Blueberry extract attenuates DSS-induced inflammatory bowel disease in mice through inhibiting ER stress-mediated colonic apoptosis in mice.
Food & function
Inflammatory bowel disease (IBD) is a chronic, debilitating condition with limited therapeutic options. Dietary components like blueberries have emerged as potential modulators of inflammation and tissue repair in gastrointestinal diseases. This study investigated endoplasmic reticulum (ER) stress-mediated apoptosis mediated protective effects of blueberries in ameliorating dextran sulfate sodium (DSS)-induced IBD. Firstly, a total of 86 anthocyanin compounds were identified in blueberry extract by LC-MS spectroscopy, including 35 cyanidin, 9 delphinidin, 14 malvidin, 10 peonidin, and 9 petunidin. Then, the animal study showed that blueberry supplementation notably ameliorated DSS-induced IBD symptoms, as evidenced by improved histopathological scores and a reduced disease activity index (DAI) score. Additionally, blueberries attenuated ER stress by inhibiting the colonic PERK/eIF2α/ATF4/CHOP signaling pathway. Furthermore, blueberries inhibited the expression of the pro-apoptotic protein, caspase-3, and decreased colonic apoptosis, as evidenced by TUNEL assay results. However, it did not affect the expression of anti-apoptotic proteins, bcl-2 and bcl-xl. Finally, blueberries enhanced the intestinal barrier by upregulating ZO-1, claudin-1, occludin, and E-cadherin. In conclusion, blueberries demonstrate therapeutic potential against DSS-induced IBD-like symptoms in mice, possibly by regulating ER stress-mediated apoptosis pathways. These findings suggest that blueberries might be an effective dietary intervention for IBD management.
10.1039/d4fo00194j
Malvidin-3-O-β glucoside, major grape anthocyanin, inhibits human macrophage-derived inflammatory mediators and decreases clinical scores in arthritic rats.
Decendit Alain,Mamani-Matsuda Maria,Aumont Virginie,Waffo-Teguo Pierre,Moynet Daniel,Boniface Katia,Richard Emmanuel,Krisa Stéphanie,Rambert Jérôme,Mérillon Jean-Michel,Mossalayi M D
Biochemical pharmacology
Polyphenolic anthocyanins are major colorful compounds in red fruits, known to prevent cardiovascular and other diseases. Grape polyphenols are a mixture of various molecules and their exact contribution to above bioactivities remains to be clarified. In the present study, we first analyzed the effect of purified grape-derived compounds on human peripheral blood mononuclear cell (PBMC) survival, proliferation, as well as for their ability to inhibit the activation of human normal macrophages. Data indicated that malvidin-3-O-β glucoside (Malβg), the major grape anthocyanin, is bioactive with no toxicity on human PBMC. Malβg decreased the transcription of genes encoding inflammatory mediators, confirmed by the inhibition of TNFα, IL1, IL-6 and iNOS-derived nitric oxide (NO) secretion from activated macrophages. As Malβg also inhibited inflammatory response of rat macrophages, we investigated the anti-inflammatory potential of Malβg in chronic rat adjuvant-induced arthritis (AIA). Malβg significantly diminished inflammatory cachexia and arthritic paw scores in AIA rats at both therapeutic and preventive levels. In vivo effects of Malβg correlated with down-regulation of NO generation from AIA rats' peritoneal macrophages ex vivo. These data indicate that Malβg, major grape anthocyanin, is a potent anti-inflammatory agent in vitro and in vivo, without detectable toxic effect.
10.1016/j.bcp.2013.06.010
Malvidin-3--Glucoside from Blueberry Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Transcription Factor EB-Mediated Lysosomal Function and Activating the Nrf2/ARE Signaling Pathway.
