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Addition of Beetroot Extract to Neoadjuvant Adriamycin Cyclophosphamide Regimen Increased Tumor Cell Apoptosis in Mammary Adenocarcinoma Rats Susilowati, Sri; Susilaningsih, Neni; Suharti, Catharina
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev12iss3pp130-136

Apoptosis is one of the anticancer targets. Currently, the concomitant use of phytotherapy products and chemotherapy regimens is common in breast cancer patients. The purpose of this study was to examine the apoptotic effect of adding beetroot extract to the neoadjuvant Adriamycin Cyclophosphamide (AC) regimen by observing the expression levels of p53 and caspase 3 in tumor tissue from mammary adenocarcinoma rats. Twenty-four rats that succeeded in growing tumor nodules were randomly divided into 4 treatment groups: without treatment, AC only treatment, AC plus beetroot extract at dose of 25 and 100 mg/kg BW, respectively. AC was given 4 cycles in doses of 5 and 50 mg/kg body weight intraperitoneally every week. Tumor tissue was dissected at 4th week for examination of p53 and caspase 3 expression levels using the qRT-PCR method. The addition of beetroot extract at doses of 25 and 100 mg/kg BW in the neoadjuvant AC regimen showed significantly higher levels of p53 and caspase 3 expression than those with AC treatment alone. These results proved that beetroot extract has a synergistic effect with neoadjuvant AC regimen by increasing tumor cells apoptosis.Keywords: Beetroot extract, Adriamycin, Cyclophosphamide, apoptosis, p53.

Healing of Radiation Dermatitis with Ozonated Aloe Vera Oil by Increasing PDGF and Epidermal Thickness in Sprague-Dawley Rats Utami, Widoasti Putri; , Yan Wisnu Prajoko; Prihharsanti, Christina H.N.; Sadhana, Udadi; Susilaningsih, Neni; Restiwijaya, Maryam; Nur, Muhammad
Folia Medica Indonesiana Vol. 58, No. 4
Publisher : Folia Medica Indonesiana

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Highlights: • This study demonstrated the effect of ozonated Aloe vera oil in the healing of radiation dermatitis wound. • Groups that received no treatment was compared with groups that received treatment using 2.5% hydrocortisone ointment and ozonated Aloe vera. • Ozonated Aloe vera oil improves the healing of radiation dermatitis wound by increasing PDGF expression and epidermal thickness. Abstract : The long-term use of corticosteroids as a standard treatment for skin disorders, such as radiation dermatitis, can cause many side effects. Alternatively, ozonated Aloe vera oil may replace corticosteroids due to its fewer side effects and benefits in wound healing process. Re-epithelialization and the formation of growth factors, such as platelet-derived growth factor (PDGF), play an important role in the healing of dermatitis wound. This study intended to demonstrate the effect of ozonated Aloe vera oil to improve the healing of radiation dermatitis wound by increasing PDGF expression and epidermal thickness. This study used a post-test only control group design. A sample of 36 Sprague-Dawley rats was divided into 6 groups (C1=without treatment, C2=2.5% hydrocortisone ointment, P1=pure Aloe vera (AV), P2=300 mg/mL ozonated Aloe vera (OAV), P3=600 mg/mL OAV, P4=1200 mg/mL OAV. The expression of PDGF was assessed using Allred scoring with immunohistochemical staining, whereas the epidermal thickness was assessed using hematoxylin and eosin (H&E) staining at 400x microscopic magnification. The PDGF expression and epidermal thickness between the control and the treatment groups showed significant differences using a Kruskal-Wallis test (P=0.001) and one-way ANOVA test (P<0.001). The groups that was given ozonated Aloe vera oil had higher average of PDGF expression and thicker epidermis than the other groups. The Spearman's correlation test showed a strong positive relationship (p<0.001 and r=0.709) between the two variables. In conclusion, ozonated Aloe vera oil improves healing of radiation dermatitis wound by increasing PDGF expression and epidermal thickness.

