ArticleLiterature Review

Effects of anthocyanins on the prevention and treatment of cancer

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Abstract

Anthocyanins are a class of water-soluble flavonoids, which show a range of pharmacological effects, such as prevention of cardiovascular disease, obesity control and antitumour activity. Their potential antitumour effects are reported to be based on a wide variety of biological activities including antioxidant; anti-inflammation; anti-mutagenesis; induction of differentiation; inhibiting proliferation by modulating signal transduction pathways, inducing cell cycle arrest and stimulating apoptosis or autophagy of cancer cells; anti-invasion; anti-metastasis; reversing drug resistance of cancer cells and increasing their sensitivity to chemotherapy. In this review, the latest progress on the anticancer activities of anthocyanins and the underlying molecular mechanisms is summarized using data from basic research in vitro and in vivo, from clinical trials and taking into account theory and practice. Linked articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

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... The most common anthocyanins are cyanidin, pelargonidin, delphinidin, and malvidin, and they are most commonly found in red-, pink-, blue-, or purple-colored fruits and vegetables [28]. The color of anthocyanins varies from orange to purple. ...
... Anti-inflammatory activity, often associated with the antioxidant properties of phytonutrients, involves several main mechanisms of action. Families of phytonutrients such as anthocyanins (cyanidin and delphinidin), tannins (proanthocyanidin), flavonoids (quercetin), phenolic acids (ferulic acid), organosulfur compounds (sulforaphane), carotenoids (lycopene), and caffeine have been described as being able to inhibit activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway, leading to a reduction in inflammation [28,55,[75][76][77][78][79]. Flavonoids (luteolin and kaempferol), organosulfur compounds (sulforaphane), anthocyanins (cyanidin and delphinidin), phenolic acids (p-coumaric acid), carotenoids (lycopene), and tannins (proanthocyanidins) can also regulate the mitogen-activated protein kinase pathway, which is also widely implicated in inflammatory processes [28,[80][81][82][83][84]. ...
... Families of phytonutrients such as anthocyanins (cyanidin and delphinidin), tannins (proanthocyanidin), flavonoids (quercetin), phenolic acids (ferulic acid), organosulfur compounds (sulforaphane), carotenoids (lycopene), and caffeine have been described as being able to inhibit activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway, leading to a reduction in inflammation [28,55,[75][76][77][78][79]. Flavonoids (luteolin and kaempferol), organosulfur compounds (sulforaphane), anthocyanins (cyanidin and delphinidin), phenolic acids (p-coumaric acid), carotenoids (lycopene), and tannins (proanthocyanidins) can also regulate the mitogen-activated protein kinase pathway, which is also widely implicated in inflammatory processes [28,[80][81][82][83][84]. ...
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Phytonutrients comprise many different chemicals, including carotenoids, indoles, glucosinolates, organosulfur compounds, phytosterols, polyphenols, and saponins. This review focuses on the human healthcare benefits of seven phytochemical families and highlights the significant potential contribution of phytonutrients in the prevention and management of pathologies and symptoms in the field of family health. The structure and function of these phytochemical families and their dietary sources are presented, along with an overview of their potential activities across different health and therapeutic targets. This evaluation has enabled complementary effects of the different families of phytonutrients in the same area of health to be recognized.
... These preventive effects might be related to inhibition of the formation of prostaspheres, 105 induction of apoptosis, 106 anti-inflammation (release of some anti-inflammatory cytokines, like IL-6, IL-1β, and granzyme B), 107,108 and anti-metastatic activities by increasing the degradation of the extracellular matrix (via uPA, MMP2,9) and targeting the VEGF signaling pathway. 104 PAs have been broadly studied in human gastric health. In a 6−26-year followup meta-analysis study, comprehensive evidence has shown that a high intake of PAs could reduce the colorectal cancer risk. ...
... Furthermore, lutein can restrain human cancers, like prostate, lung, and breast cancers, by inhibiting cell differentiation, upregulating apoptosis and cell-to-cell gap junctional communication, and preventing neoplastic transformation in animals. 104 However, it has been reported that lutein, when combined with zeaxanthin and ω-3, was effective in halting the development of age-related macular degeneration. 147 Lycopene, an anti-oxidant rich in tomatoes, 92 shows a more potent anti-proliferation effect on human cancer cells than βcarotene, 148 especially on prostate cancer. ...
... Intake of red meat 31 and β-carotene 145 are believed to increase the risk of NSCLC. However, fish, 51 anthocyanins, 91 catechin (EGCG), 98 lutein, 104 and vitamin E 210 function as chemopreventive agents. Furthermore, the role of vitamin B 164 in chemoprevention is still controversial. ...
... In summary, the promotion of antioxidant respon element (ARE)-regulated phase II enzyme expression by anthocyanins plays a role in the protection of normal cells from oxidative stress exposure. (24) Cyanidin and peonidin, the active compound of anthocyanins contained in PSP tubers have an antimutagenic property. During the transformation of normal cells into cancer cells, hypermutation occurs on somatic cells that can induced genome instability and promote cancer growth. ...
... During the transformation of normal cells into cancer cells, hypermutation occurs on somatic cells that can induced genome instability and promote cancer growth. (24) On the other hand, the anti-carcinogenic activity of anthocyanins at the stage of cancer formation was done through differentiation induction, inhibition of cellular transformation and inhibition of cell proliferation. The main manifestations of anthocyanin inhibition on cancer growth and proliferation include the inhibition of signaling pathways to block signal transduction and regulate the expression of anti-oncogenes and other signaling pathways. ...
... The anticarcinogenic activity of anthocyanins in an advanced stage of cancers development includes the induction of mitochondrial-mediated tumor cell apoptosis by dependent and independent caspase pathway. (24) This is in line with the study on Momordica charantia L fruit fractions inhibit the MDA level average in liver tissue and regenerate hepatic damage of STZ induced rats. (25) The above study is similar to our finding on PSPTEE. ...
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BACKGROUND:Purple sweet potato tuber ethanol extract (PSPTEE) has been known to have benefits in various disease, including to prevent nasopharyngeal carcinoma (NPC). However, there has been no research on PSPTEE in preventing the proliferation of nasopharyngeal mucosal epithelial cells induced by formaldehyde through the oxidative stress mechanisms and inflammatory process. Studies have proven the effect of PSP on various cancer cells, but the carcinogenesis process of the nasopharyngeal mucosal epithelium is still limited. Hence, this study aimed to demonstrate the mechanism for preventing histopathology changes with PSPTEE due to formaldehyde exposure.METHODS: Thirty-two formaldehyde-induced Wistar rats were treated with or without 1g/kgBW/day PSPTEE for 16 weeks. Malondialdehyde (MDA) level were examined with spectrophotometry method, while tumor necrosis factor (TNF)-α and p53 with enzyme linked immunosorbent assay (ELISA) method. The histopathology appearance of the nasopharyngeal epithelium was observed with hematoxylin-eosin (HE) staining.RESULTS: MDA and TNF-α levels in control and treatment group were 22.89±2.84 μM; 9.83±0.89 μM and 84.18±11.58 ng/L; 73.92±10.59 ng/L, respectively, and they showed significant difference. Meanwhile, the level of p53 showed no significant difference. Histopathology appearance showed a significant difference. Path analysis for MDA, TNF-α and p53 levels contributed 28.7% to histopathology appearance. MDA have an effect on significant direct effect on TNF-α. TNF-α has a significant direct effect to histopathological appearance. Indirect influence MDA on histopatological appearance were smaller than the direct effect. TNF-α has the greatest influence on histopatological appearance.CONCLUSION: Formaldehyde induces the histopathology appearance in nasopharyngeal epithelium. This study also demonstrates the mechanism to prevent the nasopharynx epithelial histopathology appearance by administration of PSPTEE.KEYWORDS: PSP, MDA, TNF-α, p53, nasopharynx epithelial
... Mainly, colored wheat exists in three predominant colors, i.e., black, blue, and purple, for the types and position of the anthocyanins in wheat layers. Purple wheat contains anthocyanins in the pericarp layer, blue wheat in the aleurone layer, and black wheat is a mixture of the anthocyanins in the pericarp and aleurone layers (4,5). Anthocyanins have strong antioxidant potential, protecting the cell from free radical damage by neutralizing and scavenging them (6). ...
... Anthocyanins have strong antioxidant potential, protecting the cell from free radical damage by neutralizing and scavenging them (6). Several research publications reported the health-promoting effects of anthocyanins, including anti-inflammatory, anticancer, antidiabetic, antiaging, neuroprotective, and prevention of cardiovascular diseases (5)(6)(7)(8). Colored wheat can be extensively exploited as a unique ingredient for producing value-added food products due to its positive qualities. Based on the potential of colored grains, numerous functional foods, such as chapatti (9), beer (10), biscuits (11), muffins (12), soy sauce, pasta (13), have been reported from this wheat. ...
... Anthocyanins and phenolic acids stability is the primary aim of many current findings due to their great potential applications in the food and health sector (5)(6)(7)(8). Modern food-processing technologies require high temperatures (160-300 • C), and studies showed that anthocyanin stability is decreased in foods after thermal processing (12). Because of the health benefits, there is a need to preserve the content of anthocyanins and total phenolics during thermal processing. ...
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Wheat is a vital and preferred energy source in many parts of the world. Its unique processing quality helps prepare many products such as bread, biscuit, pasta, and noodles. In the world of rapid economic growth, food security, in terms of nutritional profile, began to receive more significant interest. The development of biofortified colored wheat (black, purple, and blue) adds nutritional and functional health benefits to the energy-rich wheat. Colored wheat exists in three forms, purple, blue, and black, depending upon the types and position of the anthocyanins in wheat layers, regulated by the bHLH-MYC transcription factor. Colored wheat lines with high anthocyanin, iron, and zinc contents showed antioxidant and anti-inflammatory activity and possessed desirable product-making and commercial utilization features. The anthocyanin in colored wheat also has a broad spectrum of health implications, such as protection against metabolic syndromes like obesity, diabetes, hypertension, and dyslipidemia. The idea of developing anthocyanin-biofortified wheat shapes human beings' lifestyles as it is a staple food crop in many parts of the world. This review is a compilation of the currently available information on colored wheat in the critical aspects, including biochemistry, food processing, nutrition, genetics, breeding, and its effect on human health. Market generation and consumer awareness creation are vital challenges for its exploitation as a function food on a large scale.
... Установлено, что антиоксидантная активность коррелирует с общим содержанием фенольных соединений, в том числе с антоцианами. Это весьма мощные антиоксиданты, обладающие бо́льшей эффективностью, чем, например, витамины C и E (Lin et al., 2017;Bendokas et al., 2020). В ряде исследований показано, что умеренное потребление продукции с высоким содержанием антоцианов позволяет снизить риск сердечно-сосудистых заболеваний (Lin et al., 2017;Grobelna et al., 2019). ...
... Это весьма мощные антиоксиданты, обладающие бо́льшей эффективностью, чем, например, витамины C и E (Lin et al., 2017;Bendokas et al., 2020). В ряде исследований показано, что умеренное потребление продукции с высоким содержанием антоцианов позволяет снизить риск сердечно-сосудистых заболеваний (Lin et al., 2017;Grobelna et al., 2019). Высокая антиоксидантная активность плодов жимолости по сравнению с другими плодами -черники, ежевики, малины и красного винограда обуславливает повышенное к ним внимание в качестве мощного профилактического средства онкологических заболеваний, заболеваний сердечно-сосудистой системы (атеросклероза, инсульта, инфаркта и др.), болезни Альцгеймера, глазных болезней (глаукомы и катаракты) и др. ...
