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All Journal Bioscientia Medicina : Journal of Biomedicine and Translational Research Bioscientia Medicina : Journal of Biomedicine and Translational Research
Muhammad Irsan Saleh
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Biochemistry, Genetics & Molecular Biology Immunology & microbiology Medicine & Pharmacology Neuroscience

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Therapeutic Efficacy of Thymoquinone in Attenuating Obstructive Renal Fibrosis: A Dose-Response Analysis of Tumor Necrosis Factor-Alpha Suppression and Histopathological Remodeling Edy Nur Rachman; Suprapti; Muhammad Irsan Saleh; Ian Effendi; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (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.v10i5.1583

Abstract

Background: Chronic kidney disease is characterized by progressive renal fibrosis, a maladaptive process driven by chronic inflammation and extracellular matrix accumulation. Tumor necrosis factor-alpha (TNF-α) plays a central role in this fibrogenic cascade. Thymoquinone (TQ), the primary bioactive compound of Nigella sativa, exhibits potent anti-inflammatory properties. Methods: In this therapeutic intervention model, 107 male Wistar rats were subjected to Unilateral Ureteral Obstruction (UUO). To test TQ's ability to halt established fibrogenesis, treatment was delayed until day 7 post-obstruction. Rats were randomized to receive TQ intraperitoneally at 5, 10, or 20 mg/kg body weight for 14 days. Outcomes included renal function (urea/creatinine), tubulointerstitial injury (PAS staining), fibrosis area (Sirius Red staining), and localized TNF-α mRNA expression (reverse transcriptase PCR normalized to GAPDH). Data were analyzed using ANOVA followed by Tukey’s Honestly Significant Difference (HSD) test. Results: UUO induced significant structural injury and upregulated TNF-α expression compared to sham controls (p < 0.001). TQ intervention significantly reduced the tubulointerstitial injury score, with the greatest reduction at 20 mg/kg (p < 0.01). The positively stained fibrotic area exhibited a U-shaped response, maximally decreased at the 10 mg/kg dose (p < 0.01). Similarly, TNF-α mRNA relative expression was significantly suppressed by TQ, exhibiting a pharmacological ceiling effect at 10 mg/kg (p < 0.01). Conclusion: Thymoquinone administered therapeutically mitigates established structural renal fibrosis and tubulointerstitial injury by downregulating TNF-α-mediated inflammation. A 10 mg/kg dose represents the optimal therapeutic threshold for anti-fibrotic efficacy in obstructive nephropathy.
Dose-Dependent Amelioration of Ureteral Obstruction-Induced Kidney Fibrosis by Thymoquinone via GPx-Mediated Antioxidant Defense Chairil Makky; Suprapti; Muhammad Irsan Saleh; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (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.v10i5.1585

Abstract

Background: Chronic kidney disease inevitably progresses to renal fibrosis, driven heavily by oxidative stress and the depletion of endogenous antioxidants including Glutathione Peroxidase (GPx). Thymoquinone (TQ), a bioactive compound from Nigella sativa, exhibits potent antioxidant properties. This study investigates the dose-dependent efficacy of TQ in mitigating renal fibrosis via GPx modulation in a Unilateral Ureteral Obstruction (UUO) model. Methods: Thirty male Rattus norvegicus were randomly assigned to six groups (n=5): Sham, UUO + olive oil (Negative Control), UUO without oil, and UUO treated with TQ at 5, 10, and 20 mg/kg body weight for 14 days. Renal function (ureum, creatinine) and oxidative stress (Malondialdehyde) were measured. GPx mRNA expression was quantified using Reverse Transcription-Polymerase Chain Reaction. Tubulointerstitial injury (TII) and Positively Stained Area (PSA) for fibrosis were assessed histopathologically. Results: UUO induction significantly downregulated GPx expression (median 0.52 versus 1.40 in Sham, p=0.001) and exacerbated TII (score 3.58) and PSA (11.42%). TQ administration dose-dependently upregulated GPx expression, peaking at 20 mg/kg (median 0.62, p=0.009 versus Negative Control). Furthermore, TQ 20 mg/kg significantly reduced the TII score to 2.26 and decreased fibrotic PSA, ameliorating morphological damage. Conclusion: Thymoquinone exerts potent, dose-dependent antifibrotic and renoprotective effects in obstructive nephropathy by restoring GPx-mediated antioxidant defenses and preventing tubulointerstitial remodeling.
Therapeutic Efficacy of Thymoquinone in Attenuating Obstructive Renal Fibrosis: A Dose-Response Analysis of Tumor Necrosis Factor-Alpha Suppression and Histopathological Remodeling Edy Nur Rachman; Suprapti; Muhammad Irsan Saleh; Ian Effendi; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (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.v10i5.1583

