Health benefits of anthocyanins and molecular mechanisms: Update from recent decade

“…several excellent reviews have illustrated these natural dietary phytochemicals in terms of their absorption (McGhie and Walton, 2007), metabolism (He and Giusti, 2010), bioavailability (Fernandes et al., 2014), and pharmacokinetics (Kay, 2006) as well as their various analytical techniques…”

“The relationship between anthocyanins intake and the reduced risk of developing cardiovascular disease has been indicated in several epidemiological studies (PrRimm et al., 1991; Wallace, 2011).”

“Table 1 shows the daily consumption of anthocyanins from fruits, vegetables, and beverages obtained from the National Health and Nutrition Examination Survey (NHANES, 2001; Wu et al., 2006).”

“However, convincing epidemiological evidence indicating a positive association between the intake of anthocyanins-rich food and other cancers is needed to be further determined (Wang and Stoner, 2008).”

“In addition, an Iowa Women’s Health Study with 34,489 women showed a significant reduction in cardiovascular disease mortality associated with anthocyanins-rich strawberry intake (Mink et al., 2007).”

“Anthocyanins belong to a large group of compounds, collectively known as flavonoids, which are a subgroup of an even larger group of compounds known as polyphenolics (Mazza and Miniati, 1993; Andersen, 2001; Andersen and Markham, 2006; McGhie and Walton, 2007).”

“Anthocyanins belong to a large group of compounds, collectively known as flavonoids, which are a subgroup of an even larger group of compounds known as polyphenolics (Mazza and Miniati, 1993; Andersen, 2001; Andersen and Markham, 2006; McGhie and Walton, 2007).”

“Among them, the six most mentioned anthocyanidins in plants are pelargonidin, cyanidin, peonidin, delphinidin, petunidin, and malvidin (de Pascual-Teresa and Sanchez-Ballesta, 2008; CONTACT Fang Chen chenfangch@sina.com College of Food Science and Nutritional Engineering, China Agricultural…”

“Similarly, a large cohort study of 200,994 health professionals from the United States revealed that consumption of anthocyanins-rich foods was inversely associated with the risk of diabetes (Muraki et al., 2013).”

“A recent study of young and middle-aged women showed a high intake of anthocyanins was associated with a 32% reduction in risk of myocardial infarction (Cassidy et al., 2013).”

“The relationship between anthocyanins intake and the reduced risk of developing cardiovascular disease has been indicated in several epidemiological studies (PrRimm et al., 1991; Wallace, 2011).”

“Further, Takikawa et al. (2010) showed that the dietary anthocyanins-rich extract from bilberry reduced the blood glucose level and improved insulin sensitivity via the activation of AMPK in type 2 diabetic mice.”

“Afaq et al. (2005) reported that the animals pretreated with anthocyanins-rich extract from pomegranate fruit resulted in substantially reduced tumor incidence and lower tumor body burden in 7,12-dimethylbenz(a)anthracene-initiated CD-1 mouse through the inhibition of phosphorylation of…”

“…activity of anthocyanins for their improvement on cognitive performance, memory performance, and motor performance, indicating their potential application for the prevention of many neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) (Youdim et al., 2004).”

“During the last decade, several excellent reviews have illustrated these natural dietary phytochemicals in terms of their absorption (McGhie and Walton, 2007), metabolism (He and Giusti, 2010), bioavailability (Fernandes et al., 2014), and pharmacokinetics (Kay, 2006) as well as their various analytical techniques (We…”

“However, the low bioavailability of anthocyanins appears to be an obvious obstacle in achieving the desired beneficial effects (Xiao and H€ogger, 2015).”

“Therefore, an anthocyanins-rich dietary therapy may be used to improve the condition of SCI patients.”

“Further, Zhao et al. (2004) demonstrated that the chokeberry extracts, containing high levels of monoglycosylated cyanidin derivatives, showed a stronger chemoprotective activity than grape and bilberry extracts (BBEs).”