Article
Background. Honeysuckle is a promising berry crop for food and medical uses, which has recently become increasingly popular. Searching for sources with high content of bioactive substances to obtain new fruit cultivars with improved chemical composition continues to be relevant. Anthocyanin content and composition in honeysuckle cultivars depend on many factors, including plant reproduction conditions (temperature and humidity). Studying chemical composition of Siberian honeysuckle cultivars grown under the conditions of Western Siberia will make it possible to identify sources of high BAS content for various uses. Materials and methods. The target materials of the study were fruits of 21 honeysuckle cultivars grown in Western Siberia before and after freezing. The qualitative and quantitative composition of anthocyanins was assessed in ethanol extracts of honeysuckle fruits using HPLC technique. Results. The content of anthocyanins was higher in the fruits of honeysuckle grown in Western Siberia compared with the published data for the same cultivars reproduced in Belgorod Province (Central Black Earth Region). After freezing, the anthocyanin level in honeysuckle fruits remained the same and in some cases even increased. Conclusions. The obtained data helped to ascertain that honeysuckle fruits reproduced in Western Siberia are valuable sources of such bioactive compounds as anthocyanins.
... Moreover, anthocyanins have been reported to exhibit potent anticancer activity [35]. In the literature, anthocyanins have demonstrated their ability in altering some enzymatic activities that lead to cell death, such as activation of the caspase enzyme [56]. Caspases are the central components of apoptosis, and can possess tumor-suppressor functions [57]. ...
... Caspases are the central components of apoptosis, and can possess tumor-suppressor functions [57]. Moreover, anthocyanins enhance chemotherapy sensitivity, consequently working as a supporter for the medical interventions in cancer therapies [56]. ...
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Background: Cancer is an irregular proliferation of cells that starts with a gene mutation that alters cellular function, is triggered by several factors, and can be inherited or acquired. The aim of this review is to discuss the anticancer activity of basil and its components' strength, focusing on its implication in cancer prevention and treatment. Methods: This systematic review involves all of the studies published from 1 January 2010 through 1 January 2022. Results: In this review, 16 research articles are included to discuss the potential anticancer ability of the extracts of various Ocimum basilicum varieties at various dosages, applied to different cancer cells. Of those 16 articles, 2 were in vivo studies, 13 were in vitro studies, and 1 study conducted both in vivo and in vitro experiments. Antioxidants and other bioactive compounds in basil leaves show important potential anticancer activity at dosage of 4 mg/mL as aqueous extract or essential oil up to 200 µg/mL could slow-down tumor growth and progression with regards to cell death and viability inhibition. At dosages from 50 to 500 µg/mL is effective as anti-proliferative activities. cytotoxicity, inducing apoptosis, slowing down tumor growth, and especially cell cycle arrest, both in vivo and in vitro. Human studies show effects at dosages from 1 to 2.5 mg/daily on general vital activities and on reducing cytokines activity. Conclusions: Based on 16 published studies, basil demonstrates important anticancer activities in vivo and vitro models, and it could act as a potential cancer.
... Furthermore, anthocyanins reduce damage by cold, drought, salt, ultraviolet, and low-phosphate stresses, and boost pollination and seed dispersal by attracting animals and insects [4][5][6]. Recently, anthocyanins have been considered as a beneficial food ingredient due to their physiological and biological functions, including antiaging, antioxidant activity, and cancer prevention [7,8]. ...
... The actin gene was used as the internal control. All reactions of qRT-PCR were performed in 20 mL total volume containing 10 mL of 2 × UltraSYBR Mixture (Low ROX; CWBIO), 0.4 µL of specific primers (each), 0. 8 ...
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Purple non-heading Chinese cabbage is one of the most popular vegetables, and is rich in various health-beneficial anthocyanins. Research related to genes associated with anthocyanin biosynthesis in non-heading Chinese cabbage is important. This study performed integrative transcriptome and metabolome analysis in the purple non-heading Chinese cabbage wild type (WT) and its green mutant to elucidate the formation of purple leaves. The anthocyanin level was higher in purple than in green plants, while the contents of chlorophyll and carotenoid were higher in the green mutant than in the purple WT. Twenty-five anthocyanins were identified in purple and green cultivars; eleven anthocyanin metabolites were identified specifically in the purple plants. RNA-seq analysis indicated that 27 anthocyanin biosynthetic genes and 83 transcription factors were significantly differentially expressed between the WT and its mutant, most of them with higher expression in the purple than green non-heading Chinese cabbage. Transcriptome and metabolome analyses showed that UGT75C1 catalyzing the formation of pelargonidin-3,5-O-diglucoside and cyanidin-3,5-O-diglucoside may play a critical role in purple leaf formation in non-heading Chinese cabbage. Therefore, these results provide crucial information for elucidating the formation of purple leaves in non-heading Chinese cabbage.
... They exhibit a wide range of biological effects, including the prevention of cardiovascular disease, treatment of obesity, and antineoplastic potential. Their antitumor effects are based on a wide range of biological activities, including antioxidant, antiinflammation, differentiation induction, antimutagenesis, inhibition of proliferation by modulating signal transduction pathways, cell cycle arrest induction, and apoptosis stimulation or autophagy of cancer cells, anti-invasion, antimetastasis, and reversing drug resistance in cancer cells and boosting their sensitivity to chemotherapy [18]. ...
... Moreover, ACs exhibit a variety of effects on the blood vessels [65] and platelets [66] that may decrease the danger of coronary heart disease. The anticarcinogenic activities of ACs in the initial stage of tumorigenesis inhibit the invasion and metastasis of the tumor [18]. ...
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Background Genetic instability leads to genome mutations, changes in nucleotide sequences, rearrangements, and gains or losses of part of the chromosomes. This instability can initiate and develop cancer. This study evaluated genomic stability in methotrexate and anthocyanin-treated mammary adenocarcinoma model. Seventy albino mice were divided into seven groups: negative control, anthocyanin, methotrexate, Ehrlich’s solid tumor; Ehrlich’s solid tumor and methotrexate; Ehrlich’s solid tumor and anthocyanin; and Ehrlich’s solid tumor, methotrexate, and anthocyanin groups. Results Tumor weight and size were evaluated. Serum arylesterase activity was low in all the induced tumors and those treated with anthocyanin, methotrexate, or both. Poly[adenosine diphosphate (ADP)-ribose] polymerase activity was high, and glutathione S-transferase activity was low in the tumors treated with anthocyanin, methotrexate, or both, compared with that of the untreated tumor. There was an increase in DNA damage in the mice with solid tumors and those injected with methotrexate or methotrexate and anthocyanin, compared with that in the untreated mice. Conclusions There was a decrease in genetic instability and DNA damage in the tumor-bearing mice treated with anthocyanin, with a concomitant increase in nuclear poly[adenosine diphosphate (ADP)-ribose] polymerase activity, compared with those of the untreated group. Anthocyanin exerted positive effects in the treatment of mammary adenocarcinoma.
... 27,28 Anthocyanins are bioactive compounds with numerous therapeutic activities, including inflammatory, anticancer, and antioxidant. 28,29 Anthocyanins exert antioxidant effects by scavenging free radicals. They have also been reported to regulate the expression of the inflammatory factors via inhibition of Nuclear factor kappa B (NF-kB). ...
... They have also been reported to regulate the expression of the inflammatory factors via inhibition of Nuclear factor kappa B (NF-kB). 29,30 Studies have reported anthocyanins' inhibitory and anti-metastatic potential on breast cancer. 31,32 Thus, anthocyanins have piqued the interest of researchers, especially in oncotherapy. ...
Article
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Despite the rapid developments and advancements to improve treatments, Breast cancer remains one of the deadliest health challenges and the most frequently diagnosed tumor. One of the major problems with treatment is the unique difference that each cancerous cell exhibits. As a result, treatment of breast cancer has now become more personalized based on the specific features of the tumor such as overexpression of growth factor receptors (Epidermal growth factor receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2)), hormone receptors (Human Estrogen receptor alpha (ER)) and kinases involved in pivotal signaling associated with growth (Phosphatidylinositol 3-kinase (PI3K)). Several chemotherapeutic agents have been developed to curb the menace, but the associated adverse drug effects cannot be overlooked. To this end, this study employed a molecular modeling approach to identify novel compounds of natural origin that can potentially antagonize the receptors (mentioned above) associated with the pathophysiology of breast cancer and at the same time pose very little or no side effects. The results of the molecular model of biological interactions between a library of 118 anthocyanins and the binding pockets of the protein targets identified 5 compounds (Pelargonin, Delphinidin 3-O-rutinoside, Malvin, Cyanidin-3-(6-acetylglucoside), and Peonidin 3-O-rutinoside) with good binding affinities to the protein targets. Further MM-GBSA calculations returned high binding energies. The specific molecular interactions between the compounds and the targets were analyzed and reported herein. Also, all the compounds exhibited good pharmacokinetic profiles and are therefore recommended for further analyses as they could be explored as new treatment options for a broad range and personalized breast cancer treatments.
... The different stages of cancer development result from a dynamic process arising from the combination of a multitude of cellular and molecular events, which can be targeted by different anticancer therapeutic agents. One of the most extensively studied biological properties of anthocyanins relies on their anticancer effect (Lin et al., 2017). This class of compounds has been implicated in different targets for different types of cancers (Chen et al., 2018;Long et al., 2018;Peiffer et al., 2014;Thoppil et al., 2012). ...
Article
Over the years, anthocyanins have emerged as one of the most enthralling groups of natural phenolic compounds and more than 700 distinct structures have already been identified, illustrating the exceptional variety spread in nature. The interest raised around anthocyanins goes way beyond their visually appealing colors and their acknowledged structural and biological properties have fueled intensive research toward their application in different contexts. However, the high susceptibility of monoglycosylated anthocyanins to degradation under certain external conditions might compromise their application. In that regard, polyglycosylated anthocyanins (PGA) might offer an alternative to overcome this issue, owing to their peculiar structure and consequent less predisposition to degradation. The most recent scientific and technological findings concerning PGA and their food sources are thoroughly described and discussed in this comprehensive review. Different issues, including their physical–chemical characteristics, consumption, bioavailability, and biological relevance in the context of different pathologies, are covered in detail, along with the most relevant prospective technological applications. Due to their complex structure and acyl groups, most of the PGA exhibit an overall higher stability than the monoglycosylated ones. Their versatility allows them to act in a wide range of pathologies, either by acting directly in molecular pathways or by modulating the disease environment attributing an added value to their food sources. Their recent usage for technological applications has also been particularly successful in different industry fields including food and smart packaging or in solar energy production systems. Altogether, this review aims to put into perspective the current state and future research on PGA and their food sources.
... Through preclinical and clinical studies, the preventive effects of these natural class of compounds against various cancer types have been confirmed. Lin et al. overviewed their high cancer chemopreventive potencies in accordance with the remarkable related biological effects (e.g., anti-inflammation, antioxidant, anti-proliferation, antiinvasion, inducing cell cycle arrest, apoptosis, autophagy, anti-metastasis, etc.) [9]. As a consequence of the present review, aside from potent activities of ACDs/ACNs for the treatment of PC, their abilities to prevent this malignancy are also acknowledged. ...
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As water-soluble flavonoid derivatives, anthocyanidins and anthocyanins are the plants pigments mostly rich in berries, pomegranate, grapes, and dark color fruits. Many bioactivity properties of these advantageous phytochemicals have been reported; among them, their significant abilities in the suppression of tumor cells are of the promising therapeutic features, which have recently attracted great attention. The prostate malignancy, is considered the 2nd fatal and the most distributed cancer type in men worldwide. The present study was designated to gather the preclinical and clinical studies evaluating potencies of anthocyanidins/anthocyanins for the treatment and prevention of this cancer type for the first time. In general, findings confirm that the anthocyanins (especifically cyanidin-3-O-glucoside) indicated higher activity against prostatic neoplasms compared to their correlated anthocyanidins (e.g., delphinidin); in which potent anti-inflammatory, apoptosis, and anti-proliferative activities were analyzed. Complementary anti-prostate cancer assessment of diverse naturally occurred anthocyanidins/anthocyanins and their synthetically optimized derivatives through preclinical experiments and eventually confirmed by clinical trials can promisingly lead to discover natural-based chemotherapeutic drug options.