Xu Yang,Ke Huihui,Li Yuting,Xie Lianghua,Su Hongming,Xie Jiahong,Mo Jianling,Chen Wei
Journal of agricultural and food chemistry
Nonalcoholic fatty liver disease (NAFLD) has become a universal health issue, whereas there is still a lack of widely accepted therapy until now. Clinical research studies have shown that blueberry could effectively regulate the lipid metabolism, thereby improving obesity-related metabolic syndromes; however, the specific active substances and mechanisms remain unclear. Herein, the effects of the major 10 kinds of anthocyanins from blueberry against NAFLD were investigated using an free fatty acid (FFA)-induced cell model. Among these anthocyanins, malvidin-3--glucoside (M3G) and malvidin-3--galactoside (M3Ga) could remarkably ameliorate FFA-induced lipid accumulation. Besides, M3G and M3Ga also inhibited oxidative stress suppressing reactive oxygen species and superoxide anion overproduction, increasing glutathione levels, and enhancing activities of antioxidant enzymes. Further studies unveiled that the representative anthocyanin M3G-upregulated transcription factor EB (TFEB)-mediated lysosomal function possibly interacted with TFEB and activated the Nrf2/ARE (antioxidant responsive element) signaling pathway. Overall, this study enriched the knowledge about the health-promoting effects of blueberry anthocyanins against NAFLD and provided ideas for the development of functional foods of blueberry anthocyanins.
10.1021/acs.jafc.0c06695
Malvidin 3-Glucoside Modulated Gut Microbial Dysbiosis and Global Metabolome Disrupted in a Murine Colitis Model Induced by Dextran Sulfate Sodium.
Liu Fang,Wang Thomas T Y,Tang Qingjuan,Xue Changhu,Li Robert W,Wu Vivian C H
Molecular nutrition & food research
SCOPE:This study aims to elucidate the mechanisms of the anthocyanin malvidin 3-glucoside (MV) in alleviating gut dysbiosis using a murine colitis model induced by dextran sulfate sodium (DSS). METHODS AND RESULTS:The effect of MV on the structure and function of the colon microbiome and microbial metabolism is evaluated using 16S rRNA gene sequencing, global metabolomics, and a network algorithm based on the random-matrix theory. MV ingestion improved histopathological scores and increased IL10 expression in the colon mucosa of colitis mice. While DSS has a profound effect on the gut microbiome and significantly decreases both microbial richness and evenness, MV further reduces evenness but promotes microbial interactions and restores the Firmicutes/Bacteroidetes ratio repressed by DSS. Moreover, MV reduces the abundance of pathogenic bacteria, such as Ruminococcus gnavus, in colitis mice and has a strong modulatory effect on microbial co-occurrence patterns and gut metabolites. In addition, MV reverses several key inflammatory mediators, including sphingolipid metabolites, from elevated levels in DSS colitis mice. As a bioactive ingredient, MV exerts its effect on the gut microbiome in a mechanism that differs from the whole blueberry. CONCLUSION:MV ingestion ameliorates intestinal inflammation by modulating colon epithelium integrity, gut microbiome, and key inflammatory mediators.
10.1002/mnfr.201900455
Protective Effects of Blueberry Anthocyanins against HO-Induced Oxidative Injuries in Human Retinal Pigment Epithelial Cells.
Huang Wu-Yang,Wu Han,Li Da-Jing,Song Jiang-Feng,Xiao Ya-Dong,Liu Chun-Quan,Zhou Jian-Zhong,Sui Zhong-Quan
Journal of agricultural and food chemistry
Blueberry anthocyanins are considered protective of eye health because of their recognized antioxidant properties. In this study, blueberry anthocyanin extract (BAE), malvidin (Mv), malvidin-3-glucoside (Mv-3-glc), and malvidin-3-galactoside (Mv-3-gal) all reduced HO-induced oxidative stress by decreasing the levels of reactive oxygen species and malondialdehyde and increasing the levels of superoxide dismutase, catalase, and glutathione peroxidase in human retinal pigment epithelial cells. BAE and the anthocyanin standards enhanced cell viability from 63.69 ± 3.36 to 86.57 ± 6.92% (BAE), 115.72 ± 23.41% (Mv), 98.15 ± 9.39% (Mv-3-glc), and 127.97 ± 20.09% (Mv-3-gal) and significantly inhibited cell apoptosis (P < 0.01 for all). Mitogen-activated-protein-kinase pathways, including ERK1/2 and p38, were involved in the bioactivities. In addition, the anthocyanins decreased vascular-endothelial-cell-growth-factor levels and activated Akt-signal pathways. These combined results supported the hypothesis that blueberry anthocyanins could inhibit the induction and progression of age-related macular degeneration (AMD) through antioxidant mechanisms.
10.1021/acs.jafc.7b06135
Malvidin alleviates LPS-induced septic intestinal injury through the nuclear factor erythroid 2-related factor 2/reactive oxygen species/NLRP3 inflammasome pathway.
