Published in last 50 years
Articles published on CCl4-induced Hepatotoxicity In Rats
- Research Article
- 10.58739/jcbs/v15i3.24.98
- Sep 27, 2025
- JOURNAL OF CLINICAL AND BIOMEDICAL SCIENCES
- Savitha P N + 3 more
Mussaenda erythrophylla, a botanical treasure, has revealed numerous pharmacological potentials warranting scientific investigation. The hydroalcoholic extract of its leaves demonstrated dose-dependent analgesic, anti-inflammatory, and antipyretic activities. Notably, the leaf extract exhibited robust antioxidant activity, comparable to vitamin C, as evidenced by DPPH and NO assays. Methanolic extracts of the plant showed promising in vitro anthelmintic activity against earthworms. Additionally, root extracts in chloroform and ethanol significantly increased urine volume. Methanolic and ethyl acetate extracts of the plant protected against CCl4-induced hepatotoxicity in rats, as indicated by decreased serum enzyme levels. The plant extracts also demonstrated anti-arthritic properties through proteinase inhibition and denaturation assays. Ethanolic leaf extract showed potent anti-plasmodial activity against P. falciparum, with minimal toxicity. Furthermore, the leaf extract effectively inhibited carbon steel corrosion in a 1M HCl solution. Phytochemical analysis of floral extracts revealed the presence of steroids and triterpenoids. Keywords: Herbal remedy, Analgesic, antioxidant, Anti-arthritic, Anti-plasmodial, Corrosion inhibition
- Research Article
- 10.23975/bjvr.2025.155288.1159
- Jun 1, 2025
- Basrah Journal of Veterinary Research
- Nisreen Jasim
Assessment of Nanosilymarin's Therapeutic Efficacy in Mitigating CCl4-Induced Hepatotoxicity in Rats
- Research Article
- 10.69857/joapr.v13i2.985
- Apr 30, 2025
- Journal of Applied Pharmaceutical Research
- A.S Devadhe + 4 more
Background: This study investigated the antioxidant, hepatoprotective, and sedative modulatory effects of Nigella sativa alcoholic extract (NSAE) in CCl4-induced hepatotoxicity in rats. Methods: Male Wistar rats were divided into six groups (n=6): normal control, CCl4 control, silymarin (50 mg/kg), and NSAE (100, 200, and 400 mg/kg). Hepatoprotective effects were evaluated through biochemical parameters, oxidative stress markers, and histopathological examination. Results: NSAE treatment (400 mg/kg) significantly restored liver function markers, including SGOT (20.95 ± 0.52 IU/L, p = 0.033) and SGPT (28.61 ± 0.67 IU/L, p < 0.001), compared to CCl4 control. Total protein and albumin levels were normalized to 5.68 ± 0.54 mg/dL and 3.84 ± 0.48 mg/dL, respectively. Antioxidant parameters showed marked improvement with NSAE (400 mg/kg), increasing GSH (0.26 ± 0.029 µmol/mg) and CAT (30.19 ± 2.69 µg/mL) while reducing MDA (0.048 ± 0.008 µg/mL). Histopathological examination revealed significant protection against CCl4-induced hepatic and gastric tissue damage, particularly at the 400 mg/kg. Conclusion: NSAE exhibited marked hepatoprotective activity comparable to silymarin, predominantly through antioxidant mechanisms and the maintenance of hepatic tissue integrity, indicating its potential as a natural therapeutic agent for managing liver diseases. Because of its hepatoprotective and antioxidant properties, NSAE may be explored in clinical settings as a natural supplement to traditional liver disease therapies or as a prophylactic for people at risk of liver disorders.
- Research Article
2
- 10.1016/j.ecoenv.2024.117642
- Jan 1, 2025
- Ecotoxicology and environmental safety
- Masume Farhadi + 4 more
Enhancing the efficacy of low doses of N-acetyl-L-cysteine in mitigating CCl4-induced hepatotoxicity in animal model using physical cold plasma.
