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Anticarcinogenic Effects of Polyphenolics from Mango (Mangifera indica) Varieties
Abstract
Many polyphenolics contained in mango have shown anticancer activity. The objective of this study was to compare the anticancer properties of polyphenolic extracts from several mango varieties (Francis, Kent, Ataulfo, Tommy Atkins, and Haden) in cancer cell lines, including Molt-4 leukemia, A-549 lung, MDA-MB-231 breast, LnCap prostate, and SW-480 colon cancer cells and the noncancer colon cell line CCD-18Co. Cell lines were incubated with Ataulfo and Haden extracts, selected on the basis of their superior antioxidant capacity compared to the other varieties, where SW-480 and MOLT-4 were statistically equally most sensitive to both cultivars followed by MDA-MB-231, A-549, and LnCap in order of decreasing efficacy as determined by cell counting. The efficacy of extracts from all mango varieties in the inhibition of cell growth was tested in SW-480 colon carcinoma cells, where Ataulfo and Haden demonstrated superior efficacy, followed by Kent, Francis, and Tommy Atkins. At 5 mg of GAE/L, Ataulfo inhibited the growth of colon SW-480 cancer cells by approximately 72% while the growth of noncancer colonic myofibroblast CCD-18Co cells was not inhibited. The growth inhibition exerted by Ataulfo and Haden polyphenolics in SW-480 was associated with an increased mRNA expression of pro-apoptotic biomarkers and cell cycle regulators, cell cycle arrest, and a decrease in the generation of reactive oxygen species. Overall, polyphenolics from several mango varieties exerted anticancer effects, where compounds from Haden and Ataulfo mango varieties possessed superior chemopreventive activity.
... Several studies have shown that the mango fruit (Mangifera indica L.) contains bioactive compounds with potential chemopreventive capacity against CRC. Noratto et al. (2010) found that polyphenolic extracts of the Ataulfo mango variety had cytotoxic activity in SW480 cell line. Velderrain-Rodríguez et al. (2018) employed an in vitro model and demonstrated that phenolic compounds in the peel of the Ataulfo mango have potential antiproliferative capacity in the colon cancer cell line LS180. ...
... The present study demonstrated that LMPE can inhibit the proliferation of SW480 cells and their metastasis-derived counterparts, i.e., SW620 for the first time. Previous studies had reported the ability of mango pulp to inhibit SW480 cell proliferation (Noratto et al., 2010;Corrales-Bernal et al., 2014b). However, none of them had evaluated metastatic colon cancer lines such as SW620. ...
... mg GAE/g, respectively (Kim et al., 2010). Several phenolic compounds identified in mango fruit have been shown to inhibit cancer cell proliferation and induce apoptosis (Noratto et al., 2010;Ramos, 2007;Pan et al., 2014;Darvin et al., 2015;Velderrain-Rodríguez et al., 2018). Gallic acid (a phenolic acid) demonstrated antiproliferative activity in LS180 colon adenocarcinoma cells (Velderrain-Rodríguez et al., 2018). ...
The present study evaluated the antiproliferative capacity and possible cell death mechanisms of lyophilized mango pulp extract (LMPE), applied to human colon cancer cells (SW480) and their metastasis-derived counterparts (SW620). The total phenolic content of LMPE was estimated by the Folin-Ciocalteu method. Three assays were employed to determine its antioxidant capacity: ferric-reducing antioxidant power, oxygen radical absorbance capacity, and 2,2-diphenyl-1-picrylhydrazyl. Furthermore, the antiproliferative activity of LMPE was assessed by sulforhodamine B, clonogenic, and Ki-67 assays. Flow cytometry was employed to examine the cell cycle, production of intracellular reactive oxygen species (ROS), cell-surface phosphatidylserine, and change in mitochondrial membrane potential. LMPE exhibited a high level of total phenolic content and antioxidant activity. The mean maximal inhibitory concentration values of LMPE at 48 h of exposure were 43 and 29 mg/mL for SW480 and SW620, respectively. In the SW480 and SW620 cell lines, LMPE at 50 mg/mL and 48 h of exposure induced an increase in intracellular ROS, cell cycle arrest in the G2/M phase, and probably, apoptotic processes without mitochondrial depolarization. LMPE had an antiproliferative capacity against the human colorectal cancer cell lines SW480 and SW620. These results highlight the chemopreventive potential of LMPE in colorectal cancer treatments.
... Mango has great antioxidant and anti-proliferative properties, attributed to its phenolic content. Mango is rich in polyphenols (Noratto et al., 2010) that possesses anticancer activities. The potential cancer chemoprevention of the secondary metabolites (phenolic extracts obtained from mango samples) was evaluated using the induction of quinone reductase activity, concluding that fruit polyphenols have the potential for cancer chemoprevention (Oliveira et al., 2016). ...
... Several mango varieties (Francis, Kent, Ataulfo, Tommy Atkins, and Haden) were tested for the anticancer activities using several cell lines including Molt-4 leukemia, A-549 lung, MDA-MB-231 breast, LnCap prostate, and SW-480 colon cancer cells and the noncancer colon cell line CCD-18Co (Noratto et al., 2010). This study revealed Ataulfo mango variety selectively inhibited the growth of colon SW-480 cancer cells by approximately 72%, while the growth of non-cancer colonic myofibroblast CCD-18Co cells were not inhibited (Noratto et al., 2010). ...
... Several mango varieties (Francis, Kent, Ataulfo, Tommy Atkins, and Haden) were tested for the anticancer activities using several cell lines including Molt-4 leukemia, A-549 lung, MDA-MB-231 breast, LnCap prostate, and SW-480 colon cancer cells and the noncancer colon cell line CCD-18Co (Noratto et al., 2010). This study revealed Ataulfo mango variety selectively inhibited the growth of colon SW-480 cancer cells by approximately 72%, while the growth of non-cancer colonic myofibroblast CCD-18Co cells were not inhibited (Noratto et al., 2010). ...
... One of the most widely consumed fruits worldwide is the mango (Mangifera indica L.) [4], and it is considered a functional food due to its content of bioactive compounds [5]. Studies in vitro and murine models have shown its chemopreventive capacity against different types of cancer [6], including CRC [7][8][9][10]. ...
... When taken together, these results confirm the apoptotic activity of LMPE on these CRC cells. Different studies have demonstrated the ability of some bioactive compounds present in mango to promote apoptosis in cancer cells [33][34][35], specifically in the context of CRC, Noratto et al. showed the apoptotic effect of polyphenolic mango extracts (10 mg gallic acid equivalent/mL and 24 h exposure) on SW480 cells [9] and Lauricella et al. reported an increase in oxidative stress associated with DNA fragmentation and apoptosis in CRC Caco-2 and HCT116 cell lines treated with an ethanolic mango peel extract [8]. ...
Previous studies have indicated that mango fruit has a chemopreventive capacity against colorectal cancer cells. The objective of this research was to evaluate the effect of an aqueous extract of lyophilized mango pulp (LMPE) on colon adenocarcinoma cells (SW480) and their metastatic derivatives (SW620) death and cellular invasion. DNA fragmentation was assessed by TUNEL assay; autophagy and expression of DR4 and Bcl-2 by flow cytometry; the expression of 35 apoptosis-related proteins and of matrix metalloproteinases 7 and 9 by immunodetection; and the invasive capacity of the cells by Boyden chamber. The results showed that LMPE at 30 mg/mL and 48 h of exposure results in DNA fragmentation and apoptosis in SW480 (p < 0.001) and SW620 (p < 0.01) cells. Additionally, LMPE decreased autophagy in the SW480 and SW620 cell lines (p < 0.001), which could sensitize them to the DNA damage generated by LMPE. The LMPE did not modulate the expression of matrix metalloproteinases 7 and 9, nor did it affect cellular invasion processes in the SW480 and SW620 cell lines. In conclusion, LMPE induces apoptosis and decreases autophagy in SW480 and SW620 cells.
... The anti-cancer activity of M. indica has frequently been attributed to its polyphenolic content. Noratto et al 55 xenografts, whereby a reduction in tumor volume (>70%) was observed following treatment. 57 Various studies have investigated into the anti-breast cancer activities of individual M. indica polyphenols, instead of M. indica polyphenolic mixtures, as described below. ...
... 51 Besides, the polyphenolic extracts (10 mg GAE/L) of different M. indica varieties have also demonstrated antioxidant potentials in the oxygen radical absorbance capacity (ORAC) assay, and a strong correlation between antioxidant activity and total phenolic content has been noted. 55 Figure 2 summarises how M. indica extracts and phytochemicals exert their anti-cancer effects by activating oxidative stress-induced cell death or acting as antioxidants. ...
Globally, breast cancer is the most common cancer type and is one of the most significant causes of deaths in women. To date, multiple clinical interventions have been applied, including surgical resection, radiotherapy, endocrine therapy, targeted therapy and chemotherapy. However, 1) the lack of therapeutic options for metastatic breast cancer, 2) resistance to drug therapy and 3) the lack of more selective therapy for triple-negative breast cancer are some of the major challenges in tackling breast cancer. Given the safe nature of natural products, numerous studies have focused on their anti-cancer potentials. Mangifera indica, commonly known as mango, represents one of the most extensively investigated natural sources. In this review, we provide a comprehensive overview of M. indica extracts (bark, kernel, leaves, peel and pulp) and phytochemicals (mangiferin, norathyriol, gallotan-nins, gallic acid, pyrogallol, methyl gallate and quercetin) reported for in vitro and in vivo anti-breast cancer activities and their underlying mechanisms based on relevant literature from several scientific databases, including PubMed, Scopus and Google Scholar till date. Overall, the in vitro findings suggest that M. indica extracts and/or phytochemicals inhibit breast cancer cell growth, proliferation, migration and invasion as well as trigger apoptosis and cell cycle arrest. In vivo results demonstrated that there was a reduction in breast tumor xenograft growth. Several potential mechanisms underlying the anti-breast cancer activities have been reported, which include modulation of oxidative status, receptors, signalling pathways, miRNA expression, enzymes and cell cycle regulators. To further explore this medicinal plant against breast cancer, future research directions are addressed. The outcomes of the review revealed that M. indica extracts and their phytochemicals may have potential benefits in the management of breast cancer in women. However, to validate its utility in the creation of innovative and potent therapeutic agents to treat breast cancer, more dedicated research, especially clinical studies are needed to explore the anti-breast cancer potentials of M. indica extracts and their phytochemicals.
... Mango polyphenols have been shown to exhibit various pharmacological activities such as antioxidant, anti-bacterial, anti-inflammatory, gastroprotective, immunomodulatory, and cancer-cytotoxic effects [6,[78][79][80][81]. The anti-inflammatory activities of gallotannins and associated metabolites, gallic acid and 4-O-methylgallic acid mediated via the reduction in proinflammatory cytokines, nuclear factor kappa B (NF-κB), intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) have been well-reviewed [82]. ...
... Mango has been shown to have the potential to prevent colon cancer in several in vitro studies. Our previous study shows that two varieties-Ataulfo and Haden-were the most effective in reducing cell growth via cell cycle arrest and decreased reactive oxygen species (ROS) production in SW-480 colon carcinoma cells when compared to polyphenol extracts from other varieties Kent, Francis, and Tommy Atkins [81]. The treatment of Ataulfo mango peel polyphenols showed the highest antioxidant and antiproliferative activities in LS180 human colon adenocarcinoma cells [100]. ...
Mango is rich in polyphenols including gallotannins and gallic acid, among others. The bioavailability of mango polyphenols, especially polymeric gallotannins, is largely dependent on the intestinal microbiota, where the generation of absorbable metabolites depends on microbial enzymes. Mango polyphenols can favorably modulate bacteria associated with the production of bioactive gallotannin metabolites including Lactobacillus plantarum, resulting in intestinal health benefits. In several studies, the prebiotic effects of mango polyphenols and dietary fiber, their potential contribution to lower intestinal inflammation and promotion of intestinal integrity have been demonstrated. Additionally, polyphenols occurring in mango have some potential to interact with intestinal and less likely with hepatic enzymes or transporter systems. This review provides an overview of interactions of mango polyphenols with the intestinal microbiome, associated health benefits and underlying mechanisms.
... The most abundant phenolic compounds reported from MP are gallic acid, chlorogenic acid, epicatechin gallate, epigallocatechin gallate, kaempferol and its related conjugates, quercetin and quercetin derivatives, rutin, mangiferin, and procyanidins (Bai et al., 2018;Coelho et al., 2019;Dorta et al., 2014;Lauricella et al., 2019;López-Cobo et al., 2017;Luo et al., 2014;Velderrain-Rodríguez et al., 2018). Some of these compounds have been recognized by their antioxidant capacity (Bai et al., 2018;Kim et al., 2010;Rojas et al., 2020), and anti-tumoral effects in some cancer cell lines (Bai et al., 2018;Ediriweera et al., 2017;Kim et al., 2010;Noratto et al., 2010;Taing et al., 2015). Gallic acid-rich MP extracts exhibited antiproliferative activity (IC 50 = 46 μg/mL) against LS180 colon cancer cells, mediated by an antioxidant mechanism (Velderrain-Rodríguez et al., 2018). ...
