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The role of SIRT1 activator in preventing endothelial dysfunction: A systematic review in vitro studies evaluating senescence markers and cellular senescence-associated outcomes Rahma, Oktivani Adelathifa; Rohman, Mohammad Saifur; Akbar, Naufal Zulfikar; Rohman, Ibrahim Abdur; Nurwidyaningtyas, Wiwit
Heart Science Journal Vol. 7 No. 1 (2026): Accelerating Clinical Breakthroughs: The Journey from Molecular Discovery to Pa
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.hsj.2026.007.01.5

Abstract

Background: Endothelial dysfunction, largely driven by endothelial senescence, is a critical factor in the pathogenesis of cardiovascular diseases. SIRT1, a key regulator of vascular homeostasis, has been identified as a potential target for mitigating endothelial senescence. Activators of SIRT1 have shown promise in delaying cellular senescence by modulating senescence markers and inflammatory pathways. However, a comprehensive evaluation of their effectiveness in in vitro models is required. Methods: This systematic review follows PRISMA 2020 guidelines and SYRCLE’s risk of bias assessment. Studies from four databases (PubMed, ScienceDirect, SpringerLink, and Taylor & Francis) were screened based on eligibility criteria, focusing on in vitro studies using Human Umbilical Vein Endothelial Cells (HUVECs) treated with SIRT1 activators. Key outcomes analyzed included senescence-associated β-galactosidase (SA-β-gal), cyclin-dependent kinase inhibitors (CDKIs: p21, p53, and p16), and senescence-associated secretory phenotype (SASP). Results: A total of 20 studies met the inclusion criteria. SIRT1 activators, including dapagliflozin, rhHAPLN1, ginsenoside Rb1, resveratrol, and others, demonstrated significant reductions in SA-β-gal expression, oxidative stress, and inflammatory cytokines (IL-6, IL-1β, and CCL2). Additionally, SIRT1 activation was associated with downregulation of CDKIs and enhanced nitric oxide (NO) bioavailability, contributing to improved endothelial function. Conclusion: SIRT1 activators exhibit potential in delaying endothelial senescence by suppressing senescence markers and inflammatory mediators, thereby preserving endothelial integrity. Future studies should focus on clinical validation to explore their therapeutic applications in endothelial senescence and cardiovascular disease prevention
In silico molecular docking investigation of Morus L. bioactive compounds as potential SIRT1 activators for endothelial anti-aging therapy Rahma, Oktivani Adelathifa; Rohman, Mohammad Saifur; Akbar, Naufal Zulfikar; Rohman, Ibrahim Abdur; Nurwidyaningtyas, Wiwit
Heart Science Journal Vol. 7 No. 1 (2026): Accelerating Clinical Breakthroughs: The Journey from Molecular Discovery to Pa
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.hsj.2026.007.01.8

Abstract

Background: The silent progression of vascular aging, characterized by endothelial dysfunction, has been closely linked to a decline in SIRT1 activity. Natural polyphenols have drawn increasing attention as potential modulators of this longevity-associated enzyme, offering therapeutic promise through antioxidant and anti-inflammatory effects. Objective: This study aimed to conduct an in silico analysis of natural SIRT1 activators, compare their interactions with simvastatin, and explore their structure-activity relationships to identify potential candidates for vascular-protective nutraceuticals or therapeutic adjuvants. Methods: Molecular docking was performed using PyRx 8.0 to assess ligand-SIRT1 interactions. Pharmacokinetic properties were evaluated through Lipinski’s Rule of Five and Veber’s Rule using SwissADME, while toxicity predicted with ProTox-II. Ligand-receptor interactions were visualized using LigPlot+. Result: Moracin demonstrated the strongest binding affinity to SIRT1 (–11.3 kcal/mol), followed by resveratrol (–9.6 kcal/mol), chlorogenic acid (–9.5 kcal/mol), and quercetin (–8.9 kcal/mol), all outperforming simvastatin (–8.4 kcal/mol). Moracin, resveratrol, and quercetin satisfied key drug-likeness criteria, while chlorogenic acid showed limitations in permeability. Toxicity profiling positioned resveratrol as the safest compound (GHS class 6), with moracin and quercetin also showing favorable profiles. Simvastatin exhibited broader toxicity risks. Conclusion: In silico and molecular docking results presented evidence for the potential of Morus L. polyphenols, especially moracin and resveratrol, as SIRT1 activators for endothelial anti-aging therapy. However, these findings remain predictive and require further validation through in vitro and in vivo studies to confirm the therapeutic efficacy and safety of these compounds as anti-aging agents.
A case of cardiac myxoma with obstructive symptoms: Recognizing key early signs for improved diagnosis Filano, Marco; Kuhn, Corinna Maria; Zhao, Zihan; Laukkanen, Noora Julia; Rahimah, Anna Fuji; Karolina, Wella; Prasetya, Indra; Rohman, Mohammad Saifur
Heart Science Journal Vol. 7 No. 1 (2026): Accelerating Clinical Breakthroughs: The Journey from Molecular Discovery to Pa
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.hsj.2026.007.01.21