- Research Article
- 10.1124/jpet.409.880380
- May 13, 2024
- The Journal of Pharmacology and Experimental Therapeutics
- Olorunfemi Molehin + 3 more
Antiinflammatory and antioxidative role of pasteurized sauce produced from Capsicum spp and Lycopersicum esculentum against CCl4-induced hepatotoxicity in rats
- Research Article
2
- 10.17762/jaz.v44is6.2158
- Nov 25, 2023
- Journal of Advanced Zoology
- Kusum S Akki + 7 more
The aim of the present work is to evaluate the hepatoprotective and antioxidant effect of Nyctanthes arbor –tristis leaf fractions. The petroleum ether, ethylacetate and butanolic fractions of Nyctanthes arbor –tristis leaves were studied to evaluate the hepatoprotective and antioxidant activities in CCl4-induced hepatotoxicity in rats. Oral administration of the fractions at doses of 200 and 400 mg/kg once daily for 10 days significantly restored normalization of serum enzyme levels, viz. glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT) and markers viz. total bilirubin and direct bilirubin and the results were comparable to the effects of Liv 52. The ethylacetate and butanolic extract at the dose of 400 mg/kg was found to be more potent when compared to petroleum ether extract at similar dose. The hepatoprotection is also supported by histopathology of treated animals. In regard to antioxidant activity, ethylacetate and butanolic fractions exhibited a significant effect showing increased levels of enzymatic and non-enzymatic parameters, viz. catalase, GSH, SOD and decreased level of malondialdhyde (MDA). The results of this study strongly indicate that Nyctanthes arbor –tristis leaves have potent antioxidant and hepatoprotective action against CCl4-induced hepatic damage in rats which may be due to the presence phytoconstituents such as flavonoids.
- Research Article
3
- 10.36899/japs.2024.1.0705
- Nov 12, 2023
- The Journal of Animal and Plant Sciences
- H Nawaz + 6 more
Ficus plants have traditionally been used as potential remedies for treating various diseases. Hepatotoxicity is one of the severe threats to human health which must be adequately cured. The study was planned to investigate the hepato-protective potential of methanolic extracts of fruit and leaves of Ficus carica and Ficus benghalensis against carbon tetrachloride (CCl4)-induced hepatotoxicity in an experimental rat model. The study was planned using a randomized control design (RCD). The study included 6 groups of animals (n= 5 per group) having average body weight (230±20 g), out of which 5 groups were treated with CCl4 (15 µL kg-1 body weight), and the remaining one was left as healthy control. Four of the five CCl4-treated groups were administered individually with fruit and leaf extracts (25 mg kg-1 body weight) of F. carica and F. benghalensis, while the fifth was left as CCl4-treated control. The total serum bilirubin (TSB), total serum protein (TSP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels of the control group during the treatment period ranged from 0.54±0.16 to 0.59±0.15 mgdL-1, 8.56±0.73 to 8.66±0.75 gdL-1, 46.00±21.41 to 49.41±22.68 UL-1, 41.6±13.99 to 44.41±13.16 UL-1, and 139.80±28.72 to 145.62±28.82 UL-1, respectively. CCl4 administration significantly (p<0.05) increased the TSB, ALT, AST, and ALP levels in the range of 1.48±0.30-2.30±0.19 mgdL-1, 147.6±34.22 to 233.81±14.94 UL-1, 118.8±15.88 to 167.8±16.4143 UL-1, and 213.8±21.46 to 260±26.664 UL-1, respectively. The elevated TSB, ALT, AST, and ALP levels were significantly (p<0.05) decreased after F. carica and F. benghalens extract treatment to 1.06±0.15-1.70±0.21 mgdL-1, 115.00±28.19-190.21±25.68 UL-1, 89.8±16.29-111.8±23.81 UL-1, and 195.38±42.29-218.4±35.02 UL-1 respectively. Moreover, TSP level was significantly decreased after CCl4 administration and improved after extract treatment. It was concluded that methanolic extract from the leaf and fruit of both F. benghalensis and F. carica protects against CCl4-induced hepatotoxicity in rats. Keywords: Hepatoprotective potential, Ficus carica, Ficus benghalensis, Hepatic damage, Experimental rat model