... Several studies focusing on the anti-proliferative activity of mango by-products extracts using cancer colon cells have been carried out Castro-Vargas et al., 2019;Lauricella et al., 2019;Noratto et al., 2010;Velderrain-Rodríguez et al., 2018). HT-29 were selected as model, since it is considered as one of the most refractive colon cancer line . ...
This work includes the second/sequential stage of a green-based valorization strategy of mango peel. An exhausted biomass from a pilot-scale CO2 supercritical extraction process was reused for obtaining phenolic-rich extracts with high antioxidant and anti-proliferative activity, employing microwave-assisted extraction. The effects of microwave power (400–800 W), liquid-to-solid ratio (10–50 mL/g) and extraction time (60–120 s) on process yield, phenolic content, and antioxidant capacity were investigated using a Box-Behnken design. A solution consisting of 60% aqueous ethanol was used as extraction solvent. The results showed that microwave power and liquid-to-solid ratio were the most influential factors on the responses variables. The highest total phenolic content (52.08 mg gallic acid eq./g d. w.) and antioxidant activities (2.75 mmol trolox eq./g extract, and of 6.47 μg/mL expressed in DPPH, EC50) were obtained at 800 W, 50 g/mL, and 90 s. Mango peel extract recovered at optimal conditions provided high anti-proliferative activity against HT-29 colon cancer cells line, after 24 h treatment (IC50 = 22.98 μg/mL). Gallic acid derivatives, such as galloyl-esters, xanthones like mangiferin, flavonoids, including quercetin and quercetin glycosides were tentatively identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Most probably, the compounds responsible for the outstanding anti-proliferative activity.
... The seed extract from Kenya mango (large and round) was seen to be more cytotoxic towards the tested cell lines (HCT116, MCF7) in general screening, whereas the MTT assay for selectivity against the three cell lines (HCT116, MCF7, and MRC5) suggested Sri Lanka (large yellowish green) seed extract with the lowest IC 50 value followed by Thailand (large green) seed extract. Though various cytotoxic studies have been reported for mango fruit extract including the following: aqueous flesh extract [16], peel and flesh for Australian cultivars [14], peel extract from six Brazilian cultivars [17,18], seed extract [8,19,20] as well as skin and flesh extract [21], this is a first-time study to report a comprehensive characterization for the whole mango fruit parts from eight different cultivars. With regard to phytochemicals in mango fruit, a good amount of MG was observed in all the fruit parts of these mango cultivars. ...
Mango fruit is well known for its nutritional and health benefits due to the presence of a plethora of phytochemical classes. The quality of mango fruit and its biological activities may change depending upon the variation in geographical factors. For the first time, this study comprehensively screened the biological activities of all four parts of the mango fruit from twelve different origins. Various cell lines (MCF7, HCT116, HepG2, MRC5) were used to screen the extracts for their cytotoxicity, glucose uptake, glutathione peroxidase activity, and α-amylase inhibition. MTT assays were carried out to calculate the IC50 values for the most effective extracts. The seed part from Kenya and Sri Lanka origins exhibited an IC50 value of 14.44 ± 3.61 (HCT116) and 17.19 ± 1.60 (MCF7). The seed part for Yemen Badami (119 ± 0.08) and epicarp part of Thailand (119 ± 0.11) mango fruit showed a significant increase in glucose utilization (50 μg/mL) as compared to the standard drug metformin (123 ± 0.07). The seed extracts of Yemen Taimoor seed (0.46 ± 0.05) and Yemen Badami (0.62 ± 0.13) produced a significant reduction in GPx activity (50 μg/mL) compared to the control cells (100 μg/mL). For α-amylase inhibition, the lowest IC50 value was observed for the endocarp part of Yemen Kalabathoor (108.8 ± 0.70 μg/mL). PCA, ANOVA, and Pearson’s statistical models revealed a significant correlation for the fruit part vs. biological activities, and seed part vs. cytotoxicity and α-amylase activity (p = 0.05). The seed of mango fruit exhibited significant biological activities; hence, further in-depth metabolomic and in vivo studies are essential to effectively utilize the seed part for the treatment of various diseases.
... M. indica is used in traditional medicine for the treatment of syphilis, vomiting, inflammation, cough, hiccup, hyperdipsia, burning sensation, hemorrhages, hemoptysis, hemorrhoids, wounds, ulcers, diarrhea, dysentery, pharyngoplasty, scorpion string, wounds, ulcers, anorexia, dyspepsia, gastric disorders, asthma, mouth sores, liver diseases, urinary tract infections, diabetes, rheumatism, leucorrhea, lung hemorrhage, nerve disorders, and jaundice [38][39][40]. It has been shown to be anti-inflammatory [41], antibacterial and antifungal [39], antiproliferative [42][43][44][45], antinociceptive [46], analgesic [47], neuroprotective [48], anti-diabetic [49], hepatoprotective [50], antimalarial [51], immunomodulatory [52], anthelmintic [53], antihyperlipidemia [54], and gastroprotective [55]. G. kola is used in health conditions such as nervous alertness and induction of insomnia, wound healing, cancer, stomachache, gastritis, malaria, venereal diseases, laryngitis, and poison antidote [56]. ...
Background: Despite the recognized efficiency of antibiotic therapy, the annual cases of deaths related to bacterial diseases are still growing in developing countries. In the present study, the in vitro antipseudomonal activity of the methanol extracts of nine food plants from Cameroon against the multidrug-resistant strains and isolates of Pseudomonas aeruginosa overexpressing active efflux pumps was determined. These plants included Persea americana, Syzygium jambos, Mangifera indica, Garcinia kola, Citrus sinensis, Passiflora edulis, Vernonia amygdalina, Aframomum letestuanum, and Artocarpus heterophylus.
Methods: The liquid microplate dilution method using the rapid para-Iodonitrotetrazolium chloride (INT) colorimetric method was applied to evaluate the antipseudomonal activities of botanicals, as well as their association with the efflux pump inhibitor and antibiotics.
Results: All botanicals displayed an antibacterial activity that varies from one bacterium to another, in the minimal inhibitory concentration (MIC) range of 64 µg/mL to 2048 µg/mL. The extracts from a mixture of leaves and bark of Syzygium jambos and Mangifera indica, the bark of Garcinia kola, and the leaves of Persea americana had the highest spectrum of antipseudomonal activity, with their inhibitory effects being noted in 100% of the 15 tested bacteria. Botanical from the leaves of Garcinia cola, were active against 90% of the strains tested, that from the bark of Persea americana and the leaves of Citrus sinensis were active against 70% and 60% of tested strains and isolates. Botanicals from the leaves and bark of Mangifera indica were very active against the isolates P124 and P57 with a MIC value of 64 µg/mL. At the concentration of MIC/2 and MIC/4, the extract from the leaves of Mangifera indica and Syzygium jambos potentiated the activity of four antibiotics (Penicillin, Ampicillin, Imipenem, Augmentin) on 100% (7/7) of the strains and isolates tested. Persea americana leaf extract also enhanced the activity of penicillin, tetracycline, chloramphenicol, levofloxacin, ampicillin, and augmentin in 85% (6/7) of strains and isolates tested. The activity of all tested antibiotics increased in the presence of botanicals against at least one bacterial strain. The extract of leaves and bark of Persea americana, Psidium guajava, and leaves of Syzygium jambos potentiated the activity of 80% of the antibiotics on the strains and isolates tested.
Conclusion: Finally, the methanol extracts from the leaves and bark of Mangifera indica could be used effectively alone or in combination with antibiotics in the treatment of bacterial infection caused by Pseudomonas aeruginosa including antibiotic-resistant phenotypes expressing efflux
... The plant contains quercetin, kaempferol, gallic acid, caffeic acid, catechins, tannins and mangiferin [55], careen, ocimene, terpinolene, myrcene, limonene, lupeol, lupeollinoleate, luteoxanthin, violaxanthin, neoxanthin, zeaxanthin, cryptoxanthin, chloromangiferamide, and bromomangiferic acid [54]. Its reported biological activities include the anti-inflammatory [56], antibacterial and antifungal [41], antiproliferative [57][58][59][60], antinociceptive [61], analgesic [62], neuroprotective [63], anti-diabetic [64], hepatoprotective [65], antimalarial [66], immunomodulatory [67], anthelmintic [68], antihyperlipidemia [69], and gastroprotective activities [70]. C. sinensis is an edible fruit with medicinal properties recognized in cases of constipation, cramps, colic, diarrhea, bronchitis, tuberculosis, cough, cold, obesity, menstrual disorder, angina, hypertension, anxiety, depression, stress, sore throats, indigestion, relieve intestinal gas and bloating, resolve phlegm, and additive for flavoring [71]. ...
Background: Bacterial infections continue to wreak havoc around the world with high death rates. African medicinal plants and the phytoconstituents showed high efficiency in impeding the growth of the resistance phenotypes of bacteria The present work was designed to determine the antibacterial activity of seven Cameroonian dietary plants against clinical multidrug resistant (MDR) isolates of Klebsiella sp. These plants included Persea americana Miller (Lauraceae), Psidium guajava Linn. (Myrtaceae), Mangifera indica Linn. (Anacardiaceae), Citrus sinensis Linn. (Rutaceae), Passiflora edulis Sims (Passifloraceae), Garcinia kola Heckel (Guttiferae), and Artocarpus heterophylus Lam. (Moraceae). Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) determinations on the used bacterial strains alone, in the presence of an efflux pump inhibitor, phenylalanine arginine beta naphthylamide (PAβN), and in combination with antibiotics, were performed by the microbroth dilution method using a rapid colorimetric para-Iodonitrotetrazolium chloride (INT) assay. Results: The tested botanicals had different extend of antibacterial activities, with MIC ranges of between 256 μg/mL and 2048 μg/mL. Botanicals from Persea americana, Psidium guajava, Mangifera indica, Artocarpus heterophyllus, and Garcinia kola bark had detected MIC values on all 15 tested Klebsiella strains. PAβN potentiated the activity of the botanicals on all tested bacteria, with the increase of activity ranging from 4 to more than 128-fold. The most significant increase of 4 to more than 128-fold was observed with botanicals from leaves and bark of Psidium guajava and Mangifera indica. The botanicals from the leaves of Mangifera indica potentiated the activity of eight out of ten tested antibiotics (Ceftriaxone, Chloramphenicol, Levofloxacin, Ampicillin, Tetracycline, Imipenem, Doxycycline, and Levofloxacin) against 100% of the tested bacteria. Conclusion: In the present study, it was demonstrated that botanicals from Persea Americana, Psidium guajava, Mangifera indica, Artocarpus heterophyllus, and Garcinia kola had the highest spectrum of activity, and can be used to combat the resistance of Klebsiella species
... Mango peel has several bioactive compounds such as ascorbic acid, carotenoids, and phenolic compounds (phenolic acids, flavonoids, and anthocyanins) [3][4][5]. In several studies, these compounds were demonstrated to have beneficial health properties such as antioxidative, anticarcinogenic, antiatherosclerosis, antimutagenic, and angiogenesis-inhibitory properties; hence, it can be considered a great source to use to promote health [2,[6][7][8][9]. Among others, the antioxidant activity reported from mango peel has been highlighted. ...
Phenolic compounds present in mango peel byproducts have been reported to have several beneficial health properties. In this study, we carried out an optimization of phenolic compounds using ultrasound-assisted extraction via ultrasonic bath and sonotrode. To optimize the variables of extraction, a Box–Behnken design was used to evaluate the best conditions to obtain high total phenolic compound extraction and high antioxidant activity evaluated by different methods (DPPH, ABTS, and FRAP). The optimal ultrasonic bath conditions were 45% ethanol, 60 min, and 1/450 ratio sample/solvent (w/v) whereas optimal sonotrode conditions were 55% ethanol, 18 min, and 65% amplitude. The extracts obtained at the optimal conditions were characterized by HPLC–ESI-TOF-MS. A total of 35 phenolic compounds were determined and, to our knowledge, several of them were tentatively identified for the first time in mango peel. The samples were composed mainly by phenolic acids derivatives, specifically of galloylglucose and methylgallate, which represented more than 50% of phenolic compounds of mango peel byproducts. In conclusion, sonotrode is a valuable green technology able to produce enriched phenolic compound extracts from mango peel byproducts that could be used for food, nutraceutical, and cosmeceutical applications.
... Some of these polyphenols that have been identified and characterized are mangiferin, flavonoids which include quercetin and kaempferol glycosides, phenolic acids and galloyl glycosides. [16] These compounds can be found in all the parts including the fruit, leaves, pulp, seed kernel, peel, bark and roots of which distribution and concentration vary based on different factors. Different factors may include harvest conditions at the time of sampling; processing which includes the methods of drying and storage; environmental factors; and variety of mango. ...
