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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

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

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.

Dose-Dependent Anti-Fibrotic Effect of Thymoquinone on Renal TGF-β1 Expression in Wistar Rats with Unilateral Ureteral Obstruction M Zulfikar Abadi; Suprapti; Muhammad Irsan Saleh; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (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.v10i7.1626

Background: Renal fibrosis is the final common pathway of chronic kidney disease (CKD), regulated by the pro-fibrotic cytokine Transforming Growth Factor-β1 (TGF-β1). Thymoquinone, the principal bioactive constituent of Nigella sativa, has antioxidant, anti-inflammatory and anti-fibrotic activity in pre-clinical models, but its dose-response profile in obstructive nephropathy is incompletely characterised. Methods: This in-vivo experimental study used a post-test-only with control-group design in 30 male Wistar rats (200–250 g) randomised into six groups (n=5): sham + olive-oil; UUO + olive-oil; UUO without olive-oil; and UUO with intra-peritoneal thymoquinone at 5, 10 or 20 mg/kg body-weight daily for 14 days. The primary outcome was renal cortical TGF-β1 mRNA expression by RT-PCR; secondary outcomes were IL-6 expression, serum urea and creatinine, Sirius-red percentage of positively-stained area (PSA) and a PAS-stained tubular injury score. Results: UUO produced renal injury: urea rose from 41.3 ± 6.2 to 57.7 ± 7.6 mg/dL (p=0.003) and TGF-β1 expression rose from 473,500 ± 32,797 to 679,922 ± 27,998 densitometric units (p=0.001). Thymoquinone reduced TGF-β1 dose-dependently to 644,571 ± 25,457, 612,143 ± 23,822 and 581,571 ± 24,128 a.u. at 5, 10 and 20 mg/kg (ANOVA p=0.004); the 20 mg/kg dose was superior to lower doses (p<0.05). PSA and tubular injury improved in parallel and correlated strongly with TGF-β1 (r=0.85). Conclusion: Thymoquinone exerts a dose-dependent anti-fibrotic effect via TGF-β1 down-regulation in obstructive nephropathy, supporting its evaluation as a complementary anti-fibrotic adjunct in CKD.

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

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

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.

Dose-Dependent Anti-Fibrotic Effect of Thymoquinone on Renal TGF-β1 Expression in Wistar Rats with Unilateral Ureteral Obstruction M Zulfikar Abadi; Suprapti; Muhammad Irsan Saleh; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 7 (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.v10i7.1626

Background: Renal fibrosis is the final common pathway of chronic kidney disease (CKD), regulated by the pro-fibrotic cytokine Transforming Growth Factor-β1 (TGF-β1). Thymoquinone, the principal bioactive constituent of Nigella sativa, has antioxidant, anti-inflammatory and anti-fibrotic activity in pre-clinical models, but its dose-response profile in obstructive nephropathy is incompletely characterised. Methods: This in-vivo experimental study used a post-test-only with control-group design in 30 male Wistar rats (200–250 g) randomised into six groups (n=5): sham + olive-oil; UUO + olive-oil; UUO without olive-oil; and UUO with intra-peritoneal thymoquinone at 5, 10 or 20 mg/kg body-weight daily for 14 days. The primary outcome was renal cortical TGF-β1 mRNA expression by RT-PCR; secondary outcomes were IL-6 expression, serum urea and creatinine, Sirius-red percentage of positively-stained area (PSA) and a PAS-stained tubular injury score. Results: UUO produced renal injury: urea rose from 41.3 ± 6.2 to 57.7 ± 7.6 mg/dL (p=0.003) and TGF-β1 expression rose from 473,500 ± 32,797 to 679,922 ± 27,998 densitometric units (p=0.001). Thymoquinone reduced TGF-β1 dose-dependently to 644,571 ± 25,457, 612,143 ± 23,822 and 581,571 ± 24,128 a.u. at 5, 10 and 20 mg/kg (ANOVA p=0.004); the 20 mg/kg dose was superior to lower doses (p<0.05). PSA and tubular injury improved in parallel and correlated strongly with TGF-β1 (r=0.85). Conclusion: Thymoquinone exerts a dose-dependent anti-fibrotic effect via TGF-β1 down-regulation in obstructive nephropathy, supporting its evaluation as a complementary anti-fibrotic adjunct in CKD.

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