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Hepatoprotective Effect of Enicostemma littorale blume and Eclipta alba During Ethanol Induced Oxidative Stress in Albino Rats
Abstract
The leaves of Enicostemma littorale blume (Ens) and Eclipta alba (Ecl) have been used for skin infection, antiviral and antibacterial activity in traditional medicine. The present study is aimed at to evaluate the hepato-protective effect of the aqueous leaf extracts of the above two plants during ethanol induced oxidative stress in albino rats. The aqueous leaf extracts of Enicostemma littorale and Eclipta alba combine (1:1) at dose level of 250 mg kg<sup>-1</sup> b.wt. were tested for hepato-protective and antioxidant effects during ethanol induced oxidative stress in liver tissue of wistar male albino rats. The degree of hepatoprotection was assessed by measuring the activity levels of the marker enzymes such as serum aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). Free radicals generated lipid peroxidation was assessed by measuring the tissue levels of thiobarbituric acid reacting substances (TBARS) and the activity levels of the tissue antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD). The ethanol supplemented rats recorded elevated activity levels of serum AST, ALT and ALP revealing ethanol induced hepatotoxicity. The increased levels of TBARS in liver and decreased activity levels of SOD and CAT in ethanol fed animal’s revealed oxidative stress. The aqueous leaf extracts supplementation of Ens+Ecl in 1:1 produced significant hepatoprotection and antioxidative effect during ethanol induced hepatotoxicity. The study can be concluded that the therapeutic effect of aqueous leaf extracts of Ens+Ecl in 1:1 is not only hepatoprotective but also possess significant antioxidant property.
... The kidney and liver are vital organs in the body that excrete metabolic waste, regulate fluid and electrolyte balance and detoxification, plasma protein synthesis, and glycogen storage respectively (Asiwe et al. 2021). Infections such as hepatitis A, B, C and E, alcohol damage, chemical pollutants, cancer, and drug damage are among the diseases that affect the kidney and liver leading to dysfunction and these dysfunctions remain one of the most serious health issues (Baranisrinivasan et al. 2009, Kumar et al. 2009, Parmar et al. 2012. Chronic hepatitis or long-term chemical intoxication can harm renal tissues and hepatocytes. ...
Aim
Liver and kidney has been implicated in Lead toxicity and this has been linked to oxidative damage. On the other hand, cabbage is one of the widely consumed vegetables with a plethora of health benefits. This present study investigated the protective effect of cabbage juice on lead-induced toxicity in male Wistar rats.
Methods
Twenty male Wistar rats were randomly divided into four groups (n = 5) and were treated with distilled water (1 ml/100 g b.wt), Lead acetate (25 mg/kg b.wt), cabbage juice (1 ml/100 g b.wt) and Lead acetate plus cabbage juice respectively. All treatments were administered orally for 28 days. Following euthanasia, blood was collected and serum decanted for biochemical assay and liver and kidney tissues were harvested, prepared for antioxidant activity and histological study.
Result
Cabbage juice significantly attenuated Lead-induced liver and kidney dysfunction by lowering serum concentrations of urea, creatinine, ALP, AST and ALT. Antioxidants (SOD, CAT, GSH) were also upregulated in liver and kidney tissues. Cabbage juice restored the histoarchitectural changes caused by lead intoxication.
Conclusion
Cabbage juice consumption protected the liver and kidney against lead-induced toxicity by enhancing in vivo anti-oxidant defense system.
... Sing showed that E. alba is safe up to 2 g/kg in mice [64], and later, Lal demonstrated the LD 50 5 g/kg [66]. e aqueous extract of E. alba leaf showed protection against liver damage induced by either CCl 4 or ethanol in rat via reduced oxidative stress on the liver by elevating the antioxidant enzyme level (Table 2) [65,67]. Another study conducted by Lal showed that the MeOH extract of leaves and CHCl 3 extracts of roots reduced the level of lysosomal enzyme and protected from hepatic damage in CCl 4 -treated rats [66]. ...
