Hepatoprotective activity of Balsamodendron mukul extract against Paracetamol-induced liver toxicity in rats: In vivo pharmacological and toxicological evaluation

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Hepatoprotective evaluation of Anogeissus latifolia： In vitro and in vivo studies

AIM： To evaluate the hepatoprotective activity of a hydroalcoholic extract of the bark of Anogeissus latifolia; in vitro in primary rat hepatocyte monolayer culture and in vivo in the liver of Wistar rats intoxicated by carbon tetrachloride （CCl4）. METHODS： In the in vitro study, a primary hepatocyte monolayer culture was treated with CCh and extract of Anogeissus latifolia. Hepatoprotective activity was demonstrated in the CCh damaged primary monolayer culture. In the in vivo study, the hepatoprotective activity of a hydroalcoholic extract ofAnogeissus latifolia was analyzed in liver injured CCh-treated rats. Biochemical parameters including serum transaminases [aspartate aminotransferase （AST） and alanine aminotransferase （ALT）] and alkaline phosphatase （ALP） in serum wereanalyzed. The biochemical findings were supplemented with histopathological examination of rat liver sections. RESULTS： In vitro： primary hepatocyte monolayer cultures were treated with CCh and extract of Anogeissus latifolia. A protective activity could be demonstrated in the CCh damaged primary monolayer cultUre. In vivo： Hydroalcoholic extract of Anogeissus latifolia （300 mg/kg） was found to have protective activity in rats with CCh-induced liver damage as judged from serum marker enzyme activity. CONCLUSION： The above findings lead to the conclusion that the hydroalcoholic extract of Anogeissus latifol/a is hepatoprotective. Hence, we suggest that the inclusion of this plant in the management of liver disorders is justified.     

水飞蓟制剂肝病临床应用专家共识

随着水飞蓟制剂循证医学证据的积累,水飞蓟制剂已被多部肝病诊疗指南列为抗炎保肝治疗药物。但限于篇幅,上述指南均未就水飞蓟制剂的具体临床应用展开论述,也未能给出详尽的循证医学证据。为此,我们根据临床水飞蓟制剂在各种肝病临床应用的结果作为循证医学的证据,参照肝病治疗、诊疗各项指南和共识,结合肝病治疗的发展趋势,讨论并撰写本专家共识,以期为临床医生进一步提供更为可靠的用药依据。     

Antihepatotoxic effect of corn peptides against Bacillus Calmette-Guerin/lipopolysaccharide-induced liver injury in mice

Hepatitis is a severe disease with a high incidence rate around the world [Hwang, J.M., Tseng, T.H., Tsai, Y.Y., Lee, H.J., Chou, F.P., Wang, C.J., Chu, C.Y., 2005. Protective effects of baicalein on tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes. J. Biomed. Sci. 12, 389–397]. Corn gluten meal is a byproduct of starch industry with abundant protein. However, the application of corn protein is limited because of its low solubility and short of essential amino acids such as lysine and tryptophan. The hepatoprotective activity of corn peptides (CP) from corn gluten meal hydrolysate was evaluated against Bacillus Calmette-Guerin (BCG)/lipopolysaccharide (LPS) induced immunological liver injury (ILI) in mice. Results showed that ILI was manifested by a significant increase in levels of serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and liver malondialdehyde (MDA)/nitric oxide (NO) levels (p < 0.01), and by a significant decrease in levels of superoxide dismutase (SOD)/glutathione peroxidase (GPX) and glutathione (GSH) in liver (p < 0.01). Pretreatment of mice with CP reversed these altered parameters to normal values. The effect of CP was further demonstrated by histopathological examination of liver sections. The best hepatoprotective effect of CP treatment was observed at the dose of 600 mg/kg bw, which was evidenced from biochemical parameters and liver histopathological characters. Results of this study revealed that CP could afford a significant protection against BCG/LPS-induced hepatocellular injury. It will broaden the application and increase the value of corn gluten meal, byproduct from starch industry.     

