Cyclooxygenase (COX) and lipoxygenase (LOX) enzymes play a pivotal role in producing pro-inflammatory eicosanoids, including prostaglandins (PGs) and leukotrienes (LTs), in the inflammation process. Mitragynine is a primary alkaloid contained in the kratom’s leaves and has been reported to show anti-inflammatory activity by suppressing COX-2 mRNA translation to lowering PGs synthesis. In this study, the Kratom’s alkaloid extract containing ~ 46% mitragynine was found to exhibit dual inhibition activity towards COX-2/5-LOX enzymes at concentrations below 25 ppm in the LPS-induced RAW 264.7 macrophage cells. At these levels, no cell toxicity was observed while the cells became death (e.g., 10–46% viability at 50–100 ppm) and only COX-2 inhibition activity was observed after exposed with more than 25 ppm of alkaloid extract. In contrast, the methanolic-crude extract of Kratom’s leaf containing ~ 5% mitragynine showed no inhibition toward COX-2/5-LOX enzymes and did not toxic onto the cells, even after treated at 100 ppm. The alkaloid extract suppressed several antiinflammation parameters, including ROS (64% reduction at 25 ppm), NO (30% reduction at 25 ppm), TNF-α (~ 50% reduction at 25 ppm), and IL-6 production (60% reduction at 6.25 ppm). In silico molecular studies indicated strong binding affinity of Kratom alkaloids to COX-2 and 5-LOX active sites, supporting the Kratom’s alkaloids to have great potential dual inhibition activity towards COX-2/5-LOX enzymes and to be developed as a safer NSAIDs with fewer side effects.

Breast cancer ranks as the second leading cause of death among women, but early screening and self-awareness can help prevent it. Hormone therapy drugs that target estrogen levels offer potential treatments. However, conventional drug discovery entails extensive, costly processes. This study presents a framework for analyzing the quantitative structure–activity relationship (QSAR) of estrogen receptor alpha inhibitors. Our approach utilizes supervised learning, integrating self-attention Transformer and molecular graph information, to predict estrogen receptor alpha inhibitors. We established five classification models for predicting these inhibitors in breast cancer. Among these models, our proposed MATH model achieved remarkable precision, recall, F1 score, and specificity, with values of 0.952, 0.972, 0.960, and 0.922, respectively, alongside an ROC AUC of 0.977. MATH exhibited robust performance, suggesting its potential to assist pharmaceutical and health researchers in identifying candidate compounds for estrogen alpha inhibitors and guiding drug discovery pathways.

The human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) plays a significant role in viral replication and is one of the targets for anti-HIV. However, a mutation in viral strains rapidly developed the resistance of the com-pounds to the protein, reducing the effectiveness of the inhibitors. This work seeks to utilize machine learning-based quantitative structure-activity relationship (QSAR) analysis in combination with molecular docking simulations to forecast the presence of active compounds derived from medicinal plants. Specifically, the objective is to identify com-pounds that have the potential to operate as inhibitors of HIV-1 reverse transcriptase (RT), encompassing both wild-type and mutant variants. It is demonstrated that some substances are no longer suitable as inhibitors due to changes in the HIV-1 RT enzyme. Based on the screening results, four medicinal plants, Melissa officinalis, Punica granatum, Psidium guajava, and Curcuma longa, are worth further investigation. Nevertheless, the findings from the in vitro study suggest that extracts derived from pomegranate rind and guava leaves exhibit significant promise as HIV-1 RT inhibitors.

Emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone) is an anthraquinone bioactive compound used as a lead compound because it exhibits potential anticancer properties. Structural modifications were made at the C3 position and its relationship to cytotoxic activity against the HepG2 cell line to determine the pharmacophore group of this compound. The hydroxy group at C3 emodin is converted to an ester group to produce 3-acetyl emodin. In addition, docking simulations into the cancer target protein casein kinase-2 were also carried out to predict molecular interactions. Emodin was reacted with anhydrous acetate and confirmed the product confirmation using LCMS/MS, FTIR, 1H-NMR, and 13C-NMR. Emodin and 3-acetyl emodin were tested for cytotoxicity against HepG2 cells in vitro. Cytotoxic emodin and 3-acetyl emodin tests on HepG2 cells resulted in Cytotoxic concentrations 50 (CC50) of 0.54 mM and 0.42 mM, respectively. The results showed that modifying the C3 hydroxyl group with acetyl can increase the cytotoxic effect more than emodin. This research is expected to provide information regarding the structure-activity relationship of emodin in cancer cells and the expansion of new drug applications for additional cancers.

Cyclooxygenase (COX) and lipoxygenase (LOX) enzymes play a crucial role in the production of pro-inflammatory eicosanoids, including prostaglandins and leukotrienes (LTs) via arachidonic acid (AA) pathways. Non-steroidal anti-inflammatory drugs (NSAIDs) typically work by inhibiting COX enzymes (COX-1, COX-2) to alleviate inflammatory responses in our bodies. However, the use of these selective COX inhibitors results in an upregulation of the AA pathway. This condition stimulates the LOX enzymes to increase LT production, exacerbating the severity of the disorders. In this study, the alkaloid extract derived from the leaf of Mitragyna speciosa (Kratom) demonstrated a dual inhibitory effect on COX-2/5-LOX enzymes in lipopolysaccharides (LPS)-induced RAW 264.7 macrophage cells. The alkaloid extract containing ~ 46% mitragynine inhibited COX-2 and 5-LOX activity at concentrations of less than 25 ppm with no toxicity to the cells. Above 25 ppm, the alkaloid extract exhibited toxicity to the cells (e.g,, ~ 46% viability at 50 ppm) and only inhibited COX-2 activity. In contrast, the Kratom crude extract containing ~ 5% mitragynine did not inhibit COX-2 or 5-LOX activity in LPS-induced RAW 264.7 macrophage cells at more than 25 ppm and did not exhibit toxicity to the cells even at 100 ppm. The alkaloid compounds in the Kratom leaf are likely responsible for this activity, as the alkaloid extract containing these biomolecules suppressed reactive oxygen species (ROS), nitric oxide (NO), inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Molecular studies also suggested a strong binding affinity of Kratom alkaloids to the active sites of COX-2 and 5-LOX. The dual inhibitory activity of the Kratom alkaloids against COX-2 and 5-LOX provides insights into their potential as safer NSAIDs.