The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 13: 2267 - 2276

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.13.001

Feature Reports：Cardiovascular diseases

Mechanism of curcumin and its metabolite tetrahydrocurcumin in ameliorating myocardial injury in type 2 diabetic mice based on the Hippo signaling pathway

  • Xuexun LI ,
  • Bangzhao ZENG ,
  • Xin ZHAO ,
  • Shuangshuang ZHAO ,
  • Mengxue ZHANG ,
  • Fuli YA
Expand
  • Department of Nutrition，School of Public Health，Dali University，Dali 671000，Yunnan，ChinaCommunication author： YA Fuli E?mail： yafuli@yeah. net

Received date: 2026-04-17

  Online published: 2026-07-14

Fold

Abstract

Objective This study compared the protective effects of curcumin （CUR） and Tetrahydrocurcumin （THC） against T2DM-related myocardial injury and delved into the differences in their mechanisms. Methods A mouse model of Type 2 diabetes mellitus （T2DM） was established by using a high-fat diet in combination with low-dose streptozotocin. The mice were randomly divided into four groups： the normal control group， the model group， the CUR dietary intervention group （800 mg/kg diet）， and the THC dietary intervention group （800 mg/kg diet）. Dietary supplements were administered concurrently with model induction. Myocardial morphology， fibrosis， and glycogen deposition were evaluated through hematoxylin and eosin （HE）， Masson， and periodic acid-Schiff （PAS） staining. Oxidative stress indicators and plasma cardiac injury markers， such as lactate dehydrogenase （LDH） and cardiac troponin I （cTnI）， were measured via colorimetric assays. Differentially expressed proteins were screened by proteomics， and the expression levels of pathway-related proteins were verified by Western blotting. Results Compared with the model group， both THC and CUR significantly alleviated myocardial disarray， diminished interstitial fibrosis （P 0.01） and glycogen deposition （P 0.05）， and decreased plasma levels of LDH and cTnI （P 0.05）. Moreover， they reduced myocardial malondialdehyde （MDA） levels （P 0.001） and enhanced total antioxidant capacity （T-AOC） （P 0.01）， superoxide dismutase （SOD） （P 0.05）， and glutathione （GSH） activities （T2DM+THC vs. T2DM， P 0.01）. Notably， THC exhibited more pronounced improvement than CUR across all these parameters. Correlation analysis indicated a significant positive correlation between fasting blood glucose levels and the cardiac injury markers LDH and cTnI， implying that the improvement of glycemic control is closely related to myocardial protection （P 0.001）. Mechanistically， proteomics combined with Western blot validation showed that THC more effectively inhibited the over-activation of the STK3-LATS1 axis in the Hippo pathway compared with CUR， as manifested by a remarkable down-regulation of the phosphorylation levels of STK3 and LATS1 induced by T2DM （P 0.001）. Conclusion THC may alleviate myocardial injury in T2DM mice by inhibiting the Hippo signaling pathway. It exhibits more potent cardioprotective effects than CUR， and therefore has the potential to serve as a natural dietary supplement for the prevention and treatment of T2DM-related myocardial injury.

Key words： curcumin; tetrahydrocurcumin; type 2 diabetes mellitus; myocardial injury; proteomics; Hippo signaling pathway

Cite this article

Xuexun LI , Bangzhao ZENG , Xin ZHAO , Shuangshuang ZHAO , Mengxue ZHANG , Fuli YA . Mechanism of curcumin and its metabolite tetrahydrocurcumin in ameliorating myocardial injury in type 2 diabetic mice based on the Hippo signaling pathway[J]. The Journal of Practical Medicine, 2026 , 42(13) : 2267 -2276 . DOI: 10.3969/j.issn.1006-5725.2026.13.001

