Mizaton Hazizul Hasan

Antioxidant properties of phenolic Schiff bases: Structure-activity relationship and mechanism of action

AbstractPhenolic Schiff bases are known for their diverse biological activities and ability to scavenge free radicals. To elucidate (1) the structure–antioxidant activity relationship of a series of thirty synthetic derivatives of 2-methoxybezohydrazide phenolic Schiff bases and (2) to determine the major mechanism involved in free radical scavenging, we used density functional theory calculations (B3P86/6-31+(d,p)) within polarizable continuum model. The results showed the importance of the bond dissociation enthalpies (BDEs) related to the first and second (BDEd) hydrogen atom transfer (intrinsic parameters) for rationalizing the antioxidant activity. In addition to the number of OH groups, the presence of a bromine substituent plays an interesting role in modulating the antioxidant activity. Theoretical thermodynamic and kinetic studies demonstrated that the free radical scavenging by these Schiff bases mainly proceeds through proton-coupled electron transfer rather than sequential proton loss electron transfer, the latter mechanism being only feasible at relatively high pH.

Apoptosis induction by polygonum minus is related to antioxidant capacity, alterations in expression of apoptotic-related genes, and S-phase cell cycle arrest in HepG2 cell line

Polygonum minus (Polygonaceae) is a medicinal herb distributed throughout eastern Asia. The present study investigated antiproliferative effect of P. minus and its possible mechanisms. Four extracts (petroleum ether, methanol, ethyl acetate, and water) were prepared by cold maceration. Extracts were subjected to phytochemical screening, antioxidant, and antiproliferative assays; the most bioactive was fractionated using vacuum liquid chromatography into seven fractions (F1–F7). Antioxidant activity was measured via total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Antiproliferative activity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most active fraction was tested for apoptosis induction and cell cycle arrest in HepG2 cells using flow cytometry and confocal microscopy. Apoptotic-related gene expression was studied by RT-PCR. Ethyl acetate extract was bioactive in initial assays. Its fraction, F7, exhibited highest antioxidant capacity (TPC; 113.16 ± 6.2 mg GAE/g extract, DPPH; EC50: 30.5 ± 3.2 μg/mL, FRAP; 1169 ± 20.3 μmol Fe (II)/mg extract) and selective antiproliferative effect (IC50: 25.75 ± 1.5 μg/mL). F7 induced apoptosis in concentration- and time-dependent manner and caused cell cycle arrest at S-phase. Upregulation of proapoptotic genes (Bax, p53, and caspase-3) and downregulation of antiapoptotic gene, Bcl-2, were observed. In conclusion, F7 was antiproliferative to HepG2 cells by inducing apoptosis, cell cycle arrest, and via antioxidative effects.

Anti-proliferative effect of Tinaspora crispa (L.) Hook. F. & Thompson and Gelam (Melaleuca sp.) honey on several cancer cell lines

Tinaspora crispa and Gelam (Melaleuca sp.) honey were identified as potential anti-proliferative agents due to presence of high antioxidant activity. In this research, human breast adenocarcinoma (MCF-7), human colorectal carcinoma (HCT116), human hepatocellular carcinoma (HepG2) and adenocarcinoma human alveolar basal epithelial (A549) cell lines were treated with both extracts and further diagnosed the viability using 3- (4,5 - dimethylthiazol-2-y) - 5 - (3-carboxymetaxyphenyl) 2- (4- sulphophenyl) - 2H - tetrazolium (MTS) assay. T.crispa and Gelam honey have showed anti-proliferative effects to selected cancer cell lines. The maximal effect of T. crispa and Gelam honey were demonstrated on HepG2 (IC50 = 9.13 µg/ml) and HCT116 (IC50 = 3.98 %, v/v) accordingly. In addition, we revealed that Gelam honey exhibited anti-proliferative effect on MCF-7. While the finest preparation of T.crispa crude extract revealed a potential result compared to previous studies. Total phenolic content may play the major role in demonstrating anti-proliferative effect, which was measured parallel as the main source of antioxidant activity.

