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Effectiveness of Andrographis paniculata Extract Nanoparticle on The Expression of CD4+ and CD8+ of Rats Listeriosis Iffiyana, Alifatul; Farida, Helmia; Susilaningsih, Neni
El-Hayah:Jurnal Biologi Vol 10, No 2 (2025): EL-HAYAH (VOL 10, NO 2 Maret 2025)
Publisher : Program Study of Biology, Science and Technology Faculty, UIN Maulana Malik Ibrahim Malang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18860/elha.v10i2.32207

Listeria monocytogenes is a Gram-positive bacterium that causes listeriosis known as foodborne disease. L. monocytogenes infection will activate both innate and adaptive immune responses. Androghrapis paniculata has an effect as immunostimulant. Nanocapsulation-chitosan can increase solubility and reduce the particle size making it easier for compounds to enter the cell. This research focuses on the utilization of nanoparticle A. paniculata as an immunomodulator against CD4+ and CD8+. Study design was an experimental study with post only control group trial. A total of 30 male Wistar rats divided into 6 groups, with 5 rats in each group. All groups were injected by L. monocytogenes intravenous except Normal Group. EAP 200 group was administered oral crude extract of A. paniculata at dose 200 mg/kg BW for 7 days. nEAP 100, nEAP 200 and nEAP 400 groups were administered oral Nanoparticle-Extract of A. paniculata at dose of 100 mg/kg BW, 200 mg/kg BW, and 400 mg/kg BW respectively for 7 days. CD4+ and CD8+ cells were detected by isolating PBMC cells then analyzed using flow cytometry. Statistical analysis applied ANOVA. Both crude extract of EAP 200 and nanoparticles nEAP 400 significantly increase the number of CD4+ (P= 0.050) and CD8+ (P= 0.010). Crude and nanoparticles extract of A. paniculata increase the production of CD4+ and CD8+ cells in rats infected with L. monocytogenes.

Mapping the Research Landscape of Natural Compounds for Tuberculosis Treatment: A Bibliometric Approach Hakam, Abdul; Susilaningsih, Neni; Mexitalia, Maria; Susanto, Hardhono; SyarofilAnam, Moh.
Jurnal Locus Penelitian dan Pengabdian Vol. 4 No. 5 (2025): JURNAL LOCUS: Penelitian & Pengabdian
Publisher : Riviera Publishing

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.58344/locus.v4i5.3981

Tuberculosis (TB) remains a global health crisis, exacerbated by rising drug resistance in Mycobacterium tuberculosis. While conventional therapies like BPaL/BPaLM regimens and shorter rifapentine-based treatments show promise 11–33, the need for novel anti-TB agents persists. Natural compounds, particularly from biodiverse regions like Indonesia 77, offer untapped potential, yet prior bibliometric analyses lack comprehensive integration of computational and multi-omics approaches to guide future research. This study maps the research landscape of natural compounds for TB treatment (2015–2025) through bibliometric analysis, identifying gaps and proposing AI-driven, multi-disciplinary strategies to accelerate drug discovery. PubMed-derived data (23 articles) were analyzed using VOSviewer to visualize co-authorship, keyword co-occurrence, and thematic clusters. Trends in authorship, geographic contributions, and research foci (e.g., molecular docking, drug resistance) were evaluated. China dominated research output (11/23 studies), with clusters emphasizing computational methods (e.g., virtual screening), bacterial enzymes, and animal models. Keyword analysis revealed a strong focus on drug resistance and synergism, yet limited exploration of AI, multi-omics, or ethnopharmacology. Notably, studies like Romulo et al. (2018) highlighted Indonesian plants’ anti-TB potential 77, but systematic integration with modern technologies remains underexplored. This study identifies a critical gap: the need to merge traditional natural compound research with AI-aided drug design, multi-omics (e.g., transcriptomics 1616), and nanodelivery systems. By proposing a framework that bridges computational predictions (e.g., molecular docking 1515) with experimental validation, this research advances a novel, scalable approach to combat drug-resistant TB, leveraging global biodiversity and cutting-edge technologies.

Andrographis paniculata Leaves Extract Inhibit TNF-α and Caspase-3 Expression of Septic Rats’ Intestinal Tissues Ardika, Ryco Giftyan; Budiono, Bernardus Parish; Widiastiti, Nyoman Suci; Maharani, Nani; Susilaningsih, Neni; Sandra, Ferry
The Indonesian Biomedical Journal Vol 16, No 1 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i1.2727

