Mitragyna speciosa ethanolic extract: Extraction, anti-inflammatory, cytotoxicity, and transdermal delivery assessments

Abstract

This study aimed to investigate the efficiency of extraction procedures for Mitragyna speciosa Korth (M. speciosa) as well as the anti-inflammatory, cytotoxicity, and transdermal delivery potential of M. speciosa ethanolic extract. Extraction of M. speciosa leaves was conducted using three different methods: maceration, ultrasonic-assisted extraction (UAE), and UAE with maceration. The extraction yields obtained were 9.3–23.1% with a mitragynine content of 7.9–10.2%. Mitragynine remaining of M. speciosa extracts was greater than 97% after 30-d storage at various conditions. Cytotoxicity study towards various skin cells reveals that cell growth half inhibitory concentrations (IC50) of M. speciosa extract ranged from 1.4 ± 0.0 to 2.5 ± 0.2 mg/mL. M. speciosa extract exhibited dose-dependent inhibitory effects on nitric oxide production (IC50 = 147.8 ± 9.0 µg/mL) and suppressed pro-inflammatory cytokine expression levels. Ex vivo assessment using porcine ear skin reveals that skin permeation of mitragynine from M. speciosa extract was restricted with permeation flux ranging from 0.4 ± 0.1 to 11.6 ± 1.1 µg·cm−2·h−1 and skin deposition at 24 h ranged from 8.7 ± 2.6 to 60.5 ± 16.2 µg·cm−2. Vehicle composition and lipophilicity were found to be determinants of mitragynine permeation. The mixture of hydrophilic chemical enhancers—propylene glycol and diethylene glycol monoethyl ether—as M. speciosa extract vehicle yielded the highest skin permeability coefficient of mitragynine. These findings offer valuable information that can be utilized for the transdermal and/or topical product development of mitragynine and M. speciosa extract.