Malvidin induces hepatic stellate cell apoptosis via the endoplasmic reticulum stress pathway and mitochondrial pathway

Abstract

Blueberries have great beneficial effects due to high level of anthocyanins, especially malvidin. Hepatic stellate cells (HSCs) can be activated and increase excessive extracellular matrix (ECM) components, which play a central role in liver fibrogenesis. Therefore, activated HSC’s apoptosis can be induced to recover liver fibrosis. Malvidin's effects on apoptosis in rat activated hepatic stellate T6 cells (HSC‐T6) in vitro were investigated here. High concentration of malvidin was found to significantly induce apoptosis, activate caspase‐3, increase malondialdehyde, upregulate Bax, but downregulate Bcl‐2. Moreover, malvidin upregulated the protein levels of some endoplasmic reticulum stress (ERS)‐typical markers, including caspase‐12, glucose‐regulated protein 78 (GRP78), and CCAAT/enhancer‐binding protein (C/EBP) homologous protein (CHOP), suggesting that malvidin induced HSC apoptosis by the ERS apoptosis pathway as well as the mitochondrial‐dependent pathway. These findings indicated that blueberry anthocyanins, especially malvidin, could induce activated hepatic stellate cell apoptosis and might act as one kind of functional food ingredient or a novel nutraceutical beneficial for liver health.

Dried Bilberry (Vaccinium myrtillus L.) Alleviates the Inflammation and Adverse Metabolic Effects Caused by a High-Fat Diet in a Mouse Model of Obesity

“…Delphinidin was reported to inhibit lipid accumulation and cyanidin reactive oxygen species production in HepG2 hepatocytes [ 47 , 48 ]. Malvidin was found to reduce the development of liver fibrosis by inducing hepatic stellate cell apoptosis and to inhibit TNFα and interleukin (IL)-1β secretion from activated macrophages [ 49 , 50 ]. A combination of malvidin and peonidin was reported to downregulate the expression of inflammation-related genes in adipocytes exposed to lipopolysaccharide [ 51 ].…”

In silico-based screening for natural product’s structural analogs as new drugs candidate against leishmaniasis

“…Also, the Target Product Profile (TPP) proposed by the Drugs for Neglected Diseases initiative (DNDi), includes regard for the oral route of administration for new candidates [61], while the ADME profile of the compound shows its potential for oral route administration and high bioavailability [62][63][64]. Furthermore, Malvidin has shown the potential to be an antioxidant, anti-hypertensive, antiinflammatory, anti-obesity, anti-osteoarthritis, anti-proliferative, and anticancer drug candidate [65][66][67][68][69].…”

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

“…Malvidin Inducing HSCs apoptosis via the endoplasmic reticulum stress pathway and mitochondrial pathway [192] Pelargonidin Suppressing the ROS-NLRP3-IL-1 β axis via activating the Nrf2 pathway [193] Isoliquiritigenin Alleviates LF through caveolin-1-mediated hepatic stellate cells ferroptosis [194] Kaempferol Regulating miR-26b-5p/Jag1 axis and Notch pathway [195] Dihydroartemisinin [128,196,197] Hesperidin Inhibiting NF-κB/IL-1β/IL-10 and TGFβ/Smad2/3/CTGF signaling pathways [198] Carvacrol Inhibiting TRPM7 and modulating the MAPK signal [199] Small Ellagic Acid Regulates inflammatory mediators to inhibit TGF-β-mediated HSC activation [223] Sulforaphane Through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway [224] Tanshinone IIA Intervening TGFβ/ Smad signaling pathway [225] Protocatechuic acid [265] Byakangelicin [266] Quercetin [267] Gooseberry anthocyanins [268] Naringin (NIN) [268] Germacrone [269] Small-molecule natural products…”

“…Malvidin induces HSCs apoptosis though mitochondria-dependent as well as ERS pathways. Blueberry anthocyanins, particularly malvidin, provide clues as a potential nutrient beneficial to liver health [192] . The adjusting of TGF-β/Smad pathway though anthocyanins is principally carried out though quelling the phosphorylation of receptor-activated Smad as well as obstructing TGFα/Smad pathway to achieve liver protection.…”