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All Journal Eureka Herba Indonesia Scientific Journal of Pediatrics Sriwijaya Journal of Internal Medicine
Vania Delma
Department of Nursing, Brasilia Familia Clinic, Brasilia, Brazil
Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Nursing Public Health

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Network-Pharmacology-Guided Validation of Phyllanthus niruri Nephroprotection Against Doxorubicin: An In Vitro–In Vivo Translational Study Rachmat Hidayat; Vania Delma; Indri Yani Septiana
Eureka Herba Indonesia Vol. 6 No. 2 (2025): Eureka Herba Indonesia
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v6i2.140

Abstract

Doxorubicin is a corner-stone anthracycline chemotherapeutic whose clinical utility is constrained by dose-limiting nephrotoxicity, and no approved pharmacological prevention currently exists. Phyllanthus niruri L. (Family Phyllanthaceae) — locally known in Indonesia as meniran — is a phytotherapeutic herb whose constituents (phyllanthin, hypophyllanthin, quercetin, rutin, gallic acid, and corilagin) target oxidative-stress and inflammatory pathways implicated in doxorubicin renal injury. We applied a tiered translational design: (i) network-pharmacology discovery using SwissTargetPrediction, TCMSP, GeneCards, and OMIM intersected six P. niruri active compounds with 842 nephrotoxicity-associated genes, identifying six hub targets (TNF, IL6, NFKB1, CASP3, BAX, BCL2) and four enriched KEGG pathways (TNF signaling, MAPK, PI3K-Akt, Apoptosis); (ii) in vitro validation in HK-2 human proximal tubular cells exposed to doxorubicin (2 µM, 24 h) with or without standardised P. niruri 70% ethanolic extract (25, 50, 100 µg/mL); and (iii) in vivo validation in 48 male Sprague-Dawley rats (eight per arm) given a single intraperitoneal dose of doxorubicin (15 mg/kg) and oral P. niruri at 100, 200, or 400 mg/kg/day for 14 days. P. niruri produced a dose-dependent rescue of HK-2 viability (84.6% at 100 µg/mL versus 41.8% in doxorubicin-only controls; p < 0.001) and reduced serum creatinine, blood urea nitrogen, urinary KIM-1, and NGAL by 55–70% at the 400 mg/kg dose with concordant restoration of glutathione and superoxide dismutase. Network-pharmacology hub targets showed transcriptionally coherent modulation. The findings support standardised P. niruri ethanolic extract as a mechanism-anchored herbal candidate for adjunctive prevention of doxorubicin-induced kidney injury, warranting clinical translation.
Apoptotic Induction and Cell-Cycle Arrest in Triple-Negative Breast Cancer Cells by Annona muricata Acetogenin Fractions: An In Silico and In Vitro Study Lestini Wulansari; Leonardo Simanjuntak; Vania Delma
Eureka Herba Indonesia Vol. 6 No. 2 (2025): Eureka Herba Indonesia
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v6i2.142

Abstract

Triple-negative breast cancer (TNBC) is an aggressive molecular subtype that lacks oestrogen, progesterone and HER2 receptors and retains cytotoxic chemotherapy as its principal systemic option, creating a rationale for adjunctive phytotherapy. Annona muricata L. (Annonaceae), known in Indonesia as sirsak, contains Annonaceous acetogenins with well-documented mitochondrial and apoptotic activity. This study integrated molecular docking with in vitro pharmacology to characterise the anticancer effects of an HPLC-standardised acetogenin-enriched fraction (AEF) from Indonesian A. muricata leaves on TNBC cells. Annonacin, bullatacin, squamocin and muricatacin were docked against EGFR, Bcl-2, CDK2, caspase-3 and topoisomerase II-α (AutoDock Vina); AEF was tested on MDA-MB-231 and MDA-MB-468 TNBC cells with MCF-10A non-tumorigenic controls (n = 6 independent biological replicates per arm). Outcomes included viability (MTT), apoptosis (Annexin-V/PI), cell-cycle distribution (propidium iodide), caspase-3/7 luminescence, Western blotting (Bcl-2, Bax, cleaved caspase-3, cyclin D1, p21) and mitochondrial ΔΨm/ROS. Bullatacin showed the strongest binding to Bcl-2 (ΔG = −9.6 kcal/mol) and caspase-3 (ΔG = −8.9 kcal/mol). AEF inhibited MDA-MB-231 viability with IC50 12.4 µg/mL (95% CI 10.8–14.1) and yielded a selectivity index of 4.20 over MCF-10A. Apoptotic cells increased 4.62-fold, the G1 fraction rose from 41.2% to 64.8% (p < 0.001), caspase-3/7 activity rose 3.81-fold and the Bcl-2/Bax ratio decreased by 61%. In conclusion, bullatacin-rich Annona muricata acetogenins selectively induce intrinsic apoptosis and G1 arrest in TNBC cells, supporting their further translational development as Indonesian phytotherapeutic leads for hormone-refractory breast cancer.
Non-Invasive Neuromodulation for Drug-Resistant Epilepsy in Children: A Randomized Controlled Trial of Transcranial Magnetic Stimulation (TMS) versus Vagus Nerve Stimulation (VNS) in Jakarta, Indonesia Febria Suryani; Rinna Azrida; Linda Purnama; Vania Delma; Desiree Montesinos
Scientific Journal of Pediatrics Vol. 3 No. 1 (2025): Scientific Journal of Pediatrics
Publisher : Phlox Institute: Indonesian Medical Research Organization

