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Eureka Herba Indonesia
Published by HM Publisher
ISSN : -     EISSN : 27465152     DOI : https://doi.org/10.37275/ehi.v1i1.1
Core Subject : Health,
Medicine & Pharmacology
Eureka Herba Indonesia (EHI) is peer review scientific journal that focused on reserach in exploration potential Herba of Indonesia for enhancing healthy. EHI focused on : 1. Medicinal Plants. 2. Efficacy of Herba Study. 3. Safety of Herba Study. 4. Animals that potential for developing as healthy products. 5. Minerals that potential for developing as healthy products.
Arjuna Subject : Kedokteran - Kedokteran Komplemen dan Alternatif
Articles 121 Documents
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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 in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v6i2.141

Abstract

Background: Centella asiatica (L.) Urban (Apiaceae), known as pegagan in Indonesian Jamu and as Mandukaparni (regionally Brahmi) in Ayurveda, contains triterpene saponins with reported neuroprotective properties, yet the epigenetic mechanisms underlying these effects remain poorly understood. Objective: This study investigated whether a triterpene-enriched fraction (TEF) standardized to asiaticoside (28.4%) and madecassoside (22.7%) modulates activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway through promoter demethylation and histone acetylation in oxidatively stressed SH-SY5Y neuroblastoma cells. Methods: Cells were pre-treated with TEF (25, 50, and 100 μg/mL) for 24 h before H2O2 (200 μM) challenge. Cell viability, reactive oxygen species (ROS), Nrf2 and HO-1 expression, Nrf2 promoter methylation (bisulfite sequencing), DNA methyltransferase 1 (DNMT1) protein, and histone H3 lysine-27 acetylation (H3K27ac) at the Nrf2 promoter were quantified. Results: 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. Conclusion: 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.
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 in collaboration with CMHC Research Center

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

Abstract

Background: Triple-negative breast cancer (TNBC) is an aggressive molecular subtype that lacks oestrogen, progesterone and human epidermal growth factor receptor 2 (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. Objective: This study integrated molecular docking with in vitro pharmacology to characterise the anticancer effects of a high-performance liquid chromatography (HPLC)-standardised acetogenin-enriched fraction (AEF) from Indonesian A. muricata leaves on TNBC cells. Methods: Annonacin, bullatacin, squamocin and muricatacin were docked against epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), cyclin-dependent kinase 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 (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT), apoptosis (Annexin-V/propidium iodide, PI), cell-cycle distribution (PI), caspase-3/7 luminescence, Western blotting (Bcl-2, Bax, cleaved caspase-3, cyclin D1 and p21) and mitochondrial transmembrane potential (ΔΨm)/reactive oxygen species (ROS). Results: 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 an IC50 of 12.4 µg/mL (95% confidence interval [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%. 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.
Tinospora crispa Phytosome Enhances Oral Bioavailability and Glycemic Control in Streptozotocin-Induced Diabetic Rats Dedi Sucipto; Taufiq Indera Jayadi; Bryan Helsey
Eureka Herba Indonesia Vol. 7 No. 1 (2026): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v7i1.143

Abstract

Background: Diabetes mellitus remains a major global health challenge with rising prevalence in Southeast Asia, where traditional herbal remedies continue to play a significant role in disease management. Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae), known locally as brotowali in Indonesian jamu medicine, exhibits anti-diabetic properties attributed to its alkaloid and diterpenoid constituents; however, the oral bioavailability of its key bioactive compound berberine remains below 5%. Objective: To evaluate the pharmacokinetic enhancement and anti-diabetic efficacy of a Tinospora crispa phytosome in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty male Wistar rats were allocated to five groups (n = 6): normal control, diabetic control, diabetic plus metformin (200 mg/kg), diabetic plus T. crispa free extract (400 mg/kg), and diabetic plus T. crispa phytosome (400 mg/kg), given orally for 28 days; a separate single-dose pharmacokinetic study used 12 healthy rats. Results: The phytosome achieved a 3.14-fold enhancement in relative oral bioavailability (AUC0–24: 1524.7 ± 185.4 versus 486.3 ± 62.8 ng·h/mL, p < 0.001) and a higher peak plasma berberine concentration (Cmax: 387.2 ± 42.3 versus 124.5 ± 18.7 ng/mL, p < 0.001). After 28 days, the phytosome group showed reductions in fasting blood glucose (148.6 ± 19.2 versus 328.4 ± 42.5 mg/dL, p < 0.001) and HbA1c (6.1 ± 0.6 versus 9.2 ± 1.1%, p < 0.001), with an improved lipid profile comparable to metformin and large effect sizes (Cohen’s d: 3.51–6.22). Conclusion: Phytosome technology increases the bioavailability and anti-diabetic efficacy of T. crispa, supporting its development as a standardized herbal complementary therapy for diabetes mellitus.
Cardioprotective Mechanisms of Hibiscus sabdariffa Anthocyanins Against Myocardial Ischaemia–Reperfusion Injury via the PI3K/Akt Pathway Rachmat Hidayat; Abhimanyu Putra
Eureka Herba Indonesia Vol. 7 No. 1 (2026): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v7i1.144

