scholarly journals Hepatoprotective Activity of BV-7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol-Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl4, Induced Liver Damage in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Debendranath Dey ◽  
Sunetra Chaskar ◽  
Narendra Bhatt ◽  
Deepa Chitre

Excessive alcohol consumption is a worldwide threat with severe morbidity and mortality. Other than abstinence, there is still no FDA-approved drug for alcoholic liver disease (ALD). Liver is the primary site of ethanol metabolism and hence gets the most damage from excessive drinking. It triggers multiple signalling events including inflammation, leading to an array of hepatic lesions like steatosis, hepatitis, fibrosis, and cirrhosis. Similarly, when medications or xenobiotic compounds are ingested orally, the liver gets the highest exposure of those metabolites, which in turn can cause severe liver toxicity. BV-7310 is a standardized mixture of four Ayurvedic plants, namely, Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata. In different systems of traditional medicine, each of these plants has been known to have use in gastrointestinal disorders. We wanted to assess the combined effect of these plant extracts on alcohol-induced liver damage. First, we investigated the hepatoprotective activity of BV-7310 against alcohol-induced toxicity in human liver HepG2 cells. Ethanol treatment (120 mM for 48 hours) significantly showed toxicity (around 42%) in these cells, and coincubation with BV-7310 prevented ethanol-induced cell death in a dose-dependent manner. Interestingly, the formulation BV-7310 showed synergistic activity than any individual extract tested in this assay. BV-7310 also showed potent antioxidant activity in 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Next, we induced hepatitis in Sprague–Dawley (SD) rats using repeated alcohol (40%) dosing, and carbon tetrachloride (CCl4) 24 hours before termination. Both oral doses of BV-7310 (250 and 500 mg/kg body weight) protected the alcohol-induced body weight loss and significantly improved the elevated levels of liver enzymes compared to the vehicle treated group. Thus, BV-7310 prevents alcohol-induced toxicity in both in-vitro and in-vivo models and could be beneficial for the treatment of ALD or other conditions, which may cause liver toxicity.

2018 ◽  
Vol 315 (2) ◽  
pp. E196-E203 ◽  
Author(s):  
Long The Nguyen ◽  
Hui Chen ◽  
Crystal Mak ◽  
Amgad Zaky ◽  
Carol Pollock ◽  
...  

Recent studies indicate that sirtuin-1 (SIRT1), an important metabolic sensor and regulator of life span, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (25 mg/kg ip every 2 days) or vehicle control for 6 wk and examined for metabolic disorders. MHF exacerbated offspring body weight and insulin resistance in the offspring exposed to postnatal HFD (OHF). These metabolic changes were associated with reduced hepatic lipid droplet accumulation but increased plasma levels of alanine aminotransferase (ALT), a marker of liver damage. SRT1720 significantly decreased offspring body weight, adiposity, glucose intolerance, and hyperleptinemia due to OHF and reversed hyperinsulinemia and adipocyte hypertrophy due to the additive effects of MHF. Although SRT1720 suppresses liver lipogenesis, inflammation, and oxidative stress markers, it also reduces antioxidants and increased liver collagen deposition in OHF offspring independent of MHF. Hepatic steatosis was attenuated only in MC/OHF offspring in association with elevated plasma ALT levels. The study suggests that postnatal SRT1720 administration can mitigate obesity and insulin resistance in the offspring due to maternal and postnatal HFD exposure. However, the possibility of liver toxicity needs to be further examined.


Author(s):  
Varkung Valte ◽  
M. Premchand Singh ◽  
Indira Raleng ◽  
Losica R. K.