Mangifera indica is a widely-distributed crop with known pharmacological properties. Knowing that sample preparation techniques could affect the chemical composition of natural products, we studied the effect of three common sample preparation methods-airdrying, oven-drying, and grinding in liquid-nitrogen-on the compositions and bioactivities of n-hexane, ethyl-acetate, and methanol extracts of M. indica. By leveraging the Feature-Based Molecular Networking (FBMN) of GNPS coupled with feature-detection of MS-DIAL, as well as simple orthogonal analyses using TLC and PLS-DA, we were able to show the variation of several compound superclasses as affected by sample preparation. In general, the addition of thermal energy or long exposure to ambient conditions, significantly reduced the amount of heat-and environment-sensitive compounds such as polyketides and phenylpropanoids, and organoheterocyclic compounds in the ethyl-acetate and methanol extracts. By utilizing FBMN, we were also able identify structurally-related compounds in the n-hexane, ethyl-acetate, and methanol extracts, providing insights into the chemodiversity of these extracts. In terms of bioactivity, we found that the oven-and air-dried samples exhibited the best percent cytotoxicity against lung cancer cells (A549). This is the first report that utilized FBMN to analyze the effects of sample preparation on a plant extract's metabolomic and bioactivity profiles.
... Several other anticancer agents, such as campothecin derivatives, homoharringtonine, vinca alkaloids, podophyllotoxin derivatives, and taxanes have been isolated from medicinal plants [21][22][23]. Some other medicinal plants reported for the treatment of cancer ( Figure 2) include Allium sativum (Allicin) [24,25], Camellia sinensis [26,27], Achyranthes aspera [28,29], Apis mellifera [30,31], Andrographis paniculate [32], Cannabis sativa [33,34], Astralagus hedysarum [35,36], Bidens Pilosa [37,38], Bolbostemma paniculatum [39,40], Centaurea ainetensis [41,42], Gossypium hirustum or Gossypium herbaceumalso [43][44][45], Hydrocotyle [46][47][48], Salvia miltiorrhiza [49,50], Hypericin perforatum [51], Annona muricata [52,53], Daphne mezereum [54,55], Picrorrhiza kurroa [56,57], Mangifera indica [58,59], Nervelia fordii [10,36,60], Rubia cordifolia [61][62][63], Silybum marianum [64,65], Scutellaria [66][67][68], Oroxylum indicum [69,70], Smilax china [71], Strychnos nuxvomica [72][73][74], Terminalia chebula [75,76], Vernonia amygdalina [77][78][79], Taraxacum officinale [80,81], Withania somnifera (Withanolides) [82,83], Brugmansia suaveolens [84] Zingiber Major types of cancer treatment methods used by physicians and oncologists depending on the cancer type, stage, and severity. The targeted therapeutic method is using of drugs which identify and attack a specific type of cancer cell in the body. ...
Cancer is a serious and significantly progressive disease. Next to cardiovascular disease,
cancer has become the most common cause of mortality in the entire world. Several factors, such as environmental factors, habitual activities, genetic factors, etc., are responsible for cancer. Many cancer patients seek alternative and/or complementary treatments because of the high death rate linked with cancer and the adverse side effects of chemotherapy and radiation therapy. Traditional medicine has a long history that begins with the hunt for botanicals to heal various diseases, including cancer.
In the traditional medicinal system, several plants used to treat diseases have many bioactive compounds with curative capability, thereby also helping in disease prevention. Plants also significantly contributed to the modern pharmaceutical industry throughout the world. In the present review, we have listed 33 medicinal plants with active and significant anticancer activity, as well as their anticancer compounds. This article will provide a basic set of information for researchers interested in developing a safe and nontoxic active medicinal plant-based treatment for cancer. The research will give a scientific foundation for the traditional usage of these medicinal herbs to treat cancer.
... Mangifera indica (mango) is a perennial tropical fruit plant belonging to the Anacardiaceae family and is one of the varieties of mangoes with an apple-like shape (Shah et al. 2010;Noratto et al. 2010). The dicotyledonous plant has long spear-shaped leaves that are 30 cm in length. ...
The crosstalk between androgens and Wnt signaling pathways is critical in the hair growth cycle. Therefore, natural products that target these two pathways for the inhibition of hair loss are sought after. In this study, we investigated the effect of water extracts of Mangifera indica leaves (WEML) on hair growth. WEML treatment significantly reduced the expression levels of both dickkopf-1 (DKK1) and type 2 5α-reductase (SRD5A2) involved in Wnt signal suppression activity and dihydrotestosterone (DHT) synthesis, respectively, in human follicle dermal papilla cells (HFDP). In addition, WEML treatment effectively upregulated Wnt target genes and downregulated DKK1 expression that was increased by DHT treatment. Degranulation analysis in rat basophilic leukemia mast cell line (RBL-2H3) using β-hexosaminidase release assay confirmed that WEML did not exhibit allergenic activity. Furthermore, hair growth was significantly enhanced in in vivo mice model treated with WEML. These results suggest that M. indica leave extract contains bioactive materials that can be used to treat hair loss.
... It is appreciated for its nutritional value, attributable also to the presence of health-enhancing compounds; it is considered a good source of ascorbic acid, carbohydrates, dietary fiber, carotenoids, organic acids, and phenolic compounds [5]. In particular, several studies have shown that mango extract possesses anticancer activity [6] and plays an anti-inflammatory function in numerous chronic pathological disorders associated with an inflammatory response [7,8]. In our previous study, we evaluated the protective effect of mango leaf extract (MLE) on murine adipose tissue inflammation, validating that the phytochemical compounds of mango leaves show functional activity toward adipocytes, improving lipid metabolism and functionality [9]. ...
It is well recognized that functional foods rich in antioxidants and antiinflammation agents including polyphenols, probiotics/prebiotics, and bioactive compounds have been found to have positive effects on the aging process. In particular, fruits play an important role in regular diet, promoting good health and longevity. In this study, we investigated on biological properties of extract obtained from Mangifera indica L. leaves in preclinical in vitro models. Specifically, the profile and content of bioactive compounds, the antimicrobial potential toward food spoilage and pathogenic bacterial species, and the eventually protective effect in inflammation were examined. Our findings revealed that MLE was rich in polyphenols, showing a content exclusively in the subclass of benzophenone/xanthone metabolites, and these phytochemical compounds demonstrated the highest antioxidant capacity and greatest in vitro antibacterial activity toward different bacterial species such as Bacillus cereus, B. subtilis, Pseudomonas fluorescens, Staphylococcus aureus, and St. haemolyticus. Furthermore, our data showed an in vitro anti-inflammatory, antioxidant, and antifibrotic activity.
... Lythrum salicaria showed cytotoxic activities against colon carcinoma (HT-29), leukemia (K-562), breast ductal carcinoma (T47D), and T47D cancer cell lines (497)(498) . Mangifera indica possessed anticancer activity against Molt-4 leukemia, A-549 lung, MDA-MB-231 breast, LnCap prostate, SW-480 colon cancer cells, and breast cancer cells (MDA-MB-231 and MCF-7) (499)(500)(501) . Marrubium vulgare exhibited anticancer activity againt Ehrlich tumor cell lines, human tumor cell lines U251 and MCF7 (brain tumor and breast carcinoma cell lines), HeLa cell lines, K562, K562R (imatinib-resistant), and 697 human leukemia cell lines (502)(503)(504)(505) . ...
Cancer is the second leading cause of death worldwide. The alternative natural therapies are required as they considered to have less toxic side effects compared to current chemotherapy. In the current review Web Science, PubMed, Scopus and Science Direct, were searched to provide information about medicinal plants that have shown anticancer activity against various forms of cancer.
... The main strategies to block and delay carcinogenesis are as follows: (a) Preventive approach, in which cancer can be blocked at early stages by protecting cellular targets by reducing oxidative stress; improving DNA repair and increasing carcinogen detoxification. (b) Delaying cancer cell promotion through apoptosis, cell cycle modulation, and regulating signaling pathways involved in tumor malignancy (Noratto et al., 2010). (c) Suppressing progression by regulating important factors for tumor invasion and metastasis. ...
Osteosarcoma (OS) is a primary malignant bone tumor mainly affecting children, teenagers and young adults, being associated with early metastasis and poor prognosis. The beneficial effects of polyphenols have been investigated in different areas, including their potential to fight OS. Polyphenols are believed to reduce morbidity and/or slow down the development of cancer. This review aimed to assess the effect of polyphenols in OS and investigate their molecular mechanisms. It was observed that the broad spectrum of health-promoting properties of plant polyphenols in OS occurs mainly due to modulation of reactive oxygen species, anti-inflammatory activity, anti-angiogenesis, apoptosis inducer, inhibition of invasion and metastasis. However, it is worth mentioning that although the promising effects of polyphenols in the fight against OS, most of the studies have been performed using in vitro and in vivo animal models. Therefore, studies in humans are needed to validate the effectiveness of polyphenols in OS treatment.
Practical applications
Polyphenols are widely used for various diseases, however, until now, their real role in the treatment of osteosarcoma remains unknown. This review provides a broad spectrum of research conducted with polyphenols and their potential as adjuvant therapy in the treatment of osteosarcoma. However, prior to their clinical application for osteosarcoma treatment, there is a need to isolate and identify specific polyphenolic compounds with high antitumor activity, increase their oral bioavailability, and to investigate their interactions with chemotherapeutic drugs being used in clinical practice.
... Mangoes are rich in vitamins, organic acids, carbohydrates, amino acids, phenolic acids (e.g., gallic acid, caffeic acid, and tannic acid), and certain volatile compounds. Pharmacological studies found the phenolic acid content in mangoes, considered a strong antioxidant, anti-diabetic, anti-inflammatory, antilytic, and anti-carcinogenic [24]. ...
The environmental impact of food is one of the drivers of cities’ growing interest in the developed food system in urban areas, one of which is campus green space. Green spaces (GS) on campus accompany native trees, landscaping, and water features for nurturing wildlife and people in the surrounding campus. In addition, GS can provide food sources such as fruit, alternative food, seeds, and nuts. This study aims to identify food trees in 120 hectares of the University Sumatera Utara campus area through field inventory methods. Our research showed that 49 species belong to 18 families and 1536 individuals USU campus produce beneficial food for people surrounding campus, either fruit, nuts, and alternative food. Thus, we conclude that the university’s green space can support the urban area’s vision as food providers and ecological services for achieving urban sustainability. Furthermore, gathering and gleaning from green space provides opportunities for inhabitants to maintain urban resources and deeply interact with nature.
... The recent study has proven that polyphenols from two mango varieties (Ataulfo and Haden) possessed superior anticancer activity against MDA-MB-231 human breast cancer cells [9]. Vitamin C, commonly known as ascorbic acid, is the dominant nutrient in ripe mango fruit. ...
The aim of study was to determine optimal formulation and microwave parameter to pasteurize mango juice products to maintain the most nutrients and organoleptic level. Raw material and drinking product were assessed for properties including vitamin C content (mg/100ml), total polyphenol content (mgGAE/100ml) and antioxidant activity (% free radical scavenging ability). Besides, factors influencing the quality of mango juice including material to water ratio (w/w), material to syrup ratio (w/w), citric acid content (w/w), microware power (watt) and microware time (minutes) was examined. As a results, the mango: water dilution ratio as 1:2 (w/w); rate of mango: syrup as 1:2 (w/w); citric acid content as 0.3% (w/w); microwave power as 400 watt and microwave time of 3 minutes were suitable for achieving product with good nutritional and sensory quality. At these conditions, vitamin C content was 8.42 mg/100ml, total polyphenol content was 47.543 mgGAE/100ml, and DPPH free radical activity was 11.191%. The results also justified the role of mango as a new ingredient in beverage industry and suggested using microwave to pasteurize as an appropriate method for manufacturing drinking products from fruit.
... Mangiferin compounds (1,3,6,7-tetrahydroxyflavonoid-C2-β-Dglucoside) ( fig. 1) are the compounds derived from the leaves and skin of mango [24,25]. Several studies have shown that the natural compound mangiferin has an anticancer activity where this compound can increase the sensitivity of cancer cells to anticancer drugs [26,27]. Mangiferin also showed anti-inflammatory, antidiabetic, antioxidants, hypolipidemic, antiviral, immunomodulators, analgesics, and hepatoprotective activity [28][29][30]. ...
Cancer is a disease that is causing an increase in mortality all over the world. Cancer treatment is expensive and has a variety of side effects. Natural compound treatment is an attempt to reduce the side effects of cancer therapy. Mangiferin is a natural compound with anticancer and immunomodulatory activity. The immunomodulatory activity of mangiferin from mango (Mangifera indica L.) in cancer was discussed in this article. The literature used in this review was obtained from several databases, including the Cochrane Library, Google Scholar, PubMed, ProQuest, ScienceDirect, and the Wiley Online Library, for articles published over the last ten years. Mangiferin influenced anticancer activity by inhibiting NF-κB, affects the regulation of -catenin, EMT, MMP2, MMP9, LDH, NO, ROS, and inhibits classical macrophages activation. Mangiferin has an immunomodulatory effect that can be developed as a candidate drug for anticancer therapy.
... According to Ojokoh (2007), mango peel fiber is a good source of dietary fiber and its chemical composition may be compared to citrus fiber. Mango peels also demonstrated higher values of anticancer properties because of polyphenolic extracts (Noratto et al., 2010) . Chemical in peels of certain mango cultivars have also been shown to prevent the formation of fat cells through disrupting adipogenesis (Taing et al., 2012) which is the key in development of obesity (Min et al., 2013).MPP can be used as a functional ingredient in developing healthy food products such as noodles, bread, biscuits, sponge cakes and other bakery products (Aziz et al., 2012). ...