Liver diseases are quite prevalant in many densely populated countries, including Bangladesh. The liver and its hepatocytes are targeted by virus and microbes, as well as by chemical environmental toxicants, causing wide-spread disruption of metabolic fuctions of the human body, leading to death from end-stage liver diseases. The aim of this review is to systematically explore and record the potential of Bangladeshi ethnopharmacological plants to treat liver diseases with focus on their sources, constituents, and therapeutic uses, including mechanisms of actions (MoA). A literature survey was carried out using Pubmed, Google Scholar, ScienceDirect, and Scopus databases with articles reported until July, 2020. A total of 88 Bangladeshi hepatoprotective plants (BHPs) belonging to 47 families were listed in this review, including Euphorbiaceae, Cucurbitaceae, and Compositae families contained 20% of plants, while herbs were the most cited (51%) and leaves were the most consumed parts (23%) as surveyed. The effect of BHPs against different hepatotoxins was observed via upregulation of antioxidant systems and inhibition of lipid peroxidation which subsequently reduced the elevated liver biomarkers. Different active constituents, including phenolics, curcuminoids, cucurbitanes, terpenoids, fatty acids, carotenoids, and polysaccharides, have been reported from these plants. The hepatoameliorative effect of these constituents was mainly involved in the reduction of hepatic oxidative stress and inflammation through activation of Nrf2/HO-1 and inhibition of NF-κB signaling pathways. In summary, BHPs represent a valuable resource for hepatoprotective lead therapeutics which may offer new alternatives to treat liver diseases.
... [88] Barani srinivasan et al., 2009 have found that the leaves of E. littorale and Eclipta alba combine (1:1) at dose level of 250 mg -1 body weight produced significant hepato-protection and anti-oxidative effect on ethanol induced oxidative stressin wistar male albino rats. [89] Gite et al., 2009 have found that the water extract of aerial parts of E. axillare shown very significant hepatoprotection against CCl4induced hepatotoxicity in albino rats in reducing serumtotal bilirubin, SALP, SGPT, SGOT levels and liver homogenates LPO, SOD, CAT, GPX, GST and GSH levels. [90] Jaishree et al., 2010 have found that the ethyl acetate extract of E. axillare (100 / 200 mg/Kg body weight) has shown the more potent hepatoprotective activity against CCl4 induced hepatic injury in rats. ...
Vellarugu {Enicostemma littorale Blume (E. littorale)} (Gentian family) is a highly nutritious perennial medicinal plant and used as a medicine in Siddha Medical System to treat several disease conditions such as diabetes mellitus, rheumatism (Vata diseases), skin diseases (Pitta diseases), constipation, abdominal ulcers, swelling, obesity and insect poisoning. It is a rainy season herb, growing on moist, damp and shady ridges and slopes of the borders of cultivated fields and widely distributed in India, Eastern and Southern Africa, South America, and Asia. Whole plant, Leaves, Flowers, stem and Roots are mostly used for the treatment. Although there are numerous scientific studies related to multiple usage of Vellarugu plant, this study attempts to collect all available information and prepare a monograph about the E. littorale for documentation purpose. E. littorale has a number of anti-oxidative phytochemicals which include five alkaloids, catechins, saponins, two sterols, triterpinoids, phenolic acid, flavonoids, xanthones and volatile oil, swetiamerin, and gentianine. Higher percentage of total ash, water soluble ash and acid insoluble ash also were found in this plant. E. littorale has very low toxicity and is a safe and the presence of heavy metals was below the WHO/FDA permissible limits. Numerous studies stated that E. littorale has the therapeutic pharmacological actions such as anti-diabetic, antioxidant, hypolipidaemic, hepatoprotective, anti-inflammatory, analgesic, anti-arthritic, anti-microbial, anti tumour, and etc. This monograph may provide and confirmed the documentary evident for multiple medicinal and therapeutic uses and pharmacological effects of the E. littorale.
... The effect of M. oleifera on the oxidative stress was clear in some parameters, and the result of five groups were represented in figures (1)(2)(3)(4)(5)(6)(7)(8)(9). In figures the data were presented as five columns; control group, aluminium treated, M. oleifera treated, administration of M. oleifera for four weeks after administration of aluminium for four weeks and administration of M. oleifera along with aluminium for eight weeks. ...
This study evaluates the effect of Moringa oleifera leaf extract (300 mg/Kg/day) on oxidative stress after chronic exposure to aluminium (aluminium chloride, AlCl3, 50 mg/Kg/day) on brain of male albino rats. Male rats (250.0±10.0 g) were divided into five groups of ten animals each, and the doses were supplemented with gastric tube. Group 1 served as control, group 2 supplemented with AlCl3 dose, group 3 supplemented with M. oleifera extract dose, group 4 supplemented with AlCl3 dose for 4 weeks then M. oleifera dose for 4 weeks and group 5 supplemented with AlCl3 and M. oleifera doses for 8 weeks.