Inflammopharmacology
Emerging evidence suggests that the gastrointestinal tract plays a crucial role in the pathophysiology of sepsis, a leading cause of mortality among patients admitted to the intensive care unit (ICU). Malvidin, belonging to the flavonoid family of compounds, exhibits a range of capabilities including anti-inflammatory and antioxidant properties. Studies have demonstrated that Malvidin exhibits a dose-dependent effect in mitigating sepsis-induced intestinal injury. The advantageous impact of Malvidin in safeguarding against sepsis-induced intestinal injury is associated with its capacity to counteract oxidative stress, inhibit cellular apoptosis, diminish the secretion of pro-inflammatory cytokines, and regulate the synthesis of inflammasomes. The findings indicate that Malvidin, a natural compound, exhibits protective effects on the gut by activating the nuclear factor erythroid 2-related factor 2/reactive oxygen species/NLRP3 inflammasome pathway. These results have significant implications for potential clinical applications and offer valuable insights into the treatment of sepsis-induced intestinal injury.
10.1007/s10787-023-01378-8
Malvidin protects against lipopolysaccharide-induced acute liver injury in mice via regulating Nrf2 and NLRP3 pathways and suppressing apoptosis and autophagy.
European journal of pharmacology
Sepsis-related acute liver injury (ALI) is a fatal disease associated with many complications. Recent studies indicate that malvidin, an active flavonoid, has multiple bioactivities including anti-oxidant and anti-inflammation. However, the protective roles of malvidin against LPS-induced ALI are unknown. The purpose of this research is to explore whether malvidin has biological activities on LPS-induced ALI in mice and the underlying mechanisms. Male C57 mice were injected intraperitoneally with malvidin for five days and the mice were euthanized 6 h after LPS (10 mg/kg body weight) intraperitoneal injection. Multiple methods of H&E staining, biochemical kits, qRT-PCR assay, western blotting analysis, TUNEL and transmission electron microscope (TEM) were used. Results showed that decreased ALT, AST levels and alleviated histopathological damage of liver tissue were observed in malvidin pretreatment group in mice. Then, malvidin prevented LPS-induced reduction of antioxidant enzyme activities such as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) via up-regulating nuclear factor E2-related factor2 (Nrf2) pathway. In addition, in malvidin pretreatment groups, mRNA levels of pro-inflammatory cytokines (TNF-α，IL-1β, IL-6) and protein levels of NOD-like receptor protein 3 (NLRP3) inflammasome in the liver were significantly down-regulated. We also found that the malvidin could reduce the expression of apoptosis key protein and TUNEL-labeled apoptotic hepatocytes. Furthermore, malvidin inhibited the protein expression of ATG5, p62 and the ratio of LC3-II/LC3-I. In conclusion, our study firstly suggests that malvidin is a potentially protective agent against LPS-induced ALI through up-regulating Nrf2 signaling pathway, suppressing NLRP3 inflammasome and inhibiting apoptosis and autophagy.
10.1016/j.ejphar.2022.175252
Malvidin Protects against and Repairs Peptic Ulcers in Mice by Alleviating Oxidative Stress and Inflammation.
Fagundes Felipe Leonardo,Pereira Quélita Cristina,Zarricueta Melina Luzzi,Dos Santos Raquel de Cássia
Nutrients
Peptic ulcer episodes cause damage to the stomach and intestine, with inflammatory cell infiltration and oxidative stress as the main players. In this study, we investigated the potential of anthocyanidin malvidin for preventive and curative peptic ulcer treatment. The anthocyanidin effects were examined in gastric ulcer mouse models induced by ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (IR), acetic acid and duodenal ulcer induced by polypharmacy. Expression levels of oxidative and inflammatory genes were measured to investigate the mechanism of anthocyanin activity. At a dose of 5 mg·kg, Malvidin prevented gastric ulcer induction by ethanol, NSAID and repaired the tissue after 6 days of IR. Moreover, the anthocyanidin accelerated the healing of acetic acid-induced ulcer, increased the gene expression of EGF and COX-1, and downregulated MMP-9. Anthocyanin treatment mitigated the effect of polypharmacy on inflammation and oxidative stress observed in the intestine. Additionally, the compound downregulated cytokine expression and TLR4 and upregulated HMOX-1 and IL-10, exhibiting protective activity in the mouse gut. Malvidin thus prevented gastric and duodenal ulcers due to prominent anti-inflammatory and antioxidative effects on the gastrointestinal tract that were related to gene expression modulation and an increase in endogenous defense mechanisms.
