Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice

Ashok Kumar Pandurangan,1,2 Nooshin Mohebali,2 Mohd Esa Norhaizan,1,3 Chung Yeng Looi2 1Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Laboratory of Molecular Medicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaAbstract: Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA.Keywords: IL-21, NQO1, MDA, enzymic antioxidants, Nrf

In-silico and in-vitro toxicological evaluation of Tiktakam kashayam

“TIKTAKAM KASHAYAM” is evaluated by in-silico study using PASS online software. Its having anti-inflammatory activity and also having anti-neoplastic activity especially colon cancer. In-vitro heavy metal analysis shows lead and mercury below the detection limit, cadmium not detected and arsenic is present below the approved range. Some important toxicities like hepatotoxicity shown by the compound azadirachtin present in Azadiracta indica, neurotoxic shown by the compound biflorne present Inoldenlandia corymbosa, Ototoxicity shown by the compound sweroside, reproductive dysfunction produced by the compound luteolin present in Gentiana kuro. Neurotoxic by kobusone, respiratory failure by swertiamarin, ototoxicity by sweroside present in the plant swertia chirayata. Parkinsonism like effect produced by the compound piperine and   pipperitin by Piper longum. The ayurvedic formulation “TIKTAKAM KASHAYAM” possess anti-inflammatory activity and will be beneficial for the treatment of inflammatory bowel disease

Sustained release of anticancer agent phytic acid from its chitosan-coated magnetic nanoparticles for drug-delivery system

Farahnaz Barahuie,1,2 Dena Dorniani,1,3,* Bullo Saifullah,1,* Sivapragasam Gothai,4 Mohd Zobir Hussein,1 Ashok Kumar Pandurangan,5 Palanisamy Arulselvan,4 Mohd Esa Norhaizan6 1Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Zabol University of Medical Sciences, Zabol, Iran; 3Department of Chemistry, University of Sheffield, Sheffield, UK; 4Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 5Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 6Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia *These authors contributed equally to this work Abstract: Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell. Keywords: nanocomposite, drug delivery, chitosan, phytic acid, HT-29 cell line, controlled releas