“Notably, this study showed that the mixture of the two purified anthocyanins caused a greater anti-inflammatory effect than single anthocyanin, which suggested that different anthocyanins might have additive or synergistic effects onmediating anti-inflammatory response (Zhu et al., 2013).”

“…reviews have illustrated these natural dietary phytochemicals in terms of their absorption (McGhie and Walton, 2007), metabolism (He and Giusti, 2010), bioavailability (Fernandes et al., 2014), and pharmacokinetics (Kay, 2006) as well as their various analytical techniques (Welch et al., 2008).”

“Moreover, Jing et al. (2008) used human colon cancer HT29 cell line to compare the anticancer properties of anthocyanins-rich extract from purple corn, chokeberry, bilberry, purple carrot, grape, radish, and elderberry.”

“…liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical cancer (Rugin a et al., 2012), lung cancer…”

“…by delphinidin 3-Oglucoside and cyanidin 3-O-glucoside through the activation of the NO-cGMP signaling pathway in hypercholesterolemic individuals (Zhu et al., 2011), inhibition of mitochondria-mediated apoptotic signaling pathway in human umbilical vein endothelial cells and bovine aortic…”

“…observed, indicating that anti-inflammatory response might also participate in the protection against atherosclerosis (Mauray et al., 2010), and its mechanism of action was possibly inhibiting atherosclerotic plaque progression and increasing the stability of vulnerable plaque (Xia et al., 2006).”

“Hou et al. (2005) reported that inhibition of COX-2 expression by blocking the activation of MAPK signaling pathway, including JNK, ERK, and p38 kinase contributed to the anti-inflammatory property of delphinidin.”

“Dopaminergic cell death is suggested to be involved in the progression of PD. Strathearn et al. (2014) demonstrated that anthocyanins-rich extract from blueberries, grape seed, hibiscus, blackcurrant, and Chinese mulberry significantly suppressed rotenone-induced dopaminergic cell death via interference with microglia…”

“In another study, anthocyanins-rich extract from mulberry significantly inhibited the accumulation of Ab and improved learning and memory ability in a senescence-accelerated mice model (Shih et al., 2010).”

“, 2014), and pharmacokinetics (Kay, 2006) as well as their various analytical techniques (Welch et al.”

“…of inflammation-associated diseases or disorders such as colitis (Akiyama et al., 2012), peyronie disease (Sohn et al., 2014), periodontal disease, laryngopharyngeal reflux (Samuels et al., 2013), postprandial inflammatory response (Edirisinghe et al. 2011), and pain behavior (Tall et al., 2004).”

“…have been demonstrated to inhibit the initiation, promotion, and progression of several cancers, such as breast cancer (Singletary et al., 2007; Hui et al., 2010; Devi et al., 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal…”

“Similarly, Tsuda et al. (2004) demonstrated that anthocyanins enhanced adipocytokine (adiponectin and leptin) secretion and the expression of PPARg, lipoprotein lipase (LPL), adipocyte fatty acid binding protein (aP2), and uncoupling protein 2 (UCP2) in isolated rat adipocytes.”

“…prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical…”

“Poulose et al. (2012) also showed that pretreatment of BV-2 microglial cells with the anthocyanins-rich extract from acai pulp was protective against lipopolysaccharide (LPS)-induced NO release, iNOS production, and COX-2 expression.”

“, 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al.”

“…Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical cancer (Rugin a et al., 2012), lung cancer (Aqil et al., 2012), fibrosarcoma (Filipiak et al., 2014), and metastatic melanoma (Bunea et al., 2013).”

“In an early study, the anthocyanins-rich extract from Aronia meloncarpa induced G1/G0 and G2/M cell cycle arrest in HT-29 colon cancer cells by increasing the expression of p21WAF1 and p27KIP1 and decreasing the expression of cyclin A and cyclin B (Malik et al., 2003).”

“Similarly, anthocyanin extract from mulberry also decreased macrophage death and foam cell formation in Cu2C-mediated oxLDL (Liu et al. 2008).”

