Berberine for gastric cancer prevention and treatment: Multi-step actions on the Correa's cascade underlie its therapeutic effects

作者全名："Liu, Qingsong; Tang, Jianyuan; Chen, Shuanglan; Hu, Shuangyuan; Shen, Caifei; Xiang, Juyi; Chen, Nianzhi; Wang, Jundong; Ma, Xiao; Zhang, Yi; Zeng, Jinhao"

作者地址："[Liu, Qingsong; Chen, Shuanglan; Hu, Shuangyuan; Shen, Caifei; Xiang, Juyi; Wang, Jundong; Zhang, Yi] Chengdu Univ Tradit Chinese Med, Chengdu 610072, Peoples R China; [Tang, Jianyuan; Zeng, Jinhao] Chengdu Univ Tradit Chinese Med, TCM Regulating Metab Dis Key Lab Sichuan Prov, Chengdu 610072, Peoples R China; [Chen, Nianzhi] Chongqing Med Univ, State Key Lab Ultrasound Med & Engn, Coll Biomed Engn, Chongqing 400016, Peoples R China; [Ma, Xiao] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China"

通信作者："Zhang, Y (通讯作者)，Chengdu Univ Tradit Chinese Med, Chengdu 610072, Peoples R China.; Zeng, JH (通讯作者)，Chengdu Univ Tradit Chinese Med, TCM Regulating Metab Dis Key Lab Sichuan Prov, Chengdu 610072, Peoples R China.; Ma, X (通讯作者)，Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China."

来源：PHARMACOLOGICAL RESEARCH

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000876306100002

JCR分区：Q1

影响因子：9.3

年份：2022

卷号：184

期号：　

开始页：　

结束页：　

文献类型：Review

关键词：Berberine; Gastric carcinoma; Correa's cascade; Gastric precancerous lesions; Atrophic gastritis; Intestinal metaplasia; Dysplasia

摘要："Gastric carcinoma (GC) is a complex multifactorial disease occurring as sequential events commonly referred to as the Correa's cascade, a stepwise progression from non-active or chronic active gastritis, to gastric precancerous lesions, and finally, adenocarcinoma. Therefore, the identification of novel agents with multi-step actions on the Correa's cascade and those functioning as multiple phenotypic regulators are the future direction for drug discovery. Recently, berberine (BBR) has gained traction owing to its pharmacological properties, including antiinflammatory, anti-cancer, anti-ulcer, antibacterial, and immunopotentiation activities. In this article, we investigated and summarized the multi-step actions of BBR on Correa's cascade and its underlying regulatory mechanism in gastric carcinogenesis for the first time, along with a discussion on the strength of BBR to prevent and treat GC. BBR was found to suppress H. pylori infection, control mucosal inflammation, and promote ulcer healing. In the gastric precancerous lesion phase, BBR could reverse mucosal atrophy and prevent lesions in intestinal metaplasia and dysplasia by regulating inflammatory cytokines, promoting cell apoptosis, regulating macrophage polarization, and regulating autophagy. Additionally, the therapeutic action of BBR on GC was partly realized through the inhibition of cell proliferation, migration, and angiogenesis; induction of apoptosis and autophagy, and enhancement of chemotherapeutic drug sensitivity. BBR exerted multi-step actions on the Correa's cascade, thereby halting and even reversing gastric carcinogenesis in some cases. Thus, BBR could be used to prevent and treat GC. In conclusion, the therapeutic strategy underlying BBR's multi-step action in the trilogy of Correa's cascade may include ""prevention of gastric mucosal inflammation (Phase 1); reversal of gastric precancerous lesions (Phase 2), and rescue of GC (Phase 3)"". The NF-kappa B, PI3K/Akt, and MAPK signaling pathways may be the key signaling transduction pathways underlying the treatment of gastric carcinogenesis using BBR. The advantage of BBR over conventional drugs is its multifaceted and long-term effects. This review is expected to provide preclinical evidence for using BBR to prevent gastric carcinogenesis and treat gastric cancer."

基金机构：National Natural Science Foundation of China [82174346]; Project of Sichuan Administration of Traditional Chinese Medicine [2021MS104]

基金资助正文：This work was supported by the National Natural Science Foundation of China (Grant no. 82174346) and Project of Sichuan Administration of Traditional Chinese Medicine (Grant no. 2021MS104).