Comparative brain proteome analysis of an Indole Alkaloid of Kratom, Mitragynine and Kratom juice in rats.

Mitragyna speciosa, commonly known as kratom, is a medicinal plant that is widely used for various medical conditions. The major alkaloid in kratom is mitragynine which binds partially to opioid receptors to produce opioid-like effects. In this study, we compared the effects of mitragynine various doses with kratom juice on neurobehavioral, neurochemical changes as well as calretinin protein expression. Sprague-Dawley rats were divided into ten groups (n = 6) and respectively received the following treatment: group 1 (20 % Tween 80), group 2 (morphine 10 mg/kg), groups 3-9, mitragynine graded doses (0.25, 0.5, 1, 5, 10, 15, and 30 mg/kg) and group 10 was given kratom juice (500 mg/kg). All the treatments were given as a single dosing and then for four consecutive days. On day 5, an open field test box was used for the assessment of behavioural parameters using global scoring. Whole brains were harvested and the effects of the treatments on some neurotransmitters related to addiction were determined using ELISA kits. Proteomic analysis was also conducted using two-dimensional gel electrophoresis and a western blot was conducted to determine the changes in the expression level of calretinin. Mitragynine but not kratom juice significantly increased some behavioural signs. Mitragynine doses above 5 mg/kg significantly increased dopamine, 5-HT, and GABA concentrations, whereas kratom juice only elevated GABA levels. Rat brain proteome analysis revealed that mitragynine significantly up-regulated calretinin. Western blot analysis shows that mitragynine but not kratom juice, significantly increased the expression level of calretinin. These findings suggest that kratom juice at the dose tested (500 mg/kg) may pose less risk of addiction compared to pure mitragynine at various doses.