A bibliographic search was conducted in different specialized virtual platforms such as Google Scholar, Scielo and PubMed using different keywords, as listed below: pistachio, pistachio nuts, pistachio composition, Pistacia vera tree, pistachio world production, pistachio benefits, health pistachio, pistachio waste, recycling of pistachio wastes, pistachio PC, pistachio encapsulation, among others.

The information gathered on the nutritional composition of pistachio nuts was arranged and organized using tables, which allowed to compare the different origins of the nut. Daily intake recommendations from the WHO and the FAO were also taken into account in the disscusion.

A literature search was conducted on the scientific evidence of the beneficial effects commonly attributed to pistachio consumption. This allowed to know the most recent advances. Complementarily, several textbooks were used to understand more general or theoretical issues.

A revision was carried out to characterize the waste caused by pistachio industry. Articles about possible applications of bioactive compounds from pistachio waste in encapsulated systems were discussed.

When it was possible a statistical analysis was performed. The assumptions on normality and homogeneity of variance were checked. Using quantile-quantile (Q-Q) plot, Shapiro-Wilks test and Levene test (P = 0.708) it could be assumed that the fatty acids data presented a normal distribution. Then, for the analysis of the fatty acids results, a single factor one-way ANOVA was used. The Fisher’s least significant differences (LSD) were calculated by comparing the means at a 95% confidence level using the InfoStat 2018 software.

Proteins are important macromolecules from a nutritional point of view. They contain essential amino acids, which cannot be synthesized by the human body and must be obtained from foods. According to Table 2 the amount of each amino acid of the pistachio nuts proteins and in an ideal protein recommended by WHO/FAO [22]. Salinas et al. [23] found that Argentine pistachios have high levels of lysine (Lys), threonine (Thr), leucine (Leu), tyrosine (Tyr), and phenylalanine (Phe), providing an amount of 50% more than that recommended by WHO/FAO [16, 22, 24]. Furthermore, proteins contain approximately 2.5 g of histidine (His), 5.5 g of valine (Val), 4.4 g of isoleucine (Ile) and 1 g threonine (Trp) per 100 g of proteins [16, 23–25]. Regarding the non-essential amino acids, it can be observed that the maximum content of aspartic acid (Asp) + glutamic acid (Glu) is about 29.69% which corresponds to Argentinean pistachio proteins [23], while in those from the US, the amount was 13.1% [25] (Table 2). Besides, pistachios proteins have a high proportion of arginine (Arg; 10.08 g per 100 proteins), which is involved in the cardioprotective and antihypertensive effects of this seed, as described in the following sections.

Triglycerides (TG) are the major compounds in the lipid fraction of pistachios. Oleic acid, linoleic acid and α-linolenic acid are the major unsaturated fatty acids found in the kernel [26]. Linoleic acid (18:2-ω6) and α-linolenic acid (18:3-ω3) are considered essential because the organism does not possess an enzymatic system for the synthesis, elongation, and desaturation of fatty acids beyond C-9 [27]. Both essential fatty acids are key molecules for the formation of structural lipids (skin and nerve tissue phospholipids) and are precursors of hormones such as eicosanoids-prostaglandins, which are essential for the regulation of blood pressure, kidney function, immune function, and uterine contraction [28, 29]. Pistachios had similar percentages of saturated fatty acids (SFA) such as palmitic acid (9.5% to 12.4%) and stearic acid (1% to 2.6%) and similar levels of palmitoleic acid (0.7% to 1.3%) [20, 30, 31]. The main differences were found in monounsaturated fatty acids (MUFAs) with 18 carbon atoms where the samples from Argentina, the US, Iran presented similar percentages of C18:1 (from 55.1% to 55.3%) and different from that of Italy, Greece, and Turkey, which presented the highest values of oleic acid (68.3% to 72.0%, P = 0.0004; Figure 2). These differences could be related to climatic factors such as temperature, which varies according to the area where the fruit is grown. This factor affects the activity of the enzymes (desaturases) involved in the synthesis of linoleic acid from oleic acid, increasing their activity in cold areas [32, 33]. The α-linolenic acid (18:3) content was similar in all pistachios (Figure 2).

Due to the differences in the fatty acid profile, the ω6:ω3 ratio varies. The ω6:ω3 ratio recommended in the diet is between 5:1 and 10:1 to avoid CVD risks [34]. The ω6:ω3 ratio in pistachios from Italy, Greece, and Turkey was 33, 31, and 29, respectively [31], while in pistachios from Argentina, the US and Iran it was between 48 and 59 [20, 30, 31]. This difference is an indicator that the fatty acids profile of pistachios is dependent on their high-altitude cultivation, geographical origin and the maturity of the fruit [35].

