Eureka Herba Indonesia

Quantitative Mapping of Phytochemical Synergy in Psidium guajava and Piper betle for Antidiarrheal Therapy: A Systematic Review and Meta-Analysis Using Radar Chart Analysis and AUC

Kintoko — 2026-02-27

Background: Infectious diarrhea is a major global health burden characterised by gastrointestinal hypermotility, fluid hypersecretion, and mucosal inflammation. Conventional antimotility agents and broad-spectrum antibiotics carry significant limitations, notably antimicrobial resistance and adverse systemic effects. Psidium guajava and Piper betle offer a complementary approach, yet the magnitude of their combined synergy has not been quantified.

Objective: To quantify and map the combined antidiarrheal, antimicrobial, and antioxidant synergy of Psidium guajava and Piper betle, and to identify their respective pathophysiological targets.

Methods: A systematic review and meta-analysis were conducted following PRISMA 2020. Primary studies reporting quantitative antidiarrheal, antimicrobial, and antioxidant parameters of both extracts were identified across major databases. Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model, and therapeutic capacity was mapped by Radar Chart Analysis (RCA) and Area Under the Curve (AUC) integration.

Results: Psidium guajava markedly suppressed gastrointestinal motility and intestinal fluid accumulation (pooled SMD = −2.45; 95% CI −3.10 to −1.80), whereas Piper betle showed broad-spectrum bactericidal and free-radical-scavenging activity (pooled SMD = 3.85; 95% CI 2.95 to 4.75). AUC integration indicated that combining both phytochemical profiles expanded the total therapeutic coverage by 42%.

Conclusion: The framework indicates a synergistic mechanism in which Psidium guajava targets hypermotility and secretory dysfunction while Piper betle addresses the pathogenic etiology and oxidative tissue damage, supporting the development of combined botanical therapeutics.

Spirulina platensis Extract Stabilizes Hepatic HIF-1α and Activates Caspase-3 in Aging Wistar Rat Liver

Reni Paramita — 2026-02-27

Background: Liver aging is accompanied by progressive hypoxia, impaired redox homeostasis, and dysregulated programmed cell death, for which safe complementary interventions are needed. Spirulina platensis (Arthrospira platensis), a marine cyanobacterium rich in the antioxidant phycobiliprotein C-phycocyanin, is widely used in Indonesian complementary medicine, yet its effect on the hepatic hypoxia–apoptosis–autophagy network across biological age is undefined.

Objective: To examine whether oral Spirulina extract modulates hepatic HIF-1α, caspase-3, and p62/SQSTM1 in young (12-week) and older (24-week) male Wistar rats.

Methods: Animals (n = 5 per group) received Spirulina extract 200 mg/kg body weight or aquabidest vehicle once daily for 29 days; livers were harvested and marker concentrations quantified by ELISA, with one-way ANOVA, Tukey HSD, η², Cohen’s d, and Pearson correlation.

Results: Spirulina increased hepatic HIF-1α by 60.0% in older rats (688.0 ± 55.0 versus 430.0 ± 40.0 pg/mg protein; p < 0.001; Cohen’s d = 5.37) but not in young rats (p = 0.539). Caspase-3 rose 21.2% in older rats (145.68 ± 12.80 versus 120.23 ± 11.00 ng/mg protein; p = 0.010; d = 2.13), whereas p62 was unchanged (ANOVA p = 0.903). HIF-1α and caspase-3 were strongly correlated (r = 0.879; 95% CI 0.714–0.951; p < 0.001). Spirulina also raised the hepatosomatic ratio and attenuated body-weight gain.

Conclusion: Spirulina engages the hepatic hypoxia–apoptosis axis in an age-dependent manner while preserving autophagy, providing mechanistic support for its use as a herbal hepatoprotective modality.

Tinospora crispa Phytosome Enhances Oral Bioavailability and Glycemic Control in Streptozotocin-Induced Diabetic Rats

Dedi Sucipto — 2026-02-27

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 (AUC_0–24: 1524.7 ± 185.4 versus 486.3 ± 62.8 ng·h/mL, p < 0.001) and a higher peak plasma berberine concentration (C_max: 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 HbA_1c (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 — 2026-02-28

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 — 2026-02-28

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.