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Garcinia mangostana L. Nanoextract Improves Early Inflammatory Phase Bone Fracture Healing in Diabetes Mellitus by Targeting IL-1β and TNF-α: A Comprehensive Meta-Analysis Gregorius Gathot Garudanto; Yuriz Bakthiar; MI Widiastuti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 4 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i4.1260

Background: Diabetic fracture healing is often impaired due to prolonged and exaggerated inflammation, characterized by elevated levels of pro-inflammatory cytokines like IL-1β and TNF-α. Garcinia mangostana L. (mangosteen) has demonstrated anti-inflammatory properties, and nanoformulations may enhance its bioavailability and efficacy. This meta-analysis aimed to evaluate the effect of Garcinia mangostana L. nanoextract on IL-1β and TNF-α levels during the early inflammatory phase of fracture healing in diabetic models. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library databases for studies published between 2013 and 2024. Studies investigating the effects of Garcinia mangostana L. nanoextracts on IL-1β and TNF-α levels in in vivo or in vitro models of diabetic fracture healing were included. Data on cytokine levels, fracture healing parameters (where available), and study characteristics were extracted. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using the I² statistic. Results: Nine studies met the inclusion criteria. Meta-analysis revealed that Garcinia mangostana L. nanoextract significantly reduced IL-1β levels (SMD = -2.85, 95% CI: -3.97 to -1.73, p < 0.00001; I² = 88%) and TNF-α levels (SMD = -2.14, 95% CI: -3.08 to -1.20, p < 0.00001; I² = 82%) compared to control groups in diabetic fracture healing models. Subgroup analyses indicated significant reductions in both in vivo and in vitro studies. Conclusion: This meta-analysis provides evidence that Garcinia mangostana L. nanoextract significantly reduces IL-1β and TNF-α levels during the early inflammatory phase of fracture healing in diabetic models. These findings suggest that Garcinia mangostana L. nanoextract holds therapeutic potential for improving fracture healing outcomes in individuals with diabetes mellitus.

Mangosteen Nanoextract and Bone Regeneration in Diabetes: A Meta-Analysis of ALP and Osteocalcin Modulation during Fracture Callus Formation Chrisantus Ronald Bria Seran; Yuriz Bakthiar; MI Widiastuti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 4 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i4.1261

Background: Diabetic fracture healing is often impaired, leading to prolonged recovery and increased risk of non-union. Garcinia mangostana L. (mangosteen) possesses anti-inflammatory, antioxidant, and potentially osteogenic properties. This meta-analysis investigates the effect of mangosteen nanoextract on bone regeneration in diabetic fracture models, focusing on the modulation of alkaline phosphatase (ALP) and osteocalcin (OCN) levels during callus formation. Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library databases, covering publications from January 2013 to May 2024. Studies evaluating the effects of mangosteen nanoextract on ALP and OCN levels in in vivo diabetic fracture models were included. Data on ALP and OCN levels at various time points during callus formation were extracted. A random-effects model was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CIs) for ALP and OCN levels between mangosteen nanoextract-treated and control groups. Heterogeneity was assessed using the I² statistic. Results: Five studies met the inclusion criteria, encompassing a total of 150 diabetic animal models (rats or mice) with induced fractures. Mangosteen nanoextract treatment was associated with a significant increase in ALP levels during the early phase of callus formation (SMD = 1.25; 95% CI: 0.80, 1.70; p < 0.001; I² = 65%). Similarly, OCN levels were significantly higher in the nanoextract-treated group during the later stages of callus formation (SMD = 0.98; 95% CI: 0.55, 1.41; p < 0.001; I² = 58%). Conclusion: This meta-analysis suggests that mangosteen nanoextract may enhance bone regeneration in diabetic fracture models by modulating ALP and OCN levels, key biomarkers of osteoblast activity and bone formation. Further research, including well-designed clinical trials, is warranted to confirm these findings and translate them into clinical practice.

