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Article(id=1280817605883695592, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1280817479555462000, articleNumber=null, orderNo=null, doi=10.13343/j.cnki.wsxb.20260100, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1769961600000, receivedDateStr=2026-02-02, revisedDate=null, revisedDateStr=null, acceptedDate=1773676800000, acceptedDateStr=2026-03-17, onlineDate=1783300313682, onlineDateStr=2026-07-06, pubDate=1783094400000, pubDateStr=2026-07-04, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1783300313682, onlineIssueDateStr=2026-07-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1783300313682, creator=13701087609, updateTime=1783300313682, updator=13701087609, issue=Issue{id=1280817479555462000, tenantId=1146029695717560320, journalId=1192105938417971205, year='2026', volume='66', issue='7', pageStart='3121', pageEnd='3677', issueExtLink='null', onlineDate='null', pubDate='1783094400000', pubDateStr='2026-07-04', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1783300283564, creator='13701087609', updateTime=1783326087324, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1280925708813832745, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1280817479555462000, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1280925708813832746, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1280817479555462000, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3438, endPage=3450, ext={EN=ArticleExt(id=1280817606273765865, articleId=1280817605883695592, tenantId=1146029695717560320, journalId=1192105938417971205, language=EN, title=Anti-fatigue efficacy and mechanism of curcumin fermented by Lactobacillus delbrueckii subsp. bulgaricus CCFM1520, columnId=1192149543992045670, journalTitle=Acta Microbiologica Sinica, columnName=Research Article, runingTitle=null, highlight=null, articleAbstract=

Objective Curcumin exhibits diverse pharmacological activities, yet its clinical and industrial applications are largely limited by its poor water solubility and low oral bioavailability. The present study was designed to evaluate the anti-fatigue efficacy of curcumin fermented by Lactobacillus delbrueckii subsp. bulgaricus CCFM1520 and to preliminarily elucidate the underlying mechanism responsible for its anti-fatigue effects. Methods The bioconversion efficiency of curcumin and its metabolites by CCFM1520 were quantified viain vitro bioconversion assays. A mouse model of fatigue was established by combining forced swimming with chronic restraint stress. Mice were randomized into six groups: blank control, model, curcumin, CCFM1520, CCFM1520-curcumin synbiotic, and CCFM1520-fermented curcumin. The anti-fatigue efficacy of fermented curcumin was comprehensively assessed from behavioral parameters, serum level of oxidative stress markers [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA)], and cerebral levels of neurotransmitters [dopamine (DA) and norepinephrine (NE)]. Real-time quantitative PCR was performed to examine the mRNA expression profiles of genes associated with the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway in the skeletal muscle and the brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF/TrkB) signaling pathway in the brain tissue. Results CCFM1520 converted curcumin at an efficiency of 62.39%, efficiently converting it into tetrahydrocurcumin. Compared with unfermented curcumin, the fermented product significantly improved behavioral outcomes, including prolonged exhaustive swimming time, shortened escape latency in the water maze, and increased swimming distance. In addition, the fermented product significantly enhanced the activities of SOD and GSH-Px and reduced the content of MDA in the serum, and simultaneously elevated the levels of DA and NE in the mouse brain. Mechanism studies revealed that fermented curcumin up-regulated the mRNA levels of Nrf2 and HO-1 in the muscle tissue and BDNF and TrkB in the brain tissue. Conclusion L. delbrueckii subsp. bulgaricus CCFM1520efficiently converts curcumin into more bioactive metabolites. These metabolites exert a pronounced anti-fatigue effect by enhancing antioxidant capacity and modulating neurotransmitter balance. This study provides a novel strategy and a theoretical basis for developing high-efficacy anti-fatigue functional foods.

, authors=Mengdi SUN, Xin TANG, Fei LIU, Bingyong MAO, Qiuxiang ZHANG, Jianxin ZHAO, Wei CHEN, Shumao CUI, authorsList=Mengdi SUN, Xin TANG, Fei LIU, Bingyong MAO, Qiuxiang ZHANG, Jianxin ZHAO, Wei CHEN, Shumao CUI, authorCompany=null, correspAuthors=Xin TANG, authorNote=null, correspAuthorsNote=
E-mail:
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目的 姜黄素具有多种药理活性，但其水溶性差、口服生物利用度低，限制了其应用。本研究旨在评价德氏乳杆菌保加利亚亚种CCFM1520发酵姜黄素的抗疲劳功效，并初步解析其作用机制。 方法 通过体外转化实验测定CCFM1520对姜黄素的转化效率及代谢产物；构建强迫游泳结合慢性束缚诱导的小鼠疲劳模型，将小鼠随机分为空白组、模型组、姜黄素组、CCFM1520组、CCFM1520-姜黄素合生制剂组、CCFM1520发酵姜黄素组，共6组。从行为学、氧化应激指标[超氧化物歧化酶(superoxide dismutase, SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)、丙二醛(malondialdehyde, MDA)]和神经递质[多巴胺(dopamine, DA)、去甲肾上腺素(norepinephrine, NE)]水平综合评价发酵姜黄素的抗疲劳效果；并采用实时荧光定量PCR技术检测肌肉Nrf2/HO-1通路及脑内BDNF/TrkB通路相关基因表达变化。 结果 CCFM1520对姜黄素的体外转化率达62.39%，可将其高效转化为四氢姜黄素。与未发酵姜黄素相比，发酵姜黄素显著延长力竭游泳时间、缩短水迷宫潜伏期、增加运动距离；提高血清中SOD、GSH-Px活性，降低MDA含量；提升脑内DA和NE水平。机制研究表明，发酵姜黄素可上调肌肉Nrf2、HO-1 mRNA表达，并增强脑组织BDNF、TrkB基因表达。 结论 德氏乳杆菌保加利亚亚种CCFM1520可高效转化姜黄素为活性更高的代谢产物，通过增强机体抗氧化能力与调节神经递质平衡发挥更显著的抗疲劳作用，为高效抗疲劳功能性食品的研发提供了新的研究思路与理论支撑。

