Lili Chen, Huihui Cao, Xin Zhang, Xintong Du, Yang Guan, Mei Li, Alan K. Chang, Xianran He, Xiaolong Li and Xiuli Bi
{"title":"莱菔硫烷(SFN)及其衍生物 SLL-III-9 和 SLL-III-120 的抗抑郁作用及其基于微生物群-肠-脑轴的潜在内在机制。","authors":"Lili Chen, Huihui Cao, Xin Zhang, Xintong Du, Yang Guan, Mei Li, Alan K. Chang, Xianran He, Xiaolong Li and Xiuli Bi","doi":"10.1039/D3FO05278H","DOIUrl":null,"url":null,"abstract":"<p >Broccoli (<em>Brassica oleracea</em> L.) is a vegetable with numerous nutritional properties, with sulforaphane (SFN) being the most abundant and unique bioactive ingredient. SFN has anti-inflammatory, antioxidant, and anti-cancer activities. In this study, a series of SFN derivatives were synthesized and screened for improved antidepressant effects. Among these, the SFN derivatives SLL-III-9 and SLL-III-120 were the best candidates, and the potential antidepressant mechanism of SFN, SLL-III-9, and SLL-III-120 associated with their effects in a chronic unpredictable mild stress (CUMS) mouse model was explored based on the microbiota–gut–brain axis. All three compounds were able to relieve depression-like behaviors in CUMS mice and regulate the composition of the gut bacteria Firmicutes, Actinobacteria, Parabasalia, and Tenericutes at the phylum level and <em>Bacteroidales bacterium</em>, <em>Lachnospiraceae bacterium A4</em>, <em>Muribaculum intestinale</em>, <em>Muribaculaceae bacterium</em>, and <em>Prevotella</em> sp. <em>MGM1</em> at the species level, possibly altering their function associated with the anti-inflammatory effect. Additionally, SFN and its derivatives upregulated the expression of the tight junction proteins ZO-1, occludin, and claudin and increased the concentration of IL-10, dopamine (DA), 5-hydroxytryptamine (5-HT) and the brain-derived neurotrophic factor (BDNF), while downregulating the expressions of proteins related to the NF-κB/NLRP3 pathway and reducing the concentration of TNF-α. Further <em>in vitro</em> studies revealed significant inhibition of the production of inflammatory factors IL-1β, IL-18, IL-6, and TNF-α in LPS-activated BV2 cells <em>via</em> the NF-κB/NLRP3 pathway when these cells were treated with SFN or its two derivatives. Taken together, the results suggested that SFN and its two derivatives, SLL-III-9 and SLL-III-120, could be considered potential compounds for the development of a promising and safe agent for combating depression.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antidepressant effects of sulforaphane (SFN) and its derivatives SLL-III-9 and SLL-III-120 and their potential underlying mechanisms based on the microbiota–gut–brain axis†\",\"authors\":\"Lili Chen, Huihui Cao, Xin Zhang, Xintong Du, Yang Guan, Mei Li, Alan K. Chang, Xianran He, Xiaolong Li and Xiuli Bi\",\"doi\":\"10.1039/D3FO05278H\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Broccoli (<em>Brassica oleracea</em> L.) is a vegetable with numerous nutritional properties, with sulforaphane (SFN) being the most abundant and unique bioactive ingredient. SFN has anti-inflammatory, antioxidant, and anti-cancer activities. In this study, a series of SFN derivatives were synthesized and screened for improved antidepressant effects. Among these, the SFN derivatives SLL-III-9 and SLL-III-120 were the best candidates, and the potential antidepressant mechanism of SFN, SLL-III-9, and SLL-III-120 associated with their effects in a chronic unpredictable mild stress (CUMS) mouse model was explored based on the microbiota–gut–brain axis. All three compounds were able to relieve depression-like behaviors in CUMS mice and regulate the composition of the gut bacteria Firmicutes, Actinobacteria, Parabasalia, and Tenericutes at the phylum level and <em>Bacteroidales bacterium</em>, <em>Lachnospiraceae bacterium A4</em>, <em>Muribaculum intestinale</em>, <em>Muribaculaceae bacterium</em>, and <em>Prevotella</em> sp. <em>MGM1</em> at the species level, possibly altering their function associated with the anti-inflammatory effect. Additionally, SFN and its derivatives upregulated the expression of the tight junction proteins ZO-1, occludin, and claudin and increased the concentration of IL-10, dopamine (DA), 5-hydroxytryptamine (5-HT) and the brain-derived neurotrophic factor (BDNF), while downregulating the expressions of proteins related to the NF-κB/NLRP3 pathway and reducing the concentration of TNF-α. Further <em>in vitro</em> studies revealed significant inhibition of the production of inflammatory factors IL-1β, IL-18, IL-6, and TNF-α in LPS-activated BV2 cells <em>via</em> the NF-κB/NLRP3 pathway when these cells were treated with SFN or its two derivatives. Taken together, the results suggested that SFN and its two derivatives, SLL-III-9 and SLL-III-120, could be considered potential compounds for the development of a promising and safe agent for combating depression.</p>\",\"PeriodicalId\":77,\"journal\":{\"name\":\"Food & Function\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Food & Function\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/fo/d3fo05278h\",\"RegionNum\":1,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Food & Function","FirstCategoryId":"97","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/fo/d3fo05278h","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Antidepressant effects of sulforaphane (SFN) and its derivatives SLL-III-9 and SLL-III-120 and their potential underlying mechanisms based on the microbiota–gut–brain axis†
Broccoli (Brassica oleracea L.) is a vegetable with numerous nutritional properties, with sulforaphane (SFN) being the most abundant and unique bioactive ingredient. SFN has anti-inflammatory, antioxidant, and anti-cancer activities. In this study, a series of SFN derivatives were synthesized and screened for improved antidepressant effects. Among these, the SFN derivatives SLL-III-9 and SLL-III-120 were the best candidates, and the potential antidepressant mechanism of SFN, SLL-III-9, and SLL-III-120 associated with their effects in a chronic unpredictable mild stress (CUMS) mouse model was explored based on the microbiota–gut–brain axis. All three compounds were able to relieve depression-like behaviors in CUMS mice and regulate the composition of the gut bacteria Firmicutes, Actinobacteria, Parabasalia, and Tenericutes at the phylum level and Bacteroidales bacterium, Lachnospiraceae bacterium A4, Muribaculum intestinale, Muribaculaceae bacterium, and Prevotella sp. MGM1 at the species level, possibly altering their function associated with the anti-inflammatory effect. Additionally, SFN and its derivatives upregulated the expression of the tight junction proteins ZO-1, occludin, and claudin and increased the concentration of IL-10, dopamine (DA), 5-hydroxytryptamine (5-HT) and the brain-derived neurotrophic factor (BDNF), while downregulating the expressions of proteins related to the NF-κB/NLRP3 pathway and reducing the concentration of TNF-α. Further in vitro studies revealed significant inhibition of the production of inflammatory factors IL-1β, IL-18, IL-6, and TNF-α in LPS-activated BV2 cells via the NF-κB/NLRP3 pathway when these cells were treated with SFN or its two derivatives. Taken together, the results suggested that SFN and its two derivatives, SLL-III-9 and SLL-III-120, could be considered potential compounds for the development of a promising and safe agent for combating depression.
期刊介绍:
Food & Function provides a unique venue for physicists, chemists, biochemists, nutritionists and other food scientists to publish work at the interface of the chemistry, physics and biology of food. The journal focuses on food and the functions of food in relation to health.