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All Journal Indonesian Journal of Pharmaceutical Science and Technology Universa Medicina Molecular and Cellular Biomedical Sciences (MCBS) Journal of Health and Nutrition Research Gema Lingkungan Kesehatan
Eko Setiawan
Department of Biomedical Sciences, Faculty of Medicine, Sultan Agung Islamic University, Semarang, Indonesia
Biochemistry, Genetics & Molecular Biology Computer Science & IT Dentistry Environmental Science Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Nursing Public Health

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Potential of Glycine max-Based Cream in Restoring Skin Structure Through PDGF and Collagen Modulation After UVB Exposure Bayu Murdalin; Agung Putra; Eko Setiawan
Gema Lingkungan Kesehatan Vol. 23 No. 2 (2025): Gema Lingkungan Kesehatan
Publisher : Poltekkes Kemenkes Surabaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.36568/gelinkes.v23i2.209

Abstract

Premature aging is caused by excessive activity in the sun, causing oxidative stress and inflammatory reactions, which include changes in skin structure such as shortening and thickening of collagen fibers, damage to elastic fibers, and changes in the proportion of collagen types in the dermis. The purpose of this study was to determine the effect of administering soy extract cream (Glycine max (L.) Merr) on PDGF concentration and collagen density in BALB/c mice exposed to UVB rays. The experimental study used a Post Test Only Control Group Design with 30 BALB/c mice divided into five treatment groups: a group of healthy mice (K1), a negative group without exposure to UVB rays (K2), a positive group exposed to UVB rays and smeared with vitamin E cream (K3), and a treatment group with a dose of soy extract cream (KEKD) 10% (K4) and 20% (K5). Data analysis used the One Way Anova statistical test. The results of the study showed significant differences in the average PDGF levels in each group: (K1) 149.5±7.1 ng/mL, (K2) 40.4±4.4 ng/mL, (K3) 88.6±41.7 ng/mL, (K4) 323.2±86.1 ng/mL, and (K5) 330.2±34.3 ng/mL, with the One Way Anova test obtaining a p value = 0.001 (p<0.05). The average collagen density of group (K1) was 50.10±12.33%, (K2) 32.75±6.6%, (K3) 33.07±7.48%, (K4) 41.07±10.8%, and (K5) 41.9±13.4%, with One Way Anova test showing p=0.088 (p>0.05), which means there is no significant difference in collagen density between groups. Administration of soy extract cream (KEKD) affected PDGF levels, but did not show a significant difference in collagen density in BALB/c mice exposed to UVB light.
Hypoxia-preconditioned mesenchymal stem cells attenuate proinflammatory cytokines in collagen loss animal model Fristiani, Yeni; Putra, Agung; Sumarawati, Titiek; Setiawan, Eko; Ibrahim, Sugeng; Pramukarso, Dodik Tugasworo Pramukarso
Universa Medicina Vol. 44 No. 2 (2025)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2025.v44.131-140