Finally, the most important minerals present in pistachios grown in Argentina [36], US, Turkey, Iran [37], Spain [38], and Italy [18] are summarized in Figure 3. In all pistachio nuts, the most important mineral was potassium (K), mainly in Iranian pistachio nuts (1,589 mg/100 g) [37] (Figure 3A); while the Na content reported is very low, ranging from 8.72 mg/100 g [36] to 26.4 mg/100 g [38] (data not shown). Both minerals are important because they regulate the membrane potential of tissue-forming cells and are involved in nerve impulse transmission mechanisms. Intracellular K regulates water-electrolyte balance, osmotic pressure and is required for enzyme activity and protein synthesis, while extracellular K is involved in muscle contractility and blood pressure regulation [28]. Therefore, in order to reduce blood pressure and the risk of CVD, a high K intake with a low sodium intake is suggested [39]. However, with a recommended dietary intake (RDI) of 2,400 mg/day, the sodium content of a 30 g serving of pistachios is negligible.

Regarding calcium (Ca), Iranian pistachios had the highest Ca content (175.2 mg Ca/100 g) [37], while the phosphorus (P) content was between 416 mg/100 g and 816.4 mg/100 g (data not shown). Ca and P are essential for preventing the risk of bone fractures by providing skeletal rigidity [40], and they are present in the bone structure as hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂] or as calcium phosphate. Calcium is also involved in the mechanisms of coagulation, contraction of muscles, and transmission of nerve impulses; also influences the permeability of cells membranes and is an activator of enzymes such as ATPase and lipases. Phosphorous is also found in DNA, RNA, phospholipids of the lipid bilayer of cell membranes, and in energy molecules such as ATP and ADP [28].

Pistachios from the Middle East (Turkey and Iran) had the highest magnesium (Mg) content, followed by those from Spain and Italy (around 115 mg/100 g). In contrast, American pistachios (Argentina and US) contained around 100 mg Mg/100 g (Figure 3A). In addition to its structural function, this mineral acts as an essential co-factor for over 300 enzymes and is involved in energy metabolism, glucose utilization, protein synthesis, fatty acid synthesis and degradation, and is necessary for stabilizing the helical structure of the DNA and RNA molecules [36, 41].

Iron (Fe), zinc (Zn), copper (Cu) and manganese (Mn) are trace minerals important for nutrition. Fe is a structural component of hemoglobin (oxygen transport proteins) and myoglobin, of the enzyme cytochrome (in oxidative metabolism), of enzymes involved in the mechanisms of thyroid hormone and bile acid synthesis, and in the control of signals between neurotransmitters such as dopamine and serotonin [28]. Pistachios from Italy, US and Argentina contain the highest amounts of Fe (3.7–4.5 mg Fe/100 g pistachios; Figure 3B). According to the recommendations (around 14 mg/day), one serving of pistachios would provide < 10% of the RDI [40]. With regard to Zn and Cu, no differences were observed in their content depending on the geographical origin, containing about 2 mg of Zn and 1 mg of Cu per 100 g of pistachios (Figure 3B). Zn is a component of enzymes involved in the synthesis and degradation of carbohydrates, lipids, proteins and nucleic acids, it stabilizes the structure of components and cell membranes, and it is involved in the immune system. The presence of Cu influences the activity of enzymes in oxidative reactions [28]. Although both minerals are present in small amounts in the pistachio fruit, based on nutritional requirements, one serving of pistachios would provide about 8% of the RDI of Zn and 48% of the RDI of Cu. In Figure 3B, it can be observed that pistachios contain approximately 1 mg Mn/100 g of pistachios, however, pistachios grown in Italy and Spain had lower amounts of this mineral, 0.3 mg/100 g [18] and 0.69 mg/100 g of pistachio [38], respectively.

Pistachios contain lipophilic vitamins (A and E) and water-soluble vitamins such as vitamin C and some of the B complex like pyridoxine (B₆), thiamine (B₁) and riboflavin (B₂). This information is summarized in Table 3.

