Md. Moklesur Rahman Sarker

Preliminary study of the immunostimulating activity of an ayurvedic preparation, Kanakasava, on the splenic cells of BALB/c mice in vitro

Context: Immunostimulant plays an important role to prevent infections when defensive capacity of body is impaired, commonly occur with aging, cancer, diabetes, and sepsis. Kanakasava (KNK) is a polyherbal ayurvedic preparation used since ancient times for the treatment of respiratory diseases and to improve immunity. Objective: The present study evaluated the immunostimulating potential of KNK. Materials and methods: The immunostimulating activity of KNK was evaluated by measuring immunoglobulin M (IgM) production and splenocyte proliferation in vitro. BALB/c mice splenocytes were treated with 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, and 4% (v/v) of KNK, and the cells were subcultured at 37°C, humidified atmosphere containing 5% CO2 for 120 h. The production of IgM in cultured supernatants were determined by an enzyme-linked immunosorbent assay (ELISA) and the proliferations of cells were measured by the 3-(4,5-dimethylthiazol-2-y)-2,5-diphenylterazolium bromide (MTT) method. Results and discussion: KNK at the doses of 0.25, 0.5, 0.75, 1, and 1.5% (v/v) significantly augmented polyclonal IgM production (1.211, 1.260, 1.274, 1.180, and 1.028 µg/mL, respectively) compared to control (0.246 µg/mL). Similarly, the same doses stimulated the proliferation of splenocytes as well (Abs. 0.270, 0.281, 0.368, 0.328, and 0.301, respectively, measured at 570 nm) compared to untreated cells (Abs. 0.137). The activity of KNK was not retarded by the treatment of cells with polymixin B. Thus, our results demonstrate that KNK possesses immunostimulating potential that acts through the induction of lymphocytes for proliferation and IgM production. Conclusion: KNK may be useful for strengthening immune responses in case of insufficient or impaired immunity.

Interplay of the Quality of Ciprofloxacin and Antibiotic Resistance in Developing Countries

Ciprofloxacin, a second generation broad spectrum fluoroquinolone, is active against both Gram-positive and Gram-negative bacteria. Ciprofloxacin has a high oral bioavailability and a large volume of distribution. It is used for the treatment of a wide range of infections including urinary tract infections caused by susceptible bacteria. However, the availability and use of substandard and spurious quality of oral ciprofloxacin formulations in the developing countries has been thought to have contributed toward increased risk of treatment failure and bacterial resistance. Therefore, quality control and bioequivalence studies of the commercially available oral ciprofloxacin formulations should be monitored. Appropriate actions should be taken against offending manufacturers in order to prevent the sale of substandard and spurious quality of ciprofloxacin formulations.

Antiproliferative and apoptosis inducing effects of citral via p53 and ROS-induced mitochondrial-mediated apoptosis in human colorectal HCT116 and HT29 cell lines

Despite various anticancer reports, antiproliferative and apoptosis inducing activity of citral in HCT116 and HT29 cells have never been reported. This study aimed to evaluate the cytotoxic and apoptosis inducing effects of citral in colorectal cancer cell lines. The citral-treated cells were subjected to MTT assay followed by flow cytometric Annexin V-FITC/PI, mitochondrial membrane potential and intracellular reactive oxygen species (ROS) determination. The apoptotic proteins expression was investigated by Western blot analysis. Citral inhibited the growth of HCT116 and HT29 cells by dose- and time-dependent manner without inducing cytotoxicity in CCD841-CoN normal colon cells. Flow cytometric analysis showed that citral (50-200μM; 24-48h) induced the externalization of phoshpotidylserine and reduced the mitochondrial membrane potential in HCT116 and HT29 cells. Citral elevated intracellular ROS level while attenuating GSH levels in HCT116 and HT29 cells which were reversed with N-acetycysteine (2mM) pre-treatment indicating that citral induced mitochondrial-mediated apoptosis via augmentation of intracellular ROS. Citral induced the phosphorylation of p53 protein and the expression of Bax while decreasing Bc-2 and Bcl-xL expression which promoted the cleavage of caspase-3. Collectively, our data suggest that citral induced p53 and ROS-mediated mitochondrial-mediated apoptosis in human colorectal cancer HCT116 and HT29 cells.

Evaluation of the Pharmaceutical Quality of Different Brands of Ranitidine Tablets Manufactured in Bangladesh: A Pharmaceutical and Public Health Prospective

Drug counterfeiting and production of substandard drug is a global problem. This study was aimed to assess the pharmaceutical quality of ranitidine hydrochloride tablets manufactured in Bangladesh. Tablets were collected from different parts of Bangladesh and quality parameters were evaluated according to the United States Pharmacopoeia and the British Pharmacopoeial methods. The potency of tablets was measured spectrophotometrically. Weight variation and disintegration time were performed according to pharmaceutical monographs. Among 43 brands tested, 8 failed to comply with the USP specification (active ingredient: 90±10%) due to containing of less amount of ranitidine of which 6 brands were spurious and 2 were substandard in nature. Two brands did not comply with the specification for weight variation of tablets whereas all brands passed disintegration time test. The findings clearly demonstrate the production of substandard ranitidine tablets in Bangladesh. The drug control authority of Bangladesh should take effective steps to prevent the production of substandard drugs to secure public health.

Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae) Exert Antinociceptive and Neuropharmacological Effects in Mice

Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3′,5,6,7,8-hexamethoxy-4′,5′-methylenedioxyflavone (1), 3,3′,4′,5′,5,6,7,8-octamethoxyflavone (exoticin) (2), 6,7,4′,5′-dimethylenedioxy-3,5,3′-trimethoxyflavone (3), and 3,3′,4′,5,5′,8-hexamethoxy-6,7-methylenedioxyflavone (4), isolated and identified from N. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1, 3, and 4 (12.5–25 mg/kg b.w.) exhibited dose-dependent and significant (p < 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K+ channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound 1, 3, and 4 (12.5 mg/kg b.w.) demonstrated significant (p < 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAA receptor in the action of compound 3 and 4 was evident from the reversal effects of flumazenil. In addition, compounds 1 and 4 (12.5–25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1–4) from N. Plumbaginifolia could be considered as suitable candidates for the development of analgesic and anxiolytic agents.

Effect of compounds identified in the active fraction of pericampylus glaucus on blood glucose and lipid profiles in streptozotocin-induced diabetic rats

Objective The present study was designed to determine the effect of compounds identified in the active fraction of Pericampylus glaucus on blood glucose and lipid profiles in streptozotocin (STZ)-induced diabetic rats. Materials and methods Initially, the antidiabetic activity of petroleum ether, n-hexane, chloroform, and ethanolic extracts of P. glaucus was evaluated in STZ-induced diabetic rats at a dose of 400 mg/kg body weight. Then, the potential extract was fractionated by different solvent systems to obtain various fractions. Next, fractions were investigated again at a dose of 100 mg/kg body weight to find the active fraction. The active fraction was examined using STZ-induced diabetic rats for 21 days. The blood glucose levels were observed weekly and various biochemical parameters were determined on the day the rats were killed. Results The active fraction was subjected to gas chromatography mass spectrometry to find the compounds present in the active fraction of ethanolic extract of P. glaucus. The ethanolic extract was noted to have significant (P<0.001) antidiabetic activity in diabetic rats compared with the other extracts. Four fractions (FA, FB, FC, and FD) were collected from the active ethanolic extract. Among these, fraction B, which was collected from a mixture of petroleum ether and ethyl acetate, was found to have a high (P<0.001)-attenuation effect on blood glucose levels compared with the others, except for ‘fraction D’ (P<0.01), which was collected from ethanol. The data showed that the active fraction (fraction B) also induced significant (P<0.05, <0.01, <0.001) attenuation in the levels of triglyceride, total cholesterol, and LDL and a significant (P<0.01) improvement in the level of HDL. In gas chromatography mass spectrometry analysis, 10 peaks were noted, which suggests the presence of 10 compounds in the active fraction responsible for the blood glucose-lowering effect and biochemical parameters. Conclusion The present study confirmed the presence of compounds identified in P. glaucus responsible for the attenuation of blood glucose and lipid parameters.

Structural characterization and antidiabetic potential of a novel heteropolysaccharide from Grifola frondosa via IRS1/PI3K-JNK signaling pathways

A novel heteropolysaccharide from Grifola frondosa named GFP-W has been isolated and purified by DEAE Sephadex A-52 chromatography. Gas chromatography, fourier transform infrared spectroscopy, one-dimensional (1H- and 13C-) and two-dimensional (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC) nuclear magnetic resonance spectroscopy were used to characterize its structure. The average molecular weight of GFP-W was 66.1 kDa. GFP-W mainly contained four kinds of linkage type units as β-D-GlcpA→, 1,2,6-α-Gal, →2)-α-Manp→, and →3)-α-L-Fucp-(1→. It could significantly increase the uptake of glucose in dexamethasone induced insulin resistant HepG2 cells by improving the mRNA and protein expression of insulin receptor substrate 1, phosphatidylinositol-3-kinase, and glucose transporter 4 upregulation and c-Jun N-terminal Kinase 1 downregulation. Moreover, antidiabetic activities of GFP-W were associated with significant changes in the extent of protein lysine acetylation, crotonylation, and succinylation levels. Our results provide a new hypoglycemic therapeutic role and an in-depth analysis on molecular mechanisms upon polysaccharides from G. frondosa.