In a Rat Model of Acute Liver Failure, Icaritin Improved the Therapeutic Effect of Mesenchymal Stem Cells by Activation of the Hepatocyte Growth Factor/c-Met Pathway.

Acute liver failure (ALF) is a serious life-threatening condition. Mesenchymal stem cells (MSCs) may be an effective treatment for this condition and a good alternative to liver transplantation. Icaritin (ICT) is an active ingredient of the genus Epimedium, a traditional Chinese medicine, with the potential to enhance the proliferation of MSCs. The purpose of this study was to explore whether ICT increased the therapeutic effects of MSCs and explore its underlying mechanisms. For in vivo experiments, a rat ALF model was established by intraperitoneal injection of D(+)-galactosamine/ lipopolysaccharide. MSCs cocultured with ICT were used to treat ALF rats and the protective effects assessed as survival rate, levels of serum AST and ALT, and histological changes in liver tissue. For in vitro experiments, MSCs were treated in serum-free culture for 72 h to simulate the disruption of intrahepatic microcirculation. MSCs apoptosis was examined to determine whether ICT rescued impaired MSCs. The role of the hepatocyte growth factor (HGF)/c-Met pathway in MSCs was assessed by constructing genetically modified MSCs overexpressing c-Met and by using the c-Met receptor inhibitor (crizotinib). The results showed that MSCs increased the survival rate of ALF rats and reduced liver damage. MSCs cocultured with ICT exerted a greater therapeutic effect than MSCs alone. Further, the HGF/c-Met pathway played a key role in the antiapoptotic activity of MSCs, which was associated with the optimized efficacy of ICT. In conclusion, this study demonstrated that ICT enhances the therapeutic effect of MSCs in a model of ALF, improving the antiapoptotic potential of MSCs by upregulation of the HGF/c-Met pathway. The combination of stem cell therapy with traditional herbal extracts may improve MSC-based clinical applications.

NMR based metabolomic comparison of the antitussive and expectorant effect of Farfarae Flos collected at different stages.

Farfarae Flos (FF) is widely used for the treatment of cough, bronchitis, and asthmatic disorders in the Traditional Chinese Medicine (TCM). According to the experience of TCM, only the flower bud can be used as herbal drug, and its medicinal quality becomes lower after blooming. However, the underlying scientific basis for this phenomenon is not fully understood. In this study, the chemical components and the bioactivities of the FF collected at three different development stages were compared systematically. NMR based fingerprint coupled with multivariate analysis showed that the flower buds differed greatly from the fully opened flower both on the secondary and primary metabolites, and the animal experiments showed that the fully opened flower exhibited no antitussive or expectorant effect. In addition, the endogenous metabolites correlated with the antitussive and expectorant effect of FF were also identified. These findings are useful for understanding the rationality of the traditional use of FF, and also suggested the components responsible for the antitussive and expectorant effect of FF.

Metabolomics coupled with similarity analysis advances the elucidation of the cold/hot properties of traditional Chinese medicines.

It recently becomes an important and urgent mission for modern scientific research to identify and explain the theory of traditional Chinese medicine (TCM), which has been utilized in China for more than four millennia. Since few works have been contributed to understanding the TCM theory, the mechanism of actions of drugs with cold/hot properties remains unclear. In the present study, six kinds of typical herbs with cold or hot properties were orally administered into mice, and serum and liver samples were analyzed using an untargeted nuclear magnetic resonance (NMR) based metabolomics approach coupled with similarity analysis. This approach was performed to identify and quantify changes in metabolic pathways to elucidate drug actions on the treated mice. Our results showed that those drugs with same property exerted similar effects on the metabolic alterations in mouse serum and liver samples, while drugs with different property showed different effects. The effects of herbal medicines with cold/hot properties were exerted by regulating the pathways linked to glycometabolism, lipid metabolism, amino acids metabolism and other metabolic pathways. The results elucidated the differences and similarities of drugs with cold/hot properties, providing useful information on the explanation of medicinal properties of these TCMs.

Integrative drug efficacy assessment of Danggui and European Danggui using NMR-based metabolomics.

Danggui (DG) is a commonly used herbal drug in traditional Chinese medicine, and usually adulterated with European Danggui (EDG) due to the increasing demand. In present study, global metabolic profiling with NMR coupled with integrative drug efficacy evaluation methods was performed to compare and discover underlying blood-enriching regulation mechanisms of DG and EDG on blood deficiency rats induced by acetyl phenylhydrazine (APH). Totally, the contents of 12 key metabolites in serum and 4 in urine of DG group, 7 in serum and 4 in urine of EDG group were significantly reversed in comparison with model group. DG was more effective than EDG as revealed by the relative distance, efficacy index and similarity analysis. The metabolism pathways analysis showed that the better effect of DG maybe related with the regulatory effect on valine, leucine and isoleucine biosynthesis, synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, as well as nicotinate and nicotinamide metabolism. The results presented here showed that metabolomic coupled with efficacy index and similarity analysis made it possible to disclose the subtle biological difference between DG and EDG, which highlight the potential of metabolomic approach to quantitatively compare the pharmacological effect of the herbal drugs.