, authors=孙梦迪, 唐鑫, 刘飞, 毛丙永, 张秋香, 赵建新, 陈卫, 崔树茂, authorsList=孙梦迪, 唐鑫, 刘飞, 毛丙永, 张秋香, 赵建新, 陈卫, 崔树茂, authorCompany=null, correspAuthors=唐鑫, authorNote=

作者贡献声明

孙梦迪：实验规划、数据整理与分析、文章撰写；唐鑫：实验指导、论文修改；刘飞：文章构思；毛丙永：文章讨论；张秋香：提供建议；赵建新：提供资源；陈卫：稿件审阅；崔树茂：监督管理。

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Frontiers in Pharmacology, 2023, 14: 1269878., articleTitle=Signaling pathways regulated by natural active ingredients in the fight against exercise fatigue: a review, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1280925029139452189, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, xref=null, ext=[AuthorCompanyExt(id=1280925029164618014, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, companyId=1280925029139452189, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China), AuthorCompanyExt(id=1280925029286252831, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, companyId=1280925029139452189, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=江南大学 食品学院，江苏 无锡)])], figs=[ArticleFig(id=1280925037188321617, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=EN, label=Figure 1, caption=LC-MS/MS profiles of curcumin and tetrahydrocurcumin before and after fermentation, and metabolite profile of the fermented curcumin broth. A: LC-MS/MS chromatogram of curcumin reference standard; B: LC-MS/MS chromatogram of curcumin before fermentation; C: LC-MS/MS chromatogram of curcumin after fermentation; D: LC-MS/MS chromatogram of tetrahydrocurcumin reference standard; E: LC-MS/MS chromatogram of tetrahydrocurcumin before fermentation; F: LC-MS/MS chromatogram of tetrahydrocurcumin after fermentation; G: Metabolite profile of CCFM1520-fermented curcumin broth., figureFileSmall=3kypch9CZfKh6+Q2n9amCQ==, figureFileBig=uA8sgNA5T6ZXRX8vdVl4Kw==, tableContent=null), ArticleFig(id=1280925037263819090, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=CN, label=图1, caption=发酵前后姜黄素与四氢姜黄素的LC-MS/MS谱图及发酵姜黄素液代谢物谱图, figureFileSmall=3kypch9CZfKh6+Q2n9amCQ==, figureFileBig=uA8sgNA5T6ZXRX8vdVl4Kw==, tableContent=null), ArticleFig(id=1280925037372870995, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=EN, label=Figure 2, caption=Exhaustion swimming time, latency period, and total distance moved in mice. A: Exhaustive swimming time; B: Latency; C: Distance traveled. **: P<0.01; ***: P<0.001., figureFileSmall=zcUwaqrMKml4SunSMedN+g==, figureFileBig=Cxx5/eIe8+k7YE+szcOJdQ==, tableContent=null), ArticleFig(id=1280925037439979860, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=CN, label=图2, caption=小鼠力竭游泳时间、潜伏期及移动距离, figureFileSmall=zcUwaqrMKml4SunSMedN+g==, figureFileBig=Cxx5/eIe8+k7YE+szcOJdQ==, tableContent=null), ArticleFig(id=1280925037536448853, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=EN, label=Figure 3, caption=Representative histological images of the mouse gastrocnemius muscle (20×)., figureFileSmall=oAFgbPSU8Vvcj+30C+EwfA==, figureFileBig=kCCosjKH0GQjE4y/XqkxKA==, tableContent=null), ArticleFig(id=1280925037628723542, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=CN, label=图3, caption=小鼠腓肠肌组织切片(20×), figureFileSmall=oAFgbPSU8Vvcj+30C+EwfA==, figureFileBig=kCCosjKH0GQjE4y/XqkxKA==, tableContent=null), ArticleFig(id=1280925037720998231, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=EN, label=Figure 4, caption=Oxidative stress-related parameters in mouse serum. A: SOD level in mouse serum; B: MDA level in mouse serum; C: GSH-Px level in mouse serum. *: P<0.05; **: P<0.01; ***: P<0.001., figureFileSmall=Philx7w16SoRlzLo7Xhzzg==, figureFileBig=d7HqLldPzl6aFv8Un133xg==, tableContent=null), ArticleFig(id=1280925037821661528, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=CN, label=图4, caption=小鼠血清氧化应激相关指标, figureFileSmall=Philx7w16SoRlzLo7Xhzzg==, figureFileBig=d7HqLldPzl6aFv8Un133xg==, tableContent=null), ArticleFig(id=1280925037897159001, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=EN, label=Figure 5, caption=Analysis of neurotransmitter levels in mouse brain tissue. A: DA level in mouse brain tissue; B: NE level in mouse brain tissue. *: P<0.05; **: P<0.01; ***: P<0.001., figureFileSmall=mWddel4WtafFQgqpbbMZOg==, figureFileBig=V7FOGCcR7Eol2RMoXqYOWA==, tableContent=null), ArticleFig(id=1280925037989433690, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=CN, label=图5, caption=小鼠脑组织神经递质水平, figureFileSmall=mWddel4WtafFQgqpbbMZOg==, figureFileBig=V7FOGCcR7Eol2RMoXqYOWA==, tableContent=null), ArticleFig(id=1280925038085902683, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=EN, label=Figure 6, caption=Gene expression of Nrf2 and HO-1 in mouse muscle tissue. 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A: Relative BDNF mRNA expression; B: Relative TrkB mRNA expression. *: P<0.05; ***: P<0.001., figureFileSmall=L6PSFUOVmB6wMtLtRXVukA==, figureFileBig=9RVfLoHjY2M+DapOkn/KsA==, tableContent=null), ArticleFig(id=1280925038341755230, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=CN, label=图7, caption=大脑 BDNF 、 TrkB 的基因表达, figureFileSmall=L6PSFUOVmB6wMtLtRXVukA==, figureFileBig=9RVfLoHjY2M+DapOkn/KsA==, tableContent=null), ArticleFig(id=1280925038425641311, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=EN, label=Table 1, caption=

