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All Journal Jambi Medical Journal : Jurnal Kedokteran dan Kesehatan Majalah Kedokteran Sriwijaya Biomedical Journal of Indonesia Molecular and Cellular Biomedical Sciences (MCBS) Indonesian Journal of Kidney and Hypertension Jurnal Menara Medika Open Access Indonesian Journal of Medical Reviews Bioscientia Medicina : Journal of Biomedicine and Translational Research PHARMACOLOGY, MEDICAL REPORTS, ORTHOPEDIC, AND ILLNESS DETAILS (COMORBID) Journal Of World Science Jurnal Penyakit Dalam Indonesia
Zulkhair Ali
Department Of Internal Medicine, Dr. Mohammad Hoesin Hospital, Palembang, Indonesia / Department Of Internal Medicine, Faculty Of Medicine, Universitas Sriwijaya, Palembang, Indonesia
Biochemistry, Genetics & Molecular Biology Computer Science & IT Dentistry Economics, Econometrics & Finance Engineering Health Professions Immunology & microbiology Law, Crime, Criminology & Criminal Justice Medicine & Pharmacology Neuroscience Nursing Public Health Social Sciences

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Modulation of TGF-β/Smad and Nrf2 Signaling Pathways by Thymoquinone in the Attenuation of Renal Fibrosis: A Systematic Review and Meta-Analysis of Pre-clinical Models Chairil Makky; Ian Effendi; Zulkhair Ali; Novadian; Suprapti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i1.1491

Abstract

Background: Renal fibrosis is the irreversible, final common pathway for all progressive forms of chronic kidney disease (CKD), leading to end-stage renal disease. Its pathogenesis is characterized by the over-activation of pro-fibrotic signaling, chiefly the Transforming Growth Factor-beta (TGF-β)/Smad pathway, and the failure of endogenous cytoprotective mechanisms like the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response. Thymoquinone (TQ), the primary bioactive constituent of Nigella sativa, is a pleiotropic compound with known anti-inflammatory and antioxidant properties. This study was designed to systematically quantify its mechanistic efficacy in modulating the core Nrf2 and TGF-β pathways in established pre-clinical models of renal fibrosis and injury. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. We performed a comprehensive search of major databases (including PubMed and Scopus) for pre-clinical in vivo studies published between 2014 and 2025 that investigated TQ monotherapy or TQ-dominant combination therapy in rodent models of renal injury. The eight studies that met the inclusion criteria utilized diverse models: Unilateral Ureteral Obstruction (UUO), cisplatin-induced nephrotoxicity, gentamicin-induced nephrotoxicity, 5-fluorouracil (5-FU)-induced acute kidney injury (AKI), lipopolysaccharide (LPS)-induced inflammation, carfilzomib (CFZ)-induced renal impairment, and ischemia-reperfusion (IRI). Primary outcomes were the expression of renal Nrf2 and TGF-β1. Secondary outcomes included markers of fibrosis (collagen deposition, histology scores), renal function (BUN, creatinine), oxidative stress (MDA, SOD, GSH, CAT), and inflammation (TNF-α, NF-κB, IL-6, IL-1β). Data were pooled using a random-effects model, and primary analyses were stratified by injury model subgroup. Results: Thymoquinone treatment resulted in a profound and significant upregulation of the protective Nrf2 pathway (SMD: 2.38; 95% CI [1.05, 3.71]; p < 0.001; 3 studies) and its downstream target Heme Oxygenase-1 (HO-1). Concurrently, TQ treatment markedly suppressed the primary pro-fibrotic driver, TGF-β1 (SMD: -2.09; 95% CI [-2.99, -1.19]; p < 0.001; 2 studies). This pivotal dual modulation translated into significant functional and structural improvements. TQ robustly attenuated renal fibrosis scores (SMD: -1.89; 95% CI [-2.55, -1.23]; p < 0.001; 2 studies). Stratified subgroup analysis showed TQ significantly improved renal function in both chemotoxic AKI models (BUN SMD: -2.31; 95% CI [-3.22, -1.40]) and chronic obstructive/fibrosis models (BUN SMD: -1.17; 95% CI [-1.75, -0.59]). This functional protection was underpinned by potent, broad-spectrum reversal of oxidative stress and inflammation across all subgroups. Conclusion: Thymoquinone consistently ameliorates renal injury and fibrosis across a wide spectrum of pre-clinical models. Its mechanism of action is multifaceted, critically involving the dual modulation of opposing pro-fibrotic and protective pathways: it suppresses the TGF-β1 cascade while simultaneously activating and restoring the Nrf2 antioxidant response. This body of evidence strongly supports Thymoquinone as a high-potential candidate for translational research and development as a novel, network-targeting therapy for human renal fibrosis.
Beyond Phosphate Binding: A Systematic Review and Meta-Analysis on the Efficacy and Safety of the Novel Paracellular Phosphate Inhibitor, Tenapanor, for Hyperphosphatemia in Dialysis Patients Eva Julita; Ian Effendi; Zulkhair Ali; Novadian; Suprapti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i1.1492