Provitamin A is found in plants as carotenoids (mainly β-carotene). This vitamin is essential for maintaining good vision and influencingprotein metabolism. Additionally, it has a protective effect against the progression of chronic diseases due to the antioxidant activity of β-carotene [28]. Table 3 shows that pistachios from the US had the highest level of vitamin A (34.07 μg retinol/100 g) [42], followed by Iranian pistachios with 21.25 μg retinol/100g [19]. Vitamin E is a lipid-soluble vitamin with high antioxidant capacity that is susceptible to oxidation by high temperatures. Plants synthesize α-, β-, γ-, δ-tocopherols and α-, β-, γ-, δ-tocotrienols [48]. α-Tocopherol has a greater antioxidant activity than γ-tocopherol, which participates in enzymatic processes and plays an important role in platelet aggregation. Table 3 shows that γ-tocopherol is the predominant (30,600 µg/100 g to 37,600 µg/100 g pistachios) [42, 45, 47]. Vitamin B₁ is phosphorylated to B₁ pyrophosphate and acts as a coenzyme in catabolic reactions involved in the initiation of the Krebs cycle and in the synthesis of pentose, which is essential for the formation of nucleic acids [40]. This is a water-soluble vitamin that is sensitive to prolonged heat treatment. Vitamin B₂ is a component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). FMN is involved in redox reactions and the respiratory chain, while FAD is involved in the oxidation of fatty acids, the formation of niacin (B₃) from Try, and the reduction of folic acid (B₉). It is sensitive to light and heat at pH > 7 [49]. Vitamin B₆ is an enzymatic cofactor involved in metabolic reactions such as the biosynthesis and catabolism of amino acids and the biosynthesis of vitamin B₃ from Try, among others [28]. Pistachios contain lower values of B₁ [42, 44, 47] respect to vitamin B₆ (Table 3). The amount of vitamin B₂ in pistachio was between 160 μg/100 g and 447 μg/100 g. One serving of pistachios provides about 20% of the RDI of B₁, 10% of B₂, and 39% of B₆. Ascorbic acid or vitamin C, is an antioxidant that participates as an enzymatic cofactor in hydroxylation, oxidation, and amino acid biosynthesis reactions [28]. This vitamin is thermolabile and sensitive to oxidation. Table 3 shows that the fruits may contain up to 3,480 µg/100 g, covering 6% of the RDI.

Carotenoids are pigments divided into two classes: xanthophylls and carotenes. Lutein and zeaxanthin are two xanthophyllic compounds present in pistachios (Table 4), they are responsible for the color and the antioxidant activity [42]. Pistachios from the US contain high amounts of β-carotene [42] and also of xanthophyll (lutein + zeaxanthin). Besides, Bulló et al. [19] reported lower values of lutein + zeaxanthin in Iranian pistachios. The values reported by the US Department of Agriculture (USDA) [47] for roasted pistachios (RPs) were lower, possibly due to the thermal sensitivity of these carotenoid compounds.

Phytosterols are plant sterols found in the lipidic fraction of plants. They are structural components of cell membranes that stabilize the lipid membranes. They are considered functional compounds because of their hypocholesterolemic effect, since they inhibit the absorption of cholesterol at the intestinal level, they reduce cholesterol re-esterification in enterocytes by inhibiting the activity of the enzyme acyl-CoA:cholesterol acyltransferase (ACAT), and finally stimulate the outflow of non-esterified cholesterol from enterocytes into the intestinal lumen [52]. According to literature, the total phytosterol content is around 250 mg/100 g for all pistachios, containing mainly β-sitosterol (83% of total phytosterols; Table 4).

Several antioxidant compounds are found in pistachios. Noguera-Artiaga et al. [53] evaluated the total phenolic compound content of seven different varieties of P. vera L. and reported values ranging from 500 mg to 6,065 mg gallic acid equivalent (GAE)/100 g pistachios. In addition, several authors have investigated PC and their antioxidant activity in P. vera L. variety Kerman from Argentina [36], US [54] and variety Bronte from Italy [55]. In general, all the authors found higher levels of phenolics, flavonoids and anthocyanins in the skin than in the kernel (Table 5). Italian pistachios of Bronte variety presented a higher content of PC than pistachios of the Kerman variety from Argentina and the US. Regarding flavonoids, catechin was the main flavonoid while cyanidin-3-O-galactoside is the predominant anthocyanin [36, 54, 55].

