Wisnu Wardhana Putra
Department of Neurology, CMHC Research Center, Palembang, Indonesia

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Asiaticoside and Madecassoside from Centella asiatica Demethylate the Nrf2 Promoter and Enhance Neuroprotection In Vitro Akmal Hasan; Wisnu Wardhana Putra
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.v6i2.141

Abstract

Centella asiatica (L.) Urban (Apiaceae), known as pegagan in Indonesian Jamu and Brahmi in Ayurveda, contains triterpene saponins with reported neuroprotective properties, yet the epigenetic mechanisms remain poorly understood. This study investigated whether a triterpene-enriched fraction (TEF) standardized to asiaticoside (28.4%) and madecassoside (22.7%) modulates Nrf2/HO-1 pathway activation through promoter demethylation and histone acetylation in oxidatively stressed SH-SY5Y neuroblastoma cells. Cells were pre-treated with TEF (25, 50, 100 μg/mL) for 24 hours before H2O2 (200 μM) challenge. TEF at 100 μg/mL restored cell viability to 82.4 ± 4.3% versus 47.8 ± 4.1% in H2O2-only cells (p < 0.001, Cohen’s d = 8.22), reduced ROS to 1.52 ± 0.15-fold (p < 0.001), and upregulated Nrf2 mRNA 2.83 ± 0.21-fold and HO-1 protein 3.14 ± 0.24-fold. Bisulfite sequencing revealed dose-dependent Nrf2 promoter demethylation from 67.8 ± 4.2% to 31.2 ± 2.6% (p < 0.001), paralleled by DNMT1 suppression (2.74 to 1.12-fold) and H3K27ac enrichment (0.34 to 1.43-fold) at the Nrf2 locus. A strong inverse correlation between methylation and Nrf2 expression (r = −0.912) and closely aligned IC50 values for ROS suppression (62.4 μg/mL) and demethylation (58.7 μg/mL) support a coordinated epigenetic-transcriptional mechanism. These findings provide the first evidence that Centella asiatica triterpenes activate neuroprotective pathways through dual epigenetic remodeling, offering a molecular rationale for the traditional cognitive-enhancing applications of this ethnopharmacologically significant herb.
Bridging the Digital Divide: A Mixed-Methods Evaluation of the Efficacy, Accessibility, and Impact of Web-Based Mental Health First Aid Training for Community Health Volunteers (Kader) in Rural Indonesia Zahra Amir; Ni Made Nova Indriyani; Iis Sugandhi; Husin Sastranagara; Muhammad Rusli; Wisnu Wardhana Putra
Indonesian Community Empowerment Journal Vol. 5 No. 2 (2025): Indonesian Community Empowerment Journal
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/icejournal.v5i2.46

Abstract

Significant disparities in mental health service access persist in rural Indonesia, where community health volunteers (known as Kader) represent a vital but undertrained resource. Digital training platforms offer a scalable solution to build mental health literacy, yet their efficacy and accessibility in low-resource, digitally diverse settings remain under-evaluated. This study aimed to evaluate the efficacy, accessibility, and user experience of a novel, web-based Mental Health First Aid (MHFA) training program for Kader in rural Indonesia. We employed a convergent parallel mixed-methods design with a single-group, pre-test/post-test framework. A total of 165 Kader from 15 rural districts across North Sumatra, West Sumatra, and South Sumatra provinces were recruited. Participants completed a 4-week, self-paced, web-based MHFA course. Quantitative data were collected using the Mental Health Knowledge Questionnaire (MHKQ), the Community Attitudes toward the Mentally Ill (CAMI) scale, and the System Usability Scale (SUS) at baseline and post-intervention. Qualitative data were gathered through semi-structured focus group discussions (FGDs) with a purposive subsample of 32 participants to explore user experience and perceived impact. The intervention yielded a highly significant improvement in mental health knowledge, with mean MHKQ scores increasing from 48.5 (SD=10.2) at pre-test to 89.7 (SD=8.8) at post-test (t(164) = -35.1, p < 0.001). Stigmatizing attitudes significantly decreased, as reflected by an increase in mean CAMI scores from 55.3 (SD=12.5) to 81.4 (SD=11.9) (t(164) = -18.9, p < 0.001). The platform's usability was rated favorably, with a mean SUS score of 81.2 (SD=13.4), indicating excellent user-friendliness. Qualitative analysis revealed three primary themes: (1) Digital Empowerment and Overcoming Barriers; (2) Cultural Resonance and Practical Skill Acquisition; and (3) The Emergence of a Supported Community of Practice. In conclusion, web-based MHFA training is an effective, accessible, and well-accepted modality for empowering Kader in rural Indonesia. This digital approach successfully bridges geographical and educational divides, significantly enhancing mental health literacy and reducing stigma. Scaling this model holds immense potential for strengthening community-based mental health services and narrowing the treatment gap in Indonesia and similar low- and middle-income countries.