Insight into Lotusine and Puerarin in Repairing Alcohol-Induced Metabolic Disorder Based on UPLC-MS/MS

Abstract

Alcohol is an essential element in human culture. However, alcoholism has contributed to numerous health issues, including alcoholic fatty liver and sudden death. We found that the alkaloid lotusine possessed hepato- and neuroprotection against alcohol injuries. Lotusine showed comparable protective effects to puerarin, a widely recognized antagonist against alcohol damage. To better understand the metabolic response to alcohol injury and antagonist molecules, we applied sensitive zebrafish and LC-ESI-MS to collect metabolites related to alcohol, puerarin and lotusine exposure. LC-MS identified 119 metabolites with important physiological roles. Differential metabolomic analysis showed that alcohol caused abnormal expression of 82 metabolites (60 up-regulated and 22 down-regulated). These differential metabolites involved 18 metabolic pathways and modules, including apoptosis, necroptosis, nucleotide and fatty acid metabolism. Puerarin reversed seven metabolite variations induced by alcohol, which were related to necroptosis and sphingolipid metabolism. Lotusine was found to repair five metabolites disorders invoked by alcohol, mainly through nucleotide metabolism and glutathione metabolism. In phenotypic bioassay, lotusine showed similar activities to puerarin in alleviating behavioral abnormalities, neuroapoptosis and hepatic lipid accumulation induced by alcohol exposure. Our findings provided a new antagonist, lotusine, for alcohol-induced damage and explored the roles in repairing abnormal metabolism.

Lotusine ameliorates propionic acid‐induced autism spectrum disorder‐like behavior in mice by activating D1 dopamine receptor in medial prefrontal cortex

“…Lotusine, an alkaloid extracted from Nelumbinis Plumula , is well‐established as a safe compound (Harishkumar & Selvaraj, 2020; Xu et al, 2022). Research in zebrafish larvae demonstrated the absence of malformations following exposure to lotusine below 200 μM for seven consecutive days (Xu et al, 2022).…”

“…Lotusine, an alkaloid extracted from Nelumbinis Plumula , is well‐established as a safe compound (Harishkumar & Selvaraj, 2020; Xu et al, 2022). Research in zebrafish larvae demonstrated the absence of malformations following exposure to lotusine below 200 μM for seven consecutive days (Xu et al, 2022). Lotusine has exhibited effectiveness in addressing conditions such as erectile dysfunction (Zhao et al, 2022), heart diseases, hypertension (Zhan et al, 2023), and neurological diseases (Xu et al, 2022).…”

“…Research in zebrafish larvae demonstrated the absence of malformations following exposure to lotusine below 200 μM for seven consecutive days (Xu et al, 2022). Lotusine has exhibited effectiveness in addressing conditions such as erectile dysfunction (Zhao et al, 2022), heart diseases, hypertension (Zhan et al, 2023), and neurological diseases (Xu et al, 2022). Our findings extend its potential utility to alleviate social impairment and cognitive dysfunction in the ICV‐PPA mouse model.…”

“…Lotusine, as a main active ingredient of Nelumbinis Plumula , is a natural alkaloid known for its antioxidant (Harishkumar & Selvaraj, 2020), antihypertensive (Zhan et al, 2023), and cardiovascular properties (Harishkumar & Selvaraj, 2020). Recent research also suggests that lotusine holds promise in treating neurological diseases by restoring abnormal behavior and neuron apoptosis in zebrafish larvae following alcohol exposure (Xu et al, 2022). However, its therapeutic potential in the context of ASD remains largely unexplored.…”