Inflammation and oxidative stress must be controlled because they play an important role in the pathogenesis and progression of CVD and other pathologies such as atherosclerosis. Oxidative stress is the imbalance between oxidant and antioxidant components in which reactive oxygen species (ROS) predominate. Several clinical and animal studies have shown that pistachio consumption helps to promote the antioxidant status and the anti-inflammatory balance (Table 6). Kocyigit et al. [56] conducted a randomized controlled trial (RCT) in healthy individuals (n = 44) who were divided into two groups: one group consumed a regular diet containing foods from all groups without nuts or nut by-products, and the other group consumed a regular diet supplemented with pistachios (65–75 g/day). They evaluated the antioxidant potential (AOP) and malonaldehyde (MDA) levels in plasma, both parameters indicative of oxidative status. MDA is one of the secondary products of lipid peroxidation of polyunsaturated fatty acid (PUFA) and is studied as an indicator of this process. After three weeks, the pistachio consumption group had an 85% increase in plasma AOP levels and a decrease in MDA levels [56]. Sari et al. [57] conducted a prospective study with 32 young men who consumed a Mediterranean diet rich in vegetables and fish but limited in red meat, fatty foods and eggs for the first 4 weeks. Then, RPs were included as a replacement to the MUFA for the next 4 weeks. Total oxidative status (TOS), MDA levels, lipid hydroperoxides (LOOH), and superoxide dismutase (SOD) enzyme activity were determined on blood samples at the beginning and the end of each dietary period. These authors found that the pistachio diet decreased LOOH, TOS and MDA levels and increased the SOD enzyme activity from 0.42 to 1.55 IU/mL. In addition, Sari et al. [57] studied the anti-inflammatory effect by measuring high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum and plasma samples. CRP is a circulating plasma protein that increases in response to inflammation, and its expression is regulated by IL-6 and IL-1 and TNF-α [69]. IL-6 is a cytokine with anti-inflammatory and pro-inflammatory activity secreted by macrophages, T cells, endothelial cells and fibroblasts. The release of IL-6 is induced by IL-1 and is increased in response to TNF-α [70]. TNF-α is also a pro-inflammatory cytokine secreted by the immune system and by adipocytes [71]. Sari et al. [57] reported a significant reduction in serum IL-6 levels in participants consuming a pistachio diet, without significant changes in CRP and TNF-α levels. Paterniti et al. [58] analyzed the potential anti-inflammatory and antioxidant properties of polyphenolic extracts of natural pistachios (NPs) and RPs, inducing the inflammatory process in an in vitro assay using a culture of lipopolysaccharide (LPS)-stimulated macrophage cells. These authors found that phenolic extracts of NP reduced the degradation of inhibitors of nuclear kappa B and both (NP, RP) reduced the TNF-α and IL-1β production in a dose-dependent manner. This indicated that the inflammatory process was controlled. Bagheri-Hosseinabadi and Abbasifard [72] attributed the inhibition of the transcription NF-κB to pistachio flavonoids. In terms of oxidative power, these authors found that phenolic extracts significantly reduced the cellular expression of cyclooxygenase-2 (COX-2) and the inducible nitric oxide (NO) synthetase (iNOS) enzymes and decreased NO production. As a result, the PC prevented the generation of an oxidative environment and attenuated cellular damage [73]. Paterniti et al. [58] also performed in vivo studies on rats after a subplantar injection of carrageenan (CAR). The histological examinations showed that CAR treatment disorganized edema muscle fibers in shape and size, lost normal muscle architecture, together with an accumulation of inflammatory cells and an increase in myeloperoxidase (MPO, marker of neutrophilic infiltration) enzyme activity. However, after the treatment with the NP phenolic extract, the researchers observed a normal appearance of the muscle fibers, with a decrease in infiltrating inflammatory cells, MPO activity, and in edema volume.

The endothelium is the inner lining of blood vessels and the lymphatic system and is therefore in direct contact with the blood. Its functions include regulation of vascular tone, maintenance of blood fluidity and coagulation, and the production of cytokines and regulation of vascular inflammatory function. Chronic inflammation and oxidative stress are associated with an increase in endothelial dysfunction, an event that precedes the process of atherosclerosis and CVD. Atherosclerosis is characterized by narrowing of the arteries and the formation of atheroma due to inflammation, lipid accumulation, cell death and fibrosis [74, 75].

In general, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and TG in the blood are parameters that indicate the risk of CVD. High levels of TC, TG and/or LDL indicate an increased risk of atherogenesis, while high levels of HDL are desirable as they are responsible for lowering blood cholesterol [74].

Several authors investigated the cardioprotective effects of pistachios. In this regard, Kocygit et al. [56] and Sari et al. [57] showed that addition of pistachio in the diet increased HDL content and decreased plasma TC, LDL and TG (Table 6). This may be due to the presence of phytosterols and MUFAs in pistachio.

Endothelial functionality is usually studied using non-invasive methods, such as brachial artery flow-mediated vasodilation (BAFMVD) and arterial stiffness measurement, such as arterial pulse wave velocity (PWV), which assess endothelium-dependent vasodilation as an indicator to predict CVD risk. A high BAFMVD and a low PWV are associated with a high degree of vasodilation.

Sari et al. [57] found an increase in BAFMVD (Table 6) with an improvement in vasodilation in participants who consumed pistachios. Relaxation of the vascular endothelium may be impaired by decreased NO synthesis. NO is a free radical produced by the enzyme endothelial NO synthetase (eNOS) from the amino acid L-Arg, and is an endogenous vasodilator compound whose deficiency produces arterial hypertension. Some factors can decrease the expression of eNOS, such as high levels of oxidized LDL. Pistachios have high levels of L-Arg (Table 2) and a high proportion of antioxidants (Table 5), which contribute to the proper function of the endothelium and the maintenance of a normal blood pressure [76].

Other authors have also investigated the effect of pistachios on endothelial function. Kasliwal et al. [59] performed an RCT with 60 volunteers with dyslipidemia (altered blood lipid levels) divided into two groups, one group consumed a regular diet, while the others consumed the regular diet supplemented with 40 g/day of pistachio for 12 weeks. The results showed favorable changes in endothelial function (> BAFMVD and < PWV) in individuals who consumed pistachios. In addition, the participants had an increase in HDL level and a reduction in the fasting glucose levels, LDL and TC/HDL ratio [59]. This improvement in the lipid profile of dyslipidemia individuals may be a consequence of the lower amount of SFA along with a higher proportion of MUFAs, PUFAs, and dietary fiber in pistachios (Figure 2).