... Their fruits are rich in antioxidant vitamins A and C, B6 (pyridoxine), folate, potassium and omega-3 and -6 polyunsaturated fatty acids which all benefit human health (Dautt-Castro et al., 2015;Srivastava et al., 2016). Mango has also been reported to have antibacterial and anti-carcinogenic action (Noratto et al., 2010). Mango can be processed to make juices, ice creams, fruit bars, smoothies and spicy chilli paste (Fasoli and Righetti, 2013). ...
Some allergens have previously been identified in mango (Mangifera indica Linn), including profilins, Bet v 1-like proteins and chitinase. In this paper, we identified the deepest investigation of mango potential allergens using high-throughput Illumina sequencing. RNA-Seq generated 11,751,123 contigs that were assembled into 99,328 unigenes with 16,848 unigenes of >1000 bp. A total of 230,242 unigenes were annotated using public protein databases, with a cut-off E-value above 10−5, of which 27,295, 46,030, 24,227 and 14,023 unigenes were assigned to gene ontology terms, Nr, Swiss-Prot and clusters of orthologous groups, respectively. A total of 66 potential allergen genes were identified, and their relative expressions were evaluated using Illumina RNA-Seq technology. Allergens mainly belonged to pollen allergen, pathogenesis-related protein Bet v I family and NADPH-dependent FMN reductase. We selected c61327.graph_c0, highly expressed in fruit and annotated as Pollen Ole e 1, was used as a template to obtain homologous protein structure in the RCSB PDB bank (PDB: 4z8w). We over-expressed and purified c61327.graph_c0, which could bind to human IgE by immunoblotting analysis. The epitope (74-SFRQEVKTEKHGEFKVHLPFSVSEHV-99) was speculated to confer allergic reactions. Therefore, this study provided a comprehensive systemic view of the transcriptome between mango leaf and fruit allergens endowed with biological activities, which will be useful for further genomic research studies and breeding of lower allergenic mango cultivars. Keywords: Mangifera indica Linn; transcriptome analysis; allergens; protein structure
... Phenolics, flavonoids, and tannins are secondary metabolites and are distributed ubiquitously in the plant kingdom [32,33] and possess numerous biological activities like antioxidant activity, anti-inflammatory, antibacterial activities etc., [2,[34][35][36]. Recent literature has demonstrated the uniqueness of the plant extracts and their compounds with exceptional biomedical and food applications [37][38][39][40][41][42]. ...
Calligonum polygonoides L. (Phog) is an endemic perennial herb with highly resistant to all type of abiotic stresses and dominant biomass as well as phytochemicals producer in its natural habitat of the 'Thar Desert' of Rajasthan, India. The present study was conducted to evaluate effect of extremes of environmental conditions on the phenolic, flavonoids, tannin content, and total antioxidant activities of C. polygonoides foliage harvested during different months. It exhibited a significant variation in the content of phenolic compounds, flavonoids, tannins and antioxidant activity with harvesting time and all parameters are positively correlated to each other. The highest phenolic compounds and antioxidant activity was observed during severe winter and summer months, when monthly average environmental temperature was lowest and highest of the year, respectively. On the basis of results, two harvests of C. polygonoides foliage during June and December is advised to maximize the phenolic compound production wit highest antioxidant activity. These results demonstrate C. polygonoides which is a dominant biomass producer under the harsh climatic conditions can be an important source for the development of the functional foods rich in antioxidants in hot arid regions.
... Ethnomedicinal uses of some parts (leaves, bark, roots, fruits, and flowers) of the plant have been reported in the treatment of disorders including cough, hemorrhages, wounds, diarrhoea, ulcers, anorexia, dyspepsia, chronic dysentery, anemia, piles, kidney stones, tuberculosis, intestinal disorders, blood purification, nasal bleeding, and sunstroke [120,121]. The reported phytochemical constituents include vitamins, carotenoids, polyphenols, sterols, amino acids, flavonoids, and terpenes [122]. The reported pharmacological properties include antidiarrheal, gastroprotective, antioxidant, antidiabetic, hypolipidemic, anticancer, antiparasitic, antifungal, anti-HIV, antibacterial, and antispasmodic properties [120,123,124]. ...
Background:
The growth or multiplication of harmful microorganisms in addition to harmful human activities has led to many disorders in humans. Consequently, there is a search for medications to treat these disorders. Interestingly, medicines of plant origin are known to be among the most attractive sources of new drugs and have shown promising results in the treatment of various diseases including peptic ulcers. This review, therefore, is aimed at obtaining knowledge on some Ghanaian ethnomedicinal plants used to treat peptic ulcers, their folkloric uses, their phytochemicals, and their antiulcer and related pharmacological activities as well as finding areas for prospective studies.
Methods:
Published peer-reviewed articles on ethnomedicinal plants used for the management of peptic ulcers in Ghana from 1967 to 2020 were sourced and used for the study.
Results:
In this review, 13 plants were identified which belong to 10 different families including Sapindaceae, Apocynaceae, and Bignoniaceae. The parts most often used for most preparations were the leaves (53%), followed by stem bark and roots (both having the same percentage of use of 17.6%), the whole plant (5.9%), and the rhizomes (5.9%). Azadirachta indica was the only plant that had undergone some patient studies in addition to animal studies. Conclusion. A discussion of various antiulcer activity studies using ulcer models carried out on selected medicinal plants used for the management of peptic ulcer disease in addition to brief information on their folkloric uses and their phytochemical and other pharmacological properties is presented. These medicinal plants may be used in developing herbal products for the management of peptic ulcer disease.
... Mangiferin was one in the list, where mangiferintreated cells resulted in a signi cant increase in cell survival under H 2 O 2 stress that gives mangiferin a useful perspective in preventing oxidative stress-related diseases (Lou et al., 2012) . Mangiferin is also found to have various bioactivities, such as anti-in ammatory (Carvalho et al., 2009), anti-diabetes (Muruganandan et al., 2005) , immunomodulators (Guha et al., 1996) , anti-tumor (Noratto et al., 2010;Rajendran et al., 2008), and antioxidants (Dar et al., 2005;Barreto et al., 2008). It can promote endothelial cell migration during angiogenesis and may have promising preventive and therapeutic potential in vascular disease (Daud et al., 2020) . ...
Bees produce honey from plant nectar, plant secretions, and excretions of plant-sucking insects. Indonesian local honey contains active compounds that have the potential effect as antioxidant and anticancer. The composition and biological effects of honey vary depending on the flower sources; seasonal and environmental factors can also influence the composition and the physical products. This research was conducted to identify the chemical compounds found in several honey samples produced by beekeepers in Indonesia with LCMS/MS method and to determine the profiles of the honey from Indonesia with the Chemspider and MassBank Database. Honey samples were collected from several regions in Indonesia. The results of the analysis showed that the honey’s diastase number vary from region to region and showed that the HMF contents are relatively low. The compounds that were allegedly found through LCMS/MS analysis include and have been traced based on literature studies had bioactive activity and beneficial to health, include: millefin (potential for treating heart disease and cancer), mangiferin (anti-inflammatory, anti-diabetes, immunomodulators, anti-tumor, antioxidants), rhamnetin (anti-inflammatory), tricin (antioxidant-like), acacetin (inhibit tumor angiogenesis agents), aurantiamide acetate (antiviral or anti-inflammatory, therapeutic agent for the treatment of influenza), salvigenin (controlling inflammation, acute and chronic pain), brucine (modulates anti-inflammatory and analgesic properties), dehydrocostus lactone (anti-inflammatory), santonin (anthelmintic activity), dimethylesculetin (bilirubin clearance), imidazole 4- acetic acid (neuropharmacological properties), propafenone (antiarrhythmic), yohimbine (affected sexual performance), Velutin (anti-inflammatory), narigenin (linked to cardiovascular disease protection). Eventually, honey is is such a natural product with a number of salient therapeutic properties. However, there are still components that were found but their roles cannot be described in detail. Therefore, it is recommended that further meticulous studies should bring to light the other hidden properties of the honey compounds.
... In the present study, the observed cytotoxic activity in MK and MP powder may be related to its high phenolic acids and flavonoids contents (Table 5). Noratto et al., (2010) evaluated the antiproliferative ability of phenolic extracts obtained from the flesh of various mango cultivars on several cancer cell lines (breast cancer MDA-MB-231, leukaemia Molt-4, lung cancer A-549, prostate cancer LnCap, and colon cancer SW-480).They found that the phenolics in the extracts were linked with an increase in the mRNA expression of the pro-apoptotic and cell-cycle regulator biomarkers, as well as a decrease in the generation of reactive oxygen species (antioxidant activity). ...
... These metabolites inhibit cancer cell proliferation [8] by up-regulating pro-apoptotic biomarkers, cell cycle regulators, cell cycle arrest and lowering reactive oxygen species formation. [9] Mango pulp extracts from 'Keith' mango had chemotherapeutic potential against breast cancer by affecting PI3K/AKT pathway and miR-126. [10] However, the mechanism of antioxidants was not thoroughly examined in these studies. ...
Mango (Mangifera indica L. cv. Chaunsa Sumer bahist) fruit is renowned for its flavor and aroma. Besides, it had been found to have large antioxidant content as well as anti-cancer and anti-diabetic properties. However, experiments to test both the antioxidant content and health benefits are still needed. Here, in the ripe mango mesocarp, we have measured the expression of 11 genes playing a role in flavor and aroma development. An up-regulation in expression of fructose-bisphosphate_aldolase (MiFBA6), glutamate decarboxylase (MiGAD), catalase (MiCAT1), glutathione-S-transferase (MiGSTF6) and nucleoredoxin (MiNRX1) genes was recorded. MiGAD gene expression indicated the presence of γ-aminobutyric acid (GABA) metabolite in mesocarp tissue of Chaunsa mango. Metabolite profiling was carried out by gas chromatography-mass spectrometry. A total of five antioxidant compounds with known anticancer activities were characterized in mango mesocarp. It was found metabolites belong to various chemical groups such as: monoterpene alcohols, aroma volatiles, glycoside, monosaccharides, disaccharides, trisaccharides, oligosaccharides, sugar alcohols, sugar acids, essential oils, amino acids, ketone bodies, phytohormones and fatty acids. Seven antioxidant metabolites with known anticancer activities were characterized in mango mesocarp including: 3-hydroxybutyric acid, linalool, geraniol, erythritol, L-(+)-tartaric acid, myo-inositol and lactitol. A total of eight distinct aroma generating siloxanes were characterized in this cultivar. Positive antioxidant activity was also observed in the ethanolic extract of Chaunsa fruit pulp. Chemotherapeutic potential of phenolic compounds found in the ethyl acetate (EtOAc) extract on human breast cancer cell line AU565 was also investigated. The EtOAc extracts effectively suppressed adenocarcinoma growth indicating the anticancer potential of Chaunsa mango fruit.
... The polyphenolic profile of mango is associated with reducing the risk of developing a number of chronic diseases and their related complications [4,5]. Several in vitro and in vivo animal studies support anti-diabetic [6,7], anti-cancer [8,9], anti-inflammatory [10,11], anti-oxidant [12,13] and anti-bacterial [14] activities linked with the intake of mango pulp, peel, seed, juice, extracts and other mango products. Additionally, bioavailability and bioaccessibility analyses of isolated compounds (mangiferin) or extracts from mango leaf and mango seed kernel have been conducted in pre-clinical and in vitro models [15][16][17][18][19]. ...
Pharmacokinetic (PK) evaluation of polyphenolic metabolites over 24 h was conducted in human subjects (n = 13, BMI = 22.7 ± 0.4 kg/m2) after acute mango pulp (MP), vitamin C (VC) or MP + VC test beverage intake and after 14 days of MP beverage intake. Plasma and urine samples were collected at different time intervals and analyzed using targeted and non-targeted mass spectrometry. The maximum concentrations (Cmax) of gallotannin metabolites were significantly increased (p < 0.05) after acute MP beverage intake compared to VC beverage alone. MP + VC beverage non-significantly enhanced the Cmax of gallic acid metabolites compared to MP beverage alone. Pyrogallol (microbial-derived metabolite) derivatives increased (3.6%) after the 14 days of MP beverage intake compared to 24 h acute MP beverage intake (p < 0.05). These results indicate extensive absorption and breakdown of gallotannins to galloyl and other (poly)phenolic metabolites after MP consumption, suggesting modulation and/or acclimation of gut microbiota to daily MP intake.
... The anticancer properties of polyphenolic extracts from several mango varieties in cancer lines, including Molt-4 leukemia cell line, A-549 lung cancer cell line, MDA-MB-231 breast cancer cell line, LNCap prostate adeno carcinoma cells, SW-480 colon cancer cells and non-cancer colon cell line CCD-18Co(Noratto et al., 2010). The ethanol extract had significant cytotoxicity to HeLa cells and the bioactive fraction from the crude extract had antiproliferative effects with an IC50 value of <10μg/ml(Ali et al., 2012;Timsina et al., 2015). ...