Animal experimental design

, figureFileSmall=null, figureFileBig=null, tableContent=
GroupAbbreviationGavage substance
Control groupNCNormal saline
Modeling groupMCNormal saline
Curcumin groupCUR100 mg/kg CUR
Lactobacillus delbrueckii subsp. bulgaricus CCFM1520 strain groupCCFM15205×109 CFU/mL
Lactobacillus delbrueckii subsp. bulgaricus CCFM1520-curcumin combination preparation groupSyn100 mg/kg CUR and 5×109 CFU/mL viable CCFM1520 bacteria
Lactobacillus delbrueckii subsp. bulgaricus CCFM1520 fermented curcumin groupFmtCCFM1520-CUR fermentation broth with a CUR dosage of 100 mg/kg before fermentation
), ArticleFig(id=1280925038496944480, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=CN, label=表1, caption=

动物实验方案

, figureFileSmall=null, figureFileBig=null, tableContent=
GroupAbbreviationGavage substance
Control groupNCNormal saline
Modeling groupMCNormal saline
Curcumin groupCUR100 mg/kg CUR
Lactobacillus delbrueckii subsp. bulgaricus CCFM1520 strain groupCCFM15205×109 CFU/mL
Lactobacillus delbrueckii subsp. bulgaricus CCFM1520-curcumin combination preparation groupSyn100 mg/kg CUR and 5×109 CFU/mL viable CCFM1520 bacteria
Lactobacillus delbrueckii subsp. bulgaricus CCFM1520 fermented curcumin groupFmtCCFM1520-CUR fermentation broth with a CUR dosage of 100 mg/kg before fermentation
), ArticleFig(id=1280925038639550817, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=EN, label=Table 2, caption=

Primers used in this study

, figureFileSmall=null, figureFileBig=null, tableContent=
Primer namesPrimer sequences (5′→3′)
β-actinF: CCTTCCTTCTTGGGTATGGA
R: GGTCTTTACGGATGTCAACG
Nrf2F: TCTTGGAGTAAGTCGAGAAGTGT
R: GTTGAAACTGAGCGAAAAAGGC
HO-1F: AAGCCGAGAATGCTGAGTTCA
R: GCCGTGTAGATATGGTACAAGGA
BDNFF: CCCGGTGTCGCCCTTAAAAA
R: TCTCACCTGGTGGAACTTCTTT
TrkBF: CTGGGGCTTATGCCTGCTG
R: AGGCTCAGTACACCAAATCCTA
), ArticleFig(id=1280925040317272418, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817605883695592, language=CN, label=表2, caption=

本研究所用引物

, figureFileSmall=null, figureFileBig=null, tableContent=
Primer namesPrimer sequences (5′→3′)
β-actinF: CCTTCCTTCTTGGGTATGGA
R: GGTCTTTACGGATGTCAACG
Nrf2F: TCTTGGAGTAAGTCGAGAAGTGT
R: GTTGAAACTGAGCGAAAAAGGC
HO-1F: AAGCCGAGAATGCTGAGTTCA
R: GCCGTGTAGATATGGTACAAGGA
BDNFF: CCCGGTGTCGCCCTTAAAAA
R: TCTCACCTGGTGGAACTTCTTT
TrkBF: CTGGGGCTTATGCCTGCTG
R: AGGCTCAGTACACCAAATCCTA
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德氏乳杆菌保加利亚亚种CCFM1520发酵姜黄素的抗疲劳功效及机制解析
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孙梦迪 , 唐鑫 , 刘飞 , 毛丙永 , 张秋香 , 赵建新 , 陈卫 , 崔树茂
微生物学报 | 研究报告 2026,66(7): 3438-3450
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微生物学报 |研究报告 2026 , 66 (7) : 3438 -3450
德氏乳杆菌保加利亚亚种CCFM1520发酵姜黄素的抗疲劳功效及机制解析
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孙梦迪, 唐鑫 , 刘飞, 毛丙永, 张秋香, 赵建新, 陈卫, 崔树茂
作者信息
  • 江南大学 食品学院，江苏 无锡
作者简介:

作者贡献声明

孙梦迪：实验规划、数据整理与分析、文章撰写；唐鑫：实验指导、论文修改；刘飞：文章构思；毛丙永：文章讨论；张秋香：提供建议；赵建新：提供资源；陈卫：稿件审阅；崔树茂：监督管理。