Regarding the blood pressure, Sari et al. [57] observed no differences in this parameter in healthy young men during the period of pistachio consumption. However, Dumandan et al. [60] demonstrated the inhibitory activity of total soluble protein hydrolysates from pistachios on angiotensin-converting enzyme (ACE) in in vitro studies (Table 6). This enzyme converts angiotensin I to angiotensin II, which increases blood pressure [77]. Therefore, more studies should be conducted in order to elucidate the real effect of pistachio consumption on blood pressure.

PS is a lignocellulosic waste with important industrial applications [79]. It is mainly composed of cellulose (38.1–54.0%), hemicellulose (15.2–31.4%) and lignin (25.2–29.4%) [80] and it is a water absorbent material, effective against certain pollutant species. According to a recent review by Igwegbe et al. [81], most research interest in pistachio adsorption has come majorly for heavy metals and dyes and its removal efficiency has been demonstrated to be up to 90% in most of the cases. Moreover, PS is also valued as a biomass feedstock for bioenergy. It has a low moisture content (3.6–5.7%), high volatile matter (79.8–83% dry matter basis) and low ash content (0.4–1.9% dry matter basis) required for bioenergy generation [79, 82].

Application of PS in foods is limited, nevertheless it is a potential source of natural bioactive compounds. Cardullo et al. [83] proposed an extraction procedure based on microwaves irradiation and identified in the extracts through high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS), gallic acid, pentagalloylglucose and kaempferol as the main phenolics. Their results showed that the latest would be the responsible of the high antioxidant activity found in PS. Moreover, other researchers have indicated that kaempferol and its glycosides present several health benefits such as cardiovascular, neuroprotective, anti-inflammatory and anti-diabetic effects, making PS a promising material for pharmacological studies [83]. Furthermore, Jadhav et al. [84], used subcritical water and a Ni-Graphene catalyst at 240°C to depolymerize lignin extracted from PS. Their results suggest that PS could be a good source of phenolic monomers such as vanillin and syringaldehyde.

PS has also been proposed as a potential candidate for xylan isolation and production of xylooligosaccharides. The interest in these compounds relies in their prebiotic activity and the induction of selective growth of the beneficial microflora such as Bifidobacterium. Hesam et al. [85] optimized the conditions for xylan extraction from PS using an alkaline solution of hydrogen peroxide followed by an enzymatic hydrolysis. This procedure generated a potential prebiotic mixture from xylan which contained xylobiose and xylotriose that could be applied in the development of functional foods and in the pharmaceutical industry. In line with this, Hazal et al. [86] demonstrated that xylo-oligosaccharides and xylose could also be extracted from the hemicellulose fraction of PS through microwave-assisted high-pressure CO₂/H₂O hydrolysis. These authors found that in the optimum conditions the extraction yield could reach up to 60% of xylose.

PGH is the external green colored mesocarp and epicarp of the pistachio fruit. This fraction is separated from the seed by the processing industry and it represents about 35–40% of the weight of the fruit [79]. PGH is primarily discarded, but due to its large amount of water (˃ 70%) it is prone to microbial contamination and it should be dried immediately [87, 88]. Thus, this waste product represents an important environmental issue.

According to Hamed et al. [89] dry PGH of Tunisia is largely composed of carbohydrates (39.70% ± 1.04%), lipids (20.41% ± 0.24%), proteins (11.23% ± 0.24%), water (10.46% ± 0.52%) and ash (14.74% ± 0.12%). Similar results were found by Moghaddam et al. [90] in PGH of Iran who reported 13.1% ± 1.2% of proteins, 9.67% ± 0.12% of lipids and 13.1% ± 0.24% of ash; while PGH from Turkey present 11.40% ± 0.41% ash; 8.54% ± 0.37% proteins [91]. The amount of ash in PGH, highlighted by Behgar et al. [92], was higher than in cotton seed hull (2.8% ash); sunflower hull (1.6% ash) and ground peanut hull (4.0% ash). The mineral content of PGH analyzed by Behgar et al. [92] was 560 mg of Ca and 3,680 mg of K per 100 g of product; more than twice the amount of Ca and K present in the pistachio nut (Figure 3). The amount of P in the PGH was found to be 240 mg/100 g, slightly lower than in the kernel [92].