Abstract

Background Repeated ultraviolet-B (UVB) exposure induces significant collagen degradation, primarily through overproduction of reactive oxygen species, which subsequently drives an inflammatory cascade. Hypoxia-preconditioned mesenchymal stem cells (H-MSCs) constitute a promising therapeutic approach to counteract collagen loss by modulating inflammatory pathways. This study aimed to evaluate the potential of H-MSCs in regulating NF-κB p65 and IL-1β expression in a collagen loss rat model, highlighting their therapeutic efficacy. Methods Twenty-five healthy male Wistar rats were randomly assigned to five groups: K1 (healthy controls), K2 (collagen loss), K3 (collagen loss + hyaluronic acid), K4 (collagen loss + 2.5 × 10⁵ H-MSCs), and K5 (collagen loss + 5 × 10⁵ H-MSCs). Collagen loss was induced by UVB radiation (peak wavelength: 302 nm) for 2 weeks. mRNA expression of NF-κB p65 was quantified by qRT-PCR, while IL-1β levels were assessed using ELISA. The rats were maintained for 14 days before being sacrificed, to allow the H-MSCs to exert their therapeutic effects. Data analysis was by One-way ANOVA with Tukey’s post-hoc test. Results The administration of H-MSCs significantly reduced IL-1β levels in groups K4 (633.14±63.76 pg/mL) and K5 (520.80±123.82 pg/mL) compared to group K2 (931.93±205.80 pg/mL) (p<0.05), with group K5 showing the most substantial reduction. Moreover, H-MSC injection in groups K4 and K5 effectively reduced NF-κB p65 expression levels (1.13±0.50 a.u. and 0.72±0.22 a.u., respectively), compared to group K2 (2.47±0.50 a.u.) (p<0.05), with group K5 providing optimum inhibition. Conclusion This study demonstrated that H-MSCs effectively attenuate UVB-induced inflammation and modulate key inflammatory pathways.
Mesenchymal Stem Cell-Derived Exosomes Enhance FGF-1 and SDF-1 Expression in Rats with Second Degree Burns Hariani, Nova Putri; Putra, Agung; Subchan, Prasetyowati; Setiawan, Eko
Molecular and Cellular Biomedical Sciences Vol 9, No 2 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i2.635

Abstract

Background: Second-degree burns cause extensive damage to the skin and pose significant health challenges, with current treatments facing limitations such as donor skin shortages and complications. Fibroblast growth factor 1 (FGF-1) and stromal-derived growth factor 1 (SDF-1) are critical for tissue repair. Emerging evidence suggests that mesenchymal stem cell-derived exosomes (E-MSCs) are a promising cell-free therapeutic option for enhancing wound healing through the modulation of FGF-1 and SDF-1. This study investigated the effect of E-MSCs on the expression of FGF-1 and SDF-1 genes in rats with second-degree burns.Materials and methods:  This experimental study used a second-degree burn model in Wistar rats, treated with subcutaneous injections of E-MSCs at doses of 100 µL and 200 µL. Gene expression of FGF-1 and SDF-1 was quantified using qRT-PCR. Histological validation confirmed burn severity, and flow cytometry was used to characterize E-MSCs and exosomes.Results: An increase in FGF-1 and SDF-1 expression was observed in exosome-treated groups compared to the NaCL-treated group. The 200 µL E-MSCs-treated group showed the most significant enhancement in both growth factors, with statistically significant differences (p<0.05). These findings underline the efficacy of E-MSCs in modulating critical genes involved in wound healing.Conclusion: E-MSCs significantly upregulate FGF-1 and SDF-1 expression, promoting tissue repair and regeneration in second-degree burn models. This study highlights the potential of E-MSCs as a non-invasive therapeutic approach.  Keywords: exosomes, FGF-1, mesenchymal stem cells, SDF-1
Exosome Hypoxic-MSCs, Glutathione, and Vitamin C: Effect on IL-10 Levels and CD-163 Expression Utami, Wulan Dyah; Muhar, Adi Muradi; Sumarawati, Titiek; Putra, Agung; Setiawan, Eko; Ibrahim, Sugeng; Taskworo, Dodik; Haitamy, Mohammad Nurrizki
Indonesian Journal of Pharmaceutical Science and Technology Vol 12, No 3 (2025)
Publisher : Indonesian Journal of Pharmaceutical Science and Technology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24198/ijpst.v12i3.60941

