Potential of phenolic compounds from pomegranate (Punica granatum L.) by-product with significant antioxidant and therapeutic effects: A narrative review

The wealth of epidemiological evidence in the scientific world underscores the possibility that a plant-based diet can reduce the prevalence of common diseases such as diabetes, cardiovascular disease, cancer, and stroke. The therapeutic effects of plant sources are partly explained by phenolic secondary metabolites or polyphenolic compounds. Therefore, polyphenolic compounds, which are widely distributed in plants, are of great interest for the development of effective specific drugs with antioxidant and anti-inflammatory effects. Moreover, polyphenol compounds have no harmful effects due to their natural biocompatibility and safety. Numerous studies have highlighted the potential of some industrial food wastes from plant material processing, including apple peels and mashed potatoes, grape skins, tomato and carrot peels, pomegranate peels and seeds, and many others. These byproducts are considered low-cost sources of natural biological compounds, including antioxidants, which have beneficial effects on human health.The polyphenol complex of pomegranate peel (Punica granatum L.), which makes up half of the pomegranate fruit, has more pronounced antioxidant and anti-inflammatory properties than other parts. And the most important active components of pomegranate peel, which are found only in this plant, are punicalagin, followed by ellagic acid and gallic acid. It is known that these polyphenolic compounds of pomegranate peel have the most pronounced therapeutic effect. Several studies have shown the protective effect of ellagic acid, punicalagin, against oxidative stress damage caused by free radicals. The potential of pomegranate peel as an antioxidant and therapeutic component in various biological systems is high, according to scientific sources.However, despite extensive research in recent years, a review of sources has shown that there is insufficient evidence to support the therapeutic effects of polyphenolic compounds from pomegranate peels. The role of pomegranate peel polyphenolic compounds, including flavonoids, as antioxidants in various biological systems also requires further research. Of particular importance are the mechanisms by which antioxidants influence the cellular response against oxidative stress. The purpose of this review was to report our current knowledge of plant polyphenolic compounds and their classification, and to evaluate the potential of phenolic compounds from pomegranate peels with significant antioxidant and therapeutic effects.     

A "White" Anthocyanin-less Pomegranate (Punica granatum L.) Caused by an Insertion in the Coding Region of the Leucoanthocyanidin Dioxygenase (LDOX; ANS) Gene

Color is an important determinant of pomegranate fruit quality and commercial value. To understand the genetic factors controlling color in pomegranate, chemical, molecular and genetic characterization of a "white" pomegranate was performed. This unique accession is lacking the typical pomegranate color rendered by anthocyanins in all tissues of the plant, including flowers, fruit (skin and arils) and leaves. Steady-state gene-expression analysis indicated that none of the analyzed "white" pomegranate tissues are able to synthesize mRNA corresponding to the PgLDOX gene (leucoanthocyanidin dioxygenase, also called ANS, anthocyanidin synthase), which is one of the central structural genes in the anthocyanin-biosynthesis pathway. HPLC analysis revealed that none of the "white" pomegranate tissues accumulate anthocyanins, whereas other flavonoids, corresponding to biochemical reactions upstream of LDOX, were present. Molecular analysis of the "white" pomegranate revealed the presence of an insertion and an SNP within the coding region of PgLDOX. It was found that the SNP does not change amino acid sequence and is not fully linked with the "white" phenotype in all pomegranate accessions from the collection. On the other hand, genotyping of pomegranate accessions from the collection and segregating populations for the "white" phenotype demonstrated its complete linkage with the insertion, inherited as a recessive single-gene trait. Taken together, the results indicate that the insertion in PgLDOX is responsible for the "white" anthocyanin-less phenotype. These data provide the first direct molecular, genetic and chemical evidence for the effect of a natural modification in the LDOX gene on color accumulation in a fruit-bearing woody perennial deciduous tree. This modification can be further utilized to elucidate the physiological role of anthocyanins in protecting the tree organs from harmful environmental conditions, such as temperature and UV radiation.     

