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.
Aquatic-based collagens have attracted much interest due to their great potential application for biomedical sectors, including the tissue engineering sector, as a major component of the extracellular matrix in humans. Their physical and biochemical characteristics offer advantages over mammalian-based collagen; for example, they have excellent biocompatibility and biodegradability, are easy to extract, and pose a relatively low immunological risk to mammalian products. The utilization of aquatic-based collagen also has fewer religious restrictions and lower production costs. Aquatic-based collagen also creates high-added value and good environmental sustainability by aquatic waste utilization. Thus, this study aims to overview aquatic collagen’s characteristics, extraction, and fabrication. It also highlights its potential application for tissue engineering and the regeneration of bone, cartilage, dental, skin, and vascular tissue. Moreover, this review highlights the recent research in aquatic collagen, future prospects, and challenges for it as an alternative biomaterial for tissue engineering and regenerative medicines.
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.
The sponge is one of the potential sources of bioactive compounds. Among them, the sponge Aaptos has been a promising source of leading drugs including aaptamine (1). This study investigated the aaptamine (1), spectroscopically determined, from Aaptos sp. collected from Bunaken National Park, Indonesia, as an anticancer agent, specifically targeting colorectal cancers (CRCs). Compound 1 showed potent cytotoxicity against DLD-1 and Caco-2 with IC50 values of 30.3 and 236.8 μg/mL, respectively. In addition, the exposure of compound 1 on those colorectal cancer cells could promote cell cycle arrest and induce necrotic cell death.