Cold-hot nature identification of Chinese herbal medicines based on the similarity of HPLC fingerprints.

The nature theory of Chinese herbal medicines (CHMs) is the core theory of traditional Chinese medicine (TCM). Cold-hot nature is an important part of CHM nature. It is found that the material basis of cold-hot nature is CHM ingredients. To test the scientific hypothesis that "CHMs with similar cold-hot nature should have similar material basis," we explored an intelligent method for cold-hot nature identification of CHMs based on the feature similarity of CHM ingredients in this work. Sixty one CHMs were selected for cold-hot nature identification. High performance liquid chromatography (HPLC) was used to separate the chemical ingredients of CHMs and extract the feature information of CHM ingredients. A distance metric learning algorithm was then learned to measure the similarity of HPLC fingerprints. With the learned distance metric, cold-hot nature identification scheme (CHNIS) was proposed to build an identification model to evaluate the cold-hot nature of CHMs. A number of experiments were designed to verify the effectiveness and feasibility of the proposed CHNIS model. The total identification accuracy rate of 61 CHMs is 80.3%. The performance of the proposed CHNIS algorithm outperformed that of the compared classical algorithms. The experimental results confirmed our inference that CHMs with similar cold-hot nature had similar composition of substances. The CHNIS model was proved to be effective and feasible.

Study on the antibacterial activities of emodin derivatives against clinical drug-resistant bacterial strains and their interaction with proteins.

BACKGROUND: Novel haloemodin (HEI2) synthesized by modifying emodin, a traditional Chinese medicine component, possesses remarkable antibacterial activity, being much more effective than its parent nucleus, emodin. METHODS: Firstly, we discovered that HEI2 increases bacterial cell membrane permeability to potassium ions more drastically than emodin. We thus further investigated the interaction of haloemodin and protein using a fluorescence quenching and circular dichroism (CD) study based on bovine serum albumin (BSA). RESULTS: HEI2 spontaneously bound to BSA at Trp 212 residue (subdomain IIA) by hydrogen bonds and van der Waals interactions to forms HEI2-BSA complexes, and this binding decreased the α-helical content of BSA. We also confirmed that emodin bound to BSA by hydrophobic interaction alone. CONCLUSIONS: These results suggest that the main responses for the substantial antibacterial activities of HEI2 are a disruption of the bacterial plasma membrane function and the interaction with biological functional proteins. Furthermore, the study of the interaction of drugs with BSA, which has a fluorescent group tryptophan residue similar to many bio-functional proteins, will be a simple and inexpensive scope-reducing method in screening new drugs.

Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I.

Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial topoisomerase I and DNA gyrase, and not on the topoisomerases of human origin. In principle, it shows remarkable antibacterial activities against laboratory and clinically isolated Gram-positive bacteria, including vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus. We further expanded its antibacterial spectrum into against Gram-negative bacteria with the assistance of polymyxin B nonapeptide, which helps haloemodin to penetrate through the bacterial outer membrane. Finally, the therapeutic effect of haloemodin in vivo was confirmed in curing S. aureus-induced keratitis on rabbit model. With distinctive structural difference from the antibiotics we used, the haloemodins are of value as promising antibacterial pharmacophore, especially for combat the infections caused by drug-resistant pathogens.

In vitro evaluation of hepatic transporter-mediated clinical drug-drug interactions: hepatocyte model optimization and retrospective investigation.

To assess the feasibility of using sandwich-cultured human hepatocytes (SCHHs) as a model to characterize transport kinetics for in vivo pharmacokinetic prediction, the expression of organic anion-transporting polypeptide (OATP) proteins in SCHHs, along with biliary efflux transporters, was confirmed quantitatively by liquid chromatography-tandem mass spectrometry. Rifamycin SV (Rif SV), which was shown to completely block the function of OATP transporters, was selected as an inhibitor to assess the initial rates of active uptake. The optimized SCHH model was applied in a retrospective investigation of compounds with known clinically significant OATP-mediated uptake and was applied further to explore drug-drug interactions (DDIs). Greater than 50% inhibition of active uptake by Rif SV was found to be associated with clinically significant OATP-mediated DDIs. We propose that the in vitro active uptake value therefore could serve as a cutoff for class 3 and 4 compounds of the Biopharmaceutics Drug Disposition Classification System, which could be integrated into the International Transporter Consortium decision tree recommendations to trigger clinical evaluations for potential DDI risks. Furthermore, the kinetics of in vitro hepatobiliary transport obtained from SCHHs, along with protein expression scaling factors, offer an opportunity to predict complex in vivo processes using mathematical models, such as physiologically based pharmacokinetics models.