Although lipids are the second most abundant macrocomponent in PGH, its characterization is scarce. Grace et al. [93] evaluated on a non-polar extract the fatty acid profile of PGH of American pistachio, and indicated that the unsaturated fatty acids comprised 87% of the total. Besides, their results showed that the polyunsaturated linoleic acid (18:2) accounts for 50% of total fatty acids content and the oleic acid (18:1) 36.5 %. In line with this result, Mahoney et al. [94] founded in the lipid fraction from PGH collected over the 2011 in California, that linoleic acid (18:2) was the predominant fatty acid. On the contrary, other authors evaluated PGH from Turkey and Iran and suggested that oleic acid (18:1) was the most abundant in their samples. Therefore, as well as in the kernel, this result would indicate that the fatty acid profile of the hull is dependent on the geographical origin.

It has been also indicated that PGH is a good source of non-digestible carbohydrates [95]. Several authors reported for different pistachio varieties values of neutral and acid detergent fiber [92, 96, 97] in the range of 18.25–22.49% and 14.3–18.29%, respectively.

The prebiotic effect of PGH water soluble polysaccharides was evaluated by Akbari-Alavijeh et al. [98]. According to their findings, the polysaccharides were predominantly composed of xylose, glucose, arabinose, and fructose (molar ratio of 1.00:2.50:19.67:28.81) and the dominant fraction (83.2%) had a molecular weight of 3.71 × 10⁶ Dalton. Moreover, the in vitro digestion process showed that 94.3% of this structure remained undigested, and it could stimulate the growth of prebiotic bacteria such as L. plantarum PTCC 1896 and L. rhamnosus GG. Therefore, these authors suggested that PGH polysaccharides can be proposed as potential prebiotics in foods and could positively modify the gut microbiota while improving the host health.

Hamed et al. [99] extracted and identified from pistachio external hull a type II arabinogalactan and proved that these heteropoly-saccharide exhibited an immunomodulatory activity by stimulating B lymphocytes in vitro and could be considered an immunoregulatory agent in health therapeutics.

Moreover, PGH has been considered a potential promising source of pectin that could be used to deal with the high demand of this ingredient [100]. According to Arjeh et al. [88] the amount of pectin in this waste is around 18–19%, similar to other well-known sources of pectin such as apple pomace (15%) and orange peel (18%). Therefore, different studies have been conducted in order to optimize the extraction of PGH-pectin. Chaharbaghi et al. [101] found that the maximum acidic extraction of pectin (22.1% ± 0.5%) could be reached at 90℃ during of 30 min with a very acid solution (pH = 0.5) and a liquid/solid ratio of 50 v/w. Kazemi et al. [100] found a similar result (18.13% of extraction yield) with a microwave-assisted procedure with a power of 700 W, irradiation time of 165 s, and pH 1.5. According to these authors, the extracted pectin was low-methoxyl (about 12.1%) a molecular weight of 1.659 kg/mol and the emulsifying activity of 58.3%. PGH pectin has been used for food applications. In a recent publication, Kazemi et al. [102] formulated low protein and low-Phe cookies for phenylketonuria patients with an extract of PGH pectin and PC. Their results indicated that this addition enhanced the quality of samples, positively affected the overall acceptability and improved the antioxidant activity, while it did not have an impact on the Phe content of the biscuits. Fathi et al. [103] explored the development of a new biodegradable film with PGH-pectin poly vinyl alcohol and different curcumin levels. The latest showed that this novel material could be employed as an intelligent packaging for fatty foods and showed antibacterial activity against Escherichia coli and Staphylococcus aureus.

It has been suggested that PGH has an important nutraceutical potential and various food applications associated to their high proportion of PC [79]. Polyphenols extracted from PGH have attracted special attention because of their antioxidant, anti-inflammatory, and other biological activities [96]. According to Erşan et al. [104] the phenolic content of PGH ranged from 6,120 mg/100 g ± 45 mg/100 g to 10,000 mg/100 g ± 48 mg/100 g of dry matter depending on the variety. This is much higher than the values found in the kernel (Table 5). Nevertheless, some authors found lower amounts of PC (2,130–3,930 mg/100 g) [12, 105]. A wide variety of PC were identified and determined in PGH such as hydroxybenzoic acid and its derivatives, like p-hydroxybenzoic, vanillic, dihydroxybenzoic, gallic, protocatechuic and syringic acids. According to many authors, gallic acid is one of the main PC in PGH [93, 104–110]. However, its extraction rate is strongly dependent on the extraction solvent and the conditions used. Rajaei et al. [13] evaluated the effect of different solvents on PC extraction yield. Their results indicate that water was the most adequate extraction solvent followed by an ethanol/water mixture, methanol and ethanol. In agreement, a high amount of gallic acid [5,480 µg/g dry weight (d.w.)] was determined by Seifzadeh et al. [109] in an aqueous extract of PGH, while Özbek et al. [105] found a lower amount of gallic acid (3,072.9 µg/g d.w.) through an ethanol/water (50:50) microwave-assisted extraction. These last authors determined high quantities of others PC like p-hydroxybenzoic acid (2,054.2 µg/g d.w.) and protocatechuic acid (314.9 µg/g d.w.) and lower amounts of syringic acid (19.0 µg/g d.w.) [105].

