Allicin and Capsaicin Ameliorated Hypercholesterolemia by Upregulating LDLR and Downregulating PCSK9 Expression in HepG2 Cells

Abstract

Hypercholesterolemia is a common cause of cardiovascular diseases (CVDs). Although allicin and capsaicin possess hypolipidemic effects through several molecular mechanisms, their effects on LDLR and PCSK9 expression are still unknown. This study aimed to investigate the effects of allicin and capsaicin on LDLR and PCSK9 expression in HepG2 cells. The effects of allicin and capsaicin on cell viability were evaluated by MTT assay and trypan blue exclusion assay. Low-density lipoprotein receptor (LDLR) levels and LDL uptake were determined by flow cytometry and confocal laser scanning microscopy (CLSM), respectively. RT-qPCR and Western blot analyses were performed to evaluate the expression of PCSK9, LDLR, SREBP-2, and HNF1α. ELISA was used to measure PCSK9 levels in culture media. Allicin and capsaicin increased the protein expression levels of LDLR via activation of the transcription factor SREBP2. However, allicin and capsaicin decreased the expression of PCSK9 protein and the secretion of PCSK9 in culture media via the suppression of HNF1α. Moreover, allicin and capsaicin increased LDL uptake into HepG2 cells. The efficacies of the hypolipidemic effects of allicin (200 µM) and capsaicin (200 µM) were comparable to that of atorvastatin (10 µM) in this study. In conclusion, allicin and capsaicin possessed hypolipidemic effects via the upregulation of LDLR and downregulation of PCSK9 expression, thereby enhancing LDL uptake into HepG2 cells. This indicates that allicin and capsaicin should be used as potent supplements to ameliorate hypercholesterolemia.

Investigating the Hypolipidemic Mechanism of Anthocyanins Combined with Allicin in Rats Using Network Pharmacology

“…According to Nawaka N et al, allicin increases the absorption of LDL by HepG2 cells by upregulating LDLR and downregulating PCSK9 expression. This suggests that using allicin as a supplement to treat hyperlipidemia is possible [7] . According to studies, allicin can reduce the production of lipid rafts and boost LXRαactivity to treat staphylococcus aureus mastitis [8] .…”

Therapeutic potentials of allicin in cardiovascular disease: advances and future directions

“…Lin et al [ 41 ] found that allicin reduced cholesterol levels in foam cells and enhanced cholesterol efflux by activating the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor alpha (LXRα) signalling pathway, thereby reducing lipid accumulation. Nantiya et al [ 42 ] demonstrated that allicin possessed hypolipidemic effects by upregulating low-density lipoprotein receptor (LDLR) expression through the activation of sterol regulatory element binding proteins 2 (SREBP2) and downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9) expression via the suppression of hepatocyte nuclear factor 1α (HNF1α), thereby enhancing the uptake of LDL by HepG2 cells. Moreover, as mentioned earlier, the study also revealed that the efficacy of allicin (200 μM) in lowering blood lipids was comparable to atorvastatin’s effect (10 μM).…”

Bioavailability, Health Benefits, and Delivery Systems of Allicin: A Review

“…The cardiac enzymes cardiac troponin I (cTnI), cardiac troponin T (cTnT), creatine kinase isoenzyme-MB (CK-MB), and lactate dehydrogenase (LDH) were restored to standard levels, indicating that allicin has a substantial protective effect against cardiotoxicity. Nawaka et al examined the hypolipidemic activity of allicin and its potential mechanisms using HepG2 cells . The results showed that allicin upregulated low-density lipoprotein receptor (LDLR) expression through the sterol regulatory element-binding protein 2 (SREBP2) pathway and increased low-density lipoprotein (LDL) uptake in HepG2 cells.…”

“…Nawaka et al examined the hypolipidemic activity of allicin and its potential mechanisms using HepG2 cells. 55 The results showed that allicin upregulated low-density lipoprotein receptor (LDLR) expression through the sterol regulatory element-binding protein 2 (SREBP2) pathway and increased low-density lipoprotein (LDL) uptake in HepG2 cells. Allicin also decreased the protein expression levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and hepatocyte nuclear factor 1 homeobox alpha (HNF1α) in cells, which plays an important role in cholesterol homeostasis.…”