八种水果中的多酚含量及其抗氧化性

测定了苹果、石榴、橄榄、芒果、香蕉、菠萝、葡萄和龙眼的壳、肉及核中的多酚含量及其抗氧化性。以70%丙酮(v/v)为提取溶剂,室温下超声波辅助浸提样品后得到提取液。采用普鲁士兰(Prussian blue)法测定了提取液中多酚和单宁的含量,利用FRAP法测定其抗氧化性。结果表明:提取液中多酚和单宁的含量均与其抗氧化性成正相关关系;石榴、橄榄、芒果、葡萄和龙眼等水果的壳与核有望成为天然抗氧化剂的新来源。     

Free radical scavenging and antioxidant potential of mangrove plants: a review

Free radicals derived from reactive oxygen species and reactive nitrogen species are generated in our body by normal cellular metabolism which is enhanced under stress conditions. The most vulnerable biological targets of free radicals are cell structures including proteins, lipids and nucleic acids. Since antioxidants synthesized in the body are not sufficient under oxidative stress, their exogenous supply is important to prevent the body from free radical-induced injury. Recent researches have shown that antioxidants of plant origin with free radical scavenging property could have great importance as therapeutic agents in management of oxidative stress. Mangrove plants growing in inhospitable environment of the intertidal regions of land and sea in tropics and sub-tropics are equipped with very efficient free radical scavenging system to withstand the variety of stress conditions. These mangrove plants possess variety of phytochemical and are rich in phenolic compounds such as flavonoids, isoflavones, flavones, anthocyanins, coumarins, lignans, catechins, isocatechins, etc., which served as source of antioxidants. Isolation and identification of these antioxidant compounds offer great potential for their pharmaceutical exploitations. However, no comprehensive literature is available on antioxidants’ studies in mangrove plants in particular. Hence, the present review discusses the antioxidant potential of mangrove plants with its specific role under salt stress as well as the progress made so far in evaluation of antioxidant activities of different mangrove species.     

Evaluating the Potential Role of Pomegranate Peel in Aluminum-Induced Oxidative Stress and Histopathological Alterations in Brain of Female Rats

Studies have shown that pomegranate, Punica granatum Linn. (Lythraceae), has remarkable biological and medicinal properties. However, the effects of pomegranate peel methanolic extract (PPME) on the aluminum-induced oxidative stress and histopathological change have not been reported yet. To determine the effect of PPME (200?mg/kg bwt) on the aluminum chloride (AlCl₃; 34?mg/kg bwt)-induced neurotoxicity, aluminum accumulation in brain and oxidant/antioxidant status were determined. The change of brain structure was investigated with hematoxylin and eosin, and anti-apoptosis effects of PPME were analyzed by immunohistochemistry. The present study showed an indication of carcinogenicity in the AlCl₃-treated group representing an increase in tissue tumor markers such as tumor necrosis factor-?? and angiogenin and inflammation by inducing an increase in prostaglandin E2 and prostaglandin F2??. PPME protected brain through decreasing the aluminum accumulation and stimulating antioxidant activities and anti-apoptotic proteins namely Bcl-2. Therefore, these results indicated that pomegranate peel methanolic extract could inhibit aluminum-induced oxidative stress and histopathological alternations in brain of female rats, and these effects may be related to anti-apoptotic and antioxidants activities.     