Garavand et al. [111] determined cinnamic acid derivatives in PGH. Their results indicate the presence of sinapic acid (26.5 µg/g), and p-coumaric acid (13.9 µg/g) using a microwave-assisted extraction with water. Similar amounts of p-coumaric acid (17.1 µg/g) were reported in microwave-assisted ethanol:water extracts, together with caffeic acid (11.8 µg/g) by Özbek et al. [105]. Another derivate of cinnamic acid found in PGH was caffeic acid-O-hexose (150.9 µg/g d.w.) [109].

PGH is also a source of natural flavonoids such as as quercetin-3-O-rutinoside, quercetin 3-O-galactoside, quercetin 3-O-glucuronide and quercetin-3-O-glucoside (Table 7). The maximum amount of quercetin-3-O-rutinoside and quercetin-3-O-glucoside was 1,280 µg/g d.w. and 2,030 µg/g d.w., respectively according to Seifzadeh et al. [109] while the minimum amount was reported in ethanol extracts by Barreca et al. [106]. Another flavonoid found in PGH was eriodictyol-7-O-glucoside, and the maximum concentration was informed in methanolic extracts of PGH (1,333.73 µg/g d.w.) by Seifzadeh et al. [109].

Also, some representative compounds from the tannin family have been found in PGH. Gallotannins and galloyl were identified by Grace et al. [93] through mass spectrometry. Gallotannins are characterized by the presence of galloyl groups linked to a sugar molecule. Luteic acid, theogallin, galloyl-O-hexoside (penta-O-galloyl-β-D-glucose), β-glucogallin, galloyl quinic and shikimic acids were found by Seifzadeh et al. [109]. Moreover, these authors found a higher amount of galloyl shikimic acid (5,670 µg/g d.w.) through an aqueous extraction than Erşan et al. [104] (842.5 µg/g d.w.) who used a methanolic extraction.

Some of the previous authors not only determined the quantities of the PC in PGH, but they also carried out in vitro experiments to elucidate their beneficial effects. Grace et al. [93] demonstrated the antioxidant and anti-inflammatory properties of a polar PGH extract which inhibited the release of ROS and NO. Also, they reported positive effect on the gene expression of biomarkers responsible of inflammatory response.

Barreca et al. [106] demonstrated the radical scavenging activity of PGH extracts against 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion and 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS⁺). This work evaluated the cytoprotective effect of ethanolic and methanolic extracts of PGH, through their ability to inhibit erythrocyte membranes lipid peroxidation and their potential to protect the blood lymphocytes from cytotoxicity.

Moreover, Lalegani et al. [108] evaluated the in vitro capacity of PGH to inhibit α-amylase and α-glucosidase, carbohydrate digestion enzymes, by colorimetric methods. They found an inhibitory effect of different concentrations of PGH extract against porcine pancreatic α-amylase. Their results indicate a PGH extract (610 μg GAE/mL) dose dependent inhibition. They concluded that the α-amylase inhibitory activity was related to the tannin fraction of the PGH extract.

Finally, antifungal property against Candida species was evaluated by Gharibi et al. [110]. Their results indicated that pistachio extracts had a lower minimum inhibitory concentration against C. albican, C. glabrata and C. auri, than that of fluconazole treatment. These authors attribute this property to cyanidin-3-O-galactoside as the mayor polyphenol. However, they pointed out that probably the complete polyphenol profile contribute to the observed result. All this information related to polyphenol bioactivity is summarized in Table 7.

Pistachio wastes are important due to there are a source of bioactive compounds that can be extracted and incorporated in small particles and also they could also be used as encapsulation materials.

The CNC extracted from PS are excellent candidates as a carrier for encapsulation and for stabilization of oil-water emulsions. Kasiri and Fathi [112] extracted and purified CNC from PS (diameter 36.6 nm ± 8.9 nm) and evaluate its capacity to encapsulate peppermint oil. Their results showed that diffusion transport was the main mechanism for the release of peppermint oil from CNC while no significant differences in the crystallinity of CNC occurred after encapsulation. Furthermore, Kasiri and Fathi [113] evaluated the emulsifier ability of CNCs as a pickering agent in oil in water emulsions. These authors found that by increasing CNC concentration from 0.1% to 1.5%, the size of the emulsion droplets significantly decreased from 17.31 µm to 2.34 µm while the stability of the emulsions against temperature, stresses and storage time were enhanced. Therefore, they could conclude that the potential application of CNC from PS in the food industry is remarkable.

Moreover, pectin extracted from PGH is a promising encapsulation material. Its use has several benefits, such as being an emulsion stabilizer, it has gelling properties and it is generally considered a safe ingredient. Barış et al. [114] evaluated the potential use of the extracted pectin as an emulsifying agent in an oil-in-water emulsion.