Anticancer activity against selected herbal plants, biosynthesize, characterization and optimization
... However, several authors have proposed it as a rich source of polyphenols, anthocyanins and carotenoids that also exhibits a good antioxidant activity by effectively scavenging several free radicals, such as DPPH, hydroxyl radical and peroxyl radical, and by reducing ferric ion to ferrous ion (Ajila et al., 2007;Masibo and He, 2009). Within this wide variety of bioactive compounds, there is mangiferin, a xanthone that has attracted attention due to its various biological activities, such as antiviral, anticancer, antidiabetic, immunomodulatory, hepatoprotective and analgesic, all attributed primarily to its antioxidant capacity (Barreto et al., 2008;Muruganandan et al., 2005;Noratto et al., 2010). ...
Natural products (NPs) have greatly contributed to the development of novel treatments for human diseases such as cancer, metabolic disorders, and infections. Compared to synthetic chemical compounds, primary and secondary metabolites from medicinal plants, fungi, microorganisms, and our bodies are promising resources with immense chemical diversity and favorable properties for drug development. In addition to the well-validated significance of secondary metabolites, endogenous small molecules derived from central metabolism and signaling events have shown great potential as drug candidates due to their unique metabolite-protein interactions. In this short review, we highlight the values of NPs, discuss recent scientific and technological advances including metabolomics tools, chemoproteomics approaches, and artificial intelligence-based computation platforms, and explore potential strategies to overcome the current challenges in NP-driven drug discovery.
In this study, jabuticaba peel purified phenolic extracts were studied regarding their potential inhibitory effects on digestive enzymes linked to diabetes mellitus (DM) and obesity, inhibitory activities towards glycation of bovine serum albumin (BSA), and antioxidant activities. The impact of in vitro gastrointestinal digestion (GID) on the stability of anthocyanins and bioactivities was also evaluated. The analyzed extracts exhibited significant inhibitory activities of α-glucosidase (IC50: 0.47–5.20 mg/mL), α-amylase (IC50: 0.45–1.88 mg/mL), and lipase (IC50: 13.52–111.51 mg/mL). The extracts also inhibited the glycation of BSA (IC50: 0.23–7.07 mg/mL) and showed relevant antioxidant activities. The correlation analysis indicated anthocyanins as one of the main contributing compounds to the bioactivities studied. Cyanidin-3-glucoside was the major anthocyanin identified in the extracts by HPLC analysis. After GID, there was a decrease in the total anthocyanin content (72.77% ± 1.67%) and, consequently, a reduction in the inhibitory activities of carbohydrate digestive enzymes and BSA glycation. This research provided scientific data about the functional properties of jabuticaba peel extracts, which may be a source of dietary compounds with hypoglycaemic, antiglycation, and antioxidant effects.
In this chapter, the traditional use, the phytochemical composition, and the pharmacological activities of African medicinal plants displaying antibacterial effects were reported. We have pooled together the plants and phytochemicals active in pathogens of the family Enterobacteriaceae, as well as Pseudomonas aeruginosa, Gram-positive bacteria, and Mycobacteria. We also identified potent antibacterial medicinal plants of Africa having other pharmacological activities such as anti-inflammatory, anticancer, anti-diabetic, central nervous system, cardiovascular, anti-parasitic, hepatoprotective, immunomodulatory, nephroprotective, reproduction and digestive systems, antiviral, and wound healing activities. The documented plants can be further investigated globally by scientists to develop new herbal drugs to combat various types of bacterial infections.
The World Health Organization predicts a 70% increase in cancer incidents in developing nations over the next decade, and it will be the second leading cause of death worldwide. Traditional plant-based medicine systems play an important role against various diseases and provide health care to a large section of the population in developing countries. Indigenous fruits and their bioactive compounds with beneficial effects like antioxidant, antiproliferative, and immunomodulatory are shown to be useful in preventing the incidence of cancer. India is one of the biodiversity regions and is native to numerous flora and fauna in the world. Of the many fruiting trees indigenous to India, Mango (Mangifera indica), Black plum (Eugenia jambolana or Syzygium jambolana), Indian gooseberry (Emblica officinalis or Phyllanthus emblica), kokum (Garcinia indica or Brindonia indica), stone apple or bael (Aegle marmelos), Jackfruit (Artocarpus heterophyllus), Karaunda (Carissa carandas) and Phalsa (Grewia asiatica), Monkey Jackfruit (Artocarpus lakoocha) and Elephant apple (Dillenia indica) have been shown to be beneficial in preventing cancer and in the treatment of cancer in validated preclinical models of study. In this review, efforts are also made to collate the fruits' anticancer effects and the important phytochemicals. Efforts are also made at emphasizing the underlying mechanism/s responsible for the beneficial effects in cancer prevention and treatment. These fruits have been a part of the diet, are non-toxic, and easily acceptable for human application. The plants and some of their phytochemicals possess diverse medicinal properties. The authors propose that future studies should be directed at detailed studies with various preclinical models of study with both composite fruit extract/juice and the individual phytochemicals. Additionally, translational studies should be planned with the highly beneficial, well-investigated and pharmacologically multifactorial amla to understand its usefulness as a cancer preventive in the high-risk population and as a supportive agent in cancer survivors. The outcome of both preclinical and clinical studies will be useful for patients, the healthcare fraternity, pharmaceutical, and agro-based sectors.
This study intended to enhance fruit quality, extend shelf life and maintain quality of ‘Keitt’ mango (Mangifera indica L.) by using edible compounds without affecting quality or taste. Pre-harvest foliar treatment using calcium lactate (CaL) was applied at 1 and 2% alone or in combination with one of the post-harvest dipping treatments of 2% ascorbic acid (AsA) or 0.3% kojic acid (KA), before storage at 4°C for 12 days during two successive seasons. Pre-harvest treatment with calcium lactate at 2% significantly enhanced the quality of ‘Keitt’ mango fruits at harvest. It was observed that all the conducted treatments were effective in maintaining the quality of the pre-prepared ‘Keitt’ mango as compared to the untreated ones. Pre-harvest application of 2% CaL + post-harvest 2% AsA was the most effective treatment under experimental conditions in terms of total phenols, ascorbic acid, TSS/acid ratio, overall appearance, colour purity, browning incidence, and decay percentage. CaL at 2% showed the lowest significant values of CPLW and it maintained the highest significant firmness compared with control.
Among the different types of mango species, Mangifera indica (MI) and Mangifera zeylanica (MZ) are well known for their therapeutic potential. MI is a pharmacologically and phytochemically diverse plant. Extracts prepared from different parts (bark, leaves, roots, seeds, flowers and fruits) of MI and major mango phytochemicals have been reported to exert a range of pharmacological effects. MZ is a plant endemic to Sri Lanka. The bark of MZ has been used in the Sri Lankan traditional medicine for the treatment of various ailments and conditions, including cancer. Recently, substantial efforts have been made to provide a scientific validation for its traditional use in the treatment of cancer. The present review article describes the pharmacological activities, including anti-inflammatory, antioxidant, anticancer, anti-microbial, anti-diabetic and anti-obesity properties of MI. Furthermore, the anticancer potential of MZ bark extracts and information on compounds isolated from MZ and their bio-activities are also described. The effects of major Mangifera compounds on epigenetic modifications have been widely studied. Therefore, the ability of Mangifera compounds to function as epigenetic drugs in the context of cancer drug discovery has become a promising area of investigation. However, an assessment of the clinical efficacy, and potential adverse and toxic effects of mango extracts is essential prior to their use in clinical practice.
Background: Fruits are an important dietary component, which supply vitamins, minerals, as well as dietary fiber. In addition, they are rich sources of various biological and pharmacologically active compounds. Among these, temperate fruits are well studied for their pharmacological potentials, whereas tropical/subtropical fruits are less explored for their health impacts. In India, most of the consumed fruits are either tropical or subtropical.
Objectives: The present review aims to provide a health impact of major tropical and sub-tropical fruits of India, emphasizing their anticancer efficacy. In addition, the identified bioactive components from these fruits exhibiting anticancer efficacy are also discussed along with the patent literature published.
Methods: The literature was collected from various repositories, including NCBI, ScienceDirect, Eurekaselect, and Web of Science; literature from predatory journals was omitted during the process. Patent literature was collected from google patents and similar patent databases.
Results: Tropical fruits are rich sources of various nutrients and bioactive components including polyphenols, flavonoids, anthocyanin, etc. By virtue of these biomolecules, tropical fruits have been shown to interfere with various steps in carcinogenesis, metastasis, and drug resistance. Their mode of action is either by activation of apoptosis, regulation of cell cycle, inhibition of cell survival and proliferation pathways, increased lipid trafficking or inhibiting inflammatory pathways. Several molecules and combinations have been patented for their anticancer and chemoprotective properties.
Conclusion: Overall, the present concludes that Indian tropical/ subtropical fruits are nutritionally and pharmacologically active and may serve as a source of novel anticancer agents in the future.
Purple sweet potatoes (PSP) are widely used as color enhancers in food formulations. Investigations on the stability of PSP polyphenolics during simulated digestion and subsequent absorption in a Caco-2 cell monolayer model were accomplished. Measures of bioactive activities were also assessed in vitro. PSP whole polyphenolic extracts as a control (WC) were compared to isolates enriched in anthocyanins (AC) or non-anthocyanin phenolics (NAP). Anthocyanins were also alkali-hydrolyzed to remove acylated moieties. Compounds were subjected to simulated gastro-intestinal digestions where non-hydrolyzed anthocyanins showed higher stability compared to alkali-hydrolyzed. For many alkali-hydrolyzed anthocyanins, the transport through a Caco-2 cell monolayer was reduced. PSP fractions significantly increased the generation of reactive oxygen species in HT-29 cells and was suppressive in the CCD-18Co cells while down-regulated mRNA expression of inflammatory markers. Results indicate the importance of PSP composition and the effects of acyl moieties on anthocyanin stability and functional properties for food colors.
Infectious disease that affect virtually fifty thousand individuals daily still unfold and became a serious world drawback and also the key rationalization is that the emergence of multi-drug resistance in microorganism strains. This perturbing scenario has led to seek for new and natural antimicrobial substances with bigger bioactivity and no aspect effects. In practical foods, bioactive compounds exist and might defend the United States of America through many mechanisms against diseases to safeguard against diseases associated with aerophilous stress, the anti-oxidant properties of many BaCs area unit necessary. Fruit consumption provides the United States of America with anti-oxidants that may work to safeguard synergistically. Solely the pulp is employed in mango fruit, whereas all alternative items area unit discarded and cause environmental pollution. Because of its high nutraceutical and dedicative worth, the recognition of mangos is on the rise. Polyphenolic compounds area unit is higher in pulp and better in mango leaves and stem barks and associated bioactivity in fruit. Their area unit varied Polyphenols in mango, however, Mangiferin is bioactive. So to produce bigger insights into their medical, nutritionary, and industrial applications, yet as their role(s) in defensive the plant, all bio-active constituents in mango have to be compelled to be studied. The high nutritional value of ripe mango has been shown to have high matter and anti-carcinogenic effects, with high quite Polyphenols and distinctive supermolecule contents, making it a high potential candidate for nutraceutical usage. The technology at intervals that freeze-dried mango powder retains identical quality as recent ripe mango pulp has already been developed. The goal of this analysis is to assist with the proper use of mangoes to enhance nutrition and health, as well as to improve our understanding of the plant defense mechanisms that depend on these compounds. There is also great potential for use of alternative drying techniques for the popularization of fruit bar processing.
The present study was undertaken to explore the phytochemical screening, anti-bacterial and anti-oxidant activities of the hydro-methanolic leaves extract of Mangifera indica using standard screening methods such as disc diffusion and DPPH methods. In phytochemical screening, Mangifera indicaextract showed presence of secondary metabolites such as carbohydrate, phenols, tanins and proteins whereas Saponins were absent. It also showed antibacterial activities against almost all the test organisms. The extracts possessed potent hydroxyl radical scavenging activity against the positive control standard Ascorbic acid. Results denote the presence of hydroxyl radical scavenging principles in the extracts.
Objectives
Mangifera indica is a medicinal plant that is folklorically used in the treatment of certain disorders connected with women reproductive organs, especially, uterine fibroids. This study investigated the effect of methanol fraction of M. indica (MFMI) extract on oestradiol valerate (OV)-induced endometrial hyperplasia (EH).
Materials and Methods
The animals were randomly divided into four groups of seven rats each. These include a control group, an MFMI-alone group, a model (OV-alone) group and MFMI treatment (OV+MFMI) group. The EH was induced by intraperitoneal injection of OV. The levels of oestrogen (E2), progesterone (PG) and total cholesterol (TC) were determined using ELISA technique. The uterine histological and immunohistochemical assessments of oestrogen receptor, β-catenin and Ki-67 were carried out. Fibroblast cell count/μm ² using histomorphometry as well as gas chromatography–mass spectrometry (GCMS) analysis of MFMI was carried out.
Results
Severe EH was induced on oestradiol valerate administration. The MFMI was able to improve the pathological features of the animal model. Furthermore, the levels of oestrogen, PG and TC were reduced by MFMI. The immune reactive expression of oestrogen receptor alpha, β-catenin and Ki-67 was downregulated by MFMI coadministration. The histomorphometric analysis of the fibroblast cell count/μm ² showed increased cell count density in the OV-treated group which was significantly ameliorated by MFMI coadministration. The GC– MS analysis revealed the presence of some pharmacologically relevant phytochemicals.
