Identification of Chemical Markers for the Discrimination of Radix Angelica sinensis Grown in Geoherb and Non-Geoherb Regions Using UHPLC-QTOF-MS/MS Based Metabolomics.

This research aimed to discover chemical markers for discriminating radix Angelica sinensis (RAS) from different regions and to explore the differences of RAS in the content of four active compounds and anti-inflammatory activities on lipopolysacchride (LPS)-induced RAW264.7 cells and calcium antagonists on the HEK 293T cells of RAS. Nine compounds were selected as characteristic chemical markers by ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS), based on metabolomics, in order to rapidly discriminate RAS from geoherb and non-geoherb regions. The contents of senkyunolide I and butylidenephthalide in geoherb samples were higher than those in non-geoherb samples, but the contents of ferulic acid and levistolide A were lower in the geoherb samples. Furthermore, the geoherbs showed better nitric oxide (NO) inhibitory and calcium antagonistic activities than the non-geoherbs. These results demonstrate the diversity in quality of RAS between geoherbs and non-geoherbs.

Sinigrin Enhanced Antiasthmatic Effects of Beta Adrenergic Receptors Agonists by Regulating cAMP-Mediated Pathways.

Millions of patients suffer from asthma worldwide. However, the first-line drugs used to treat asthma, namely, the beta-adrenergic receptors agonists (ß-agonists), are not recommended for use as monotherapy because of their severe dose-related side effects. This limitation has prompted the search for new therapies, which can be used in conjunction with ß--agonists so that lower doses can be administered. Sinigrin is a major compound found in many antiasthmatic medicinal plants. In this study, we explored the antiasthmatic activity of sinigrin when used in combination with ß-agonists and its underlying mechanism. Sinigrin enhanced the asthma-relieving effects of isoproterenol and reduced the effective isoproterenol dose in an acute-asthma model in guinea pigs. Mechanistically, sinigrin enhanced the cAMP levels induced by ß-agonists by inhibiting PDE4. The resulting increase in cAMP levels stimulated the activity of the downstream effector protein kinase A, which would be expected to ultimately induce the relaxation of airway smooth muscle. In conclusion, sinigrin enhances the asthma-relieving effects of ß-agonists by regulating the cAMP signaling pathway and represents a potential add-on drug to ß-agonists for the treatment of asthma.

Effect of N-methyltyramine on the regulation of adrenergic receptors via enzymatic epinephrine synthesis for the treatment of gastrointestinal disorders.

BACKGROUND: Citri Reticulatae Pericarpium (CRP), Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are all important Citrus species used in traditional Chinese medicines (TCMs) for the treatment of gastrointestinal disorders. Although they have been used since ancient times and are still in use today, the mechanistic basis for their regulation of adrenergic receptors (ARs) is still not clear. PURPOSE: In this study, we aimed to determine the active components and mechanisms of action of CRP, AFI and AF in treating gastrointestinal disorders related to ARs. METHODS: First, the phenethylamine alkaloid components of CRP, AFI and AF were identified and compared across 30 samples of three Citrus species by UPLC-Q/TOF-MS in combination with content difference analysis. Second, the effect of the main active alkaloid component on AR-based gastrointestinal disorders was investigated by an in vivo small intestinal propulsive test and an in vitro relaxing small intestinal smooth muscle activity test. The mechanism of AR regulation of the active alkaloid was further studied by evaluating its effect on relaxing small intestinal smooth muscle in the presence of an inhibitor. Lastly, the enzymes, which played an important role in epinephrine synthesis and AR regulation, were detected by immunohistochemistry. RESULTS: Three phenethylamine AR regulators (N-methyltyramine, synephrine and hordenine) in CRP, AFI and AF were characterized. It was found that N-methyltyramine could relax mouse small intestinal smooth muscle and inhibit small intestinal propulsion. The effect of N-methyltyramine on relaxing small intestinal smooth muscle could be inhibited by a-methyl-l-tyrosine. The enzymes related epinephrine synthesis and AR function were found in the mouse small intestine. The biotransformation process that converts N-methyltyramine to epinephrine was determined. CONCLUSION: The treatment of gastrointestinal disorders of CRP, AFI and AF is associated with their alkaloid component N-methyltyramine via the regulation of ARs, and the mechanism is considered to be the biotransformation of N-methyltyramine to epinephrine by serial synthase, which takes place at the nerves cells in small intestine.