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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.

Adjuvant Resveratrol Reduces Albuminuria and Serum Transforming Growth Factor-β Without Improving Glomerular Filtration Rate in Diabetic Kidney Disease: A 12-Week Randomized Controlled Trial Eva Julita; Zulkhair Ali; Yulianto Kusnadi; Legiran
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.v10i7.1627

Background: Diabetic kidney disease (DKD) progresses through inflammation and fibrosis, with transforming growth factor-β (TGF-β) as the principal profibrotic mediator and albuminuria as a clinical surrogate of glomerular injury. Methods: We conducted a 12-week, double-blind, placebo-controlled randomized trial at Dr. Mohammad Hoesin General Hospital, Palembang, between October 2025 and January 2026 to evaluate adjuvant resveratrol on serum TGF-β, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). Results: Of 61 randomized adults with DKD on standard care, 54 were analyzed (resveratrol n=27 received 25 mg twice daily, derived from Polygonum cuspidatum in 95% lecithin; placebo n=27). Within the resveratrol group, serum TGF-β fell from 123.7 to 77.1 pg/mL (p=0.008) and UACR from 94.1 to 89.8 mg/g (p=0.017); within placebo, UACR rose from 81.9 to 112 mg/g (p=0.029) while TGF-β change was non-significant (p=0.428). Between-group ΔUACR was significant (p<0.001), whereas ΔTGF-β (p=0.303) and ΔeGFR (p=0.567) were not. Multivariable linear regression identified resveratrol as an independent predictor of UACR reduction (B=−394.12 mg/g; 95% CI −659.53 to −128.71; p=0.004; adjusted R²=0.129). Baseline TGF-β was the dominant predictor of ΔTGF-β (B=−0.81; p<0.001; adjusted R²=0.701), and baseline LFG stage predicted ΔeGFR (B=−4.76; p=0.021). Mild bloating was reported in 14.8% of resveratrol versus 11.1% of placebo recipients; no serious adverse events occurred. Conclusion: Adjuvant low-dose resveratrol reduces albuminuria and serum TGF-β over 12 weeks in DKD without short-term improvement in eGFR, supporting an antifibrotic biomarker signal that warrants longer trials.

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.

Adjuvant Resveratrol Reduces Albuminuria and Serum Transforming Growth Factor-β Without Improving Glomerular Filtration Rate in Diabetic Kidney Disease: A 12-Week Randomized Controlled Trial Eva Julita; Zulkhair Ali; Yulianto Kusnadi; Legiran
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.v10i7.1627

Background: Diabetic kidney disease (DKD) progresses through inflammation and fibrosis, with transforming growth factor-β (TGF-β) as the principal profibrotic mediator and albuminuria as a clinical surrogate of glomerular injury. Methods: We conducted a 12-week, double-blind, placebo-controlled randomized trial at Dr. Mohammad Hoesin General Hospital, Palembang, between October 2025 and January 2026 to evaluate adjuvant resveratrol on serum TGF-β, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). Results: Of 61 randomized adults with DKD on standard care, 54 were analyzed (resveratrol n=27 received 25 mg twice daily, derived from Polygonum cuspidatum in 95% lecithin; placebo n=27). Within the resveratrol group, serum TGF-β fell from 123.7 to 77.1 pg/mL (p=0.008) and UACR from 94.1 to 89.8 mg/g (p=0.017); within placebo, UACR rose from 81.9 to 112 mg/g (p=0.029) while TGF-β change was non-significant (p=0.428). Between-group ΔUACR was significant (p<0.001), whereas ΔTGF-β (p=0.303) and ΔeGFR (p=0.567) were not. Multivariable linear regression identified resveratrol as an independent predictor of UACR reduction (B=−394.12 mg/g; 95% CI −659.53 to −128.71; p=0.004; adjusted R²=0.129). Baseline TGF-β was the dominant predictor of ΔTGF-β (B=−0.81; p<0.001; adjusted R²=0.701), and baseline LFG stage predicted ΔeGFR (B=−4.76; p=0.021). Mild bloating was reported in 14.8% of resveratrol versus 11.1% of placebo recipients; no serious adverse events occurred. Conclusion: Adjuvant low-dose resveratrol reduces albuminuria and serum TGF-β over 12 weeks in DKD without short-term improvement in eGFR, supporting an antifibrotic biomarker signal that warrants longer trials.

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