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Exploring Hepatoprotective and Regenerative Natural and Synthetic Compounds for the Treatment of Hepatitis

Thesis Info

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Author

Hamid Ali

Program

PhD

Institute

University of Karachi

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2015

Thesis Completion Status

Completed

Subject

Molecular Medicine

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/13283/1/Hamid_Ali_Molecular_Medicine_2014_HSR-UoK_Karachi_01.09.2016.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726163160

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It is widely known that hepatitis and its complications such as cirrhosis or hepatocellular carcinoma are one of the major health problems of the world especially since no specific treatment is available. In the present study we investigated the hepatoprotective and regenerative potential of the methanolic extract of the whole plant of Dodonaea viscosa and its ethyl acetate, aqueous, butanol and n-hexane fractions against carbon tetrachloride (CCl4) induced hepatoxicity in rats. Hepatoprotection was assessed in terms of reduction in serum enzymes (ALT, AST, and ALP) that occur after CCl4 injury, and by histopathology and immunohistochemistry. The methanolic extract reduced the serum enzyme level (ALT, AST, and ALP) down to control levels despite CCl4 treatment. It also reduced the CCl4-induced damaged area to 0% as assessed by histopathology. The CD68+ macrophages were also reduced in number around the central vein area by the methanolic extract. These hepatoprotective effects were better than the positive control silymarin. Similar hepatoprotective activities were found with the ethyl acetate, and aqueous fractions of the methanolic extract. The butanol and n-hexane fractions showed elevated levels of ALT, AST and ALP as compared to the positive control silymarin. Histopathology showed ~30% damage to the liver cells with the butanol and n-hexane fractions which still showed some protective activity compared to the CCl4 treated control. HPLC fingerprinting suggested that hautriwaic acid and viscosine present in the methanolic extract and its ethyl acetate, and aqueous fractions may be responsible for this hepatoprotective activity of Dodonaea viscosa which was confirmed by in-vivo experiments. Another, novel approach was used to investigate the hepatoprotective and anti-cirrhotic effect of silymarin and viscosine coated gold nanoparticles, a trend towards nanomedicine.
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یہ زخم اپنے دل کا تو سل بھی سکتا تھا

یہ زخم اپنے دل کا تو سِل بھی سکتا تھا
تُو کن اگر جو کہتا وہ مل بھی سکتا تھا
پژمردہ سا یہ غنچہ ہم دل ہیں جس کو کہتے
گر ساتھ وہ جو چلتا تو کھل بھی سکتا تھا

گرو نانک کے جانشین اور سکھ مت کے ارتقاء میں ان کی اہمیت

This article is an attempt to know about “The Succeeds of Guru Nanak and Their Significance in the Development of Sikhism. There have been nine Succeeds of Guru Nanak in the history of Sikhism. They took significant role in the field of development of Sikhism. It has been studied the major works of these succeeds in this articles. It throws light on the methodology and strategies of the succeeds of Guru Nanak in their reign. Gurdwara panja sahib is one of the holiest places in Sikhism which is believe hold a rock hand print of Guru Nanak. Every year, hundreds and thousands of pilgrims from various parts of the world, especially India and rural areas of Sindh, visit this temple to offer religious rituals in Connection with various occasion like Rakhi, Besakhi, Birth and death anniversary of Guru Nanak Ddev, Joti Jott Mela, death anniversary 05th Guru of Sikhism Guru Arjun Dev. And last emperor of Punjab Maharaja Ranjeet Singh. The lager (holy Food) served at the temple is part of the teachings of Guru Nanak dev Ji, the founder of Sikhism.