“…of inflammation-associated diseases or disorders such as colitis (Akiyama et al., 2012), peyronie disease (Sohn et al., 2014), periodontal disease, laryngopharyngeal reflux (Samuels et al., 2013), postprandial inflammatory response (Edirisinghe et al. 2011), and pain behavior (Tall et al., 2004).”

“Guo et al. (2007) showed that dietary anthocyanins-rich extract from black rice was capable of preventing the development of insulin resistance in fructose-fed rats, and the underlying mechanism might be related mainly to inhibiting oxidative stress and improving the plasma lipid profile.”

“…Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical cancer (Rugin a et al., 2012), lung cancer (Aqil et al., 2012), fibrosarcoma (Filipiak et al., 2014), and metastatic melanoma (Bunea et al., 2013).”

“For example, anti-proliferative effects of anthocyanins-rich extract from blackberry on colon cancer HT-29, breast cancer MCF-7, lung cancer A549, and leukemia HL-60 cells have been determined (Dai et al., 2009; Aqil et al., 2012).”

“Excessive production of NO appears to be associated with the progression of many inflammatory diseases (Li et al., 2014).”

“Further, longer-term exposure with berry extract markedly reduced the expression levels of glucose transporter 2 (Glut2) and sodium-dependent glucose transporter 1 (SGLT1), and resulted in significant inhibition of glucose uptake (Alzaid et al., 2013).”

“…such as breast cancer (Singletary et al., 2007; Hui et al., 2010; Devi et al., 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al.,…”

“An early study by Tsuda et al. (2002) demonstrated that cyanidin 3-O-b-glucoside suppressed the zymosaninduced inflammatory response in rats by reducing the level of iNOS, tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6 in the peritoneal exudate cells.”

“In a retinal inflammatory mouse model, an anthocyanins-rich extract from bilberry showed anti-inflammatory activity by suppressing the expression of signal transducers and activators of transcription 3 (STAT3) and IL-6 through the reduction of NF-kB activation (Miyake et al., 2012).”

“Moreover, anthocyanins could even improve the developmental competence by stimulating nuclear reprogramming through the increased transcription factor expression (You et al., 2010).”

“In addition, a recent study by Peiffer et al. (2014) has demonstrated that protocatechuic acid (PCA), Figure 1.”

“Longo et al. (2008) found that anthocyanin-induced autophagy was characterized by the upregulation of eukaryotic initiation factor 2asubunit (eIF2a) and downregulation of mammalian target of rapamycin (mTOR) and Bcl-2.”

“…of mitochondria-mediated apoptotic signaling pathway in human umbilical vein endothelial cells and bovine aortic endothelial cells (Zapolska-Downar et al., 2008; Paix~ao et al., 2011) as well as the activation of cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells (Liu et al., 2014).”

“…et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical cancer (Rugin a et al., 2012), lung cancer (Aqil et al.,…”

“Cyanidin 3-O-glucoside has been shown to exert its neuroprotective effect against ischemic stroke in mice by blocking AIF release from mitochondria (Min et al., 2011).”

“Similarly, Forester et al. (2014) also found that three anthocyanin metabolites, gallic acid, 3-O-methylgallic acid, and 2,4,6-trihydroxybenzaldehyde, could decrease cell viability and cause cell cycle arrest and apoptosis in colon cancer Caco-2 cells.”

“Excessive production of NO appears to be associated with the progression of many inflammatory diseases (Li et al., 2014).”

“Konczak-Islam et al. (2003) demonstrated the anticancer property of the anthocyanins-rich extract from sweet potato in HL-60 cells.”

“…many fruits and vegetables have been demonstrated to inhibit the initiation, promotion, and progression of several cancers, such as breast cancer (Singletary et al., 2007; Hui et al., 2010; Devi et al., 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011),…”

“…Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical cancer (Rugin a et al., 2012), lung cancer (Aqil et al., 2012), fibrosarcoma (Filipiak et al., 2014), and metastatic melanoma (Bunea et al., 2013).”