Soursop Leaf Extract Reduces AST, ALT, Bilirubin Levels, and Liver Damage Scores in Sorafenib-treated Wistar Rats with Hepatocellular Carcinoma Susilaningsih, Neni; Prajoko, Yan Wisnu; Budijitno, Selamat; Prabowo, Erik; Istiadi, Hermawan; Muniroh, Muflihatul; Riwanto, Ignatius
The Indonesian Biomedical Journal Vol 18, No 1 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i1.3883

BACKGROUND: Sorafenib, the standard therapeutic agent for advanced hepatocellular carcinoma (HCC), may induce hepatic dysfunction, thereby necessitating adjunctive therapy to mitigate this adverse effect. While preliminary research has suggested that Soursop (Annona muricata) leaves exhibit anti-tumor and hepatoprotective properties, their efficacy in mitigating liver damage associated with sorafenib treatment remains unexplored. This study was conducted to assess the liver-protective effects of soursop leaf extract in Wistar rats receiving sorafenib for HCC treatment.METHODS: Ethanol extract of soursop leaves was prepared using the maceration method. Twenty-nine Wistar rats were divided into five groups: healthy control (HC) group, HCC groups receiving no treatment, sorafenib only, sorafenib + 50 mg/kgBW/day soursop extract, and sorafenib + 100 mg/kgBW/day soursop extract. All groups, except the HC group, were given Diethyl Nitrosamine (DEN) to cause HCC. Following a two-week treatment period, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed using colorimetric methods, while total bilirubin was assessed using diazo with sulphanilic acid method. From histopathological specimen, relative liver weight was measured and liver damage score was assessed using Hematoxylin and Eosin.RESULTS: Administration of sorafenib resulted in a reduction of AST, ALT, total bilirubin, relative liver weight, and liver damage scores. Furthermore, the combined administration of sorafenib with soursop leaf extract at dosages of 50 and 100 mg/kgBW/day led to a dose-dependent amelioration of these indicators. The most pronounced improvement was observed with the highest dose of soursop extract, which significantly reduced AST, ALT, total bilirubin, relative liver weight, and liver damage scores compared to the sorafenib-only group.CONCLUSION: Soursop leaf extract at 100 mg/kgBW/day effectively reduced AST, ALT, bilirubin levels, and liver damage score in sorafenib-treated Wistar rats with HCC, indicating its hepatoprotective effects. These findings suggest that soursop leaf extract may be a promising adjuvant therapy for mitigating sorafenib-induced hepatotoxicity in HCC treatment.KEYWORDS: Annona muricata, hepatocellular carcinoma, sorafenib, AST, ALT, bilirubin, hepatoprotective

Therapeutic Potential of Curcumin in Modulating the HMGB1/TLR4/NF-κB Axis in Polymicrobial Peritonitis: A Systematic Review and Dose-Response Meta-Analysis Leonardo Aaron Hartanto; Neni Susilaningsih; Erik Prabowo
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 2 (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.v10i2.1516

Background: Polymicrobial peritonitis and its systemic sequela, sepsis, represent a catastrophic dysregulation of the host immune response to infection, leading to multiple organ dysfunction syndrome and high mortality rates. The pathophysiology is driven by a hyperinflammatory cytokine storm followed by immunoparalysis, governed centrally by the high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling axis. Curcumin, a polyphenolic compound derived from Curcuma longa, has demonstrated potent immunomodulatory properties. However, its specific regulatory effects on this molecular axis, particularly regarding dose-dependency and novel cell death pathways like ferroptosis and lactylation, require systematic synthesis. Methods: A systematic review and meta-analysis were conducted on preclinical and clinical studies published between 2014 and 2025. Ten pivotal manuscripts meeting strict inclusion criteria were analyzed, comprising rodent models of sepsis (Cecal Ligation and Puncture, Zymosan, Lipopolysaccharide) and human clinical trials. Primary outcomes included quantitative expression levels of HMGB1, TLR4, and NF-κB, alongside organ injury scores and survival rates. Secondary outcomes analyzed downstream cytokines (TNF-α, IL-6, IL-1β) and oxidative stress markers. Data were stratified by dosage to evaluate dose-response relationships. Results: The analysis included data from 218 subjects. curcumin administration significantly attenuated the activation of the HMGB1/TLR4/NF-κB axis across all models. Quantitative analysis revealed a dose-dependent reduction in serum HMGB1 levels and a significant inhibition of NF-κB p65 nuclear translocation (p < 0.001). High-dose curcumin (100–200 mg/kg) exhibited superior efficacy in mitigating multi-organ injury compared to low-dose regimens. Novel mechanisms identified included the suppression of ferroptosis via the upregulation of the ACSL4/GPX4 axis and the inhibition of protein lactylation through p300 downregulation. Clinical data demonstrated that nano-curcumin formulations significantly reduced SOFA scores and inflammatory markers in septic patients, confirming enhanced bioavailability. Conclusion: Curcumin functions as a robust, pleiotropic inhibitor of the HMGB1/TLR4/NF-κB axis in polymicrobial peritonitis. Its therapeutic efficacy is dose-dependent and involves the regulation of emerging epigenetic and cell death pathways. These findings support the clinical integration of nano-curcumin as an adjuvant therapy for surgical sepsis.

