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1.
Hum Exp Toxicol ; 38(7): 753-761, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30942101

ABSTRACT

Coconut oil (CO) is enriched with medium chain saturated fatty acids like lauric acid (LA), capric acid and caprylic acid, which are known to have several health benefits. LA, the predominant fatty acid in CO, is reported to possess anticancer activity mediated through oxidative stress-induced apoptosis; however, there is no clear information on its cellular signalling mechanism. The present study screened the anticancer potential of various fatty acids present in CO (capric acid, caprylic acid and LA) using in silico tools such as CDOCKER in Accelrys Discovery Studio by targeting proteins like epidermal growth factor receptor (EGFR), cyclin-dependent kinase and thymidine synthase (TS). The results were further confirmed using cell culture-based studies and quantitative PCR. Among the tested compounds, LA was found to be the most active and showed a higher affinity towards EGFR and TS. Corroborating with these results, LA-induced dose-dependent cytotoxicity towards HCT-15 (human colon cancer), HepG2 (human hepatocellular carcinoma) and Raw 264.7 (murine macrophages) cells exhibiting morphological characteristics of apoptosis. Further, in HCT-15 cells exposed to LA (30 and 50 µg/mL), the expression of EGFR was found to be downregulated by 1.33- and 1.58-fold. The study thus concludes that the anticancer activity of LA may be partially mediated by the downregulation of EGFR signalling and consequent reduction in cell viability through apoptosis. Since EGFR signalling is crucial in cancer cell survival and is a prime target in drug development, the present study has pharmacological significance.


Subject(s)
Coconut Oil/pharmacology , Colonic Neoplasms/metabolism , ErbB Receptors/metabolism , Fatty Acids/pharmacology , Animals , Cell Line , Cell Survival/drug effects , Down-Regulation/drug effects , Humans , Mice , Molecular Docking Simulation
2.
Toxicol Res (Camb) ; 8(2): 297-308, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30997029

ABSTRACT

In this work, silver nanoparticles (AgNP-DTa) were prepared using an aqueous seed extract of D. trifoliata. The importance of the present piece of work is viewed specially with respect to ascertaining the potential of a widely distributed under-utilized mangrove associated plant, Derris trifoliata (DT), as medicine. The as-prepared AgNP-DTa were well dispersed and stabilised in aqueous solution through biological ligands extracted from the seeds of DT. The functional groups present in the bio-ligands of DT act as reducing and stabilising agents in the formation of nanoparticles. Besides, in the present work, sunlight could induce and catalyse the reduction process of Ag+ to its corresponding silver atoms of nanoscale dimensions. The size of AgNP-DTa decreased with an increase in the duration of sunlight irradiation. Bio-augmented nanoparticles were characterized by UV-vis spectroscopy, XRD, HR-TEM, DLS, AFM and photoluminescence measurements. Preliminary phytochemical studies and FTIR analysis confirmed the presence of secondary metabolites with hydroxyl, amine and carbonyl groups as reducing/capping agents. AgNP-DTa demonstrated high DPPH scavenging activity with an IC 50 value of 8.25 µg ml-1. Greater antioxidant activity of AgNP-DTa was also confirmed from total antioxidant capacity (TAC) assay where it was found that the reducing power of 1 g of AgNP-DTa is almost equivalent to that of 1.3 g of Trolox. In addition, highly stable AgNP-DTa showed antibacterial activities against Gram positive and Gram negative bacteria. The as-prepared AgNP-DTa were observed to inhibit the growth of Klebsiella pneumonia, Staphylococcus aureus and Escherichia coli and no clear zone was obtained for Pseudomonas aeruginosa. With reference to the anti-proliferative activities, AgNP-DTa exhibited moderate activity on A549 lung cancer cell lines with a median effective concentration of 86.23 ± 0.22 µg ml-1.

3.
Hum Exp Toxicol ; 36(9): 919-930, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28466662

ABSTRACT

Hepatosteatosis is a complex disorder, in which insulin resistance and associated dyslipidemic and inflammatory conditions are fundamental. Dietary habit, especially regular consumption of fat and sugar-rich diet, is an important risk factor. Coconut and mustard oils (CO and MO) are medium-chain saturated and monounsaturated fats that are common dietary ingredients among the Indian populations. Present study analyzed the effect of prolonged consumption of the fresh and thermally oxidized forms of these oils on glucose tolerance and hepatosteatosis in male Wistar rats. Thermally oxidized CO (TCO) and MO (TMO) possessed higher amount of lipid peroxidation products and elevated p-anisidine values than their fresh forms. Dietary administration of TCO and TMO along with fructose altered glucose tolerance and increased hyperglycemia in rats. Dyslipidemia was evident by elevated levels of triglycerides and reduced high density lipoprotein cholesterol (HDLc) levels in fructose and edible oil-fed group ( p < 0.05). Additionally, hepatic antioxidant status was diminished and oxidative stress markers were elevated in TCO- and TMO-fed rats. Substantiating these, hike in liver function marker enzyme activities were also observed in these animals. Supporting this, histological analysis revealed higher incidence of microvesicles and hepatocellular ballooning. Results thus suggest that consumption of thermally oxidized fats may cause hepatic damage.


Subject(s)
Coconut Oil/toxicity , Mustard Plant/toxicity , Plant Oils/toxicity , Animals , Blood Glucose/analysis , Cholesterol, HDL/blood , Coconut Oil/chemistry , Diet , Dyslipidemias/etiology , Dyslipidemias/metabolism , Dyslipidemias/pathology , Fatty Liver/etiology , Fatty Liver/metabolism , Fatty Liver/pathology , Fructose/toxicity , Hot Temperature , Insulin Resistance , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Mustard Plant/chemistry , Oxidation-Reduction , Oxidative Stress/drug effects , Plant Oils/chemistry , Rats, Wistar , Triglycerides/blood
4.
Hum Exp Toxicol ; 35(2): 205-12, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25805601

ABSTRACT

Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties.


Subject(s)
Alkylating Agents/toxicity , Cyclophosphamide/antagonists & inhibitors , Cyclophosphamide/toxicity , Plant Oils/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacology , Blood Urea Nitrogen , Coconut Oil , Creatinine/metabolism , Dietary Supplements , Edema/pathology , Edema/prevention & control , Formaldehyde , Inflammation/chemically induced , Inflammation/prevention & control , Liver/enzymology , Male , Mice , Mice, Inbred BALB C , Thiobarbituric Acid Reactive Substances/metabolism
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