Phytochemical and Biological Activities in Limonium Species Collected in Different Biotopes of Tunisia

A particular interest is nowadays given to natural antioxidants occurring in foods which can reduce the risk of several diseases through their protective effect. The genus Limonium is widely distributed in different salt regions of Tunisia and known in traditional medicine for the presence of highly effective viral and bacterial replication inhibitors. Limonium leaves have possible beneficial effects on human health for their antioxidant activities and free radical scavenging abilities. To exploit the potential of plants from extreme environments as new sources of natural antioxidants, we studied the extracts from leaves of eight Limonium species growing in extreme environments in Tunisia. Antioxidant molecules (polyphenols, flavonoids, flavonols, ascorbate, tocopherols), in vitro (DPPH, ORAC) and ex vivo antioxidant potential on human erythrocytes, antioxidant enzymes activities (superoxide dismutase, peroxidases, glutathione reductase) were evaluated to identify the species with the best antioxidant capacity. The results showed variability among the species considered in function of the environmental conditions of their natural biotopes, as for the antioxidants measured. In particular, L. vulgare from Oued Rane biotope, characterized by dryness and high temperatures, was the species with the highest enzymatic activity and antioxidant capacity, making it interesting as possible edible halophyte plant or as food complement.     

Antioxidant actions of plant foods: Use of oxidative DNA damage as a tool for studying antioxidant efficacy

Plant-food-derived antioxidants and active principles such as flavonoids, hydroxycinnamates (ferulic acid, chlorogenic acids, vanillin etc.), β-carotene and other carotenoids, vitamin E, vitamin C, or rosemary, sage, tea and numerous extracts are increasingly proposed as important dietary antioxidant factors. In this endeavor, assays involving oxidative DNA damage for characterizing the potential antioxidant actions are suggested as in vitro screens of antioxidant efficacy. The critical question is the bioavailability of the plant-derived antioxidants.     

Black carrot anthocyanins exhibit neuroprotective effects against MPP+ induced cell death and cytotoxicity via inhibition of oxidative stress mediated apoptosis

Parkinson’s disease (PD) is a common chronic neurodegenerative disease induced by the death of dopaminergic neurons. Anthocyanins are naturally found antioxidants and well-known for their preventive effects in neurodegenerative disorders. Black carrots (Daucus carota L. ssp. sativus var. atrorubens Alef.) are a rich source of anthocyanins predominantly including acylated cyanidin-based derivatives making them more stable. However, there have been no reports analysing the neuroprotective role of black carrot anthocyanins (BCA) on PD. In order to investigate the potential neuroprotective effect of BCA, human SH-SY5Y cells were treated with MPP+?(1-methyl-4-phenylpyridinium) to induce PD associated cell death and cytotoxicity. Anthocyanins were extracted from black carrots and the composition was determined by HPLC–DAD. SH-SY5Y cells were co-incubated with BCA (2.5, 5, 10, 25, 50, 100 µg/ml) and 0.5 mM MPP+?to determine the neuroprotective effect of BCA against MPP+?induced cell death and cytotoxicity. Results indicate that BCA concentrations did not have any adverse effect on cell viability. BCA revealed its cytoprotective effect, especially at higher concentrations (50, 100 µg/ml) by increasing metabolic activity and decreasing membrane damage. BCA exhibited antioxidant activity via scavenging MPP+?induced reactive oxygen species (ROS) and protecting dopaminergic neurons from ROS mediated apoptosis. These results suggest a neuroprotective effect of BCA due to its high antioxidant and antiapoptotic activity, along with the absence of cytotoxicity. The elevated stability of BCA together with potential neuroprotective effects may shed light to future studies in order to elucidate the mechanism and further neuro-therapeutic potential of BCA which is promising as a neuroprotective agent.

     

Mesophyll versus epidermal anthocyanins as potential in vivo antioxidants: evidence linking the putative antioxidant role to the proximity of oxy-radical source

