The safety assessment assumptions suggest that the use of Mitragyna speciosa Korth leaves within the range of pharmacologically active doses as reported in the literature is probably safe however caution should be taken as MSE toxicity in this study was found to be enhanced by metabolism particularly by CYP 2E1. Thus the combination consumption of Mitragyna speciosa Korth leaves with CYP 2E1 inducers may shift toxicity closer to doses that are pharmacologically active. Based on the current findings observed in the present studies it is concluded that the methanol-chloroform extract (MSE) of the Mitragyna speciosa Korth (Kratom) leaves and its dominant alkaloid mitragynine (MIT) have potential to cause cytotoxicity to mammalian cells at high doses and is possibly harmful to human users. Kratom Interactions Ssri mIT is proposed to be a major contributor to MSE cytotoxicity. The main target system of MSE and MIT cytotoxicity is the central nervous system as shown by sensitivity of neuroblastoma cell lines (SH-SY5Y) throughout the studies.
As shown in the table 3. MLA results for MIT in the presence or absence of rat liver S9 kratom bali dose show no evidence of genotoxicity. The outcome of this experiment would seem to be contrary to what was seen for MSE. In the absence of rat liver S9 (Table 3.
The pellet was then resuspended in 5 ml pre-warmed PBS and re-centrifuged second times and supernatant was removed as before. C (5% CO2) for 24 hours. CM0 volume (ml) 2.
The main target system of MSE and MIT cytotoxicity is the central nervous system as shown by sensitivity of neuroblastoma cell lines (SH-SY5Y) throughout the studies. In general MSE and to a lesser extent MIT were found to exert their dose dependant cytotoxicity effects in all human cell lines examined both
in acute treatment and also in the longer Kratom Interactions Ssri term as assessed by the clonogenicity assay. M arrest for HEK 293 cells. MIT has a lesser effect and cells arrest mainly at G1 phase in SH-SY5Y cells. The cell arrest occurring at high doses of MIT was found to be correlated with p53 and p21 expression although the expression changes were marginal compared to control and lower dose groups. The mechanism for cell cycle arrest in the cells treated with high doses of MSE remains unclear as there was no correlation with p53 and p21 as both proteins were lost after the treatment.
As shown in fig. A there was a non-significant difference noted for caspase 3 and 7 activities for MSE treated cells compared to control groups at 4 hr incubation time point. For MIT treated cells does kratom drug test (Fig.
Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death?. Evaluation of Kratom Interactions Ssri triacetyloleandomycin erowid kratom liver alpha-naphtoflavone and dietyldithiocarbamate as selectivechemical probes for inhibition of human cytochrome P450.
Arch Biochem Biophys. Drug discovery from natural sources. The AAPs Journal 8: E239-E253. A Block N.
This finding supports the cytological examinations previously noted where the cells were predominantly necrotic and in the late stage of apoptosis. Control 1 10 50 100 250 91. Q2 (%) 3. Q4 (%) 0. Annexin V conjugate and 7-AAD.
Bio-rad laboratories (Hemel Hempstead U. Cell cycle analysis by flow cytometry HEK 293 or SH-SY5Y cells (105 cells per well) or MCL-5 cells (3. After pre-equilibration period of 24 hrs for HEK 293 or SH-SY5Y cells and 2 hrs for MCL-5 cells they were exposed to various concentrations of MSE and MIT for the designated period of treatment.
D ) in MSE and MIT treated SH-SY5Y cells as determined by the Trypan blue exclusion assay. Values are the mean of quadruplet cultures of MSE experiment and duplicate cultures of MIT experiment. Bars are SEM. ANOVA with Dunnet post test. IC50 values (Inhibition concentration that caused 50% cell death) of 24 hr treatment with MSE and MIT treated cell lines.
In parallel caspase inhibitors were employed to confirm the outcome of the former assays. The caspase-8 and caspase-9 colorimetric assays purchased from Invitrogen U. IETD and LEHD respectively. These assays were carried out according to manufacturer instructions.