Towards Polypharmacokinetics: Pharmacokinetics of Multicomponent Drugs and Herbal Medicines Using a Metabolomics Approach.

Towards polypharmacokinetics: pharmacokinetics of multicomponent drugs and herbal medicines using a metabolomics approach.

Evid Based Complement Alternat Med. 2013; 2013: 819147
Lan K, Xie G, Jia W

Determination of pharmacokinetics (PKs) of multicomponent pharmaceuticals and/or nutraceuticals (polypharmacokinetics, poly-PKs) is difficult due to the vast number of compounds present in natural products, their various concentrations across a wide range, complexity of their interactions, as well as their complex degradation dynamics in vivo. Metabolomics coupled with multivariate statistical tools that focus on the comprehensive analysis of small molecules in biofluids is a viable approach to address the challenges of poly-PK. This paper discusses recent advances in the characterization of poly-PK and the metabolism of multicomponent xenobiotic agents, such as compound drugs, dietary supplements, and herbal medicines, using metabolomics strategy. We propose a research framework that integrates the dynamic concentration profile of bioavailable xenobiotic molecules that result from in vivo absorption and hepatic and gut bacterial metabolism, as well as the human metabolic response profile. This framework will address the bottleneck problem in the pharmacological evaluation of multicomponent pharmaceuticals and nutraceuticals, leading to the direct elucidation of the pharmacological and molecular mechanisms of these compounds. HubMed – drug

Apoptosis Effect of Girinimbine Isolated from Murraya koenigii on Lung Cancer Cells In Vitro.

Evid Based Complement Alternat Med. 2013; 2013: 689865
Mohan S, Abdelwahab SI, Cheah SC, Sukari MA, Syam S, Shamsuddin N, Rais Mustafa M

Murraya koenigii Spreng has been traditionally claimed as a remedy for cancer. The current study investigated the anticancer effects of girinimbine, a carbazole alkaloid isolated from Murraya koenigii Spreng, on A549 lung cancer cells in relation to apoptotic mechanistic pathway. Girinimbine was isolated from Murraya koenigii Spreng. The antiproliferative activity was assayed using MTT and the apoptosis detection was done by annexin V and lysosomal stability assays. Multiparameter cytotoxicity assays were performed to investigate the change in mitochondrial membrane potential and cytochrome c translocation. ROS, caspase, and human apoptosis proteome profiler assays were done to investigate the apoptotic mechanism of cell death. The MTT assay revealed that the girinimbine induces cell death with an IC50 of 19.01? ? M. A significant induction of early phase of apoptosis was shown by annexin V and lysosomal stability assays. After 24?h treatment with 19.01? ? M of girinimbine, decrease in the nuclear area and increase in mitochondrial membrane potential and plasma membrane permeability were readily visible. Moreover the translocation of cytochrome c also was observed. Girinimbine mediates its antiproliferative and apoptotic effects through up- and downregulation of apoptotic and antiapoptotic proteins. There was a significant involvement of both intrinsic and extrinsic pathways. Moreover, the upregulation of p53 as well as the cell proliferation repressor proteins, p27 and p21, and the significant role of insulin/IGF-1 signaling were also identified. Moreover the caspases 3 and 8 were found to be significantly activated. Our results taken together indicated that girinimbine may be a potential agent for anticancer drug development. HubMed – drug