The hypothesis that anthocyanins in red leaves may be potential in vivo antioxidants whose efficiency is linked to their proximity with the oxy-radical source was tested. Advantage was taken of intra-individual and intra-species variations in the anthocyanic trait and green and red leaves on the same individuals or leaves of green and red phenotypes were compared for the extent of PSII damage by reactive oxygen species generated by methyl viologen treatment in the light. Two species possessing anthocyanins in the mesophyll (Cistus creticus and Photinia x fraseri) and two in the epidermis (Rosa sp. and Ricinus communis) were used, while red actinic light (which is not absorbed by anthocyanins) allowed discrimination between an indirect sunscreen and a direct antioxidant function. Red leaves whose anthocyanins were located in the mesophyll were more resistant to methyl viologen treatment than their green counterparts. In one of these species (Cistus creticus), where anthocyanins are induced in some individuals within the natural population after bright cool days in winter, both green and future-red morphs displayed the same sensitivity to methyl viologen before anthocyanin induction. Immediately after reddening, however, resistance to methyl viologen was considerably increased in the red morphs. By contrast, red leaves whose anthocyanins were restricted to epidermal cells were more sensitive to the herbicide. Total leaf phenolic levels in green/red pairs were similar. The results indicate that vacuolar anthocyanins may be an effective in vivo target for oxy-radicals, provided that the oxy-radical source and the anthocyanic detoxifying sink are in close vicinity.     

Antioxidant potential of microalgae in relation to their phenolic and carotenoid content

In the past decades, food scientists have been searching for natural alternatives to replace synthetic antioxidants. In order to evaluate the potential of microalgae as new source of safe antioxidants, 32 microalgal biomass samples were screened for their antioxidant capacity using three antioxidant assays, and both total phenolic content and carotenoid content were measured. Microalgae were extracted using a one-step extraction with ethanol/water, and alternatively, a three-step fractionation procedure using successively hexane, ethyl acetate, and water. Antioxidant activity of the extracts varied strongly between species and further depended on growth conditions and the solvent used for extraction. It was found that industrially cultivated samples of Tetraselmis suecica, Botryococcus braunii, Neochloris oleoabundans, Isochrysis sp., Chlorella vulgaris, and Phaeodactylum tricornutum possessed the highest antioxidant capacities in this study and thus could be a potential new source of natural antioxidants. The results from the different types of extracts clearly indicated that next to the well-studied carotenoids, phenolic compounds also contribute significantly to the antioxidant capacity of microalgae.     

Hyperoxia-induced changes in antioxidant capacity and the effect of dietary antioxidants.

We investigated, by measuring oxygen radical absorbance capacity (ORAC), whether hyperoxia causes alterations in antioxidant status and whether these alterations could be modulated by dietary antioxidants. Rats were fed for 8 wk a control diet or a control diet supplemented with vitamin E (500 IU/kg) or with aqueous extracts (ORAC: 1.36 mmol Trolox equivalents/kg) from blueberries or spinach and then were exposed to air or >99% O2 for 48 h. Although the constituents of the extracts were not extensively characterized, HPLC indicated that blueberry extract was particularly rich in anthocyanins, and the spinach extract did not contain any anthocyanins. The ORAC was determined in samples without proteins [serum treated with perchloric acid (PCA); ORACPCA] and with proteins (ORACtot). Hyperoxia induced a decrease in serum protein concentration, an increase in serum ORACPCA, decreases in lung ORACPCA and ORACtot, and an equilibration of proteins and ORACPCA between serum and pleural effusion. These alterations suggested a redistribution of antioxidants between tissues and an increase in capillary permeability during hyperoxia. Only the blueberry extract was effective in alleviating the hyperoxia-induced redistribution of antioxidants between tissues.     