Therapeutic Potential of Curcumin in Modulating the HMGB1/TLR4/NF-κB Axis in Polymicrobial Peritonitis: A Systematic Review and Dose-Response Meta-Analysis Leonardo Aaron Hartanto; Neni Susilaningsih; Erik Prabowo
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 2 (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.v10i2.1516

Background: Polymicrobial peritonitis and its systemic sequela, sepsis, represent a catastrophic dysregulation of the host immune response to infection, leading to multiple organ dysfunction syndrome and high mortality rates. The pathophysiology is driven by a hyperinflammatory cytokine storm followed by immunoparalysis, governed centrally by the high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling axis. Curcumin, a polyphenolic compound derived from Curcuma longa, has demonstrated potent immunomodulatory properties. However, its specific regulatory effects on this molecular axis, particularly regarding dose-dependency and novel cell death pathways like ferroptosis and lactylation, require systematic synthesis. Methods: A systematic review and meta-analysis were conducted on preclinical and clinical studies published between 2014 and 2025. Ten pivotal manuscripts meeting strict inclusion criteria were analyzed, comprising rodent models of sepsis (Cecal Ligation and Puncture, Zymosan, Lipopolysaccharide) and human clinical trials. Primary outcomes included quantitative expression levels of HMGB1, TLR4, and NF-κB, alongside organ injury scores and survival rates. Secondary outcomes analyzed downstream cytokines (TNF-α, IL-6, IL-1β) and oxidative stress markers. Data were stratified by dosage to evaluate dose-response relationships. Results: The analysis included data from 218 subjects. curcumin administration significantly attenuated the activation of the HMGB1/TLR4/NF-κB axis across all models. Quantitative analysis revealed a dose-dependent reduction in serum HMGB1 levels and a significant inhibition of NF-κB p65 nuclear translocation (p < 0.001). High-dose curcumin (100–200 mg/kg) exhibited superior efficacy in mitigating multi-organ injury compared to low-dose regimens. Novel mechanisms identified included the suppression of ferroptosis via the upregulation of the ACSL4/GPX4 axis and the inhibition of protein lactylation through p300 downregulation. Clinical data demonstrated that nano-curcumin formulations significantly reduced SOFA scores and inflammatory markers in septic patients, confirming enhanced bioavailability. Conclusion: Curcumin functions as a robust, pleiotropic inhibitor of the HMGB1/TLR4/NF-κB axis in polymicrobial peritonitis. Its therapeutic efficacy is dose-dependent and involves the regulation of emerging epigenetic and cell death pathways. These findings support the clinical integration of nano-curcumin as an adjuvant therapy for surgical sepsis.

EFFECTIVENESS OF SILVER SULFADIAZINE ON WOUND HEALING AND INFECTION IN SPRAGUE DAWLEY RATS Almeric Rosali; Bernardus Parish Budiono; Neni Susilaningsih; Yora Nindita; Endang Mahati
Jurnal Kedokteran Diponegoro (Diponegoro Medical Journal) Vol 15, No 5 (2026): JURNAL KEDOKTERAN DIPONEGORO (DIPONEGORO MEDICAL JOURNAL)
Publisher : Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14710/dmj.v15i5.49093

Background: Surgical Site Infections (SSIs) are postoperative infections categorized into superficial, deep, and organ/ space infections, mostly caused by endogenous bacteria. Silver sulfadiazine as topical antimicrobial are widely used, though its effectiveness in SSIs remains unproven. Current research focuses on its impact on lymphocyte and collagen levels in animal models to better understand its role in SSI management. Objective: This study aimed to verify the use of silver sulfadiazine in Sprague Dawley rat models in improving healing process of SSIs. Methods: The study used a post-test only control group design to evaluate wound treatments on infected wound in rats. Thirty rats were divided into three groups: negative control (0.9% NaCl), positive control (0.9% NaCl + gentamicin), and treatment (0.9% NaCl + silver sulfadiazine). Standard wounds were treated accordingly and on day 14, tissue samples were analyzed for fibroblasts, neutrophils, macrophages, collagen, and wound diameter. Data were analyzed using One-Way ANOVA or Kruskal-Wallis for significant differences (p < 0.05). Results: Study showed treatment group had significantly higher fibroblast (p = 0.04), neutrophil (p = 0.00), and macrophage counts (p = 0.00), as well as collagen levels (p = 0.00), compared to both positive and negative control group. Wound size in treatment group was also significantly smaller. Conclusion: Silver sulfadiazine significant reduced fibroblast, neutrophil, macrophage, and collagen counts, as well as wound size.

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