PASS-predicted hepatoprotective activity of Caesalpinia sappan in thioacetamide-induced liver fibrosis in rats.
The antifibrotic effects of traditional medicinal herb Caesalpinia sappan (CS) extract on liver fibrosis induced by thioacetamide (TAA) and the expression of transforming growth factor β1 (TGF-β1), α-smooth muscle actin (αSMA), and proliferating cell nuclear antigen (PCNA) in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS) Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v) in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY), and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson's trichrome staining, immunohistochemical analysis, and western blotting. In vivo determination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1), and matrix metalloproteinases (MPPS) was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1, αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.
Department of Anatomy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Farkaad A
FA
Kadir
Department of Anatomy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Normadiah M
NM
Kassim
Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Mahmood Ameen
MA
Abdulla
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Behnam
0000-0001-8530-8124
B
Kamalidehghan
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Fatemeh
F
Ahmadipour
Nanotechnology & Catalysis Research Centre (NANOCAT), University of Malaya, Block 3A, Institute of Postgraduate Studies Building, 50603 Kuala Lumpur, Malaysia.
Wageeh A
WA
Yehye
D000818:Animals; D029911:Caesalpinia; D005544:Forecasting; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*; D018515:Plant Leaves; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity*; D016896:Treatment Outcome
D010936:Plant Extracts; D013853:Thioacetamide