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Title of Thesis

Aqeel Ahmad
Institute/University/Department Details
Department of Microbiology/ University of Karachi
Number of Pages
Keywords (Extracted from title, table of contents and abstract of thesis)
alkaloids, prosopis juliflora, juliflorine, julifloricine. antibiotics, prosopis, mesquite, antimicrobial activity, antibacterial activity

Antimicrobial activity of the juliflorine, julifloricine and a benzene insoluble alkaloidal fraction isolated from Prosopis juliflora was studied against 36 bacteria, 23 fungi, 5 isolates of Entamoeba histolytica and 2 viruses in comparison with the commonly used antibiotics.

All these alkaloids were found to possess significant antibacterial activity and showed a remarkable effect against Gram positive bacteria. MICs of juliflorine and julifloricine against Gram positive bacteria were determined as 1-30 μg/ml and for benzene insoluble alkaloidal fraction 1-40 μg/ml. Apart from Campylobacter species both juliflorine and julifloricine exhibited poor activity against Gram negative bacteria and had MIC ≥ 50 μg/ml. While the fraction was more effective against Gram negative bacteria, with few exception, it inhibited the growth of most bacteria at < 40 μg/ml. Campylobacter species were found to be susceptible to all the alkaloids. Juliflorine susceptibility was found to be stable characteristic and most of the Campylobacter strains (35) gave a zone of 10 mm with 1 0 μg disc. This property of juliflorine could be used as diagnostic differential characteristic between Campylobacter and other enteropathogens.

All the alkaloids were also found to possess significant anticandidal activity and had MIC 0.5-5 μg/ml. juliflorine and the alkaloidal fraction were also found significantly effective against dermatophytes. MICs of juliflorine and the alkaloidal fraction, against majority of dermatophytic fungi were found to be ≤ 2.5 and ≤5 μg/ml respectively. Only benzene insoluble alkaloidal fraction was found effective against filamentous fungi and. superior to griseofulvin and clotrimazole against Aspergillus species. Griseofulvin was found less effective than the alkaloidal fraction and juliflorine against may fungi.

Comparison were also made between the alkaloids and commonly used antibiotics. Resistance pattern was observed against commonly used antibiotics, but some strains resistant to the antibiotics were found susceptible to the alkaloids. Generally antibiotics were found superior to the alkaloids. But against some organisms the alkaloids were found more superior.

The antiprotozoal activity was determined against 5 isolates It of E. histolytica and the MIC value was found to be 5 μg/ml for benzene insoluble alkaloidal fraction and 10 μg/ml for juliflorine and julifloricine. Comparing to the cytotoxicity none of the alkaloid was found to possess significant antiprotozoal activity. None of the alkaloid was found to possess antiviral activity.

All these alkaloids were also studied for their toxicity, mutagenicity, antigenicity and also for their immunomodulating and therapeutic efficacies.

Toxicological studies were carried out both in vitro Pseudomonas fluorescens assay, Ames test and on Tissue culture) and in vivo ( Mice, rabbits, chick and chick embryos). Generally the benzene insoluble fraction was found more toxic, juliflorine comparatively less and julifloricine the least. None of the alkaloids was found mutagenic up to 500 μg.

Benzene insoluble alkaloidal fraction, when administered orally or intraperitoneally, caused some respiratory problems but post-mortem examination did not reveal any significant change. In chick embryos, no apparent change was observed in post-mortem examination of dead or live embryos but the hatched embryos (injected with high dose) were found weak and could not survived for longer period.

Subsequent injection of juliflorine in rabbits produced some toxic response which included swelling, suppuration, tissue degeneration etc.

Local application of the alkaloids on the shaved skin also showed some toxicity with 1 %, 2.5% and 5%in PEG-400 of benzene insoluble alkaloidal fraction, juliflorine and julifloricine respectively. While low concentration of these alkaloids was. Found safe.

Therapeutic trials were also carried out on artificially produced Staphylococcal and derm3tophytic infection in rabbits. Some encouraging results were obtained. These alkaloids showed some therapeutic efficacies in both infection and a dose related clinical and microbiological efficacies were observed. Therapeutic trial in Staphylococcal infection showed curing of 25-100% lesion of Staphylococcus aureus in 2 weeks treatment and 25-75% lesion of Trichophyton mentagrophytes in 3 weeks treatment with 0.1-2.5% ointment of juliflorine. But some time recurrence of infection was observed when treatment was discontinued. Benzene insoluble alkaloidal fraction was found more effective but toxic also. Julifloricine did not produce pronounced effect.

All these alkaloids were also studied for their immunomodulating activity in rabbits against Listeria hemolysin. Juliflorine was found to stimulate immune response and produced 1 :1280 titre of antihemolysin with the 30 mg/Kg of juliflorine booster doses, which was; even higher than the Freund's adjuvant injected rabbits. But this concentration of juliflorine also appeared toxic and showed hemolytic activity and tissue degeneration.

Julifloricine and the alkaloidal fraction did not stimulate immune response in the concentration used.

Pharmacological studies show that all the alkaloids react or metabolised inside the body and could not be detected in the urine, faeces and serum. Though the traces of julifloricine and benzene insoluble alkaloidal fraction were detected in 15 minutes serum samples.

Juliflorine coated bentonite particles, when injected in 12-14 days old chick embryos, were detected in the heart and few in kidney and in muscular tissues, showing high affinity for cardiac tissues and little for kidney and other tissues. Juliflorine was also found to react or precipitate with serum which resulted in partial decrease of its antibacterial activity

All these alkaloids were also found to adsorbed on leucocytes surface and in some fields phagocytosis was also observed.

Download Full Thesis
1435.44 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
106.66 KB
2 1 Introduction 1
24.26 KB
3 2 Review Of Literature 4
296.38 KB
  2.1 Alkaloids 27
  2.2 Prosopis( Mesquite ) 37
  2.3 Prosopis Juliflora 42
  2.4 Alkaloids Of Prosopis Juliflora 43
4 3 Materials And Methods 53
290.72 KB
  3.1 Extraction Of Alkaloids From The Leaves Of Prosopis Juliflora 53
  3.2 In Vitro Antimicrobial Studies Of The Alkaloids 58
  3.3 Toxicological Studies Of The Alkaloids 69
  3.4 Chemotherapeutic Studies Of The Alkaloids 85
  3.5 Immunomodulating Studies Of The Alkaloids 89
  3.6 Serum Binding Property Of The Alkaloids 95
  3.7 Pharmacological Studies Of The Alkaloids 97
  3.8 Study The Interaction Of The Alkaloids With Leucocytes 101
5 4 Results 102
146.44 KB
  4.1 Antimicrobial Activity Of The Alkaloids 102
  4.2 Toxicological Studies Of The Alkaloids 113
  4.3 Chemotherapeutic Studies Of The Alkaloids 122
  4.4 Immunomodulating Studies Of The Alkaloids 125
  4.5 Pharmacological Studies Of The Alkaloids 130
  4.6 Study The In Vitro Interaction Of Leucocytes And The Alkaloids 132
6 5 Discussion 133
749.99 KB
  5.1 Tables 145
  5.2 Figures 211
7 6 References 225
128.94 KB
  6.1 Publication 240