In Vitro and in Vivo Effects of Three Different Mitragyna speciosa Korth Leaf Extracts on Phase II Drug Metabolizing Enzymes—Glutathione Transferases (GSTs)

Abstract

In the present study, we investigate the effects of three different Mitragyna speciosa extracts, namely methanolic, aqueous and total alkaloid extracts, on glutathione transferase-specific activity in male Sprague Dawley rat liver cytosol in vitro and in vivo. In the in vitro study, the effect of Mitragyna speciosa extracts (0.01 to 750 µg/mL) against the specific activity of glutathione transferases was examined in rat liver cytosolic fraction from untreated rats. Our data show concentration dependent inhibition of cytosolic GSTs when Mitragyna speciosa extract was added into the reaction mixture. At the highest concentration used, the methanolic extract showed the highest GSTs specific activity inhibition (61%), followed by aqueous (50%) and total alkaloid extract (43%), respectively. In in vivo study, three different dosages; 50, 100 and 200 mg/kg for methanolic and aqueous extracts and 5, 10 and 20 mg/kg for total alkaloid extract were given orally for 14 days. An increase in GST specific activity was generally observed. However, only Mitragyna speciosa aqueous extract with a dosage of 100 mg/kg showed significant results: 129% compared to control.

Intrahepatic Cholestasis Following Abuse of Powdered Kratom (Mitragyna speciosa)

“…The effect of recently published substances in M. speciosa (alkaloids, flavonoids, saponins, triterpenoid saponins, and glycoside derivatives) [29] on health and, in particular, on the liver are not studied well. A recent study showed a slight elevation in glutathione-S-transferase in mice after administration of M. speciosa extracts [30] as a possible sign of strain on the liver. Other than that, toxicity studies are rare and do not show relevant toxicity in most reports.…”

Mitragyna speciosa Leaf Extract Exhibits Antipsychotic-Like Effect with the Potential to Alleviate Positive and Negative Symptoms of Psychosis in Mice

“…4.44 μg /ml or equally to 4.4% w/w of mitragynine was quantified in MMS which was consistent with earlier published reports (Jansen and Prast, 1988a; Ponglux et al, 1994; Chittrakarn et al, 2010). Mitragynine, being the maximum dominant active alkaloid present in M. speciosa is responsible for the diverse pharmacological activities of this plant (Azizi et al, 2010). Interestingly, mitragynine significantly inhibited the dopamine (D 2 ) and serotonin (5-HT 2 ) receptors in a radioligand-binding assay (Boyer et al, 2008).…”

Unlike Morphine, Long-Term Exposure to Analgesic Mitragynine, 7-Hydroxymitragynine, Paynantheine, and Speciociliatine Alkaloids Does Not Contribute to Antinociceptive Tolerance of μ-Opioid Receptors

“…Since they share a typical chemical skeleton with different structural conformation or substitution patterns. On the other hand, toxicity is a truly complex phenomenon that is in uenced by several factors like cellular penetration, diffusion, distribution, metabolism, innate toxicity of the agent, and target cell speci cations [23][24].…”