As previously explained, PGH is a good source of bioactive compounds, but their application in food has several limitations. The PC may be lost during the food processing, storage time or digestion process, and in addition, they would leave to unpleasant taste in the products. Besides, the PC may present with low bioavailability in the food matrix because of their interaction with other components [115]. Therefore, recent reports have indicated that the encapsulation of bioactive compounds from pistachio waste would be a possible solution to overcome these problems. Ghandehari et al. [116] achieved the encapsulation of PGH PC by spray-dryer using maltodextrin as a carrier? and they showed that the microencapsulation improved the thermal and storage stability of PC. Moreover, Rafiee et al. [115] prepared nanoliposomes of PGH PC with lecithin (1%; particle size 92.05 nm ± 0.59 nm). These nonoliposomes were considerable stable during 2 months at 4℃, remaining approximately 75% of the phenolics in the nanoliposomes after that period with a slightly increase (3.85% increase) in the particle size. Finally, Oskoueian et al. [117] extracted PGH PC with ethyl acetate, incorporated them in nanoliposomes (96.3 nm ± 7.18 nm) and analyzed their antioxidant activity against free radicals. However, these authors did not evaluate their addition into a food material, but indicated their potential application in the pharmaceutical industry.

Other authors analyzed the incorporation of encapsulated PGH phenolics in food products such as mayonnaise [118], soybean oil [14], ice cream [119] and as a preservative for fruits [120]. A strategy for preventing lipid oxidation is the incorporation of antioxidant compounds. The food industry uses antioxidants molecules such as tert-butyl hydroquinone (TBHQ), butylated hydroxyl anisole (BHA), and butylated hydroxyl toluene (BHT); although the actual tendency is to search natural antioxidants. As it was previous mentioned, PGH is a good source of polyphenols with antioxidant properties. Therefore, Rafiee et al. [118] encapsulated PC from PGH extract into nanoliposome systems using a suspension of lecithin and water. The purpose was to incorporate them in mayonnaise and evaluate the physicochemical characteristics and microbial properties during four months of storage at 25°C. The encapsulated PC acted as antioxidants by reducing peroxide and thiobarbituric acid values. In this food system, encapsulated PGH extracts demonstrated an important inhibitory effect on microbial growth; some of the PC presented antimicrobial effect. The access and release of PC is facilitated by the affinity of liposomes for the cell membrane. This mayonnaise presented higher taste score and overall acceptability by sensory evaluation with semi-trained panelist.

Good results were also found when incorporating these encapsulates in soybean oil [14]. Nanoliposomes containing 500 ppm of PC from PGH allowed to obtain a stable soybean oil with antioxidant activity during storage demonstrated by the low peroxide and thiobarbituric acid value, primary and secondary products of lipid oxidation. They attributed this benefit to the control release of phenolic compound from liposomes, depending on the type of bounds between phenolics and phospholipids.

It was feasible to produce an ice cream enriched with microcapsules of pistachio peel extract (MPPE) [119]. Different percentages of microcapsules (0–2%) were added before the ice cream pasteurization stage. The microcapsules were made with maltodextrin. Textural parameters were evaluated, finding that viscosity, hardness and stickiness increase when the microcapsules of pistachio are incorporated. The authors concluded that MPPE improved the melting resistance, antioxidant activity and total phenolic content of the ice cream, without affecting sensorial properties.

The encapsulation of essential oil from Pistacia atlantica subsp. into chitosan nanoparticles allowed to demonstrate in vivo antifungal effect on strawberry fruit against Botrytis cinereal [120]. On the eighth day of storage the strawberry fruit immersed chitosan nanoparticles showed symptoms of spoilage, compare to the spoilage revealed on the control at the fourth day. Growth retardation of Botrytis (B.) cinereal was also demonstrated on the treated fruit. These results promise an alternative to extend the shelf-life of strawberries.

Although pistachio trees show good adaptability to a variety of climate conditions, the quality of the product can decline because of intense optical radiation and high temperatures [121]. Therefore, the development of new techniques to determine the most suitable sites for pistachio cultivation is of major importance. Everest [122] evaluate the requirements for pistachio cultivation and transferred the data to a geographic information system (GIS). With overlay analysis, these authors were able to determine the most suitable places for pistachio production. Similar methodologies were used to identify the optimal area for medicinal plants through the analytic hierarchy process (AHP) and GIS [123]. Moreover, the population growth increases the need for land for non-agricultural proposes and intensifies the competition for territory. In order to overcome these problems, Aliabad et al. [124] developed a new method for monitor of new constructions in urban areas, using imaging by unmanned aerial vehicle (UAV) and the time series of Sentinel-2 images. Therefore, image analysis could be a good option to analyze the best location for pistachio production. Future studies should analyze the association between the geographical and climate characteristics and the nutritional profile of the pistachio nut.