... As a type of water-soluble flavonoid compounds, anthocyanin is responsible for the red coloration in pear peel [1]. Dietary anthocyanin has a preventive effect on cancer, cardiovascular diseases, and other chronic diseases due to its strong antioxidant capacity [2,3]. ...
Article
Red-skinned pears are favored by people for their attractive appearance and abundance of anthocyanins. However, the molecular basis of anthocyanin biosynthesis in red pears remains elusive. Here, a comprehensive transcriptome analysis was conducted to explore the potential regulatory mechanism of anthocyanin biosynthesis in 'Red Zaosu' pear (Pyrus pyrifolia × Pyrus communis). Gene co-expression analysis and transcription factor mining identified 263 transcription factors, which accounted for 6.59% of the total number of transcription factors in the pear genome in two gene modules that are highly correlated with anthocyanin biosynthesis. Clustering, gene network modeling with STRING-DB, and local motif enrichment analysis (CentriMo) analysis suggested that PpPIF8 may play a role in anthocyanin biosynthesis. Furthermore, eight PIFs were identified in the pear genome, of which only PpPIF8 was rapidly induced by light. Functional studies showed that PpPIF8 localizes in the nucleus and is preferentially expressed in the tissue of higher levels of anthocyanin. The overexpression of PpPIF8 in pear peel and pear calli promotes anthocyanin biosynthesis and upregulates the expression of anthocyanin biosynthesis genes. Yeast-one hybrid and transgenic analyses indicated that PpPIF8 binds to the PpCHS promoter to induce PpCHS expression. The positive effect of PpPIF8 on anthocyanin biosynthesis is different from previously identified negative regulators of PyPIF5 and MdPIF7 in pear and apple. Taken together, our data not only provide a comprehensive view of transcription events during the coloration of pear peel, but also resolved the regulatory role of PpPIF8 in the anthocyanin biosynthesis pathway.
... Numerous reports on in vitro and in vivo experiments positively implicate anthocyanins in human health. In addition to their well-known antioxidant activities (Julia et al. 2012), many other therapeutic effects of anthocyanins, such as antidiabetic and anti-obesity effects (Gowd, Jia, and Chen 2017), antiangiogenic and anti-thrombotic effects (Krga and Milenkovic 2019), and anticancer (Lin et al. 2017), neuroprotective (Li et al. 2017), and vision-protective effects (Miyake et al. 2012), have been demonstrated. ...
Article
Anthocyanins are widely distributed in nature and exhibit brilliant colors and multiple health-promoting effects; therefore, they are extensively incorporated into foods, pharmaceuticals, and cosmetic industries. Anthocyanins have been traditionally produced by plant extraction, which is characterized by high expenditure, low production rates, and rather complex processes, and hence cannot meet the increasing market demand. In addition, the emerging environmental issues resulting from traditional solvent extraction technologies necessitate a more efficient and eco-friendly alternative strategy for producing anthocyanins. This review summarizes the efficient approach for green extraction and introduces a novel strategy for microbial biosynthesis of anthocyanins, emphasizing the technological changes in production.
... Other effects of anthocyanins may be through the inhibition of proliferation of cancer cells and migration of metastatic cells [265]. Anthocyanins interfered with cell signalling pathways related to cell growth and differentiation, apoptosis, oxidative stress and inflammatory responses in cell culture studies [266,267]. Three important signalling pathways have been identified in these chemopreventive effects of anthocyanins-AMPactivated protein kinase, PI3K/AKT/mTOR and JAK-STAT pathways [263]. Lack of suitable responses in human studies in preventing or reversing various cancers may suggest the need for further human studies in cancer patients with appropriate doses and duration of treatment. ...
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Anthocyanins are mainly purple-coloured phenolic compounds of plant origin that as secondary metabolites are important in plant survival. Understanding their health benefits in humans requires sourcing these unstable compounds in sufficient quantities at a reasonable cost, which has led to improved methods of extraction. Dark-coloured fruits, cereals and vegetables are current sources of these compounds. The range of potential sustainable sources is much larger and includes non-commercialised native plants from around the world and agri-waste containing anthocyanins. In the last 5 years, there have been significant advances in developing the therapeutic potential of anthocyanins in chronic human diseases. Anthocyanins exert their beneficial effects through improvements in gut microbiota, oxidative stress and inflammation, and modulation of neuropeptides such as insulin-like growth factor-1. Their health benefits in humans include reduced cognitive decline; protection of organs such as the liver, as well as the cardiovascular system, gastrointestinal tract and kidneys; improvements in bone health and obesity; and regulation of glucose and lipid metabolism. This review summarises some of the sources of anthocyanins and their mechanisms and benefits in the treatment of chronic human diseases.
... A study by Kongpichitchoke et al. [145] revealed that algal anthocyanin plays a pivotal role in the electron transfer pathway by donating electrons to the free radicals with unpaired electrons. The compound possessed different kind of properties such as anticancer, anti-diabetic, anti-inflammatory, anti-obesity, and reduced fasting sugar [146]; [147]; [148]; [149]; [150]; [151]; [144]. ...
Article
In numerous food businesses, natural pigments are frequently utilized as food colorants. Colorants give nutritional value to food items in addition to improving its appeal, acceptability and flavor. Consumers have a tendency to believe that natural colours are safer than synthetic colours. Therefore, there is a constant desire to explore possible substitutes for synthetic food colorants. Marine algae are known for many naturally occurring colour compounds with sensorial and other health improving qualities. Pigments, phenolic derivatives, proteins and glycosides are among the colorants obtained from marine algae. Colorants from natural sources have been well documented; however, a comprehensive review of natural colorants, especially marine algae, with their chemicals and health benefits, is scarce. In addition, several marine algal colour compounds such as fucoxanthin, zeaxanthin, β-carotene, lutein, anthocyanin, phlorotannins, phycobiliproteins, etc. have been shown to provide a number of health benefits, including antioxidant and anti-diabetic action. This paper discusses the current advancement of marine algae colorants, their potential applications in the food industry and the health benefits they have as antioxidants and anti-diabetics.
... Among them, anthocyanins (members of the flavonoid group) have emerged as beneficial in animal and human studies [16,17]. As reviewed by Mazza [18], many studies have revealed that anthocyanins show an extensive variety of biological actions, such as antioxidant [19,20], anti-inflammatory [21,22], and anti-carcinogenic activities [23]; induction of apoptosis [24]; and neuroprotective effects [25,26]. Moreover, anthocyanins show a diversity of properties on blood vessels [27,28] and platelets [29] that may diminish the incidence of coronary heart disease [30]. ...
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Obesity is a risk factor for cardiovascular diseases, frequently related to oxidative stress and inflammation. Dietary antioxidant compounds improve heart health. Here, we estimate the oxidative grade and inflammation in the heart of dietary-induced obese (DIO) rats after exposure to a high-fat diet compared to a standard diet. The effects of tart cherry seed powder and seed powder plus tart cherries juice were explored. Morphological analysis and protein expressions were performed in the heart. The oxidative status was assessed by the measurement of protein oxidation and 4-hydroxynonenal in samples. Immunochemical and Western blot assays were performed to elucidate the involved inflammatory markers as proinflammatory cytokines and cellular adhesion molecules. In the obese rats, cardiomyocyte hypertrophy was accompanied by an increase in oxidative state proteins and lipid peroxidation. However, the intake of tart cherries significantly changed these parameters. An anti-inflammatory effect was raised from tart cherry consumption, as shown by the downregulation of analyzed endothelial cell adhesion molecules and cytokines compared to controls. Tart cherry intake should be recommended as a dietary supplement to prevent or counteract heart injury in obese conditions.
... However, expression of the antioxidant enzymes SOD, CAT, and GPx is controlled by the redox sensitive transcription factor nuclear factor-erythroid 2 p45related factor 2 (Nrf2) [67]. It is well known that anthocyanins, but also their gut-derived metabolites, are able to activate the Nrf2 pathway and consequently upregulate the defense against ROS and oxidative stress [68,69]. Compared with cells from the primary tumor site, metastatic cancer cells displayed higher ROS concentrations [6]. ...
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Cancer mortality is mainly due to metastasis. Therefore, searching for new therapeutic agents suppressing cancer cell migration is crucial. Data from human studies regarding effects of anthocyanins on cancer progression, however, are scarce and it is unclear whether physiological concentrations of anthocyanins and their metabolites reduce cancer cell migration in vivo. In addition, interactions with chemotherapeutics like 5-fluorouracil (5-FU) are largely unknown. Thus, we combined a placebo-controlled, double-blinded, cross-over study with in vitro migration studies of colon cancer cell lines to examine the anti-migratory effects of plasma-isolated anthocyanins and their metabolites (PAM). Healthy volunteers (n = 35) daily consumed 0.33 L of an anthocyanin-rich grape/bilberry juice and an anthocyanin-depleted placebo juice for 28 days. PAM were isolated before and after intervention by solid-phase extraction. HT-29 and Caco-2 cells were incubated with PAM in a Boyden chamber. Migration of HT-29 cells was significantly inhibited by PAM from juice but not from placebo. In contrast, Caco-2 migration was not affected. Co-incubation with 5-FU and pooled PAM from volunteers (n = 10), which most effectively inhibited HT-29 migration, further reduced HT-29 migration in comparison to 5-FU alone. Therefore, PAM at physiological concentrations impairs colon cancer cell migration and may support the effectiveness of chemotherapeutics.
... Overall, the anthocyanin-rich Illawarra plum inhibited cell proliferation by blocking signal transduction pathways, regulating gene expression, and inducing apoptosis. Previously, these events were shown to be triggered by the most common phenolic compounds including anthocyanins and flavanols (Jeong et al. 2009;Lin et al. 2017). However, the study by Symonds, Konczak, and Fenech (2013) did not report the chemical profile of the Illawarra plum extract. ...
Article
Australian native plants have adapted themselves to harsh climatic conditions enabling them to produce unique and high levels of secondary metabolites. Native fruits and vegetables have been an integral part of the Indigenous Australian diet and Bush Medicine for centuries. They have recently gained popularity owing to their rich dietary fibre, minerals, polyphenolic and antioxidant contents. This review presents a comprehensive summary and critical assessment of the studies performed in the last few decades to understand the phytochemical and nutritional profiles and therapeutic properties of Australian native fruits and vegetables. Furthermore, the potential of these fruits and vegetables as functional food ingredients and in the prevention and treatment of different diseases is discussed. Research on the nutritional and phytochemical profiles and therapeutic activity of Australian vegetables is limited with most studies focused on native fruits. These fruits have demonstrated promising antioxidant, anticancer, anti-inflammatory and antimicrobial activities mostly in in vitro models. More research to a) identify novel bioactive compounds, b) define optimal post-harvest and extraction methods, and c) understand molecular mechanisms of pharmacological activity through preclinical and clinical studies is prudent for the prospective and wider use of Australian native fruits and vegetables by the food, pharmaceutical, and nutraceutical industries.
... Anthocyanins exert core functions in plants such as attracting pollinators and protecting against biotic and abiotic stresses (de Pascual-Teresa et al. 2010;Jimenez-Garcia et al. 2013). Although there is some controversy concerning their direct effect on the human body, anthocyanins are thought to offer potential health benefits including anti-inflammatory and anti-carcinogenic properties, as well as the potential to prevent cardiovascular disease and to control obesity or diabetes (Cassidy et al. 2011;He and Monica Giusti 2010;Khoo et al. 2017;Lin et al. 2017;Speer et al. 2020). Since anthocyanins have both aesthetic value and potential health benefits, breeding cultivars of various crops with increased anthocyanin contents has become a priority (Allan and Espley 2018). ...
