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The emergence of drug resistance in Plasmodium falciparum tremendously affected the chemotherapy worldwide while the intense distribution of chloroquine-resistant strains in most of the endemic areas added more complications in the treatment of malaria. The situation has even worsened by the lack of molecular mechanism to understand the resistance conferred by Plasmodia species. Recent studies have suggested the association of antimalarial resistance with P. falciparum multidrug resistance protein 1 (PfMDR1), an ATP-binding cassette (ABC) transporter and a homologue of human P-glycoprotein 1 (P-gp1). The present study deals about the development of PfMDR1 computational model and the model of substrate transport across PfMDR1 with insights derived from conformations relative to inward- and outward-facing topologies that switch on/off the transportation system. Comparison of ATP docked positions and its structural motif binding properties were found to be similar among other ATPases, and thereby contributes to NBD domains dimerization, a unique structural agreement noticed in Mus musculus Pgp and Escherichia coli MDR transporter homolog (MsbA). The interaction of leading antimalarials and phytochemicals within the active pocket of both wild-type and mutant-type PfMDR1 demonstrated the mode of binding and provided insights of less binding affinity thereby contributing to parasite's resistance mechanism.

India is one of the endemic areas where control of malaria has become a formidable task. Artesunate is the current antimalarial drug used to treat malaria, especially chloroquine resistant. The objective of the present study was to investigate the dose-dependent effect of oral administration of artesunate on the oxidative parameters in testes of adult male Swiss albino mice and ameliorative efficacy of curcumin, a widely used antioxidant. An oral dose of 150 mg/kg body weight (bwt; low dose) and 300 mg/kg bwt (high dose) of artesunate was administered for a period of 45 days to male mice, and ameliorative efficacy of curcumin was also assessed. The results revealed that artesunate caused significant alteration in oxidative parameters in dose-dependent manner. Administration of artesunate brought about significant decrease in activities of superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase, whereas lipid peroxidation and glutathione-S-transferase activity were found to be significantly increased. The results obtained show that oxidative insult is incurred upon the intracellular antioxidant system of testis tissue by artesunate treatment. Further, administration of curcumin at the dose level of 80 mg/kg bwt along with both doses of artesunate attenuated adverse effects in male mice.

The present study was conducted to screen the efficacy of curcumin against chloroquine phosphate (CQ)-induced reproductive toxicity in adult male Swiss albino mice. Animals were given oral doses of 100, 200, 300 mg/kg body weight (b.w.), and high dose of CQ (300 mg/kg b.w.) + curcumin (80 mg/kg b.w.) for 45 days. Animals of the withdrawal group were given high dose of CQ (300 mg/kg b.w.) for 45 days and, at day 46, were kept for another 45 days. Effects were observed on some key enzymes, such as alkaline phosphatase, which was found to be decreased, whereas acid phosphatase was increased and succinate dehydrogenase and adenosine triphosphatase were decreased. Oxidative parameters, such as superoxide dismutase declined, whereas thiobarbituric acid-reactive substances were found to be elevated. Protein level was also decreased. Gravimetric indices were also recorded. Results obtained indicated adverse effects of CQ in a dose-dependent manner. The presence of curcumin with CQ alleviated its toxic effects. Hence, it can be concluded that curcumin has beneficial influences and appears able to ameliorate CQ toxicity.

The use of natural antioxidants as mitigating agents has become prevalent. Garlic (Allium sativum) is one such agent which has been proven to have antibacterial, antiseptic, antifungal, antiparasitic, anticoagulant and antitumor properties. The present investigation deals with the ameliorative effects of Allium sativum on the antimalarial drug induced hepato-toxicity. Artesunate is being used as an alternative anti-malarial drug against conventional drugs like chloroquine. Experimental animals were divided into six groups of six mice each. Group A served as the control group. Group B and Group C animals were given 150 mg/kg b.wt and 300 mg/kg b.wt of artesunate respectively while Group D mice were given 100 mg/kg b.wt of Allium sativum. Group E and F mice were given 150 mg/kg b.w of artesunate+100 mg/kg b.wt Allium sativum and 300 mg/kg b.wt of artesunate+100 mg/kg b.wt Allium sativum respectively. Results exhibited recovery and re-establishment of various altered indices as opposed to Artesunate treated groups. Thus, Allium sativum might be used as a potent mitigating agent against anti-malarial drug toxicity. However, further research is needed to completely elucidate the ameliorative efficacy of Allium sativum.

