Herbal Induced Hepatoprotection and Hepatotoxicity: A Critical Review.

Traditional herbal drugs are wonderful remedies for the treatment of various devastating disorders. Recently, there has been a change in a universal fashion from synthetic to herbal medicine, which is like homecoming to nature. In the present situation, the dietary changes lead to liver disorders like non-alcoholic and alcoholic fatty liver disorders. India is one of the world's twelve leading biodiversity centers with the presence of over 45,000 diverse plant species, out of this about 15,000-20,000 plants have good medicinal and therapeutic properties of which only about 7,000-7,500 are being used by traditional practitioners. Hepatic injury accounts for 3.5%-9.5% of all adverse drug reaction reports and up to 14.7% of fatal adverse reaction. Hepatic disorders/toxicity can occur by several mechanisms like Cytochrome P450 activation, lipid peroxidation, Induction of nitric acid synthase, mitochondrial dysfunction, activation of pro-inflammatory mediators and Bile acid-induced liver cell death. There are a number of drugs or therapies available for the treatment of hepatic disorders, but still there is a need for the novel drug discovery which can target multiple disease pathways. Traditional medicines have exhaustive ancient and scientific literature for curing a lot of life threatening disorders with less or no side effects. There are number of scientifically proved hepatoprotective herbal drugs like Andrographis paniculata, Ocimum sanctum, Solanum nigrum, Silybum marianum, Phyllanthus niruri etc. which are widely used for the treatment of liver disorders. However, there are various herbal plants and phytoconstituents, which are found to be hepatotoxic like Lanata camra Linn, Symphytum officinale, Azadirachta indica, Amantia phalloides etc. This review emphasizes on both sides of the coin like crucial aspects of phytoconstituents with reference to their hepatoprotective as well as hepatotoxic effects linked to use of herbal preparations.

Anti-inflammatory and antihyperalgesic effects of the combination of ibuprofen and hemin in adjuvant-induced arthritis in the Wistar rat.

AIM: Although, pharmacological activation of heme oxygenase (HO)-1 has shown to produce ameliorative effects in various experimental models of inflammation, but such beneficial effects have not been observed in adjuvant-induced arthritis. Further, the upregulated activity of HO-1 has been implicated in the pathogenesis of adjuvant arthritis. The present study was designed to investigate the anti-inflammatory and antihyperalgesic effects of the prophylactic use of hemin alone and/or in combination with ibuprofen using adjuvant-induced arthritis in Wistar rat. METHODS: Arthritis was induced by an intradermal injection of complete Freund's adjuvant (CFA) into left hind paw. Paw volume, thermal hyperalgesia, mechanical allodynia, joint stiffness and mobility behaviors (score) were measured. RESULTS: Administration of ibuprofen (8.75, 17.5, 35 mg/kg/day, p.o.) and hemin (1, 5, 10 mg/kg/day, i.p.) were significantly effective in suppressing CFA-induced paw oedema, thermal and mechanical hyperalgesia, joint stiffness and mobility. The combination of low doses of ibuprofen (8.75 mg/kg, p.o.) and hemin (1 mg/kg, i.p.) significantly reduced paw volume, thermal and mechanical hyperalgesia, as compared to the individual dose of the ibuprofen and hemin alone. CONCLUSIONS: Hence, it may be concluded that the prophylactic administration of either hemin produced significantly enhanced anti-inflammatory and analgesic effects. Further, concurrent low dose administration of hemin and ibuprofen produced significantly enhanced anti-inflammatory and analgesic effects, as compared to the either treatment alone, in CFA-induced arthritis in Wistar rats.

Antiepileptic potential of flavonoids fraction from the leaves of Anisomeles malabarica.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Chodara (Anisomeles malabarica R.Br. Family: Lamiaceae) has numerous therapeutic utilities in folk medicine. AIM OF THE STUDY: To isolate and evaluate the anti-epileptic potential of fractions from the ethyl acetate extract (EAE) of Anisomeles malabarica leaves. MATERIALS AND METHODS: The EA extract (2.12% w/w) of the leaves of Anisomeles malabarica was prepared and fractionated into total flavonoids fraction (AMFF) and tannins fraction (AMTF), which subsequently evaluated for the antiepileptic activity against PTZ- and MES model in wistar rats. Diazepam and phenytoin (2mg/kg and 25mg/kg, i.p., respectively), were used as a reference drugs. Further, the presence of flavonoid was confirmed by chemical test, TLC and HPTLC were done for the identification of the number of flavonoids with reference to standard. RESULTS: Single dose pretreatment with AMFF (25 and 50mg/kg, i.p.) has found to be effective against both MES and PTZ-convulsions, but associated with a marked decrease in locomotor activity and motor activity performance (i.e., neurotoxic effects), similar to that of diazepam treatment. Interestingly, chronic treatment with AMFF at lower doses (6.25 and 12.5mg/kg, i.p., 1 week) has also produced significant antiepileptic activity, but without causing neurotoxic effects. CONCLUSION: Thus, it may be concluded that the flavonoids fraction of the EA extract of Anisomeles malabarica leaves has antiepileptic potential against both MES and PTZ convulsion models. Acute treatment (25 and 50mg/kg, i.p.) is associated with neurotoxic activity. Whereas, chronic treatment (6.25 and 12.5mg/kg, i.p., 1 week) also shown significant antiepileptic effect without causing neurotoxic side effects. However, further research is in progress to determine the component(s) of the flavonoids fraction of Anisomeles malabarica involved and their mechanism of action in bringing about the desirable anti-epileptic effect.

Bronchospasm potentiating effect of methanolic extract of Ficus religiosa fruits in guinea pigs.

ETHNOPHARMACOLOGICAL RELEVANCE: The sacred tree Peepal (Ficus religiosa family: Moraceae) has numerous therapeutic utility in folk medicine. AIM OF THE STUDY: It has been reported to be used in ethno medical treatment of asthma and also in epilepsy due to its high serotonin content, which has been implicated in pathophysiology of asthma, this led us to carry out the present study. MATERIALS AND METHODS: The in vivo studies of histamine induced bronchospasm in guinea pigs and in vitro isolated guinea pig tracheal chain and ileum preparation. RESULTS: Pre-treatment of guinea pigs with ketotifen (1 mg/kg, p.o.) has significantly delayed the onset of histamine aerosol induced pre-convulsive dyspnea, compared with vehicle control (281.8(a)±11.7 vs. 112.2±9.8). The administration of methanolic extract (125, 250 and 500 mg/kg, p.o.) did not produced any significant effect on latency to develop histamine induced pre-convulsive dyspnea. On the other hand, methanolic extract of the fruits at the doses employed (i.e., 0.5, 1 and 2 mg/ml) has significantly potentiate the EC(50) doses of both histamine and acetylcholine in isolated guinea pig tracheal chain and ileum preparation. In addition, HPLC analysis of the methanolic extract showed the presence of high amounts of serotonin (2.89%, w/w). CONCLUSIONS: On the basis of data, it may be concluded that Ficus religiosa fruits have been found to be ineffective against histamine induced bronchospasm in guinea pigs. In addition, methanolic extract of the fruits have shown to potentiate the bronchoconstriction induced by both histamine and acetylcholine on guinea pig tracheal chain preparation.