- Research Article
- 10.52783/tjjpt.v44.i4.1482
- Nov 1, 2023
- Tuijin Jishu/Journal of Propulsion Technology
- Velmurugan R, Asaithambi V
The hepatoprotective and anti-inflammatory effects of Terminalia catappa L. and Pergularia daemia hydroalcoholic extracts in albino rats with CCl4-induced liver damage (HAETC and HAEPD, respectively). The extracts significantly reduced the harm induced by CCl4 when given orally at a dosage of 200mg/kg. They also showed strong hepatoprotective and antioxidant properties. Wistar albino rats in good health were divided into seven groups, each with six animals. Group I acted as the control and received no treatment, whereas Group II was given 30% CCl4 (1ml/kg, intraperitoneally) to cause hepatotoxicity. After administering Silymarin (25 mg/kg, orally) as per protocol, Group III underwent CCl4 therapy. The CCl4-induced rats showed significant reductions in antioxidant enzymes like SOD, catalase, glutathione peroxidase (GPX), and glutathione-S-transferase (GST), as well as increases in serum marker enzymes like SGOT, SGPT, alkaline phosphatase (ALK), ACP, LDH, and lipid peroxidation (LPO) activity. However, rats given HAEPD and HAETC showed significant improvements, returning these parameters to levels that are almost normal (P 0.001).The hepatoprotective and antioxidant benefits of Terminalia catappa L. (HAETC) and Pergularia daemia (HAEPD) against CCl4-induced hepatotoxicity in rats were further validated by histopathological analysis of liver tissues. It encourages the use of pre-trained CNN architectures, such as VGG16 and ResNet (Residual Network), in the proposed method, which uses convolutional neural networks (CNNs) for histopathological image analysis to assess the hepatoprotective properties of Pergularia daemia and Terminalia catappa L. leaf extracts against CCl4-induced hepatotoxicity. These well-known CNN models may be modified for precise and effective histopathological image interpretation, assisting in the evaluation of the impact of plant extracts on liver health.
- Research Article
- 10.21608/ejchem.2023.217103.8126
- Jul 17, 2023
- Egyptian Journal of Chemistry
- Sahar Hussein + 3 more
Ephedra alata family Ephedraceae is a Libyan medicinal plants that are traditionally used in folk medicine for treating many diseases. This study designed to evaluate the phytochemical investigation of its methanolic extract and to analyze their phenolic and flavonoid constituents by using HPLC chromatography. The ameliorative effect of the methanolic extract of Ephedra alata veill leaves towards the CCl 4 induced hepatotoxicity in male Wister rats was investigated. The CCl 4 -treated rats showed a significant decline in the studied serum levels of high-density lipoprotein (HDL), albumin (ALB) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). The HPLC chromatography revealed the presence of Phenolic acids which identified as gallic, chlorogenic, catechin, , caffeic, syringic, ellagic, coumaric, cinnamic, ferulic acid, taxifolin beside kaempferol, methyl gallate , pyrocatechol and vanillin. Biochemical investigation showed that the administration of Ephedra alata methanol extract significantly enhanced all the examined biochemical parameters. Moreover, results indicated that Wistar rats exposed to high doses of CCl 4 could experience both certain metabolic changes and liver damage. The investigation on tissue histology was also included. The bioactive phenolic compounds in methanol extract of Ephedra alata, which scavenges free radicals, enhances liver functions, and normalizes the histological architecture of the liver, are therefore may be promising candidates for treating CCl 4 -induced hepatotoxicity.
