Sri Widyarti

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, while currently available first-line therapies are often constrained by systemic toxicity, resistance, and limited single-target mechanisms. Therefore, safer and broader-spectrum therapeutic strategies are urgently needed. This study evaluated the antitumor efficacy of oxyhydrogen nanobubbles (HHOnbs), an innovative multigas nanosystem that simultaneously delivers O₂, H₂, and low-dose H₂O₂, and hypothesized that HHOnbs would suppress HCC progression through multitarget modulation of the tumor microenvironment. A true experimental study was conducted using diethylnitrosamine/carbon tetrachloride (DEN/CCl₄)-induced HCC in male Wistar rats. Six groups were assigned: negative control, positive control, HHOnbs (200 million particles/mL; 0.1 mL per intravenous injection) administered every 2 days for a total of 12 or 24 treatments, and Lenvatinib (1.2 mg/kg body weight, orally) administered in 3- or 5-dose regimens. Antitumor activity was evaluated by immunohistochemical analysis of CD31, CD68, and FoxP3 expression, representing angiogenesis, macrophage-mediated inflammation, and regulatory T-cell-associated immunosuppression, respectively. In addition, TERT gene amplification was quantified using PCR. Compared with the positive control, HHOnbs significantly reduced CD31 by 42.07–43.55%, CD68 by 42.61–48.02%, and FoxP3 by 44.96–48.71% (all p < 0.001), with greater effects observed at higher treatment frequencies. TERT gene amplification was suppressed by up to 47.89% in the 24-administration group. These effects were comparable to those of Lenvatinib, while HHOnbs showed more consistent frequency-dependent responses across all biomarkers. In conclusion, HHOnbs demonstrated significant multitarget antitumor activity in experimental HCC and represent a promising nanotherapeutic candidate for liver cancer management.

Curcuma xanthorrhiza , a commonly used Indonesian medicinal plant, has been widely utilized in traditional remedies, yet its antiviral potential against SARS‐CoV‐2 remains poorly defined. The current study was aimed at investigating the effect of C. xanthorrhiza ethanol extract on inhibiting viral entry through in silico and in vitro studies. The active compounds of C. xanthorrhiza were characterized using liquid chromatography–high‐resolution mass spectrometry (LC‐HRMS). The identified compounds were screened according to the Lipinski, Ghose, Veber, and Egan rules, and their antiviral activity was predicted using the PASS server. Molecular docking and dynamic simulations were employed to determine binding affinity and stability between the selected compounds and the SARS‐CoV‐2 Spike D614G protein. The virus‐like particle (VLP) of SARS‐CoV‐2 G614D was produced in HEK‐293T cells via cotransfection of plasmids encoding spike‐EGFP, membrane, and envelope proteins, and its morphology was verified by transmission electron microscopy (TEM). The IC ₅₀ value of C. xanthorrhiza extract on 16HBE14o‐ cells was analyzed using the WST‐1 method. 16HBE14o‐ cells were exposed to VLP and treated with C. xanthorrhiza at 2.5, 5, 10, 40, and 125 μ g/mL for 24 and 48 h. The EGFP intensity of VLP‐internalized cells was assessed through fluorescent microscopy. Curcumin, curcumin II, piperine, (+)‐ar‐turmerone, and peruvinine showed the strongest binding affinities (−7.5 to −6.2 kcal/mol), while curcumin, curcumin II, and (+)‐ar‐turmerone exhibited the most stable binding interactions. TEM confirmed successful VLP formation with a mean diameter of 52.94 ± 27.32 nm, and the IC ₅₀ of the extract was 125 μ g/mL. Furthermore, C. xanthorrhiza extract at 2.5 μ g/mL significantly reduced VLP internalization after 24 h. These findings highlight C. xanthorrhiza as a promising natural candidate for SARS‐CoV‐2 inhibition, supported by consistent computational and experimental evidence.

