Xibining inhibition of the PI3K-AKT pathway reduces M1 macrophage polarization to ameliorate KOA synovial inflammation and nociceptive sensitization

IF 6.7 1区 医学 Q1 CHEMISTRY, MEDICINAL
Lishi Jie , Li Zhang , Houyu Fu , Junfeng Kang , Zeling Huang , Zaishi Zhu , Songjiang Yin , Peng Wu , Peimin Wang , Wei Mei , Xiaochen Li
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引用次数: 0

Abstract

Background

Pain is the most critical symptom of knee osteoarthritis(KOA), which seriously affects the quality of life of patients. Xibining (XBN), a traditional herbal compound, has achieved good results in the clinical treatment of KOA, and its mechanism of action is worth exploring in depth.

Objective

In vivo and in vitro models of KOA were constructed, and the potential drug action mechanism of XBN in improving osteoarthritis pain was explored in combination with transcriptomics.

Methods

In vitro experiments were also conducted to explore the effects of different treatments of BMDMs on TRP channels in DRG neurons by constructing a coculture system of BMDMs and DRG neurons. The specific mechanism by which XBN affects BMDMs was explored via participatory transcriptomics.

Results

Our results showed that KOA aggravated macrophage infiltration in synovial tissues and DRG tissues and increased the transcriptional and translational levels of TRPA1, TRPV1, and TRPM8 in synovial tissues and DRG tissues; XBN treatment improved inflammation in synovial tissues and macrophage infiltration in DRG tissues, and it decreased the transcriptional and translational levels of TRPA1, TRPV1, and TRPM8, consistent with the results of behavioral tests to improve nociceptive sensitization induced by KOA. The results from in vitro experiments showed that promoting macrophage M1-type polarization exacerbated TRP channel activation in DRG neurons and that XBN acted by inhibiting macrophage M1-type polarization. A reference transcriptome study showed that XBN may play a role in inhibiting M1 macrophage-type polarization in KOA by suppressing the PI3K-AKT pathway in BMDMs. We verified the conclusions obtained from transcriptomics via in vitro experiments. We place greater emphasis on the role that the intrinsic immune system plays in the area of pain control in osteoarthritis.

Conclusion

XBN improve KOA nociceptive sensitization by modulating the PI3K/Akt signaling pathway, attenuating the level of synovial inflammation and inhibiting M1-type macrophage polarization in synovial and DRG tissues in KOA mice.
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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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