Many polyphenols found in dates have been studied as isolated compounds in in vitro and ex vivo systems with respect to their effects on markers of vascular function. Protocatechuic acid, a metabolite of the anthocyanin cyanidin-3-glucoside , and its phase II metabolites were effective in modulating the production of the key inflammatory mediators IL-6 and vascular cell adhesion molecule-1 at dietary-relevant concentrations as low as 100 nmol L−1 , with maximum reduction observed for the sulfate conjugates in human umbilical vein endothelial cells stimulated with either oxidized LDL or a cluster of differentiation CD40L. In the same study, C3G and its metabolites reduced IL-6 production in CD40L-stimulated cells, whereas both C3G and its metabolite, ferulic acid, reduced VCAM-1 production. Anthocyanins and ferulic acid have also been found to significantly reduce monocyte adhesion to HUVECs under physiologically relevant conditions, an important step in reducing atherosclerosis development . In human intestinal cells in vitro, the addition of a freeze-dried date extract from California-grown dates with a total proanthocyanidin content of 13% was demonstrated to act as a potent co-agonist ligand for the farnesoid x receptor , a nuclear structure important for maintaining triglyceride and cholesterol homeostasis. This study provides a potential mechanism by which dates may exert a hypotriglyceridemic effect, as observed in the human study noted above. The tea catechin, epigallocatechin- 3-gallate , plastic pot plant containers has also been shown to modulate FXR in a tissue- and gene-specific manner. Further studies are warranted with dates and their extracts using both wild-type and FXR knockout mouse models.
While the above in vitro work is promising, data from dietary interventions that specifically examine the association between circulating date polyphenols or phenolic metabolites with physiological effects have yet to be reported. Additionally, clinical studies are needed, since in vitro and animal studies, while potentially relevant as preclinical models, do not directly assess outcomes such as the vascular effects in humans. Clinical and mechanistic data on the biological effects of polyphenols derived from dates are limited . Such evidence is crucial for agriculture, health professionals and consumers, particularly as the concept of personalized nutrition grows more popular. In addition to randomized clinical trials on the fruit in general, more data is needed to identify which polyphenols are the most vasculoprotective and then determine how best to cultivate, harvest and process the fruit for maximum bioactivity. The efficacy of date consumption also needs further interrogation in various at-risk groups such as those with lipid disorders, hypertension, obesity or diabetes. Since all fruits are not equal in composition, identification of unique bioactive compounds or fractions in dates would help define benefits that may not be obtained from other fruits or plant-based foods.Dates contain folic acid and vitamin C. Folic acid is required to metabolize homocysteine to methionine. Elevated levels of serum homocysteine have been associated with increased risk for CVD. Although the mechanisms by which increased homocysteine promotes CVD are incompletely defined, suggested alterations include impaired vascular tone due to decreases in NO bio-availability and increases in ET-1, promotion of damaging ROS, and endothelial inflammation and the activation of the coagulation cascade. The vitamin C in dates, while modest in amount compared to most citrus fruits, can nonetheless help to scavenge free radicals via enzymatic and non-enzymatic activities, and help protect lipoproteins from oxidative damage. In addition, vitamin C can improve measures such as arterial stiffness and endothelial function, and low serum concentrations of vitamin C have been linked to increased CVD risk and mortality. Some of the cardioprotective effects of dates have been ascribed to dietary fibers, which have a well-established lipid-lowering effect . Serum triacylglycerol, total cholesterol, and LDL-C levels were significantly lowered in rats given 100 g/kg of date dietary fibers.
Most of the fibers in dates are insoluble. These fibers can bind to cholesterol and triacylglycerols in the intestine and facilitate their excretion, which helps lower circulating cholesterol levels. As a result, less lipoprotein is also susceptible to oxidation, thus reducing the impact on atherogenesis. Further, fiber-rich foods can promote production of beneficial commensal bacteria while limiting the growth of known opportunistic pathogens. A high-fiber diet was reported to increase acetate producing microbiota, lower blood pressure and decrease cardiac hypertrophy and fibrosis in hypertensive mice. Bacterial fermentation of prebiotic soluble fiber generates short chain fatty acids, which are thought to exert several beneficial effects including differentiation of immune regulatory T cells, and decreasing the expression and activation of peroxisome proliferator-activated receptor-γ. Downregulation of PPAR-γ activates a mitochondrial uncoupling protein 2 and an AMP-activated protein kinase network, shifting metabolism in adipose and liver tissue from lipogenesis to fatty acid oxidation. Conversely, activation of PPAR-γ has been shown to have antiinflammatory effects, promote the expression of genes for fatty acid oxidation, and decrease lipotoxicity in macrophages. The interaction of date fibers and polyphenols may also impact vascular function. The gut microbiota are critical for enhanced bio-availability and activity of ingested polyphenols, as most parent compounds are not well absorbed in the small intestine. Following the ingestion of polyphenols, typically in their glycosylated forms, bacteria in the gastrointesti-nal tract metabolize these molecules to low-molecular-weight phenolic compounds that are then absorbed by intestinal epithelial cells. Polyphenols have been shown to undergo a variety of enzymatic processes by bacterial populations in the gastrointestinal tract, including the hydrolysis of glycosylated flavonoids, acylation of flavanol-3-ols and esterification of hydroxycinnamic acids. A detailed description of these mechanisms can be found elsewhere.While the health promoting cardiovascular benefits of a number of fruits, nuts and berries rich in select polyphenols have been characterized through animal and human studies, no such data exists for dates to our knowledge. Given the polyphenol and fiber content of dates, vascular function and gut microbiome studies would be useful. Vascular function is commonly assessed by two noninvasive techniques: flow-mediated dilation of the brachial artery and peripheral arterial tonometry in the fingertip. Both methods have demonstrated prognostic value for the assessment of cardiovascular risk factor burden. High dietary intakes of select polyphenols, such as the flavanols and PACs found in berries, tea, red grapes, and cocoa have been reported to significantly improve FMD and PAT in various population groups. Importantly, no data exists with respect to the impact of date products and their polyphenols on vascular dysfunction via measurement of FMD and PAT. An inherent challenge with most nutrition studies is the identification of suitable controls. This is particularly difficult when examining the potential health effects of whole foods that contain a multitude of compounds that are bioactive either separately or through their interaction with other constituents in the food matrix. One model for testing foods or extracts is to use a control product that is closely matched in calories, large plastic gardening pots macro- and micronutrients, taste, and color, but devoid of the test fraction or compound. This model has been used successfully in studies that assess the effects of a dietary strawberry powder and a flavanol-rich cocoa drink. Another model is to employ a no-intervention control group, although operationally, this may skew the results since a number of those assigned to the control group may withdraw from the study prior to its completion, and those remaining may not fully represent the population initially enrolled. Future human research on dates must select the study population carefully, and focus mainly on groups at risk for CVD. Accordingly, hormonal status, age and sex are factors that can produce significant interindividual variability in cardiometabolic responses to phenolic compounds and must be considered. Factors such as microbial metabolism and genetic polymorphisms may be other contributors to outcome variability. Recent attention has also emphasized the challenge of reproducibility and accuracy in human nutrition research. As noted above, more complete compositional profiles of dates are needed rather than simply recognizing the total amount of GAEs, a gross index of flavonoid content.
