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Characterization of the Active Components of Aurantii fructus Causing Dry Mouth by Analysis of Aquaporin 5 Expression

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Aurantii fructus, the dried immature fruit of Citrus aurantium L., Rutaceae, or its cultivated variants, has been used in traditional Chinese medicine for thousands of years. Unprocessed Aurantii fructus can trigger various side effects, collectively known as “zao”. Dry mouth is the obvious symptom. Fengyan pieces, a processed product of Aurantii fructus, can relieve dry mouth but does not affect its efficacy. In order to analyze this mechanism, the effect on the gastrointestinal tract was characterized by measuring the levels of gastrin, a vasoactive intestinal peptide, in rat serum. Chemical analysis of Aurantii fructus pieces (raw product) and Fengyan pieces was performed by ultra-performance liquid chromatography-mass spectrometry (quadrupole time-of-flight) in combination with chemometrics methods to dereplicate the characteristic components. Aquaporin 5 expression in human submandibular gland cells was measured to validate the effect of the identified components. The results showed that serum gastrin content was different between the different dose groups, and Fengyan pieces showed lower levels of serum vasoactive intestinal peptide than Aurantii fructus pieces. 3,5,6,7,8,3′,4′-Heptamethoxyflavone was the distinctive component, and it has most effectively downregulated aquaporin 5 expression in the submandibular glands of mice. It also reduced aquaporin 5 mRNA and protein expression in human submandibular gland cells. Collectively, these results suggest that processing did not affect the efficacy of Fengyan pieces, but did relieve dry mouth and that 3,5,6,7,8,3′,4′-heptamethoxyflavone was the Aurantii fructus component responsible for dry mouth. This study provides a new scientific basis for reduction of the dry mouth effects of Aurantii fructus from processing.


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Special thanks to Jiangxi University of traditional Chinese medicine for its support of this research.


This work was supported by National Key R&D Program - Special Topics for Modernization of Traditional Chinese Medicine (No. 2018YFC1707206), National Natural Science foundation of China (No.81560651) and Jiangxi Province’s double first-class discipline (Traditional Chinese Medicine) construction project.

Author information

HR analyzed all data and wrote the article; XL performed the chemical study and analyses of data; CW was in charge of cell experiments; LX executed literature search; ML and NL accomplished the pharmacological study; HO advisor and implemented corrections in the article; YL and JZ conceptualized and designed the experimental plan.

Correspondence to Yanju Liu or Hui Ouyang or Jinlian Zhang.

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The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).

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Ren, H., Luo, X., Wan, C. et al. Characterization of the Active Components of Aurantii fructus Causing Dry Mouth by Analysis of Aquaporin 5 Expression. Rev. Bras. Farmacogn. (2020). https://doi.org/10.1007/s43450-020-00001-z

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  • Aurantii fructus
  • Fengyan pieces
  • Dry mouth
  • Aquaporin 5
  • Methoxylated flavone