18 were obtained from the genus Phyllodium initially. Subsequently, the isolated compounds were evaluated for their in vitro hepatoprotective effects on the human normal hepatocyte cell line L-O2 injured by d-galactosamine and radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH). The flavonoids (-)-epigallocatechin (5) and (-)-epicatechin (6) exhibited prominent hepatoprotective activities with higher cell viability values (65.53% and 62.40% at 10 μM·mL-1, respectively) than the positive control, silymarin (61.85% at 10 μM·mL-1). In addition, compared with the positive control of vitamin C (IC50: 5.14 μg·mL-1), (-)-gallocatechin (3) and (-)-epigallocatechin (5) exhibited stronger antioxidant activities with IC50 values of 3.80 and 3.97 μg·mL-1, respectively. Furthermore, the total flavonoids from P. pulchellum were characterized using a high-performance liquid chromatography-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC-LTQ-Orbitrap-MS). In total, 34 flavonoids were tentatively identified, which had not been previously reported from P. pulchellum. In addition, we performed a semi-quantitative analysis of the isolated flavonoids. The contents of compounds 1⁻11 were 3.88, 17.73, 140.35, 41.93, 27.80, 4.34, 0.01, 0.20, 9.67, 795.85, and 5.23 μg·g-1, respectively. In conclusion, this study revealed that the flavonoids that were isolated from P. pulchellum showed hepatoprotective and antioxidant activities, indicating that, besides alkaloids, the flavonoids should be the potential pharmacodynamic ingredients that are responsible for the hepatoprotective and antioxidant activities of P. pulchellum.

Project description:The aim of the presented work involves the isolation, characterization, and evaluation of hepatoprotective potential of Clerodendrum paniculatum flower extracts. For this purpose, petroleum ether, chloroform, ethyl acetate, alcohol, and water extracts of C. paniculatum flower were screened for the flavonoid and phenolic content and quantified. Various antioxidant activity assays including 2,2'-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) radical scavenging, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing ability were carried out. Of the above methods, the alcoholic extract exhibited high antioxidant potential and was selected further for the hepatoprotective evaluations. Hepatoprotective evaluation of the alcoholic extract was carried out for carbon tetrachloride (CCl4)-intoxicated model systems. Enzymes associated with liver functions were estimated, and histopathological evaluations were carried out to monitor the liver architecture. Prominently, reduced levels of various associated enzymes along with increased protein content were observed when the liver specimen was pretreated with the extract. Moreover, the liver architecture was almost comparable to that of the normal control group. The column chromatographic analysis of the extract revealed 13 fractions to possess high phenolics and flavonoid contents. The best two fractions were identified for in vitro hepatoprotective evaluation in the goat liver model. Furthermore, the GC-MS analyses of the fractions were carried out followed by a library search, to identify the constituents responsible for the hepatoprotective activity which revealed the presence of four major constituents-pilocarpine, glyceric acid, pangamic acid, and gallic acid. An in vitro hepatoprotective study of the isolated fractions showed better activity compared to the whole alcoholic extract, and the results were comparable to the normal group taken as a control. The investigations with an in vitro model suggest that the isolated fraction with rich flavonoid content showed better hepatoprotective activity. GC-MS analysis of the fractions that displayed good hepatoprotective activity suggested the presence of pilocarpine, glyceric acid, pangamic acid, and gallic acid, while HPTLC analysis revealed the presence of quercetin.

Project description:Anogeissus acuminata is used to treat wounds, diarrhoea, dysentery, and skin ailments. However, its hepatoprotective effect against ethanol-induced liver damage is yet to be reported. The phenolic-enriched ethyl acetate fraction of Anogeissus acuminata (AAE) was evaluated for hepatoprotective activity against ethanol-induced liver toxicity in rats. The intoxicated animals were treated with a phenolic-rich fraction of Anogeissus acuminata (AAE) (100 and 200 mg/kg) and silymarin (100 mg/kg). The antioxidant activity of AAE was analysed. Biochemical markers (ALT, AST, ALP, GGT, and TBL) for liver injury in ethanol-administered animals resulted in higher levels of key serum biochemical injury markers, as evidenced by increased levels of ALT (127.24 ± 3.95), AST (189.54 ± 7.56), ALP (263.88 ± 12.96), GGT (91.65 ± 3.96), and TBL (2.85 ± 0.12) compared to Group I ALT (38.67 ± 3.84), AST (64.45 ± 5.97), GGT (38.67 ± 3.84), and TBL (0.53 ± 064) (p < 0.05). AAE administration decreased serum biochemical liver injury markers as manifested in Group III animals’ ALT (79.56 ± 5.16), AST (151.76 ± 6.16), ALP (184.67 ± 10.12), GGT (68.24 ± 4.05), TBL (1.66 ± 0.082) (p < 0.05), and Group IV ALT (55.54 ± 4.35), AST (78.79 ± 4.88), ALP (81.96 ± 9.43), GGT (47.32 ± 2.95), TBL (0.74 ± 0.075) (p < 0.05). Group IV exhibited the most significant reduction in serum biochemical markers as compared to Group III (p < 0.05) and close to silymarin-treated Group V ALT (44.42 ± 3.15), AST (74.45 ± 5.75), ALP (67.32 ± 9.14), GGT (42.43 ± 2.54), TBL (0.634 ± 0.077). Gene expression indices and histoarchitecture were evaluated to demonstrate the potential of AAE. The bioactive fraction of Anogeissus acuminata was rich in phenolics and flavonoid content. GC−MS analysis identified gallic acid, palmitic acid, cis-10-heptadecenoic acid, 9-octadecenoic acid, epigallocatechin, 2,5-dihydroxyacetophenone, and catechin. Oral administration of AAE (100 and 200 mg/kg) lowered the elevated levels of the biochemical markers and interleukin, and enhanced the level of enzymatic antioxidant. It also downregulated the expression level of proapoptotic genes and upregulated the expression level of the antiapoptotic gene along with improved liver histopathology.

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Antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica and its bioactive component ellagic acid against diclofenac induced oxidative stress and hepatotoxicity.

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Antioxidant, anti-inflammatory and hepatoprotective activities of <i>Terminalia bellirica</i> and its bioactive component ellagic acid against diclofenac induced oxidative stress and hepatotoxicity.

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