Metabolomics highlights pharmacological bioactivity and biochemical mechanism of traditional Chinese medicine.

Metabolomics provides an opportunity to develop the systematic analysis of the metabolites and has been applied to discovering biomarkers and perturbed pathways which can clarify the action mechanism of traditional Chinese medicines (TCM). TCM is a comprehensive system of medical practice that has been used to diagnose, treat and prevent illnesses more than 3000 years. Metabolomics represents a powerful approach that provides a dynamic picture of the phenotype of biosystems through the study of endogenous metabolites, and its methods resemble those of TCM. Recently, metabolomics tools have been used for facilitating interactional effects of both Western medicine and TCM. We describe a protocol for investigating how metabolomics can be used to open up ‘dialogue’ between Chinese and Western medicine, and facilitate lead compound discovery and development from TCM. Metabolomics will bridge the cultural gap between TCM and Western medicine and improve development of integrative medicine, and maximally benefiting the human. Copyright © 2014 John Wiley & Sons, Ltd.

The application of metabolomics in traditional Chinese medicine opens up a dialogue between Chinese and Western medicine

Enantiomers of an Indole Alkaloid Containing Unusual Dihydrothiopyran and 1,2,4-Thiadiazole Rings from the Root of Isatis indigotica

The gut microbiota is increasingly recognized to influence brain function through the gut-brain axis. Albiflorin, an antidepressant natural drug in China with a good safety profile, is difficult to absorb and cannot be detected in the brain after oral administration. Accordingly, the antidepressant mechanism of albiflorin in vivo has not been elucidated clearly. Methods: We identified benzoic acid as the characteristic metabolite of albiflorin in vivo and in vitro, then discovered the roles of gut microbiota in the conversion of albiflorin by carboxylesterase. Pharmacodynamic and pharmacokinetic studies were performed for the antidepressant activities of albiflorin in animals, and the efficacy of benzoic acid in inhibiting D-amino acid oxidase (DAAO) in brain was further investigated. Results: We validated that gut microbiota transformed albiflorin to benzoic acid, a key metabolite in the intestine that could cross the blood-brain barrier and, as an inhibitor of DAAO in the brain, improved brain function and exerted antidepressant activity in vivo. Intestinal carboxylesterase was the crucial enzyme that generated benzoic acid from albiflorin. Additionally, the regulatory effect of albiflorin on the gut microbiota composition was beneficial to alleviate depression. Conclusion: Our findings suggest a novel gut-brain dialogue through intestinal benzoic acid for the treatment of depression and reveal that the gut microbiota may play a causal role in the pathogenesis and treatment of the central nervous system disease.

Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin.

Radix isatidis (R. isatidis) (Banlangen) is a traditional Chinese medicine (TCM) famous for its broad antiviral activity. Its clinical medical history spans several thousands of years in China. Many scientists and scholars have conducted systematic research on this herb from its pharmacognosy to pharmaceuticals, especially in China. Through our research and literature reports, we inferred that the antiviral activity of R. isatidis mostly depended on the water-soluble part, including amino acids, IRPS, nucleosides, and sulfur-containing alkaloids. By playing a role in directly killing pathogenic viruses or regulating the immune system to enhance anti-virus ability, R. isatidis's biological activities mostly depend on the synergistic effect of its multiple components. This article aims to expand understanding of R. isatidis in the following aspects including medicinal resources, chemical constituents, pharmacological activities, clinical applications, and separation and analytical technologies.

Research progress of Chinese herbal medicine Radix isatidis (banlangen).

Metabolomics has been frequently used in pharmacodynamic studies, especially those on traditional Chinese medicine (TCM). Radix Paeoniae Alba and Radix Paeoniae Rubra are popularly used in TCM, and both have hepatoprotective effects. In this study, a CCl4-induced acute liver injury rat model was established and confirmed by the observed serum aminotransferase activities. The metabolomics approach was applied to study the influence of Radix Paeoniae Alba and Radix Paeoniae Rubra on the metabolic changes in rats with acute liver injury. The partial least-squares-discriminant analysis (PLS-DA) of rat serum and their ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) fingerprints allowed discrimination of controlled, acute liver injury-model rats after administration of the two types of TCMs. The time-dependent PLS-DA plots showed that the changes in the metabolic patterns of the rats, which were administered with the TCMs, had stabilized within 2 h after they received the intraperitoneal CCl4 injection. The results indicated the protective effect of TCMs against liver injury. Several potential biomarkers were detected and identified, which included creatine, deoxycholic acid, choline, 5-methylenetetrahydrofolate, folic acid, and glycocholic acid. The physiological significance of these metabolic changes was discussed.

