Effect and molecular mechanism research of Astragalus membranaceus on inhibiting intestinal absorption of six alkaloids of Aconitum carmichaelii in spleen deficiency rats

Xulong Chen; Xinli Liang; Xiaoqiang Kong; Miaomiao Ji; Abid Naeem; Cheng Li; Hao Zheng; Mingxia Gao; Zhenggen Liao

doi:10.1016/j.chmed.2021.07.001

Effect and molecular mechanism research of Astragalus membranaceus on inhibiting intestinal absorption of six alkaloids of Aconitum carmichaelii in spleen deficiency rats

Chin Herb Med. 2021 Jul 9;14(1):117-124. doi: 10.1016/j.chmed.2021.07.001. eCollection 2022 Jan.

Authors

Xulong Chen^{1

2}, Xinli Liang¹, Xiaoqiang Kong¹, Miaomiao Ji¹, Abid Naeem¹, Cheng Li², Hao Zheng¹, Mingxia Gao¹, Zhenggen Liao¹

Affiliations

¹ Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
² Affiliated Hospital, Jiujiang University, Jiujiang 332000, China.

Abstract

Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier.

Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method.

Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity.

Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.

Keywords: Aconitum carmichaelii Debx.; Astragalus membranaceus (Fisch.) Bge.; BCRP; MRP2; alkaloids; intestinal absorption; spleen deficiency; tight junction.