Phenolics as potential antioxidant therapeutic agents: mechanism and actions

Accumulating chemical, biochemical, clinical and epidemiological evidence supports the chemoprotective effects of phenolic antioxidants against oxidative stress-mediated disorders. The pharmacological actions of phenolic antioxidants stem mainly from their free radical scavenging and metal chelating properties as well as their effects on cell signaling pathways and on gene expression. The antioxidant capacities of phenolic compounds that are widely distributed in plant-based diets were assessed by the Trolox equivalent antioxidant capacity (TEAC), the ferric reducing antioxidant power (FRAP), the hypochlorite scavenging capacity, the deoxyribose method and the copper-phenanthroline-dependent DNA oxidation assays. Based on the TEAC, FRAP and hypochlorite scavenging data, the observed activity order was: procyanidin dimer > flavanol > flavonol > hydroxycinnamic acids > simple phenolic acids. Among the flavonol aglycones, the antioxidant propensities decrease in the order quercetin, myricetin and kaempferol. Gallic acid and rosmarinic acid were the most potent antioxidants among the simple phenolic and hydroxycinnamic acids, respectively. Ferulic acid displayed the highest inhibitory activity against deoxyribose degradation but no structure–activity relationship could be established for the activities of the phenolic compounds in the deoxyribose assay. The efficacies of the phenolic compounds differ depending on the mechanism of antioxidant action in the respective assay used, with procyanidin dimers and flavan-3-ols showing very potent activities in most of the systems tested. Compared to the physiologically active (glutathione, -tocopherol, ergothioneine) and synthetic (Trolox, BHA, BHT) antioxidants, these compounds exhibited much higher efficacy. Plant-derived phenolics represents good sources of natural antioxidants, however, further investigation on the molecular mechanism of action of these phytochemicals is crucial to the evaluation of their potential as prophylactic agents.     

Plant growth regulators and signal molecules enhance resistance against bacterial blight disease of pomegranate

Bacterial blight caused by Xanthomonas axonopodis pv. punicae is a devastating disease causing huge economic losses in major pomegranate growing areas. Thus, this study has been undertaken to assess the effect of plant growth regulators (PGRs) and signal molecules on disease incidence of bacterial blight in addition to its impact on yield and productivity under field condition in disease endemic area. Considering the environmental concern for reduction in synthetics and antibiotics, PGRs offers cost‐effective and an eco‐friendly schedule for management of this disease. Foliar application of ethylene at 200 ppm resulted in significant reduction in disease incidence in leaves (from 33.01% to 4.87%), fruits (from 25.77% to 2.05%) and twigs (from 1.76% and 0.97% to 0%), as compared to untreated plants. Treatment with salicylic acid and paclobutrazol also resulted in reduction of disease incidence. Further, higher accumulation of total phenols and anthocyanin content in rind as well as in arils was observed in ethylene treatment with enhanced fruit yield in pomegranate plants. The enhanced disease tolerance by recording less disease incidence with increased accumulation of defence compounds like phenols and anthocyanins by ethylene, salicylic acid and paclobutrazol treatments resulted in improving fruit yield and quality of pomegranate fruits. Thus, judicious application of PGRs and signal molecules contributed for induction of resistance while improving developmental and reproductive parameters of pomegranate and thus could be a viable option for their synergistic use in pomegranate farming.     

Methyl jasmonate affects phenolic metabolism and gene expression in blueberry (Vaccinium corymbosum)

Blueberry (Vaccinium corymbosum) is a fruit very much appreciated by consumers for its antioxidant potential and health‐promoting traits. Its beneficial potential properties are mainly due to a high content of anthocyanins and their amount can change after elicitation with methyl jasmonate. The aim of this work is to evaluate the changes in expression of several genes, accumulation of phenolic compounds and alterations in antioxidant potential in two different blueberry cultivars (‘Duke’ and ‘Blueray’) in response to methyl jasmonate (0.1 mM). Results showed that 9 h after treatment, the expression of phenylalanine ammonium lyase, chalcone synthase and anthocyanidin synthase genes was stimulated more in the ‘Blueray’ variety. Among the phenols measured an increase was recorded also for epicatechin and anthocyanin concentrations. ‘Duke’ is a richer sourche of anthocyanins compared to ‘Blueray’, treatment with methyl jasmonate promoted in ‘Blueray’ an increase in pigments as well as in the antioxidant potential, especially in fully ripe berries, but treated ‘Duke’ berries had greater levels, which were not induced by methyl jasmonate treatment. In conclusion, methyl jasmonate was, in some cases, an effective elicitor of phenolic metabolism and gene expression in blueberry, though with different intensity between cultivars.     

