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Title of Thesis

Khalid Hussain Janbaz
Institute/University/Department Details
University of Karachi/ Department of Pharmacology
Number of Pages
Keywords (Extracted from title, table of contents and abstract of thesis)
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

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

Download Full Thesis
2382.01 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
182.11 KB
2 1 General Introduction 1-19
179.16 KB
  1.1 Xenogbiotics 1-2
  1.2 Biotransformation 2-3
  1.3 Toxic Metabolites Formaltion 3-5
  1.4 Calcium And Toxic Cell Death 5-7
  1.5 Cellular Protective Measures 7-8
  1.6 Natural Products And Modern Therapy 8-12
  1.7 References 12-19
3 2 General Experimnetal 20-30
107.76 KB
  2.1 Plant Selection 20
  2.2 Extraction Of The Plant Materials 20
  2.3 Pharmacological Materials And Animals 21
  2.4 Paracetamol-Induced Lethality Study In Mice 22
  2.5 Induction Of Hepatic Injury 22
  2.6 Multiple Dose Pre-Treatment In Rats 23
  2.7 Multiple Dose Post-Treatment In Rats 23
  2.8 Pentobarbital-Induced Sleeping Time In Mice 24
  2.9 Strychnine-Induced Lethality In Mice 25
  2.10 Cci4-Induced Prolongation Of Pentobarbital Sleep Interval 26
  2.11 Evaluation Of Ca2+ Channel Blocking Activity 26
  2.12 Statistical Analysis 28
  2.13 References 28-30
4 3 Artemisia Absinthium 31-43
227.27 KB
  3.1 Summary 31
  3.2 Plant Description/Literature Survey 32
  3.3 Materials And Methods 32
  3.4 Results 33-43
  3.5 Discussion 43-49
  3.6 References 49-65
5 4 Artemisia Martima 57-74
167.31 KB
  4.1 Summary 57
  4.2 Plant Description 58
  4.3 Materials And Methods 58
  4.4 Results 59-67
  4.5 Discussion 67-70
  4.6 References 70-74
6 5 Artemisia Scoparia 57-129
448.69 KB
  5.1 Summary 75
  5.2 Plant Description/Literature Survey 76-79
  5.3 Materials And Methods 79
  5.4 Results 80-104
  5.5 Discussion 100
  5.6 References 108-129
7 6 Berberis Aristata 130-173
345.96 KB
  6.1 Summary 131
  6.2 Plant Description/Literature Survey 132
  6.3 Materials And Methods 132-133
  6.4 Results 133-156
  6.5 Discussion 156-162
  6.6 References 162-173
8 7 Cichorium Intybus 174-211
336.65 KB
  7.1 Summary 174
  7.2 Plant Description/Literature Survey 175-176
  7.3 Materials And Methods 177
  7.4 Results 178-196
  7.5 Discussion 196-199
  7.6 References 212-228
9 8 Cyperus Scariosus 212-228
150.73 KB
  8.1 Summary 212
  8.2 Plant Description 213
  8.3 Materials And Methods 214
  8.4 Results 214-223
  8.5 Discussion 223-225
  8.6 References 225-228
10 9 Rubia Cordifolia 229-247
175.12 KB
  9.1 Summary 229
  9.2 Plant Description 230
  9.3 Materials And Methods 230
  9.4 Results 231-240
  9.5 Discussion 240-242
  9.6 References 243-247
11 10 General Discussion 248-263
167.28 KB
12 11 Appendics 264-299
251.94 KB
13 12 Publications & Communications 300-302
37.82 KB