Anti-fatigue efficacy and mechanism of curcumin fermented by Lactobacillus delbrueckii subsp. bulgaricus CCFM1520
Mengdi SUN, Xin TANG , Fei LIU, Bingyong MAO, Qiuxiang ZHANG, Jianxin ZHAO, Wei CHEN, Shumao CUI
Affiliations
  • School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
出版时间: 2026-07-04 doi: 10.13343/j.cnki.wsxb.20260100
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摘要
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目的 姜黄素具有多种药理活性，但其水溶性差、口服生物利用度低，限制了其应用。本研究旨在评价德氏乳杆菌保加利亚亚种CCFM1520发酵姜黄素的抗疲劳功效，并初步解析其作用机制。 方法 通过体外转化实验测定CCFM1520对姜黄素的转化效率及代谢产物；构建强迫游泳结合慢性束缚诱导的小鼠疲劳模型，将小鼠随机分为空白组、模型组、姜黄素组、CCFM1520组、CCFM1520-姜黄素合生制剂组、CCFM1520发酵姜黄素组，共6组。从行为学、氧化应激指标[超氧化物歧化酶(superoxide dismutase, SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)、丙二醛(malondialdehyde, MDA)]和神经递质[多巴胺(dopamine, DA)、去甲肾上腺素(norepinephrine, NE)]水平综合评价发酵姜黄素的抗疲劳效果；并采用实时荧光定量PCR技术检测肌肉Nrf2/HO-1通路及脑内BDNF/TrkB通路相关基因表达变化。 结果 CCFM1520对姜黄素的体外转化率达62.39%，可将其高效转化为四氢姜黄素。与未发酵姜黄素相比，发酵姜黄素显著延长力竭游泳时间、缩短水迷宫潜伏期、增加运动距离；提高血清中SOD、GSH-Px活性，降低MDA含量；提升脑内DA和NE水平。机制研究表明，发酵姜黄素可上调肌肉Nrf2、HO-1 mRNA表达，并增强脑组织BDNF、TrkB基因表达。 结论 德氏乳杆菌保加利亚亚种CCFM1520可高效转化姜黄素为活性更高的代谢产物，通过增强机体抗氧化能力与调节神经递质平衡发挥更显著的抗疲劳作用，为高效抗疲劳功能性食品的研发提供了新的研究思路与理论支撑。

德氏乳杆菌保加利亚亚种  /  姜黄素  /  益生菌转化  /  抗疲劳

Objective Curcumin exhibits diverse pharmacological activities, yet its clinical and industrial applications are largely limited by its poor water solubility and low oral bioavailability. The present study was designed to evaluate the anti-fatigue efficacy of curcumin fermented by Lactobacillus delbrueckii subsp. bulgaricus CCFM1520 and to preliminarily elucidate the underlying mechanism responsible for its anti-fatigue effects. Methods The bioconversion efficiency of curcumin and its metabolites by CCFM1520 were quantified viain vitro bioconversion assays. A mouse model of fatigue was established by combining forced swimming with chronic restraint stress. Mice were randomized into six groups: blank control, model, curcumin, CCFM1520, CCFM1520-curcumin synbiotic, and CCFM1520-fermented curcumin. The anti-fatigue efficacy of fermented curcumin was comprehensively assessed from behavioral parameters, serum level of oxidative stress markers [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA)], and cerebral levels of neurotransmitters [dopamine (DA) and norepinephrine (NE)]. Real-time quantitative PCR was performed to examine the mRNA expression profiles of genes associated with the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway in the skeletal muscle and the brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF/TrkB) signaling pathway in the brain tissue. Results CCFM1520 converted curcumin at an efficiency of 62.39%, efficiently converting it into tetrahydrocurcumin. Compared with unfermented curcumin, the fermented product significantly improved behavioral outcomes, including prolonged exhaustive swimming time, shortened escape latency in the water maze, and increased swimming distance. In addition, the fermented product significantly enhanced the activities of SOD and GSH-Px and reduced the content of MDA in the serum, and simultaneously elevated the levels of DA and NE in the mouse brain. Mechanism studies revealed that fermented curcumin up-regulated the mRNA levels of Nrf2 and HO-1 in the muscle tissue and BDNF and TrkB in the brain tissue. Conclusion L. delbrueckii subsp. bulgaricus CCFM1520efficiently converts curcumin into more bioactive metabolites. These metabolites exert a pronounced anti-fatigue effect by enhancing antioxidant capacity and modulating neurotransmitter balance. This study provides a novel strategy and a theoretical basis for developing high-efficacy anti-fatigue functional foods.