Abstract

Hyperpigmentation of the skin is a result of ultraviolet B (UVB) exposure, which causes oxidative stress due to increased reactive oxygen species (ROS), leading to various skin problems, including melanin accumulation. Exosomes can affect melanocyte activity. Exosomes, as small vesicles released by cells, can affect melanocyte activity and play an important role in various hyperpigmentation processes. The study aims to determine the effect of exosome mesenchymal stem cell hypoxia (EH-MSC) and glutathione with vitamin C on IL-10 levels and CD163 expression. IL-10 gene expression was measured using qRT-PCR, while CD163 expression was analyzed via immunohistochemical staining. A total of 30 male C57BL/6 mice were used and randomly assigned to five different treatment groups. The highest expression of IL-10 was observed in the EH-MSCs-treated group (K4), although the difference was not statistically significant compared to the control (p = 0.135). In contrast, the group receiving a combination of EH-MSCs with glutathione and vitamin C (K5) exhibited the highest percentage of CD163 expression, with a statistically significant difference (p = 0.00). These findings demonstrate that the administration of EH-MSC and glutathione with vitamin C significantly increased the expression of CD163, but insignificantly increased IL-10 in C57BL/6 mice with a UVB-induced hyperpigmentation model.
Hypoxia-Exosome Mesenchymal Stem Cells Therapy Reduces Interleukin-6 Levels and CD86 Expression Isfandiari, Adelia Bayu; Putra, Agung; Setiawan, Eko
Molecular and Cellular Biomedical Sciences Vol 9, No 3 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i3.660

Abstract

Background: UVB exposure activates type 1 macrophages (CD86) and increases IL-6, both contributing to collagen loss. exosome hypoxia mesenchymal stem cells (EH-MSC) has anti-inflammatory properties, suggesting its potential role in modulating CD86 activation and IL-6 secretion. This study examines the effects of EH-MSC injections on CD86 and IL-6 levels in UVB-exposed skin with collagen loss.Materials and methods: Experimental research post-test only control group design was conducted with 30 male Wistar rats (Rattus norvegicus, strain: Wistar Han) divided into five groups. G1: healthy rats, G2: UVB-exposed with a subcutaneous injection of 0.9% NaCl, G3: UVB-exposed with Hyaluronic Acid, and G4 & G5: UVB-exposed with EH-MSC injections of 200 µL and 300 µL, respectively. IL-6 and CD86 levels were analysed using ELISA and qRT-PCR at 14 days post-treatment continue with statistical analysis.Results: IL-6 analysis showed that levels in G4 (107.70±47.86 pg/mL) and G5 (58.68±25.37 pg/mL) were notably lower than in G2 and G3 (p<0.05). Compared to G1 (32.28±14.65 pg/mL), G4 exhibited a statistically distinct increase (p<0.05), whereas G5 showed no significant difference (p>0.05). Meanwhile, CD86 data analysis showed that G4 (0.53±0.14 pg/mL) were lower than in G1 (1.03±0.01 pg/mL) and G2 (1.47±0.43 pg/mL), but not significantly different from G3 (0.87±0.1 pg/mL) and G5 (0.36±0.08 pg/mL). Similarly, CD86 expression in G5 decreased relative to G1 and G2 (p<0.05) but remained similar to G3 and G4.Conclusion: EH-MSC injections (200 µL and 300 µL) significantly reduced IL-6 and CD86 levels in collagen loss rats, supporting its potential as a therapeutic approach for UVB-induced skin damage.Keywords: collagen loss, CD86, EH-MSC, IL-6, UVB
Exosome Therapy from Hypoxia-treated Mesenchymal Stem Cells Reduces TNF-α and Increases VEGF Levels in Fluconazole-Induced Alopecia Model Sulistami, Siska Marlina; Mulyani, Sri Priyantini; Putra, Agung; Setiawan, Eko
Molecular and Cellular Biomedical Sciences Vol 9, No 3 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i3.642