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Key Message The novel gene CaAN3 encodes an R2R3 MYB transcription factor that regulates fruit-specific anthocyanin accumulation. Abstract The key regulatory gene CaAN2 encodes an R2R3 MYB transcription factor that regulates anthocyanin biosynthesis in various tissues in pepper (Capsicum annuum). However, CaAN2 is not expressed in certain pepper accessions showing fruit-specific anthocyanin accumulation. In this study, we identified the novel locus CaAN3 as a regulator of fruit-specific anthocyanin biosynthesis, using an F2 population derived from a hybrid cultivar with purple immature fruits and segregating for CaAN3. We extracted total RNA, assembled two RNA pools according to fruit color, and carried out bulked segregant RNA sequencing. We aligned the raw reads to the pepper reference genome Dempsey and identified 6,672 significant single nucleotide polymorphisms (SNPs) by calculating the Δ(SNP-index) between the two pools. We then conducted molecular mapping to delimit the target region of CaAN3 to the interval 184.6–186.4 Mbp on chromosome 10. We focused on Dem.v1.00043895, encoding an R2R3 MYB transcription factor, as the strongest candidate gene. Sequence analysis revealed four insertion/deletion polymorphisms in the promoter region of the green CaAN3 allele. We employed virus-induced gene silencing and transient overexpression assays to characterize the function of the candidate gene. When Dem.v1.00043895 was silenced in pepper, anthocyanin accumulation decreased in the pericarp, while the transient overexpression of Dem.v1.00043895 in Nicotiana benthamiana leaves resulted in the accumulation of anthocyanins around the infiltration sites. These results showed that Dem.v1.00043895 is CaAN3, an activator of anthocyanin biosynthesis in pepper fruits.
... ACNs, featuring six common glycosylated forms of anthocyanidins (i.e., malvidin, pelargonidin, cyanidin, petunidin, delphinidin and peonidin) with hydroxyl (OH) moieties in their structure at the 3 position on the C-ring are water-soluble pigments belonging to flavonoids responsible for producing various colors in fruits, berries and vegetables that exert a protective effect against diabetes, cardiovascular and neurodegenerative diseases and cancers (including LC) [23][24][25]. ...
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In traditional medicine, different parts of plants, including fruits, have been used for their anti-inflammatory and anti-oxidative properties. Plant-based foods, such as fruits, seeds and vegetables, are used for therapeutic purposes due to the presence of flavonoid compounds. Proanthocyanidins (PCs) and anthocyanins (ACNs) are the major distributed flavonoid pigments in plants, which have therapeutic potential against certain chronic diseases. PCs and ACNs derived from plant-based foods and/or medicinal plants at different nontoxic concentrations have shown anti-non-small cell lung cancer (NSCLC) activity in vitro/in vivo models through inhibiting proliferation, invasion/migration, metastasis and angiogenesis and by activating apoptosis/autophagy-related mechanisms. However, the potential mechanisms by which these compounds exert efficacy against nicotine-induced NSCLC are not fully understood. Thus, this review aims to gain insights into the mechanisms of action and therapeutic potential of PCs and ACNs in nicotine-induced NSCLC.
... Hemp was the best matrix for fortification with each gram of the fortified hemp flour potentially delivering the equivalent of anthocyanins present in 20 g of fresh berries. This is particularly important considering that anthocyanins have been extensively studied for their health benefits, including the prevention of cardiovascular disease [28][29][30], anti-cancer properties [31][32][33] and to benefit people living with type 2 diabetes mellitus [34][35][36]. Furthermore, buckwheat and hemp flours beneficially modulated gastrointestinal hormones and promoted satiety in healthy volunteers [7]. ...
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Facing a climate emergency and an increasingly unhealthy population, functional foods should not only address health issues but must be prepared from sustainable ingredients while contributing to our sustainable goals, such as tackling waste and promoting a healthy environment. High-protein crop flours, i.e., buckwheat, hemp and fava bean, are investigated as potential matrices to be fortified with key bioactive phytochemicals from soft fruits to explore potential waste valorization and to deliver sustainable functional food ingredients. Hemp flour provided the best matrix for anthocyanin fortification, adsorbing of 88.45 ± 0.88% anthocyanins and 69.77 mg/kg of additional phytochemicals. Buckwheat and fava bean absorbed 78.64 ± 3.15% and 50.46 ± 2.94% of anthocyanins 118.22 mg/kg and 103.88 mg/kg of additional phytochemicals, respectively. During the fortification, there was no detectable adsorption of the berry sugars to the flours, and the quantities of free sugars from the flours were also removed. One gram of fortified hemp flour provides the same amount of anthocyanins found in 20 g of fresh bilberries but has substantially less sugar. The optimum conditions for high protein flour fortification with anthocyanins was established and showed that it is a viable way to reduce and valorize potential agricultural waste, contributing to a circular and greener nutrition.
... The regular intake of these compounds could contribute to reducing the risk of various diseases whose biological genesis is due to oxidative stress caused by the excess of free radicals [68]. Studies over the years have pointed out the potential health benefits promoted by phenolic compounds, such as anti-inflammatory [69] and anticancer effects [70,71,7] and the reduction of chronic non-communicable diseases appearance [65,72]. Besides the modulation of inflammation and oxidative stress, anthocyanins have many beneficial biological activities, such as inhibition of cancer cell growth, induction of apoptosis in cancer cells, and other beneficial intracellular and metabolic actions [67,73,74]. ...
Article
Anthocyanins are an important group of phenolic compounds responsible for pigmentation in several plants, and regular consumption is associated with a reduced risk of several diseases. However, the application of anthocyanins in foods represents a challenge due to molecular instability. The encapsulation of anthocyanins in nanostructures is a viable way to protect from the factors responsible for degradation and enable the industrial application of these compounds. Nanoencapsulation is a set of techniques in which the bioactive molecules are covered by resistant biomaterials that protect them from chemical and biological factors during processing and storage. This review comprehensively summarizes the existing knowledge about the structure of anthocyanins and molecular stability, with a critical analysis of anthocyanins’ nanoencapsulation, the main encapsulating materials (polysaccharides, proteins, and lipids), and techniques used in the formation of nanocarriers to protect anthocyanins. Some studies point to the effectiveness of nanostructures in maintaining anthocyanin stability and antioxidant activity. The main advantages of the application of nanoencapsulated anthocyanins in foods are the increase in the nutritional value of the food, the addition of color, the increase in food storage, and the possible increase in bioavailability after oral ingestion. Nanoencapsulation improves stability for anthocyanin, thus demonstrating the potential to be included in foods or used as dietary supplements, and current limitations, challenges, and future directions of anthocyanins’ have also been discussed.
... Flavonoids are ubiquitous secondary metabolites that possess a variety of biological activities, such as defense against ultraviolet rays and biological and abiotic stresses (Harborne and Williams, 2000;Treutter, 2005;Nenaah, 2014). Additionally, flavonoids are believed to be good for human health, serving such functions as preventing cardiovascular diseases and controlling obesity and antitumoral effects (Lin et al., 2016). Branches of the flavonoid biosynthetic pathway are involved in the production and regulation of anthocyanins, proanthocyanins and flavonols. ...
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During natural evolution and artificial selection, the fruit color of many species has been repeatedly gained or lost and is generally associated with mutations in genes encoding R2R3-MYB transcription factors, especially MYB10. In this study, we show that a heterozygous frameshift mutation (FaMYB10AG-insert/FaMYB10wild ) is responsible for the loss of anthocyanins in the flesh of cultivated strawberry. Comparative transcriptomic and metabolomic analyses of red- and white-fleshed strawberry indicated that the low expression level of FaUFGT (flavonol-O-glucosyltransferases) was responsible for the loss of anthocyanins and accumulation of proanthocyanidin in the white-fleshed strawberry and was the crucial gene that encodes enzymes of the anthocyanin biosynthesis pathway. Accordingly, overexpression and silencing of FaUFGT altered anthocyanin content and changed the flesh color of strawberry fruits. Furthermore, whole-genome resequencing analyses identified an AG insertion in the FaMYB10 coding region (FaMYB10AG-insert ) of white-fleshed strawberry. Y1H and EMSA assays showed that FaMYB10wild was able to bind to the promoter of the FaUFGT gene, while the FaMYB10AG-insert could not. The skin and flesh color were tightly linked to the number of fully functional FaMYB10 copies in the selfing progeny of white-fleshed strawberry. Our results suggested that heterozygous frameshift mutation of FaMYB10 resulted in the loss of the ability to activate the expression of the FaUFGT gene, was responsible for the natural formation of red and white-fleshed strawberry.
... These beneficial health effects include antioxidant and antimicrobial activity, anti-inflammation, anti-mutagenesis, induction of differentiation, inhibition of cancer cells proliferation, anti-metastasis, and heavy metal sequestration. Anthocyanins use different biological pathways to protect organism from the negative impact of the environment such as mitogen-activated protein kinase (MAPK) pathway, free-radical scavenging pathway, cyclooxygenase pathway, or inflammatory cytokines signaling [143,144]. ...
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Rapid urbanization and industrialization have led to alarming cadmium (Cd) pollution. Cd is a toxic heavy metal without any known physiological function in the organism, leading to severe health threat to the population. Cd has a long half-life (10–30 years) and thus it represents serious concern as it to a great extent accumulates in organs or organelles where it often causes irreversible damage. Moreover, Cd contamination might further lead to certain carcinogenic and non-carcinogenic health risks. Therefore, its negative effect on population health has to be minimalized. As Cd is able to enter the body through the air, water, soil, and food chain one possible way to defend and eliminate Cd toxicities is via dietary supplements that aim to eliminate the adverse effects of Cd to the organism. Naturally occurring bioactive compounds in food or medicinal plants with beneficial, mostly antioxidant, anti-inflammatory, anti-aging, or anti-tumorigenesis impact on the organism, have been described to mitigate the negative effect of various contaminants and pollutants, including Cd. This study summarizes the curative effect of recently studied bioactive substances and mineral elements capable to alleviate the negative impact of Cd on various model systems, supposing that not only the Cd-derived health threat can be reduced, but also prevention and control of Cd toxicity and elimination of Cd contamination can be achieved in the future.
... GTP-binding proteins are involved in the translocation of GLUT4-containing vesicles to the plasma, suggesting the Ras/MAP kinase pathway acts in the signaling pathway of insulin toward glucose uptake [23,24]. However, most studies on effects of Ras-MAPK signaling pathways by anthocyanins were carried out in cancer research [25,26]. In the present study, we found that both HBRE and CBRE stimulated the phosphorylation of IRS-1 in a dose-dependent manner from 10 to 100 µg/mL. ...
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Anthocyanin from black rice was reported to have beneficial effects on diabetes, but the molecular mechanisms are still largely unknown. Black rice cultivated from different regions in Taiwan (Hualien and Changhua) were included in this study. Concentrations of anthocyanin were significantly higher using the ethanol extraction method than those using water; therefore, ethanol extracts from Hualien and Changhua black rice (HBRE and CBRE) were used for further investigation. 2-NBDG glucose uptake analysis revealed that both HBRE and CBRE promote glucose uptake in C2C12 myotubes. The membrane expression levels of GLUT4 and phosphorylation of IRS-1 also had been markedly increased by both HBRE and CBRE, which was in accordance with the glucose uptake results. CBRE did not affect the downstream of IRS-1 but significantly enhanced protein levels of p-AMPK/AMPK. In contrast, HBRE was shown to target various signaling participated in GLUT4 glucose uptake, including PI3K/Akt and the p38 MAPK/ERK. Overall, we demonstrated that anthocyanin-rich extracts from black rice stimulate GLUT4 glucose uptake via upregulation of PI3K/Akt and AMPK/p38 MAPK signaling in C2C12 myotubes. Our findings revealed that anthocyanin-rich black rice might be a promising functional food for the prevention and treatment of insulin resistance and diabetic hyperglycemia.
... Cyanidin, delphinidin, malvidin, peonidin, petunidin, and pelargonidin are the six common anthocyanidins and share the C6-C3-C6 flavan or 2-phenylbenzodihydropyran skeleton [124]. Their potential antitumor effects are attributed to their antioxidant, anti-inflammatory, antimutagenesis, antiproliferative, anti-invasive, proapoptotic, and autophagy-promoting activity in cancer cells [125]. ...