Abstract

Background: Hyperphosphatemia is a critical driver of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) undergoing dialysis. Current management, reliant on phosphate binders, is hampered by high pill burden and poor adherence. Tenapanor, a first-in-class, minimally-absorbed sodium/hydrogen exchanger 3 (NHE3) inhibitor, reduces paracellular phosphate absorption. We performed a systematic review and meta-analysis of all available Phase 3 trials to quantify its efficacy and safety. Methods: We searched PubMed, Embase, and Cochrane CENTRAL through October 2025 for Phase 3 clinical trials evaluating tenapanor for hyperphosphatemia in dialysis patients. Data were extracted from 6 eligible studies (N=1573). We conducted separate random-effects meta-analyses for different study designs: 1) parallel-group monotherapy vs. placebo, 2) withdrawal-design monotherapy vs. placebo, 3) parallel-group add-on therapy vs. placebo, and 4) safety (diarrhea incidence) vs. placebo. Efficacy was measured by Mean Difference (MD) in serum phosphate change; safety by Risk Ratio (RR). Results: Tenapanor demonstrated significant efficacy across all study designs. In parallel-group monotherapy (1 study, N=167), tenapanor was superior to placebo (MD: -1.89 mg/dL; 95% CI: -2.36 to -1.42). In withdrawal-design studies (2 RCTs, N=373), tenapanor maintained serum phosphate levels significantly better than placebo (Pooled MD: -0.75 mg/dL; 95% CI: -1.05 to -0.45; I2=0%). As an add-on therapy (1 RCT, N=235), tenapanor provided additional phosphate reduction versus binders alone (MD: -0.65 mg/dL; 95% CI: -0.96 to -0.35). Tenapanor significantly increased the risk of diarrhea versus placebo (3 RCTs, N=521; Pooled RR: 4.10; 95% CI: 2.50 to 6.72; I2=30%), which was the primary adverse event leading to discontinuation. Conclusion: Tenapanor represents a new mechanistic paradigm for hyperphosphatemia management. It is a highly effective phosphate-lowering agent, both as monotherapy and add-on therapy, but is associated with a significant, mechanism-based risk of gastrointestinal side effects.
Hubungan Kadar Malondialdehida (MDA) Serum dan Fraksi Ejeksi Ventrikel Kiri pada Pasien Hemodialisis Reguler Amir, Teguh Setiadi; Indrajaya, Taufik; Ali, Zulkhair
Jurnal Penyakit Dalam Indonesia
Publisher : UI Scholars Hub