“Atherosclerosis is characterized by vascular obstruction from the deposits of lipids, resulting in reduced blood flow (Mauray et al., 2012).”

“…2010; Devi et al., 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai…”

“In line with these findings, a crosssectional study suggested consumption of high amounts of anthocyanins might have beneficial effect on improving lipid profile in Chinese women, indicating the efficacy of anthocynins for the treatment of obesity (Li et al., 2013).”

“Xia et al. (2007) demonstrated that intracellular tumor necrosis factor receptor-associated factors’ (TRAFs) translocation to lipid rafts played pivotal role in CD40-mediated NF-kB activation, which induced inflammatory response in human endothelial cells.”

“…et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical cancer (Rugin a et al.,…”

“Jurgo nski et al. (2013) reported that the anthocyanins-rich extract from Kamchatka honeysuckle berry was able to ameliorate disturbances in lipid and glucose metabolism in rats.”

“Ghosh and Konishi (2007) summarized the antidiabetic and eye function properties of anthocyanins. de Pascual-Teresa (2014) discussed the beneficial effects of anthocyanins on the prevention of cardiovascular diseases and neurological conditions.”

“Graf et al. (2013) observed that rats fed with anthocyanins-rich grape–bilberry juice showed reduced levels of serum cholesterol, TG, leptin, and resistin.”

“…factor exists in an inactive state in the cytosol by binding to IkB; upon its activation and translocation into the nucleus, genes involved in pro-inflammatory responses are induced, leading to the expression of cytokines and inflammatory enzymes, including iNOS and COX-2 (Taverniti et al., 2014).”

“Continuous hyperglycemia could enhance lipolysis of triglycerides (TG) in the adipocytes, resulting in elevated levels of plasma-free fatty acids (FFAs), which have been demonstrated to potentially link obesity (Guo et al., 2012).”

“…2010; Devi et al., 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai…”

“…such as breast cancer (Singletary et al., 2007; Hui et al., 2010; Devi et al., 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al.,…”

“…with anthocyanins-rich extract from purple sweet potato reduced Ab-induced apoptosis by inhibiting the reactive oxygen species (ROS) generation, lipid peroxidation, caspase-3 activity, and decreasing levels of intracellular Ca2C and membrane potential loss in PC12 cells (Ye et al., 2010).”

“…to inhibit the initiation, promotion, and progression of several cancers, such as breast cancer (Singletary et al., 2007; Hui et al., 2010; Devi et al., 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et…”

“was indicated by both stabilizing the red blood cell membrane and inhibiting polymerization of hemoglobin (Mpiana et al., 2010).”

“Xia et al. (2009) demonstrated that cyanidin 3- O-b-glucoside and peonidin 3-O-b-glucoside also significantly prevented CD40-induced endothelial activation and apoptosis by inhibiting the production of pro-inflammatory cytokines and matrix metalloproteinases (MMP-1 and MMP-9).”

“CX3CL1, and TNFRSF14) was also observed, indicating that anti-inflammatory response might also participate in the protection against atherosclerosis (Mauray et al., 2010), and its mechanism of action was possibly inhibiting atherosclerotic plaque progression and increasing the stability of vulnerable plaque (Xia et al.”

“Inflammatory responses are a series of well-coordinated events that are controlled by several factors, including cytokines, enzymes, lipid mediators, and vasoactive mediators (Hassimotto et al., 2013).”

“Anthocyanin extract from Hibiscus was demonstrated to inhibit oxLDL and foam cell formation by downregulating the expression of CD36 and increasing nuclear peroxisome proliferator-activated receptor g (PPARg) protein levels in mouse macrophage J774A.1 cells (Kao et al., 2009).”

“Barrios et al. (2010) demonstrated that the anthocyanins-rich extract from Pourouma cecropiifolia fruits, a tropical plant, significantly reduced the viability of laryngeal cancer HEp-2, gastric cancer MKN-45, and breast cancer MCF-7 cells.”