Conclusion
This study suggests that MFMI contains phytochemicals that can ameliorate OV-induced EH in female Wistar and the possible mechanism of action involves modulation of oestrogen signalling pathway.
Today, an improved understanding of cancer cell response to cellular stress has become more necessary. Indeed, targeting the intracellular pro-oxidant/antioxidant balance triggering the tumor commitment to cell demise could represent an advantageous strategy to develop cancer-tailored therapies. In this scenario, the present study shows how the peel extract of mango—a tropical fruit rich in phytochemicals with nutraceutical properties—can affect the cell viability of three colon cancer cell lines (HT29, Caco-2 and HCT116), inducing an imbalance of cellular redox responses. By using hydro-alcoholic mango peel extract (MPE), we observed a consistent decline in thiol group content, which was accompanied by upregulation of MnSOD—a mitochondrial scavenger enzyme that modulates the cellular response against oxidative damage. Such an effect was the consequence of an early production of mitochondrial superoxide anions that appeared after just 30 min of exposure of colon cancer cells to MPE. The effect was accompanied by mitochondrial injury, consisting of the dissipation of mitochondrial membrane potential and a decrease in the level of proteins localized in the mitochondrial membrane—such as voltage-dependent anion-selective channel (VDAC1), mitofilin, and some members of Bcl-2 family proteins (Mcl-1, Bcl-2 and Bcl-XL)—with the mitochondrial release of apoptogenic factors (cytochrome C and AIF). The analysis of the cytotoxic effects exerted by the different constituents of MPE (gallic acid, mangiferin, citric acid, quinic acid, pentagalloyl glucose, and methyl gallate) allowed us to identify those phytochemicals responsible for the observed anticancer effects, sustaining their future employment as chemopreventive or therapeutic agents.
The main objective of this work was to extract antioxidant compounds from by-products from the mango processing industry by means of microwave-assisted extraction (MAE). For this, two steps were proposed, first, a kinetics modeling, and then a Box–Behnken design to study the effect of the variables time, power and ethanol concentration on the responses: total extraction yield (TEY), total phenolic content (TPC), total flavonoids content (TFC), and total carotenoids content (TCC). In the kinetics study, all models described a high correlation with the experimental data from bioactive compounds extraction from mango peel. Among these, the two-site mathematical model better described the experimental data (R² > 95%). Optimization results using response surface methodology have shown great adjustments to the quadratic models for TPC, TFC, and TCC; showing that the Box–Behnken design for this subject of research can be of great use when it does not comply with the technical conditions to realize a central design.
Practical Applications
The present study focused on the mathematical modeling of microwave-assisted extraction of bio-compounds from industrial mango peel by-products. Modeling tools such as kinetics studies or response surface methodologies allow the optimization of extraction and process cost reduction. Extracts were obtained at high yield regarding phenolics, flavonoids, and carotenoids content, with high antioxidant activity. These results show that extracts with high antioxidant properties may be applicable in a wide range of foods.
This review presented a comprehensive overview of the phytochemical and pharmacological profile of Mangifera indica, which used for therapeutic purposes as traditional medicine across the world by various cultures. Phytochemical screening of Mangifera indica showed it contained steroids, tannins, alkaloids, flavonoids, phlobatannins, terpenoids, volatile oil, phenol, resins, saponins, protein, carbohydrates and glycosides. Mangifera indica possessed many pharmacological effects included antimicrobial, antiparasitic, antiinflammatory, antipyretic, analgesic, immune- modulatory, anticancer, antidiabetic, reproductive, dermatological, cardiovascular, hypolipidemic, anti- obesity, antioxidant, hepatoprotective, nephroprotective, CNS and neuro- protective, gastrointestinal, anti-anemic and anti-snake venom activitiy. In the current review, databases including Web Science, PubMed, Scopus and Science Direct, were searched to investigate the chemical constituents and pharmacological effects of Mangifera indica.
Some ripe mangoes were collected from the mango orchard located at Digha in Patna district, in Patna of Bihar. The pulp and peels of these mangoes were separated and they were lyophilized and stored at 20°C and thereafter they were analyzed separately for total phenolics in the pulp and the peels of these mangoes of Maldah Cultivar (principle). The total content of phenolics in the pulp and peels of the ripe Maldah mangoes were estimated using folin-ciocatten reagent at 75 nm in an UV-Vis Spectrophotometer using galic acid for expressing the standard curve and subsequently the total result was expressed as mg GAE (Galic Acid Equivalent/100g of fresh weight). Surprisingly the result shows the greater content of phenolics in peels in respect of the pulps.
Mangiferin is a naturally occurring polyphenol, widely distributed in Thymeraceae families, and presents pharmacological activity, including anti-cancer activities in many human cancer cell lines. Mangiferin has also been reported to affect immune responses; however, no available information concerning the effects of mangiferin on immune reactions in leukemia mice in vivo. In the present study, we investigated the effects of mangiferin on leukemia WEHI-3 cell generated leukemia BLAB/c mice. Overall, the experiments were divided into two parts, one part was immune responses experiment and the other was the survival rate experiment. The immune responses and survival rate study, 40 mice for each part, were randomly separated into five groups (N = 8): Group I was normal animals and groups II-V WEHI-3 cell generated leukemia mice. Group II mice were fed normal diet as a positive control; group III, IV, and V mice received mangiferin at 40, 80, and 120 mg/kg, respectively, by intraperitoneal injection every 2 days for 20 days. Leukocytes cell population, macrophage phagocytosis, and NK cell activities were analyzed by flow cytometry. Isolated splenocytes stimulated with lipopolysaccharide (LPS) and concanavalin A (Con A) were used to determine the proliferation of B and T cells, respectively, and subsequently were analyzed by flow cytometry. Results indicated that mangiferin significantly increased body weight, decreased the liver and spleen weights of leukemia mice. Mangiferin also increased CD3 T-cell and CD19 B cell population but decreased Mac-3 macrophage and CD11b monocyte. Furthermore, mangiferin decreased phagocytosis of macrophages from PBMC and peritoneal cavity at 40, 80, and 120 mg/kg treatment. However, it also increased NK cell activity at 40 and 120 mg/kg treatment. There were no effects on T and B cell proliferation at three examined doses. In survival rate studies, mangiferin significantly elevated survival rate at 40 and 120 mg/kg treatment of leukemia mice in vivo.
This study was designed to explore and record various medicinal plants integrated into the traditional system of medicine for the treatment of cancer. The traditional system of medicine is a routine practiced among the indigenous ethnic groups of Sokoto state. A semi-structured questionnaire was designed and used for data collection around the selected Local Government Areas. A substantial number of plant species were identified, recorded, and collected for preservation. Data collected for each specie was analysed to assess its frequent use among the medicinal plants. A total of 67 species belonging to 31 families have been identified and recorded. Out of the 473 frequency of citation (FC), Acacia nilotica was the most frequently cited specie (32 FC, 64% FC, 0.6 RFC), followed by Guiera senegalensis (27 FC, 54% FC, 0.5 RFC), Erythrina sigmoidea (17 FC, 34% FC, 0.3 RFC), and subsequently Combretum camporum (15 FC, 30% FC, 0.3 RFC). The most common parts of the plants used include the barks (55.2%), the roots (53.2%), and the leaves (41.8%). Additionally, decoction (74.6%), powdered form (49.3%), and maceration (46.3%) are the most frequently used mode of preparation. The historical knowledge of a traditional system of medicine practiced by the native traditional healers of Sokoto for the treatment of cancer has been documented. The present study further provides a baseline for future pharmacological investigations into the beneficial effects of such medicinal plants for the treatment of cancer.
Mangifera indica L. (mango), a long-living evergreen plant belonging to the Anacardiaceae family, has been cultivated for thousands of years in the Indian subcontinent for its excellent fruits which represent a rich source of fiber, vitamin A and C, essential amino acids, and a plethora of phytochemicals. M. indica is extensively used in various traditional systems of medicine to prevent and treat several diseases. The health-promoting and disease-preventing effects of M. indica are attributed to a number of bioactive phytochemicals, including polyphenols, terpenoids, carotenoid and phytosterols, found in the leaf, bark, edible flesh, peel, and seed. M. indica has been shown to exhibit various biological and pharmacological activities, such as antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antidiabetic, antiobesity, and anticancer effects. There are a few studies conducted that have indicated the nontoxic nature of mango constituents. However, while there are numerous individual studies investigating anticancer effects of various constituents from the mango tree, an up-to-date, comprehensive and critical review of available research data has not been performed according to our knowledge. The purpose of this review is to present a comprehensive and critical evaluation of cancer preventive and anticancer therapeutic potential of M. indica and its phytochemicals with special focus on the cellular and molecular mechanisms of action. The bioavailability, pharmacokinetics, and safety profile of individual phytocomponents of M. indica as well as current limitations, challenges, and future directions of research have also been discussed.
Tropical fruits speak to one of the most significant harvests on the planet. The ceaselessly developing worldwide market for the primary tropical fruits is at present evaluated at 84 million tons, of which around half is lost or squandered all through the entire handling chain. In addition, the anticancer activity of the different types of fruit extracts and their possible application can be used in pharmaceutical industries. Thus this review presents the ideas of tropical fruits as a natural drug to cure much dread full cancer in the world.
We evaluated the antiproliferative effect of aqueous extracts of 14 plant foods consumed in Mexico on the breast cancer cell line MCF-7. The plant foods used were avocado, black sapote, guava, mango, prickly pear cactus stems (called nopal in Mexico, cooked and raw), papaya, pineapple, four different cultivars of prickly pear fruit, grapes and tomato. beta-Carotene, total phenolics and gallic acid contents and the antioxidant capacity, measured by the ferric reducing/antioxidant power and the 2,2-diphenyl-1,1-picrylhydrazyl radical scavenging assays, were analyzed in each aqueous extract. Only the papaya extract had a significant antiproliferative effect measured with the methylthiazolydiphenyl-tetrazolium bromide assay. We did not notice a relationship between the total phenolic content and the antioxidant capacity with antiproliferative effect. It is suggested that each extract of plant food has a unique combination of the quantity and quality of phytochemicals that could determine its biological activity. Besides, papaya represents a very interesting fruit to explore its antineoplastic activities.
Certain members of the Bcl-2 family inhibit apoptosis while others facilitate this physiological process of cell death. An expression screen for proteins that bind to Bcl-2 yielded a small novel protein, denoted Bim, whose only similarity to any known protein is the short (nine amino acid) BH3 motif shared by most Bcl-2 homologues. Bim provokes apoptosis, and the BH3 region is required for Bcl-2 binding and for most of its cytotoxicity. Like Bcl-2, Bim possesses a hydrophobic C-terminus and localizes to intracytoplasmic membranes. Three Bim isoforms, probably generated by alternative splicing, all induce apoptosis, the shortest being the most potent. Wild-type Bcl-2 associates with Bim in vivo and modulates its death function, whereas Bcl-2 mutants that lack survival function do neither. Significantly, Bcl-xL and Bcl-w, the two closest homologues of Bcl-2, also bind to Bim and inhibit its activity, but more distant viral homologues, adenovirus E1B19K and Epstein-Barr virus BHRF-1, can do neither. Hence, Bim appears to act as a 'death ligand' which can only neutralize certain members of the pro-survival Bcl-2 sub-family.
The Myt1 protein kinase functions to negatively regulate Cdc2-cyclin B complexes by phosphorylating Cdc2 on threonine 14 and tyrosine 15. Throughout interphase, human Myt1 localizes to the endoplasmic reticulum and Golgi complex, whereas Cdc2-cyclin B1 complexes shuttle between the nucleus and the cytoplasm. Here we report that overproduction of either kinase-active or kinase-inactive forms of Myt1 blocked the nuclear-cytoplasmic shuttling of cyclin B1 and caused cells to delay in the G
2
phase of the cell cycle. The COOH-terminal 63 amino acids of Myt1 were identified as a Cdc2-cyclin B1 interaction domain. Myt1 mutants lacking this domain no longer bound cyclin B1 and did not efficiently phosphorylate Cdc2-cyclin B1 complexes in vitro. In addition, cells overproducing mutant forms of Myt1 lacking the interaction domain exhibited normal trafficking of cyclin B1 and unperturbed cell cycle progression. These results suggest that the docking of Cdc2-cyclin B1 complexes to the COOH terminus of Myt1 facilitates the phosphorylation of Cdc2 by Myt1 and that overproduction of Myt1 perturbs cell cycle progression by sequestering Cdc2-cyclin B1 complexes in the cytoplasm.