Show Abstract | Download Original | Original Source | Check in Google Scholar

Abstract

Introduction. Malondialdehyde (MDA) is a marker of oxidative stress that is elevated in chronic kidney disease (CKD) patients undergoing regular hemodialysis. Oxidative stress can affect cardiac function especially left ventricular function. This study aimed to evaluate the relationship between serum MDA levels with left ventricular function in regular hemodialysis patients at Dr. Mohammad Hoesin Genaral Hospital, Palembang. Methods. This study was an analytic observational study with a cross-sectional design conducted on regular hemodialysis patients in the Hemodialysis Installation of Dr. Mohammad Hoesin Genaral Hospital, Palembang. The MDA levels were examined from the serum of post-hemodialysis patients using ELISA method. Echocardiography was then performed to determine left ventricular function. Statistical analysis was performed using STATA version 15 with Spearman correlation and Chi-square tests. Results. Among 121 subjects, median serum MDA levels was 4.05 (0.68-27.21) μmol/L. Correlation analysis demonstrated a significant moderate negative correlation between serum MDA levels and LVEF (r = −0.38, p < 0.0001). Mann–Whitney analysis showed that patients with reduced LVEF had significantly higher MDA levels than those with normal LVEF (median: 10.035 vs. 3.112 μmol/L). Furthermore, elevated MDA levels were significantly associated with reduced LVEF, with patients having high MDA levels exhibiting a 4.8-fold greater odds of reduced LVEF (OR 4.826, 95% CI 1.611–17.310). Conclusions. Elevated serum MDA levels were significantly associated with impaired left ventricular function in patients with stage V CKD undergoing regular hemodialysis at Mohammad Hoesin General Hospital, Palembang. Patients with high serum MDA levels had a 4.8-fold higher odds of reduced LVEF than those with lower MDA levels.
Co-Authors Abdul Hakim R Ade Yonata Ade Yonata, Ade Agustina H Akbar, Kgs. M. Yusuf Arief Akbar, M Yusuf Arief Ali Ghanie Alif Fathur Rachman, Muhammad Alwi Shahab Alwi Shahab Amir, Teguh Setiadi Anggelia Puspasari Arief Akbar, Kgs M Yusuf Arif, Cut Wulan Chairil Makky Christin, Theresia Citra Maharani Deddy Primadona Mulia Devi, SNA Ratnasari Dila Siti Hamidah Eddy Mart Salim Edy Nur Rachman Effendi, Ian Elfiani Elfiani Elfiani Emilia Emilia Erial Bahar Erial Bahar Erial Bahar, Erial Erwin Sukandi Eva Julita Fadil Pramudhya Hoesain Fadil Pramudhya Husein Fadil Pramudya Fauzan Azhari, Fauzan Ferawaty, Ferawaty Ferry Usnizar Ferry Yusrizal Fitri Rahmariani Fitria Koeshardani Harahap, Huntari Harun Hudari Ian Effendi Ian Effendi Ian Effendi Ika Kartika Ika Kartika Edi P Indrajaya, Taufik Irawan, Rico Irfannuddin Irfannuddin Istiqomah, Amelia Junaidi A Kartika, Herleni Kendenan, Margaretha Kgs M Yusuf Arief Akbar Kgs. M. Yusuf Arief Akbar kurniati, nova Kusrini, Ida Legiran Legiran Lidiawati Handayani Lilik Pranata M Yusuf Arief Akbar Mediarty Mediarty Syahrir Muhammad Irsan Saleh Muhammad Yusri Mulia, Deddy Primadona Nova Kurniati Novadian Novadian Novadian Novadian, Novadian Novadian Suhaimi Novadian Suhaimi Novadian Suhaimi Novandra AP Nurul Ramadhani Umareta Nyimas Natasha Ayu Shafira R.M. Suryadi Tjekyan Radiyati Umi Partan Ramadhan, Philosophia Ratna Maila Dewi Anggraini Reinanda Marizki R Rery TF Yuniarti RM Suryadi Tjekyan Rostika Dewi Shahab, Alwi Slamet, Suprapti SNA Ratnasari Devi Suhaimi, Novadian Suprapti Suprapti Slamet Suprapti Suprapti Suprapti Suprapti Syahpri Putra Wangsa Taufik Indrajaya Taufik Indrajaya Trinovita Andraini Wangsa, Syahpri Putra Yudhie Tanta Yulianto kusnadi