Identification of a β-Carboline Alkaloid from Chemoselectively Derived Vanilla Bean Extract and Its Prevention of Lipid Droplet Accumulation in Human Hepatocytes (HepG2)

Abstract

Targeting bioactive compounds to prevent lipid droplet accumulation in the liver, we explored an antioxidative extract from vanilla bean (Vainilla planifolia) after chemo-selective derivatization through heating and acid modification. The chemical analysis of vanilla bean extract through chemoselective derivatization resulted in the identification of sixteen compounds (34–50) using LC-MS/MS analysis. A β-carboline alkaloid with a piperidine C-ring and a vanillin moiety at C-1 (34) was identified by molecular networking and diagnostic fragmentation filtering approaches. β-carboline alkaloid 34 exhibited significant inhibitory activity of lipid droplet accumulation (LDAI) in oleic acid-loaded hepatocellular carcinoma HepG2 cells. The LDAI activity was associated with both activation of lipolysis and suppression of lipogenesis in the cells. The study indicates that crude plant extracts, following chemoselective derivatization, may contain bioactive compounds that could be beneficial in preventing hepatosteatosis and could serve as a source of lead compounds for drug development. This approach may be useful to investigate other mixtures of natural products and food resources.

Inhibition of Lipid Accumulation and Oxidation in Hepatocytes by Bioactive Bean Extracts

“…Previous research has also suggested that phenolic metabolites play a role in preventing metabolic diseases such as MAFDL/MASH. These results suggest that bioactive bean extracts could be a potential resource for the development of nutraceuticals and furthering natural drug discovery for the prevention and management of MAFLD/MASH and oxidative stress-related diseases [28]. Additional research is required to assess the bioavailability of bioactive metabolites from various natural and food extracts.…”

“…Previous research has also suggested that phenolic metabolites play a role in preventing metabolic diseases such as MAFDL/MASH. In this study, we tested the ability of the bioactive LDAI extracts to inhibit both neutral lipids TAG and oxidized species of TGOOH, which are implicated in metabolic disorders through oxidative stress [12,28,32].…”

“…However, it is noteworthy that HepG2 cells are more suitable for use in the stable screening of antioxidants than primary cells because of the availability and easy growth of HepG2 cells. Thus, the proposed method using HepG2 cells is a promising tool that can be used worldwide [12,28,32]. Finally, an oxidative lipidomics study of food extracts and derived food compounds under individual FFAs and the combination of FFAs to clarify the effect of LDAI on prevention and drug discovery related to MAFLD/MASH and related metabolic disorders was linked to the excessive production of LDs and oxLDs.…”

“…These results suggest that β-carboline alkaloids may be potentially useful in preventing MAFLD. Crude extracts, including medicinal plants and functional foods, are potential sources of LDAI candidates [12,28]. Therefore, functional foods and nutraceuticals may be beneficial in the management of chronic diseases, including MAFLD/MASH, and offer a potential target for drug discovery and developments.…”

“…Following this approach, we collected familiar beans from the Hokkaido region for use as edible foodstuffs. We examined their effects on hepatocytes as a source of potential natural bioactive substances regulating LDAI, TAG and TGOOH [12,28,29]. Beans are essential crops used as the main vegetable in many countries.…”