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Discrimination of the significance of astragalosides in Astragalus radix based on the in vivo exposure levels and
Hui Jiang1, Wei Liu2, Liming Zheng3
1National Key Laboratory of Discovery and Utilization of Functional Components of Traditional Chinese Medicine, Key Laboratory for Standardization of Chinese Medicines, Ministry of Education, Shanghai Key Laboratory for Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201203, Shanghai, China.
Astragalus Radix (AR) quality control can be improved by using multiple astragalosides (ASⅠ, ASⅡ, ASⅢ, ASⅣ) as markers. ASⅠ and ASⅢ show superior conversion to cycloastragenol (CA) in vivo, supporting their role in quality assessment.
Area of Science:
- Pharmacology
- Natural Products Chemistry
- Analytical Chemistry
Background:
- Astragali Radix (AR) is a traditional Chinese tonic with diverse bioactive saponins, including astragaloside Ⅰ (ASⅠ), ASⅡ, ASⅢ, ASⅣ, and cycloastragenol (CA).
- Current quality control of AR primarily relies on ASⅣ, potentially overlooking the contribution of other significant astragalosides.
- Establishing a comprehensive quality control system is crucial for accurately reflecting AR's medicinal value.
Purpose of the Study:
- To evaluate the in vivo pharmacokinetic profiles of ASⅠ, ASⅡ, ASⅢ, ASⅣ, and CA after oral administration of AR.
- To determine the conversion rates and efficiencies of these saponins to cycloastragenol (CA) in vivo.
- To provide a scientific basis for a multi-component quality control system for AR using ASⅠ, ASⅡ, ASⅢ, and ASⅣ as markers.
Main Methods:
- Development and validation of an ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method for pharmacokinetic analysis.
- Assessment of in vivo conversion of individual astragalosides and AR water extract (WEA) into CA in rats.
- Establishment of a UHPLC-evaporative light scattering detector (UHPLC-ELSD) method for quantifying ASⅠ, ASⅡ, ASⅢ, and ASⅣ in AR samples.
Main Results:
- UHPLC-ESI-MS/MS method demonstrated high specificity, accuracy, precision, and stability.
- Following oral administration, astragalosides were primarily detected as the metabolite CA in rat blood.
- ASⅠ and ASⅢ exhibited superior conversion kinetics and efficiency to CA compared to ASⅡ and ASⅣ, with ASⅠ showing prolonged persistence.
Conclusions:
- ASⅠ and ASⅢ are more efficiently converted to CA in vivo than ASⅡ and ASⅣ, highlighting their importance.
- A multi-index quality control system incorporating ASⅠ, ASⅡ, ASⅢ, and ASⅣ is proposed for AR.
- Analyzing in vivo ADME characteristics of active components offers an effective strategy for identifying objective quality markers for traditional medicines.
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