In Ayurvedic medicine (a system used in India), there are 26 different formulations containing AP that are used to treat liver disorders. AP's four related medicinal compounds were tested for a protective effect against liver toxicity produced in mice by giving them carbon tetrachloride (a cleaning solvent), proprietory, or other toxic chemicals. These chemicals damage the liver by causing lipid peroxidation. This is a process whereby free radicals (reactive molecules) produced by the chemical attack and destroy cellular membranes that surround liver cells. When the AP compounds were given to animals three days before the toxic chemicals, there was a significant protective effect in the liver. This effect was attributed to the antioxidant ability of the AP compounds, which was effective as silymarin (another plant antioxidant from milk thistle).
In another study, andrographolide from AP was shown to produce a significant increase in bile flow. Bile is produced in the liver and stored in the gallbladder and aids in digestion. When a chemical, paracetamol, was given to animals pretreated with andrographolide, the usual decrease in bile production seen with this chemical was prevented. In this case. andrographolide was more potent than silymarin.
Infective hepatitis is an acute inflammatory condition of the liver. It is often followed by liver cirrhosis and may progress to a coma and death. In India, where ancient physicians used AP to treat similar liver ailments, a study was conducted to evaluate the effect of AP in infective hepatitis. There was marked improvement in the majority of patients tested, when given a decoction or infusion of AP. Appetite improved on the fifth day of treatment, jaundice (yellow color of conjunctive of the eye and skin) gradually diminished and completely disappeared within 24 days, and fever subsided after 7 days on average. Other indications of effectiveness of AP included improvement in liver function tests. The researchers concluded that AP was a useful remedy for treatment of infective hepatitis.
The andrographolides present in AP are potent stimulators of gallbladder function. In animal experiments, those that received andrographolides for seven consecutive days showed an increase in bile flow, bile salts, and bile acids. These increases are beneficial and result in enhanced gallbladder function. Use of AP might, therefore, decrease the probability of gallstone formation and might also aid fat digestion. The andrographolides also prevented decreases in the amount of bile that are caused by acetaminophen toxicity.
An aqueous extract of the plant Phyllanthus niruri inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis B virus in vitro. The extract also inhibits woodchuck hepatitis virus (WHV) DNA polymerase and binds to the surface antigen of WHV in vitro. The extract, nontoxic to mice, was tested for antiviral activity in woodchucks (Marmota monax). In a trial using six long-term WHV-carrier woodchucks, five treated animals showed a faster decrease in woodchuck hepatitis virus surface antigen titer compared to one untreated control. In animals recently infected with WHV, the extract was effective when administered i.p. in three out of four animals in reducing and within 3-6 weeks eliminating both the surface antigen titer and DNA polymerase activity in serum. The treatment was discontinued after 10 weeks, and the treated animals have remained free of detectable markers of WHV for more than 45 weeks. In contrast, three untreated controls remained positive for both markers for WHV. One of the controls died after 8 weeks; the other two controls have remained positive for WHV markers for more than 45 weeks. In a third trial with long-term carriers, test animals treated subcutaneously with the extract for 12 weeks did not respond; but on switching the mode of administration to i.p., two out of the five animals showed a significant decrease in woodchuck hepatitis virus surface antigen titer compared to controls.
Hepatitis B is one of the major diseases inflicting the human population. Conventional treatment with interferon-alpha is very expensive and has many serious side effects. Alternative herbal medicine using extracts of Phyllanthus niruri (amarus) and Phyllanthus urinaria has been reported to be effective against hepatitis B and other viral infections. The purpose of this study is to quantitatively determine the antiviral effect of these herbs in a well defined in vitro system.
Antiviral activity induced by the herbal extract was measured as inhibition of the cytopathic effect (CPE) which normally results from infection of untreated MDBK cells with vesicular stomatitis virus (VSV). Aqueous extract of P. urinaria (prepared from dried herbs) and P. niruri were serially titrated and their activities were compared to a positive control, interferon-alpha2b. Pretreatment of MDBK cells with interferon-alpha2b, as expected, inhibited the CPE from VSV infection dose-dependently. The extract of P. niruri produced a concentration-dependent antiviral activity at dilutions 1:2560 to 1:160. Maximal activity (70% inhibition of CPE) was found at 1:160 dilution. The extract of P. urinaria was less effective; the highest tolerable concentration (1:80 dilution) produced a 28% inhibition of CPE.
