Pharmacokinetics of Panaxynol in Mice.

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.

Panaxynol, a bioactive component of American ginseng, targets macrophages and suppresses colitis in mice.

Ulcerative colitis has a significant impact on the quality of life for the patients, and can substantially increase the risk of colon cancer in patients suffering long-term. Conventional treatments provide only modest relief paired with a high risk of side effects, while complementary and alternative medicines can offer safe and effective options. Over the past decade, we have shown that both American ginseng and its hexane fraction (HAG) have anti-oxidant and anti-inflammatory properties that can suppress mouse colitis and prevent colitis-associated colon cancer. With the goal of isolating a single active compound, we further fractionated HAG, and found the most abundant molecule in this fraction was the polyacetylene, panaxynol (PA). After isolating and characterizing PA, we tested the efficacy of PA in the treatment and prevention of colitis in mice and studied the mechanism of action. We demonstrate here that PA effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. This study provides additional mechanistic evidence that American ginseng can be used for conventional treatment of colitis and other diseases associated with macrophage dysfunction.

Molecules from American Ginseng Suppress Colitis through Nuclear Factor Erythroid-2-Related Factor 2.

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.

Looking for the best anti-colitis medicine: A comparative analysis of current and prospective compounds.

Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon, which, while untreated, has a relapsing and remitting course with increasing risk of progression toward colorectal cancer. Current medical treatment strategies of UC mostly focus on inhibition of the signs and symptoms of UC to induce remission and prevent relapse of disease activity, minimizing the impact on quality of life, but not affecting the cause of disease. To date, however, there is no single reliable treatment agent and/or strategy capable of effectively controlling colitis progression throughout the patient's life without side effects, remission, or resistance. Taking into consideration an urgent need for the new colitis treatment strategies, targets and/or modulators of inflammation, we have tested current and prospective compounds for colitis treatment and directly compared their anti-colitis potency using a dextran sulfate sodium (DSS) mouse model of colitis. We have introduced a composite score - a multi-parameters comparison tool - to assess biological potency of different compounds.

Identification of new miRNA biomarkers associated with HER2-positive breast cancers.

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.