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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.

Doxorubicin is an effective chemotherapeutic agent in the treatment of solid hematological and non-hematological carcinoma. However, its long-term usage could result in side effects, such as cardiomyopathy, chronic heart failure, neurotoxicity and cancer cell resistance. In this study, we reported the sensitivity enhancement of A549 human lung cancer cells on doxorubicin at a low dose (0.1 ppm) in combination with 10–60 ppm of crude and alkaloid extracts derived from the leaves of Kratom (Mitragyna speciosa (Korth.) Havil. Rubiaceae). A549 cancer cell lines were insensitive to the crude extract containing low mitragynine (MG) (4–5%), while these cells were moderately inhibited by the alkaloid extract containing 40–45% MG (IC50 of 48–55 ppm). The alkaloid extract was found to inhibit A549 cancer cells via apoptosis as suggested by the higher relative fluorescence intensity with Annexin compared to that in propidium iodide (PI), i.e., a positive Annexin and a negative PI. The combination of crude extract and doxorubicin sensitized A549 cancer cells to doxorubicin by 1.3 to 2.4 times, while the combination with the alkaloid induced a 2.6- to 3.4-fold increase in sensitivity. The calculated combination index (CI) for doxorubicin with the crude and alkaloid extracts was 0.6 and 0.3, respectively, showing potential synergistic combinations to reduce the level of dosage of doxorubicin used in chemotherapy. In addition, the synergistic enhancement effect of crude extract on the cytotoxic activity of doxorubicin provides insights into the plausibility of non-alkaloids to influence the biological activities of Kratom.

Tuberculosis (TB) remains a world health problem due to the high number of affected individuals, high mortality rates, prolonged treatment durations, and the increasing prevalence of resistance to commercial TB drugs. The emergence of resistance to anti-TB drugs has necessitated urgent research into drug discovery and development, focusing on novel mechanisms of action against Mycobacterium tuberculosis resistant strains. Natural products, with their remarkable structural diversity and bioactivity, are promising sources for the development of new TB drugs or the identification of potential chemical scaffolds exhibiting potent and novel biological activity with minimal or no cytotoxicity to host cells. This review focuses on potent anti-TB natural products with minimum inhibitory concentration (MIC) values below 5 µg mL –1 and examines their structure–activity relationship (SAR). Significant characteristics and relevant biological properties of each compound were analysed using a Random Forest, machine learning algorithm, to explore SAR. Using molecular docking, AutoDock Vina was utilised to assess molecular interactions with protein targets, and predictive accuracy was enhanced using the XGBoost machine learning model. These analyses provide insights into the mode of action of these compounds and help identify key structural features contributing to their anti-TB activity. In addition, this review examines the correlation between the potency of selected anti-TB compounds and their cytotoxicity, offering valuable insights for the identification of promising scaffolds in TB drug discovery. Graphical Abstract

Background Kratom alleviates pain by activating μu-opioid receptors (MOR), which trigger serotonin release to produce analgesia. Serotonin also interferes drug abuse effect. This study aimed to determine the role of serotonin in kratom-induced pain relief and withdrawal symptoms in mice. Methods The analgesic effect was assessed using the hot-plate test. To induce withdrawal symptoms, mice received naloxone after being treated with kratom extracts for five days at increasing doses. Another group of morphine-dependent mice was treated with kratom extracts to ameliorate their withdrawal symptoms. A molecular docking study and molecular dynamics were conducted to predict the binding target of alkaloid kratom for increasing serotonin levels. Results Chronic administration of kratom alkaloid extract (20 mg/kg) produced analgesic effects comparable to morphine (10 mg/kg). In contrast, kratom crude extracts (10 mg/kg and 20 mg/kg) demonstrated lower analgesia activity. This analgesic effect was mediated by MOR activation, leading to decreased intracellular cAMP and increased serotonin transmission. Repeated and increasing doses of crude or alkaloid kratom extracts (8 mg/kg to 45 mg/kg) produced less severe withdrawal symptoms than morphine. Increased dopamine and serotonin levels contributed to the onset of withdrawal symptoms. In the morphine group, treatment with kratom extracts increased serotonin levels while reducing dopamine. Molecular docking and molecular dynamics result revealed that kratom alkaloids interacts more readily with tryptophan hydroxylase, the enzyme responsible for serotonin biosynthesis. Conclusions Kratom extracts have the potential to provide analgesic effects and withdrawal symptoms, both of which are mediated by elevated serotonin release. Highlights • The alkaloid extract of kratom produces an analgesic effect similar to morphine but with a longer duration of action. • MOR activation, decreased cAMP, and increased serotonin levels contribute to the analgesic effect, while dopamine levels remain unaffected. • Compare to morphine, alkaloid and crude extracts of kratom cause less severe withdrawal symptoms. • MOR activation, increased cAMP, elevated serotonin and dopamine levels contribute to the emergence of withdrawal symptoms. • In morphine-dependent mice, treatment with alkaloid and crude extracts of kratom increased serotonin levels but decreased dopamine levels.