A cell-based assay has been developed to examine the antiviral effect of herbal extracts from the genus Phyllanthus. Aqueous extracts of P. niruri and P. urinaria protect MDBK cells from viral infection. In addition, they do not display cytotoxicity in uninfected normal cells. These findings support clinical studies by others that regular intake of these herbal supplements may be beneficial for chronic hepatitis B patients.
Singh B, et al conducted a study on the proprietory extract of fresh leaves of the plant Eclipta alba (Ea), previously reported for is hepatoprotective activity. The extracts were fractionated into three parts to chemically identify the most potent bioactive fraction. The hepatoprotective potential of the fraction prepared from extract was studied in vivo in rats and mice against carbon tetrachloride induced hepatotoxicity. The hepatoprotective activity was determined on the basis of their effects on parameters like hexobarbitone sleep time, zoxazolamine paralysis time, bromosulphaline clearance, serum transaminases and serum bilirubin. Fraction EaII (10-80 mg/kg, p.o.) containing coumestan wedelolactone and desmethylwedelolactone as major components with apigenin, luteolin, 4-hydroxybenzoic acid and protocateuic acid as minor constituents exhibited maximum hepatoprotective activity and is the active fraction for hepatoprotective activity of Eclipta alba leave. The acute toxicity studies have shown that like Ea, Fraction EaII also high safety margin
In a separate study, the hepatoprotective effect of the ethanol/water (1:1) extract of Eclipta alba (Ea) has been studied at subcellular levels in rats against CCl4-induced hepatotoxicity. Ea significantly counteracted CCl4-induced inhibition of the hepatic microsomal drug metabolising enzyme amidopyrine N-demethylase and membrane bound glucose 6-phosphatase, but failed to reverse the very high degree of inhibition of another drug metabolising enzyme aniline hydroxylase. The loss of hepatic lysosomal acid phosphatase and alkaline phosphatase by CCl4 was significantly restored by Ea. Its effect on mitochondrial succinate dehydrogenase and adenosine 5'-triphosphatase was not significant. The study shows that hepatoprotective activity of Ea is by regulating the levels of hepatic microsomal drug metabolising enzymes.
Tephrosia purpurea, known as Sarapunkha in Ayurveda for its hepatoprotective action, was evaluated for its efficacy in rats by inducing hepatotoxicity with D-galactosamine HCI (acute) and carbon tetrachloride (chronic). Tephrosia purpurea (aerial parts) powder was administered orally at a dose of 500 mgkg. Serum levels of transaminases (SGOT and SGPT) and bilirubin were used as the biochemical markers of hepatotoxicity. Histopathological changes in the liver were also studied. The results of the study indicated that the administration of Tephrosia purpurea along with the hepatotoxins offered a protective action in both acute (D- galactosamine) and chronic (CC14 models.)
Effect of Ocimum sanctum leaf extract was studied on paracetamol induced hepatic damage in rats. O.sanctum was found to protect the rats from hepatotoxic action of paracetamol as evidenced by significant reduction in the elevated serum enzyme levels. Histopathological studies showed marked reduction in fatty degeneration in animals receiving O.sanctum along with paracetamol as compared to the control group. It is stipulated that the extract treated group was partially protected from hepatic cell damage caused by paracetamol.
Azadirachta indica, a plant used widely in Ayurveda, has been reported to have anti-inflammatory, immunomodulatory and adaptogenic properties. In a study conducted by Yanpallewar SU; et al the hepatoprotective activity of the drug was evaluated. Fresh juice of tender leaves of Azadirachta indica (200 mg/kg body wt. p.o.) inhibited paracetamol (2 g/kg body wt. p.o.)-induced lipid peroxidation and prevented depletion of sulfhydryl groups in liver cells. There was an increase in serum marker enzymes of hepatic damage (aspartate transaminase, alanine transaminase and alkaline phosphatase) after paracetamol administration. Azadirachta indica pretreatment stabilized the serum levels of these enzymes. Histopathological observations of liver tissues corroborated these findings.
In a separate study, the effect of aqueous leaf extract of Azadirachta indica (A. indica) was evaluated in paracetamol induced hepatotoxicity in rats. Liver necrosis was produced by administering single dose of paracetamol (2 g/kg, p.o.). The liver damage was evidenced by elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (gamma-GT) and by histopathological observations of liver sections. Aqueous A. indica leaf extract (500 mg/kg, p.o.) significantly (P < 0.01) reduced these elevated levels of AST, ALT and gamma-GT. Paracetamol induced liver necrosis was also found to be reduced as observed macroscopically and histologically.