- Research Article
13
- 10.1016/j.heliyon.2023.e15370
- Apr 1, 2023
- Heliyon
- Shynggys Sergazy + 6 more
Blueberry and cranberry extracts mitigate CCL4-induced liver damage, suppressing liver fibrosis, inflammation and oxidative stress
- Research Article
16
- 10.1016/j.sajb.2022.05.037
- May 20, 2022
- South African Journal of Botany
- Md Mehedi Hasan + 11 more
Morinda angustifolia Roxb. is used to treat jaundice in the indigenous system of medicine in Bangladesh. The objective of the present study was to assess the hepatoprotective potential and in silico-based identification of the active constituents of M. angustifolia bark extract. In vivo hepatoprotective activity was evaluated in CCl4-induced hepatotoxicity in rats. The secondary metabolite content of the extract was identified by ultra-performance liquid chromatography coupled with a quadrupole orbitrap mass spectrometer (UHPLC-Q/Orbitrap/MS). Furthermore, UHPLC-Q/Orbitrap/MS identified compounds of the extract were assessed for their effect on liver-protective enzymes, namely superoxide dismutase, catalase, and peroxidase, using an in-silico study. The extract revealed significant (p<0.05) in vivo hepatoprotective potential evident from the change in the levels of liver biomarker enzymes ALT, AST, and ALP. The flavonoids cosmosiin, wogonin, and baicalein are among the seven compounds identified by the LC-MS analysis of the extract. A molecular docking study of LC-MS identified compounds confirmed the therapeutic potential in free radical-induced hepatotoxicity, with good binding affinities (-6.0 to -10.4 Kcal/mol) and interaction patterns. Furthermore, in Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA), wogonin revealed the best stable complex in catalase, with a binding energy of 104.091 KJ/mol. In contrast, digoxigenin formed the supreme stable complex in peroxidase (35.277 KJ/mol) and superoxide dismutase (27.505 KJ/mol). Both experimental and computational studies supported the folkloric use of M. angustifolia in hepatic disorders. Besides, the in silico study indicates a possible role of baicalein, digoxigenin, and wogonin in amelioration of oxidative damage of the liver
- Research Article
- 10.5281/zenodo.6330402
- Feb 28, 2022
- Zenodo (CERN European Organization for Nuclear Research)
- Estelle Youl + 9 more
Acute toxicity, hepato-curative activity of extracts of a combination of plants on CCL4-induced hepatotoxicity in rats and antiradical activity
- Research Article
3
- 10.30574/gscbps.2022.18.2.0077
- Feb 28, 2022
- GSC Biological and Pharmaceutical Sciences
- Estelle Noëla Hoho Youl + 9 more
Traditional healers combine four medicinal plants (Cochlospermum tinctorium, Terminalia macroptera, Leptadenia hastata and Commiphora Africana to treat hepatitis in Burkina Faso. The aimed was to evaluate the hepato-curative activity of lyophilized aqueous decoction (LAD) and hydroethanolic macerate (LHM) of plant extracts on CCl4-induced hepatitis in rats. We assessed the acute toxicity and scavenging activity of the 2, 2-Diphenyl-1-picrylhydrazyl (DPPH). Hepato-curative activity study included nine groups with five rats each. We used rats as followed: group 1 as neutral controls, group 2 as negative controls, and the other groups were experimental groups. Rats in groups 2-9 received a single dose (1 mL/kg) of CCl4 in intraperitoneal injection to induce hepatitis. We fed orally the rats for seven consecutive days with sylimarin in group 3, LAD and LHM respectively in groups 4-6 and groups 7-9 by 400, 200 and 100 mg/kg/day. This study revealed LAD and LHM had a LD50> 2000 mg/kg and both showed radical-scavenging properties with IC50= 5.95 and 8.66 µg/mL respectively. All experimental rats regardless of the treatment group showed a significantly reduced plasma transaminases level as compared to negative controls. LAD and LHM at 400, 200 mg/kg significantly reduced alkaline phosphatase and gamma-glutamyl transferase. Histologically, treated rats showed normal to almost normal liver in a dose-dependent manner as compared to the controls. Conclusion: LAD and LHM decreased liver enzyme and allowed a dose-Dependent liver damage recovery after CCl4-induced hepatitis in rats.
