Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 μM concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence potential. Thus, both thymoquinone and curcumin appeared to be promising anthelmintic compounds for further investigations.

Helminth parasites of veterinary importance cause huge revenue losses to agrarian economy worldwide. With the emergence of drug resistance against the current formulations, there is a need to focus on the alternative approaches in order to control this menace. In the present study, biocompatible zinc oxide nanoparticles (ZnO NPs) were used to see their in vitro effect on the biliary amphistomes, Gigantocotyle explanatum, infecting Bubalus bubalis because these nanoparticles are involved in generation of free radicals that induce oxidative stress, resulting in disruption of cellular machinery. The ZnO NPs were synthesized by using egg albumin as a biotemplate and subsequently characterized by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray Diffraction and Spectrophotometrical, which showed that ZnO NPs were highly purified wurtzite type polycrystals, with a mean size of 16.7 nm. When the parasites were treated with lower concentrations (0.004% and 0.008%) of the ZnO NPs, the worms mounted a protective response by stimulating the antioxidant system but the treatment of G. explanatum with 0.012% ZnO NPs produced significant inhibition of the antioxidant enzymes like superoxide dismutase (SOD) (p< 0.05) and glutathione S- transferase (GST) (p<0.01), while the level of malondialdehyde (MDA), a lipid peroxidation marker, was significantly (p< 0.01) elevated. SEM and histopathology revealed pronounced tegumental damage showing the disruption of surface papillae and the annulations, particularly in the posterior region near acetabulum. The under expression of a number of polypeptides, loss of worm motility in a time dependent manner, further reflect strong anthelmintic potential of ZnO NPs. It can be concluded that the anthelmintic effect might be due to the production of reactive oxygen species that target a variety of macromolecules such as nucleic acid, protein and lipids which are involved in different cellular processes.

Our study provides strong evidence that hypoxic preconditioning with cobalt chloride enhances physical performance and protects muscle from exercise-induced oxidative damage via GSH, HO-1 and MT-mediated antioxidative capacity.

Iron oxide nanoparticles (IONPs) are known to induce cytotoxicity in various cancer cell lines through the generation of reactive oxygen species (ROS). However, the studies on its potential to induce toxicity in normal cell lines and in vivo system are limited and ambiguity still exists. Additionally, small molecules are known to interact with the DNA and cause damage to the DNA. The present study is designed to evaluate the potential interaction of IONPs with DNA along with their other toxicological effects and subsequent attenuation by thymoquinone both in vitro (primary lymphocytes) and in vivo (Wistar rats). IONPs were characterized by TEM, SEM-EDS, and XRD. The results from DNA interaction studies showed that IONPs formed a complex with DNA and also got intercalated between the base pairs of the DNA. The decrease in percent cell viability of rat’s lymphocytes was observed along with an increase in ROS generation in a dose-dependent manner (50, 100, 200, 400 and 800 μg/ml of IONPs). The genetic damage in in vivo might be due to the generation of ROS as depletion in anti-enzymatic activity was observed along with an increase in lipid peroxidation in a dose–dependent manner (25, 50, 100 mg/kg of IONPs). Interestingly, supplementation of thymoquinone in combination with IONPs has significantly ( P < 0.05) attenuated the genetic and oxidative damage in a dose-dependent manner both in vitro and in vivo . It can be concluded that thymoquinone has the potential to attenuate the oxidative stress and genetic toxicity in vitro and in vivo .

Inflammasomes are multiprotein complexes having nucleotide-binding domain and leucine-rich repeat consisting members along with pyrin and HIN domain family. An inflammasome mainly consists of cytoplasmic sensor molecule, such as NLRP3, the adaptor apoptosisassociated speck-like protein containing caspase recruitment domain) protein along with effector procaspase-1. The inflammasome regulates caspase-1 activation, resulting in secretion of interleukin- 1β and interleukin-18. The inflammasome activation is linked with infection, stress, or other immunological signals involved in inflammation. The pathophysiological role of NLRP3 inflammasome in immune regulation, inflammatory receptor-ligand interactions, microbial-associated molecular patterns, danger as well as pathogen associated molecular patterns has been demonstrated in last few years. Furthermore, the role of the inflammasome in peripheral and central nervous system involved with cytokine and chemokine inflammatory responses has been demonstrated in preclinical and clinical studies. The understanding of molecular regulation of inflammasome associated pathways is crucial for drug design and delivery. The use of natural product as an alternate therapy is gaining focus because of easy access and cost effectiveness. A number of herbal extracts and its bioactive constituents known as phytochemicals have shown to be effective in inflammatory response mediated by NLRP3 inflammasomes pathways. To understand the interaction of phytochemicals and inflammasome at the molecular level, it is vital to develop effective drugs that can be evaluated further in the clinical settings. Therefore, this review renders an extensive account of all the phytochemicals which are evaluated either in inflammatory experimental animal models or in immortalized human/animal cell lines that modulate NLRP3 inflammasome mediated pathways to mitigate inflammatory responses with the hope that this pathway modulation by phytochemicals may provide a another class of drugs in the armamentarium as well as novel molecular mechanism of natural products targeting NLRP3 inflammasome.