Background: Traditionally, the bark of Pavetta Indica Linn., in decoction or pulverized, is administered, especially to children, to correct visceral obstructions. The decocted leaves are used externally to alleviate the pains caused by hemorrhoids. The root, pulverized and mixed with the ginger and rice-water, is given in dropsy. A local fomentation with the leaves is useful in relieving the pain of piles. Paracetamol (PCM) toxicity generates free radicals and raised serum enzyme levels-SGPT, SGOT, Alkaline Phosphatase and S. Albumin. It causes necrosis, congested vessels, multifocal area of fatty changes nuclear disintegration, sinusoidal dilation, kuffer cell hyperplasia. The reverse is considered as the index of hepatoprotective activity. The present study is being taken up to screen hepatoprotective action of P. Indica Linn.Methods: The acute liver damage in albino rats was induced by per oral administration of a single dose of 2000mg/kg b.w. PCM suspension in 0.5% Carboxy methyl cellulose (CMC) and chronic liver damage by giving the same dose of PCM on the 7th day. The hepatoprotective activity was monitored biochemically by estimating S. transaminase, S. bilirubin and S. Protein on the 8th day of experiment.Results: Ethanol extract of P. Indica inhibited PCM induced liver toxicity in albino rats at 100mg/kg and 200mg/kg b.w as assessed by the biochemical values.Conclusions: Ethanol extract of “P. Indica” exhibited significant hepatoprotective activity.


Author(s):  
Ameaka Fatima Nkempu ◽  
Tembe Estella Fokunang ◽  
Bayaga Hervé Narcisse ◽  
Eustace Bonghan Berinyuy ◽  
Tabi Yves Omgba ◽  
...  

Introduction: Liver toxicity has become a public health concern as more people globally get exposed to xenobiotics with the potential to cause liver damage and consequent liver cirrhosis. The increase in liver toxicant abuse has necessitated the exploration of xenobiotic exposure levels when addressing therapeutic measures using alternative herbal remedies. The increasing use of herbal products as alternative therapy needs regulatory alignment through evidence-based support for the safety and efficacy of these natural products. To undertake preclinical discovery of new metabolites from medicinal products, the objective of this study was to investigate the systemic serum exposure and acute toxicity of the aqueous extract of Curcuma longa (Zingiberaceae) rhizomes on Wistar rat models. Methods: Phytochemical screening was carried out on the aqueous extract obtained by maceration of the dried plant rhizomes. Standard screening techniques for plant metabolites were used to screen blood serum after animal exposure with the extract. After a 500mg/Kg dose, systemic exposure was evaluated in blood samples collected at 30-minute intervals for one hour. For acute toxicity, a single 2000mg/Kg by body weight dose of the plant extract and the reference (Silymarin 50mg/Kg) were administered to rats, and they were observed for 14 days. Biochemical markers of toxicity such as ALAT, ASAT, GGT, Bilirubin were quantified, and histological studies of the liver were carried out. Results: No secondary metabolites were identified at 30 mins and 1hr in rat serum following a 500 mg/Kg oral dose. Administration of a 2000 mg/Kg oral dose to rats was well tolerated, and there were no deaths or significant target organ toxicity. The plant showed no lethality at the dose of 2000mg/kg body weight and decreased liver toxicity markers such as ASAT, ALAT, GGT, and Bilirubin. Histology revealed no significant damage to liver hepatocytes, no central vein occlusion, and no evidence of fibrosis. Conclusion: There were no systemically available secondary metabolites at a dose of 500 mg/Kg after the qualitative screening; more sensitive and specific methods are required to test these secondary metabolites in serum. This study confirmed the safety margin of Curcuma longa with no lethality following a single oral dose of 2000mg/Kg and after observation for 14 days. There was a low expression of biochemical markers of toxicity ALAT, ASAT, and no histological indication of liver damage.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mesfin Yimam ◽  
Ping Jiao ◽  
Breanna Moore ◽  
Mei Hong ◽  
Sabrina Cleveland ◽  
...  

Some botanicals have been reported to possess antioxidative activities acting as scavengers of free radicals rendering their usage in herbal medicine. Here we describe the potential use of “SAL,” a standardized blend comprised of three extracts fromSchisandra chinensis,Artemisia capillaris, andAloe barbadensis, in mitigating chemically induced acute liver toxicities. Acetaminophen and carbon tetrachloride induced acute liver toxicity models in mice were utilized. Hepatic functional tests from serum collected at T24 and hepatic glutathione and superoxide dismutases from liver homogenates were evaluated. Histopathology analysis and merit of blending 3 standardized extracts were also confirmed. Statistically significant and dose-correlated inhibitions in serum ALT ranging from 52.5% (p=0.004) to 34.6% (p=0.05) in the APAP and 46.3% (p<0.001) to 29.9% (p=0.02) in the CCl4models were observed for SAL administered at doses of 400–250 mg/kg. Moreover, SAL resulted in up to 60.6% and 80.2% reductions in serums AST and bile acid, respectively. The composition replenished depleted hepatic glutathione in association with an increase of hepatic superoxide dismutase. Unexpected synergistic protection from liver damage was also observed. Therefore, the composition SAL could be potentially utilized as an effective hepatic-detoxification agent for the protection from liver damage.