Evaluation of the water soluble extractive of astragali radix with different growth patterns using 1H-NMR spectroscopy.

Astragali radix (AR), known in China as huangqi, is commonly used in traditional Chinese medicine. Water soluble extractive (WSE) values play an important role in the quality evaluation of herbal drugs. In this study, WSE of wild and cultivated AR were compared systematically. The WSE value of cultivated AR was significantly higher than that of the wild AR, and their UV-absorbance in the range of 250-400 nm was also different. The chemical compositions of different WSE were further compared by 1H NMR spectroscopy combined with multivariate analysis. Results from the principal component analysis and the hierarchical cluster analysis showed a clear separation between the WSEs of wild and cultivated AR. The differential metabolites responsible for the separation were identified by orthogonal projections to latent structures discriminant analysis and recursive support vector machine. The WSE of wild AR contained more arginine, valine, threonine, asparagine, succinate, and glutamine, while the cultivated AR contained more sucrose. Thus, the WSE can be used as a simple and reliable method for discrimination of wild and cultivated ARs, and the results obtained in this study extend the potential use of WSE in the quality evaluation of herbal drugs.

[Chemical comparison of different Farfarae Flos by NMR-based metabolomic approaches].

1H NMR-based metabolomic approach combined with multivariate statistical analysis was used to evaluate the quality of 21 Farfarae Flos (FF) samples from different growth regions. Principal component analysis showed that wild and cultivated FF could be separated clearly, suggesting a big chemical difference existed between them. Supervised PLS-DA analysis indicated that the wild samples showed higher levels of secondary metabolites, such as bauer-7-ene-3ß, 16α-diol, chlorogenic acid, rutin, 7-(3'-ethylcrotonoyloxy)-1α-(2'-methyl-butyryloxy)-3, 14-dehydro-Z-notonipetranone (EMDNT), tussilagone, ß-sitosterol and sitosterone. This is consistent with traditional experience that the quality of wild samples are better than that of cultivated ones. The content of pyrrolizidine alkaloids senkirkine also differed greatly among samples from different habitats. The Pearson correlation analysis showed that senkirkine is positively correlated with 4, 5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, rutin, kampferol analogues, to a statistically significant extent. The correlation between the toxic compounds and the bioactive components in FF should be further studied.

Comparative analysis of Danggui and European Danggui using nuclear magnetic resonance-based metabolic fingerprinting.

Danggui is a widely used herbal drug in traditional Chinese medicine, and adulteration with European Danggui is frequently encountered in the market. We compared the chemical compositions and biological effects of Danggui and European Danggui using proton nuclear magnetic resonance spectroscopy coupled with multivariate analysis. Results showed that Danggui and European Danggui differed in both primary and secondary metabolites. Danggui contained higher levels of alanine, γ-aminobutyrate, adenosine, arginine, sucrose, α-glucose, ß-glucose, tryptophan, and cis-Z,Z'-3a.7a',7a.3a'-dihydroxyligustilide than European Danggui. Meanwhile, European Danggui contained higher contents of valine, proline, fumaric acid, phenylalanine, nicotinamide derivative, Z-butylidenephthalide, coniferyl ferulate, ferulic acid, Z-ligustilide, and Z,Z-6,6'7,3a-diligustilide than Danggui. A blood deficiency model was used to compare the biological effects of the two drugs. Despite its higher levels of Z-ligustilide and ferulic acid, European Danggui showed a weaker blood enriching effect than Danggui. Thus, the bioactive compounds responsible for the blood enriching effect in Danggui and their possible synergistic effects should be further studied.

Literature review and analysis of the development of health outcomes assessment instruments in Chinese medicine.

OBJECTIVE: To evaluate the development of health outcomes assessment instruments in Chinese medicine. METHODS: A comprehensive literature search for all published articles in China National Knowledge Infrastructure Database, Chongqing VIP Database and WANFANG Data was conducted. The studies that met the inclusion and exclusion criteria were used to extract information according to a predesigned assessment instrument. RESULTS: A total of 97 instruments for health outcome assessment in Chinese medicine were identified. Of these questionnaires, 7 were generic, 12 were condition-specific and 78 were disease-specific. All instruments were suitable for adults, children, and both men and women. These instruments aimed to evaluate the health-related quality of life, signs and symptoms as well as patient satisfaction and doctor-reported outcome. However, the descriptions were poorly constructed for some of the most basic parameters, such as the domains and items, administrative mode, response options, memory recall periods, burden evaluation, format, copyright, content validity, and other properties. CONCLUSION: The instrument development for health outcomes assessment in Chinese medicine is increasing rapidly; however, there are many limitations in current methodologies and standards, and further studies are needed.