Lactobacillus delbrueckii subsp. bulgaricus  /  curcumin  /  probiotic conversion  /  anti-fatigue
孙梦迪, 唐鑫, 刘飞, 毛丙永, 张秋香, 赵建新, 陈卫, 崔树茂. 德氏乳杆菌保加利亚亚种CCFM1520发酵姜黄素的抗疲劳功效及机制解析. 微生物学报, 2026 , 66 (7) : 3438 -3450 . DOI: 10.13343/j.cnki.wsxb.20260100
Mengdi SUN, Xin TANG, Fei LIU, Bingyong MAO, Qiuxiang ZHANG, Jianxin ZHAO, Wei CHEN, Shumao CUI. Anti-fatigue efficacy and mechanism of curcumin fermented by Lactobacillus delbrueckii subsp. bulgaricus CCFM1520[J]. Acta Microbiologica Sinica, 2026 , 66 (7) : 3438 -3450 . DOI: 10.13343/j.cnki.wsxb.20260100
正文
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疲劳是亚健康的主要表现之一，严重影响现代人的生活质量[1]。它不仅是多种疾病的潜在前兆，更可引发睡眠障碍、代谢紊乱及免疫功能障碍等一系列生理问题[2-3]。若长期疲劳得不到缓解，将导致精神萎靡、情绪障碍(如抑郁、焦虑)以及记忆认知功能下降，严重损害个体生活质量与工作效率[4]。目前研究表明，疲劳的发生与代谢产物蓄积、氧化应激以及神经递质分泌紊乱等多种机制密切相关[5-6]。针对疲劳的干预，现有策略主要包括药物与非药物疗法[7]。药物治疗，如中枢兴奋剂(莫达非尼等)，虽能取得一定效果，但存在副作用及依赖风险，且多局限于症状控制[8]。运动、认知行为疗法、膳食补充等非药物干预手段虽安全性较高，但普遍存在起效缓慢、抗疲劳效果个体差异大等问题[9]。更重要的是，鉴于疲劳发生机制的多元性与复杂性，单一靶点的干预策略常难以取得全面、持久的效果。因此，寻找一种能多靶点调节疲劳相关生理过程且安全易行的新策略成为当前重要的研究方向。
姜黄素(curcumin, CUR)是一种天然多酚类化合物，大量研究表明其具有抗炎[10]、抗氧化[11]、抗疲劳[12]及神经保护[13]等多种药理活性，在抑制炎症反应、神经退行性疾病及心血管疾病等方面显示出潜在价值。然而，其水溶性差、口服生物利用度低等缺点严重限制了其临床应用[14]。值得注意的是，肠道菌群可将姜黄素代谢转化为四氢姜黄素等生物利用度更高、稳定性更强的活性衍生物，这些转化产物可能在其宿主效应中发挥关键作用[15]。微生物转化是提升姜黄素生物利用度与生物活性的重要技术手段，其中乳杆菌因安全性高、代谢调控能力强成为姜黄素生物转化的优选菌株。已有研究表明，植物乳植杆菌、嗜酸乳杆菌等多种乳杆菌可通过胞内酶系将姜黄素转化为四氢姜黄素、六氢姜黄素等还原产物，这类产物的水溶性、稳定性及生物活性均显著优于姜黄素[16-17]；同时，乳杆菌的发酵过程还可产生有机酸、短链脂肪酸等次级代谢产物，与姜黄素转化产物协同发挥生理功能[18]。因此，乳杆菌介导的姜黄素生物转化成为功能食品开发的研究热点。这提示，利用特定益生菌对姜黄素进行定向生物转化，或为突破其应用瓶颈、增强其生理功效的有效策略，也为微生物转化技术提升姜黄素生物活性提供了新的研究思路。
本研究以可高效转化姜黄素为四氢姜黄素的德氏乳杆菌保加利亚亚种CCFM1520为研究菌株，通过构建强迫游泳联合慢性束缚诱导的小鼠复合疲劳模型，综合评价该菌株发酵姜黄素对小鼠疲劳行为、氧化损伤及认知功能损伤的缓解效应，并从氧化应激、神经递质调节相关信号通路入手，探讨其潜在抗疲劳机制，以期为高效抗疲劳功能性食品的研发提供理论依据。
1 材料与方法
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1.1 材料
1.1.1 菌株来源
本实验所用德氏乳杆菌保加利亚亚种CCFM1520，由江南大学食品微生物菌种保藏中心(Culture Collection of Food Microorganisms, CCFM)分离保藏并提供。该菌株从传统发酵酸奶中分离获得，经形态学鉴定、16S rRNA基因测序鉴定为德氏乳杆菌保加利亚亚种，保藏编号为CCFM1520。
1.1.2 主要试剂和仪器
姜黄素(纯度≥98%)、四氢姜黄素(纯度≥98%)，上海源叶生物科技有限公司；丙二醛(malondialdehyde, MDA)、超氧化物歧化酶(superoxide dismutase, SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)试剂盒，南京建成生物工程研究所；多巴胺(dopamine, DA)、去甲肾上腺素(norepinephrine, NE)试剂盒，上海酶联生物科技有限公司；BCA蛋白浓度测定试剂盒，上海碧云天生物技术股份有限公司；RNA提取试剂盒、逆转录试剂盒、实时荧光定量试剂盒，南京诺唯赞生物科技股份有限公司；核因子E2相关因子2 (nuclear factor-erythroid 2-related factor 2, Nrf2)、血红素加氧酶1 (heme oxygenase-1, HO-1)、脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)、酪氨酸激酶受体B (tyrosine kinase receptor B, TrkB)引物，生工生物工程(上海)股份有限公司；通用型组织固定液(中性)，武汉赛维尔生物科技有限公司。其他所有试剂均购自国药集团化学试剂有限公司。