Abstract

Background: LA myxoma is the most common primary cardiac tumor, often presenting with obstructive symptoms when the tumor prolapses into the mitral valve during diastole. On the other hand, rheumatic MS leads to fixed obstruction of the mitral valve. The coexistence of both conditions is extremely rare and can exacerbate the severity of mitral inflow obstruction. Early recognition of this dual pathology through careful clinical evaluation and echocardiographic assessment is crucial for timely and effective management. Case Presentations: A 66-year-old female patient presented with progressive dyspnea. Transthoracic echocardiography detected a mobile mass in the left atrium and later identified it as a cardiac myxoma. Further evaluation revealed severe rheumatic mitral stenosis (MS) with a mitral valve area (MVA) measured by planimetry at 1.23 cm², restricting the mass from slipping into the left ventricle during the diastolic phase. Based on the conference decision, tumor resection was performed, and the histopathological examination revealed a left atrial (LA) myxoma. The dual obstruction caused by mitral valve stenosis and a left atrial myxoma resulted in life-threatening symptoms due to diastolic obstruction of mitral inflow. In isolated LA myxoma, the tumor pushes into the mitral valve opening during the heart's relaxation phase, blocking blood flow from the left atrium to the left ventricle and raising pressure in the atrium and lungs. When significant MS is present, the narrowed valve further worsens this obstruction, leading to higher atrial pressure and more severe heart failure symptoms. Both conditions commonly present with early symptoms such as exertional dyspnea, palpitations, signs of heart failure like edema and pulmonary crackles, diastolic murmur, and sometimes syncope caused by reduced cardiac output. Conclusions: This case highlights the critical importance of identifying early obstructive symptoms indicative of cardiac myxoma. Timely identification of these clinical manifestations can facilitate earlier diagnosis, improve patient outcomes, and prevent potentially fatal complications.
Effects of green tea and green coffee extracts, empaglyphozin, and metformin on CAMLG mRNA expression in aortic calcification in Sprague Dawley rats induced by an atherogenic diet Riswati, Harnanik Puji; Rohman, Mohammad Saifur; Cholid Tri Tjahjono
Heart Science Journal Vol. 7 No. 1 (2026): Accelerating Clinical Breakthroughs: The Journey from Molecular Discovery to Pa
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.hsj.2026.007.01.10

