Molecular networking analysis and clinical study of the plant extract mixture for hangover relief

Abstract

Molecular networking analysis and clinical study of the plant extract mixture for hangover relief Eun Kyu Lee Department of Pharmacy The Graduate School Hanyang University Hangover is characterized by uncomfortable physiological symptoms primarily arising from the toxic substance acetaldehyde generated in the alcohol metabolism process. Rapid breakdown of acetaldehyde, metabolized by alcohol dehydrogenase (ADH), is crucial for alleviating symptoms induced by alcohol. In this study, enzyme activity in three plants Mesembryanthemum crystallinum, Pueraria lobata flower and Artemisia indica was identified for ADH and aldehyde dehydrogenase (ALDH). These plant extracts exhibited significant enzyme activity in laboratory experiments and were combined to create the extract mixture known as HY_IPA. A molecular networking approach was employed to identify marker compounds. Consequently, seven effective substances eupatilin, rutin, isoquercitrin, daidzein, umbelliferone, esculetin and indol-3-carboxaldehyde were discovered within HY_IPA. These compounds exhibited various research- proven effects, including liver protection and anti-inflammatory properties, leading to the expectation that HY_IPA could relieve hangover symptoms. To test this hypothesis, a randomized, double-blind, parallel-group, placebo-controlled clinical trial was conducted on 80 individuals experiencing hangover symptoms. ethanol intake was proportionate to body weight at 0.9 g/bw, with 40% whiskey. The total acute hangover scale scores were significantly lower in the HY_IPA group compared to the placebo group (5.24 ± 5.78 vs. 18.54 ± 18.50, p < 0.0001). All nine indicators on the hangover symptom questionnaire showed significant improvement in the HY_IPA group (p < 0.01). Blood ethanol and acetaldehyde concentrations in the HY_IPA group rapidly decreased from 30 minutes post- drinking (p < 0.05). The accelerated hangover relief is attributed to increased ADH and ALDH activity. The administration of the hangover relief agent was compared to the placebo group. At 0.5 and 1 hour after drinking, the HY_IPA group showed significantly lower blood ethanol concentrations (p < 0.05), and there was a trend of decreased Tmax (p < 0.05) and Cmax in the HY_IPA group (p = 0.0586). Blood acetaldehyde levels were significantly lower in the HY_IPA group at 0.5, 1, 2, and 4 hours compared to the control group (p < 0.05), with a significant decrease in AUC and Cmax (p < 0.05). The hangover severity score demonstrated a significant correlation with ethanol and acetaldehyde concentration, and ADH and ALDH activity at 1 hour after ethanol consumption (ethanol: r = 0.3570, p = 0.0301; acetaldehyde: r = 0.4335, p = 0.0074; ADH: r = -0.1529, p = 0.3662; ALDH: r = 0.489, p = 0.0021). These results suggest that the hangover relief agent increases ALDH enzyme activity, effectively promoting the metabolism of acetaldehyde, indicating its potential as a hangover relief agent. Keywords: Plant-based extract mixture; Hangover; Acute Hangover Scale; Alcohol metabolism; Alcohol dehydrogenase; Acetaldehyde dehydrogenase, Molecular Networking