Synthesis and Biological Studies of Some Isatins-3-Hydrazones Imines and Their Metal Chelates

The main focus of this thesis is on the synthesis and biological studies of some novel isatin-derived hydrazones, imines and their metal chelates/complexes. Thus, initially, three series of target potential biologically active hydrazones and imines i.e. (47-54), (55-93) and (94-100) were prepared and evaluated for selected biological activities in the present study. The synthesized hydrazones (47-54) were screened for their in vitro antibacterial, antifungal and cytotoxicity potential. Of these, (50), (51) and (54) showed significant antibacterial activity against P. aeruginosa. Similarly, in antifungal assay, compounds (49-52) displayed significant activity against T. longifusus. Also, compounds (49), (51) and (52) proved to be active in a brine shrimp (Artemia salina) lethality bioassay, exhibiting a high degree of cytotoxic activity with LD50 values 3.82×10-5, 2.34×10-5 and 1.53×10-5 M, respectively. The synthetic hydrazones (55-93) were evaluated for their antibacterial, antifungal, phytotoxic, cytotoxic and urease inhibitory effects. In antibacterial assay, none of these was found to be active against any of the tested bacteria. On the contrary, in antifungal assay, twenty six compounds i.e. (55-59), (62-64), (66), (69-70), (72), (78), (80-85) and (87-93) were found to be active, exhibiting weak or non-significant activity (10-30%) against one, two, or three tested fungi. Similarly, in phytotoxicity assay, six compounds i.e. (63), (76), (77), (79), (86) and (91) demonstrated weak or non-significant activity (5-30%) at the highest tested concentration (500μg/mL). To the contrary, in the brine shrimp assay, all the compounds gave LD50 values >1.62 x 10-4 – 2.16 x 10-4 M and, therefore, considered to be almost inactive. However, in urease inhibition assay, they proved to be potent inhibitors of the enzyme, showing IC50 values ranging from 3.70 ± 0.62 to 849 ± 2.26 μM. Compounds (57), (61-63), (65), (68), (70), (71), (77), (79), (80), (82-84), (88), (92) and (93) were found to be relatively more potent, displaying antiurease activity (IC50 = 3.70 ± 0.62 – 20.9 ± 0.57 μM) even better than the reference inhibitor, thiourea (IC50 = 22.3 ± 1.12 μM). Molecular docking studies were also carried out for the hydrazones (55-93) to elucidate their relationship with the binding pockets of the enzyme. Like compounds (55-93), the synthesized bis-imines (94-100) were screened for their in vitro antibacterial, antifungal, phytotoxic, anticancer and antiurease influences. All the compounds were found to be active in antibacterial assay, demonstrating weak to moderate activity against one or more bacterial stains. Similarly, in antifungal assay, all except (100) proved to be active, displaying weak to significant activity against one or more fungi. Furthermore, all the imines also appeared to be active in phytotoxicity assay, showing varied degree of plant growth inhibition (5-100%) at the highest tested concentration (500μg/mL) but much inferior to the reference compound, paraquat, which shows 100 % growth inhibition at 0.015 μg/mL concentration. In sulphorhodamine B (SRB) assay, however, they were found to possess good anticancer activity (IC50 = 2.32 ± 0.11 − 3.88 ± 0.34 μM) against lung carcinoma (H157) cells and low cytotoxicity at Vero cells. Also, in urease inhibition assay, they proved to be potent inhibitors of the enzyme, exhibiting IC50 values in the range 0.04 ± 0.004 – 25.2 ± 1.34 μM. The synthetic bis-imines or Schiff bases (94-100) were used as ligands for synthesizing their Cu(II) complexes (101-107), which were evaluated for their antibacterial, antifungal, anticancer and antiurease potential. All the compounds except (107) were found to be active in antibacterial assay, exhibiting weak to moderate activity against one or more bacterial stains. Similarly, in antifungal assay, all except (102) and (107) displayed weak to good antifungal activity against one or two fungal strains. In anticancer (SRB) assay, coordination/chelation of the Schiff base ligands (94-100) to metal ion was found to cause significant enhancement of activity in all the cases. However, in urease inhibition bioassay, it was found to cause reduction in the enzymatic activity of all the compounds except (105).