Abstract

Background: Alopecia is a condition with partial or complete hair loss, leading to psychological distress. Current treatments, such as minoxidil and finasteride, have limited efficacyand side effects. Recent studies suggest that mesenchymal stem cells (MSCs)-derived exosomes offer regenerative potential by modulating inflammation and enhancing hair follicle regeneration, though optimal dosage remains unclear. Tumor necrosis factor-alpha (TNF-α)  inhibits hair follicle growth, while vascular endothelial growth factor (VEGF) promotes hair regrowth. This study evaluates  exosome therapy from hypoxia (Hypo-Exo)-treated MSCs in modulating TNF-α and VEGF in a fluconazole-induced alopecia-like model..Materials and methods: An experimental post-test only control group design was used with 30 male Wistar rats, divided into five groups:  Healthy group, 0.9% NaCl-treated group, 5% Minoxidil-treated group, 100 μg/mL Hypo-Exo MSCs-treated group, and 200 μg/mL Hypo-Exo MSCs-treated group. TNF-α and VEGF levels were analyzed using ELISA on day 14 post-treatment. Results: The highest TNF-α level was found in the 0.9% NaCl-treated group (307.46 ± 20.68 pg/mL) and significantly reduced (p<0.05) in 100 μg/mL Hypo-Exo MSCs-treated group (65.38±15.05 pg/mL) and 200 μg/mL Hypo-Exo MSCs-treated group (37.16±7.14 pg/mL). VEGF levels were the highest in the 200 μg/mL Hypo-Exo MSCs-treated group (189.11±9.75 pg/mL) and 100 μg/mL Hypo-Exo MSCs-treated group (158.50±5.33 pg/mL), compared to the 0.9% NaCl-treated group (69.60±15.39 pg/mL). Conclusion: Hypo-Exo MSCs significantly reduced TNF-α and increased VEGF levels, supporting their potential as a novel regenerative therapy for alopecia. Keywords: alopecia, TNF-α, VEGF, exosome, hypoxia, mesenchymal stem cells 
Exosomes from Hypoxic Mesenchymal Stem Cells Enhance TGF-β Expression and Promote Collagen Regeneration in Wistar Rats with Collagen Loss Kusumawardani, Ade Ifalliah Putri; Subchan, Prasetyowati; Sumarawati, Titiek; Setiawan, Eko
Molecular and Cellular Biomedical Sciences Vol 9, No 3 (2025)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v9i3.647

Abstract

Background: Ultraviolet B (UVB) exposure triggers reactive oxygen species (ROS) formation, inhibits procollagen synthesis via the transforming growth factor-beta (TGF-β)/Smad pathway, and leads to collagen loss. Exosomes derived from hypoxia-conditioned mesenchymal stem cells (EH-MSCs) are more effective than those from normoxic MSCs due to their higher content of miRNAs and cytokines with anti-inflammatory and regenerative properties. This study aims to evaluate the effect of EH-MSC injection on TGF- β levels and collagen density in Wistar male rats with UVB-induced collagen loss. Materials and methods: This in vivo experimental study used a post-test only control group design with 30 rats, divided into five groups: Healthy group, 0.9% NaCl-treated group, hyaluronic acid (HA)-treated group, 200μL EH-MSC-treated group, and 300μL EH-MSC-treated group. TGF-β levels were analyzed using ELISA, while collagen density was assessed with Masson trichrome staining.Results: Highest mean TGF-β levels were observed in the 300μL EH-MSC-treated group (155.56±99.84 pg/mL), while the highest collagen density was found in the Healthy group (23.07±1.81 pg/mL). Mann-Whitney test indicated a significant increase (p=0.008) in TGF-β levels in treatment groups compared to the 0.9% NaCl-treated group. Post Hoc LSD Tamhane test for collagen density also showed a significant increase (p=0.000) in treatment groups compared to the 0.9% NaCl-treated group. Conclusion: EH-MSC injection significantly increased TGF-β levels and collagen density, indicating its potential for promoting skin repair in UVB-induced collagen loss.Keywords: EH-MSC, collagen loss, TGF-β, collagen density 
Hypoxic mesenchymal stem cell-derived secretome and alkaline water synergistically reduce apoptosis and insulin resistance in type 2 diabetes mellitus rat model Mawarini, Melisa Septi; Setiawan, Eko; Putra, Agung
Universa Medicina Vol. 44 No. 3 (2025): Ahead Of Print
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2025.v44.310-317