Anthocyanins, colour and antioxidant properties of eggplant (Solanum melongena L.) and violet pepper (Capsicum annuum L.) peel extracts

Acetone extracts from eggplant (Solanum melongena L.) and violet pepper (Capsicum annuum L.) peels both belonging to the Solanaceae plant family were characterized with respect to their anthocyanin profiles, colour qualities and antioxidant capacities. According to HPLC-DAD-MS3 analyses the major anthocyanin in eggplant was delphinidin-3-rutinoside, while the predominant pigment in violet pepper was assigned to delphinidin-3-trans-coumaroylrutinoside-5-glucoside. Since virtually all anthocyanins were delphinidin-based, the effect of acylation and glycosylation patterns on colour stability and antioxidant capacity could be assessed. Application of two in vitro-assays for antioxidant capacity assessment revealed that eggplant generally exhibited higher values compared to violet pepper which was ascribed to 3,5-diglycosylated structures predominating in the latter. The higher extent of acylation in violet pepper was reflected by a more purplish colour shade of the extracts, but did not translate into a higher stability against fading which again was attributed to additional glycosyl substitution at C5. These findings support the relevance of structure-related activities of anthocyanins both for understanding food colour and their particular nutritional value.     

Variation in Phenolic Content,Profile, and Antioxidant Activity of Seeds among Different Paeonia ostii Cultivated Populations in China

The purpose of this study was to analyze the phenolic profiles of seeds from fifteen Paeonia ostii cultivated populations in China and identify their relationship with antioxidant activities and associated environmental factors. Thirteen individual phenolic compounds were quantitatively determined by HPLC, and (+)‐catechin was the most abundant phenolic compound in the seeds. Correlation analysis showed that phenolics were the most effective antioxidant compound class by evaluating DPPH, ABTS, and hydroxyl radical scavenging activities as well as ferric reducing antioxidant power. Latitude and annual rainfall had significant effects on the contents of many phenolic compounds, and elevation was only significantly correlated with gallic acid content. Within fifteen P. ostii cultivated populations, the seeds of Tongling population exhibited the highest phenolic contents and strongest antioxidant activities. These results suggest that Tongling population has a relatively high utilization value and a potential for sources of natural antioxidants.     

Responses of antioxidant enzymes to cold and high light are not correlated to freezing tolerance in natural accessions of Arabidopsis thaliana

Low temperatures and high light cause imbalances in primary and secondary reactions of photosynthesis, and thus can result in oxidative stress. Plants employ a range of low‐molecular weight antioxidants and antioxidant enzymes to prevent oxidative damage, and antioxidant defence is considered an important component of stress tolerance. To figure out whether oxidative stress and antioxidant defence are key factors defining the different cold acclimation capacities of natural accessions of the model plant Arabidopsis thaliana, we investigated hydrogen peroxide (H₂O₂) production, antioxidant enzyme activity and lipid peroxidation during a time course of cold treatment and exposure to high light in four differentially cold‐tolerant natural accessions of Arabidopsis (C24, Nd, Rsch, Te) that span the European distribution range of the species. All accessions except Rsch (from Russia) had elevated H₂O₂ in the cold, indicating that production of reactive oxygen species is part of the cold response in Arabidopsis. Glutathione reductase activity increased in all but Rsch, while ascorbate peroxidase and superoxide dismutase were unchanged and catalase decreased in all but Rsch. Under high light, the Scandinavian accession Te had elevated levels of H₂O₂. Te appeared most sensitive to oxidative stress, having higher malondialdehyde (MDA) levels in the cold and under high light, while only high light caused elevated MDA in the other accessions. Although the most freezing‐tolerant, Te had the highest sensitivity to oxidative stress. No correlation was found between freezing tolerance and activity of antioxidant enzymes in the four accessions investigated, arguing against a key role for antioxidant defence in the differential cold acclimation capacities of Arabidopsis accessions.