Comprehensive identification of metabolites and metabolic characteristics of luteolin and kaempferol in Simiao Yong'an Decoction in rats by UHPLC-LTQ-Orbitrap MS/MS / 中国中药杂志

Simiao Yong'an Decoction is a classic prescription for treating gangrene. Modern medical evidence has proven that Si-miao Yong'an Decoction has therapeutic effects on atherosclerosis(AS), vascular occlusion angeitides, and hypertension, while its pharmacodynamic mechanism remains unclear. The evidence of network pharmacology, molecular docking, literature review, and our previous study suggests that luteolin and kaempferol are two major flavonoids in Simiao Yong'an Decoction and can inhibit macrophage inflammation and exert anti-AS effects. However, due to lack of the metabolism studies in vivo, little is known about the metabolic characteristics of luteolin and kaempferol. This study employed ultra-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS/MS) and relevant software to identify the metabolites and metabolic pathways of luteolin and kaempferol in rat plasma, urine, and feces, after oral administration of luteolin and kaempferol, respectively. After the administration of luteolin, 10, 11, and 3 metabolites of luteolin were detected in the plasma, urine, and feces, respectively. After the administration of kaempferol, 9, 3, and 1 metabolites of kaempferol were detected in the plasma, urine, and feces, respectively. The metabolic pathways mainly involved methylation, glucuronidation, and sulfation. This study enriches the knowledge about the pharmacological mechanism of luteolin and kaempferol and supplies a reference for revealing the metabolic process of other flavonoids in Simiao Yong'an Decoction, which is of great significance for elucidating the pharmacological effects and effective substances of this decoction in vivo.

Exploration on origin of Simiao Yong'an Decoction / 中国中药杂志

Simiao Yong'an Decoction is composed of Lonicerae Japonicae Flos, Scrophulariae Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizome, which was chosen as one of the 100 classic prescriptions in Catalogue of Ancient Classics Prescription(the first batch). Through tracing to the source, It was found that the Simiao Yong'an Decoction(but not named) originated from the Shi Shi Mi Lu, and was later cited by books such as Ancient and Modern Book Integration-Full Record of Medical Department and New Edition of Useful Prescriptions. Literature shows that this prescription was not named until first reported in the Effect of Traditional Chinese Medicine on Arterial Embolism Gangrene in 1956 by a journalist LYU Min. This article recorded that SHIJIA Baoshan, a monk from Hebei Province, used self-named "Simiao Yong'an Decoction" to treat local arterial embolic gangrene. After comparison, there was two difference between ancient books and SHIJIA Baoshan's records. Firstly, according to ancient books, the composition and dosage of Simiao Yong'an Decoction is Lonicerae Japonicae Flos 90 g, Scrophulariae Radix 90 g, Angelicae Sinensis Radix 60 g, Glycyrrhizae Radix et Rhizome 30 g", and the ratio is 3∶3∶2∶1. By SHIJIA Baoshan's record, the composition and dosage are: Lonicerae Japonicae Flos 66 g, Scrophulariae Radix 132 g, Angelicae Sinensis Radix 99 g, Glycyrrhizae Radix et Rhizome 33 g, and the ratio changed to 2∶4∶3∶1. Secondly, ancient books show that patients can be healed after taking seven or ten days of the previous prescription, however, it would take 3 or 4 months, even 7 months in SHIJIA Baoshan's records. It can be considered that the previous prescription should be used at the beginning of gangrene, while the modified Simiao Yong'an Decoction by SHIJIA Baoshan is widely used in the middle and late stages of gangrene, even the critical condition, that is the reason for longer treatment and larger dosage. Nowadays, Simiao Yong'an Decoction is not limited to the treatment of gangrene and bulla in clinic. Relevant studies have confirmed that Simiao Yong'an Decoction has the effects such as anti-inflammatory, plaque stabilization, lipid-lowering, vascular protection, improvement of hemorheology, anticoagulation, inhibition of thrombosis and fibrinolysis, etc. In the follow-up, we should carry out the analysis of the compatibility of this four medicines, and redefine the scope of its clinical application under the theory of traditional Chinese medicine.