I. Made Artika

Background/Objectives: Extraction conditions can influence the chemical profile and antioxidant properties of medicinal plant extracts. This study aimed to optimize ethanol-based extraction of Justicia gendarussa leaves and characterize the optimized extract through UHPLC-HRMS metabolite profiling, with application to cultivated plant materials. Methods: A two-level half-fractional factorial design was used to assess the effects of five extraction factors—liquid-to-solid ratio, temperature, ethanol concentration, extraction time, and pH—on three response variables: total flavonoid content (TFC), DPPH radical-scavenging activity, and ferric reducing antioxidant power (FRAP). The optimized condition was validated experimentally, characterized by UHPLC-Q Exactive Plus Orbitrap HRMS with data-dependent MS/MS, and applied to cultivated leaf and stem materials under six fertilization treatments, analyzed using two-way ANOVA (organ × treatment). Results: The liquid-to-solid ratio × temperature interaction was the dominant determinant of TFC, and the liquid-to-solid ratio alone dominated both DPPH and FRAP. Desirability-based optimization identified a condition of 100 mL g⁻¹ liquid-to-solid ratio, 30 °C, 20% ethanol, 30 min, and pH 2. Confirmatory extraction resulted in 16.43 ± 0.30 mg QE g⁻¹ DW TFC, 12.30 ± 0.02 µmol TE g⁻¹ DW DPPH, and 190.56 ± 2.58 µmol TE g⁻¹ DW FRAP, in close agreement with model predictions (0.10–1.54% error). UHPLC-HRMS/MS detected 52 putatively annotated metabolites, including a candidate gendarusin A/B (apigenin di-C-arabinoside)-type C-glycosylflavone. Leaves showed significantly higher TFC, CUPRAC, and FRAP than stems regardless of fertilization treatment (organ effect p < 0.0001), whereas the leaf–stem difference in DPPH capacity varied significantly with treatment (interaction p = 0.0010). Conclusions: These findings provide a validated extraction condition for the measured responses and support further targeted metabolite evaluation of J. gendarussa.

This study systematically reviews the determinants of Zinc (Zn) bioavailability in rice (Oryza sativa) and evaluates strategies to improve its nutritional contribution. A PRISMA-based systematic literature review was conducted using Scopus, PubMed, SINTA, and Garuda databases. From 768 identified publications, 14 studies met the inclusion criteria and were analyzed. T Quantitative evidence from the reviewed studies shows that disrupting phytic acid via genetic mutation increases Zn bioavailability by 1.8- to 2.2-fold, while reducing phytate by >50% through milling or cooking linearly enhances free Zn release by 15–25%. T. Biofortification strategies could increase Zn content, but their nutritional impact depended on simultaneous reduction of antinutritional factors. Overall, improving Zn bioavailability in rice requires an integrated approach involving genetic improvement, optimized processing techniques, and agronomic strategies to enhance the nutritional quality of rice-based diets.

Java Ginseng has long been used by Indonesian communities as a medicinal plant and is traditionally consumed as an alternative therapy, even in managing Diabetes Mellitus (DM). The present study aimed to evaluate the effects of the decoction of Javanese ginseng leaf simplicia (DJGLS) on blood glucose levels, serum superoxide dismutase (SOD), the levels and expression intensity of SOD, and pancreatic histopathology in DM rats. Twenty adult male rats were randomly assigned to four groups. The normal control group (GJ-0, n = 5), the DM group (GJ-1, n = 5) received a placebo, and the DM groups (GJ-2, n = 5 and GJ-3, n = 5) were administered a DJGLS (100 g/100 mL, w/v powder simplicia), at volume of 0.5 mL and 1 mL/100 g body weight, respectively for 21 consecutive days. Blood glucose levels were measured using a glucometer. Serum and pancreatic SOD levels were determined using an ELISA kit. Pancreatic histopathology was evaluated using hematoxylin and eosin staining, while pancreatic SOD expression was assessed by immunohistochemical staining. In addition, phytochemical screening was performed on the Javanese ginseng leaf simplicia powder. The present study demonstrated that the phytochemical analysis of Java Ginseng leaf simplicia powder revealed the presence of alkaloids, flavonoids, saponins, tannins, and steroids. DJGLS treatment reduced blood glucose levels and serum SOD levels in diabetic rats, with a significant reduction observed in the GJ-3 group compared with the GJ-1. Administration of DJGLS in the GJ-2 and GJ-3 groups significantly increased pancreatic SOD levels compared with the GJ-1. The DJGLS treatment in the GJ-2 and GJ-3 groups demonstrated restorative effects, as evidenced by the recovery of the Islets of Langerhans area and increased intensity of pancreatic SOD expression compared with the GJ-1. In conclusion, DJGLS treatment was able to reduce blood glucose levels and serum SOD levels, although these values had not fully returned to normal conditions, and it increased pancreatic SOD levels. The DJGLS indicated potential for promoting recovery of the pancreatic Islets of Langerhans area.