Nanostructured Garcinia mangostana Extract Modulates RANKL Signaling and Calcium Homeostasis to Enhance Fracture Healing in Diabetic Bone: A Systematic Review of In Vivo Evidence Adhimas Wicaksono; Yuriz Bakthiar; MI Widiastuti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 4 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i4.1263

Background: Diabetic fracture healing is often impaired due to chronic hyperglycemia, oxidative stress, and inflammation, leading to dysregulation of bone remodeling. Receptor activator of nuclear factor kappa-Β ligand (RANKL) and calcium homeostasis are critical regulators of this process. Garcinia mangostana (mangosteen) extract, particularly in nanostructured form, has shown promise in modulating these pathways. This systematic review evaluates the in vivo evidence for the effects of nanostructured G. mangostana extract on RANKL signaling, calcium levels, and bone healing outcomes in diabetic fracture models. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase databases from January 2013 to May 2024. Studies were included if they utilized in vivo diabetic animal models with induced fractures, administered nanostructured G. mangostana extract, and assessed outcomes related to RANKL expression, calcium levels (serum or bone), and/or bone healing parameters (histology). Risk of bias was assessed using the SYRCLE's tool. Data were extracted and synthesized narratively. Results: Seven studies met the inclusion criteria. All studies used rodent models (rats or mice) with induced type 1 or type 2 diabetes. Nanostructured G. mangostana extract, primarily containing xanthones, was administered via various routes (oral gavage, intraperitoneal injection). The majority of studies (6 out of 7) reported a significant decrease in RANKL expression and/or an increase in the osteoprotegerin (OPG)/RANKL ratio in the fracture callus of treated animals compared to diabetic controls. Serum calcium levels were generally normalized (5 out of 7 studies) in treated groups. Furthermore, treated animals exhibited improved histological evidence of enhanced callus formation and remodeling (all 7 studies). Risk of bias varied across studies, with some limitations in blinding and allocation concealment. Conclusion: Nanostructured G. mangostana extract shows significant potential for improving fracture healing in diabetic bone by modulating RANKL signaling and calcium homeostasis. Further high-quality, pre-clinical studies are warranted to optimize dosage, delivery methods, and to fully elucidate the underlying mechanisms before clinical translation.

Garcinia mangostana L. Nanoextract Improves Early Inflammatory Phase Bone Fracture Healing in Diabetes Mellitus by Targeting IL-1β and TNF-α: A Comprehensive Meta-Analysis Gregorius Gathot Garudanto; Yuriz Bakthiar; MI Widiastuti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 4 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i4.1260

Background: Diabetic fracture healing is often impaired due to prolonged and exaggerated inflammation, characterized by elevated levels of pro-inflammatory cytokines like IL-1β and TNF-α. Garcinia mangostana L. (mangosteen) has demonstrated anti-inflammatory properties, and nanoformulations may enhance its bioavailability and efficacy. This meta-analysis aimed to evaluate the effect of Garcinia mangostana L. nanoextract on IL-1β and TNF-α levels during the early inflammatory phase of fracture healing in diabetic models. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library databases for studies published between 2013 and 2024. Studies investigating the effects of Garcinia mangostana L. nanoextracts on IL-1β and TNF-α levels in in vivo or in vitro models of diabetic fracture healing were included. Data on cytokine levels, fracture healing parameters (where available), and study characteristics were extracted. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using the I² statistic. Results: Nine studies met the inclusion criteria. Meta-analysis revealed that Garcinia mangostana L. nanoextract significantly reduced IL-1β levels (SMD = -2.85, 95% CI: -3.97 to -1.73, p < 0.00001; I² = 88%) and TNF-α levels (SMD = -2.14, 95% CI: -3.08 to -1.20, p < 0.00001; I² = 82%) compared to control groups in diabetic fracture healing models. Subgroup analyses indicated significant reductions in both in vivo and in vitro studies. Conclusion: This meta-analysis provides evidence that Garcinia mangostana L. nanoextract significantly reduces IL-1β and TNF-α levels during the early inflammatory phase of fracture healing in diabetic models. These findings suggest that Garcinia mangostana L. nanoextract holds therapeutic potential for improving fracture healing outcomes in individuals with diabetes mellitus.