The results showed significant changes in brain parameters of AlCl3 supplemented (group 2) in comparison to brain parameters of M. oleifera supplemented (group 5). Supplementation of M. oleifera improves the activity of the enzymes superoxide dismutase (SOD), catalase (CAT), Glutathione S-transferase (GST), glutathione peroxidase (GPx), monoamine oxidase (MAO) and acetylcholinesterase (AChE), and decrease in the activity of the enzymes xanthine oxidase (XO), and creatine kinase (CK) and decrease the oxidative stress parameter malondialdehyde (MDA) level in AlCl3 and M. oleifera leaf extract treated group (group 5). The results point to that M. oleifera is a potent antioxidant that has ameliorative effect against changes in antioxidant enzymes and oxidative stress biomarker in rat brain exposed to aluminium.
... If during all such exposures to the above mentioned challenges the natural protective mechanisms of the liver are overpowered, the result is hepatic injury 2 . Liver diseases remain one of the serious health problems 3 . In spite of tremendous strides in the modern medicine, there are not much drugs available for the treatment of liver diseases. ...
The hepatoprotective activity of hydro-alcohol extract of roots of Alocasia indica Linn. (AI-E) was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. The AI-E at dose of 400 mg/kg is administered orally once daily for fourteen days. The substantially elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), glutamate pyruvate transaminase (ALT), alkaline phosphatase (ALP), total lipoprotein (TP), total cholesterol (TC), triglyceride (TG), albumin (ALB), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD), hyaluronic acid (HA) Â and liver index were restored towards normalization significantly by the AI-E at dose of 400 mg/kg. AI-E 400mg/kg dose exhibited significant hepatoprotective activity against carbon tetrachloride induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that roots of Alocasia indica have potent hepatoprotective activity against carbon tetrachloride induced hepatic damage in experimental animals. This study suggests that possible mechanism of this activity may be due to the presence of flavonoids and phenolics compound in the AI-E which may be responsible to hepatoprotective activity.
... Serious health problems, such as cancer, cardiovascular disorder, inflammation, depression, and liver diseases, caused by proteins, lipids, and DNA oxidation have been reported worldwide [2]. Therefore, numerous attempts to evaluate the scientific basis of herbs and fruits rich in natural antioxidants have been made to reduce the serious effects of ROS [24]. The present study demonstrated that the different R. tingitanus leaves extracts exhibited a strong antioxidant capacity on oxidative stress and liver damage induced by CCl 4 exposure in rats. ...
Over the last few decades, Rumex species have been recognized as a promising source of new compounds with numerous pharmacological activities. Therefore, the antioxidant activity of Rumex tingitanus (R. tingitanus) leaves extracts was evaluated in vitro and then confirmed in vivo as well as the antidepressant-like and toxicological effects of the extracts. The ethyl acetate fraction (Rt EtOAcF) followed by hydroalcoholic extract (Rt EtOH-H 2 O) showed a remarkable in vitro antioxidant activity. The hydroalcoholic extract (Rt EtOH-H 2 O) showed significant hepatoprotective activity against carbon tetrachloride- (CCl 4 -) induced liver toxicity which is seen from inhibition of the malondialdehyde (MDA) accumulation and enhancement of the liver antioxidant enzymes activities. The Rt EtOH-H 2 O and Rt EtOAcF extracts were able to reduce the immobility time in mice and then elicited a significant antidepressant-like effect. The ethyl acetate fraction (Rt EtOAcF) was purified and resulted in the identification of a new antioxidant component called 4′- p -acetylcoumaroyl luteolin. The Rt EtOAcF and the 4′- p -acetylcoumaroyl luteolin revealed a strong antioxidant activity using DPPH test with IC 50 of 11.7 ± 0.2 and 20.74 ± 0.6 μ g/ml, respectively, and AAI of 3.39 and 1.92 better than that of BHT, used as control.