Cancer rates are expected to increase, with Src kinase playing a crucial role in cancer metabolism. This study explored bioactive compounds in royal jelly (RJ) as novel anticancer agents targeting Src kinase using computational methods. QM-AM1 was used for structure preparation, while MD simulations assessed protein-ligand stability, and advanced analyses provided post-MD data. The results indicated that, among the bioactive compounds in RJ, formononetin was promising, with a binding energy of 8.243 kcal/mol and interactions with the active sites of two Src kinase pockets. DFT calculations for formononetin suggested good stability and low reactivity. MD simulations demonstrated that the Src kinase–Formononetin complex adopted a stable, favorable binding pose, and subsequent MM-PBSA analysis indicated a markedly stronger binding affinity than that of the reference inhibitor AP23451. PCA analysis revealed overlapping energy distributions and a positive correlation between RMSDca and DCCM plots, providing insights into the stability and conformation of the Src kinase-formononetin complex. This study proposes formononetin as a novel anticancer inhibitor candidate through comprehensive in silico computational analysis, while acknowledging that further validation through in vitro and in vivo studies is required.

Cancer remains a major health issue, and Bcl-2 inhibits apoptosis. This study explored the phytochemicals of Codiaeum variegatum as potential Bcl-2 inhibitors. Receptor–ligand docking was conducted with YASARA, followed by 300 ns MD using AMBER14. ADME and DFT analyses were used to characterize the pharmacokinetics and electronic properties of the inhibitor candidates. The large-scale data generated from the 300-nanosecond MD simulations were further processed to map the energy landscapes using PCA and DCCM analysis in R Studio. We successfully applied the QM-AM1 method to the preparation and execution of molecular docking studies. Among the 17 phytochemical compounds isolated from C. variegatum, taraxerol demonstrated the most promising binding energy, with a docking score of −8.868 kcal/mol, which is comparable to that of the co-crystallized reference ligand, venetoclax. Taraxerol also satisfied the ADME criteria based on Lipinski’s Rule of Five, with only a single rule violation, and DFT calculations confirmed its stability, exhibiting an energy gap of −0.1805 eV. Furthermore, a 300 ns MD simulation revealed that the binding energy of taraxerol, computed using the MM-PBSA method, was more favorable than that of venetoclax, with taraxerol yielding 303.235 kJ/mol in complex with Bcl-2, compared to 291.115 kJ/mol for venetoclax. PCA and DCCM analyses additionally supported the dynamic stability of taraxerol as a potential Bcl-2 inhibitor. Although ADME predictions suggest a favorable safety profile, further in vitro and in vivo validation is required to substantiate its therapeutic potential.

Breast cancer remains a leading cause of cancer-related mortality worldwide, necessitating the identification of novel therapeutic targets. Royal jelly (RJ), a functional food rich in bioactive compounds, has been reported to exhibit chemopreventive properties; however, its potential molecular interactions with key breast cancer–associated target receptors, including Bcl-2, EGFR, and HER-2, remain insufficiently characterized. This study aimed to explore, at a computational level, the putative interactions between selected RJ-derived compounds and their target receptors to generate mechanistic hypotheses. Molecular docking was performed using YASARA Structure after systematic protein and ligand preparation, with structural validation assessed using Ramachandran plots. The predicted pharmacokinetic properties were evaluated using ADMET analysis. In addition, molecular dynamics (MD) simulations combined with normal mode analysis (NMA) were employed to examine the stability of the selected protein–ligand complexes. Docking analyses indicated favorable binding affinities of quercetin for Bcl-2 and naringin for EGFR and HER-2. Normal mode analysis–based simulations supported the intrinsic flexibility and favorable dynamic behavior of the docked complexes. Collectively, these in silico findings provide a hypothesis-generating framework suggesting that quercetin and naringin may warrant further experimental investigation as potential modulators of breast cancer–related targets. Experimental validation through in vitro and in vivo studies is required to substantiate these computational predictions.

Threats to Malaria Elimination Program (MEP) are arising, such as drug‐resistant parasites, insecticide‐resistant mosquitos and zoonotic malaria. In Southeast Asia, zoonotic emergence of macaque malaria, Plasmodium knowlesi , has been a major concern to the MEP. This parasite is recently established and potentially localised in wild populations of Macaca fascicularis (long‐tailed macaques), which are indigenous to South‐East Asia. Besides P. knowlesi infection, the macaque is also infected by P. inui and P. cynomolgi , which could be transmissible to humans. However, the parasitology data from Indonesian macaque populations are sparse. Noninvasive sampling methods are the primary tool for primate infectious disease ecology. The present study aimed to investigate Plasmodium spp from faecal samples collected (of long‐tailed macaques) in Indonesia. Faecal samples from semicaptive breeding sites and wild M. fascicularis have been collected. A total of 122 M. fascicularis faecal samples were collected from Java (West Java) and Sumatra (Lampung, Palembang and Jambi). DNA samples were extracted and subjected to nested polymerase chain reactions (nPCR) analysis using sets of mitochondrial DNA (mtDNA) primers to detect Plasmodium genus. There were 46 (37.7%) samples positive of malaria, and four species of Plasmodium parasites ( P. inui , P. cynomolgi , P. coatneyi and P. fieldi ) were detected in their natural host. None of the faecal samples were identified as being P. knowlesi positive. This study provides baseline information on the occurrence and diversity of simian malaria parasites in M. fascicularis populations in Indonesia using noninvasive samples and highlights the importance of further studies on simian malaria parasites in wildlife hosts.