Biologia ◽  
2009 ◽  
Vol 64 (6) ◽  
Author(s):  
Ayyavu Mahesh ◽  
Jabbith Shaheetha ◽  
Devarajan Thangadurai ◽  
Dowlathabad Muralidhara Rao

AbstractThe present study was undertaken to investigate the protective effect of Indian honey on acetaminophen induced oxidative stress and liver damage in rat. Honey serves as a source of natural medicine, which is effective to reducing the risk of heart disease, liver toxicity and inflammatory processes. The hepatoprotective activity of the Indian honey was determined by assessing levels of Serum transaminases, ALP and total bilirubin. Finally, the effects of the test substances on the antioxidant enzymes of the liver were also studied by assessing changes in the level of reduced glutathione, glutathione peroxidase, catalase and superoxide dismutase. Serum transaminase, ALP and total bilirubin level were significantly elevated and the antioxidant status in liver such as activities of SOD, CAT, GPx and the levels of GSH were declined significantly in APAP alone treated animals. Pretreatment with honey and silymarin prior to the administration of APAP significantly prevented the increase in the serum levels of hepatic enzyme markers and reduced oxidative stress. The histopathological evaluation of the livers also revealed that honey reduced the incidence of liver lesions induced by APAP. Results suggest that the Indian honey protects liver against oxidative damage and it could be used as an effective hepatoprotector against APAP induced liver damage.


Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
W Shebaby ◽  
M El-Sibai ◽  
M Mroueh ◽  
K Bodman-Smith ◽  
R Taleb ◽  
...  

Author(s):  
Hawraa M. Murad ◽  
Tamadhur Hani Hussein ◽  
Audai Sulaiman Khudhair ◽  
Manal Muhi Murad ◽  
Jawad Kadhim Faris

This study was conducted to find out hepatoprotective activity of hesperidin (HES) 100mg/kg body weight (b.w.) against ciprofloxacin (CPX) 100 mg/kg induced hepatotoxicity in local breed rabbits .CPX is a broad spectrum antibiotic used for treatment of many bacterial infections. Twenty four male rabbits were divided into four groups ,group1: control, (1 ml/kg Saline orally) group 2: CPX (100 mg/kg orally) for (14) consecutive days , group 3: HES (100 mg//kg) orally for (14) consecutive days group 4: CPX (100 mg/kg orally) plus HES (100 mg//kg orally ) for (14) consecutive days. All the rabbits were killed on the (15) day of the experiment, and then the blood, and livers samples were taken. CPX induced hepatotoxicity was proved by a significant (p less than 0.01) reduction in the body weight ,and a significant (p less than 0.01) increased serum aspartate transaminase (AST), alanine transaminase (ALT) , Malonaldehyde enzyme (MAD) and histopathological changes. Protective hepatic toxicity effect and oxidative damage caused by CPX significantly (p less than 0.01) increasing in body weight and significantly (p less than 0.01) decreasing AST , ALT, MAD and improving tissue morphology in HES (100 mg//kg) . These results assure that HES (100 mg//kg) antioxidant effects can protect CPX-induced hepatotoxicity in rabbits.


Author(s):  
Irfan Aziz ◽  
Birendra Shrivastava ◽  
Chandana Venkateswara Rao ◽  
Sadath Ali

Tephrosia purpurea possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Tephrosia purpurea would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Tephrosia purpurea is very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of aTephrosia purpurea of 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt.Tephrosia purpureaextract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Tephrosia purpurea extract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats.


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