液相色谱-质谱联用仪，赛默飞世尔科技公司；恒温培养箱，上海森信实验仪器有限公司；实时定量PCR仪器、实时定量基因扩增仪，Bio-Rad公司；高速冷冻离心机，Eppendorf公司；蒸汽灭菌锅，SANYO公司；高通量组织研磨仪，宁波新芝生物科技股份有限公司；数字切片扫描仪，3DHISTECH公司；多功能酶标仪，上海智城分析仪器制造有限公司。
1.2 姜黄素的发酵
将CCFM1520菌株接种于MRS液体培养基中，37 ℃恒温培养48 h，而后在含姜黄素的发酵基料中，加入体积分数为5%培养获得的CCFM1520菌液，37 ℃恒温发酵48 h。发酵完成后，发酵上清液用0.22 μm无菌微孔滤膜过滤，并于4 ℃冷藏保存待用。
1.3 体外转化效率测定
采用LC-MS/MS法测定发酵前后姜黄素及代谢物的含量。色谱条件：流动相A为100%水溶液，流动相B为乙腈；梯度洗脱程序：0-1 min，95% B；1-14 min，95%-65% B；14-16 min，65%-40% B；16-18 min，40%-95% B。自动进样器温度设为15 ℃，流速为0.3 mL/min，柱温为40 ℃，进样量2 μL。质谱条件：电喷雾离子源(electrospray ionization, ESI)；正离子电喷雾离子源喷雾电压3.8 kV；负离子电喷雾离子源喷雾电压2.8 kV；毛细管温度320 ℃；鞘气流速35 arb；质谱采集模式设为数据依赖性全扫描模式。
1.4 动物实验设计
36只6周龄雄性C57BL/6J小鼠随机分为6组，分别为空白组、模型组、姜黄素组、CCFM1520组、CCFM1520-姜黄素合生制剂组、CCFM1520发酵姜黄素组(表1)。小鼠适应性饲养1周后开始实验干预，除空白对照组外，其余各组均采用6 min强迫游泳联合4 h慢性束缚的方式构建疲劳模型[19]。第5周进行行为学训练。本研究所有动物实验获得江南大学动物伦理委员会批准，编号为JN.No20241030c1360110[558]。
1.5 行为学表现测定
力竭游泳时间测定：将小鼠放入水中，尾部负重6%体重的铅块，记录小鼠头部在水面以下超过5 s的时间，即为游泳力竭时间[20]。
水迷宫实验测定：游泳池被分为4个象限，圆形逃生平台放在第二象限水面以下2 cm处，记录小鼠回到平台的时间和轨迹[19]。如时间超过1 min则视为实验失败。
行为学旷场测定：采用四格旷场行为检测仪对小鼠进行旷场实验，通过动物行为视频跟踪系统记录每只小鼠6 min内的自主运动轨迹[19]。
1.6 氧化损伤指标测定
小鼠经麻醉后行眼眶取血，将血液样品3 000×g离心15 min，取上清。按照试剂盒说明书检测SOD、MDA、GSH-Px。
1.7 神经递质指标测定
在冰浴条件下迅速分离小鼠大脑组织，按照试剂盒说明书检测DA、NE。
1.8 组织病理学分析
取小鼠腓肠肌组织，置于4%多聚甲醛溶液中固定48 h后，经石蜡包埋、切片制作、苏木精和伊红(hematoxylin-eosin, H&E)染色处理[21]。使用数字切片扫描仪进行自动扫描。
1.9 实时荧光定量PCR
采用RNA提取试剂盒从组织中提取总RNA，经逆转录试剂盒逆转录所得cDNA后，使用实时荧光定量试剂盒进行RT-qPCR检测，分析目标基因的mRNA相对表达水平。所用引物序列如表2所示。
1.10 统计学方法
采用GraphPad Prism 10.1.2进行统计分析和绘图，实验数据以平均值±标准差(SD)表示，组间差异采用单因素方差分析(one-way ANOVA)进行检验，统计显著性判定标准：*P<0.05、**P<0.01、***P<0.001。
2 结果与分析
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2.1 CCFM1520转化姜黄素代谢产物的鉴定
通过检测发酵前后溶液中姜黄素及其代谢产物的变化发现，发酵后(图1C)溶液中姜黄素含量较发酵前(图1B)显著降低，由82.51 μg/mL减少至13.10 μg/mL。发酵前溶液中未检出四氢姜黄素(图1E)，而发酵后(图1F)该产物含量为43.78 μg/mL，表明姜黄素在发酵过程中被转化为四氢姜黄素，经计算其转化率为62.39%。采用LC-MS/MS对发酵液进行代谢物检测(图1G)，结果显示发酵液中除四氢姜黄素外，未检测到六氢姜黄素、八氢姜黄素等姜黄素的其他还原产物，也未检测到阿魏酸等姜黄素分解小分子产物，证实四氢姜黄素是CCFM1520转化姜黄素的核心特异性代谢产物，也是发酵液中发挥抗疲劳生理活性的主要物质基础。
2.2 CCFM1520发酵姜黄素对小鼠行为学表现的影响
通过力竭游泳实验观察记录小鼠从开始入水到力竭的时间，以此反映运动耐力和药物抗疲劳效果[22]。实验结果如图2所示，与模型组相比，姜黄素组小鼠游泳时间有所增加，但无显著差异；而合生制剂组和发酵组小鼠游泳时间显著增加，相较于姜黄素组分别提高了30.65% (P<0.01)、38.93% (P<0.001)。与模型组相比，发酵组可显著缩短小鼠水迷宫逃避潜伏期(P<0.01)，且其改善效果优于姜黄素组。在提高小鼠移动距离方面，发酵组更具优势(P<0.01)。上述结果表明，CCFM1520发酵姜黄素可更高效地提升小鼠的运动耐力及认知行为表现。
