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INVESTIGATION OF HEPATOPROTECTIVE ACTIVITY OF HERBAL CONSTITUENTS

Janbaz, Khalid Hussain (1995) INVESTIGATION OF HEPATOPROTECTIVE ACTIVITY OF HERBAL CONSTITUENTS. PhD thesis, University of Karachi, Karachi.

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Abstract

The aqueous-methanolic extracts from indigenous plants and some of the pure compounds were subjected to preliminary for their possible protective effects against lethal dose of paracetamol (1 g/kg) in mice. The hepatoprotective effect was studied further in rats, using paracetamol-and carbon tetrachloride (CC!4)-induced hepatotoxicity as in vivo model. The cytoplasmic enzymes (i.e. GOT, GPT and ALP) are released into serum upon hepatocellular damage and the serum values of such enzymes are reliable indices to assess the extent of hepatic damage. The enzyme values were found to be high in toxin treated animals, whereas the serum enzyme values in the animals pretreated with plant materials were found to be significantly lower than those of the toxic control group and similar to the normal values indicating hepatoprotective effect To resolve whether the hepatoprotective effect was mediated through inhibition of microsomal drug metabolizing enzymes (MDME), the plant material was co-administered with penotabarbital (PB) to observe possible prolongation in pentobarbiral-induced sleep in mice. The test material that was found to prolong the PB sleep were further subjected to strychnine-induced toxicity in mice to clarify whether the prolongation in PB sleep was solely due to inhibitory action on MDME or central depressive activity Since some known calcium channel blockers (CCBs) also exhibit hepatoprotective action and the facility for measuring CCBs-activity was available in the laboratory, the plant materials were also tested for this activity by using isolated tissue experiments (i.e. rabbit jejunum). Plant material with inhibitory action on the spontaneous contraction of jejunum was further tested against the high K+(>mM)-induced spastic contractions as well as in the Ca2+-free medium The post-treatment (Curative) experiments were performed in selected cases where the test material was found to be inhibitory against MDME and was helpful in deciding whether the he-patoprotective activity was solely due to MDME inhibition or some other mechanism was also in operation Artemisia absinthium (shoots), Berberis aristata (shoot and fruits) and berberine (an alkaloid from Berberis aristata) were found to be protective against both paracetamol-and CCI4-induced liver damage and also showed MDME inhibitory activities. These were also capable to show curative effect against paracetamol but unable to mitigate the toxicity due to CCI4, suggesting that baside MDME inhibitory activity other mexhanisms may also be involved in the hepatoprotective response Artemisia maritime (shoots), Artemisia scoparia (shoots), Cichorium intybus (shoots and seeds), Cyperus scariosus (rhizomes), Rubia cordifolia (roots) extracts, and pure compounds from hepatoprotection against both extracts, quercetin as well as Artemisia absinthium extract exhibited Ca2+ channel blocking activities, hence this property may partly be responsible for the observed hepatoprotection The plant materials were found to be relatively safe in acute toxicity testing in mice and this study rationalizes the folkore use of plants in the hepatobiliary disorders

Item Type:Thesis (PhD)
Uncontrolled Keywords:hepatoprotective activity, herbal constituents, aqueous-methanolic extracts, microsomal drug metabolizing enzymes (mdme), calcium channel blockers (ccbs), paracetamol, lethality study, cci4, rubia cordifolia, cyperus scariosus, cichorium intybus, berberis aristata, artemisia scoparia, artemisia martima, artemisia absinthium
Subjects:Biological & Medical Sciences (c) > Medical Sciences (c2) > Pharmacy(c2.5)
ID Code:1078
Deposited By:Mr. Muhammad Asif
Deposited On:20 Dec 2006
Last Modified:04 Oct 2007 21:04

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