- Research Article
2
- 10.21608/ejchem.2021.76599.3753
- Jul 22, 2021
- Egyptian Journal of Chemistry
- Hadeel Elhattab + 3 more
Carbon tetrachloride (CCl4) is a known ecological hazardous xenobiotic that could motivate hepatotoxicity. We aimed to examine, for the first time, the therapeutic potential of nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex versus CCl4-induced hepatotoxicity in rats. We used six rat groups of ten animals each. The negative control, vehicle, normal rats injected i.p. with the complex (2.4 mg/kg/day), positive control rats injected i.p. with CCl4, and treated rats administered complex via injection at low and high concentrations of 1.2 and 2.4 mg/kg/day, respectively at the same time as CCl4 injection for short-term (3-weeks) and long-term (8-weeks) treatment. Intoxicated-rodents exhibited significant elevations in the liver index, hepatic serum markers, and oxidative stress with significant reductions in the hepatic, antioxidants, nucleic acids, and proteins. Complex co-treatment with CCl4 significantly suppressed the elevated liver enzyme activities, attenuated oxidative stress, reactivated antioxidant-system components, and amended the hepatic tissue injury. The complex high dose was more efficient than the low dose. Results of negative control were analogous to those of normal rats injected with the complex high dose. The histopathological analysis also supported the above findings. These results show that complex has good antioxidant and therapeutic properties, which can help in treating and preventing CCl4-induced hepatotoxicity.
- Research Article
9
- 10.1186/s43094-021-00243-1
- May 7, 2021
- Future Journal of Pharmaceutical Sciences
- Radhika S Kodoli + 5 more
BackgroundThe liver is the vital organ which plays a major role in metabolism with numerous functions in the human beings such as protein synthesis, hormone production, and detoxification. Present research work is focused on hepatoprotective potential of chloroform (PNFC) and ethyl acetate (PNFEA) endophytic fractions from Phyllanthus niruri Linn. against CCl4-induced hepatotoxicity in albino Wistar rats. To test our hypothesis, both endophytic fungal fractions were tested for vitro antioxidant and in vivo hepatoprotective activity. Serum biochemical parameters like SGOT, SGOT, SALP, cholesterol, bilirubin, and protein were estimated to assess hepatoprotective activity.ResultsGroup of rats treated with CCl4 possess marked hepatic damage and oxidative stress which indicates that cellular leakage and loss of functional integrity of cell membrane in liver. PNFC and PNFEA fractions of endophyte from Phyllanthus niruri Linn. stem have significantly reduced the elevated levels of biomarkers like SGPT, SGOT, SALP, bilirubin, cholesterol, and total protein in CCl4-induced hepatotoxicity in rats. The results obtained confirm hepatoprotective activity of endophytic fractions (PNFC and PNFEA) mediated through the stabilization of plasma membrane, repair of hepatic tissue damage, return of biochemical marker levels to normal, and regeneration of hepatocytes. Histopathological observations revealed improvement in the liver architecture after the treatment of secondary metabolites of endophytic fractions against CCl4-induced liver damage. Both fungal endophytes PNFC and PNFEA showed DPPH scavenging activity with IC50 of 97.79 μg/ml and 108.40 μg/ml, respectively, and possess antioxidant potential. Presence of flavonoids in the both fractions of endophytes may be a possible reason for its antioxidant potential and identified as Eurotium amstelodami strain.ConclusionBoth fungal endophytes PNFC and PNFEA possess hepatoprotective potential due to the presence of secondary metabolites of fungi, i.e., Eurotiumam stelodami strain which support the claim endophytes and act as a potent biomedicine for treatment of various chronic diseases.