Abstract

BACKGROUNDType 2 Diabetes Mellitus (T2DM) is characterized by chronic inflammation and insulin resistance. These factors contribute to pancreatic β-cell apoptosis, reducing insulin production and impairing glucose homeostasis. This study aims to evaluate the protective effects of hypoxic mesenchymal stem cell-derived secretome (HMSCS) and alkaline water on inflammation, apoptosis, and insulin resistance in a T2DM rat model. METHODSAn experimental study was conducted involving 24 male Wistar T2DM model rats (aged 6-8 weeks, 200-250g). They were randomized into four groups: T2DM rats only as negative control (K-), T2DM rats with metformin as positive control (K+), HMSCS treatment (P1), and HMSCS plus alkaline water group (P2). Caspase-3 expression was measured to assess apoptosis levels using RT-PCR, while homeostatic model assessment for insulin resistance (HOMA-IR) was measured using ELISA. One way ANOVA followed by a post hoc LSD test were used to analyse the data. RESULTSThe P1 group (3.03 ± 1.26 a.u) and P2 group (2.93 ± 0.52 a.u.) had significantly lower caspase-3 expression compared to K- group (6.66 ± 2.76 a.u.) (p<0.05), but were not significantly different from K+ group (3.83 ± 1.61 a.u.) (p>0.05). Additionally, P2 group (6.76 ± 0.96) had a significantly lower HOMA-IR than K- group (18.92 ± 2.63) and K+ group (10.85 ± 1.39) (p<0.05), and similarly the P1 (7.71 ± 0.53) group also showed significant difference from K- and K+ groups (p<0.05). CONCLUSIONHigher doses of HMSCS and alkaline water are associated with reduced pancreatic β-cell apoptosis and improved insulin sensitivity, highlighting its potential as a novel therapeutic approach for T2DM.
Modulation of GLUT4 and FOXO1 Expression by SH-MSC and Alkaline Water in Experimental Type 2 Diabetes Mellitus Fatmawati, Dian; Putra, Agung; Setiawan, Eko
Journal of Health and Nutrition Research Vol. 4 No. 3 (2025)
Publisher : Media Publikasi Cendekia Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.56303/jhnresearch.v4i3.562

Abstract

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance, which is associated with the dysregulation of glucose transporter 4 (GLUT4) and forkhead box protein O1 (FOXO1). The secretome from hypoxia-preconditioned mesenchymal stem cells (SH-MSC) and alkaline water have been proposed as potential therapies to modulate these molecular targets and improve glycemic control; however, their combined effects remain unexplored.  Using an experimental post-test-only control group design, this study aimed to assess the possible additive effect of SH-MSC and alkaline water on the expression of GLUT4 and FOXO1 in Wistar rats with type 2 diabetes. Twenty-five male Wistar rats were split into five groups: healthy control (G1), T2DM control (G2), T2DM with metformin (G3), T2DM with SH-MSC (G4), and T2DM with SH-MSC and alkaline water (G5).  Streptozotocin and nicotinamide were utilized to induce T2DM, and qRT-PCR was used to measure the expression of GLUT4 and FOXO1 in pancreatic tissue. One-way ANOVA and a post hoc LSD test were used for statistical analysis. The findings recognized that while GLUT4 expression was decreased, T2DM induction markedly increased fasting blood glucose levels and FOXO1 expression. SH-MSC treatment significantly upregulated GLUT4 and downregulated FOXO1 equated to the control T2DM group, and while the addition of alkaline water showed a further trend of improvement, this difference was not statistically significant. These findings suggest that SH-MSC therapy effectively improves glucose metabolism by modulating GLUT4 and FOXO1 expression, with the potential for alkaline water as an adjunctive therapy in T2DM management
Co-Authors Agung Putra Agung Putra Bayu Murdalin Fatmawati, Dian Fristiani, Yeni Haitamy, Mohammad Nurrizki Hariani, Nova Putri Ibrahim, Sugeng Isfandiari, Adelia Bayu Kusumawardani, Ade Ifalliah Putri Mawarini, Melisa Septi Muhar, Adi Muradi Pramukarso, Dodik Tugasworo Pramukarso Prasetyowati Subchan, Prasetyowati Sri Priyantini Mulyani Sulistami, Siska Marlina Taskworo, Dodik Titiek Sumarawati Utami, Wulan Dyah