Context: Parkinson´s disease (PD) is caused by protein aggregates composed of α-synuclein (αSyn) and its pathologies, such as mitochondrial dysfunction, loss of dopamine neurons, dysregulation of the dopamine transporter (DAT), and absorption of αSyn. Treatment with L-DOPA could not overcome it. Therefore, it requires complementary therapy with H2O2 low dose. Aims: To evaluate the potential of H2O2 as a complementary therapy with L-DOPA. Methods: The three-dimensional (3D) ligand and protein target structures were retrieved from PubChem and Protein Data Bank (PDB). H2O2, as ligand, was converted using the Open Babel, which integrated with PyRx v.0.9.8. The molecular docking program used AutoDock Vina as a plug-in in PyRx v.0.9.8. Docking visualization results were analyzed using PyMOL v.2.5.5 (Schrodinger, LLC) and Discovery Studio 2021 Client v21.1.0.20298. The protein-protein docking program used an HDOCK server (Lab of Biophysics and Molecular Modeling, Huazhong University). Molecular dynamics simulation used YASARA Structure v.23.9.29. Results: H2O2 could prevent the formation of αSyn fibrils by reducing the binding affinity between αSyn proteins. H2O2 could avoid mitochondrial dysfunction and loss of dopamine neurons by preventing αSyn binding to VDAC. Dysregulation of the DAT could be avoided by the ability of H2O2 to prevent αSyn binding DAT and avoid αSyn uptake by preventing αSyn binding to LRP1. Conclusions: The H2O2 low dose has the potential to be a complementary therapy with L-DOPA.

It is well known that bitter gourd and noni fruit contain high levels of beneficial chemicals, but tastes and flavour are less appealing. Due to enzymatic transformation, fermentation can change bioactive compounds that minimize bad taste and unpleasant odor. This study aimed to assess the phenol and flavonoid content and antioxidant activity of bitter gourd (Momordica charantia L.) and noni fruit (Morinda citrifolia) during fermentation in honey. Blendered-bitter gourd (BG) or noni fruit (NF) each is mixed with honey and distilled water in a ratio of 3:1:10, then fermented for 90 days at room temperature and anaerobic conditions. Total phenol (TPC), total flavonoid content (TFC), and antioxidant activity were measured every two weeks. TPC in fermented NF increased from 56.62 mg GAE/gr to 156.59 GAE in the 6-week. TPC in BG increased from 56.96 GAE/g to 146.39 GAE/g during 12-week fermentation. TFC of fermented NF increased from 4.55 mg QC/g to 12.92 mg QC/g in 12-week fermentation. TFC of fermented BG increased from 9.86 QC/g to 41.69 QC/g in 12 weeks of fermentation. The antioxidant activity of fermented BM and BP showed the highest antioxidant activity in the 6-week (0,574 mg TEAC/g and 0.528 mg TEAC/g). The results indicate that fermentation in honey can increase total phenol and flavonoid content, and the antioxidant activity of bitter gourd and noni fruit.

Hydrogen has emerged as a promising candidate due to its antioxidant properties and potential to modulate electron flow, enhancing mitochondrial energy metabolism and reducing oxidative stress. In this study, hypercholesterolemia male Wistar rats were utilized to investigate the safety and efficacy of intravenous hydrogen nanobubble solution (HNB). The study assessed serum lipid levels, complete blood count, and organ health following HNB administration compared to positive (simvastatin) and negative controls. Bayesian statistics were used to validate the findings. The administration of HNB did not adversely affect the immediate survival of the rats on a high-fat diet (HFD), whereas simvastatin significantly reduced survival rates. It showed a dose-dependent immunomodulatory effect, reducing white blood cell, lymphocyte, and monocyte counts. It also influenced erythropoiesis, as indicated by increased red blood cell counts and hemoglobin levels. A significant elevation in platelet counts was observed, suggesting potential effects on platelet production or lifespan. The study also noted changes in liver enzyme levels, with HNB indicating potential hepatoprotective effects. Furthermore, HNB treatment decrease in mean fat droplet count, suggesting a mitigation of diet-induced hepatic steatosis. The findings suggest that HNB may serve as a protective agent against the deleterious effects of a high-fat diet, offering immunomodulatory and hepatoprotective benefits. This study provides a foundation for considering HNB as a potential therapeutic intervention for hypercholesterolemia and warrants further investigation into the long-term impacts of nanobubble treatment on diet-induced pathologies. The consistency of results across traditional statistical significance and Bayesian evidence strengthens the validity of the observed treatment-specific effects.

