J Ethnopharmacol. 2009 Aug 12; Wang J, van der Heijden R, Spruit S, Hankermeier T, Chan K, van der Greef J, Xu G, Wang MChinese herbal Medicines, often referred as Chinese Materia Medica (CMM), are comprised of a complex multicomponent nature. The activities are aimed at the system level via interactions with a multitude of targets in the human body. This review aims at the toxicity aspects of CMM and its preparations at the different steps of production; harvesting, processing and the final formulation. The historic perspective and today's issues of the safety of CMM are introduced briefly, followed by the descriptions of the toxic CMM in the current Chinese pharmacopoeia (2005). Subsequently, several aspects of safety are illustrated using a typical example of a toxic CMM, Aconitum roots, and some recent findings of our own research are included to illustrate that proper processing and multi-herbs formulation can reduce the level of toxic components. This also explains that in CMM, some herbs, such as Aconitum, Ephedra species are never used as single herb for intervention and that aconite is only used when it is processed and in combination with specific matched other herbs. The formulation principle of multi-herbs intervention strategy is a systems approach for the treatment and prevention of disease. In this light, the role of systems toxicology in the safety and quality of Chinese herbal medicine is proposed as a promising method. Moreover the principles of practiced-based and evidence-based research are discussed from a symbiotic perspective.

Bioorg Med Chem Lett. 2009 Jul 28; Fu L, Jiang Z, Cai Z, Liu X, He H, Yang YA phosphate prodrug strategy was investigated to address the problem of poor aqueous solubility of pleuromutilin analogues. Water-soluble phosphate prodrugs 6a, 6b and 6c of pleuromutilin analogues were designed and synthesized. Three compounds all exhibited excellent aqueous solubility (>50mg/mL) at near-neutral pH and sufficient stability in buffer solution. In particular, the phenol pleuromutilin prodrug 6c displayed favourable pharmacokinetic profiles and comparable potency with vancomycin against MSSA and MRSA strains in vivo.

J Nat Prod. 2009 Aug 17; Xiao WL, Gong YQ, Wang RR, Weng ZY, Luo X, Li XN, Yang GY, He F, Pu JX, Yang LM, Zheng YT, Lu Y, Sun HDThree new nortriterpenoids, schigrandilactones A-C (1-3), along with eight known compounds, were isolated from an organic solvent extract of Schisandra grandiflora. Compounds 1 and 2 feature a spirocyclic moiety in their structures, and compound 3 was characterized with a new oxygenated pattern. The relative configurations of 1 and 3 were determined through single-crystal X-ray experiments. In addition, compounds 1 and 2 displayed cytotoxic activity against two human cancer cell lines, and compound 3 showed anti-HIV-1 inhibition in infected C8166 cells.

Toxicol Appl Pharmacol. 2009 Aug 11; Zhou J, Huang KAccumulating evidence suggests that peroxynitrite (ONOO(-)) is involved in the pathogenesis of insulin resistance. In the current study, we investigated whether insulin resistance in vivo could be mediated by nitration of proteins involved in the early steps of the insulin signal transduction pathway. Exogenous peroxynitrite donated by 3-morpholinosydnonimine hydrochloride (SIN-1) induced in vivo nitration of the insulin receptor beta subunit (IRbeta), insulin receptor substrate (IRS)-1 and protein kinase B/Akt (Akt) in skeletal muscle of mice, and dramatically reduced whole-body insulin sensitivity and muscle insulin signaling. Moreover, in high-fat diet (HFD)-fed insulin resistant mice, we observed enhanced nitration of IRbeta and IRS-1 in skeletal muscle, in parallel with impaired whole-body insulin sensitivity and muscle insulin signaling. Reversal of nitration of these proteins by treatment with the peroxynitrite decomposition catalyst FeTPPS yielded an improvement in whole-body insulin sensitivity and muscle insulin signaling in HFD-fed mice. Taken together, these findings provide new mechanistic insights for the involvement of peroxynitrite in the development of insulin resistance, and suggest that nitration of proteins involved in the early steps of insulin signal transduction is a novel molecular mechanism of HFD-induced muscle insulin resistance.