Lychee seed polyphenol ameliorates DR via inhibiting inflammasome/apoptosis and angiogenesis in hRECs and db/db mice

Xiao-Hong Xiang; Jing Wei; Xiao-Fang Wang; Qin Xu; Chong-Lin Yu; Chang-Long He; Tao Long; Ming-Song Guo; Xue Chen; Xiao-Gang Zhou; Jian-Ming Wu; Da-Lian Qin; An-Guo Wu; Yong Tang; Hong-Bin Lv

doi:10.1016/j.biopha.2023.115478

Lychee seed polyphenol ameliorates DR via inhibiting inflammasome/apoptosis and angiogenesis in hRECs and db/db mice

Biomed Pharmacother. 2023 Nov:167:115478. doi: 10.1016/j.biopha.2023.115478. Epub 2023 Sep 11.

Authors

Xiao-Hong Xiang¹, Jing Wei², Xiao-Fang Wang³, Qin Xu⁴, Chong-Lin Yu⁵, Chang-Long He⁶, Tao Long⁷, Ming-Song Guo⁸, Xue Chen⁹, Xiao-Gang Zhou¹⁰, Jian-Ming Wu¹¹, Da-Lian Qin¹², An-Guo Wu¹³, Yong Tang¹⁴, Hong-Bin Lv¹⁵

Affiliations

¹ Department of Ophthalmology in the Affiliated Hospital of Southwest Medical University, Luzhou, China. Electronic address: xnydxxh@163.com.
² Department of Ophthalmology in the Affiliated Hospital of Southwest Medical University, Luzhou, China; Eye School and Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection of Chengdu University of TCM, Chengdu, China. Electronic address: weijingswmu@163.com.
³ Department of Human Anatomy School of Preclinical Medicine Southwest Medical University, Luzhou, China. Electronic address: wang991288171@163.com.
⁴ Department of Ophthalmology in the Affiliated Hospital of Southwest Medical University, Luzhou, China. Electronic address: xuqin7890@163.com.
⁵ Department of Human Anatomy School of Preclinical Medicine Southwest Medical University, Luzhou, China. Electronic address: 8056ycl@swmu.edu.cn.
⁶ Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica of Southwest Medical University, Luzhou, China. Electronic address: 284400200@qq.com.
⁷ Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica of Southwest Medical University, Luzhou, China. Electronic address: 575769313@qq.com.
⁸ Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica of Southwest Medical University, Luzhou, China. Electronic address: dididigms@163.com.
⁹ Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica of Southwest Medical University, Luzhou, China. Electronic address: cx790465521@163.com.
¹⁰ Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica of Southwest Medical University, Luzhou, China. Electronic address: zxg@swmu.edu.cn.
¹¹ Department of Human Anatomy School of Preclinical Medicine Southwest Medical University, Luzhou, China. Electronic address: jianmingwu@swmu.edu.cn.
¹² Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica of Southwest Medical University, Luzhou, China. Electronic address: dalianqin@swmu.edu.cn.
¹³ Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica of Southwest Medical University, Luzhou, China. Electronic address: wuanguo@swmu.edu.cn.
¹⁴ Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica of Southwest Medical University, Luzhou, China; State Key Laboratory of Quality Research in Chinese Medicine of Macau University of Science and Technology, Macau, China. Electronic address: tangy1989@yeah.net.
¹⁵ Department of Ophthalmology in the Affiliated Hospital of Southwest Medical University, Luzhou, China. Electronic address: oculistlvhongbin@163.com.

PMID: 37703661
DOI: 10.1016/j.biopha.2023.115478

Abstract

Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We previously found that Lycopene seed polyphenols (LSP) maintained BRB integrity by inhibiting NLRP3 inflammasome-mediated inflammation. However, it is still unknown whether LSP inhibits retinal neovascularization with abnormal capillaries and its mechanism of action. Here, we employed db/db mice and hRECs to find that LSP increases the level of glycolipid metabolism, maintains the morphology of retinal endothelial cells and inhibits acellular capillary neogenesis. Mechanistic studies revealed that LSP inhibits the NLRP3 inflammasome, reduces cell apoptosis in retinal tissue, increases tight junction protein (TJ) expression, and reduces vascular endothelial growth factor (VEGF) and Ve-Cadherin in vivo and in vitro. Collectively, this study finds that LSP inhibits inflammation and angiogenesis to improve BRB function to ameliorate DR.

Keywords: Angiogenesis; Apoptosis; Diabetic retinopathy; Inflammasome; Lychee seed polyphenols.

MeSH terms

Animals
Apoptosis
Diabetic Retinopathy* / pathology
Endothelial Cells / metabolism
Inflammasomes / metabolism
Inflammation / metabolism
Litchi*
Mice
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Polyphenols / metabolism
Polyphenols / pharmacology
Vascular Endothelial Growth Factor A / metabolism

Substances

Inflammasomes
Polyphenols
NLR Family, Pyrin Domain-Containing 3 Protein
Vascular Endothelial Growth Factor A