Abstract

Background: Metabolic syndrome (MetS) in rat models, typically induced by high-fat or high-fructose diets, mirrors human features such as central obesity, insulin resistance, dyslipidemia, and hypertension. These metabolic disturbances create a pro-inflammatory, oxidative environment that actively drives vascular calcification through osteogenic transformation of vascular smooth muscle cells (VSMCs). Diet-induced obesity models have shown that high-fat diets can trigger and accelerate aortic calcification in vivo. Objective: This study aimed to determine whether MetS promotes vascular calcification and alters aortic CAMLG mRNA expression in rats, and to evaluate the effects of green tea/coffee extract, metformin, and empagliflozin on CAMLG modulation. Methods: Twenty-five male Sprague-Dawley rats were divided into five groups: negative control, MetS (high-fat/high-sucrose diet plus streptozotocin), and three treatment groups (green tea/coffee extract, metformin 500 mg/kg, empagliflozin 30 mg/kg). After nine weeks, aortic calcification was assessed via hematoxylin-eosin staining, and CAMLG mRNA expression was quantified by qRT-PCR. Data were analyzed with Kruskal-Wallis and post-hoc tests. Result: MetS induction promoted vascular calcification. CAMLG mRNA expression was higher in the MetS group compared to controls, though not statistically significant. All treatments modestly reduced CAMLG levels, but differences were not significant (p = 0.051), possibly due to multifactorial influences. Conclusion: MetS may tend to vascular tissues for calcification altering CAMLG mRNA expression. Therapies targeting oxidative stress, inflammation, or glucose metabolism could potentially modulate CAMLG-related pathways, warranting further exploration of underlying mechanisms.
Comparison of decaffeinated green tea and green coffee with metformin and empagliflozin on the GALNT2 and GALNT3 mRNA expression in metabolic syndrome rats Bahar, Mokhamad Aswin; Rohman, Mohammad Saifur; Kurnianingsih, Novi
Heart Science Journal Vol. 7 No. 1 (2026): Accelerating Clinical Breakthroughs: The Journey from Molecular Discovery to Pa
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.hsj.2026.007.01.7

Abstract

Background: Aberrant protein glycosylation mediated by the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase (GALNT) family has been implicated in the pathogenesis of metabolic syndrome (MetS), yet the roles of GALNT2 and GALNT3 remain poorly characterized. Objective: This study aimed to evaluate the modulatory effects of decaffeinated green tea and green coffee on GALNT2 and GALNT3 mRNA expression in MetS rats, compared with standard therapies, metformin and empagliflozin. Methods: Twenty-five male Sprague Dawley (SD) rats were divided into five groups randomly: (1) MetS rats (METS), (2) MetS rats treated with 300 mg/kgBW decaffeinated green tea and 200 mg/kgBW decaffeinated green coffee (TKD), (3) MetS rats treated with 500 mg/kgBW metformin (MFN), (4) MetS rats treated with 30 mg/kgBW empagliflozin (EMPA), and (5) negative control (NC). The MetS model was induced using a high-fat, high-sucrose (HFHS) diet followed by streptozotocin injection (30 mg/kgBW). After 10 weeks, the treatment groups received interventions for 9 weeks. GALNT2 and GALNT3 mRNA expression was investigated using reverse transcription polymerase chain reaction (RT-PCR).. Result: TKD and MFN tended to decrease GALNT2 and increase GALNT3 mRNA expression, although the differences were not significant statistically compared to the METS group (p>0.05). EMPA decreased GALNT2 and increased GALNT3 mRNA expression significantly compared to the METS group (p<0.05). Conclusion: The significant effect of EMPA on GALNT2 and GALNT3 mRNA expression suggests its therapeutic potential in targeting glycosylation pathways in MetS. Although TKD and MFN exhibited similar trends with EMPA, the lack of statistical significance suggests the need for further study.
Clinical and molecular perspective of coronary artery calcification Rohman, Mohammad Saifur; Firdaus, Dylan Hanny
Heart Science Journal Vol. 7 No. 1 (2026): Accelerating Clinical Breakthroughs: The Journey from Molecular Discovery to Pa
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.hsj.2026.007.01.1

Abstract

Coronary artery calcification (CAC) has been known related to worse procedural outcome, repeated revascularization and increase major cardiovascular events. CAC is caused by chronic progressive inflammation result in deposition of calcium crystallization and phosphate in the form of hydroxyapatite which leads also to an ectopic mineralization formation. Current guidelines on treating CAC emphasized on multimodal approach using not only intravascular imaging but also debulking or lithotripsy device. Future studies are exploring the potential of molecular and genetic therapeutic targets to prevent disease progression.
Pengaruh Pemberian Ekstrak Buah Mengkudu (Morinda citrifolia L.) Terhadap Aktivasi NF-ĸβ dan Ekspresi Protein (TNF-α, ICAM-1) pada Kultur Sel Endotel (HUVECs) Dipapar Ox-LDL Rastini, Endah Kusuma; Widodo, Mohammad Aris; Rohman, Mohammad Saifur
The Journal of Experimental Life Science Vol. 1 No. 1 (2011)
Publisher : Graduate School, Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (864.623 KB) | DOI: 10.21776/ub.jels.2011.001.01.06