Abstract

Background: Myocardial ischaemia–reperfusion (I/R) injury contributes up to 50% of the final infarct size after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction, yet pharmacological cardioprotection in the clinic remains elusive. Hibiscus sabdariffa L. (Malvaceae), known in Indonesia as rosella, is rich in delphinidin-3-O-sambubioside (D3S) and cyanidin-3-O-sambubioside (C3S) anthocyanins. Objective: To determine whether an HPLC-DAD–standardised anthocyanin-rich H. sabdariffa calyx extract (HSE) protects rat myocardium from I/R injury through PI3K/Akt activation. Methods: Sprague–Dawley rats (n = 48; six arms of n = 8) were randomised to sham, I/R control, HSE 100, 200 or 400 mg/kg/day p.o. for 14 days, or HSE 200 mg/kg + LY294002 (PI3K inhibitor); rats underwent 30-min left anterior descending (LAD) coronary occlusion plus 120-min reperfusion. H9c2 cardiomyoblasts underwent 6 h hypoxia plus 12 h reoxygenation, and D3S and C3S were docked against PI3K-p110α and Akt1. Results: HSE 200 mg/kg reduced infarct size from 41.8% to 18.4% of area at risk (F(5, 42) = 98.4, p < 0.001, partial η² = 0.92), lowered serum cardiac troponin I (cTnI) from 8.42 to 2.96 ng/mL (p < 0.001), and increased p-Akt(Ser473) 3.4-fold and the Bcl-2/Bax ratio 5.6-fold. D3S docked PI3K-p110α at ΔG = −9.2 kcal/mol. LY294002 abolished cardioprotection, demonstrating PI3K/Akt-dependence. Conclusion: H. sabdariffa anthocyanins exert PI3K/Akt-mediated cardioprotection against myocardial I/R injury, supporting their development as Indonesian phytotherapeutic adjuncts for elective PCI.
Synergistic Effects of Standardized Moringa oleifera Leaf Extract and a Probiotic Consortium on Intestinal Permeability and Environmental Enteric Dysfunction Biomarkers in Indonesian Children: A Randomized Controlled Trial Habiburrahman Said; Aline Hafidzah; Yi-Fen Huang
Eureka Herba Indonesia Vol. 7 No. 1 (2026): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v7i1.145

Abstract

Background: Environmental enteric dysfunction (EED) underlies much of the residual stunting and anemia that persist in Indonesian children despite nutrition programs. Moringa oleifera Lam. (Moringaceae) leaves contain quercetin, kaempferol, chlorogenic acid, β-sitosterol and glucomoringin-derived isothiocyanates that reinforce tight junctions and dampen mucosal NF-κB signaling, whereas Lactobacillus and Bifidobacterium probiotics generate short-chain fatty acids and displace enteropathogens. Objective: To determine whether standardized M. oleifera leaf extract co-administered with a defined probiotic consortium reduces intestinal permeability and EED biomarkers in Indonesian children aged 12–59 months. Methods: In a three-arm, double-blind, placebo-controlled randomized trial, 150 children aged 12–59 months with biomarker-confirmed EED received, for 12 weeks, either standardized 50% ethanolic M. oleifera leaf extract 500 mg/day plus a probiotic consortium of Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis Bb-12 and Lactobacillus plantarum Dad-13 (1×1010 CFU/day) [Moringa + Probiotic], M. oleifera plus placebo probiotic [Moringa alone], or double placebo [Placebo]. The primary outcome was the change in the urinary lactulose-to-mannitol (L:M) ratio at week 12. Results: In intention-to-treat analysis the L:M ratio fell from 0.42 ± 0.09 to 0.18 ± 0.06 with Moringa + Probiotic, from 0.41 ± 0.10 to 0.27 ± 0.08 with Moringa alone and from 0.43 ± 0.09 to 0.39 ± 0.10 with placebo (p < 0.001; d = 1.42 for Moringa + Probiotic versus placebo). EED remission occurred in 62.0%, 36.0% and 18.0% of recipients, respectively (OR 4.82, 95% CI 2.31–10.06, p < 0.001). Fecal myeloperoxidase, alpha-1-antitrypsin and neopterin, serum zonulin, lipopolysaccharide-binding protein and hs-CRP, hemoglobin and height-for-age Z-score all improved more with the combination, and adverse events were comparable across arms. Conclusion: Co-administration of standardized M. oleifera leaf extract with a multi-strain probiotic consortium restored intestinal barrier function and suppressed EED biomarkers in Indonesian children, supporting a scalable herbal–microbial complementary therapy.
Precision Modulation of Gut Microbiota by Zingiber officinale Polysaccharides Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice Rachmat Hidayat; Moon Kaeun; Sonya Syarifah
Eureka Herba Indonesia Vol. 7 No. 2 (2026): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v7i2.146