The study was conducted to evaluate the hepatoprotective activity of Solanum nigrum and Cichorium intybus. Hepatotoxicity was induced in albino rats with 1:1(v/v) mixture of CCL4 in olive oil, administered at the dose of 1.5 mg kg(-1) i.p on 7th day. The extract of Solanum nigrum and Cichorium intybus were administered to the experimental rats. The hepatoprotective effect of these extracts was evaluated by the assay of serum protein, Serum bilirubin and serum enzymes like Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Markers for oxidative stress like Glutathione (GSH), Superoxide Dismutase (SOD), Lipid Peroxidase (LPO) and histopathological studies of liver. In the groups where hepatic injury induced by CCL4 and extract were given simultaneously, the toxic effect of CCL4 was controlled significantly (<0.05) by maintenance of structural integrity of hepatocyte cell membrane and normalisation of functional status of liver. Histology of liver sections from Solanum nigrum and Cichorium intybus + CCL4 treated rats revealed moderate centrilobular hepatocytes degeneration, few areas of congestion with mild fatty changes. The extract of Solanum nigrum and Cichorium intybus possess significant hepatoprotective activity in comparison to standard drug Silymarin.
The anti-inflammatory effect of the plant of Eclipta alba (Family - Asteraceae) was evaluated using carrageenin, mediators such as histamine and serotonin induced paw oedema, and cotton pellet induced granuloma tests for their effect on acute and chronic phase inflammation models in rats. Maximum inhibition (55.85%) was noted at the dose of 500 mg/kg after 3 hr of drug treatment in carrageenin induced paw oedema, whereas the Indomethacin (standard drug ) produced 61.30% of inhibition. In the chronic model (cotton pellet induced granuloma) the CEEA and standard drug showed decreased formation of granuloma tissue by 49.7,41.5,22.1% and 53.48 % respectively. The results indicate the potent anti-inflammatory effect and therapeutic efficacy of Eclipta alba extract on animal models, which is compared with Indomethacin.
The effect of administration of N-acetylcysteine on ethanol induced hepatotoxicity was studied in female rats and siblings. There was increased activities of serum transaminases and phosphatase in the alcohol fed group. The number of litters born as well as the average birth weight in alcoholic rats were lower. Histopathological alterations were observed in the liver of both mother and litter in the alcohol fed group. The concentration of thiobarbituric acid reactive substances (TBARS) and free fatty acids also increased in the liver. In N-acetylcysteine treated rats, the number of litters as well as the average birth weight were close to that of control animals. The activities of serum transaminases and phosphatase in female rats was higher than the control, but lower than the alcohol fed group. The levels of TBARS and free fatty acids in liver were also decreased both in the mother and litters when compared with alcohol fed animals. Histopathological studies also showed the protective effect of N-acetylcysteine in both mother and litters.
Study of in vitro antibacterial activity of extracts from the plants T. chebula, E. alba and O. sanctum was carried out by the disk diffusion technique. All showed such activity against human pathogenic Gram positive and Gram negative bacteria. The activity against Salmonella organisms was shown only by T. chebula; against Shigella organisms by T. chebula and E. alha; but not by O. sanctum. The widest spectrum of antibacterial activity was shown by T. chebula. It was also most potent. The antibacterial spectrum of E. alba was in between that of T. chebula and O. sanctum. The narrowest spectrum of antibacterial activity was also most potent. The antibacterial spectrum of E. alba was in between that of T. chebula and O. sanctum. The narrowest spectrum of antibacterial activity was observed in O. sanctum.
The thiobarbituric acid reacting material produced during enzymatic microsomal lipid peroxidation has been identified as malonaldehyde. The malonaldehyde was condensed with urea to form 2-hydroxy-pyrimidine, which was identified by its ultraviolet spectrum, chromato-graphic properties, and mass spectrum. Incubations with phosphatidyl choline labelled with tritiated arachidonate yielded 2-hydroxy-pyrimidine with a specific activity nearly equal to that of the phospholipid arachidonate. Incubations with tritiated arachidonic acid yielded 2-hydroxy-pyrimidine with a specific activity nearly 2 orders of magnitude less than that of free arachidonic acid. Therefore, phospholipid arachidonate has been established as the major source of the malonaldehyde produced during microsomal lipid peroxidation.
Acetaminophen (APAP) is considered one of the safest of all minor analgesics, but when taken in large doses (greater than 10 g) toxicity occurs. Severely poisoned patients experience hepatic and/or renal failure. The major metabolic pathway of APAP is formation of glucuronide and sulfate conjugates. A minor pathway is formation of a reactive metabolite that conjugates with glutathione (GSH). When GSH is depleted, the reactive metabolite causes necrosis of hepatic and other tissues. Treatment of APAP toxicity involves supplying alternate sulfhydryl donors or inhibiting oxidative formation of the reactive metabolite. Estimation of plasma APAP levels is necessary for effective treatment.