Antroquinonol from ethanolic extract of mycelium of Antrodia cinnamomea protects hepatic cells from ethanol-induced oxidative stress through Nrf-2 activation

Aim of the study

In recent years, the medicinal mushroom Antrodia cinnamomea, known as “niu-chang chih” has received much attention with regard to its possible health benefits; especially its hepatoprotective effects against various drugs, toxins, and alcohol induced liver diseases. However, the molecular mechanism underlying this protective effect of Antrodia cinnamomea and its active compound antroquinonol was poorly understood. In the present study we evaluated to understand the hepatoprotective efficacy of antroquinonol and ethanolic extracts of mycelia of Antrodia cinnamomea (EMAC) in vitro and in vivo.

Materials and methods

The protective mechanism of antroquinonol and EMAC against ethanol-induced oxidative stress was investigated in cultured human hepatoma HepG2 cells and ICR mice model, respectively. HepG2 cells were pretreated with antroquinonol (1-20 μM) and oxidative stress was induced by ethanol (100 mM). Meanwhile, male ICR mice were pretreated with EMAC for 10 days and hepatotoxicity was generated by the addition of ethanol (5 g/kg). Hepatic enzymes, cytokines and chemokines were determined using commercially available assay kits. Western blotting and real-time PCR were subjected to analyze HO-1 and Nr-2 expression. EMSA was performed to monitor Nrf-2 ARE binding activity. Possible changes in hepatic lesion were observed using histopathological analysis.

Results

Antroquinonol pretreatment significantly inhibited ethanol-induced AST, ALT, ROS, NO, MDA production and GSH depletion in HepG2 cells. Western blot and RT-PCR analysis showed that antroquinonol enhanced Nrf-2 activation and its downstream antioxidant gene HO-1 via MAPK pathway. This mechanism was then confirmed in vivo in an acute ethanol intoxicated mouse model: serum ALT and AST production, hepatocellular lipid peroxidation and GSH depletion was prevented by EMAC in a dose-dependent manner. EMAC significantly enhanced HO-1 and Nrf-2 activation via MAPKs consistent with in vitro studies. Ethanol-induced hepatic swelling and hydropic degeneration of hepatocytes was significantly inhibited by EMAC in a dose-dependent manner.

Conclusions

These results provide a scientific basis for the hepatoprotective effects of Antrodia cinnamomea. Data also imply that antroquinonol, a potent bioactive compound may be responsible for the hepatoprotective activity of Antrodia cinnamomea. Moreover, the present study highly supported our traditional knowledge that Antrodia cinnamomea as a potential candidate for the treatment of alcoholic liver diseases.     

当飞利肝宁防治抗结核药致肝损害的效果观察

目的探讨当飞利肝宁胶囊在抗痨治疗中的保肝作用。方法将112例初治结核患者随机分为两组,治疗组55例,对照组57例,抗痨治疗前肝功能均正常。两组均以2EHRZ/4HRE方案服用抗结核药,治疗组加用当飞利肝宁胶囊,对照组不服保肝药。每个月复查肝功能,如出现肝功损害则口服当飞利肝宁胶囊保肝治疗。结果治疗组肝损害发生率3.64%,对照组21.05%,差异有统计学意义（P〈0.05）;对照组肝损害患者服用当飞利肝宁治疗两周后轻中度肝损害者肝功能复常率达72.73%,有效率100%。结论当飞利肝宁胶囊能有效预防和治疗抗痨药引起的肝损害。     

Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats

Amalkadi Ghrita (AG), a polyherbal formulation, was evaluated for its hepatoprotective activity against carbon tetrachloride (CCl₄)-induced hepatic damage in rats. The hepatoprotective activity of AG was evaluated by measuring levels of serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and acid phosphatase (ACP). The serum levels of total proteins and bilirubin were also estimated. The histological studies were also carried out to support the above parameters. Silymarin was used as standard drug. Administration of AG (100 and 300 mg/kg, p.o.) markedly prevented CCl₄-induced elevation of levels of serum GPT, GOT, ACP, ALP, and bilirubin. The decreased level of total proteins due to hepatic damage induced by CCl₄ was found to be increased in AG-treated group. The results are comparable to that of silymarin. A comparative histopathological study of liver exhibited almost normal architecture, as compared to CCl₄-treated group. Hepatoprotective effect of AG is probably due to combined action of all ingredients.     

