No abstract

Background: Cancer is a debilitating disease that is on the increase in both developed and developing countries. The plant extract of A. muricata have been known to have a variety of anticancer effects, including anti-angiogenic potential. An in silico study is needed as a preliminary study to understand the mechanism underline this process. Objective: The aim of this study was to investigate the potential of the bioactive compounds of A. muricata in regulating angiogenesis process, primarily by the regulation of hypoxia inducible factor (HIF)-1α expression by in silico study. Methods: This study was performed by in silico analysis including the bioactive compounds preparation, biological activity prediction, protein target and pathway analysis, 3D protein modelling, protein-ligand and protein-protein docking, and the visualization of docking results. Results: There are 3 bioactive compounds of A. muricata with the ability to inhibit HIF-1α expression, including kaempferol, genistein, and glycitein. The inhibition of HIF-1α expression was associated with phosphoinositide 3-kinases (PI3K)/Akt signaling pathway, which involved tyrosine kinase receptor activity on the cell membrane. Based on the silico analysis in this study, we shown that kaempferol, genistein, and glycitein inhibit HIF-1α expression through the disruption of interleukin (IL)-6R and toll-like receptor (TLR)-4 and their respective ligands interaction. Conclusion: The findings of this study show that A. muricata bioactive compounds could inhibit HIF-1α expression through disruption of the tyrosine kinase receptor binding with its ligand.

Squamocin is one of the annonaceous acetogenins produced by the Annonaceae family and displays potent anti-cancer activity against cancer cell lines. This study aimed to investigate the growth inhibition activity of squamocin coupled with nanodiamond on rats (Rattus norvegicus)-induced breast cancer. Twenty-five female R. norvegicus were divided into five groups (n = 5), including normal control (without any treatment), negative control, group treated with nanodiamond only (ND), group treated with squamocin only (SQ), and the group treated with squamocin coupled with nanodiamond (NDSQ). All of the animal models were induced for breast cancer, except for the normal control group. Breast cancer induction was performed using two doses of N-nitroso-N-methylurea (NMU) injection (50 and 30 mg/kg body weight) intraperitoneally and waited for 22 weeks until the tumor was detected to formed. Nanodiamond coupled with squamocin were administered by intraperitoneal injection (1.5 mg/kg body weight) for 5 weeks, one injection per 3 days. This study showed that the treatment with squamocin coupled with nanodiamond (NDSQ) significantly reduced the proliferation (Ki-67) and induced apoptosis (Caspase-3) of breast cancer cells, corresponding to the reduction of the thickness of the mammary ductal epithelium (p<0.001) and the lower level of CA-153 in serum. In addition, the treatment significantly reduced the malondioldehyde (MDA) and PI3KCA and increased the p53 level significantly. Altogether, in this study, we are the first to report the anti-cancer activity of squamocin in rat-induced breast cancer and the potency of nanodiamond as a carrier of squamocin to increase its anti-cancer activity.

Sodium nitrite (NaNO2) found in vegetables, drinking water, and cured meats, can damage tissue because it is an oxidant. Plant phytochemicals such as quercetin are antioxidants. This study aimed to determine the potential of red okra pods ethanol extract (ROE) to repair kidney damage in mice (Mus musculus) induced by NaNO2. The red okra pods were extracted three times with saturated ethanol. The experiment used 36 male BALB/c mice aged 6-8 weeks and body weight of about 28 g. There are six research groups, namely, normal control, negative control (exposure to NaNO2 50 mg/kg BW), treatment of exposure to NaNO2 and administration of ROE at doses of 25, 50, 75, and 100 mg/kg BW. Sodium nitrite and ROE were given daily for 23 days by gavage. On day 24, the serum was isolated. Blood urea nitrogen (BUN) and creatinine (Cre) levels are measured to assess kidney function, as well as measuring the oxidant malondialdehyde (MDA) and the antioxidant enzyme of superoxide dismutase (SOD). The kidneys were made histological preparations and analyzed on the proximal convoluted tubule (PCT).  All data were statistically analyzed (α=0.05). This study indicated that the administration of ROE at a 100 mg/kg BW dose is the most optimal in repairing damage to the PCT with increased normal cells and reduced necrosis. Besides, it degraded BUN, Cre, and MDA levels in the serum of mice exposed to NaNO2 compared to the other treatments. All doses of ROE promoted the SOD level. ROE restore kidney tissue, especially on PCT to normal. Kidney damage due to exposure to NaNO2 preservatives can be reduced by administering ROE. ROE prevents kidney damage through an increase in antioxidant enzymes. ROE can be used as a food ingredient as a source of antioxidants, thereby reducing the impact of oxidant compounds.