The Kratom-Derived Alkaloid Mitragynine Upregulates the Cortisol Steroidogenic Pathway In a Human Adrenocortical Cell Line

Abstract

<b>Abstract ID 52920</b> <b>Poster Board 424</b> Kratom is a tropical evergreen tree indigenous to Southeast Asia whose leaves and decoctions have long been used in traditional folk medicine for the relief of pain and enhancement of vitality. In recent years kratom use has increased in the United States, where an estimated 10-15 million people use the herb for the self-management of pain and opioid withdrawal. Kratom leaves contain over 40 active alkaloids. Previous studies in our laboratory demonstrated that mitragynine was the only kratom alkaloid that enhanced cortisol secretion in a human adrenocortical cell line. To further investigate the molecular mechanism by which mitragynine enhances cortisol secretion, we examined the effect of mitragynine on the expression of the steroidogenic enzymes and cofactors involved in cortisol production. HAC15 cells were exposed to vehicle or mitragynine (10 μM). After 72 h, mRNA expression of the following steroidogenic enzymes, cofactors, and receptors was examined: CYP11A1, HSD3B2, CYP21A2, CYP11B1, StAR, FDXR, FDX1, and MC2R. While mRNA expression was upregulated for all of these steroidogenic factors, CYP11B1 was induced to the greatest extent (fold change: vehicle, 1.0±0.2; 10 μM mitragynine, 18.4±1.5; n=6). Analysis of protein levels of these steroidogenic factors is underway. These data indicate that mitragynine enhances cortisol secretion <i>in&nbsp;vitro</i> via upregulation of the cortisol synthesis enzymatic pathway. This mechanism may contribute to anti-inflammatory and analgesic actions of kratom <i>in&nbsp;vivo</i>. Additional studies are currently being done to determine what receptor is mediating this stimulation of the cortisol pathway.