A more detailed characterization of products, reagents, and model systems used, as well as better rigor and reporting of experimental designs, protocols, and data analysis, will help achieve this goal. Worthy of note, many of these elements were limiting factors in the in vitro and in vivo animal reports discussed above.While dates have positive biological effects, concerns have been raised about their potential concentrations of heavy metals. Exposure to heavy metals can result in cardiovascular diseases, encephalopathy, renal dysfunction, dementia, and certain cancers. A recent study of seven date varieties collected from different locations in Saudi Arabia noted that aluminum, chromium, and antimony were within a safe range based on the maximum allowable levels set by the World Health Organization, while arsenic, lead, and cadmium exceeded the upper limit in some of the date cultivars. Numerous environmental factors can increase concentrations of heavy metals such as mining, fertilizer applications and industrial emissions, as well as naturally occurring amounts normally found in some soils.Tephritid fruit flies are well-known agricultural pests, and there are approximately 4500 species worldwide . As typical herbivores, host plant expansion is an important survival strategy for tephritid flies, especially when introduced into new areas. Host plant expansion is the ability of an herbivore to use novel host plants without losing their ability to use their original hosts , which facilitates the establishment of tephritids when entering new geographic areas and expanding their damage . Therefore, understanding the mechanism of host plant expansion will be helpful for the control of tephritid pests. Host expansion is well documented in the most destructive species of the genera Anastrepha, Bactrocera, Ceratitis, Dacus, and Rhagoletis among tephritid flies because they have expanded their range worldwide . For example, the ancestral hosts of Zeugodacus cucurbitae in India are primarily cucurbits, but it began to infest papaya in Hawaii , and it expanded its host range to include mango in Africa . The peach fruit fly Bactrocera zonata expanded to oranges and tomatoes when introduced from southeastern Asia to Egypt . Because of the typical frugivorous pest, the tephritids spend some stages of life from eggs and larvae to pupae in the fruit of host plants. Therefore, the microenvironment of host fruits to which flies try to expand will have an important influence on the survival and adaptation of fruit flies. Therefore, when tephritids successfully expand their host range from ancestral host fruits to new hosts, they must adapt well to the chemical and nonchemical properties of the microenvironment from the novel host fruits, including theirphytochemicals, color, and phenology. The color of the host fruit is an important cue to many fruit-infesting insects when selecting a new host . The phenology of the novel host, such as the timing of flowering and fruiting, also affects the ability of a tephritid to use a new host . Importantly, host chemicals are key drivers when herbivores encounter a novel host and serve as attractants and barriers to adaptation . Phytochemicals include volatile compounds and secondary metabolites that serve as attractants or defensive compounds to herbivores, such as tephritids. Volatile compounds allow tephritid adults to select among potential hosts while in fight, similar to fruit color. Once tephritid flies overcome the volatile chemicals of a potential new host, they eventually make contact with the host fruit, and then they must adapt to any secondary metabolites present to successfully colonize the host fruit. These chemical and nonchemical cues of a potential novel host fruit act as selective pressures on tephritids when a novel host is encountered . These selective pressures involve visual identification; behavioral selection; and physical, chemical, and neurophysiological responses by tephritid flies to the novel host fruit . There is likely a genetic basis for each of these processes, which suggests that various genes are involved in regulating the host plant expansion of tephritids. Therefore, increasing our knowledge of the categories and roles of these genes in regulating host expansion will deepen our understanding and allow for improved management strategies for tephritid fruit flies. Gene regulation of host plant expansion has been revealed in several herbivorous insects, including Subpsaltria yangi Chen , Drosophila mettleri Heed , and Chilo suppressalis Walker . For example, research on host plant expansion in a cactophilic fly, Drosophila mojavensis , revealed cytochrome P450, glutathione S-transferases, and UDPglycosyl transferases as major gene classes involved in new host use . Therefore, the present review summarizes current knowledge on the categories and roles of the genes involved in host plant expansion in tephritids and the related regulatory mechanisms and relates these findings to the development of new control methods for tephritid species.