Green tea, mainly through its constituents epigallocatechin gallate, epigallocatechin, epicatechin gallate and epicatechin, has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer, although less is known about colorectal cancer. Quercetin, the major flavonoid present in vegetables and fruit, exerts potential anticarcinogenic effects in animal models and cell cultures, but less is known about quercetin glucosides. The objectives of this study were to investigate (i) the antioxidant activity of the phenolic compounds epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside; (ii) the cytotoxicity of different concentrations of epicatechin, epigallocatechin gallate, and gallic acid; (iii) the cellular uptake of epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside and (iv) their effect on the cell cycle. Human colon adenocarcinoma cells were used as experimental model. The results of this study indicate that all dietary flavonoids studied (epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside) show a significant antioxidant effect in a chemical model system, but only epigallocatechin gallate or gallic acid are able to interfere with the cell cycle in Caco2 cell lines. These data suggest that the antioxidant activity of flavonoids is not related to the inhibition of cellular growth. From a structural point of view, the galloyl moiety appears to be required for both the antioxidant and the antiproliferative effects.
British Journal of Cancer (2002) 86, 1645–1651. DOI: 10.1038/sj/bjc/6600295 www.bjcancer.com
© 2002 Cancer Research UK
Gallotannin (GT), a plant polyphenol, has shown anticarcinogenic activities in several animal models including colon cancer. In our previous study, we showed that GT inhibits 1,2-dimethylhydrazine-induced colonic aberrant crypt foci and tumors in Balb/c mice, thus supporting a role for GT as a chemopreventive agent in colon cancer. However, at the molecular level, GT's mechanism of chemoprevention is still unclear. In this study, we aim at identifying GT's potential molecular mechanisms of action in in vitro studies. We show that GT differentially inhibits the growth of two isogenic HCT-116 (p53+/+, p53-/-) human colon cancer cells versus normal human intestinal epithelial cells (FHs 74Int). DNA flow cytometric analysis showed that GT induced S-phase arrest in both HCT-116 cell lines. Cell-cycle arrest in p53 (+/+) cells was associated with an increase in p53 protein levels and p21 transcript and protein levels. The inhibition of cell-cycle progression of HCT-116 p53 (+/+) cells by GT correlated with a reduction in the protein levels of cyclin D(1), pRb, and the Bax/Bcl-2 ratio. Although GT did not induce apoptosis in p53 (+/+) cells, a significant induction of apoptosis was observed in p53 (-/-) cells as shown by TUNEL staining and flow cytometry analysis. Apoptosis induction in p53 (-/-) cells was associated with a significant increase in Bax/Bcl-2 protein levels. Our results demonstrate that GT inhibits the growth of HCT-116 colon cancer cells in a p53-independent manner but exhibits differential sensitivity to apoptosis induction in HCT-116 cells with distinct p53 status.
This work was carried out to investigate the pulp composition of four mango cultivars (Haden, Tommy Atkins and Ubá) at the ripening stage in relation to three components with antioxidant potential (total phenolics, carotenoids and ascorbic acid). Total phenolic compound content was estimated by the Folin-Ciocalteu reagent and total carotenoid content by spectrophotometry at 450 nm. The contents of beta-carotene and total vitamin C (ascorbic acid and dehydroascorbic acid) were quantified by high performance liquid chromatography. Differences were found among the four mango cultivars in all the components analyzed. The content of phenolic compounds ranged from 48.40 (Haden) to 208.70 mg/100 g (Ubá); total carotenoid from 1.91 (Haden) to 2.63 mg/100 g (Palmer); beta-carotene from 661.27 (Palmer) to 2,220 microg/100 g (Ubá) and total ascorbic acid ranged from 9.79 (Tommy Atkins) to 77.71 mg/100 g (Ubá). These results corroborated previous information that mangoes are a good source of antioxidants in human diet.
There is a probable association between consumption of fruit and vegetables and reduced risk of cancer, particularly cancer of the digestive tract. This anti-cancer activity has been attributed in part to anti-oxidants present in these foods. Raspberries in particular are a rich source of the anti-oxidant compounds, such as polyphenols, anthocyanins and ellagitannins.
A "colon-available" raspberry extract (CARE) was prepared that contained phytochemicals surviving a digestion procedure that mimicked the physiochemical conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was assessed for anti-cancer properties in a series of in vitro systems that model important stages of colon carcinogenesis, initiation, promotion and invasion.
The phytochemical composition of CARE was monitored using liquid chromatography mass spectrometry. The colon-available raspberry extract was reduced in anthocyanins and ellagitannins compared to the original raspberry juice but enriched in other polyphenols and polyphenol breakdown products that were more stable to gastrointestinal digestion. Initiation--CARE caused significant protective effects against DNA damage induced by hydrogen peroxide in HT29 colon cancer cells measured using single cell microgelelectrophoresis. Promotion--CARE significantly decreased the population of HT29 cells in the G1 phase of the cell cycle, effectively reducing the number of cells entering the cell cycle. However, CARE had no effect on epithelial integrity (barrier function) assessed by recording the trans-epithelial resistance (TER) of CACO-2 cell monolayers. Invasion--CARE caused significant inhibition of HT115 colon cancer cell invasion using the matrigel invasion assay.
The results indicate that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro.
Various epidemiologic and experimental in vivo and in vitro studies have suggested that polyphenols derived from fruits, vegetables and beverages might decrease the risk of developing
lifestyle diseases, such as cardiovascular disorders and cancer. Apples are a major dietary source of polyphenols. Here we
investigated the antitumor activity of apple polyphenols (APs) and procyanidins, namely condensed tannins, both in vitro and in vivo studies. APs and procyanidins inhibited the growth of transplanted B16 mouse melanoma cells and BALB-MC.E12 mouse mammary
tumor cells, and increased the survival rate of the host mice-transplanted B16 cells. Among the APs, the apple procyanidins
specifically, rather than other polyphenols such as chlorogenic acid, (−)-epicatechin, phloridzin and procyanidin B2, had
a major effect on cell proliferation and induced apoptosis in vitro. The apple procyanidins increased mitochondrial membrane permeability and cytochrome c release from mitochondria and activated caspase-3 and caspase-9 within the tumor cells. In addition, we separated eight procyanidin
fractions according to the degree of polymerization using normal-phase chromatography, and detected strong anti-tumor activity
in the procyanidin pentamer and higher degree fractions. Our results indicate that the oral administration of apple procyanidins
inhibits the proliferation of tumor cells by inducing apoptosis through the intrinsic mitochondrial pathway.
The present study is an effort to identify a potent chemopreventive agent against cancer, in which oxidative stress plays an important causative role. The modulatory effect of mangiferin on mitochondrial lipid peroxidation (LPO), tricarboxylic acid (TCA) cycle key enzymes and electron transport chain complexes was investigated against lung carcinogenesis induced by benzo(a)pyrene (50 mg kg(-1) b/w orally) in Swiss albino mice. Decreased activities of electron transport chain complexes and TCA cycle key enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH), in lung cancer bearing animals were observed. Pre- and post-treatment with mangiferin (100 mg kg(-1) b/w orally) for 18 weeks, prevented the above biochemical changes, which were inclined towards normal control animal values. This study further confirms the chemopreventive and chemotherapeutic effect of mangiferin and these results are consistent with our hypothesis that mangiferin is a promising chemopreventive agent.
Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 mumol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.
We have recently shown that penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG), a naturally occurring hydrolyzable gallotannin, inhibited the in vivo growth of human androgen-independent p53-mutant DU145 prostate cancer (PCa) xenograft in athymic nude mice without adverse effect on their body weight. We have also shown that PGG induced caspase-mediated apoptosis in the DU145 cells and the androgen-dependent human p53-wild-type LNCaP cells. Here, we investigated the cell cycle effects of PGG in these and other PCa cells. Our data show that treatment with subapoptotic doses of PGG induced S-arrest, whereas higher doses of PGG induced not only S-arrest but also G(1) arrest. We show, for the first time, that irrespective of the p53 functional status of the PCa cell lines, PGG exerted a rapid (within 2 h) and potent inhibition (inhibitory concentration by 50% approximately 6 microM) of 5-bromo-2'-deoxyuridine incorporation into S phase cells. In isolated nuclei, PGG inhibited DNA replicative synthesis with superior efficacy than a known DNA polymerase alpha inhibitor, aphidocolin. In addition to the S-arrest action, we have found a close association of downregulation of cyclin D1 with G(1) arrest induced by PGG. Overexpressing this G(1) cyclin abolished G(1) arrest, but hastened the S-arrest induction by PGG. Together, our data indicate that PGG induced PCa S-arrest probably through DNA replicative blockage and induced G(1) arrest via cyclin D1 downregulation to contribute to anticancer activity. Our data raise the hypothesis that PGG may be a novel inhibitor of DNA polymerases.
Methods for the quantitative analysis of anthocyanins, leuco-anthocyanins, flavanols and total phenols in plant tissue extracts are critically examined and suitable modifications of existing methods are described.
Phenolic compounds and antioxidant activities of four mango varieties cultivated in Brazil were analyzed. The profile of flavonol-O-glycosides and xanthone-C-glycosides was characterized in pulps from Haden, Tommy Atkins, Palmer, and Ubá cultivars and in the agro-industrial residues from Ubá variety by LC–ESI–MS analysis. The first three varieties were collected from conventional production, whereas Ubá was obtained from organic production. The total phenolic content of the peels and seed kernel extracts was analyzed utilizing Folin-Ciocalteu’s reagent. The aqueous-methanolic extracts of pulp, peel and seed kernels were analyzed for antioxidant activity (AA) by free radical-scavenging and reducing power. A total of 12 flavonoids and xanthones were identified in the pulps, peels and seed kernels, with larger amounts of these compounds being present in the organically grown Ubá variety. The Ubá mango pulp presented higher AA and the peel and seed kernel extracts showed higher AA than did a commercial standard.
The mango is a rich source of various polyphenolic compounds. The major polyphenols in the mango in terms of antioxidative capacity and/or quantity are: mangiferin, catechins, quercetin, kaempferol, rhamnetin, anthocyanins, gallic and ellagic acids, propyl and methyl gallate, benzoic acid, and protocatechuic acid. The nutraceutical and pharmaceutical significance of mangiferin, which is a special polyphenol in the mango has been extensively demonstrated and continues to attract much attention especially in its potential to combat degenerative diseases like heart diseases and cancer. The amounts of the different polyphenolic compounds in the mango vary from part to part (pulp, peel, seed, bark, leaf, and flower) with most polyphenols being found in all the parts. Mango polyphenols, like other polyphenolic compounds, work mainly as antioxidants, a property that enables them to protect human cells against damage due to oxidative stress leading to lipid peroxidation, DNA damage, and many degenerative diseases. Use of pure isolated compounds has been found to be less effective than the use of crude mixtures from the particular mango part suggesting that synergism of the various mango polyphenols is important for maximum antioxidative activity. In this article, we review the major mango polyphenols, looking at their proposed antioxidative activity, estimated amounts in the different parts, their structures, suggested modes of action, and related significance to human health, with great emphasis on mangiferin.
Tropical fruits such as mangoes destined for import into the United States are commonly required to have a thermal treatment against invasive pests, which could be combined with controlled atmosphere (CA) storage to prolong shelf life and preserve fruit quality. Changes in antioxidant phytochemicals and resultant quality during storage and ripening were investigated in fresh mangoes, as influenced by application of CA in combination with a hot water immersion quarantine treatment (46 °C for 75 min). Mature-green mangoes with or without a hot water treatment, were held in air, 3% O2 + 97% N2, or 3% O2 + 10% CO2 + 87% N2 and evaluated for external quality and phytochemical differences after storage for 2 weeks at 10 °C and after subsequent ripening in air at 25 °C. Visible appearance of anthracnose during ripening was effectively inhibited by the hot water treatments combined with CA. Concentrations of gallic acid and numerous hydrolysable tannins and their resultant antioxidant capacity were unaffected by the hot water treatment, while total polyphenolics naturally decreased throughout fruit ripening, regardless of hot water treatment or storage atmosphere. However, the overall decline in polyphenolic concentration was inhibited by the CA treatments, as a result of delayed ripening. Quality parameters such as flesh colour and titratable acidity provided supporting evidence that the CA conditions helped to delay fruit ripening.
Witch hazel (Hamamelis virginia) extracts are used in traditional medicine. They are particularly rich in gallate esters included in proanthocyanidins, hydrolyzable tannins (galloylated sugars), and methyl gallate. This study examines the response of human colon cancer cells to treatment with fractions obtained from a witch hazel polyphenolic extract. The results are compared with those obtained previously with homologous fractions from grape (less galloylated) and pine (nongalloylated). Witch hazel fractions were the most efficient in inhibiting cell proliferation in HT29 and HCT116 human colon cancer cell lines, which clearly shows that the more galloylated the fractions, the more effective they were at inhibiting proliferation of colon cancer cells. Witch hazel fractions were, in addition, more potent in arresting the cell cycle at the S phase and inducing apoptosis; they also induced a significant percentage of necrosis. Interestingly, the apoptosis and cell cycle arrest effects induced were proportional to their galloylation. Moreover, witch hazel fractions with a high degree of galloylation were also the most effective as scavengers of both hydroxyl and superoxide radicals and in protecting against DNA damage triggered by the hydroxyl radical system. These findings provide a better understanding of the structure-bioactivity relationships of polyphenolics, which should be of assistance in choosing an appropriate source and preparing a rational design for formulations of plant polyphenols in nutritional supplements.