References

[1] SUN H， SAEEDI P， KARURANGA S， et al. IDF Diabetes Atlas： Global， regional and country-level diabetes prevalence estimates for 2021 and projections for 2045［J］. Diabetes Res Clin Pract， 2022， 183： 109119. doi： 10.1016/j.diabres.2021.109119 .
[2] ONG K L， STAFFORD L K， MCLAUGHLIN S A， et al. Global， regional， and national burden of diabetes from 1990 to 2021， with projections of prevalence to 2050： A systematic analysis for the Global Burden of Disease Study 2021［J］. Lancet， 2023， 402（10397）： 203-234. doi： 10.1016/s0140-6736（23）01301-6 .
[3] CHEN D， SINDONE A， HUANG M L H， et al. Diabetic cardiomyopathy： Insights into pathophysiology， diagnosis and clinical management［J］. J Mol Cell Cardiol， 2025， 206： 55-69. doi： 10.1016/j.yjmcc.2025.06.013 .
[4] LI D， ZHANG L， GONG Q， et al. The role of myocardial energy metabolism perturbations in diabetic cardiomyopathy： From the perspective of novel protein post-translational modifications［J］. Clin Epigenetics， 2025， 17（1）： 15. doi： 10.1186/s13148-025-01814-2 .
[5] ABDULLAH A R， SELIEM M A， KHIDR E G， et al. A comprehensive review on diabetic cardiomyopathy （DCM）： Histological spectrum， diagnosis， pathogenesis， and management with conventional treatments and natural compounds［J］. Naunyn Schmiedeberg′s Arch Pharmacol， 2025， 398（8）： 9929-9969. doi： 10.1007/s00210-025-03980-9 .
[6] MITHAIWALA A， GODAD A. Exploring hippo YAP/TAZ signaling： A novel avenue for cardiovascular disorders［J］. Cell Biol Int， 2025， 49（9）： 1079-1101. doi： 10.1002/cbin.70052 .
[7] ZHENG A， CHEN Q， ZHANG L. The Hippo-YAP pathway in various cardiovascular diseases： Focusing on the inflammatory response［J］. Front Immunol， 2022， 13： 971416. doi： 10.3389/fimmu.2022.971416 .
[8] MIA M M， SINGH M K. New insights into hippo/YAP signaling in fibrotic diseases［J］. Cells， 2022， 11（13）： 2065. doi： 10.3390/ cells11132065 .
[9] 黄翠霞， 张雅倩， 杨爱萍， 等. 基于Hippo/YAP信号通路探讨穿心莲内酯抗三阴性乳腺癌的作用机制［J］. 实用医学杂志， 2023， 39（16）： 2050-2056. doi： 10.3969/j.issn.1006-5725.2023. 16.007 .
[10] HARVEY K F， TANG T T. Targeting the hippo pathway in cancer［J］. Nat Rev Drug Discov， 2025， 24（11）： 852-869. doi： 10.1038/s41573-025-01234-0 .
[11] SHAO Y， LI M， WANG Y， et al. GDF11 mitigates high glucose-induced cardiomyocytes apoptosis by inhibiting the ALKBH5-FOXO3 -CDR1as/Hippo signaling pathway［J］. Biochim Biophys Acta Mol Cell Res， 2024， 1871（3）： 119656. doi： 10.1016/j.bbamcr.2023.119656 .
[12] ZOHNY M H， EL-FAR Y M， KABIL M F， et al. Ferulic acid lipid nano capsules versus its native form in alleviating diabetic nephropathy induced in rats through TGF-β1/Hippo pathway crosstalk modulation［J］. Sci Rep， 2025， 15： 10979. doi： 10.1038/s41598-024-81175-7 .
[13] WEI L， GAO J， WANG L， et al. Hippo/YAP signaling pathway： A new therapeutic target for diabetes mellitus and vascular complications［J］. Ther Adv Endocrinol Metab， 2023， 14： 20420188231220134. doi： 10.1177/20420188231220134 .
[14] MPHASHA M， MOTHIBA T. Personalised nutrition approaches in the prevention and management of type 2 diabetes： A narrative review of evidence and practice［J］. Int J Environ Res Public Health， 2025， 22（7）： 1047. doi： 10.3390/ijerph22071047 .
[15] GHAZALA S J， SAWI M R EL， EL-DEIN M A. Restorative potential of Stevia Leaves against cardiomyopathy associated with type 2 diabetes through multiple interdependent pathways［J］. Pak J Biol Sci， 2025， 28（9）： 610-631. doi： 10.3923/pjbs. 2025.610.631 .
[16] HAO M， ZHANG C， WANG T， et al. Pharmacological effects， formulations， and clinical research progress of curcumin［J］. Front Pharmacol， 2025， 16： 1509045. doi： 10.3389/fphar.2025. 1509045 .