Proinflammatory cytokines play an important role in alcohol-induced liver injury. The role of anti-inflammatory cytokines in the initiation and progression of alcoholic liver disease has received little attention. This study tested the hypothesis that an imbalance exists between pro- and anti-inflammatory cytokines in the liver during chronic exposure to alcohol. Alcohol exposure results in predominantly proinflammatory cytokine secretion and liver injury.
IL-10 knock-out and their C57BL/6J counterpart wild-type mice were fed alcohol in drinking water for 7 weeks. At the end of alcohol feeding, Gram-negative bacterial lipopolysaccharide (LPS) was administered, and the animals were killed after 3 and 8 hr. Liver histology, plasma alanine aminotransferase and aspartate aminotransferase activity, tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-10 levels, and liver cytokine messenger RNA levels were measured.
Alcohol feeding and LPS treatment did not change plasma enzyme activity levels in wild-type mice. In the IL-10 knock-out mice, LPS alone increased aspartate aminotransferase and alanine aminotransferase enzyme activity, and this was potentiated by alcohol. Alcohol induced liver steatosis in both wild-type and knock-out mice. LPS markedly enhanced the histological effects further, especially in the knock-out mice, with the emergence of focal necrosis, polymorphonuclear infiltration, and microabscesses in the liver. Plasma tumor necrosis factor-alpha and IL-1beta levels were not affected by alcohol alone. Proinflammatory cytokine levels were increased by LPS and further enhanced by alcohol treatment, particularly in the IL-10 knock-out mice. IL-10 plasma levels in the wild-type animals were down-regulated by alcohol. Changes in liver cytokine messenger RNA paralleled those seen in plasma cytokine levels.
Alcohol-induced liver sensitization to LPS in wild-type mice may involve down-regulation of IL-10. This anti-inflammatory cytokine, known for its hepatoprotective effects, is secreted simultaneously with proinflammatory cytokines. IL-10 may also limit alcohol-induced liver damage by counteracting the effects of proinflammatory cytokines.
Cytochrome P450 (CYP) 2E1 is induced by ethanol and is postulated to be a source of reactive oxygen species during alcoholic liver disease. However, there was no difference in liver pathology and radical formation between wild-type and CYP2E1 knockout mice fed ethanol. Other CYP isoforms may contribute these effects if CYP2E1 is inhibited or absent. The purpose of this study was, therefore, to determine if blocking most of the P450 isoforms with 1-aminobenzotriazole (ABT; 100 mg/kg i.g.), has any effect on liver damage and oxidative stress due to alcohol in rats and mice. Male C57BL/6 mice and Wistar rats were fed either high-fat control or ethanol-containing enteral diet for 4 weeks. ABT had a significant inhibitory effect on many P450 isoforms independent of concomitant alcohol administration. However, ABT did not protect against liver damage due to alcohol in either species. Indices of oxidative stress and inflammation were also similar in livers from vehicle-treated and ABT-treated animals fed ethanol. In summary, suppression of P450 activity with ABT had no apparent effect on oxidative stress caused by alcohol in both rats and mice. These data support the hypothesis that oxidative stress and liver damage can occur independently of CYP activities in both rats and mice during early alcohol-induced liver injury.
The present study investigates the effect of oral administration of an aqueous Enicostemma littorale whole plant extract on some key carbohydrate metabolic enzymes and antioxidant defence in alloxan-induced diabetes in rats. Rats were rendered diabetic by alloxan (150 mgkg(-1) body weight) administration. Oral administration of E. littorale extract for 45 days increased the activity of hexokinase and decreased the activities of glucose 6-phosphatase and fructose 1,6-bisphosphatase significantly in the serum, liver and kidney of diabetic rats. The extract lowered the concentration of thiobarbituric acid reactive substances and lipid hydroperoxides significantly in brain and increased it significantly in heart in diabetic rats. E. littorale administration increased the concentration of reduced glutathione and the activity of glutathione peroxidase in diabetic rats. The activities of superoxide dismutase and catalase were increased significantly by E. littorale treatment in diabetic rats. The effect of a 2 g kg(-1) dose was greater than that of a 1 gkg(-1) dose. Insulin (6 units kg(-1)) normalized all the parameters in diabetic rats. Our study has provided evidence for the antidiabetic activity of E. littorale aqueous extract. This study can also be extrapolated to clinical studies in future.