- Research Article
1
- 10.21608/ejchem.2021.73347.3632
- May 4, 2021
- Egyptian Journal of Chemistry
- Sahar Hussein + 4 more
Mangifera indica (Tommy Atkins) peels, commonly known as mango, is a pharmacologically, ethnomedically, and phytochemically diverse plant. Peels is a major by-product during processing of mango fruit into pulp. In the present study, Thirteen pure bioactive compounds were isolated from methanolic peels extract. Six of them are new ellagitannins,namely,1,2,3,4,6 -Penta-O-galloyl-s-4C1-glupyranose (3); 2,3,6-Tri-O-galloyl-(α/β)-4C1-glucopyranose(4); 2,3-Di-O-galloyl-(α/β)-4C1-glucopyranose,Nilocitin(6);3,6-Di-O-galloyl-(α/β)-4C1-glucopyranose(8);1,6 -Di-O-galloyl- β-4C1-glucopyranose (9) ; 1,3-Di-O-galloyl-β-4C1- glucose (11), which were analyzed for the first time from M. indica (Tommy Atkins) peels. The ameliorative effect of the methanolic extract of M. indica (Tommy Atkins) peels towards the CCl4-induced hepatotoxicity in male Wistar rats through measuring certain biochemical parameters content in the liver were analyzed. The CCl4-treated rats showed a significant decline in the studied the serum levels of high-density lipoprotein (HDL), albumin (A) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). In contrast, the administration of methanol extract, notably improved all the studied parameters. This study showed that CCl4 administration to Wistar rats, at a high dose level, could induce a hepatic injury in addition to certain metabolic alterations. The work was extended to investigate tissue histopathology. Thus, results suggest that the peels extract can be a potential source of an attractive candidate for ameliorating of hepatotoxicity induced by CCl4 through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture.
- Research Article
- 10.9734/ajrb/2021/v8i330183
- Apr 23, 2021
- Asian Journal of Research in Biochemistry
- Mahmoud Suleiman Jada + 2 more
Aim: This study is aimed at evaluating the effects of the aqueous stem bark extract of Stereospermum kunthianum on CCl4-induced hepatotoxicity in rats.
 Methodology: Analysis of qualitative phytochemical components and antioxidant activity were carried out. Experimental rats were randomly divided into six groups of five rats each. Group 1: served as the normal control group. Group 2: was administered with CCl4 only at a dose of 3 ml/kg b.wt by single intraperitoneal administration. Group 3: served as the standard control group. Group 4: was administered with 200 mg/kg b.wt of the aqueous stem bark extract + CCl4. Group 5: was administered with 400 mg/kg b.wt of the aqueous stem bark extract + CCl4. Group 6: was administered with 600 mg/kg b.wt of the aqueous stem bark extract+ CCl4.
 Results: The phytochemical analysis showed the presence of flavonoid, phenols, saponins, and terpenoid while tannins and alkaloids were absent. The antioxidant activity showed that the extract significantly (P<0.05) inhibits Ferric Reducing Antioxidant Power (FRAP) and Thiobarbituric Acid Reactive Substances (TBARS), giving high activity as the concentration of the extract increases. The elevated levels of ALT and AST coupled with Conjugated bilirubin, Total bilirubin, and total protein caused by CCl4 administration were all reduced significantly (P<0.05) by the extract in dose dependent manner.
 Conclusion: These findings demonstrated that stem bark extract of Stereospernmum kunthianum could be an alternative medication for liver injury.
- Research Article
12
- 10.19852/j.cnki.jtcm.2020.06.006
- Nov 19, 2020
- Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan
- Hassan Barakat + 1 more
Phenolic compounds and hepatoprotective potential of Anastatica hierochuntica ethanolic and aqueous extracts against CCl4-induced hepatotoxicity in rats.