Abstract

Background: Ulcerative colitis (UC) is a rising cause of chronic gastrointestinal morbidity in Asia, and mesalazine-refractory disease drives demand for affordable adjunctive phytotherapies. Zingiber officinale Roscoe (Zingiberaceae; Indonesian jahe) rhizome polysaccharides (ZOP) remain under-studied despite escaping upper-gut digestion and reaching the colon for saccharolytic fermentation. Objective: To characterize standardized ZOP from Indonesian ginger rhizome and to evaluate their dose-dependent efficacy against dextran sulfate sodium (DSS)-induced colitis in mice, benchmarked against mesalazine. Methods: ZOP were prepared by hot-water extraction, Sevag deproteinization and ethanol precipitation (molecular weight 1.8×104–6.4×105 Da; galacturonic-acid–rhamnose–arabinose–xylose–glucose backbone). Sixty male BALB/c mice were randomized into six groups (n = 10): normal control; DSS 3% w/v; DSS plus mesalazine 100 mg/kg; and DSS plus ZOP 100, 200 or 400 mg/kg/day by oral gavage for 14 days. Results: High-dose ZOP reduced the Disease Activity Index from 3.62 ± 0.19 to 1.08 ± 0.12 (p < 0.001), preserved colon length (7.2 ± 0.20 versus 5.1 ± 0.26 cm), lowered histology score (3.8 ± 0.24 versus 9.8 ± 0.41) and colonic myeloperoxidase (2.14 ± 0.17 versus 6.18 ± 0.29 U/g), and restored Shannon α-diversity (3.56 ± 0.13 versus 2.14 ± 0.18). It expanded Lactobacillus, Bifidobacterium, Faecalibacterium and Akkermansia, contracted Proteobacteria, raised caecal butyrate 5.8-fold and up-regulated claudin-1, occludin, zonula occludens-1 (ZO-1) and mucin-2 (all p < 0.001). The high dose equalled or exceeded mesalazine on multiple endpoints. Conclusion: Standardized ginger rhizome polysaccharides reshape the gut microbiota, augment short-chain fatty-acid generation, restore mucosal barrier integrity and suppress colonic inflammation, supporting development as a complementary phytotherapy for Indonesian UC.
Antibiofilm and Microbiome-Modulatory Effects of Syzygium aromaticum Essential Oil in an In Vitro Dental Caries Polymicrobial Model Syaifudin Syaifudin; Aisyah Andina Rasyid; Johan Wirahadi Putro
Eureka Herba Indonesia Vol. 7 No. 2 (2026): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v7i2.147

