Background and purpose: Scientific research is crucial to develop therapies for various disease severity levels, as modern drugs cause side effects and are difficult to predict. Researchers are exploring herbal alternatives with fewer side effects, particularly propolis, which has been validated through in vitro, in vivo, and clinical studies. This will focus on scientific evidence and its supporting technology for developing new bioactive compounds for chronic diseases. Nanotechnology can improve the delivery and absorption of herbal medicines, which often have poor bioavailability due to their high molecular weight and solubility in water, particularly in oral medicines. This technology can enhance propolis's effects through multi-target therapy and reduce side effects. Experimental approach: All publications related to each section of this review were discovered using the search engines Google Scholar, Scopus, and Pubmed. This was only available for publication between 2013 and 2023. The selected publications were used as references in this review after being thoroughly studied. Key results: Evaluation of propolis active compounds, the classification of propolis nano formulations, design concepts, and mechanisms of action of propolis nano formulation. Additionally, the challenges and prospects for how these insights can be translated into clinical benefits are discussed. Conclusion: In the last ten years, a list of nanoformulation propolis has been reported. This review concludes the difficulties encountered in developing large-scale nanoformulations. To commercialize them, improvements in nano carrier synthesis, standardized evaluation methodology within the framework of strategy process improvement, and Good Manufacturing Practices would be required.

Inappropriate administration of antibiotics can cause resistance to bacteria. Staphylococcus aureus is one of the strong biofilm-forming bacteria that cause antibiotic resistance. Calincing (Oxalis corniculata L.) leaves have excellent antibacterial activity, but their antibiofilm activity against S. aureus has not been reported until now. Currently, the discovery of new antibiofilm against S. aureus biofilms is significant to prevent the impact of infections caused by biofilms. This study was intended to determine the effectiveness of the ethanol extract of O. corniculata leaves in inhibiting and eradicating S. aureus biofilm formation. Planktonic testing, inhibition, and biofilm eradication activity were carried out using the microtiter broth method. Antibiofilm activity of O. corniculata leaves against S. aureus biofilm was analyzed by calculating the minimum concentration of biofilm inhibitor (MBIC50) and minimum biofilm eradication concentration (MBEC50). Data were analyzed using the Statistical Package for the Social Sciences (SPSS) with a 95% confidence level. Oxalis corniculata leaves showed inhibitory activity on the formation of the tested S. aureus biofilm. The ethanol extract of 1% O. corniculata leaves gave 76.23±0.01% antibacterial activity of S. aureus and 71.32±0.01% of mid-phase antibiofilm activity, and 69.33±0.01% maturation phase. The results also prove that the ethanolic extract of O. corniculata leaves can eradicate S. aureus biofilm formation. Therefore, the ethanol extract of O. corniculata leaves can be developed as a new antibiofilm against S. aureus.

Hepatocellular Carcinoma (HCC) is commonly treated with surgery, liver transplantation, and chemotherapy, but recurrence and metastasis remain challenges. Natural complementary therapies like propolis, known for its hepatoprotective properties, are gaining interest due to limited efficacy and toxicity of conventional chemotherapy. This study aims to identify core targets for HCC, assess the therapeutic potential of East Kalimantan propolis (EKP) from stingless bees, and analyze the molecular interactions. EKP compounds were analyzed using target prediction tools related to HCC, alongside clinical data from the Gene Expression Omnibus (GEO) database, to identify overlapping genes with clinical relevance. The selected genes were then subjected to protein-protein interaction (PPI), GO and KEGG enrichment, immunohistochemical comparison and survival analysis to identify potential core targets and related pathways for HCC therapy. Furthermore, molecular docking and dynamics were conducted to verify the molecular interactions and stability of EKP compounds with targets. 108 genes have been selected as HCC potential targets, which mostly associated with MicroRNAs in cancer, chemical carcinogenesis, and viral carcinogenesis pathways. These targets were obtained by overlapping genes from GEO clinical databases and target predictors. PPI network analysis revealed 4 main targets of propolis in HCC. Furthermore, differential expression genes, survival analysis, and Immunohistochemical analysis from databases suggested that AKR1C3 and MAPK1 promote HCC progression and shorten survival rate of HCC patients. Molecular docking and dynamic studies confirmed strong binding affinity and stability of Baicalein, Chrysin, Quercetin, and Myricetin with receptor targets within simulation time. This study provides insight into the mechanism of action of EKP on HCC and identifies AKR1C3 and MAPK1 as candidate target treatments for future drug development.

