Risk Assessment via Metabolism and Cell Growth Inhibition in a HepG2/C3A Cell Line Upon Treatment with Arpadol and its Active Component Harpagoside

Abstract

Harpagophytum procumbens (Hp) has been used as antiinflammatory and analgesic agent for the treatment of rheumatic diseases. The principal active component of Hp is harpagoside (HA). We tested the toxicity of this new therapeutic agent in a hepatic cell line (HepG2/C3A). Hp was found to be cytotoxic, and HA was found to decrease the number of cells in S phase, increase the number of cells in G2/M phase and induce apoptosis. Neither Hp nor HA was genotoxic. The expression of CDK6 and CTP3A4 was reduced by Hp, and both HA and Hp caused a significant reduction of CYP1A2 and CYP3A4 expression. It is possible that the cytotoxicity caused by HA and Hp does not involve transcriptional regulation of the cyclins and CDKs tested but is instead related to the inhibition of metabolism. This is evidenced by the results of an MTT assay and changes in the expression of genes related to drug metabolism, leading to cell death. Indeed, the cells exhibited decreased proliferation upon exposure to Hp and HA. The data show that treatment with either Hp or HA can be cytotoxic, and this should be taken into consideration when balancing the risks and benefits of treatments for rheumatic diseases. Copyright © 2016 John Wiley& Sons, Ltd.

Optimization of Aqueous Extraction and Biological Activity of Harpagophytum procumbens Root on Ex Vivo Rat Colon Inflammatory Model

“…Their extracts were dissolved in dimethyl sulfoxide. These findings could indicate significant different sensitivities of the considered cell lines to Harpagophytum (Biazi et al , ). In this context, our findings showing a different sensitivity between C2C12 and HCT116 cells, following Harpagophytum treatment, could be related to a different response to the metabolic effects induced by the extract.…”

“…The rationale for the traditional use is consistent, albeit in part, with the down-regulation of multiple pathways involved in inflammation, including ROS, cytokines and prostaglandin production (Huang et al, 2006;Grant et al, 2009;Fiebich et al, 2012;Schaffer et al, 2013;Schaffer et al, 2016Günther et al, 2006. On the other hand, the possible hepatic cytotoxic effects induced by Harpagophytum and harpagoside should be taken in consideration (Biazi et al, 2016). Considering both the capability of H. procumbens to contrast inflammatory stimuli in multiple tissues (Schaffer et al, 2013), and the stability of harpagoside in artificial intestinal fluid (Chrubasik et al, 2000), the aim of the present study was to explore the possible protective role of the plant microwave-assisted aqueous extract on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell lines, and isolated rat colon specimens treated with lipopolysaccharide (LPS), a validated ex vivo model of acute ulcerative colitis (Bahar et al, 2012;Menghini et al, 2016).…”

The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process

“…All differences were considered significant when p≤0.05 (GraphPad InStat 5 software). The qPCR was analyzed through the REST program (Pfaffl et al, 2002), was considered significant difference, when the level of relative expression was p≤ 0.5 or higher than 2 (Biazi et al, 2017;Navarro et al, 2018;Rabacow et al, 2018).…”

In Vivo Antileishmanial Effect of 3,5-Diaryl-isoxazole Analogues Based on Veraguensin, Grandisin, and Machilin G: A Glance at a Preclinical Study

“…K562 cells were placed in glass slides after dilution in 20 μL of DMEM (5%, Sigma-Aldrich, supplemented with FBS) and 120 μL of agarose LMP (1.5%, Sigma-Aldrich) reaching the concentration of 2 × 10 5 cells. 54 Glass slides were incubated at 37 °C. The results were obtained after the analysis of photomicrography with LEICA DMi8 microscopy.…”