- Research Article
1
- 10.5138/09750185.2405
- Oct 21, 2020
- International Journal of Phytomedicine
- Kadriya S El Deeb + 4 more
Bougainvillea spectabilis Willd. is an ornamental plant cultivated in tropical, subtropical regions and other places as Egypt. The present study aimed to perform bioassay guided fractionation and isolation of some of the bioactive compounds from the Egyptian cultivate. The total ethanol extracts of the leaves (T.ET.L.), stems (T.ET.S.) and flowers (T.ET.F.) were screened for some pharmacological activities viz. in vivo anti-oxidant and anti-hepatotoxic, in addition to in vitro cytotoxic activities. The anti-oxidant effect was assessed by measuring serum glutathione level (GSH) in alloxan-induced diabetic rats. The anti-hepatotoxic activity was evaluated via measuring serum markers level viz . alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl4-induced hepatotoxicity in rats. In vitro cytotoxicity of the different extracts was estimated for liver cancer cell line (HEPG2) adopting Sulforhodamine B stain assay. T.ET.L. exhibited significantly potent anti-oxidant and anti-hepatotoxic activities, while T.ET.S. showed the highest cytotoxic activity. Through biological guided fractionation, leaves and stems were subjected to successive solvent extraction, whereas the leaves ethyl acetate (Et.Ac.L.) and the stems ethanol 70% (Et.70%S.) extracts showed highly potent activities. Thus, different chromatographic techniques were performed on Et.Ac.L. and Et.70%S. extracts leading to the isolation of five bioactive metabolites. Three flavonoids were isolated from Et.Ac.L.; genistein-7-O-rutinoside (1) , formononetin-7-O-rutinoside (2) and myricetin (3) , while orobol-7-O-glucoside (4) and hesperidin (5) were isolated from Et.70%S. This work demonstrated the importance of the plant as a promising anti-oxidant, anti-hepatotoxic and cytotoxic product for nutraceutical use.
- Research Article
29
- 10.3390/plants9101291
- Sep 29, 2020
- Plants
- Salman A A Mohammed + 9 more
Suaeda vermiculata, an edible halophytic plant, used by desert nomads to treat jaundice, was investigated for its hepatoprotective bioactivity and safety profile on its mother liquor aqueous-ethanolic extract. Upon LC-MS (Liquid Chromatography-Mass Spectrometry) analysis, the presence of several constituents including three major flavonoids, namely quercetin, quercetin-3-O-rutinoside, and kaempferol-O-(acetyl)-hexoside-pentoside were confirmed. The aqueous-ethanolic extract, rich in antioxidants, quenched the DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, and also showed noticeable levels of radical scavenging capacity in ABTS (2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) assay. For the hepatoprotective activity confirmation, the male rat groups were fed daily, for 7 days (n = 8/group, p.o.), either carboxyl methylcellulose (CMC) 0.5%, silymarin 200 mg/kg, the aqueous-ethanolic extract of the plant Suaeda vermiculata (100, 250, and 500 mg/kg extract), or quercetin (100 mg/kg) alone, and on day 7 of the administrations, all the animal groups, excluding a naïve (250 mg/kg aqueous-ethanolic extract-fed), and an intact animal group were induced hepatotoxicity by intraperitoneally administering carbon tetrachloride (CCl4). All the animals were sacrificed after 24 h, and aspartate transaminase and alanine transaminase serum levels were observed, which were noted to be significantly decreased for the aqueous-ethanolic extract, silymarin, and quercetin-fed groups in comparison to the CMC-fed group (p < 0.0001). No noticeable adverse effects were observed on the liver, kidney, or heart’s functions of the naïve (250 mg/kg) group. The aqueous-ethanolic extract was found to be safe in the acute toxicity (5 g/kg) test and showed hepatoprotection and safety at higher doses. Further upon, the cytotoxicity testings in HepG-2 and HepG-2/ADR (Adriamycin resistant) cell-lines were also investigated, and the IC50 values were recorded at 56.19 ± 2.55 µg/mL, and 78.40 ± 0.32 µg/mL (p < 0.001, Relative Resistance RR 1.39), respectively, while the doxorubicin (Adriamycin) IC50 values were found to be 1.3 ± 0.064, and 4.77 ± 1.05 µg/mL (p < 0.001, RR 3.67), respectively. The HepG-2/ADR cell-lines when tested in a combination of the aqueous-ethanolic extract with doxorubicin, a significant reversal in the doxorubicin’s IC50 value by 2.77 folds (p < 0.001, CI = 0.56) was noted as compared to the cytotoxicity test where the extract was absent. The mode of action for the reversal was determined to be synergistic in nature indicating the role of the aqueous-ethanolic extract.