Cirrhosis naturally progresses through three stages: compensated, decompensated, and late decompensated, which carry an elevated risk of death. Although curcumin's anti-cirrhosis effects have been studied, underlying mechanism in preventing cirrhosis progression and the correlation between curcumin's action with upregulated genes remains insufficiently explored. In this study, we employed network pharmacology approach to construct a drug-target-disease network through bioinformatics and validate the findings with molecular docking and dynamic simulation. The curcumin-targeted liver cirrhosis network encompassed 54 nodes with 282 edges in protein-protein interactions (PPI) network. By utilizing network centrality analysis, we identified eight crucial genes. KEGG enrichment pathway revealed that these crucial genes are involved in pathway of cancer, endocrine resistance, estrogen signaling, chemical carcinogenesis-receptor activation, lipid metabolism, and atherosclerosis. Notably, these eight genes predominantly participate in cancer-related pathways. Further investigation revealed upregulation of four genes and downregulation of four others in hepatocellular carcinoma patients. These upregulated genes-MAPK8, SRC, PPARG, and HSP90AA1-strongly correlated with reduced survival probability in liver hepatocellular carcinoma patients with survival times approximately under 4000 days (∼11 years). Molecular docking and molecular dynamic results exhibited curcumin's superior binding affinities and stability compared to native ligands of MAPK8, SRC, PPARG, and HSP90AA1 within 50 ns simulations. Moreover, MM-GBSA analysis showed stronger binding energy of curcumin to MAPK8, SRC, and HSP90AA1 than native ligand. In conclusion, this study provides valuable insights into curcumin's potential mechanisms in preventing liver cirrhosis progression, specifically in HCC. These findings offer a theoretical basis for further pharmacological research into anti-HCC effect of curcumin.Communicated by Ramaswamy H. Sarma.

Numerous side effects of breast cancer drugs have prompted researchers to explore more into new therapeutic approaches derived from natural substances. In this context, our study focused on uncovering the potential of East Kalimantan propolis from Trigona apicalis for breast cancer treatment including the underlying mechanisms through bioinformatics approached. We conducted integrated in vitro and bioinformatics analysis of network pharmacology, molecular docking, molecular dynamics and MM-GBSA analysis. Initially, in vitro cytotoxic assay demonstrated the anti-breast cancer activity potential of ethanol extract of East Kalimantan propolis, particularly its ethyl acetate fraction, which exhibited similar activity to doxorubicin, as indicated by their IC₅₀ value. This study revealed eight propolis compounds, consisting of flavonoids and phenolic acids, in East Kalimantan propolis. By integrating microarray datasets (GSE29431, GSE36295, and GSE42568) analysis with potential targets derived from propolis compounds, 39 shared target genes were identified. Subsequently, GO and KEGG pathway, protein–protein interaction (PPI) network, core hub genes and gene expression analysis revealed three major targets, namely, PTGS2, CXCL2, and MMP9. Among them, only MMP9 was highly expressed in breast cancer than normal. Moreover, molecular docking revealed the six of propolis compounds which exhibited pronounced binding affinity towards MMP-9, better than marimastat as control drug. Dynamic simulation confirmed the stability of chrysin and quercetin as best compounds. Additionally, MM-GBSA analysis revealed a relative binding energy for chrysin (−25.6403 kcal/mol) that was comparable to marimastat (−27.3827 kcal/mol). In conclusion, this study reveals how East Kalimantan Propolis affect breast cancer and emphasizes MMP9 as a key target for future therapeutics.