AKTIVITAS KEMOPREVENTIF FRAKSI KLOROFORM HERBA BANDOTAN (Ageratum conyzoides L.) TERHADAP EKSPRESI PROTEIN VEGF PADA HEPAR TIKUS GALUR SPRAGUE DAWLEY TERINDUKSI DMBA SECARA IN VIVO DAN IN SILICO
Abstract
Cancer deaths continue to increase annually. Hepatocellular carcinoma
(HCC) is the fifth most common cancer in men. Cancer treatment basicly
expensive and non-selective, beside that chemotherapy inducted the occurrence of
serious side effects. Therefore, a natural-based chemopreventive agent is required
to improve the effectiveness of the existing cancer treatment. Bandotan Herbs
(Ageratum conyzoides L) contains a large type of flavonoids compound that can
be used as a chemopreventive agent. The purpose of this research is to know the
chemopreventive activity of Bandotan Herbs Chloform Fraction (BHCF) due to
the expression of VEGF based on in vivo study and the inhibition nobiletin to
VEGF proteins based on in silico study. The simplisia macerated using ethanol
70% followed by fractionations using chloroform. The phytochemicals
identification of BHCF is done by the TLC method. Molecular docking test of
nobiletin compounds against VEGF proteins, COX-2 and C-Myc compared to 5-
Fluorouracil. The carcinogenesis test required 20 mice tails to be divided into 5
feeding groups. Induction is conducted on a per-oral using CMC-Na 0.5% 1
ml/200 gram, DMBA 20 mg/kgBW and BHCF at a dose of 750 mg/kgBW and
1500 mg/kgBW. DMBA is injected 2 times a week for 5 weeks. Histological
observation is done by the Immunohistochemistry and Haematoxylin-Eosin
methods. The TLC results state that BHCF contains flavonoid as a secondary
metabolites. Molecular docking proves that nobiletin is better in inhibiting the
expression of VEGF with an affinity value -7.6 kcal/mol. Induction of DMBA
causes moderate over-expression of VEGF against liver tissue. Histologically, the
introduction of BHCF at a dose of 1500 mg/kgBW provides better improvement
degrees of histology than 750 mg/kgBW. It can be concluded that BHCF has the
potential to be developed into a chemopreventive agent of liverr cancer.