Introduction:Alternative treatment for cancer from herbal medicine has gained interest due to its benefits on im-mune modulation, improving the survival and quality of life. Mitragyna speciosa (M. speciosa) or Kratom is an indig-enous plant that can be found in Thailand and northern part of Peninsular Malaysia has becomes popular in recent years due to its ability to exhibit the opioid-like effects of analgesia. Mitragynine is the main alkaloid in M. speciosa which is found to reduce gastrointestinal motility and has been used by local communities as traditional treatment for diarrhoea and many other diseases. However, there is lack of scientific evidence to show that M. speciosa has anti-oxidative and anti-cancer properties especially in colorectal cancer. Therefore, our study aims to evaluate the anti-oxidative properties of M. Speciosa methanolic extract (MSME) and its effects on colorectal cancer cell line, SW480. Methods: The anti-oxidant content and scavenging activity of MSME were determined by total phenolic content (TPC) assay and total flavonoid content (TFC) assay as well as 2,2’-azino-bis (3-ethylbenzothiazoline-6-sul-phonic acid) (ABTS) assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay respectively. Cytotoxicity and cytokine inhibitory effects of MSME on SW480 cells were determined by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) and cytokine beads array (CBA), respectively. Results: The TPC of MSME (0.1mg/ml = 85.85 ± 8.25 mg GAE/g extract; 1mg/ml = 167.43 ± 13.50 mg GAE/g extract; 10mg/ml = 408.94 ±7.17 mg GAE/g extract) was lower than pterostilbene, the positive control drug (76.37 ± 2.75; 230.52 ± 10.92; 835.44 ± 6.84 mg GAE/g extract). Conversely, the TFC of MSME (0.1mg/ml = 32.17 ± 27.92 mg QE/g extract; 1mg/ml = 347.72 ± 15.97 mg QE /g extract; 10mg/ml = 739.81 ± 5.56 mg QE /g extract) was slightly higher than pteros-tilbene (ND; 212.73 ± 17.92; 700.50 ± 3.47 mg QE/g extract). In DPPH assay, MSME showed comparatively similar antioxidant scavenging activity (IC50=4.34μg/ml) with pterostilbene (IC50=4.393μg/ml). However, MSME showed lower anti-oxidant scavenging activity (IC50=4.26μg/ml) than pterostilbene (IC50=1.556μg/ml) as measured by ABTS assay. In cytotoxicity assay, IC50 of MSME on SW480 cells was determined to be at 1.486 mg/ml. Overexpression of cytokines such as IL-6, IL-8 (CXCR8) and IL-10 could potentially promote tumour cell proliferation, growth and metastasis. Increased production of these cytokines through LPS stimulation in SW480 was slightly reduced by treat-ment with MSME. Conclusion: MSME could have a potential bioactive compound that possesses anti-oxidative and anti-cancer properties that would be beneficial as an alternative treatment of colorectal cancer.
Introduction: Glycogen synthase kinase-3 (GSK-3) is an important immune regulator that controls inflammation via inhibition of its protein kinase activities. Persistent inflammatory responses through the activation of
immune cells and excessive production of immune mediators may cause tissue destruction and implicated in the
development of chronic inflammatory diseases. The objective of this study was to examine the role of Tideglusib,
a GSK-3 inhibitor, in inflammatory responses elicited through macrophage activation by investigating the
expression of cell surface biomarkers and inflammatory molecule levels. Method: The effects of GSK-3 inhibition by Tideglusib on the expression of CD11b and CD40 and secretion of pro-inflammatory cytokines in the
lipopolysaccharide (LPS)-activated macrophage-derived RAW 264.7 cells were determined by flow cytometry, while
the presence of nitric oxide (NO) was determined by Griess assay. Results: Stimulation of RAW 264.7 cells with LPS
increased substantial levels of CD11b and CD40 expressions, and secretion of NO, TNF-α, and MCP-1. However,
the expression of these molecules was suppressed through inhibition of GSK-3. Conclusion: These findings suggest
the significant role of Tideglusib to limit the upregulation of immune responses in activated macrophages, and as a
potential anti-inflammatory drug for the intervention and treatment of inflammatory diseases.