Objective: The present study was focussed on evaluating the hepatoprotective capacity of a combination of leaf extracts of Murraya koenigii and Plumeria rubra on drug-induced toxicity in mice liver.Methods: Hydromethanolic and aqueous extracts were prepared from the leaves of Murraya koenigii and Plumeria rubra. A combination of these extracts was tested as a dual formulation (DF). The extracts were evaluated for their antioxidant activity and phytochemical content. Healthy adult male mice were treated in five groups, for 30 d: Control (Group I-Untreated), Group II (Methotrexate at 10 mg/kg Body weight, intraperitoneally), Group III (Methotrexate+Silymarin), Group IV (Methotrexate+hydromethanolic extract of DF-250 mg/kg b.w., orally), Group V (Methotrexate+aqueous extract of the DF-250 mg/kg b.w. orally). After treatment, the animals were necropsied. Blood was collected for serum parameters such as alanine transaminase (ALT), Aspartate transaminase (AST) and γ glutamyl transpeptidase (GGT). Further liver function tests like Alkaline phosphatase (ALP), Phosphorylase as well as Oxidative stress parameters like Lipid peroxidation (LPO), Superoxide dismutase (SOD), Catalase (CAT), along with the liver protein and cholesterol content were analyzed.Results: Administration of both the DF extracts significantly ameliorated the methotrexate-induced toxic effects on all the aforementioned biochemical parameters. The hydromethanolic extract showed significant recovery in the liver function tests like ALT (p<0.05) and AST (p<0.001). Antioxidant stress enzymes like SOD (p<0.001) and Catalase (p<0.001) also showed significant recovery after administration of both the extracts. The other parameters assayed also followed the same trend. Although both the extracts showed remarkable hepatoprotection, the hydromethanolic extract was found to be significantly more potent than the aqueous extract. ConclusionKeywords: Mice, Liver, Dual formulation, Hepatoprotection : The present study concludes that the Dual formulation of the extracts of Murraya koenigii and Plumeria rubra could be an effective hepatoprotective agent due to the synergistic action of the phytoconstituents of both the plants.

Deltamethrin (DLM) is a widely used pyrethroid, pest control insecticide due to restriction on the sale of organophosphate. Deltamethrin (DLM) being a potent hepatotoxic compound, that affects physiological functions of liver; however, the implications of the hepatotoxic effects of DLM on the mammalian system and its influence on the hepatic enzymatic activity are still unclear. Curcumin (CUR), a major polyphenol component of Curcuma longa Linn, is a potent antioxidant often used in traditional medicine as an ameliorative agent. However, its underlying mechanism as an anti-oxidant against DLM-toxicity remains unknown. Hence, the present study has been designed to determine the binding affinity of DLM to a hepatic enzyme marker such as Aspartate aminotransferase (AST). Moreover, the study is aimed to delineate the role of CUR on DLM-induced hepatotoxic effects through a computational approach. The molecular docking carried out demonstrated that CUR manifests a stronger binding affinity towards the liver marker enzyme, AST as compared to deltamethrin. This could explain the possible mechanism for inhibition of the toxic influence of DLM- induced reactive oxygen species on liver enzyme activity. Thus, this computational evidence validates the tenet that CUR displays anti-oxidative properties for attenuation of DLM induced hepatotoxicity, alteration in the mechanism of liver marker enzyme and its subsequent impact on hepatic tissue.