Article
Cancer is one of the leading causes of death in patients worldwide, where invasion and metastasis are directly responsible for this statement. Although cancer therapy has progressed in recent years, current therapeutic approaches are ineffective due to toxicity and chemoresistance. Therefore, it is essential to evaluate other treatment options, and natural products are a promising alternative as they show antitumor properties in different study models. This review describes the regulation of tissue inhibitors of metalloproteinases (TIMPs) expression and the role of flavonoids as molecules with the antitumor activity that targets TIMPs therapeutically. These inhibitors regulate tissue extracellular matrix (ECM) turnover; they inhibit matrix metalloproteinases (MMPs), cell migration, invasion, and angiogenesis and induce apoptosis in tumor cells. Data obtained in cell lines and in vivo models suggest that flavonoids are chemopreventive and cytotoxic against various types of cancer through several mechanisms. Flavonoids also regulate crucial signaling pathways such as focal adhesion kinase (FAK), phosphatidylinositol-3-kinase (PI3K)-Akt, signal transducer and activator of transcription 3 (STAT3), nuclear factor κB (NFκB), and mitogen-activated protein kinase (MAPK) involved in cancer cell migration, invasion, and metastasis. All these data reposition flavonoids as excellent candidates for use in cancer therapy.
... They are active in a variety of health conditions such as cardiovascular [278], neurological [279], and metabolic diseases [280]. Moreover, anthocyanins have an active role in cancer management due to their basic specification as anti-oxidants, anti-inflammatory, anti-invasion, and anti-metastatic [281]. ...
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Cancer is still one of the most widespread diseases globally, it is considered a vital health challenge worldwide and one of the main barriers to long life expectancy. Due to the potential toxicity and lack of selectivity of conventional chemotherapeutic agents, discovering alternative treatments is a top priority. Plant-derived natural products have high potential in cancer treatment due to their multiple mechanisms of action, diversity in structure, availability in nature, and relatively low toxicity. In this review, the anticancer mechanisms of the most common phytochemicals were analyzed. Furthermore, a detailed discussion of the anticancer effect of combinations consisting of natural product or natural products with chemotherapeutic drugs was provided. This review should provide a strong platform for researchers and clinicians to improve basic and clinical research in the development of alternative anticancer medicines.
... The reversal of drug resistance, increased sensitivity to chemotherapeutic agents, anti-invasion and anti-metastasis have also been suggested to be involved in ameliorating the cancerous situations. A data analysis of the basic findings, in vivo and in vitro, inferences from clinical trials, as well the herbalists and traditional healers practices based information was analyzed [311]. The anti-cancer effects of anthocyanins have also been reported by Longo et al. ...
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Anthocyanins are water-soluble, colored compounds of the flavonoid class, abundantly found in the fruits, leaves, roots, and other parts of the plants. The fruit berries are prime sources and exhibit different colors. The anthocyanins' utility as a traditional medicament for liver protection and cure and importance as strongest plants-based anti-oxidants have conferred these plants products different biological activities. These activities include anti-inflammation, liver protective, analgesic, and anti-cancers, which have provided the anthocyanins an immense commercial value and have impelled their chemistry, biological activity, isolation, and quality investigations as prime focus. Methods in extraction and production of anthocyanin-based products have assumed vital economic importance. Different extraction techniques in aquatic solvents mixtures, eutectic solvents, and other chemically reactive extractions including low acid concentrations-based extractions have been developed. The prophylactic and curative therapy roles of the anthocyanins, together with no reported toxicity have offered much-needed impetus and economic benefits to these classes of compounds which are commercially available. Information retrieval from various search engines, including the PubMed®, ScienceDirect®, Scopus®, and Google Scholar®, were used in the review preparation. This imparted an outlook on the anthocyanins occurrence, roles in plants, isolation-extraction, structures, biosynthetic as well as semi- and total-synthetic pathways, product quality and yields enhancements, including uses as part of traditional medicines, and uses in liver disorders, prophylactic and therapeutic applications in liver protection and longevity, liver cancer and hepatocellular carcinoma. The review also highlights the integrated approach to yields maximizations to meet the regular demands of the anthocyanins products, also as part of the extract-rich preparations together with a listing of marketed products available for human consumption as nutraceuticals/food supplements.
... flavonoids and anthocyanins. Anthocyanins are water-soluble pigments that exhibit not only strong antioxidant activities, but also protective effects towards cancer and tumor migration and invasion (Lin et al., 2017), as well as other medical benefits (Khoo et al., 2017). ...
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Pomegranate (Punica granatum L.) fruit peels are known to enrich the nutritional value of pomegranate juice due to their highly abundant phenolic metabolites such as hydrolyzable tannins (HTs), anthocyanins, and flavonoids, as well as the whole-fruit-based industrial extraction process. These shikimate pathway-derived metabolites also provide protection against pests and abiotic stresses for the fruit, and are important for the commercial trait of fruit peel color. To better understand the chemical diversity and biosynthetic relationships of phenolic metabolites in the outer fruit peel, we conducted metabolite profiling of outer peels from 15 pomegranate accessions largely varied in peel color using ultra high-performance liquid chromatography-diode array detection (uHPLC-DAD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 48 metabolites were (tentatively) identified through comparison to authentic standards, as well as MS or MS/MS spectral data in metabolomics databases. The 15 pomegranate accessions differ greatly in levels of anthocyanins, HTs, flavonoids, and other shikimate pathway-related metabolites, with the largest variations observed in the anthocyanin content. Negative correlations between HTs and flavonoids/anthocyanins, and between anthocyanins and proanthocyanins were observed, suggesting that these metabolites may compete for the same biosynthetic precursors for their production and are coordinately regulated.
... The neutralization of radicals by anthocyanins protects cells from oxidative damage, decreasing the risks of aging and various diseases. In this context, many in vitro and in vivo studies confirmed the health benefits attributed to anthocyanins, such as their antioxidant role [30,[37][38][39][40][41][42][43][44], anti-inflammatory action [45], neuroprotection [46][47][48][49], anticancer effects [20,[46][47][48][49][50][51][52][53][54][55][56], antiobesity effects [21,[57][58][59][60][61][62][63][64], cardiovascular protection [65][66][67], antidiabetic effects [68][69][70][71][72][73], visual protection [74][75][76], and antimicrobial properties [72,73,77,78]. A recent systematic review of 44 randomized controlled trials and 15 prospective studies relating to cardiovascular diseases and ingestion of anthocyanin-rich foods or pure anthocyanins showed strong evidence of their effect on improving the blood lipid profile and decreasing circulating proinflammatory cytokines, justifying their inclusion in a cardioprotective diet [73]. ...
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Anthocyanins are an important group of phenolic compounds responsible for pigmentation in several plants. For humans, a regular intake is associated with a reduced risk of several diseases. However, molecular instability reduces the absorption and bioavailability of these compounds. Anthocyanins are degraded by external factors such as the presence of light, oxygen, temperature, and changes in pH ranges. In addition, the digestion process contributes to chemical degradation, mainly through the action of intestinal microbiota. The intestinal microbiota has a fundamental role in the biotransformation and metabolization of several dietary compounds, thus modifying the chemical structure, including anthocyanins. This biotransformation leads to low absorption of intact anthocyanins, and consequently, low bioavailability of these antioxidant compounds. Several studies have been conducted to seek alternatives to improve stability and protect against intestinal microbiota degradation. This comprehensive review aims to discuss the existing knowledge about the structure of anthocyanins while discussing human absorption, distribution, metabolism, and bioavailability after the oral consumption of anthocyanins. This review will highlight the use of nanotechnology systems to overcome anthocyanin biotransformation by the intestinal microbiota, pointing out the safety and effectiveness of nanostructures to maintain molecular stability.
... It has been reported that some of polyphenols have obvious antitumor activity with different mechanisms of action. [38][39][40][41] It is expected to explore more polyphenolic compounds with this activity. Although we aimed to investigate the anti-metastasis effect and mechanism of hesperetin on TNBC, to some extent, the lack of in vivo experiments may be a limitation of our study. ...
Article
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Triple-negative breast cancer is an aggressive subtype of breast cancer with poor clinical outcomes and poor prognosis. Hesperetin is an active component extracted from Citrus fruits and Traditional Chinese Medicine has a wide range of pharmacological effects. Here, we assessed the anti-migration and anti-invasive effects and explored inhibitory mechanisms of hesperetin on metastasis of human triple negative breast cancer MDA-MB-231 cells. Cell viability experiments revealed that 200 μM hesperetin has a clear inhibitory effect on MDA-MB-231 cells. TGF-β1 treatment induces apparent tumor progression in MDA-MB-231 cells including aberrant wound-healing and invasion ability, which is effectively suppressed by hesperetin co-treatment. Additionally, hesperetin inhibited the TGF-β1-mediated actin stress fiber formation. Western blot results showed that hesperetin suppressed the TGF-β1-mediated (i) activation of Fyn, (ii) phosphorylation of paxillin at Y31, Y88, and Y118 sites, (iii) the increased expression of RhoA, and (iv) activation of Rho-kinase. We demonstrated the increased interaction of Fyn with paxillin and RhoA protein in the TGF-β1-induced metastasis of MDA-MB-231 cells. Small interfering RNA Fyn inhibited phosphorylation of paxillin (Y31) and activation of Rho-kinase induced by TGF-β1. In conclusion, hesperetin has a significant inhibitory effect on migration and invasion of MDA-MB-231 cells induced by TGF-β1, which might be attributed to inhibiting the Fyn/paxillin/RhoA pathway.
... Our research team has shown that Cr (VI) could induce intracellular mitophagy in DF-1 cells [29]. Anthocyanin is a natural anti-oxidant; some researchers suggested that anthocyanin plays a vital role in the development of numerous aging diseases via various anti-oxidant pathways [30]. Thus, using anthocyanins may be an effective strategy for addressing various oxidative stresses. ...
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Cr (VI) is an extremely toxic environment and professional pollutant that seriously damages mitochondrial dysfunction when it enters a cell. Anthocyanins possess anti-oxidant, antiaging, and antifatigue properties. The regulatory effect of Lycium ruthenicum Murr anthocyanin (LRMA) on Cr (VI)-induced mitophagy in DF-1 cells was determined. The experimental design was divided into blank group, groups subjected to Cr (VI) and Cr (VI), and LRMA co-treatment groups. Cell viability was determined by the CCK-8 assay. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were assessed by flow cytometry and immunofluorescence. Mitophagy was monitored by ELISA and Western blot. Data showed that Cr (VI) caused the overexpression of autophagy-related proteins (LC3, Beclin-1) and reduced the expressions of autophagy protein p62 and TOMM20. Compared with the Cr (VI) group, the LRMA group showed considerably decreased mitochondrial damage and mitophagy. LRMA decreased the mitochondrial protein expression of PINK1 and Parkin’s transfer from the cytoplasm to mitochondria. LRMA may confer protective effects by reducing PINK1/Parkin-mediated mitophagy in Cr (VI)-induced DF-1 cell models.
... Anthocyanins are mainly found in red-, purple-, and blue-colored flowers and fruits [1]. They are potential food additives for prevention of various diseases, exhibiting antidiabetic, anticancer, anti-inflammatory, and antimicrobial effects [2][3][4]. Anthocyanins are extremely sensitive to environmental conditions, such as temperature, pH, light, and oxygen. Due to their poor stability, encapsulation technologies were thoroughly investigated to improve the bioavailability of anthocyanins and to control their release in proper medium [5]. ...
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Anthocyanidins, the aglycons of anthocyanins, are known, beyond their function in plants, also as compounds with a wide range of biological and pharmacological activities, including cytostatic effect against various cancer cells. The nature and position of the substituents in the flavylium cation is essential for such biological properties, as well as the equilibrium between the multistate of the different chemical species that are generated by the flavylium cation, including quinoidal base, hemiketal, and cis- and trans-chalcones. In this work, eight new flavylium derivatives were synthesized, characterized for confirmation of the structure by FT-IR and 2D-NMR, and investigated in vitro as possible cytostatic compounds against HCT116 and HepG2 cancer cells. The most active two compounds were explored for their halochromic properties that can influence the biological activity and subjected to molecular encapsulation in β-cyclodextrin derivatives in order to increase their solubility in water and bioavailability. The anticancer effect was influenced by the position (6-, 7-, or 8-) of the methoxy group in the β-ring of the methoxy-4’-hydroxy-3’-methoxyflavylium cation, while the study of the halochromic properties revealed the important role played by the chalcone species of the pH-dependent multistate in both the uncomplexed and inclusion complex forms of these anthocyanidins.