Radix Paeoniae Rubra and Radix Paeoniae Alba Attenuate CCl4-Induced Acute Liver Injury: An Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) Based Metabolomic Approach for the Pharmacodynamic Study of Traditional Chinese Medicines (TCMs)

Radix isatidis is an important traditional Chinese medicine with antiviral efficacy. (R)- and (S)-Goitrin are its main bioactive constituents in the 2010 edition of the Chinese Pharmacopoeia. (R)- and (S)-Goitrin are the breakdown products of epiprogoitrin and progoitrin from R. isatidis. The biotransformation of glucosinolates epiprogoitrin and progoitrin to (R)- and (S)-goitrin, however, is still unclear. In the current paper, the biotransformation of glucosinolates was studied. First, the high-performance liquid chromatography methods to analyze glucosinolates and their breakdown products were developed. Then, the biotransformation of individual glucosinolates such as epiprogoitrin and progoitrin was investigated under different pH conditions. Lastly, their biotransformation under five extraction environments was studied. The results showed that (R)- and (S)-goitrin were the most noteworthy breakdown products. Their relative transformation rates were about 70-80%, and the influence of different extraction environments on the transformation rate was not significant. These results would serve as a theoretical basis for industrial production and quality control and would be helpful for further studies on the biotransformation of glucosinolates.

Biotransformation of glucosinolates epiprogoitrin and progoitrin to (R)- and (S)-Goitrin in Radix isatidis.

Lignans from Isatis indigotica roots and their inhibitory effects on nitric oxide production.

As our ongoing research project on Ban Lan Gen (Isatis tinctoria roots), a total of 23 alkaloids were obtained. Compounds 1 and 2 contain an unusual C–C bond between the 2(1H)-quinolinone moiety and the phenol moiety and between the 2(1H)-quinolinone moiety and the 1H-indole moiety, respectively. Compound 3 possesses an unusual carbon skeleton and its putative biosynthetic pathway was discussed, and Compound 23 was deduced as a new indole alkaloid glycoside. Compounds 4–7 were identified as four new natural products by extensive spectroscopic experiments. Additionally, the anti-inflammatory activity was assessed based on nitric oxide (NO) production using Lipopolysaccharide-stimulated RAW264.7 macrophages. Compounds 9, 15, and 17 showed inhibitory effects with IC50 values of 1.2, 5.0, and 74.4 μM.

https://www.mdpi.com/1420-3049/24/22/4033/pdf

Alkaloids with Nitric Oxide Inhibitory Activities from the Roots of Isatis tinctoria.

Twelve new abietane diterpenoids (1–12) and 31 known analogues (13–43) were isolated from a medicinal Chinese herb, Clerodendrum trichotomum Thunberg. The absolute configurations of 1–3 were established on the basis of ECD and X-ray crystallography data, whereas that of 4 was elucidated by comparison of experimental and calculated ECD data. Eight diterpenoids, 15,16-dehydroteuvincenone G (1), trichotomin A (4), 2α-hydrocaryopincaolide F (7), villosin C (20), 15-dehydro-17-hydroxycyrtophyllone A (22), demethylcryptojaponol (38), 6β-hydroxydemethylcryptojaponol (39), and trichotomone (43), exerted inhibitory effects against NO production with IC50 values of 5.6–16.1 μM. The structure–activity relationships of the isolated diterpenoids are also estimated.

Yanhong Shi

Papers

Radix Paeoniae Rubra and Radix Paeoniae Alba Attenuate CCl4-Induced Acute Liver Injury: An Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) Based Metabolomic Approach for the Pharmacodynamic Study of Traditional Chinese Medicines (TCMs)

Biotransformation of glucosinolates epiprogoitrin and progoitrin to (R)- and (S)-Goitrin in Radix isatidis.

Lignans from Isatis indigotica roots and their inhibitory effects on nitric oxide production.

Alkaloids with Nitric Oxide Inhibitory Activities from the Roots of Isatis tinctoria.

Abietane Diterpenoids from the Roots of Clerodendrum trichotomum and Their Nitric Oxide Inhibitory Activities