2.3 CCFM1520发酵姜黄素对小鼠肌肉组织的影响
骨骼肌是机体实现运动功能的核心执行器官，小鼠在疲劳状态下其骨骼肌常有随肌纤维损伤、排列紊乱等形态异常改变。H&E染色结果如图3所示，空白对照组小鼠肌纤维排列紧密整齐，形态规则，横截面呈多边形，肌纤维边界清晰，间隙均匀且狭窄；模型组肌纤维出现明显损伤，表现为排列紊乱、断裂，肌纤维萎缩(横截面积显著减小)，间隙明显增宽，部分区域可见炎性细胞浸润，表明已造成骨骼肌结构性损伤。姜黄素组肌纤维排列较模型组有所改善，但仍存在局部紊乱，肌间隙较宽；合生制剂组肌纤维排列趋于整齐，间隙有所缩小，但部分肌纤维仍存在形态不规则；发酵组肌纤维排列紧密整齐，形态规则，横截面积接近空白对照组，肌间隙狭窄均匀，无明显损伤迹象，表明CCFM1520发酵姜黄素可有效修复疲劳诱导的小鼠骨骼肌形态损伤，维持肌纤维的结构完整性。
2.4 CCFM1520发酵姜黄素对小鼠氧化应激的影响
机体处于疲劳状态时常伴随氧化应激反应增强，而提升机体抗氧化能力是缓解疲劳的重要途径之一[23]。实验结果表明(图4)，与模型组相比，各干预组均不同程度地提高了超氧化物歧化酶(superoxide dismutase, SOD)活性、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)水平，尤其是合生制剂组和发酵组，SOD水平分别提高了16.79% (P<0.01)、22.29% (P<0.01)，GSH-Px水平分别提高了9.70% (P<0.05)、12.65% (P<0.05)；姜黄素组相较于模型组降低了丙二醛(malondialdehyde, MDA)水平，而合生制剂组(P<0.001)和发酵姜黄素组(P<0.001)的改善效果显著优于姜黄素组。上述结果表明，CCFM1520与姜黄素制备的合生制剂及发酵姜黄素均可显著提高小鼠血清中SOD、GSH-Px抗氧化酶活力，降低MDA氧化损伤产物含量，有效缓解疲劳诱导的机体氧化损伤，且发酵姜黄素的改善效果更为显著。
2.5 CCFM1520发酵姜黄素对小鼠神经递质的影响
神经递质水平的变化会影响中枢神经系统的功能[24]。小鼠脑内多巴胺(dopamine, DA)含量下降会导致机体运动能力降低，而多巴胺能系统功能受抑是引发机体疲劳的重要原因之一[25]。如图5所示，与模型组相比，仅发酵组可显著提高小鼠脑内DA水平(P<0.05)，较模型组提升28.20%；合生制剂组与发酵组均可提高小鼠脑内去甲肾上腺素(norepinephrine, NE)水平，较模型组分别提升39.75% (P<0.05)、50.64% (P<0.01)。上述结果表明，合生制剂及发酵姜黄素均可有效改善疲劳诱导的小鼠脑内神经递质失衡状态，且发酵姜黄素的调节效果更为显著。
2.6 CCFM1520发酵姜黄素对小鼠氧化应激通路相关基因表达的影响
核因子E2相关因子2 (nuclear factor-erythroid 2-related factor 2, Nrf2)与血红素加氧酶1 (heme oxygenase-1, HO-1)是机体调节氧化应激反应的核心关键因子[26]。如图6所示，与空白对照组相比，模型组小鼠肌肉组织中Nrf2、HO-1的mRNA表达量均极显著降低(P<0.001)，表明小鼠处于疲劳状态时会出现Nrf2、HO-1基因的特征性下调；各干预组均可不同程度上调Nrf2、HO-1的mRNA表达水平，其中发酵组的上调效果更为显著，且与模型组相比存在显著差异(P<0.05)，表明CCFM1520发酵姜黄素可有效逆转模型组Nrf2、HO-1基因的表达下调，对氧化应激通路具有明显的调节作用。上述结果表明，CCFM1520发酵姜黄素可能通过调控Nrf2/HO-1通路相关基因表达参与改善疲劳模型小鼠的氧化应激病理状态。
2.7 CCFM1520发酵姜黄素对小鼠神经保护通路相关基因表达的影响
脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)与酪氨酸激酶受体B (tyrosine kinase receptor, TrkB)表达的增加对受损神经具有保护作用[27]。如图7所示，与空白对照组相比，模型组小鼠脑组织中BDNF、TrkB的mRNA表达量均极显著降低(P<0.001)，表明小鼠疲劳状态可显著抑制BDNF/TrkB通路活性。与模型组相比，各干预组均可不同程度上调BDNF、TrkB的mRNA表达，其中发酵组(P<0.001)的上调效果突出，且与模型组存在显著差异，表明该干预可有效逆转模型组的BDNF、TrkB表达下调，表现出一定的调节作用。上述结果表明，CCFM1520发酵姜黄素可能通过调控BDNF/TrkB通路相关基因表达发挥神经保护作用，进而参与改善疲劳模型小鼠的中枢神经病理状态。
3 讨论与结论
