Application of temperature-correlated mobility theory for optimizing the MEKC separation of the main lignans from Schisandra Chinensis Fructus and its prescription Yuye Decoction.

The present work shows the application of the temperature-correlated mobility theory for the optimization of the separation and peak alignment of the main lignans from water extracts of traditional Chinese medicine Schisandra Chinensis Fructus as well as its prescription Yuye Decoction (Jade Fluid Decoction; YYD). This is the first application of this theory for MEKC separations, and the data presentation allows a much easier peak tracking and thereby identification of the analytes. Most interestingly, the data obtained and presented in the mobility scale at 298 K, show that Schisantherin A, which is easily mistaken as one of the analytes using traditional time scale, was actually not detected in Schisandra Chinensis Fructus and Yuye Decoction (Jade Fluid Decoction) water extracts. This proves the value of the temperature-correlated mobility scale for method optimization of complex samples. Thus, in the temperature-correlated mobility scale, the optimization of the system conditions for the MEKC separations can easily be achieved by correcting for viscosity changes. Also, the influence of the operating temperature can be monitored in a more distinct way.

Intestinal absorption and bioavailability of traditional Chinese medicines: a review of recent experimental progress and implication for quality control.

OBJECTIVES: Experimental studies on the pharmacokinetics of traditional Chinese medicines (TCMs) have achieved great progress in recent years. This review aims to summarize the progress made on intestinal absorption and bioavailability of TCMs, and proposes the application of intestinal absorption assays as new tools for the quality and safety control of these medicines. KEY FINDINGS: Since only the absorbed constituents may produce possible therapeutic effect (except those that directly target the digestive tract), intestinal absorption is of utmost importance for the drug action of TCMs, which are usually taken orally. Meanwhile, complicated drug interactions may occur among the multiple ingredients in a herbal mixture. In this regard, the intestinal permeability assays not only provide useful pharmacokinetic data of TCMs, but have potential applications for quality and safety control. Moreover, knockout animals, 2/4/A1 in-vitro cell model and physiologically-based in-silico models based on the online TCM database can be quite useful for the prediction of absorption and bioavailability of TCMs. SUMMARY: A variety of in-vivo, in-vitro, in-situ and in-silico models for predicting the intestinal absorption and bioavailability can be applied to study the herbal interactions and screen appropriate biomarkers for the quality and safety control of TCMs.

Chrysotoxine, a novel bibenzyl compound selectively antagonizes MPP⁺, but not rotenone, neurotoxicity in dopaminergic SH-SY5Y cells.

Chrysotoxine is a naturally occurring bibenzyl compound found in medicinal Dendrobium species. We previously reported that chrysotoxine structure-specifically suppressed 6-hydroxydopamine (6-OHDA)-induced dopaminergic cell death. Whether chrysotoxine and other structurally similar bibenzyl compounds could also inhibit the neurotoxicity of 1-methyl-4-phenyl pyridinium (MPP(+)) and rotenone has not been investigated. We showed herein that chrysotoxine inhibited MPP(+), but not rotenone, induced dopaminergic cell death in SH-SY5Y cells. The overproduction of reactive oxygen species (ROS), mitochondrial dysfunction as indexed by the decrease in membrane potential, increase in calcium concentration and NF-κB activation triggered by MPP(+) were blocked by chrysotoxine pretreatment. The imbalance between the pro-apoptotic signals (Bax, caspase-3, ERK and p38 MAPK) and the pro-survival signals (Akt/PI3K/GSK-3ß) induced by MPP(+) was partially or totally rectified by chrysotoxine. The results indicated that ROS inhibition, mitochondria protection, NF-κB modulation and regulation of multiple signals determining cell survival and cell death were involved in the protective effects of chrysotoxine against MPP(+) toxicity in SH-SY5Y cells. Given the different toxic profiles of 6-OHDA and MPP(+) as compared to rotenone, our results also indicated that DAT inhibition may partially account for the neuroprotective effects of chrysotoxine.

Chrysotoxine, a novel bibenzyl compound, inhibits 6-hydroxydopamine induced apoptosis in SH-SY5Y cells via mitochondria protection and NF-κB modulation.

Some naturally occurring bibenzyl compounds have been reported as free radical scavengers. The present study tested our hypothesis that bibenzyl compounds may be neuroprotective against apoptosis induced by the neurotoxins. Five structurally similar bibenzyl derivatives were tested for their protective effect against 6-hydroxydopamine (6-OHDA) induced toxicity in the human neuroblastoma cell line SH-SY5Y. The results showed that one bibenzyl compound, namely chrysotoxine, significantly attenuated 6-OHDA-induced cell death. The subsequent mechanism study demonstrated that chrysotoxine significantly attenuated 6-OHDA-induced apoptosis characterized by DNA fragmentation and nuclear condensation in a dose-dependent manner. 6-OHDA-induced intracellular generation of reactive oxygen species (ROS), activation of p38 MAPK and ERK1/2, and mitochondrial dysfunctions, including the decrease of membrane potential, increase of intracellular free Ca2+, release of cytochrome c, imbalance of Bax/Bcl-2 ratio and activation of caspase-3 were strikingly attenuated by chrysotoxine pretreatment. Meanwhile, chrysotoxine counteracted NF-κB activation by blocking its translocation to the nucleus, thereby preventing up-regulation of inducible nitric oxide synthase (iNOS) and intracellular NO release. The data provide the first evidence that chrysotoxine protects SH-SY5Y cells against 6-OHDA toxicity possibly through mitochondria protection and NF-κB modulation. Chrysotoxine is thus a candidate for further evaluation of its protection against neurodegeneration in Parkinson's disease.

Hepatoprotective effects of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced acute liver hepatotoxicity in rats.

AIM OF THE STUDY: Coptidis rhizoma (CR, Chinese name is Huanglian) has been used in treating infectious and inflammatory diseases for two thousand years in Traditional Chinese Medicine (TCM). Its related pharmacological basis for the therapeutics has been studied intensively, but CR can also be used for vomiting of "dampness-heat type or acid regurgitation" due to "liver-fire attacking stomach" in TCM, whose symptoms seem to link the hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. To clarify this ethnopharmacological relevance, hepatoprotective effect of Coptidis rhizoma aqueous extract (CRAE) and its possible mechanism were studied in rats intoxicated with carbon tetrachloride (CCl4) in the present study. MATERIALS AND METHODS: SPRAGUE-Dawley (SD) rats aged 7 weeks old were intraperitoneally injected with CCl4 at a dose of 1.0 ml/kg as a 50% olive oil solution. The rats were orally given the CRAE at doses of 400, 600, 800 mg/kg and 120 mg/kg berberine body weight (BW) after 6 h of CCl4 treatment. At 24 h after CCl4 injection, samples of blood and liver were collected and then biochemical parameters and histological studies were carried out. RESULTS: The results showed that CRAE and berberine inhibited significantly the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and increased the activity of superoxide dismutase (SOD). Observation on the hepatoprotective effect of berberine was consistent to that of CRAE. CONCLUSION: The study is the first time to demonstrate that CRAE has hepatoprotective effect on acute liver injuries induced by CCl4, and the results suggest that the effect of CRAE against CCl4-induced liver damage is related to antioxidant property.