Simultaneous determination of isoniazid and pyrazinamide in plasma by high performance liquid chromatography

Purpose: To develop and validate a new high performance liquid chromatographic (HPLC) method for the simultaneous determination of isoniazid (INH) and pyrazinamide (PZA) in plasma.Methods: A 150 μL aliquot of plasma was mixed with 75 μL of 10 % trichloroacetic acid containing 100 mg/L of acetanilide as the internal standard (IS). After vortex mixing and centrifugation, 100 μL of the supernatant was reacted with 20 μL of 0.1 % trans-cinnamaldehyde for 10 min, and then 40 μL of 1M ammonium acetate was added. Finally, 20 μL was injected into the HPLC system. HPLC analysis was performed on reversed phase C18 column. The initial composition of the mobile phase was 4 % acetonitrile, and 96 % of 20 mM 1-hexane sulfonic acid (PH 2.7) delivered at a flow rate 1 mL/min.Results: All calibration curves were linear (r2 > 0.997). The method was accurate, and relative error (RE) was < 4.5 % for both drugs. Intra-day and inter-day precision was good for both drugs, with the highest relative standard deviation (RSD) being 8.51 %. The lower limit of quantification was 0.60 mg/L for isoniazid and 3.00 mg/L for pyrazinamide.Conclusion: The method proposed here is precise, accurate, fast, simple and suitable for therapeutic drug monitoring of INH and PZA simultaneously.Keywords: HPLC, Isoniazid, Pyrazinamide, Plasma, Simultaneous analysi

Metabolomic analysis and biochemical changes in the urine and serum of streptozotocin-induced normal- and obese-diabetic rats

Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal-and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done byevaluating their urine metabolites using proton nuclear magnetic resonance (1H NMR)-based metabolomics and comparing withcontrols at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of theserum were also investigated. The obese-diabetic model was developed by feeding the rats a high-fat diet and inducing diabeticconditions with a low dose of streptozotocin (STZ) (25 mg/kg bw). However, the normal rats were induced by a high dose of STZ(55 mg/kg bw). A partial least squares discriminant analysis (PLS-DA) model showed the biomarkers of both DM typescompared to control. The synthesis and degradation of ketone bodies, tricarboxylic (TCA) cycles, and amino acid pathwayswere the ones most involved in the variation with the highest impact. The diabetic groups also exhibited a noticeable increase inthe plasma glucose level and lipid profile disorders compared to the control. There was also an increase in the plasma cholesteroland low-density lipoprotein (LDL) levels and a decline in the high-density lipoprotein (HDL) of diabetic rats. The normal-diabetic rats exhibited the highest effect of all parameters compared to the obese-diabetic rats in the advancement of the DMperiod. This finding can build a platform to understand the metabolic and biochemical complications of both types of DM and cangenerate ideas for finding targeted drugs

Securinega alkaloids: Reinvestigation on the fresh leaves of Breynia coronate (Euphorbiaceae)

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Relationship between metabolites composition and biological activities of Phyllanthus niruri extracts prepared by different drying methods and solvents extraction

The study investigated the changes in the metabolite, antioxidant and α-glucosidase inhibitory activities of Phyllanthus niruri after three drying treatments: air, freeze and oven dryings. Water extracts and extracts obtained using different solvent ratios of ethanol and methanol (50, 70, 80 and 100%) were compared. The relationships among the antioxidant, α-glucosidase inhibitory activity and metabolite levels of the extracts were evaluated using partial least-square analysis (PLS). The solvent selectivity was assessed based on the phytochemical constituents present in the extract and their concentrations quantitatively analyzed using high performance liquid chromatography. The freeze-dried P. niruri samples that were extracted with the mixture of ethanol or methanol with low ratio of water showed higher biological activity values compared with the other extracts. The PLS results for the ethanolic with different ratio and water extracts demonstrated that phenolic acids (chlorogenic acid and ellagic acid) and flavonoids were highly linked to strong α-glucosidase inhibitory and antioxidant activities

A semisynthetic diterpenoid lactone inhibits NF-kB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model

Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG), two main diterpenoid constituents of Andrographis paniculata were previously shown to ameliorate asthmatic symptoms in a mouse model. However, due to inadequacies of both compounds in terms of drug-likeness, DDAG analogues were semisynthesised for assessment of their anti-asthma activity. A selected analogue, 3,19-diacetyl-14-deoxy-11,12-didehydroandrographolide (SRS27), was tested for inhibitory activity of NF-κB activation in TNF-α-induced A549 cells and was subsequently evaluated in a mouse model of ovalbumin (OVA)-induced asthma. Female BALB/c mice, 6–8 weeks old were sensitized on days 0 and 14, and challenged on days 22, 23 and 24 with OVA. Compound or vehicle (3% dimethyl sulfoxide) was administered intraperitoneally 1 h before and 11 h after each OVA aerosol challenge. On day 25, pulmonary eosinophilia, airway hyperresponsiveness, mucus hypersecretion, inflammatory cytokines such as IL-4, -5 and -13 in BAL fluid, gene expression of inflammatory mediators such as 5-LOX, E-selectin, VCAM-1, CCL5, TNF-α, AMCase, Ym2, YKL-40, Muc5ac, CCL2 and iNOS in animal lung tissues, and serum IgE were determined. SRS27 at 30 μM was found to suppress NF-κB nuclear translocation in A549 cells. In the ovalbumin-induced mouse asthma model, SRS27 at 3 mg/kg displayed a substantial decrease in pulmonary eosinophilia, BAL fluid inflammatory cytokines level, serum IgE production, mucus hypersecretion and gene expression of inflammatory mediators in lung tissues. SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model

Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors

A series of forty-five 1,5-diphenylpenta-2,4-dien-1-one analogues were synthesized and evaluated for their nitric oxide (NO) inhibition activity in IFN-γ/LPS-activated RAW 264.7 cells. Compounds 3h, 7a, 7d and 7e exhibited comparable or significantly higher activity than the standard, curcumin (IC50 = 14.69 ± 0.24 μM). Compound 7d, a 5-methylthiophenyl-bearing analogue, displayed the most promising NO-inhibitory activity with an IC50 value of 10.24 ± 0.62 μM. The 2D and 3D QSAR analyses performed revealed that a para-hydroxyl group on ring B and an α,β-unsaturated ketone moiety on the linker are crucial for a remarkable anti-inflammatory activity. Based on ADMET and TOPKAT analyses, compounds 3h, 7a and 7d are predicted to be nonmutagenic and to exhibit high blood–brain barrier (BBB) penetration, which indicates that they are potentially effective drug candidates for treating central nervous system (CNS) related disorders