Mangosteen Nanoextract and Bone Regeneration in Diabetes: A Meta-Analysis of ALP and Osteocalcin Modulation during Fracture Callus Formation Chrisantus Ronald Bria Seran; Yuriz Bakthiar; MI Widiastuti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 4 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i4.1261

Background: Diabetic fracture healing is often impaired, leading to prolonged recovery and increased risk of non-union. Garcinia mangostana L. (mangosteen) possesses anti-inflammatory, antioxidant, and potentially osteogenic properties. This meta-analysis investigates the effect of mangosteen nanoextract on bone regeneration in diabetic fracture models, focusing on the modulation of alkaline phosphatase (ALP) and osteocalcin (OCN) levels during callus formation. Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library databases, covering publications from January 2013 to May 2024. Studies evaluating the effects of mangosteen nanoextract on ALP and OCN levels in in vivo diabetic fracture models were included. Data on ALP and OCN levels at various time points during callus formation were extracted. A random-effects model was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CIs) for ALP and OCN levels between mangosteen nanoextract-treated and control groups. Heterogeneity was assessed using the I² statistic. Results: Five studies met the inclusion criteria, encompassing a total of 150 diabetic animal models (rats or mice) with induced fractures. Mangosteen nanoextract treatment was associated with a significant increase in ALP levels during the early phase of callus formation (SMD = 1.25; 95% CI: 0.80, 1.70; p < 0.001; I² = 65%). Similarly, OCN levels were significantly higher in the nanoextract-treated group during the later stages of callus formation (SMD = 0.98; 95% CI: 0.55, 1.41; p < 0.001; I² = 58%). Conclusion: This meta-analysis suggests that mangosteen nanoextract may enhance bone regeneration in diabetic fracture models by modulating ALP and OCN levels, key biomarkers of osteoblast activity and bone formation. Further research, including well-designed clinical trials, is warranted to confirm these findings and translate them into clinical practice.

Nanostructured Garcinia mangostana Extract Modulates RANKL Signaling and Calcium Homeostasis to Enhance Fracture Healing in Diabetic Bone: A Systematic Review of In Vivo Evidence Adhimas Wicaksono; Yuriz Bakthiar; MI Widiastuti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 4 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i4.1263

Background: Diabetic fracture healing is often impaired due to chronic hyperglycemia, oxidative stress, and inflammation, leading to dysregulation of bone remodeling. Receptor activator of nuclear factor kappa-Β ligand (RANKL) and calcium homeostasis are critical regulators of this process. Garcinia mangostana (mangosteen) extract, particularly in nanostructured form, has shown promise in modulating these pathways. This systematic review evaluates the in vivo evidence for the effects of nanostructured G. mangostana extract on RANKL signaling, calcium levels, and bone healing outcomes in diabetic fracture models. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase databases from January 2013 to May 2024. Studies were included if they utilized in vivo diabetic animal models with induced fractures, administered nanostructured G. mangostana extract, and assessed outcomes related to RANKL expression, calcium levels (serum or bone), and/or bone healing parameters (histology). Risk of bias was assessed using the SYRCLE's tool. Data were extracted and synthesized narratively. Results: Seven studies met the inclusion criteria. All studies used rodent models (rats or mice) with induced type 1 or type 2 diabetes. Nanostructured G. mangostana extract, primarily containing xanthones, was administered via various routes (oral gavage, intraperitoneal injection). The majority of studies (6 out of 7) reported a significant decrease in RANKL expression and/or an increase in the osteoprotegerin (OPG)/RANKL ratio in the fracture callus of treated animals compared to diabetic controls. Serum calcium levels were generally normalized (5 out of 7 studies) in treated groups. Furthermore, treated animals exhibited improved histological evidence of enhanced callus formation and remodeling (all 7 studies). Risk of bias varied across studies, with some limitations in blinding and allocation concealment. Conclusion: Nanostructured G. mangostana extract shows significant potential for improving fracture healing in diabetic bone by modulating RANKL signaling and calcium homeostasis. Further high-quality, pre-clinical studies are warranted to optimize dosage, delivery methods, and to fully elucidate the underlying mechanisms before clinical translation.

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