Magnoflorine from Coptis chinese has the potential to treat DNCB-induced Atopic dermatits by inhibiting apoptosis of keratinocyte

Siqi Wu; Deqing Yu; Wuyang Liu; Jian Zhang; Xiaojiang Liu; Jiankang Wang; Min Yu; Zhaoxing Li; Qianfeng Chen; Xuegang Li; Xiaoli Ye

doi:10.1016/j.bmc.2019.115093

Magnoflorine from Coptis chinese has the potential to treat DNCB-induced Atopic dermatits by inhibiting apoptosis of keratinocyte

Bioorg Med Chem. 2020 Jan 15;28(2):115093. doi: 10.1016/j.bmc.2019.115093. Epub 2019 Sep 7.

Authors

Siqi Wu¹, Deqing Yu¹, Wuyang Liu¹, Jian Zhang², Xiaojiang Liu², Jiankang Wang¹, Min Yu², Zhaoxing Li¹, Qianfeng Chen¹, Xuegang Li³, Xiaoli Ye⁴

Affiliations

¹ School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
² School of Life Sciences, Southwest University, Chongqing 400715, China.
³ School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China. Electronic address: Xuegangli@swu.edu.cn.
⁴ School of Life Sciences, Southwest University, Chongqing 400715, China. Electronic address: yexiaoli@swu.edu.cn.

PMID: 31859028
DOI: 10.1016/j.bmc.2019.115093

Abstract

Aims: In Sheng Nong's herbal classic in China, Rhizoma coptidis^a(RC) could be used to treat Atopic dermatits^b(AD), but its core ingredient(s) and mechanism remains unknown. The present study aimed to find out the ingredients against AD and expound its mechanisms.

Materials and methods: Seven alkaloids were isolated from RC to compare the inhibition against HaCaT cells by MTT assays and apoptosis of cells stimulated with TNF-α/IFN-γ by flow cytometry. The effects of target alkaloids against AD were evaluated on DNCB^c (2,4-dinitrochlorobenzene)-induced atopic dermatitis in mice.

Key findings: Seven alkaloids were isolated from RC successfully. The results from MTT and flow cytometry indicated that among these alkaloids, only magnoflorine ^d(MAG) had no obvious toxicity on cells, but could inhibit the apoptosis of the cells stimulated with TNF-α/IFN-γ. Further animal experiments confirmed that MAG significantly attenuated the AD-like symptom and inhibited the AD-induced increases in IgE/IL-4, as compared with control (P < 0.01). Moreover, MAG reduced the low Δψ_m^e(mitochondrial membrane potential) in HaCaT cells. The results of western blotting proved that MAG inhibited apoptosis of keratinocytes through decreasing the expressions of CTSB^f (cathepsin B), Cyte C^g (cytochrome C), Bid and caspase-3/7/8/9.

Significance: Overall, MAG inhibited apoptosis by decreasing the expression of apoptotic pathway-related proteins, and laid a foundation for the study of AD mechanisms.

Keywords: Anti-apoptosis; Atopic dermatitis; Keratinocytes; Magnoflorine; Rhizoma coptidis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / administration & dosage
Anti-Inflammatory Agents / pharmacology*
Apoptosis / drug effects*
Aporphines / administration & dosage
Aporphines / pharmacology*
Cell Survival / drug effects
Coptis / chemistry*
Dermatitis, Atopic / chemically induced
Dermatitis, Atopic / drug therapy*
Dermatitis, Atopic / metabolism
Dinitrochlorobenzene
Dose-Response Relationship, Drug
Female
Humans
Keratinocytes / drug effects*
Mice
Mice, Inbred BALB C
Molecular Structure
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents
Aporphines
Dinitrochlorobenzene
magnoflorine