Eureka Herba Indonesia

Precision Modulation of Gut Microbiota by Zingiber officinale Polysaccharides Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice

Rachmat Hidayat — 2026-09-30

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 — 2026-09-20

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 — 2026-09-18

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 — 2026-09-26

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 — 2026-09-21

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.