Abstract

Background: Chronic kidney disease is characterized by progressive renal fibrosis, a maladaptive process driven by chronic inflammation and extracellular matrix accumulation. Tumor necrosis factor-alpha (TNF-α) plays a central role in this fibrogenic cascade. Thymoquinone (TQ), the primary bioactive compound of Nigella sativa, exhibits potent anti-inflammatory properties. Methods: In this therapeutic intervention model, 107 male Wistar rats were subjected to Unilateral Ureteral Obstruction (UUO). To test TQ's ability to halt established fibrogenesis, treatment was delayed until day 7 post-obstruction. Rats were randomized to receive TQ intraperitoneally at 5, 10, or 20 mg/kg body weight for 14 days. Outcomes included renal function (urea/creatinine), tubulointerstitial injury (PAS staining), fibrosis area (Sirius Red staining), and localized TNF-α mRNA expression (reverse transcriptase PCR normalized to GAPDH). Data were analyzed using ANOVA followed by Tukey’s Honestly Significant Difference (HSD) test. Results: UUO induced significant structural injury and upregulated TNF-α expression compared to sham controls (p < 0.001). TQ intervention significantly reduced the tubulointerstitial injury score, with the greatest reduction at 20 mg/kg (p < 0.01). The positively stained fibrotic area exhibited a U-shaped response, maximally decreased at the 10 mg/kg dose (p < 0.01). Similarly, TNF-α mRNA relative expression was significantly suppressed by TQ, exhibiting a pharmacological ceiling effect at 10 mg/kg (p < 0.01). Conclusion: Thymoquinone administered therapeutically mitigates established structural renal fibrosis and tubulointerstitial injury by downregulating TNF-α-mediated inflammation. A 10 mg/kg dose represents the optimal therapeutic threshold for anti-fibrotic efficacy in obstructive nephropathy.
Dose-Dependent Amelioration of Ureteral Obstruction-Induced Kidney Fibrosis by Thymoquinone via GPx-Mediated Antioxidant Defense Chairil Makky; Suprapti; Muhammad Irsan Saleh; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (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.v10i5.1585

Abstract

Background: Chronic kidney disease inevitably progresses to renal fibrosis, driven heavily by oxidative stress and the depletion of endogenous antioxidants including Glutathione Peroxidase (GPx). Thymoquinone (TQ), a bioactive compound from Nigella sativa, exhibits potent antioxidant properties. This study investigates the dose-dependent efficacy of TQ in mitigating renal fibrosis via GPx modulation in a Unilateral Ureteral Obstruction (UUO) model. Methods: Thirty male Rattus norvegicus were randomly assigned to six groups (n=5): Sham, UUO + olive oil (Negative Control), UUO without oil, and UUO treated with TQ at 5, 10, and 20 mg/kg body weight for 14 days. Renal function (ureum, creatinine) and oxidative stress (Malondialdehyde) were measured. GPx mRNA expression was quantified using Reverse Transcription-Polymerase Chain Reaction. Tubulointerstitial injury (TII) and Positively Stained Area (PSA) for fibrosis were assessed histopathologically. Results: UUO induction significantly downregulated GPx expression (median 0.52 versus 1.40 in Sham, p=0.001) and exacerbated TII (score 3.58) and PSA (11.42%). TQ administration dose-dependently upregulated GPx expression, peaking at 20 mg/kg (median 0.62, p=0.009 versus Negative Control). Furthermore, TQ 20 mg/kg significantly reduced the TII score to 2.26 and decreased fibrotic PSA, ameliorating morphological damage. Conclusion: Thymoquinone exerts potent, dose-dependent antifibrotic and renoprotective effects in obstructive nephropathy by restoring GPx-mediated antioxidant defenses and preventing tubulointerstitial remodeling.
Co-Authors Chairil Makky Edy Nur Rachman Ian Effendi Novadian Suprapti Zulkhair Ali