Abstract

Background: Dental caries is a microbiome-driven disease in which acidogenic taxa dominated by Streptococcus mutans displace commensal genera and form a glucan-rich biofilm matrix that demineralises enamel. Chlorhexidine (CHX) is the standard chemical adjunct but causes staining, dysgeusia and broad commensal suppression, motivating evaluation of botanical alternatives that may rebalance the oral ecosystem. Objective: To determine the antibiofilm and microbiome-modulatory effects of standardised Indonesian Syzygium aromaticum L. (clove, Myrtaceae) bud essential oil (SAEO) on saliva-derived polymicrobial cariogenic biofilms in vitro. Methods: SAEO was hydrodistilled, characterised by gas chromatography–mass spectrometry (GC-MS), and tested at SAEO 0.25%, 0.5% and 1.0% v/v against polymicrobial biofilms grown on hydroxyapatite discs from stimulated saliva of 60 caries-active adults; CHX 0.12% was the positive control (n = 6 per arm). Endpoints were biofilm biomass, colony-forming units (CFU) on selective media, extracellular polymeric substance (EPS), biofilm pH, lactate, 16S rRNA microbiome profiling and human gingival fibroblast (HGF-1) cytotoxicity. Results: Eugenol (82.3%), β-caryophyllene (7.4%) and eugenyl acetate (4.8%) were the principal volatiles. SAEO 1.0% reduced biofilm biomass by 70.5% (95% CI 65.8–75.3; p < 0.001), S. mutans CFU by 3.22 log10 and EPS by 67.9%, while raising Shannon diversity from 1.42 to 2.08 bits and restoring Neisseria and Corynebacterium relative abundance — a dysbiosis-reversal pattern absent under CHX. Cytotoxicity reached 17.6% at SAEO 1.0% versus 31.8% for CHX 0.12%. Conclusion: Standardised SAEO is a credible complementary anticaries agent meriting clinical translation.
Hepato- and Immunoprotective Dynamics of Standardised Andrographis paniculata Extract in a Murine Polymicrobial Sepsis Model Sarah Armalia; Sudarto; Khalil Jibran; Danniel Hilman Maulana
Eureka Herba Indonesia Vol. 7 No. 2 (2026): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v7i2.148

Abstract

Background: Sepsis-associated liver injury drives mortality in polymicrobial sepsis yet lacks targeted adjunctive therapy. Andrographis paniculata (Burm. f.) Nees, known in Indonesia as sambiloto, yields andrographolide, a diterpene lactone that suppresses nuclear factor kappa B (NF-κB) and activates nuclear factor erythroid 2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1). Objective: To evaluate standardised A. paniculata ethanolic extract (APE, 30% w/w andrographolide) in a murine caecal ligation and puncture (CLP) sepsis model. Methods: Male BALB/c mice (n = 60) were randomised to Sham, CLP + vehicle, CLP + APE 100 mg/kg, CLP + APE 200 mg/kg, or CLP + imipenem/cilastatin 30 mg/kg (n = 12 per arm), treated at 1 h and 12 h post-CLP. Outcomes at 24 h were serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin; plasma tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10; hepatic NF-κB, Nrf2, HO-1 and NOD-like receptor protein 3 (NLRP3); peritoneal bacterial load; and Suzuki histology, with survival followed to 72 h. Results: APE 200 mg/kg reduced ALT by 58.4%, AST by 54.9%, TNF-α by 62.6% and IL-6 by 59.3%, and raised IL-10 2.3-fold (all p < 0.001). Hepatic p-NF-κB p65 fell 62%; nuclear Nrf2 and HO-1 rose 2.5- and 3.1-fold; peritoneal bacterial load fell 1.8 log10; the Suzuki score fell from 8.4 to 3.2; and survival at 72 h rose from 25% to 67% (log-rank p < 0.001; hazard ratio 0.42). Conclusion: Standardised APE attenuated hepatic injury and systemic hyperinflammation through dual NF-κB/Nrf2 modulation while preserving bacterial clearance, supporting its development as a complementary adjunct to antimicrobial therapy.
Pan-Cancer Immunogenomics and Reverse Pharmacophore Screening of Indonesian Mangrove Phytoconstituents (Avicennia marina, Sonneratia alba and Rhizophora mucronata) Against the PD-L1/CTLA-4/LAG-3 Immune Checkpoint Triad Nur Diana; Maria Margareth Wilson; Wisnu Wardhana Putra
Eureka Herba Indonesia Vol. 7 No. 2 (2026): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v7i2.149