Abstract

Penelitian ini bertujuan mengetahui pengaruh dan mekanisme kerja mengkudu (Morinda citrifolia) terhadap aktivasi NF-κβ, ekspresi protein TNF-α dan ICAM-1 dalam menghambat proses aterosklerosis. Penelitian dilakukan secara in vitro menggunakan kultur sel endotel vena umbilikalis manusia (HUVECs). Dibuat dua kelompok kontrol pada kultur sel endotel yaitu kontrol negatif tanpa perlakuan, kelompok yang dipapar Ox-LDL 40 μg ml-1, Kelompok perlakuan yaitu kultur sel endotel dengan pemberian dosis ekstrak mengkudu 2,5 μg ml-1, 5 μg ml-1 dan 10 μml-1 selama dua jam. Masing-masing sistem kultur dipapar Ox-LDL 40 μg ml-1. Pemaparan Ox-LDL dilakukan selama 30 menit untuk mengetahui aktivasi NF-κβ dan 24 jam untuk mengetahui ekspresi protein TNF-α dan ICAM-1. Pengukuran aktivasi NF-κβ, ekspresi protein TNF-α dan ICAM-1 menggunakan imunohistokimia. Hasil penelitian menunjukkan, ekstrak mengkudu dengan dosis 2,5 μg ml-1, 5 μg ml-1 dan 10 μg ml-1 dapat menghambat aktivasi NF-κβ, ekspresi protein TNF-α dan ICAM-1 pada kultur sel endotel manusia (HUVECs) dipapar Ox-LDL 40 μg ml-1 sebagai agen inflamasi yang dapat menimbulkan aterosklerosis. Melalui analisis ANOVA (p<0,01) diketahui terdapat hubungan negatif pada perlakuan antar dosis ekstrak mengkudu dalam menghambat aktivasi NF-κβ, ekspresi protein TNF-α dan ICAM-1 menggunakan analisis Spearman's (p<0,01). Kata kunci: aterosklerosis, ICAM-1, mengkudu (Morinda citrifolia L.), NF-κβ, Ox-LDL, TNF-α
Co-Authors Achmad Rudijanto Adhika Prastya Wikananda Adi, Andi Wahjono Aditha Satria Maulana Ahsan Ahsan Ainan, Shafa Akbar, Naufal Zulfikar Alfata, Fandy Hazzy Anditri Weningtyas Anita Surya Santoso Anjarwani, Setyasih Anna Fuji Rahimah Anna Fuji Rahimah Anna Fuji Rahimah Anna Fuji Rahimah Anna Fuji Rahimah Anna Fuji Rahimah Anna Fuji Rahimah Anna Fuji Rahimah Annisa Hasanah Ardhani Galih Prakoso Ardhino, Ardhino Ardian Rizal Ardian Rizal Ardian Rizal Arief Wibisono Arif Wicaksono Arina Madjidi Ashari, Yordan Wicaksono Astiawati, Tri Aulanni'am Aulanni'am Ayu Asri Devi Ayu Asri Devi Adityawati Aziz, Indra Jabbar Bagus H Kuncahyo Bahar, Mokhamad Aswin Bambang Kusbandono Bambang Rahardjo Bayu Aji Bayu Lestari Budi Satrijo Budi Satrijo Budi Satrijo Caesario, Fahreza Cholid Tri Tjahjono Cholid Tri Tjahjono Cholid Tri Tjahjono Candra Chomsy, Indah Nur Citra Tarannita Dadang Hendrawan Dea Arie Kurniawan Dedy Irawan Dhani, Fauzan Kurniawan Dian Nugrahenny Dian Nugrahenny Djanggan Sargowo Djanggan Sargowo Djanggan Sargowo Djanggan Sargowo Djanggan Sargowo Djanggan Sargowo Djanggan Sargowo Dwi Adi