Hypoglycemic effect of Octomeles sumatrana aqueous extract in streptozotocin-induced diabetic rats and its molecular mechanisms

OBJECTIVE To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O. sumatrana) (OS) in streptozotocin-induced diabetic rats (STZ) and its molecular mechanisms. METHODS Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in to male Sprague-Dawley rats. Rats were divided into six different groups; normal control rats were not induced with STZ and served as reference, STZ diabetic control rats were given normal saline. Three groups were treated with OS aqueous extract at 0.2, 0.3 and 0.5 g/kg, orally twice daily continuously for 21 d. The fifth group was treated with glibenclamide (6 mg/kg) in aqueous solution orally continuously for 21 d. After completion of the treatment period, biochemical parameters and expression levels of glucose transporter 2 (Slc2a2), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1) were determined in liver by quantitative real time PCR. RESULTS Administration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease (P<0.05) in blood glucose level in a dose dependent manner by 36%, 48%, and 64% at doses of 0.2, 0.3 and 0.5 g/kg, respectively, in comparison to the STZ control values. Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes. Morefore, OS treated rats, showed significantly lower levels of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and urea levels compared to STZ untreated rats. The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group. CONCLUSIONS O. sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.

Cytotoxicity studies of aqueous extracts of Curcuma longa and Quercus infectoria

Curcuma longa (CL) has been widely studied for its efficacies in assisting treatment of diseases such as Alzheimer, arthritis and many types of cancer diseases whilst Quercus infectoria (QI) possessed potential as local anaesthetic, antiseptic, antibacterial, antifungal, antiviral, anti-inflammatory and anti-diabetic. In Ayurvedic medicine, CL has been used to promote wellness after childbirth especially in wound healing and weight management. The use of QI has also been related to this beneficial use. However, not many studies were done to look into the safety of these plants especially when used in combination. This study was carried out to determine the cytotoxic effects of these aqueous plant extracts on kidney epithellial cells of monkey (Vero), Chinese Hamster Ovarian cells (CHO), human hepatoma (HepG2) and colon carcinoma (HCT116) cell lines. The viability of both aqueous extracts of CL and QI were measured using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. The viability of the cells was proportionate to the concentrations of NADH produced by dehydrogenase enzymes in metabolically active cells. Results demonstrated that QI nut galls aqueous extract was not cytotoxic. However, CL rhizomes aqueous extract showed potential as an anticancer agent with IC50 &#60; 50 µg/ml. In conclusion, QI aqueous extract was considered as safe and may be potential adjunctive anti-obesity agent marketable for weight management. On the other hand, CL aqueous extract should be further investigated for its possibility as an anticancer agent.

Hematological studies in young individuals with Down syndrome

Down syndrome (DS) is a common chromosomal abnormality occurring in about 1 in 700 live births. One of the major medical problems in DS individuals is hematologic abnormalities. This study was carried out to compare the hematological status in young individuals with DS aged 5 to 20 years old (divided into three different age groups: 1 to 7 years [n=7], 8 to 12 years [n=49] and 13 to 20 years [n=50]) and in comparison to age-matched controls and also between genders. Blood samples were collected with informed consent from 106 DS participants and another 106 controls. The blood count was evaluated by blood analyzer (Coulter T-540). There were significantly lower levels of red blood cell count in DS females than in males at the ages of 13 to 20 years (p=0.011). Hemoglobin levels in DS females were significantly lower in the age of 13 to 20 years (p=0.016). A significantly lower hematocrit level was observed in DS females at the age of 13 to 20 years (p=0.005). The mean of white blood cells count in DS was significantly lower than in controls at the ages of 1 to 7 years (p=0.014) and 8 to 12 years (p=0.021). The granulocyte levels was significantly lower in DS by about 45% than in controls aged 8 to 12 years (p=0.038) and also in DS females, aged 13 to 20 years as compared to males (p=0.04). These findings indicate that DS individuals experience hematologic abnormalities and further study should be conducted in order to understand the significance of the abnormalities.

Antioxidant, anti-inflammatory and antinociceptive activities of Mitragyna speciosa and Erythroxylum cuneatum

This study was conducted to determine the potential of both Mitragyna speciosa (MS) and Erythroxylum cuneatum (EC) aqueous leaves extracts as antioxidant, anti-inflammatory and antinociceptive agents. MS has been used traditionally by local folks to treat diarrhea, reducing cough, alleviate pain and to combat fatigue. Meanwhile, EC was used as fish poison and tonic for miscarriage. MS and EC aqueous leaf extracts have the capability to chelate iron and have potent anti-inflammatory and antinociceptive activities but were not effectively inhibiting the production of uric acid. Both extracts (50, 100, 200 and 400 mg/kg, p.o) were given to rodents in carrageenan-induced rat paw edema model and acetic acid-induced writhing in mice models to study their anti-inflammatory and antinociceptive activities, respectively. Animals given (400 mg/kg, p.o) showed significant (p<0.05) reduction in number of writhes and paw edema volume compared to control.