ABSTRACT
Malaria remains a life-threatening health problem and is responsible for the high rates of mortality and morbidity in the tropical and subtropical regions of the world. The increasing threat of drug resistance to available artemisinin-based therapy warrants an urgent need to develop new antimalarial drugs that are safer, more effective, and have a novel mode of action. Natural plants are an excellent source of inspiration in searching for a new antimalarial agent. This research reports a systematic investigation for determining the antimalarial potential of the seeds of A. squamosa. The study shows that the crude seed extract (CSE), protein, saponin, and the oily fractions of the seeds were nontoxic at a 2000 mg/kg body weight dose when tested in Wistar rats, thus revealing high safety is classified as class 5. The oily fraction, Annomaal, demonstrated pronounced antimalarial activity with low IC50 (1.25 ± 0.183 µg/mL) against P. falciparum in vitro. The CSE and Annomaal significantly inhibited the growth of P. berghei parasites in vivo with 58.47% and 61.11% chemo suppression, respectively, while the standard drug artemether showed chemo suppression of 66.75%. Furthermore, the study demonstrated that oral administration of Annomaal at a daily dose of 250 mg/kg/day for 3 days was adequate to provide a complete cure to the P. berghei-infected mice. Annomaal thus holds promise as being patient-compliant due to the shorter treatment schedule, eliminating the need for frequent dosing for extended time periods as required by several synthetic antimalarial drugs. Further studies are needed to determine the active compounds in the oily fraction responsible for antimalarial activity.
Subject(s)
Annona , Antimalarials , Malaria, Falciparum , Rats , Animals , Mice , Antimalarials/pharmacology , Plasmodium falciparum , Plasmodium berghei , Plant Extracts/pharmacology , Rats, Wistar , SeedsABSTRACT
Cancer stem cells (CSCs) are involved in recurrent hepatocellular carcinoma (HCC), yet there is a lack of effective treatment that targets these CSCs. CD44+ and CD133+ CSCs are markedly expressed in HepG2 cells and were isolated and characterized using fluorescence-activated cell sorting (FACS) analysis. Since piperine is known as an effective molecule against metastasis, we thought to investigate the effect of piperine against CD44+/CD133+ CSCs. Herein, piperine was found to be active against these CSCs. Also, it was found appropriate to respite at the 'subG0/G1 and G0/G1' phase of the cell cycle analysis, respectively. TGF-ß activated epithelial-mesenchymal transition (EMT) has been involved in the invasion and metastasis of HepG2 cells in hepatocellular carcinoma. Therefore, we next investigated the effect of piperine on different biomarkers that remarkably takes part in the process of EMT using flow cytometric analysis. Piperine was found able to repress the epithelial marker (E-cadherin) but was unable to restore the level of Vimentin (mesenchymal marker) and SNAIL (EMT-inducing transcription factor). Therefore, the findings of this study revealed that piperine could be an effective treatment strategy for recurrent hepatocarcinogenesis.
Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents/pharmacology , Benzodioxoles/pharmacology , Carcinoma, Hepatocellular/drug therapy , Epithelial-Mesenchymal Transition/drug effects , Liver Neoplasms/drug therapy , Neoplastic Stem Cells/drug effects , Piperidines/pharmacology , Polyunsaturated Alkamides/pharmacology , Alkaloids/chemical synthesis , Alkaloids/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Benzodioxoles/chemical synthesis , Benzodioxoles/chemistry , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Molecular Dynamics Simulation , Molecular Structure , Piperidines/chemical synthesis , Piperidines/chemistry , Polyunsaturated Alkamides/chemical synthesis , Polyunsaturated Alkamides/chemistry , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Pramipexole belongs to a class of nonergot dopamine agonist recently approved for the treatment of early and advanced Parkinson's disease. A validated specific stability indicating reversed-phase liquid chromatographic method has been developed for the quantitative determination of pramipexole in bulk as well as in pharmaceutical dosage forms in the presence of degradation products. Forced degradation studies were performed by exposition of drug to hydrolytic (acidic and basic), oxidative and photolytic stress conditions, as defined under ICH guideline Q1A (R2). Significant degradation was observed under hydrolytic, oxidative and photolytic conditions and the degradation products formed were identified by LC-MS.
ABSTRACT
The objective of current study was to develop a validated specific stability indicating reversed-phase liquid chromatographic method for the quantitative determination of desvenlafaxine in bulk sample and pharmaceutical dosage form in the presence of degradation products. Forced degradation studies were performed on bulk sample of desvenlafaxine as per ICH prescribed stress conditions using acid, base, oxidative and photolytic degradation to show the stability indicating power of the method. Significant degradation was observed under acidic stress condition and the degradation product formed was identified by LC-MS and a degradation pathway for drug has been proposed. Successful separation of drug from degradation products formed under stress conditions was achieved on a SymmetryShield column C18 (5 µm, 250 mm×4.6 mm, i.d.) using the mobile phase consisting of a mixture of 0.2% (v/v) triethylamine in ammonium acetate (0.05 M; pH 6.5) and methanol using isocratic gradient.