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本研究针对姜黄素水溶性差、生物利用度低的应用瓶颈，以德氏乳杆菌保加利亚亚种CCFM1520为研究菌株，对姜黄素进行体外定向生物转化，成功将姜黄素转化为活性更高的四氢姜黄素，体外转化率达62.39%。CCFM1520实现姜黄素高效转化的微生物学机制为：该菌株胞内具有较高的还原酶活性，可通过加氢还原作用将姜黄素分子中的不饱和双键还原，进而定向生成四氢姜黄素。本研究通过构建强迫游泳结合慢性束缚的复合疲劳小鼠模型，系统评价了发酵姜黄素的抗疲劳功效。结果显示，CCFM1520活菌组仅表现出微弱的抗疲劳效果，说明益生菌活菌本身并非抗疲劳的核心因素；合生制剂组虽有显著效果，但弱于发酵组，说明活菌与姜黄素的物理混合仅能通过肠道内少量转化发挥作用，效率低下；而发酵组效果最优，在提升运动耐力、改善认知功能、修复肌肉损伤等方面的效果显著优于未发酵姜黄素、益生菌单独使用及合生制剂，证实益生菌发酵是增强姜黄素抗疲劳活性的有效策略。合生制剂组与发酵组的抗疲劳效果存在显著差异，核心原因主要体现在2方面。(1) 转化产物的特异性，合生制剂中CCFM1520与姜黄素为体外混合的活菌与底物，未经过定向发酵转化，仅能在小鼠肠道内发生少量非特异性转化，四氢姜黄素的生成量低且转化效率不可控；而发酵组通过体外定向发酵，姜黄素被CCFM1520高效转化为四氢姜黄素，活性代谢产物的含量高且靶向性强，可直接被机体吸收利用，发挥抗疲劳作用。(2) 发酵过程的微生态效应，CCFM1520在发酵姜黄素的过程中除生成四氢姜黄素外，还会产生有机酸、短链脂肪酸、氨基酸等次级代谢产物，这类成分可与四氢姜黄素协同作用，进一步增强机体抗氧化能力和神经调节功能，而合生制剂无此发酵副产物的协同效应。以上两点共同决定了发酵策略相较于简单的活菌与底物混合，能更显著地提升姜黄素的抗疲劳活性，这也是发酵组效果优于合生制剂组的关键所在。
机制研究表明，发酵姜黄素的抗疲劳作用可能通过多靶点协同调控实现。(1) 增强抗氧化能力：发酵姜黄素可显著提升血清中SOD、GSH-Px活性，降低MDA含量，同时上调Nrf2、HO-1基因表达，从而减轻氧化应激损伤，这与研究报道的Nrf2抗氧化通路相关基因激活是抗疲劳的核心机制[28]相一致，且本研究中发酵姜黄素对Nrf2/HO-1通路的激活效果显著优于未发酵姜黄素，进一步证实了生物转化对姜黄素抗氧化活性的提升作用；(2) 调节神经递质平衡：发酵姜黄素可显著提升脑内DA、NE水平，改善多巴胺能系统功能，缓解疲劳相关的运动能力下降和中枢抑制，这与da Luz等[25]发现的DA代谢异常与疲劳密切相关结论相符；(3) 保护神经与肌肉组织：发酵姜黄素可激活脑组织BDNF/TrkB通路，改善疲劳诱导的认知功能损伤，这与Zhao等[29]综述中总结的BDNF/TrkB通路是天然活性成分抗疲劳的重要靶点结论一致，同时发酵姜黄素可有效修复肌肉形态损伤，维持肌纤维结构完整性，为运动功能恢复提供结构支撑，这一结果补充了乳杆菌转化姜黄素在肌肉组织保护方面的研究空白。
本研究的创新点在于：(1) 筛选出高效转化姜黄素的益生菌菌株CCFM1520，明确其代谢产物为四氢姜黄素，为姜黄素的生物转化提供了新的功能菌株；(2) 构建复合疲劳模型，从行为学、生理生化、组织形态及分子机制多层面系统评价发酵姜黄素的抗疲劳功效，结果更具说服力；(3) 揭示发酵姜黄素通过Nrf2/HO-1和BDNF/TrkB通路协同调控抗氧化能力与神经保护功能的可能作用机制，为抗疲劳功能性食品的开发提供了明确的靶点参考。
与现有研究相比，本研究的优势在于选用的CCFM1520为食品级德氏乳杆菌保加利亚亚种，其发酵姜黄素的过程安全可控，适合产业化应用；同时体外定向发酵的方式大幅提高了四氢姜黄素的生成量，解决了姜黄素生物利用度低的问题，相较于肠道内原位转化，体外发酵更易实现标准化生产。然而，本研究仍存在一定局限性：仅聚焦于四氢姜黄素的生成，发酵液中可能存在其他潜在活性代谢产物，其贡献度有待进一步鉴定；基于动物实验的研究结果，需通过临床试验验证其在人体中的有效性与安全性；未深入探讨发酵姜黄素对肠道菌群及代谢物的影响，其是否通过“肠道-脑轴”调控疲劳相关生理过程仍需进一步研究。未来可开展发酵产物的分离纯化与活性验证，结合临床试验与肠道菌群分析，全面阐明发酵姜黄素的抗疲劳机制，为其产业化应用提供更坚实的理论支撑。
综上所述，利用益生菌发酵姜黄素是一种能显著增强其生物活性与抗疲劳功效的有效策略。该策略的核心优势在于通过生物转化产生更高活性的代谢物，并实现多靶点、多通路的协同调控，为开发具有明确抗疲劳功能的功能性食品或制剂奠定了坚实的应用基础。

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2026年第66卷第7期
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doi: 10.13343/j.cnki.wsxb.20260100
  • 接收时间：2026-02-02
  • 首发时间：2026-07-06
  • 出版时间：2026-07-04
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  • 收稿日期：2026-02-02
  • 录用日期：2026-03-17
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    江南大学 食品学院，江苏 无锡

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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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