BACKGROUND: Microcirculation and cellular disturbances caused by sepsis might trigger significant intestinal damage. Andrographis paniculata extract decreases inflammatory intestinal epithelial cells with its role as an antiparasitic and anti-inflammatory agent. However, A. paniculata extract’s effect on sepsis have not been commonly studied, especially in the intestinal tissues. Therefore, this study was conducted to determine A. paniculata leaves extract (APLE) effect in sepsis-induced intestinal tissues of rats by examining the expression of inflammatory cytokines involved in sepsis, namely tumor necrosis factor (TNF)-α and Caspase-3.METHODS: Rats were divided into five groups; two groups received no pretreatment and the other three groups received 200, 400, and 500 mg/kg BW/day APLE, respectively. Three pretreated groups and one group with no pretreatment were then injected with 1 mg/200 g BW lipopolysaccharides (LPS) intraperitoneally to create septic rat models. Three days after the LPS-induction, rats were euthanized and the expression of TNF-α and Caspase-3 were assessed based on the immunohistochemical staining of rats’ intestinal tissues.RESULTS: Compared with NaCl (sham), LPS significantly (p<0.001) induced TNF-α expression from 6.60±1.36 to 25.37±1.74. Pretreatment of 200, 400, and 500 mg/kg BW/day APLE could significantly (p<0.001) inhibit the LPS-induced TNF-α expression (18.82±1.36, 11.45±1.18, and 6.89±1.90, respectively). Similar with TNF-α, compared with NaCl (sham), LPS significantly (p<0.001) induced Caspase-3 expression from 6.92±1.66 to 23.59±2.25. Pretreatment of 200, 400, and 500 mg/kg BW/day APLE could significantly (p<0.001) inhibit the LPS-induced Caspase-3 expression (17.47±1.68, 12.99±1.51, and 5.59±1.51, respectively).CONCLUSION: The pretreatment of APLE could inhibit the LPS-induced TNF-α and Caspase-3 expression, therefore APLE could be suggested as a potential sepsis-preventing agent.KEYWORDS: Andrographis paniculata, sepsis, TNF-α, Caspase-3, lipopolysaccharide

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

Show Abstract | Download Original | Original Source | Check in Google Scholar

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.

Lycopene Improves the Metformin Effects on Blood Glucose and Neutrophil Counts in Type 2 Diabetic Rats Sianturi, Medina; Susilaningsih, Neni; Nugroho, Heri; Suryani, Maria
JURNAL INDONESIA DARI ILMU LABORATORIUM MEDIS DAN TEKNOLOGI Vol 5 No 1 (2023): Step up to strengthen the laboratory system and prepare for patients care
Publisher : Universitas Nahdlatul Ulama Surabaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33086/ijmlst.v5i1.3865

In patients with type 2 diabetes mellitus (T2DM), both innate and acquired immunity are weakened by hyperglycemia. Lycopene is one of the hydrocarbon carotenoids that has been widely studied for its powerful antioxidant and anti-inflammatory properties, furthermore act as hypoglycemic and immunomodulator. Herein, we investigated the effect of lycopene and metformin combination on fasting blood glucose (FBG) and neutrophil counts. The rats were divided randomly into six groups, each containing five rats. Group 1 consisted of normal rats (N) and group 2, T2DM (DM) rats, which were administered 0.5 mL of coconut oil; group 3 T2DM rats were administered 250 mg/kg of metformin in 0.5 mL of coconut oil; groups 4,5 and 6 rats were administered a combination of metformin 250 mg/kg with 10 mg/kg (DML-10), 20 mg/kg (DML-20) and 40 mg/kg (DML-40) of lycopene in 0.5 mL of coconut oil, respectively. Treatment was administered every day for 28 days. A model of T2DM rats was induced by a high-fat diet for two weeks combined with streptozotocin–nicotinamide. Data were analyzed with a one-way ANOVA test followed by the least significant difference (LSD) test. There were significant differences in FBG levels and the number of neutrophils in all groups. Lycopene combined with metformin had lower FBG concentrations and higher neutrophil counts compared to metformin monotherapy (p<0.001), and these observations were dose-dependent. Lycopene combined with metformin can improve blood glucose and neutrophil counts in rats with diabetes. The highest effect was observed in combination with lycopene at a dose of 40 mg/kg and metformin at a dose of 250 mg/kg.

The Effect of Nanoparticles Andrographis paniculata (Sambiloto) Extract on IL-10 and TNF-α Levels in Wistar Rats Infected with Listeria monocytogenes Ulfa, Firdanianti; Farida, Helmia; Susilaningsih, Neni
Smart Medical Journal Vol 8, No 1 (2025): April
Publisher : Faculty of Medicine Universitas Sebelas Maret

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.13057/smj.v8i1.99782

Introduction: World Health Organization (WHO) determines Listeria monocytogenes as one of the four major bacteria that cause foodborne disease. During L. monocytogenes infection, TNF-α with IFN-γ activates macrophages for the inflammatory process. In the middle of infection, NK cells produce IL-10 to prevent excessive inflammation. Andrographis paniculata (sambiloto in Indonesia) has been known as a traditional medicine for generations. It has been previously known that administration of A. paniculata to mice with rheumatoid arthritis showed an increase in IL-10 cytokine activity in spleen samples. In addition, it also downregulates the production of inflammatory mediators such as Nitric Oxide (NO) and TNF-α. The extracts are converted into nano-sized particles to be easily absorbed by cells, thus allowing the delivery of active substances to the targeted location. This study aims to determine A. paniculata's effect on IL-10 and TNF-α cytokines in rats infected with L. monocytogenes.Methods: This study used 30 male Wistar rats infected with L. monocytogenes (except in the normal group). The animals were divided into 6 groups, i.e. Normal group, Negative Control group (K-), EAP200, nEAP100, nEAP200, and nEAP400. Crude extract of A. paniculata 200 mg/kg BW, nanoparticles of A. paniculata extract 100 mg/kg BW, 200 mg/kg BW, and 400 mg/kg BW were administered for 7 days to the EAP200, nEAP100, nEAP200, and nEAP400 groups, respectively.Results: The IL-10 and TNF-α levels in EAP200, nEAP100, nEAP200, and nEAP400 were significantly lower than the K- group. The lowest levels of IL-10 and TNF-α were in the nEAP400 group.Conclusion: Administration of A. paniculata extract nanoparticles decreased IL-10 and TNF-α levels in infected Wistar rats. The lowest levels of IL-10 and TNF-α were found in the nanoparticle group which received 400 mg/kg BW.

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