Hossam Tashkandi

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects millions of people worldwide and increases the risk of colorectal cancer (CRC) development. We have previously shown that American ginseng (AG) can treat colitis and prevent colon cancer in mice. We further fractionated AG and identified the most potent fraction, hexane fraction (HAG), and the most potent compound in this fraction, panaxynol (PA). Because (1) oxidative stress plays a significant role in the pathogenesis of colitis and associated CRC and (2) nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses, we examined the role of Nrf2 as a mechanism by which AG suppresses colitis. Through a series of in vitro and in vivo Nrf2 knockout mouse experiments, we found that AG and its components activate the Nrf2 pathway and decrease the oxidative stress in macrophages (mΦ) and colon epithelial cells in vitro. Consistent with these in vitro results, the Nrf2 pathway is activated by AG and its components in vivo, and Nrf2^-/- mice are resistant to the suppressive effects of AG, HAG and PA on colitis. Results from this study establish Nrf2 as a mediator of AG and its components in the treatment of colitis.

The purpose of our study is to explore the pharmacokinetic parameters of panaxynol (PA) and understand its potential and dosage used in pre-clinical animal models. For in vitro analysis, 5 μM of PA was added to liver microsomes of mouse and human species. Nicotinamide adenine dinucleotide phosphate was added to initiate enzyme reaction except for the negative control. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to measure concentrations. For in vivo studies, CD-1 mice were treated with PA by intravenous (IV) injection or oral administration (PO). Concentrations of PA were measured in plasma and tissue using LC-MS/MS. Pharmacokinetic parameters were obtained using non-compartmental analysis. Area under the curve concentration versus time was calculated using a linear trapezoidal model. In vitro, PA’s half-life is 21.4 min and 48.1 min in mouse and human liver microsomes, respectively. In vivo, PA has a half-life of 1.5 hr when IV-injected, and 5.9 hr when administered via PO, with a moderate bioavailability of 50.4%. Mice show no signs of toxicity up to 300 mg/kg PO. PA concentrations were highest in colon tissue 2 hr post-treatment at 486 ng/g of colon tissue. PA’s pharmacokinetic properties and low toxicity point to the safety and compatibility of PA with mice.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Anastasiya A. Chumanevich1, Anusha Chaparala1, Erin E. Witalison1, Hossam Tashkandi1, Anne B. Hofseth1, Corey Lane1, Edsel Pena2, Piaomu Liu2, Doug L. Pittman1, Prakash Nagarkatti3, Mitzi Nagarkatti3, Lorne J. Hofseth1 and Alexander A. Chumanevich1 1 Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, SC, USA 2 Department of Statistics, University of South Carolina, Columbia, SC, USA 3 School of Medicine, University of South Carolina, Columbia, SC, USA Correspondence to: Alexander A. Chumanevich, email: // <![CDATA[ mail("chumanev","mailbox.sc",14,"") // ]]> Keywords: colitis, colon, inflammation, dextran sulfate sodium, CAM, FDA Received: November 11, 2016 Accepted: November 15, 2016 Published: December 10, 2016

Human epidermal growth factor receptor 2 (HER2) is overexpressed/amplified in ∼30% breast cancers which are associated with poor prognosis. microRNAs are small non-coding RNA which play an important role in many physiological conditions including cancer. Here we screened and identified many miRNAs which are dysregulated by HER2 overexpression. In line with our quantitative PCR analysis data, in silico analysis of microRNA expression profiles of 1302 breast tumors revealed that miR-146a-5p is up-regulated and miR-181d and miR-195-5p are down-regulated in HER2-positive tumors. Furthermore, the expression levels of these microRNAs can significantly predict patient survival and thus potentially serve as new prognostic markers for HER2-positive breast cancer.