Abstract

Background: Immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 benefit only 15%–30% of patients with solid malignancies, largely because of tumor immune microenvironment (TIME) resistance. Indonesian mangrove biodiversity remains an untapped source of multi-target small molecules. Objective: To assess the prognostic impact of the PD-L1/CTLA-4/LAG-3 checkpoint triad across human cancers and to identify mangrove phytoconstituents predicted to engage all three checkpoints. Methods: Pan-cancer immunogenomic profiling of 10,245 patients (33 TCGA cohorts) was integrated with digital cytometry (CIBERSORT-ABS, TIMER 2.0) and Tumor Immune Dysfunction and Exclusion (TIDE) modeling of CD274 (PD-L1), CTLA4 and LAG3. Reverse pharmacophore screening (PharmMapper) of 32 mangrove bioactives was followed by AutoDock Vina v1.2 docking (exhaustiveness 32) and NCI-60 CellMiner v2.9 analysis. Results: Triad co-expression independently predicted shorter overall survival, notably in hepatocellular carcinoma (HR = 1.84, 95% CI: 1.32–2.56, p < 0.001) and colorectal adenocarcinoma (HR = 1.62, 95% CI: 1.18–2.24, p = 0.004), and correlated with CD8+ T-cell exhaustion (r = −0.385), regulatory T-cell accumulation (r = +0.482) and M2 macrophage infiltration (r = +0.542; all p < 0.001). Screening prioritized 14 candidates. Avicennone C (Avicennia marina) bound the PD-L1 dimer interface (PDB: 6R3K; ΔG = −9.2 kcal/mol), betulinic acid (Sonneratia alba) the CTLA-4 MYPPPY loop (PDB: 1I8L; −8.7 kcal/mol) and rhizophin (Rhizophora mucronata) the LAG-3 D1 cleft (PDB: 7TZG; −8.4 kcal/mol). Baseline PD-L1 expression correlated with cytotoxic sensitivity across NCI-60 lines (r = +0.482, p = 0.002). Conclusion: Indonesian mangrove phytoconstituents are predicted to disrupt the PD-L1/CTLA-4/LAG-3 triad concurrently, providing a structural basis for the development of marine-derived cancer immunotherapeutics.
Multi-Target Complementary Systems Pharmacology of a Zingiberaceae Jamu Formula (Curcuma zanthorrhiza, Curcuma longa and Zingiber officinale) in Reversing Lipotoxicity and Fibrogenesis Transcriptomics in MASH Khalil Jibran; Isadora Selestine; Sonia Vernanda
Eureka Herba Indonesia Vol. 7 No. 2 (2026): Eureka Herba Indonesia
Publisher : HM Publisher in collaboration with CMHC Research Center

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v7i2.150

Abstract

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by lipotoxicity, lobular inflammation and progressive fibrogenesis. Single-target agents show limited efficacy, underscoring the potential of traditional Indonesian Zingiberaceae Jamu combining Curcuma zanthorrhiza, Curcuma longa and Zingiber officinale, whose systems-level multi-target mechanisms remain undefined against human transcriptomes. Objective: To decipher the multi-target polypharmacological complementarity of the Zingiberaceae Jamu triad against human MASH pathophysiology using clinical biopsy RNA-Seq, network pharmacology and molecular docking. Methods: Human liver biopsy RNA-Seq transcriptomics (NCBI Gene Expression Omnibus, GEO, GSE135251; N = 216: 10 healthy controls, 51 non-alcoholic fatty liver [NAFL], 155 MASH fibrosis stages F0–F4) were integrated with bioactive metabolite profiling (Lipinski Rule of Five and Veber oral bioavailability), target prediction, protein–protein interaction (PPI) topology, KEGG enrichment and AutoDock Vina molecular docking. Results: Biopsy analysis identified 1,842 differentially expressed genes (DEGs; 1,024 upregulated, 818 downregulated), with upregulation of fibrogenic (COL1A1, TIMP1, ACTA2, TGFB1) and inflammatory genes (CCL2, CXCL8, TNF) alongside suppression of fatty acid oxidation regulators (PPARA, CPT1A, ACOX1). Intersection of 24 bioavailable phytochemicals with MASH DEGs yielded 126 shared targets (PPI: 126 nodes, 1,142 edges, average degree 18.13). Six master hub genes were identified: PPARG (degree 84), TNF (78), AKT1 (76), TGFBR1 (68), RELA (64) and MMP9 (58). Docking predicted spontaneous binding: curcumin to PPARG (ΔG = −9.4 kcal/mol) and AKT1 (−8.8); xanthorrhizol to TNF-α (−8.2); 6-shogaol to TGFBR1 (−8.6) and MMP9 (−8.4). Conclusion: The findings are consistent with a tri-pillar polypharmacological complementarity in the Zingiberaceae Jamu formula and establish a rational mechanistic framework for standardized phytopharmaceutical development against human MASH.

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