... Anthocyanins are food compounds that are mainly found in dark fruits such as blueberries, black currants, cranberries, and some vegetables such as red cabbage, radish, and eggplant [38]. e beneficial effects of anthocyanin have been reported previously, including anti-inflammatory [39], antimicrobial [40], anticarcinogenic [41], and antidiabetes [42]. Anthocyanins regulate the carbohydrate metabolism in the body by the upregulation of GLUT4 (insulin-regulated glucose transporter) translocation, increased activation of PPARc (peroxisome proliferator-activated receptor-c) in adipose tissue and skeletal muscles, and increased secretion of adiponectin and leptin [38]. ...
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Diabetes mellitus (DM) is a known systemic disease with increasing global prevalence and multi-organ complications including diabetic nephropathy (DN). The trend of using medicinal plants in the management of DM is increasing exponentially. Etlingera elatior is a medicinal plant that contains chemicals and antioxidants that delay the oxidation process. However, available data focusing on its use on DN are inconsistent and scarce. This study aims to investigate the antidiabetic and nephroprotective effects of E. elatior flower aqueous extract (EEAE) in a type 2 DM rat (T2DR) model. The T2DR model was developed using a combination of a high-fat diet (HFD) and a low dose of streptozotocin (STZ) at 35 mg/kg. Thirty-two Sprague Dawley male rats were randomly divided into four groups (n = 8): (1) control (normal rat), (2) T2DR (untreated-type 2 diabetic rat), (3) Met (250 mg/kg metformin-treated T2DR), and (4) EEAE (1000 mg/kg EEAE-treated T2DR). All treatments were administered orally for 6 weeks. EEAE significantly reduced fasting blood glucose (FBG), microalbuminuria, serum creatinine, and serum blood urea nitrogen. EEAE also reduced malondialdehyde (MDA) and enhanced the levels of antioxidant markers—superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and total antioxidant capacity (T-AOC). The inflammatory marker (interleukin (IL)-6) and fibrosis markers (transforming growth factor-beta (TGF-β), and connective tissue growth factor (CTGF)) were significantly decreased in the EEAE-treated group. The T2DR group developed DN, which was characterized by segmental sclerosis of the glomeruli associated with focal tubular atrophy and interstitial fibrosis. Interestingly, the histology of kidney tissue in the EEAE group was preserved. This effect was similar to that of the control drug metformin. In summary, the antidiabetic and nephroprotective effects might be related to the antioxidant properties and anti-inflammatory effects of the EEAE. The antidiabetic activity could be due to the presence of the active compound cyanidin-3-O-glycosides, which is an anthocyanin antioxidant, that is present in the EEAE. E. elatior has the potential to be developed as a natural source of antioxidants that can be used for the prevention or even the treatment of DM. These findings could lead to future research into the therapeutic use of E. elatior in alleviating the progression of DM and thus preventing nephropathy.
Article
Pyroptosis, an inflammatory form of lytic cell death, is a type of cell death mediated by the gasdermin (GSDM) protein family. Upon recognizing exogenous or endogenous signals, cells undergo inflammasome assembly, GSDM cleavage, the release of proinflammatory cytokines and other cellular contents, eventually leading to inflammatory cell death. In this review, we discuss the roles of the GSDM family for anti-cancer functions and various antitumor drugs that could activate the pyroptosis pathways.
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Anthocyanins contribute vibrant colors to plants, enhance a plant's ability to survive biotic and abiotic stresses, and have a positive impact on human health. Solanaceous fruit vegetables, which mainly include tomato (Solanum lycopersicum L.), eggplant (Solanum melongena L.), and pepper (Capsicum annuum L.), display natural variations of anthocyanin pigments in term of types, contents and tissue-specific patterns. Breeding anthocyanin-rich variety is the predominant avenue to improve the quality of Solanaceous fruit vegetables. Anthocyanin biosynthesis is a complicated process affected and regulated by environmental conditions and developmental cues. This article reviews the health benefits of anthocyanin, anthocyanin synthesis and transportation, transcriptional regulations, influencing factors, and strategies for increasing the anthocyanin content in Solanaceous fruit vegetables. It aims to provide a reference for further research on the biosynthesis, accumulation, and metabolism of anthocyanin, and to point out the direction for breeding and cultivation of anthocyanin-rich Solanaceous fruit vegetables.
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Twelve polyphenols from three distinct families (dihydroflavonols, flavan-3-ols, and flavanones) were studied as potential substrates of anthocyanidin synthase from Vitis vinifera (VvANS). Only flavan-3-ols of (2R,3S) configuration having either a catechol or gallol group on ring B are accepted as substrates. Only dihydroflavonols of (2R,3R) configuration are accepted as substrates, but a catechol or gallol group is not mandatory. Flavanones are not substrates of VvANS. HPLC and MS/MS analyses of the enzymatic products showed that the VvANS-catalyzed oxidative transformation of (+)-dihydroflavonols, such as dihydroquercetin, dihydrokaempferol and dihydromyricetin, leads only to the corresponding flavonols. Among the flavan-3-ols recognized as substrates, (+)-gallocatechin was only transformed into delphinidin by VvANS, whereas (+)-catechin was transformed into three products, including two major products that were an ascorbate–cyanidin adduct and a dimer of oxidized catechin, and a minor product that was cyanidin. Data from real-time MS monitoring of the enzymatic transformation of (+)-catechin suggest that its products are all derived from the initial C3-hydroxylation intermediate, i.e., a 3,3-gem-diol, and their most likely formation mechanism is discussed.
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This study investigated the protective effects of anthocyanin (AC) supplementation on lipopolysaccharide (LPS)-challenged yellow-feathered broiler chicks. A total of 480 1-d female broiler chicks were randomly assigned to 4 treatment groups: basal diet (CON), basal diet + LPS-challenge (LPS), supplementation with 100 or 400 mg/kg AC + LPS-challenge (AC100, AC400). On d 17 and d 19, birds in LPS, AC100 and AC400 received an intramuscular dose of LPS, while birds in CON received saline. The result showed that (1) LPS injection significantly decreased (P < 0.05) body weight on d 21 and average daily gain of broiler chicks from 1 to 21 days of age, and supplementation with 100 mg/kg AC increased (P < 0.05) those of LPS-challenged broilers. (2) There were no differences among the treatments (P > 0.05) in relative weights of immune organs. (3) Supplementation with AC (AC100 and AC400) increased (P < 0.05) the jejunal villus height and villus height/crypt depth ratio (AC100) of LPS-challenged birds. Challenge with LPS decreased the relative expression of OCLN (Occludin), ZO-1, JAM2, and MUC2 in jejunal mucosa of broilers, and supplementation with AC offset the relative expression of ZO-1, JAM2 (AC100 and AC400), and OCLN (AC400) in LPS-injected broilers. (4) LPS-induced increase in the malondialdehyde (MDA) concentration and decreases in activity of total superoxide dismutase (T-SOD), and expression of SOD1, CAT and GPX in jejunal mucosa, were attenuated by dietary AC supplementation. In conclusion, in yellow-feathered broiler chicks, dietary supplementation with AC alleviated LPS-induced declined growth performance and mucosal damage of the intestine through antioxidant effects.
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The haskap (Lonicera caerulea L., Caprifoliaceae) berry has been widely used in traditional medicine in Kuril Islands, Russia, Japan, and China. Cyanidin-3-O-glucoside (C3G) is the most abundant anthocyanin in haskap berries, and C3G induces antiproliferative pharmacological activity in various cancer cells. However, no study has investigated its anti-lung large-cell carcinoma (LCC) pharmacological role. Therefore, this study determined whether C3G alone or C3G combined with 5-fluorouracil (5-FU) inhibits human lung LCC. We determined the tumor growth, apoptosis, inflammation, and metastasis in the H661 lung LCC lines xenografted into BALB/c nude mice. The mice were administered saline (control), 5-FU, C3G, or both C3G and 5-FU. Relative to the control mice, those treated with C3G alone or both C3G and 5-FU exhibited impaired tumor growth; increased tumor apoptosis; decreased inflammatory cytokine levels (e.g., IL-1β, TNF-α, C-reactive protein, and IL-6); decreased inflammation-related factors, including cyclooxygenase-2 protein and nuclear factor-κB (NF-κB) mRNA; increased inhibition of NF-κB kinase α mRNA; and downregulated metastasis-related factors, such as transforming growth factor-β, CD44, epidermal growth factor receptor, and vascular endothelial growth factor. In addition, C3G alone or combined with 5-FU affected the expression of the tumor microenvironment-related factors Ki67, CD45, PDL1, and CD73. Compared with the mice treated with 5-FU or C3G alone, those treated with both C3G and 5-FU exhibited significantly impaired tumor growth, decreased tumor sizes, and increased tumor inhibition. This in vivo study demonstrated that C3G alone or combined with 5-FU may impair the growth of lung LCC and inhibit tumorigenesis. The findings indicate that C3G alone or C3G combined with 5-FU may be beneficial for treating human lung LCC.
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Patients recovering from ischemic stroke remain at risk for subsequent ischemic events. This is because multiple signaling molecules that are risk factors for stroke can themselves get upregulated as a result of vascular and neural injuries caused by ischemic stroke. Consequently, it is important to disrupt this vicious cycle of inflammation and stroke by enhancing repair mechanisms such as clot clearance, neurogenesis, and anti-inflammatory response. By discussion of various biomolecules and pathways involved in these mechanisms, this chapter aims to provide the foundational analysis necessary for comprehensive guidance of future research and therapeutic efforts in a neuro-restoration amongst stroke patients. These mechanisms shall be explored in two distinct sections, viz., (1) “Mechanisms of Clot Formation” and (2) “Enhancement of Neurogenesis.”
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The incidence of diabetes mellitus is dramatically increasing every year, causing a huge global burden. Moreover, existing anti-diabetic drugs inevitably bring adverse reactions, and the application of islet transplantation is often limited by the damage caused by oxidative stress after transplantation. Thus, new approaches are needed to combat the growing burden of diabetes mellitus. Anthocyanins are of great nutritional interest and have been documented that have beneficial effects on chronic diseases, including diabetes mellitus. Here, we describe the health effects of anthocyanins on diabetes mellitus and islet transplantation. Epidemiological studies demonstrated that moderate intake of anthocyanins leading to a reduction in risk of diabetes mellitus. Numerous experiments both animal and clinical studies also showed positive effects of anthocyanins on prevention and treatment of diabetes and diabetic complications. These effects of anthocyanins may be related to mechanisms of improving glucose and lipid metabolism and insulin resistance, antioxidant, and anti-inflammatory activities. In addition, damage and function of pancreatic islets after transplantation are also improved by anthocyanins. These findings suggest that daily intake of anthocyanins may not only improve nutritional metabolism in healthy individuals to prevent from diabetes, but also as a supplementary treatment of diabetes mellitus and islet transplantation. Thus, more evidence is needed to better understand the potential health benefits of anthocyanins.
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The exploration of plants as a source of medicinal raw materials has increased since the last few decades, both for infectious, degenerative, and malignant diseases. One of the medicinal plants currently being developed for cancer is Syzygium cumini. Powder of Syzygium cumini was extracted using 96% ethanol. Each extract was determined for its phytochemical screening, total phenolic content, and cytotoxic activity against 4T1 cell culture. Total phenolic content was determined by the Folin-Ciocalteu method and UV-VIS spectrophotometer. Cytotoxic test was performed using MTT assay with parameter IC50 value. The results showed that the total phenolic content of 96% ethanol extract of Syzygium cumini seed, leaf, and pulp was 503.01±9.21; 329.60± 20.37; 24.09 ±0.57mg GAE/g. Syzygium cumini seed, leaf, and pulp extracts exhibited cytotoxic activity with IC50 613.92±40.49; 660.18±15.02; 732.68±69.41µg/ml. Syzygium cumini seed extract has the highest total phenolic content and the most potent cytotoxic activity.