[17] ZHOU M， LI R， HUA H， et al. The role of tetrahydrocurcumin in disease prevention and treatment［J］. Food Funct， 2024， 15（13）： 6798-6824. doi： 10.1039/D3FO05739A .
[18] WU X， QU Z， LIU P. Curcumin mitigates high glucose-induced cardiac oxidative stress via Notch1 pathway activation［J］. Sci Rep， 2025， 15（1）： 23660. doi： 10.1038/s41598-025-09105-9 .
[19] 胡锦秋， 毕晓艳， 马军羽， 等. 四氢姜黄素通过下调ROS/p53信号通路抑制高糖诱导的血小板聚集和活化［J］. 实用医学杂志， 2025， 41（3）： 305-312. doi： 10.3969/j.issn.1006-5725.2025. 03.001 .
[20] 胡锦秋. 四氢姜黄素下调醛糖还原酶信号通路介导的整合素αⅡbβ3活化抑制高糖诱导的血小板高反应性［D］. 大理： 大理大学， 2025.
[21] 马军羽， 张春梅， 姜杨， 等. 基于转录组学探讨四氢姜黄素改善2型糖尿病小鼠肾损伤的作用机制［J］. 中国医科大学学报， 2025， 54（6）： 493-499. doi： 10.12007/j.issn.0258-4646. 2025.06.003 .
[22] HU J， BI X， ZHANG C， et al. Comparative efficacy of curcumin and its metabolite tetrahydrocurcumin in attenuating diabetic platelet hyperreactivity by suppressing integrin αIIbβ3 activation via an oxidative stress-dependent pathway［J］. J Agric Food Chem， 2026， 74（4）： 3655-3668. doi： 10.1021/acs.jafc.5c12711 .
[23] GIRALDO-GONZALEZ G C， ROMAN-GONZALEZ A， CA?AS F， et al. Molecular mechanisms of type 2 diabetes-related heart disease and therapeutic insights［J］. Int J Mol Sci， 2025， 26（10）： 4548. doi： 10.3390/ijms26104548 .
[24] TASHKANDI A J， GORMAN A， MCGOLDRICK MATHERS E， et al. Metabolic and mitochondrial dysregulations in diabetic cardiac complications［J］. IJMS， 2025， 26（7）： 3016. doi： 10.3390/ijms26073016 .
[25] KARATZIA L， CULLEN F， YOUNG M， et al. New model of experimental diabetic cardiomyopathy using combination of multiple doses of anomer-equilibrated streptozotocin and high-fat diet： Sex matters［J］. Diabetes， 2025， 74（5）： 760-772. doi： 10.2337/db24-0385 .
[26] KONAKTCHIEVA M， STOJCHEVSKI R， HADZI-PETRUSHEV N， et al. Curcumin and tetrahydrocurcumin as multi-organ modulators of the adipose tissue-gut-liver axis： Mechanistic insights， therapeutic potential， and translational challenges［J］. Pharmaceuticals （Basel）， 2025， 18（12）： 1791. doi： 10.3390/ph18121791 .
[27] ZHANG B， YANG J， LI X， et al. Tetrahydrocurcumin ameliorates postinfarction cardiac dysfunction and remodeling by inhibiting oxidative stress and preserving mitochondrial function via SIRT3 signaling pathway［J］. Phytomedicine， 2023， 121： 155127. doi： 10.1016/j.phymed.2023.155127 .
[28] O’CONNELL G C， SMOTHERS C G， WANG J， et al. Body-wide expression profiles of commonly assessed cardiac biomarkers in a large cohort of human tissue donors［J］. Cardiology， 2025： 1-17. doi： 10.1159/000547289 .
[29] HEDAYATI N， YAGHOOBI A， SALAMI M， et al. Impact of polyphenols on heart failure and cardiac hypertrophy： Clinical effects and molecular mechanisms［J］. Front Cardiovasc Med， 2023， 10： 1174816. doi： 10.3389/fcvm.2023.1174816 .
[30] YU S， PU J， LIU K， et al. Curcumin mediates oxidative stress to play an anti-fibrotic role， focusing on liver， renal， myocardial and pulmonary fibrosis［J］. Front Pharmacol， 2025， 16： 1636538. doi： 10.3389/fphar.2025.1636538 .
[31] PASSI M， ST?CKL J B， FR?HLICH T， et al. CDK5interacts withMST2and modulates the Hippo signalling pathway［J］. FEBS Open Bio， 2025， 15（4）： 647-660. doi： 10.1002/2211-5463. 13962 .
[32] WU W， HUYNH K， DU J C， et al. Hippo pathway activation causes multiple lipid derangements in a murine model of cardiomyopathy［J］. Biochim Biophys Acta BBA Mol Cell Biol Lipds， 2025， 1870（2）： 159590. doi： 10.1016/j.bbalip.2024.159590 .
[33] KAULICH P T， THOLEY A. Top-down proteomics： Why and when？［J］. Proteomics， 2025， 25（24）： 6-12. doi： 10.1002/pmic.202400338 .
Options
Outlines

/

〈 〉