Diabetes mellitus (DM) is a metabolic disease that can cause many complications. The occurrence of urinary tract infection is also considered to be the cause of complications in patients with DM. This study aimed to evaluate the prevalence of urinary tract infection (UTI) and antibiotic-resistant bacteria found in urine culture from patients with DM in Surabaya, Indonesia. This study was conducted with a retrospective cross-sectional study design, using a database of 1551 patients with DM admitted to Haji Hospital, Surabaya, Indonesia, from January 2017 to December 2018. Data regarding the bacteria isolated from urine and antimicrobial sensitivity were analyzed. The prevalence of UTI was 3.93% - 61 patients were confirmed with urine culture for UTI diagnosis. The predominant isolates found were (24.5%) and (8%). This study also showed multidrug-resistant organisms (MDRO) found in UTI such as MDRO (3.3 %), MDRO (3.3%), MDRO (1.6%), extended-spectrum beta-lactamase (ESBL) (3.3%). The were sensitive to fosfomycin (93%), meropenem (93%) and nitrofurantoin (67%). No significant difference in the prevalence of UTI was found among ages, sex, and duration of disease in all patients with DM. The cases of UTI seen in patients with DM show the importance of monitoring UTI occurrence in this patient category to ensure better treatment for these patients.

Antimicrobial activity of black soldier fly larvae extract against gram-positive and gram-negative pathogenic bacteria has been discovered. Water-soluble extracts have the most potential and effectiveness as antimicrobials, with MIC values ranging from 12.5 to 25 mg/mL for both gram-positive and gram-negative bacteria. BSF larvae also create peptides called defensins and cecropins, which have antibacterial properties. Defensins were the best and most effective peptides in inhibiting bacterial growth, inhibiting both gram-positive and gram-negative bacteria (MIC value = > 29.97 µM), while cecropins were more effective on gram-negative bacteria (MIC value= 0.52 – 2.07 µM) than gram-positive bacteria (MIC value not detected).

The demand of sweetpotato for fresh consumption, processed foods, and export continues to rise. Thus, the tuber characteristics should be tailored with market demand. The honey sweetpotato variety, Bima Pasru demonstrates strong adaptation in Lumajang, one of the sweetpotato central area in East Java. This variety has desired characteristics for domestic and foreign markets. The variety exhibit morphological traits such as: a semi-compact plant type, stem internode diameter 3.7 mm, stem internode length 2 cm, dominant color of tendril is greenish red, secondary color of tendril is green on shoots, shape of lobe leaf skeletal with depth of leaf lobe very deep with number of lobes are 5, forms of central lobe lanceolatus by which medium adult leaf size with green adult leaf color and reddish-green young leaves. The tuber shape oblong-beaked, the skin color of the tubers is creamy, the dominant color of the tuber flesh is pale yellow and the secondary color is orange. Bima Pasru has a sweet taste with a moisture content of around 67.75%, dry matter content 31.29%, fiber 2.38% (dw), starch ±55.68% (dw), and reducing sugar 7.51% (dw). The yield potential is high, approximately 34.60t/ha with an average yield 27.0 t/ha, the tubers reached harvest maturity 4.5 months after planting, this variety is suitable for cultivation in alluvial soils as in Lumajang Regency. With regards to its uniform tuber size and sweet taste, Bima Pasru is tailored for baked products applications.