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Aims Colon cancer (CC) is a prevalent malignancy worldwide and is one of the most easily altered cancers by dietary regulation. Petunidin 3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-D-glucopyranoside) (Pt3R5G) isolated and purified from Lycium ruthenicum Murray, which exhibits highly efficient antioxidant activity and specific anticancer effects, is the flavonoids compound. We aimed to study the effect of Pt3R5G on CC cells and elucidate the potential underlying mechanisms. Main methods Cell proliferation was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays. Cell cycle, cell apoptosis and reactive oxygen species (ROS) analysis were performed by flow cytometry. RNA-sequencing was performed to elucidate the potential underlying mechanisms. The lipid peroxidation level of cells was detected by malondialdehyde (MDA) assay. The mitochondrial morphology of cells was inspected using a transmission electron microscope. Additionally, we overexpressed SLC7A11 to perform rescue experiments. In vivo, xenograft mice assay was performed to verify the effect of Pt3R5G on the growth of colon cancer. Key findings Pt3R5G reduced the cell activity by blocking the cell cycle in G0/G1 phase, inducing the apoptosis and ferroptosis in RKO cells. The overexpressed of SLC7A11, a significantly down-regulated expression gene caused by Pt3R5G, rescued the cell proliferation inhibition and ferroptosis process. Furthermore, Pt3R5G inhibited tumor growth in nude mice. Our study suggests that Pt3R5G inhibits RKO cell proliferation through mainly reducing ferroptosis by down-regulated SLC7A11. Significance As a potential therapeutic drug, Pt3R5G showed efficient anticancer activity through a variety of pathways.
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Anthocyanins as plant pigments are responsible for the color of the grape berry. The major concern among consumers is color, quality, and appearance, therefore, skin color is the most important item that affects consumer purchases. In this study, we used three grape cultivars namely Red globe (bright red), Kyoho (purple-red), and Wink (purple-black), and evaluated color changes in three different developmental stages according to time course including 15 days after the berry color shift from green to red (V1), 25 days after the berry color shift from green to red (V2), and 35 days after the berry color shift from green to red (V3). The dynamic changes in anthocyanin content and components were detected using "High-Performance Liquid Chromatography mass spectrometry/mass spectrometry (HPLC-MS/MS)" technology. Furthermore, we performed transcriptome sequencing and identified the genes involved in the anthocyanin biosynthesis and accumulation in grape berry development. In total, we detected 13 different anthocyanin components in three grape cultivars. Malvidin, petunidin, and delphinidin derivates are the main components of dark colored grape (Kyoho and Wink), while cyanidin and pelargonidin derivates are the sources of bright-colored grape (Red globe). According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, many DEGs were enrichment in phenylpropanoid biosynthesis and flavonoid biosynthesis. We also found thirty-nine DEGs to be involved in the anthocyanin metabolism and accumulation. Furthermore, using weighted gene correlation analysis (WGCNA), three modules (blue, magenta, and tan) and nineteen hub genes were highly correlated with anthocyanin variation. Our research provided new insights for elucidating the anthocyanin metabolic pathway and related genes, signal perception and transduction during grape berries development at different stages.
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Purpose This study aims to investigate the effect of spray drying temperature and maltodextrin addition on the contents of phenolics, flavonoids, anthocyanins and antioxidant activities (2,2-diphenyl-1-picrylhydrazyl [DPPH] radical scavenging activity, ferric reducing antioxidant power and reducing power) of karonda powder. Design/methodology/approach Over the past few decades, the demands for application of natural colorants in food production have been attracting the attention of academic research and food industry. Anthocyanins, a red pigment commonly found on plants, show high potentials in the preparation of spray-dried pigment powder. This study, therefore, was conducted using full factorial design with two factors, namely, inlet temperature (150°C and 160°C) and soluble solid concentration (10, 15 and 20°Brix) with maltodextrin as carrier to produce pigment powder from karonda, an anthocyanin-rich fruit which is native to southeast Asia. Findings Increasing soluble solid content from 10 to 15°Brix resulted in a 42%–57% reduction in phenolic, flavonoid and anthocyanin contents. However, when increasing the amount of maltodextrin from 15 to 20°Brix, a lower reduction (approximately 11%–19%) was observed. In samples with the same °Brix, there was no significant variation in antioxidant contents and activities, especially at high maltodextrin ratios. In addition, the reducing power of samples dried at higher temperature (160°C) was higher than that of samples dried at lower temperature. Karonda spray-dried powder showed a good positive correlation ( p < 0.01) between antioxidant contents and DPPH• activity. Originality/value To the best of the authors’ knowledge, in this study, for the first time, the effect of spray drying conditions on the quality of karonda powder was investigated.
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Chronic wound healing has become an area of fundamental research. Wound healing for a diabetic patient is one of the significant challenges in the biomedical field. Diabetes is a globally challenging disease that has affected around 400 million people. Many therapeutic factors are introduced to treat chronic wounds, with minimal success due to difficulty in delivery of the drug to the wound location. Microneedle patches are considered an efficient medical treatment procedure to address wound healing problems. The wound healing is accelerated, and the bacterial infection is inhibited by the devices based on microneedle with the loaded active drugs (including hemostatic drugs, bacterial drugs, and anti-inflammatory drugs). The wound healing process is generally divided into three steps: inflammation, proliferation, and tissue remodeling. This chapter will discuss the significant challenges and the advantages of microneedle applications in chronic wound healing.
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In this study, we qualitatively and quantitatively characterized anthocyanins from 61 different Lonicera caerulea L. genotypes harvested from northeast China and measured their reactive oxygen species (ROS) scavenging activity. Among the anthocyanin extracts obtained, nine anthocyanins were identified, and the anthocyanin compositions could be divided into three classes and seven subtypes according to their numbers and distribution. Furthermore, their total content by fresh weight was ranged from 158.44 mg/100 g to 1751.44 mg/100 g across all genotypes; their hydroxyl radical scavenging activity and superoxide anion scavenging activity ranged from 13.3%∼99.9% and 21.5%∼82.8%, respectively. We also deployed Grey Relational Analysis to determine which anthocyanin was the key antioxidant component in the nine anthocyanins. The relation between the ROS scavenging activity and the 9 anthocyanin content was established. Our results suggest cyanidin-3,5-diglucoside has the greatest correlation to the ROS scavenging activity of the anthocyanin extractions.
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A espécie Plinia cauliflora, que produz a jabuticaba como fruto, se destaca dentro da flora brasileira pelas suas propriedades medicinais. Dentre os componentes da jabuticaba, a casca possui a maior concentração de substâncias de interesse a saúde, além de sua atividade antitumoral. O objetivo do referente projeto foi realizar um levantamento bibliográfico de artigos relacionados ao potencial carcinogênico ou anticarcinogênico de jabuticabas, em especial do extrato aquoso da casca de P. cauliflora. O presente estudo aborda uma revisão integrativa em que foi usada a questão norteadora: “O extrato aquoso da casca de jabuticaba (P. cauliflora) tem algum efeito carcinogênico ou anticarcinogênico?” Segundo revisão feita por Wu; Long; Kennelly (2013), as partes comestíveis da jabuticaba contêm evidências de atividade citotóxica, antiproliferativa, antimutagênico, regeneração celular e, especialmente, anticâncer devido a concentração de antocianinas. Lamas et. al (2020) observa que o extrato da casca de jabuticaba diminui o espectro de moléculas oxidativas e infamatórias de uma lesão provocada pelo câncer de próstata. Lin et. al. (2016) as partes da planta ou os extratos de P.caluliflora podem ter efeito benéfico contra a leucemia, pois contém compostos como ácido elágico, quercetina e antocianinas, importantes na prevenção de câncer e atividade antitumoral. Não foram detectados efeitos carcinogênicos da jabuticaba até então. Entretanto muitas pesquisas mostram inúmeros potenciais anticâncer de várias espécies de jabuticaba, mas estes estudos ainda são muito incipientes, o que requer mais pesquisas voltadas para outros tipos de câncer. Os tipos de câncer detectados nessa revisão foram câncer de cólon, próstata, mama e leucemia e foi Verificado principalmente o potencial antioxidante das jabuticabas.
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The goal of this study was to determine the effect of hirsutidin on ethanol-induced stomach ulcers in rats. Rats (n = 24 rats/group) were separated at random into the following groups: normal saline-treated (normal control), ethanol-treated (ethanol control), 10 mg/kg hirsutidin + ethanol-treated (hirsutidin 10), and 20 mg/kg hirsutidin + ethanol-treated (hirsutidin 20). All the groups received the respective treatment orally for 7 days. On day 7, i.e., after 24 h of fasting, except for the normal control group, all the groups orally received 5 mL/kg of ethanol. Four hours later, rats were anaesthetized, serum was isolated from the blood, and biochemical tests were performed. The stomach tissue was utilized for ulcer grading, histology, and biochemical analysis. The rats developed stomach acidity and ulcers after being given ethanol based on increased ulcer score, disturbed cellular architecture, increased oxidative stress, myeloperoxidase and decreased endogenous antioxidants, and nitric oxide and prostaglandin E2 concentration. Ethanol-treated rats also displayed increased tumor necrosis factor-α, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and inflammatory cytokines. The treatment with hirsutidin protected and significantly restored all serum parameters in ethanol-induced stomach ulcers and may have antiulcer activity.
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About 60% of chemotherapeutic agents used for the treatment of cancer diseases today have been derived from natural products. While some of these agents are identical to the natural molecules found in plants; the others are semisynthetic derivative of the foundational molecule found naturally in the raw sources. Cancers have been reported to express 10 specific hallmark which are used as the key points or steps for targeted therapy against these cancers. Extending the number of these hallmarks to 12 this review article throws light on 43 natural products classifying them according to their target of action. Further, the natural products under consideration are categorized according to the level of evidence present for their anticancer activities.
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Colorectal cancer is the fourth most common type of cancer worldwide, and adenocarcinoma cells that form the majority of colorectal tumors are markedly resistant to antineoplastic agents. Epidemiological studies have demonstrated that consumption of fruits and vegetables that are rich in polyphenols, is linked to reduced risk of colorectal cancer. In the present study, the effect of a standardized anthocyanin (ACN)‑rich extract on proliferation, apoptosis and cell cycle in the Caco-2 human colorectal cancer cell line was evaluated by trypan blue and clonogenic assays and western blot analysis of cleaved caspase‑3 and p21Waf/Cif1. The results of the current study demonstrated that the ACN extract markedly decreased Caco‑2 cell proliferation, induced apoptosis by activating caspase‑3 cleavage, and upregulated cyclin‑dependent kinase inhibitor 1 (p21Waf/Cif1) expression in a dose dependent manner. Furthermore, ACN extract was able to produce a dose‑dependent increase of intracellular reactive oxygen species (ROS) in Caco‑2 cells, together with a light increase of the cell total antioxidant status. In conclusion, the present study demonstrated that a standardized berry anthocyanin rich extract inhibited proliferation of Caco‑2 cells by promoting ROS accumulation, inducing caspase‑3 activation, and upregulating the expression of p21Waf/Cif1.
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Phytochemicals in red and purple bran rice have potential health benefit to humans. We determined the phytochemicals in brans of 32 red and purple global rice varieties. The description of the origin and physical traits of the whole grain (color, length, width, thickness and 100-kernel weight) of this germplasm collection are provided along with data of total flavonoid and total phenolic contents, oxygen radical absorbance capacity and total proanthocyanidin contents. The contents and proportions of individual oligomers, from degree of polymerization of monomers to 14-mers, and polymers in bran of these 32 rice varieties are presented (DOI: http://dx.doi.org/10.1016/j.foodchem.2016.04.004) [1].