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59345/sjped.v2i2.173

Abstract

Introduction: Drug-resistant epilepsy (DRE) significantly impacts the quality of life in children. While vagus nerve stimulation (VNS) is an established treatment, repetitive transcranial magnetic stimulation (rTMS) offers a non-invasive alternative. This study aimed to compare the efficacy and safety of rTMS versus VNS in a pediatric DRE population in Jakarta, Indonesia. Methods: This was a single-center, randomized, controlled, open-label trial conducted at Private Hospital, Jakarta. Children aged 5-18 years with DRE, defined as failure to achieve seizure freedom despite adequate trials of two appropriate antiepileptic drugs (AEDs), were randomly assigned (1:1) to receive either rTMS or VNS. The primary outcome was the percentage reduction in seizure frequency at 6 months post-intervention compared to baseline. Secondary outcomes included responder rate (≥50% seizure reduction), quality of life (QoL) using the PedsQL, cognitive function (using standardized neuropsychological tests), and adverse events. Results: A total of 60 children were randomized (30 rTMS, 30 VNS). At 6 months, the mean percentage reduction in seizure frequency was significantly greater in the rTMS group (48.5%, SD 15.2%) compared to the VNS group (35.2%, SD 12.8%) (p = 0.001). Responder rates were 63.3% for rTMS and 46.7% for VNS (p = 0.17). PedsQL scores showed a significant improvement in the rTMS group compared to baseline in the psychosocial health summary score (p = 0.005), but not the VNS group (p=0.1). No significant differences were observed in cognitive function between the groups. Adverse events were generally mild and transient in both groups, though VNS was associated with more voice alteration and coughing. Conclusion: rTMS demonstrated superior efficacy in reducing seizure frequency compared to VNS in this Indonesian pediatric DRE population. While VNS is an established method, rTMS may present a non-invasive and potentially more effective therapeutic alternative. Further, larger, multicenter studies are warranted to confirm these findings and explore long-term outcomes.
Cardiovascular Risk Stratification in Pregnant Women with Gestational Diabetes: A Comparative Analysis of Predictive Models in Padang, Indonesia Cinthya Callathea; Vania Delma; Muhammad Rusli; Bjorka Alma; Rinna Azrida
Sriwijaya Journal of Internal Medicine Vol. 3 No. 1 (2025): Sriwijaya Journal of Internal Medicine
Publisher : Phlox Institute: Indonesian Medical Research Organization

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59345/sjim.v2i2.177

Abstract

Introduction: Gestational diabetes mellitus (GDM) significantly increases the risk of both short-term and long-term cardiovascular disease (CVD) in women. Effective risk stratification during pregnancy is crucial for targeted interventions. This study aimed to compare the performance of established cardiovascular risk prediction models in a cohort of pregnant women with GDM in Padang, Indonesia. Methods: A prospective cohort study was conducted involving 350 pregnant women diagnosed with GDM at two major hospitals in Padang, Indonesia, between January 2022 and June 2023. Baseline demographic, clinical, and laboratory data were collected. Three established CVD risk prediction models – the Framingham Risk Score (FRS), the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equations (PCE), and a modified version of the PCE adapted for GDM (PCE-GDM) – were applied to calculate individual 10-year CVD risk scores. The primary outcome was the development of any major adverse cardiovascular event (MACE), defined as myocardial infarction, stroke, or cardiovascular death, or new-onset hypertension requiring medication, within one year postpartum. Model performance was assessed using discrimination (c-statistic) and calibration (Hosmer-Lemeshow goodness-of-fit test). Results: The mean age of participants was 32.4 ± 5.1 years. The prevalence of pre-existing hypertension was 8.6%, and the mean pre-pregnancy BMI was 28.5 ± 4.7 kg/m². During the one-year follow-up, 25 (7.1%) women experienced a MACE. The PCE-GDM model demonstrated the best discrimination (c-statistic = 0.82, 95% CI 0.76-0.88), followed by the PCE (c-statistic = 0.75, 95% CI 0.68-0.82), and the FRS (c-statistic = 0.68, 95% CI 0.60-0.76). The PCE-GDM also showed good calibration (χ² = 8.3, p = 0.41), while the FRS and PCE tended to underestimate risk (χ² = 18.5, p = 0.02 and χ² = 15.2, p = 0.06, respectively). Conclusion: The PCE-GDM model, specifically adapted for GDM, showed superior performance in predicting short-term cardiovascular risk compared to traditional models in this Indonesian cohort. These findings highlight the need for GDM-specific risk stratification tools to improve cardiovascular risk management in this vulnerable population.
Co-Authors Bjorka Alma Cinthya Callathea Desiree Montesinos Febria Suryani Indri Yani Septiana Leonardo Simanjuntak Lestini Wulansari Linda Purnama Muhammad Rusli RACHMAT HIDAYAT Rinna Azrida