Abstract
[Objective] To investigate the hypoglycemic, lipid-lowering, anti-inflammatory, and antioxidant effects of crocetin in high-fat diet (HFD)-induced diabetic mice, and to preliminarily explore its regulatory effects on hepatic insulin signaling pathways and protein S-nitrosylation levels. [Methods] An insulin resistance model was established in C57BL/6J mice by HFD feeding. Mice were administered low (5 mg/kg), medium (10 mg/kg), or high (20 mg/kg) doses of crocetin for 8 weeks, with metformin (200 mg/kg) used as a positive control. Fasting blood glucose, oral glucose tolerance, serum insulin, lipid profiles, hepatic oxidative stress, and inflammatory cytokines were measured. Western blot was used to detect phosphorylation levels of IRS1/AKT/GSK3β pathway proteins and total protein S-nitrosylation levels in liver tissues. [Results] The high-dose crocetin group significantly reduced fasting blood glucose, HOMA-IR index, and OGTT AUC in diabetic mice (P < 0.01), improved dyslipidemia, alleviated hepatic oxidative stress and inflammatory responses, restored phosphorylation of the IRS1/AKT/GSK3β signaling pathway, and decreased total hepatic protein S-nitrosylation levels (P < 0.01). [Conclusion] Crocetin significantly improves glucose and lipid metabolic disorders and insulin resistance in diabetic mice. Its mechanisms are associated with activation of the IRS1/AKT/GSK3β signaling pathway and inhibition of oxidative stress and inflammation, accompanied by reduced hepatic protein S-nitrosylation levels, suggesting that denitrosylation may be involved in its insulin-sensitizing effects.
Publication Date
7-13-2026
First Page
116
Last Page
123
DOI
10.13652/j.spjx.1003.5788.2026.80334
Recommended Citation
Jing, WEN; Si, QIN; and Chenghao, LYU
(2026)
"Ameliorative effects and mechanisms of crocetin on insulin resistance in high-fat diet-induced diabetic mice,"
Food and Machinery: Vol. 42:
Iss.
6, Article 15.
DOI: 10.13652/j.spjx.1003.5788.2026.80334
Available at:
https://www.ifoodmm.cn/journal/vol42/iss6/15
References
[1] International Diabetes Federation.IDF diabetes atlas [M].Brussels:International Diabetes Federation,2021:Chapter 3.
[2] PETERSEN M C,SHULMAN G I.Mechanisms of insulin action and insulin resistance [J].Physiological Reviews,2018,98(4):2 133-2 223.
[3] DAVIES M J,ARODA V R,COLLINS B S,et al.Management of hyperglycaemia in type 2 diabetes,2022.A consensus report by the American Diabetes Association (ADA ) and the European Association for the study of diabetes (EASD ) [J].Diabetologia,2022,65(12):1 925-1 966.
[4] 王振武,陈晓晴,丁宁,等.功能性降糖食品原料研究及应用进展 [J].食品与机械,2026,42(2):216-224.WANG Z W,CHEN X Q,DING N,et al.Research and application progress of functional raw materials for blood glucose-lowering foods [J].Food & Machinery,2026,42(2):216-224.
[5] 齐欣,路欣彤,林长青,等.紫苏叶提取物对 1型糖尿病小鼠降血糖作用 [J].食品与机械,2021,37(11):153-158.QI X,LU X T,LIN C Q,et al.Hypoglycemic effect of perilla leaf extract on type 1 diabetic mice [J].Food & Machinery,2021,37(11):153-158.
[6] 吴仲,杨江帆.武夷岩茶酸性茶多糖对 2型糖尿病大鼠胆汁酸的调节作用机制 [J].食品与机械,2024,40(10):129-135.WU Z,YANG J F.The regulatory mechanism of acidic tea polysaccharides from Wuyi rock tea on bile acids in type 2 diabetic rats [J].Food & Machinery,2024,40(10):129-135.
[7] CHEN L P,LI M X,YANG Z Q,et al.Gardenia jasminoides Ellis:ethnopharmacology,phytochemistry,and pharmacological and industrial applications of an important traditional Chinese medicine [J].Journal of Ethnopharmacology,2020,257:112829.
[8] 刘心怡,杨君,毛碧增.栀子黄色素的研究进展 [J].浙江农业科学,2024,65(12):2 997-3 004.LIU X Y,YANG J,MAO B Z.Research progress of gardenia yellow pigment [J].Journal of Zhejiang Agricultural Sciences,2024,65(12):2 997-3 004.[9] GARCÍA C J,BELTRÁN D,FRUTOS-LISÓN M D,et al.New findings in the metabolism of the saffron apocarotenoids,crocins and crocetin,by the human gut microbiota [J].Food & Function,2024,15(18):9 315-9 329.
[10] 陈诗韵,吕承豪,覃思.栀子中藏红花酸抗氧化及降糖能力研究 [J].食品安全导刊,2025 (14):96-99.CHEN S Y,LYU C H,QIN S.Study on the antioxidant and hypoglycemic abilities of crocetin in Gardenia jasminoides Ellis [J].China Food Safety Magazine,2025 (14):96-99.
[11] 王立,李娜,李言,等.栀子果功能成分及开发应用研究进展[J].食品与机械,2018,34(7):173-178.WANG L,LI N,LI Y,et al.Functional components in the fruit of Gardenia jasminoides Ellis and their application [J].Food & Machinery,2018,34(7):173-178.
[12] GUO Z L,LI M X,LI X L,et al.Crocetin:a systematic review[J].Frontiers in Pharmacology,2022,12:745683.
[13] CARVALHO-FILHO M A,UENO M,HIRABARA S M,et al.S-nitrosation of the insulin receptor,insulin receptor substrate 1,and protein kinase B/Akt [J].Diabetes,2005,54(4):959-967.
[14] ZHOU H L,GRIMMETT Z W,VENETOS N M,et al.An enzyme that selectively S-nitrosylates proteins to regulate insulin signaling [J].Cell,2023,186(26):5 812-5 825.
[15] LI J L,WU H S,LIU Y T,et al.High fat diet induced obesity model using four strains of mice:Kunming,C57BL/6,BALB/c and ICR [J].Experimental Animals,2020,69(3):326-335.
[16] ELSAYED N A,ALEPPO G,ARODA V R,et al.2.classification and diagnosis of diabetes:standards of care in diabetes:2023 [J].Diabetes Care,2023,46(Supplement 1):S19-S40.
[17] LIU L P,QIU F,WU D W,et al.Crocetin,a versatile carotenoid:novel insights into pharmacological effects,molecular mechanisms,and therapeutic potential [J].International Immunopharmacology,2025,162:115125.
[18] SHENG L,QIAN Z,SHI Y,et al.Crocetin improves the insulin resistance induced by high-fat diet in rats [J].British Journal of Pharmacology,2008,154(5):1 016-1 024.
[19] GUO H X,RUAN C Y,ZHAN X H,et al.Crocetin protected human hepatocyte LO 2 cell from TGF- β-induced oxygen stress and apoptosis but promoted proliferation and autophagy via AMPK/m-TOR pathway [J].Frontiers in Public Health,2022,10:909125.
[20] YANG L N,QIAN Z Y,JI H,et al.Inhibitory effect on protein kinase C θ by Crocetin attenuates palmitate-induced insulin insensitivity in 3T3-L1 adipocytes [J].European Journal of Pharmacology,2010,642(1/2/3):47-55.