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The development of an efficient protocol for successful hairy root induction by Agrobacterium rhizogenes is the key step toward an in vitro culturing method for the mass production of secondary metabolites. The selection of an effective Agrobacterium strain for the production of hairy roots is highly plant species dependent and must be determined empirically. Therefore, our goal was to investigate the transformation efficiency of different A. rhizogenes strains for the induction of transgenic hairy roots in Fagopyrum tataricum ‘Hokkai T10’ cultivar; to determine the expression levels of the polypropanoid biosynthetic pathway genes, such as ftpAL, FtC4H, Ft4CL, FrCHS, FrCH1, FrF3H, FtFLS1, FtFLS2, FtF3, H1, FtF3′H2, FtANS, and FtDFR; and to quantify the in vitro synthesis of phenolic compounds and anthocyanins. Among different strains, R1000 was the most promising candidate for hairy root stimulation because it induced the highest growth rate, root number, root length, transformation efficiency, and total anthocyanin and rutin content. The R1000, 15834, and A4 strains provided higher transcript levels for most metabolic pathway genes for the synthesis of rutin (22.31, 15.48, and 13.04 μg/mg DW, respectively), cyanidin 3-O-glucoside (800, 750, and 650 μg/g DW, respectively), and cyanidin 3-O-rutinoside (2410, 1530, and 1170 μg/g DW, respectively). A suitable A. rhizogenes strain could play a vital role in the fast growth of the bulk amount of hairy roots and secondary metabolites. Overall, R1000 was the most promising strain for hairy root induction in buckwheat.
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The World Health Organization predicts over a 70% increase in cancer incidents in developing nations over the next decade. Although these nations have limited access to novel therapeutics, they do have access to foods that contain chemopreventive bioactive compounds such as anthocyanins, and as such, consumption of these foods can be encouraged to combat cancer. We and others have previously characterized the anti-colon cancer properties of dietary anthocyanins from different sources. Eugenia jambolana (Java plum) is a tropical medicinal fruit rich in anthocyanins, however, its anti-colon cancer properties are not well characterized. Furthermore, recent evidence suggests that colon cancer stem cells (colon CSCs) promote resistance to chemotherapy, relapse of tumors and contribute to poor prognosis. The objectives of this study were to 1) characterize the anthocyanin profile of Java plum using HPLC-MS; and 2) determine the anti-proliferative (cell counting and MTT) and pro-apoptotic (TUNEL and caspase 3/7 glo assay) properties of Java plum fruit extract (JPE) using HCT-116 colon cancer cell line and colon CSCs (positive for CD 44, CD 133 and ALDH1b1 markers). HPLC-MS analysis showed that JPE contains a variety of anthocyanins including glucosides of delphinidin, cyanidin, petunidin, peonidin and malvidin. JPE anthocyanins suppressed (p < 0.05) proliferation in HCT-116 cells and elevated (p < 0.05) apoptosis in both HCT-116 cells and colon CSCs. JPE also suppressed the stemness in colon CSCs as evaluated using colony formation assay. These results warrant further assessment of the anti-cancer activity of JPE, and its molecular mechanisms using pre-clinical models of colon cancer.
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This review considers the bioavailability of health-protective anthocyanin pigments from foods, in light of the multiple molecular structures and complicated traffic patterns taken by anthocyanins both as flavonoid metabolites and as phenolic acid metabolites within the body. Anthocyanins have generally been considered to have notoriously poor bioavailability, based on the very low levels typically detected in routine human blood draws after ingestion. Although some investigations have assessed anthocyanin bioavailability solely based on the measurement of parent anthocyanins or phenolic acid breakdown products, more recent research has increasingly revealed the presence, qualitative diversity, relatively high concentrations, and tenacity of molecular intermediates of anthocyanins that retain the unique flavonoid C6-C3-C6 backbone structure. We argue that the persistence of anthocyanin metabolites suggests enterohepatic recycling, leading to prolonged residence time, and supports the notion that anthocyanins are far more bioavailable than previously suggested. Expected final online publication date for the Annual Review of Food Science and Technology Volume 7 is February 28, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.Wiley.com/doi/10.1111/bph.13347/full. This compilation of the major pharmacological targets is divided into eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.
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Overexpression of human epidermal growth factor receptor 2 (HER2) drives the biology of 30% of breast cancer cases. As a transducer of HER2 signaling, RAS/RAF/MAPK pathway plays a pivotal role in the development of breast cancer. In this study, we examined the molecular mechanisms underlying the chemopreventive effects of black rice anthocyanins (BRACs) extract and identified their molecular targets in HER2 + breast cancer cells. Treatment of MDA-MB-453 cells (HER2 + ) with BRACs inhibited cell migration and invasion, suppressed the activation of mitogen-activated protein kinase kinase kinase (RAF), mitogen-activated protein kinase kinase (MEK), and c-Jun N-terminal kinase (JNK), and downregulated the secretion of matrix metalloproteinase 2 (MMP2) and MMP9. BRACs also weakened the interactions of HER2 with RAF, MEK, and JNK proteins, respectively, and decreased the mRNA expression of raf , mek , and jnk . Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment. Transient transfection with small interfering RNAs (siRNAs) specific for raf , mek , and jnk inhibited their mRNA expression in MDA-MB-453 cells. Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone. In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway.
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Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results. Objective: In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer. Design: Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses’ Health Study. Results: During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk. Conclusion: Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer.
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Purpose: Pancreatic cancer is an aggressive cancer type, of which the most important characteristics are migration and metastasis. Anthocyanins (ACN) are discussed to be protective phytochemicals; however, up to now only scarce data are available regarding their effects on cancer prevention. In this study, we aimed to determine whether ACN and their metabolites from plasma (PAM), isolated from blood of healthy volunteers after ingestion of an ACN-rich juice, are effective in modulating cancer cell migration in vitro. Methods: PAM were isolated from blood of healthy volunteers (n = 10) after consumption of an ACN-rich berry juice. Before ingestion (PAM0min) and after 60 min (PAM60min), blood was taken and PAM were isolated from plasma by solid-phase extraction. Migration of pancreatic cancer cells PANC-1 and AsPC-1 was assayed in a Boyden chamber. The influence of PAM on cellular reactive oxygen species (ROS) or mitochondria-specific ROS was measured fluorimetrically. mRNA expression levels of matrix metalloproteinases (MMP-2 and MMP-9) and NF-κB mRNA were determined by real-time PCR. Results: After application of PAM60min to PANC-1, we observed a reduced cell migration, which was associated with reduced levels of endogenously generated ROS concomitant with reduced NF-κB as well as MMP-2 and MMP-9 mRNA expression levels. In AsPC-1 cells, however, migration was not affected by PAM60min. Conclusion: It can be assumed that physiologically relevant ACN and their metabolites were able to inhibit pancreatic cancer cell migration in dependency of the phenotype of cells and may thus deserve further attention as potential bioactive phytochemicals in cancer prevention.
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The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, http://www.guidetopharmacology.org) provides expert-curated molecular interactions between successful and potential drugs and their targets in the human genome. Developed by the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS), this resource, and its earlier incarnation as IUPHAR-DB, is described in our 2014 publication. This update incorporates changes over the intervening seven database releases. The unique model of content capture is based on established and new target class subcommittees collaborating with in-house curators. Most information comes from journal articles, but we now also index kinase cross-screening panels. Targets are specified by UniProtKB IDs. Small molecules are defined by PubChem Compound Identifiers (CIDs); ligand capture also includes peptides and clinical antibodies. We have extended the capture of ligands and targets linked via published quantitative binding data (e.g. Ki, IC50 or Kd). The resulting pharmacological relationship network now defines a data-supported druggable genome encompassing 7% of human proteins. The database also provides an expanded substrate for the biennially published compendium, the Concise Guide to PHARMACOLOGY. This article covers content increase, entity analysis, revised curation strategies, new website features and expanded download options.
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Cancer stem cells (CSCs) are shown to be responsible for initiation and progression of tumors in a variety of cancers. We previously showed that anthocyanin-containing baked purple-fleshed potato (PP) extracts (PA) suppressed early and advanced human colon cancer cell proliferation and induced apoptosis, but their effect on colon CSCs is not known. Considering the evidence of bioactive compounds, such as anthocyanins, against cancers, there is a critical need to study anti-cancer activity of PP, a global food crop, against colon CSCs. Thus, isolated colon CSCs (positive for CD 44, CD 133 and ALDH1b1 markers) with functioning p53 and shRNA-attenuated p53 were treated with PA at 5.0 μg/mL. Effects of baked PP (20 % w/w) against colon CSCs were also tested in vivo in mice with azoxymethane induced colon tumorigenesis. Effects of PA/PP were compared to positive control sulindac. In vitro, PA suppressed proliferation and elevated apoptosis in a p53 independent manner in colon CSCs. PA, but not sulindac, suppressed levels of Wnt pathway effector β-catenin (a critical regulator of CSC proliferation) and its downstream proteins (c-Myc and cyclin D1) and elevated Bax and cytochrome c, mitochondria-mediated apoptotic proteins. In vivo, PP reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis and suppressed tumor incidence similar to that of sulindac. Combined, our data suggests that suppression of Wnt/β-catenin signaling and elevated apoptosis via mitochondria-mediated apoptotic pathway by PP may contribute to reduced colon CSCs number and tumor incidence in vivo.
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To develop new and effective chemopreventive agents against bone metastasis, we assessed the effects of muscadine grape skin extract (MSKE), whose main bioactive component is anthocyanin, on bone turnover, using prostate and breast cancer cell models overexpressing Snail transcription factor. MSKE has been shown previously to promote apoptosis in prostate cancer cells without affecting normal prostate epithelial cells. Snail is overexpressed in prostate and breast cancer, and is associated with increased invasion, migration and bone turnover/osteoclastogenesis. CatL is a cysteine cathepsin protease that is overexpressed in cancer and involved in bone turnover. Snail overexpression in prostate (LNCaP, ARCaP-E) and breast (MCF-7) cancer cells led to increased Cathepsin L (CatL) expression/activity and phosphorylated STAT-3 (pSTAT-3), compared to Neo vector controls, while the reverse was observed in C4-2 (the aggressive subline of LNCaP) cells with Snail knockdown. Moreover, CatL expression was higher in prostate and breast tumor tissue compared to normal tissue. MSKE decreased Snail and pSTAT3 expression, and abrogated Snail-mediated CatL activity, migration and invasion. Additionally, Snail overexpression promoted osteoclastogenesis, which was significantly inhibited by the MSKE as effectively as Z-FY-CHO, a CatL-specific inhibitor, or osteoprotegerin, a receptor activator of nuclear factor kappa B ligand (RANKL) antagonist. Overall, these novel findings suggest that Snail regulation of CatL may occur via STAT-3 signaling and can be antagonized by MSKE, leading to decreased cell invasion, migration and bone turnover. Therefore, inhibition using a natural product such as MSKE could potentially be a promising bioactive compound for bone metastatic cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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This paper reviews the reported pharmacological properties of protocatechuic acid (PCA, 3,4-dihydroxy benzoic acid), a type of phenolic acid found in many food plants such as olives and white grapes. PCA is a major metabolite of anthocyanin. The pharmacological actions of PCA have been shown to include strong in vitro and in vivo antioxidant activity. In in vivo experiments using rats and mice, PCA has been shown to exert anti-inflammatory as well as antihyperglycemic and antiapoptotic activities. Furthermore, PCA has been shown to inhibit chemical carcinogenesis and exert proapoptotic and antiproliferative effects in different cancerous tissues. Moreover, in vitro studies have shown PCA to have antimicrobial activities and also to exert synergistic interaction with some antibiotics against resistant pathogens. This review aims to comprehensively summarize the pharmacological properties of PCA reported to date with an emphasis on its biological properties and mechanisms of action which could be therapeutically useful in a clinical setting.
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To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2×10⁶) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.
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The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.