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Article

Protective Effects of 5-MTP in a Rat Model of Diabetic Cardiomyopathy Through Anti-Inflammatory, Anti-Apoptotic, and Antifibrotic Mechanisms

by
Susetyo Atmojo
1,2,*,
Bambang Budi Siswanto
1,2,3,
Nurjati Chairani Siregar
1,4,5,
Aria Kekalih
6,
Fadlina Chany Saputri
7,
Budi Susetyo Pikir
8,9,
Deni Noviana
10,
Apridya Nurhafizah
2,
Wilbert Huang
2 and
Puspita Eka Wuyung
1,4,11
1
Doctoral Program in Medical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 16424, Indonesia
2
National Cardiovascular Center Harapan Kita, Jakarta 11420, Indonesia
3
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 16424, Indonesia
4
Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
5
Dr. Cipto Mangunkusumo General Hospital, Jakarta 16424, Indonesia
6
Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 16424, Indonesia
7
Department of Pharmacology-Toxicology, Faculty of Pharmacy, Universitas Indonesia, Jakarta 16424, Indonesia
8
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
9
Dr. Soetomo General Academic Hospital–Universitas Airlangga Hospital, Surabaya 60132, Indonesia
10
Division of Surgery and Radiology, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor 16680, Indonesia
11
Animal Research Facility, Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
 
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Life 2026, 16(7), 1198; https://doi.org/10.3390/life16071198
Submission received: 24 May 2026 / Revised: 19 June 2026 / Accepted: 22 June 2026 / Published: 20 July 2026
(This article belongs to the Special Issue New Insights and Advances in Heart Failure Research)
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Abstract

Background: Diabetic cardiomyopathy (DCM) is characterized by myocardial inflammation, apoptosis, and fibrosis that contribute to ventricular remodeling and dysfunction. We investigated the effects of 5-methoxytryptophan (5-MTP) on histopathological and molecular markers of myocardial remodeling in a rat model of DCM. Methods: Forty-eight Sprague–Dawley rats with DCM induced by a high-fat high-fructose diet and low-dose streptozotocin (25 mg/kg) were randomized to control or 5-MTP treatment (25, 50, or 100 mg/kg) and evaluated after 8, 16, and 32 days. Histopathological assessment using hematoxylin–eosin and Masson’s trichrome staining, along with immunohistochemical analysis of inflammatory, apoptotic, and fibrotic markers, was performed. Results: Myocardial inflammatory histopathological scores did not differ significantly among groups. Myocardial fibrosis assessed by Masson’s trichrome staining was significantly reduced at day 16 (p = 0.020), with all 5-MTP doses demonstrating lower fibrosis scores than DCM controls. Collagen I expression did not differ significantly. Caspase-3 expression was significantly reduced in all treatment groups at day 16 (p = 0.029), with persistent reduction at day 32 only in the 100 mg/kg group (p = 0.004). Early molecular modulation was observed through reduced TGF-β expression at day 8 in the 25 mg/kg and 50 mg/kg groups, followed by reduced SMAD3 expression at day 16 in the 25 mg/kg and 100 mg/kg groups. At day 16, AKT expression increased in the 25 mg/kg group, while cytoplasmic NF-κB expression decreased in the 25 mg/kg and 100 mg/kg groups. Conclusion: 5-MTP demonstrated time-dependent changes in molecular and histopathological markers associated with myocardial remodeling in experimental DCM.
Keywords: diabetic cardiomyopathy; 5-methoxytryptophan; myocardial remodeling diabetic cardiomyopathy; 5-methoxytryptophan; myocardial remodeling

Share and Cite

MDPI and ACS Style

Atmojo, S.; Siswanto, B.B.; Siregar, N.C.; Kekalih, A.; Saputri, F.C.; Pikir, B.S.; Noviana, D.; Nurhafizah, A.; Huang, W.; Wuyung, P.E. Protective Effects of 5-MTP in a Rat Model of Diabetic Cardiomyopathy Through Anti-Inflammatory, Anti-Apoptotic, and Antifibrotic Mechanisms. Life 2026, 16, 1198. https://doi.org/10.3390/life16071198

AMA Style

Atmojo S, Siswanto BB, Siregar NC, Kekalih A, Saputri FC, Pikir BS, Noviana D, Nurhafizah A, Huang W, Wuyung PE. Protective Effects of 5-MTP in a Rat Model of Diabetic Cardiomyopathy Through Anti-Inflammatory, Anti-Apoptotic, and Antifibrotic Mechanisms. Life. 2026; 16(7):1198. https://doi.org/10.3390/life16071198

Chicago/Turabian Style

Atmojo, Susetyo, Bambang Budi Siswanto, Nurjati Chairani Siregar, Aria Kekalih, Fadlina Chany Saputri, Budi Susetyo Pikir, Deni Noviana, Apridya Nurhafizah, Wilbert Huang, and Puspita Eka Wuyung. 2026. "Protective Effects of 5-MTP in a Rat Model of Diabetic Cardiomyopathy Through Anti-Inflammatory, Anti-Apoptotic, and Antifibrotic Mechanisms" Life 16, no. 7: 1198. https://doi.org/10.3390/life16071198

APA Style

Atmojo, S., Siswanto, B. B., Siregar, N. C., Kekalih, A., Saputri, F. C., Pikir, B. S., Noviana, D., Nurhafizah, A., Huang, W., & Wuyung, P. E. (2026). Protective Effects of 5-MTP in a Rat Model of Diabetic Cardiomyopathy Through Anti-Inflammatory, Anti-Apoptotic, and Antifibrotic Mechanisms. Life, 16(7), 1198. https://doi.org/10.3390/life16071198

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