Nugroho Dwi Adi Nugroho Dwi Adi Nugroho Dwi Sarbini Dwigustiningrum, Nur Kaputrin Efris Kartika Sari, Efris Kartika Endah Kusuma Rastini Evit Ruspiono Fahmi Rusnanta Fahmy Rusnanta Fahmy Rusnanta Fajar, Jonny Karunia Fandy Hazzy Alfatta Faris Wahyu Nugroho Filano, Marco Firdaus, Achmad Jauhar Firdaus, Dylan Hanny Fitranti Suciati Laitupa Ghazyarda Aqilah Setya H Hendarto Harumsari, Stefani Haryati, Lina Hendrawati Hendrawati Heny Martini Hidayat Sujuti Hikmawan Wahyu Sulistomo Hose, Victor Alvianoes Guterez Husnul Khotimah Ika Setyo Rini Ikhwan Handirosiyanto Imelda Krisnasari Imelda Krisnasari Indra Prasetya Indra Prasetya Indra Prasetya Inggita Kusumastuty Irma Kamelia Pratiwi Kahadi, Cik Karolina, Wella Krishna Ari Nugraha Kuhn, Corinna Maria Kurnianingsih, Novi KURNIAWAN, ARY Laitupa, Fitranti Suciati Laukkanen, Noora Julia Lenny Kartika Lestari, Puspa Liemena Harold Adrian Lowry Yunita Lukitasari, Mifetika Martini, Heny Maulidiyatun Nuril Faizah Mifetika Lukitasari Mifetika Lukitasari Mifetika Lukitasari Mifetika Lukitasari Millisani, Hayla Iqda Mohammad Aris Widodo Muchammad Dzikrul Haq Karimullah Muhamad Bayu Aji Muhammad Rizki Fadlan Muhammad Rizki Fadlan Muhammad Rizki Fadlan Nashi Widodo Nashi Widodo Noverike, Nikhen Novi Kurnianingsih Novi Kurnianingsih Novi Kurnianingsih Nugraha, Krishna Ari Nugraha, Yudha Tria Nugrahanti Prasetyorini Nugroho, Ira Vori Nur Ida Panca Nugraheini Nur Ida Panca Nugrahini Nur Permatasari Oktafin Srywati Pamuna Olivia Handayani Olivia Handayani Pamuna, Oktafin Srywati Pande Made Dwijayasa Pawik Supriadi Pawik Supriadi Purbaningroom, Dian Laila Putri Annisa Kamila Putri Annisa Kamila Putri, Valerinna Yogibuana Swastika Rahimah, Anna Fuji Rahma, Oktivani Adelathifa Rahmi, Koyuki Atifa Ratih Kusuma Wardani Ratna Pancasari Ratna Pancasari Renny Suwarniaty Rislan Faiz Muhammad Riswati, Harnanik Puji Riza, Mochamad Faishal Rizal , Ardian Rizal, Ardian Rochmawati, Icmi Dian Rohman, Ibrahim Abdur Sakti, Pradhika Perdana Salvatore Di Somma Sasmojo Widito Satrijo, Budi Seprian Widasmara Setiawan, Dion Setyasih Anjarwani Setyasih Anjarwani Setyowati, Danti Utami Suprayoga, Imam Mi'raj Suryanto Taufieq Ridlo Makhmud Taufiq Nur Budaya Teguh Aryanugraha Teguh Wahyu Sardjono Titi A W Tonny Adriyanto Veny Kurniawati Veny Kurniawati Wella Karolina Widito, Sasmojo Widodo Nashi Widodo Widodo Wikananda, Adhika Prastya Wira Kimahesa Anggoro Wira Kimahesa Anggoro Wiwit Nurwidyaningtyas, Wiwit Yoga Waranugraha Yoga Waranugraha Yoga Waranugraha Yogibuana, Valerinna Yoseph Budi Utomo Yusuf Arifin Zhao, Zihan