Hepatoprotective and antioxidant activities of Tetracera loureiri

Tetracera loureiri is one of the most valued herbs in Thai traditional medicine. In this study, we describe its in vitro and in vivo antioxidant and hepatoprotective activities. The ethanol extract of T. loureiri possessed potent antioxidant and strong free radical scavenging properties assayed using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), respectively. The cytoprotective effects of T. loureiri were demonstrated in ethanolic extracts of freshly isolated rat hepatocytes against the chemical toxicants paracetamol and tertiary-butylhydroperoxide. The cells pretreated with the extract maintained the GSH/GSSG ratio and suppressed lipid peroxidation in a dose dependent manner. Pretreating rats with the ethanol extract orally, one hour prior to intraperitoneal injection of toxic doses of paracetamol, significantly prevented elevations of plasma ALT and AST. These results suggest that T. loureiri may be of potential therapeutic value in some liver disorders.     

Hepatoprotective and antioxidant effects of the coffee diterpenes kahweol and cafestol on carbon tetrachloride-induced liver damage in mice.

The hepatoprotective effects of kahweol and cafestol, coffee-specific diterpenes, on the carbon tetrachloride (CCl(4))-induced liver damage as well as the possible mechanisms involved in these protections were investigated. Pretreatment with kahweol and cafestol prior to the administration of CCl(4) significantly prevented the increase in the serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced oxidative stress, such as reduced glutathione content and lipid peroxidation, in the liver in a dose-dependent manner. The histopathological evaluation of the livers also revealed that kahweol and cafestol reduced the incidence of liver lesions induced by CCl(4). Treatment of the mice with kahweol and cafestol also resulted in a significant decrease in the cytochrome P450 2E1 (CYP2E1), the major isozyme involved in CCl(4) bioactivation, specific enzyme activities, such as p-nitrophenol and aniline hydroxylation. Kahweol and cafestol exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in a mouse liver homogenate, and on superoxide radical scavenging activity. These results suggest that the protective effects of kahweol and cafestol against the CCl(4)-induced hepatotoxicity possibly involve mechanisms related to their ability to block the CYP2E1-mediated CCl(4) bioactivation and free radical scavenging effects.     

Protective effect of Rumex patientia (English Spinach) roots on ferric nitrilotriacetate (Fe-NTA) induced hepatic oxidative stress and tumor promotion response.

In this communication, we document the antioxidant potential of ethanolic extract of Rumex patientia L. (Polygonaceae) roots and its chemopreventive effects against Fe-NTA mediated hepatic oxidative stress, hepatotoxicity and tumor promotion response. The extract exhibited high polyphenolic content, potent reducing power and significantly scavenged free radicals (including several reactive oxygen species (ROS) and reactive nitrogen species (RNS)). The extract also significantly and dose dependently protected against oxidative damage to lipids and DNA. These results indicated R. patientia root extract to exert a potent antioxidant activity in vitro. The efficacy of extract was also evaluated in vivo and it was found to exert a potent protective affect in acute oxidative tissue injury animal model: ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in mice. Administration of Fe-NTA (9 mg/kg body weight, i.p.) to mice led to a significant oxidative stress and allied damage in liver tissues and induced hyperproliferation. A significant depletion was observed in GSH content and enzymes implicated in its metabolism. Attenuation also occurred in activities of other hepatic antioxidant enzymes including SOD, CAT, and GPX. Fe-NTA also incited hyperproliferation response elevating ornithine decarboxylase activity and [(3)H]-thymidine incorporation into DNA. Histopathological investigations and liver function tests (LFT) indicated Fe-NTA to cause extensive hepatic damage. However, prophylactic treatment with R. patientia root extract at a dose regimen of 100-200mg/kg body weight for a week not only restored hepatic antioxidant armory close to normal, but also significantly precluded oxidative damage restoring normal hepatic architecture and levels of hepatic damage markers. The data obtained in the present study illustrates R. patientia roots to possess potent antioxidant and free radical scavenging activities and thwart oxidative damage and hyperproliferation in hepatic tissues.