10.3390/nu13103312
Malvidin attenuates pain and inflammation in rats with osteoarthritis by suppressing NF-κB signaling pathway.
Dai Teng,Shi Keqing,Chen Gang,Shen Yimin,Pan Ting
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
OBJECTIVE:Malvidin is one of the most widespread anthocyanidins which exhibits significant antioxidant and anti-inflammatory activity. The aim of this paper is to investigate the effects of Malvidin on osteoarthritis (OA). MATERIALS AND METHODS:We created an animal model of OA using Wistar rats administered by monosodium iodoacetate (MIA). Effects of Malvidin on hyperalgesia were evaluated by paw pressure tests and compression threshold test. Articular chondrocytes were isolated from the OA rats to detect the apoptotic chondrocytes using senescence-associated β-galactosidase (SA-β-gal) staining kit. The expression levels of pro-inflammatory cytokines and matrix metalloproteinase (MMPs) were assessed by western blot and qPCR. Luciferase assay was used to determine the impact of Malvidin on nuclear factor-kappa B (NF-κB) pathway. RESULTS:Malvidin treatment exhibited significant pain-relieving effects in OA rats and decreased the expression level of apoptotic marker SA-β-gal in chondrocytes. We found that the upregulated expressions of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and MMPs induced by MIA in cartilage tissues were significantly reversed by Malvidin. Furthermore, Malvidin inhibited NF-κB pathway via an NF-κB inhibitor (IκBα)-independent manner through suppressing p65 nuclear transportation in vitro. CONCLUSIONS:Our findings suggest that Malvidin significantly attenuates the OA-induced pain and inflammation by inhibiting NF-κB signaling pathway and suppressing pro-inflammatory cytokine expression and chondrocyte apoptosis.
10.1007/s00011-017-1087-6
Malvidin promotes PGC-1α/Nrf2 signaling to attenuate the inflammatory response and restore mitochondrial activity in septic acute kidney injury.
Chemico-biological interactions
Acute kidney injury (AKI) in sepsis is a vital and dangerous organ failure caused by an infection-induced dysregulation of the host reaction. Malvidin possesses significant anti-inflammatory and antioxidant bioactivities. This study explored the critical roles of malvidin in sepsis AKI and the crosstalk among mitochondrial function, nucleotide-binding oligomerization-like receptor 3 (NLRP3) inflammasome and nuclear factor erythroid 2 (Nrf2) signaling pathway. First, C57BL/6 mice were administered lipopolysaccharide intraperitoneally for 6 h to create an AKI model of sepsis. Hematoxylin-eosin staining and serum biomarker assays showed that malvidin protected from AKI in sepsis. Real-time fluorescence quantitative polymerase chain reaction analysis revealed that malvidin was able to inhibit inflammatory cytokines and mediators. Western blot assays indicated that malvidin suppressed NLRP3 inflammasome activation and enhanced antioxidant properties. Additionally, human renal tubular epithelial cells were stimulated by lipopolysaccharide/adenosine triphosphate to establish an NLRP3 inflammasome activation model in vitro, and in line with findings in vivo, malvidin significantly inhibited NLRP3 inflammasome activation. Furthermore, our data indicate that malvidin restored mitochondrial quality and function, reduced reactive oxygen species production, increased mitochondrial membrane potential, enhanced mitochondrial DNA copy number, and promoted peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) nuclear translocation. Moreover, inhibitor blockade assays indicated that both PGC-1α and Nrf2 affected the inhibition of the NLRP3 inflammasome by malvidin. Finally, immunoprecipitation assays showed that malvidin promoted PGC-1α and Nrf2 interactions. Overall, malvidin alleviated lipopolysaccharide-induced sepsis AKI, improved mitochondrial function and mitochondrial biogenesis, and inhibited the NLRP3 inflammasome through the PGC-1α/Nrf2 signaling pathway, suggesting that malvidin might translate into clinical applications for sepsis AKI therapy.
10.1016/j.cbi.2023.110850