“…2010; Devi et al., 2011), prostate cancer (Reddivari et al., 2007), liver cancer (Bishayee et al., 2010, 2011), colorectal and intestinal cancers (Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai…”

“…(Koide et al., 1996, 1997; Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical cancer (Rugin a et al., 2012), lung cancer (Aqil et al., 2012), fibrosarcoma (Filipiak et al., 2014), and metastatic…”

“…Hagiwara et al., 2001; Bobe et al., 2006; Lala et al., 2006; Srivastava et al., 2007; Lim et al., 2013), blood cancer (Tsai et al., 2014), cervical cancer (Rugin a et al., 2012), lung cancer (Aqil et al., 2012), fibrosarcoma (Filipiak et al., 2014), and metastatic melanoma (Bunea et al., 2013).”

“Yoon et al. (2013) reported that combination of anthocyanin extracts from black soybean and ciprofloxacin has more obvious anti-inflammatory and antimicrobial effects on treating chronic bacterial prostatitis than ciprofloxacin treatment alone.”

“, 2012), peyronie disease (Sohn et al., 2014), periodontal disease, laryngopharyngeal reflux (Samuels et al.”

“…the anti-inflammatory activity of anthocyanins in foods for the amelioration of inflammation-associated diseases or disorders such as colitis (Akiyama et al., 2012), peyronie disease (Sohn et al., 2014), periodontal disease, laryngopharyngeal reflux (Samuels et al., 2013), postprandial…”

“In addition, the ameliorative effect of anthocyanin extract from black rice against dgalactose-induced senescence has been demonstrated in a mice model (Lu et al., 2014).”

“In a study of 1997 females from the United Kingdom, higher intake of anthocyanins was associated with significantly lower concentrations of high-sensitivity C-reactive protein (CRP), a marker of obesity and diabetes (Wang et al., 2013).”

“In a sodium oxonateinduced hyperuricemia mouse model, Hwa et al. (2011) reported the hypouricemic effects of anthocyanins-rich extract from the purple-fleshed sweet potato.”

“Park et al. (2014) demonstrated that anthocyanin extract from Korea wild berry Meoru effectively inhibited liver cancer Hep3B cell migration and invasion by decreasing the expression of phospho-GSK3b and b-catenin.”

“…of inflammation-associated diseases or disorders such as colitis (Akiyama et al., 2012), peyronie disease (Sohn et al., 2014), periodontal disease, laryngopharyngeal reflux (Samuels et al., 2013), postprandial inflammatory response (Edirisinghe et al. 2011), and pain behavior (Tall et al., 2004).”

“Similarly, treatment with cyanidin 3-O-b-glucoside could also reduce superoxide production, neuron cell damage, lesion volume, and neurological dysfunction in a traumatic SCI rat model (Kim et al., 2011).”

“…inhibition of mitochondria-mediated apoptotic signaling pathway in human umbilical vein endothelial cells and bovine aortic endothelial cells (Zapolska-Downar et al., 2008; Paix~ao et al., 2011) as well as the activation of cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells…”

“Therefore, an anthocyanins-rich dietary therapy may be used to improve the condition of SCI patients.”

“Two kinds of anthocyanins, cyanidin 3-O-glucoside and malvidin 3-O-glucoside, have been shown to induce FK506 binding protein 52 (FKBP52) activation, leading to the reduction of hyper-phosphorylated Tau protein aggregation, and thereby improving the treatment of AD (Hung et al., 2014).”

“In this sense, the type of aglycones, sugars, and acylated acids, and the position and degree of glycosylation and acylation seem to be the main factors influencing the anticancer property [191].”

“Also, results from animal studies suggest that Cy3G may slow or inhibit the absorption of lipids and glucose in the intestine [15,100,121,122] confirming the postulated mechanisms in cells [1,118,119]) and the physiological impact in humans [113].”