An improved method of oxygen radical absorbance capacity (ORAC) assay has been developed and validated using fluorescein (3',6'-dihydroxyspiro[isobenzofuran-1[3H],9'[9H]-xanthen]-3-one) as the fluorescent probe. Our results demonstrate that fluorescein (FL) is superior to B-phycoerythrin. The oxidized FL products induced by peroxyl radical were identified by LC/MS, and the reaction mechanism was determined to follow a classic hydrogen atom transfer mechanism. In addition, methodological and mechanistic comparison of ORAC(FL) with other widely used methods was discussed. It is concluded that, unlike other popular methods, the improved ORAC(FL) assay provides a direct measure of hydrophilic chain-breaking antioxidant capacity against peroxyl radical.
Polyphenolics were extracted from peels, pulp and kernels of mango fruits (Mangifera indica L. cv. 'Tommy Atkins') and characterized by high-performance liquid chromatography/electrospray ionization mass spectrometry. In the peel 18 gallotannins and five benzophenone derivatives were detected which were tentatively identified as galloylated maclurin and iriflophenone glucosides. Twenty-one and eight gallotannins were found in the kernels and pulp, respectively, whereas no evidence for the presence of benzophenone derivatives was obtained. Gallotannins quantified by the rhodanine assay amounted to 1.4 mg/g dm in the peels (expressed as gallic acid), while only small amounts (0.2 mg/g dm) were found in the pulp. In contrast, mango kernels contained 15.5 mg/g dm and thus proved to be a rich source of gallotannins.
Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 mumol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.
Apoptosis or programmed cell death is a process with typical morphological characteristics including plasma membrane blebbing, cell shrinkage, chromatin condensation and fragmentation. A family of cystein-dependent aspartate-directed proteases, called caspases, is responsible for the proteolytic cleavage of cellular proteins leading to the characteristic apoptotic features, e.g. cleavage of caspase-activated DNase resulting in internucleosomal DNA fragmentation. Currently, two pathways for activating caspases have been studied in detail. One starts with ligation of a death ligand to its transmembrane death receptor, followed by recruitment and activation of caspases in the death-inducing signalling complex. The second pathway involves the participation of mitochondria, which release caspase-activating proteins into the cytosol, thereby forming the apoptosome where caspases will bind and become activated. In addition, two other apoptotic pathways are emerging: endoplasmic reticulum stress-induced apoptosis and caspase-independent apoptosis. Naturally occurring cell death plays a critical role in many normal processes like foetal development and tissue homeostasis. Dysregulation of apoptosis contributes to many diseases, including cancer. On the other hand, apoptosis-regulating proteins also provide targets for drug discovery and new approaches to the treatment of cancer.
Mitochondrial permeability transition (MPT) is a Ca(2+)-dependent, cyclosporin A (CsA)-sensitive, non-selective inner membrane permeabilization process. It is often associated with apoptotic cell death, and is induced by a wide range of agents or conditions, usually involving reactive oxygen species (ROS). In this study, we demonstrated that Mangifera indica L. extract (Vimang), in the presence of 20 microM Ca(2+), induces MPT in isolated rat liver mitochondria, assessed as CsA-sensitive mitochondrial swelling, closely reproducing the same effect of mangiferin, the main component of the extract, as well as MPT-linked processes like oxidation of membrane protein thiols, mitochondrial membrane potential dissipation and Ca(2+) release from organelles. The flavonoid catechin, the second main component of Vimang, also induces MPT, although to a lesser extent; the minor, but still representative Vimang extract components, gallic and benzoic acids, show respectively, low and high MPT inducing abilities. Nevertheless, following exposure to H(2)O(2)/horseradish peroxidase, the visible spectra of these compounds does not present the same changes previously reported for mangiferin. It is concluded that Vimang-induced MPT closely reproduces mangiferin effects, and proposed that this xanthone is the main agent responsible for the extract's MPT inducing ability, by the action on mitochondrial membrane protein thiols of products arising as a consequence of the mangiferin's antioxidant activity. While this effect would oppose the beneficial effect of Vimang's antioxidant activity, it could nevertheless benefit cells exposed to over-production of ROS as occurring in cancer cells, in which triggering of MPT-mediated apoptosis may represent an important defense mechanism to their host.
The mango, Mangifera indica L., is a fruit with high levels of phytochemicals, suggesting that it might have chemopreventative properties. In this study, whole mango juice and juice extracts were screened for antioxidant and anticancer activity. Antioxidant activity of the mango juice and juice extracts was measured by 3 standard in vitro methods. The results of the 3 methods were in general agreement, although different radicals were measured in each. Anticancer activity was measured by examining the effect on cell cycle kinetics and the ability to inhibit chemically induced neoplastic transformation of mammalian cell lines. Incubation of HL-60 cells with whole mango juice and mango juice fractions resulted in an inhibition of the cell cycle in the G(0)/G(1) phase. A fraction of the eluted mango juice with low peroxyl radical scavenging ability was most effective in arresting cells in the G(0)/G(1) phase. Whole mango juice was effective in reducing the number of transformed foci in the neoplastic transformation assay in a dose-dependent manner. These techniques provide valuable screening tools for health benefits derived from mango phytochemicals.
Reactive oxygen species and tumor biology are intertwined in a complex web, making it difficult to understand which came first, whether oxidants are required for tumor cell growth, and whether oxidant stress can be exploited therapeutically. Evidence suggests that transformed cells use ROS signals to drive proliferation and other events required for tumor progression. This confers a state of increased basal oxidative stress, making them vulnerable to chemotherapeutic agents that further augment ROS generation or that weaken antioxidant defenses of the cell. In this respect, it appears that tumor cells may die by the same systems they require.
Oncogenic transformation usually leads to increase of cellular reactive oxygen species (ROS) level that renders the cells vulnerable to additional ROS production. By targeting ROS, a naturally occurring ROS-inducing compound, beta-phenylethyl isothiocyanate (PEITC), selectively kills the transformed cells but not normal cells.
Grape (Vitis vinifera) and pine (Pinus pinaster) bark extracts are widely used as nutritional supplements. Procyanidin-rich fractions from grape and pine bark extract showing different mean degrees of polymerization, percentage of galloylation (percentage of gallate esters) and reactive oxygen species-scavenging capacity were tested on HT29 human colon cancer cells. We observed that the most efficient fractions in inhibiting cell proliferation, arresting the cell cycle in G(2) phase and inducing apoptosis were the grape fractions with the highest percentage of galloylation and mean degree of polymerization. Additionally, the antiproliferative effects of grape fractions were consistent with their oxygen radical-scavenging capacity and their ability to trigger DNA condensation-fragmentation.
Ellagitannin-containing foods (strawberries, walnuts, pomegranate, raspberries, oak-aged wine, etc.) have attracted attention due to their cancer chemopreventive, cardioprotective, and antioxidant effects. Ellagitannins (ETs) are not absorbed as such but are metabolized by the intestinal flora to yield urolithins (hydroxydibenzopyran-6-one derivatives). In this study, Iberian pig is used as a model to clarify human ET metabolism. Pigs were fed either cereal fodder or acorns, a rich source of ETs. Plasma, urine, bile, lumen and intestinal tissues (jejunum and colon), feces, liver, kidney, heart, brain, lung, muscle, and subcutaneous fat tissue were analyzed. The results demonstrate that acorn ETs release ellagic acid (EA) in the jejunum, then the intestinal flora metabolizes EA sequentially to yield tetrahydroxy- (urolithin D), trihydroxy- (urolithin C), dihydroxy- (urolithin A), and monohydroxy- (urolithin B) dibenzopyran-6-one metabolites, which were absorbed preferentially when their lipophilicity increased. Thirty-one ET-derived metabolites were detected, including 25 urolithin and 6 EA derivatives. Twenty-six extensively conjugated metabolites were detected in bile, glucuronides and methyl glucuronides of EA and particularly urolithin A, C, and D derivatives, confirming a very active enterohepatic circulation. Urolithins A and B as well as dimethyl-EA-glucuronide were detected in peripheral plasma. The presence of EA metabolites in bile and in urine and its absence in intestinal tissues suggested its absorption in the stomach. Urolithin A was the only metabolite detected in feces and together with its glucuronide was the most abundant metabolite in urine. No metabolites accumulated in any organ analyzed. The whole metabolism of ETs is shown for the first time, confirming previous studies in humans and explaining the long persistency of urolithin metabolites in the body mediated by an active enterohepatic circulation.
Mitochondrial integrity and antioxidative enzyme activity are two of the determinants of intracellular reactive oxygen species (ROS) accumulation probably underlying the aging mechanism. In this study, epigallocatechin-3-gallate (EGCG) was examined for its antiaging effect on human diploid fibroblasts (HDF). EGCG was evaluated for its cytotoxicity, and LC50 values were 78.0 and 84.4 microM for young and old HDF, respectively. HDF treated with EGCG at 25 and 50 microM for 24 h considerably increased catalase, superoxide dismutase (SOD)1, SOD2, and glutathione peroxidase gene expressions and their enzyme activities, thus protecting HDF against H2O2-induced oxidative damage, accompanied with decreased intracellular ROS accumulation and well-maintained mitochondrial potential. Moreover, HDF treated with EGCG at 12.5 microM for long term showed less intracellular ROS with higher mitochondrial potential, more intact mitochondrial DNA, much elevated antioxidative enzyme efficiency, and more juvenile cell status compared to those of the untreated group. Taken together, in this study we investigated the effects of EGCG in the regulation of mitochondrial integrity and antioxidative enzyme activity of HDF, suggesting that EGCG can be considered one of the possible antiaging reagents in the future.
Prostate cancer (PCA) is one of the most invasive malignancy and second leading cause of cancer related deaths in United States and some other countries. Long latency period makes PCA an ideal disease for pharmacologic or nutritional chemoprevention. Lupeol, a triterpene present in mango and other fruits, has shown to possess anticancer properties in in vivo and in vitro assays. Here, we recorded the apoptogenic activity in mouse prostate by lupeol and mango pulp extract (MPE). Testosterone was injected subcutaneously (5 mg/kg body weight) for 14 consecutive days to male Swiss albino mice. Lupeol/MPE supplementation resulted in arrest of prostate enlargement in testosterone-treated animals. In mouse prostate tissue, lupeol and MPE supplementation resulted in a significantly high percentage of apoptotic cells in the hypodiploid region. The induction of apoptosis in mouse prostate cells was preceded by the loss of mitochondrial transmembrane potential and DNA laddering. In testosterone-induced mouse prostate, upregulation of antiapoptotic B-cell non-Hodgkin lymphoma-2 and downregulation of proapoptotic Bcl-2-associated X protein and caspase-3 were also recorded. We further observed apoptogenic activities of lupeol in an in vitro model using human prostate cancer cells [lymph node carcinoma of the prostate (LNCaP)]. The apoptogenic response of lupeol-induced changes in LNCaP cells can be summarized as early increase of reactive oxygen species followed by induction of mitochondrial pathway leading to cell death. Thus, the results of this study demonstrate that lupeol/MPE is effective in combating testosterone-induced changes in mouse prostate as well as causing apoptosis by modulating cell-growth regulators.
Ellagitannins are bioactive polyphenols that have antioxidant and anti-inflammatory bioactivities. Pomegranate juice has the highest concentration of ellagitannins of any commonly consumed juice and contains the unique ellagitannin, punicalagin. Punicalagin is the largest molecular weight polyphenol known. Ellagitannins are not absorbed intact into the blood stream but are hydrolyzed to ellagic acid. They are also metabolized by gut flora into urolithins which are conjugated in the liver and excreted in the urine. These urolithins are also bioactive and inhibit prostate cancer cell growth. Inhibition of Nuclear Factor Kappa-B activation has been shown in prostate cancer cells and in human prostate cancer xenografts in mice. In clinical studies, pomegranate juice administration led to a decrease in the rate of rise of Prostate Specific Antigen after primary treatment with surgery or radiation. Continued translational research on the chemopreventive potential of pomegranate ellagitannins is ongoing.
The contents of secondary plant substances in solvent extracts of various byproducts (barks, kernels, peels, and old and young leaves) in a range of Brazilian mango cultivars were identified and quantitated. The results show that the profiles of secondary plant substances such as xanthone C-glycosides, gallotannins, and benzophenones in different byproducts vary greatly but are fairly consistent across cultivars. The free radical scavenging activity of the solvent extracts was evaluated using a high-performance liquid chromatography-based hypoxanthine/xanthine oxidase assay and revealed dose-dependent antioxidant capacity in all extracts. Four (mangiferin, penta- O-galloyl-glucoside gallic acid, and methyl gallate) of the major phenolic compounds detected were also evaluated in additional in vitro bioassay systems such as oxygen radical absorbance capacity, 2,2-diphenyl-1-picrylhydrazyl, and ferric reducing ability of plasma. Mangiferin in particular, detected at high concentrations in young leaves (Coite = 172 g/kg), in bark (Momika = 107 g/kg), and in old leaves (Itamaraka = 94 g/kg), shows an exceptionally strong antioxidant capacity.
XX, XXXX I adenocarcinoma cells (Caco2)
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J. Agric. Food Chem., Vol. XXX, No. XX, XXXX I
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