1. Rosmarinic acid attenuates hepatic fibrogenesis via suppression of hepatic stellate cell activation/proliferation and induction of apoptosis
Naglaa M. EL-LAKKANY ; Walaa H. EL-MAADAWY ; Sayed H. SEIF EL-DIN ; Olfat A. HAMMAM ; Salwa H. MOHAMED ; Shahira M. EZZAT ; Marwa M. SAFAR ; Samira SALEH
Asian Pacific Journal of Tropical Medicine 2017;10(5):444-453
Objective To investigate the antifibrotic role of rosmarinic acid (RA), a natural polyphenolic compound, on HSCs activation/proliferation and apoptosis in vitro and in vivo. Methods The impact of RA on stellate cell line (HSC-T6) proliferation, activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo, rats were divided into: (i) normal; (ii) thioacetamide (TAA)-intoxicated rats for 12 weeks; (iii) TAA + silymarin or (iv) TAA + RA. At the end of experiment, liver functions, oxidative stress, inflammatory and profibrogenic markers, tissue inhibitor metalloproteinases type-1 (TIMP-1) and hydroxyproline (HP) levels were evaluated. Additionally, liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin (α-SMA), caspase-3 and proliferation cellular nuclear antigen (PCNA) were determined. Results RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC
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