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Cited by 7Phytochemistry and Biological ActivitiesTraditional Chinese Medicine AnalysisFlavonoids in Medical Research

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Comparative pharmacokinetic study of the five anti-inflammatory active ingredients of Inula cappa in a normal and an LPS-induced inflammatory cell model

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Huang, Jing, Chen, Ruixing, Zhou, Jie, Zhang, Qing, Xue, Cun, Li, Yueting, Zheng, Lin, Huang, Yong, Wang, Qun, Chen, Yi, Gong, Zipeng·2022·Frontiers in Pharmacology
DOI 10.3389/fphar.2022.981112PMC PMC9527281
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Abstract

Inula cappa is a commonly used medicine in the Miao area of Guizhou Province in China. We established an in vitro inflammatory model of mouse macrophage RAW264.7 cells to study the different pharmacokinetics of five anti-inflammatory active ingredients in the I. cappa extract namely luteolin (LUT), chlorogenic acid (CA), cryptochlorogenic acid (CCA), 3,4-dicaffeoylquinic acid (3,4-DCQA) and 4,5-dicaffeoylquinic acid (4,5-DCQA), in a normal and an inflammatory cell model. First, RAW264.7 cells were treated in vitro with l μg/mL lipopolysaccharide (LPS) for 24 h to establish an inflammatory cell model. Then, the pharmacokinetic characteristics of the five ingredients were compared in normal and inflammatory cells after treatment with 200 μg/ml and 800 μg/ml of I. cappa extracts. After treatment with 1 μg/ml LPS for 24 h, the volume of RAW264.7 cells was increased, the morphology was changed, the antennae were obvious, and the secretion of inflammatory factors nitric oxide and TNF-α was increased. The pharmacokinetics results showed that the five ingredients in normal and inflammatory cells exhibited an increase in C max and AUC values with increasing doses, and the C max and AUC values of five ingredients were positively correlated with the extract concentration. Each of these five ingredients presented nonlinear pharmacokinetic characteristics. After treatment with 200 μg/ml of I. cappa extract, the uptake of five ingredients increased in inflammatory cells, T max was prolonged, MRT and t 1/2 were prolonged, and CL_F and Vz_F were decreased, while after treatment with 800 μg/ml of I. cappa extract, the uptake of five ingredients decreased, T max was prolonged, absorption was faster, and MRT and t 1/2 were prolonged. The five analyzed components in I. cappa extract exerted different effects on normal cells and LPS-induced inflammatory cells. Compared to normal cells, the uptake of five ingredients in inflammatory cells was faster and the AUC and C max values increased with increasing doses, showing a dose-dependent nonlinear pharmacokinetic profile. These results indicate that the pharmacokinetic effects of the five analyzed ingredients in I. cappa extract are changed in the inflammatory state.

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Metadata

Authors
Huang, J., Chen, R., Zhou, J., Zhang, Q., Xue, C., Li, Y., Zheng, L., Huang, Y., Wang, Q., Chen, Y., & Gong, Z.
Affiliations
Guiyang Medical University (CN)
Corresponding author
  • Chen, Yi
  • Gong, Zipeng
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2022-09-19
Volume
13
Pages
981112-981112
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2022.981112
PMC
PMC9527281
OpenAlex
W4296449006
Cited by
7
References
19
Citations by year
2025: 2 · 2024: 3 · 2023: 2
FWCI
0.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81860734)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
  • Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
  • Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
Keywords
pharmacokinetics, luteolin, chlorogenic acid, cryptochlorogenic acid, caffeoylquinic acids, lipopolysaccharide-induced inflammation, RAW 264.7 macrophages, nonlinear pharmacokinetics, nitric oxide, TNF-α, traditional Chinese medicine

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