Abstract
We aimed to ascertain the mechanism underlying the effects of acteoside (ACT) from Ligustrum robustum (Roxb.) Blume (Oleaceae) on lipid metabolism and synthesis. ACT, a water-soluble phenylpropanoid glycoside, is the most abundant and major active component of L. robustum; the leaves of L. robustum, known as kudingcha (bitter tea), have long been used in China as an herbal tea for weight loss. Recently, based on previous studies, our team reached a preliminary conclusion that phenylpropanoid glycosides from L. robustum most likely contribute substantially to reducing lipid levels, but the mechanism remains unclear. Here, we conducted an in silico screen of currently known phenylethanoid glycosides from L. robustum and attempted to explore the hypolipidemic mechanism of ACT, the representative component of phenylethanoid glycosides in L. robustum, using RNA-seq technology, quantitative real-time PCR (qPCR) and Western blotting. First, the screening results for six compounds were docked with 15 human protein targets, and 3 of 15 protein targets were related to cardiovascular diseases. Based on previous experimental data and docking results, we selected ACT, which exerted positive effects, for further study. We generated a lipid accumulation model using HepG2 cells treated with a high concentration of oleic acid and then extracted RNA from cells treated for 24 h with 50 μmol/L ACT. Subsequently, we performed a transcriptomic analysis of the RNA-seq results, which revealed a large number of differentially expressed genes. Finally, we randomly selected some genes and proteins for further validation using qPCR and Western blotting; the results agreed with the RNA-seq data and confirmed their reliability. In conclusion, our experiments proved that ACT from L. robustum alters lipid metabolism and synthesis by regulating the expression of multiple genes, including Scarb1, Scarb2, Srebf1, Dhcr7, Acat2, Hmgcr, Fdft1, and Lss, which are involved several pathways, such as the glycolytic, AMPK, and fatty acid degradation pathways.
Highlights
As the global economy has increased and altered people’s lifestyles, cardio-cerebrovascular diseases have become the top cause of death in humans worldwide, and the mortality rate of these diseases has exceeded that of cancer (WHO, 2013)
Traditional analyses of the efficacy of phenylethanoid glycosides have focused on antitumor, antibacterial, and neuroprotective effects, among others, but few studies have examined their effects on cardiovascular diseases
ACT and isoacteoside docked with phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma (PIK3CG), which has an important relationship with myocardial infarction
Summary
As the global economy has increased and altered people’s lifestyles, cardio-cerebrovascular diseases have become the top cause of death in humans worldwide, and the mortality rate of these diseases has exceeded that of cancer (WHO, 2013). Effective clinical treatments must be developed and administered to lower lipid levels and improve dyslipidemia, changes that will subsequently decrease the morbidity and mortality of cardio-cerebrovascular diseases (Kopin and Lowenstein, 2010; Zoungas et al, 2014). Research on hypolipidemic therapies designed to curtail cardiovascular events has mainly focused on chemical drugs, such as statins, as a primary and effective therapy for people with high plasma cholesterol levels and increased cardiovascular risk; these drugs have been typically prescribed as lifelong therapies (Zoungas et al, 2014). The search for new compounds derived from natural products has become a research hotspot
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