Background: ROS are created when high levels of oxidative stress occur due to hypercholesterolemia. Nuclear Factor Erythroid 2-related factor (NRF2) controls the expression of antioxidant genes. Kelch-like ECH-associated protein 1 (KEAP1) therapy degrades NRF2. Chitosan 501.1 kDa from snail shells contains bioactive chemicals that can induce NRF2 activity. Objective: To evaluate the potential antioxidant activity of the bioactive compound in Mw 501.1 kDa chitosan by targeting KEAP1 and NRF2 proteins in-silico. Method: The 3D structures of the bioactive compounds chitosan and control 51M were derived from the PubChem database, and the proteins were derived from the RCSB PDB. The biological activity of chitosan bioactive compounds was predicted using the PASS Online server. Molecular docking was performed using Hex 8.0.0 Cuda with Shape+Electro+DARS and visualised with Discovery Studio. The biological activity of chitosan compounds was predicted as lipotropic and antioxidant. Result: The discovery of the bioactive compound chitosan 501.1 kDa interacted strongly with KEAP1. The bioactive compound chitosan also inhibited KEAP1 through residues GLN75 and LEU84 at the 51M-KEAP1 interaction. Conclusion: The bioactive compound chitosan 501.1 kDa could inhibit the interaction of KEAP1-NRF2 proteins so that NRF2 could transcribe antioxidant genes. Therefore, may serve as a suitable alternative.

A progressive and chronic neurological condition called MSA (Multiple System Atrophy) is characterized clinically by varying degrees of dysautonomia, cerebellar ataxia, and parkinsonism. The concept of mitochondrial dysregulation in MSA is one perspective in handling this neurodegenerative disease. Damage to functional mitochondria is driven by the presence of ɑ-Synuclein-induced mitochondrial localization. The goal of MSA treatment up until now has been to reduce symptoms. One of the innovations in the treatment of MSA could be the novel idea based on mitochondrial reprogramming pathways. Mitochondrial reprogramming can be done in various ways in which the use of hydrogen, magnesium and low-dose hydrogen peroxide.

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 995-1005, November-December 2022. DOI: https://doi.org/10.56499/jppres22.1468_10.6.995 Original Article Effect of Lissachatina fulica chitosan on the antioxidant and lipid profile of hypercholesterolemic male Wistar rats [Efecto del quitosano de Lissachatina fulica sobre el perfil antioxidante y lipídico de ratas Wistar macho hipercolesterolémicos] Umarudin1,2, Sri Widyarti1, Warsito3, Sri Rahayu1* 1Department Effect of Lissachatina fulica chitosan on the antioxidant and lipid profile of hypercholesterolemic male Wistar rats

Mucoadhesive properties of herbs are the herb’s ability to strongly interact or penetrate in binding to mucin components in the mucus. The oral preparation of polyherbal made for therapeutic purposes must have a mucoadhesive capability. This in vitro study aims to determine herbal combinations that have a potential stable interaction with MUC2. The screening of 10 herbal namely, a flower of tembelekan (Lantana camara), rosela (Hibiscus sabdariffa), and asam jawa (Tamarindus indica); rind of jeruk nipis (Citrus aurantifolia); leaf of sirih merah (Piper crocatum), kelor (Moringa oleifera), and meniran hijau (Phyllanthus niruri); rhizome of kencur (Kaempferia galanga), temulawak (Curcuma xanthorrhiza), and jahe (Zingiber officinale) based on the changes in MUC2 viscosity, interaction percentage and absorption percentage. Kencur, rosela, kelor, and meniran hijau maintains the viscosity. Therefore, the interaction process occurs without significantly changing the physicochemical properties of the mucin. While the other herbs, especially jeruk nipis, tembelekan dan asam jawa, caused an increased viscosity of MUC2. Kencur or temulawak can also reduce the possibility of asam jawa changing the viscosity of mucin. Based on these results, we recommend kencur-temulawak mix or kencur-asam jawa mix as a polyherbal because both have a positive interaction percentage value that indicates an additional percentage of precipitated mucin compared to pure mucin (MUC2).