Edible seeds from Cucurbitaceae family as potential functional foods: Immense promises, few concerns

Biomedicine & Pharmacotherapy 91 (2017) 330–337

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Edible seeds from Cucurbitaceae family as potential functional foods: Immense promises, few concerns Seema Patela,* , Abdur Raufb,** a b

Bioinformatics and Medical Informatics Research Center, San Diego State University, San Diego 92182, USA Department of Chemistry, University of Swabi, Anbar 23561, Khyber Pakhtunkhwa, Pakistan

A R T I C L E I N F O

Article history: Received 15 March 2017 Received in revised form 10 April 2017 Accepted 20 April 2017 Keywords: Cucurbitaceae Seeds Polyunsaturated fatty acid Functional food

A B S T R A C T

Cucurbitaceae family members such as pumpkin and watermelon have seeds that are discarded as the by-products of food processing. However, they have been discovered to contain a rich repertoire of nutrients such as proteins, unsaturated fatty acids, phenolic acids, carotenoids, tocopherol, phytosterol, squalene etc. Biological assays have proven the seed extracts to exert antioxidative, hypoglycemic, anticancer, antihypertensive, cardioprotective, antilipemic, gynoprotective, and anthelmintic properties. Further, the seeds do not contain any major anti-nutrients. Phytoestrogens like b-sitosterol occur, which might be acting as agonists or antagonists of estrogen and testosterone, given their validated role in gyenic and prostate health. Few instances of intestinal bezoar, and allergy, following pumpkin seeds consumption have emerged. After the risk-benefit analysis though exhaustive literature search, it can be suggested that these seeds are underutilized and they can be used to formulate a myriad of nutraceuticals. © 2017 Elsevier Masson SAS. All rights reserved.

Contents 1.

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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Phytochemistry of these seeds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1. Biological properties of the edible Cucurbitaceae seeds . . . . . . . . . . . 1.2. Antioxidant property . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.1. 1.2.2. Anti-inflammation and immunomodulation property . . . . . Hypolipidemic, antihypertensive and cardioprotective effect 1.2.3. Hypoglycemic effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.4. Anticancer property . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.5. 1.2.6. Effect on urinary health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gender-specific issues and their amelioration . . . . . . . . . . . . 1.2.7. 1.2.8. Anthelmintic effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Wound healing effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.9. 1.3. Risks of the Cucurbitaceae seed products . . . . . . . . . . . . . . . . . . . . . . Future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction * Corresponding author at: Bioinformatics and Medical Informatics Research Center, San Diego State University, 5500 Campanile Dr San Diego, CA 92182, USA. ** Corresponding author. E-mail addresses: [email protected] (S. Patel), [email protected] (A. Rauf). http://dx.doi.org/10.1016/j.biopha.2017.04.090 0753-3322/© 2017 Elsevier Masson SAS. All rights reserved.

Cucurbitaceae family (gourd family) encompasses several edible plants belonging to the genera Cucurbita, Citrullus, Cucumis, Momordica, Benincasa, and Luffa, among others [1,2]. These fruits

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and vegetables include pumpkin, winter melon, squash, zucchini, watermelon, cucumber, bitter melon, ribbed gourd, luffa etc. Most of the plants have been cultivated for consumption, since ages. The young stems, leaves, flowers of some plants in this family and most fruits (pepo) are culinary articles. The fleshy fruits are used for salad (cucumber, watermelon), stir-fry (squash, zucchini, bitter melon), curry (pumpkin), pie (pumpkin), and pasta (zucchini) among a myriad of other uses [3]. Among the Cucurbitaceae members, pumpkin (Cucurbita sp.), winter melon (Benincasa sp.) and watermelon (Citrullus sp.) seeds are big, abundant, and edible. Yet, these seeds are mostly discarded as agro-industrial wastes. In some geographical regions, pumpkin seeds are relished toasted. Some food stores sell the hull-less, processed seeds as ‘pepita’. Pumpkin seeds are pressed to extract oil, which are used for cooking [4] or as emollients. Watermelon seeds are sold as snacks. Winter melon seeds are used for dry snacks in India. However, the real potential of these nutrition-packed seeds has hardly been tapped. As food security is a real challenge in current times and future, wasting any source of nutrients is almost criminal. So, these seeds deserve attention and assessment as a dietary component. Certain Cucurbitaceae family seeds have found usage in folkloric medication. Pumpkin seeds are used in Eritrea, Africa to treat tapeworm [5]. Other traditional usages include the remedy of kidney, bladder and prostate disorders [6]. The nutritional importance of pumpkin seeds had been reviewed before [7]. Here, pumpkin as well as winter melon and watermelon seeds have been assessed as functional food ingredients. Though the seeds of latter two Cucurbitaceae members are not as popular as that of pumpkins, they are getting attention of late. This review aims to shed light on the food potential of these underutilized nutrition sources. Not only pros, but the cons have been discussed here, to project an unbiased picture. 1.1. Phytochemistry of these seeds The edible Cucurbitaceae seeds are flat, oval and of diverse colors. Among others, pumpkin (Cucurbita maxima, C. pepo and C. moschata), winter melon (Benincasa hispida), and watermelon (Citrullus lanatus) seeds hold the highest food value. The seed flesh is nutty in taste and is rich in protein, polyunsaturated fatty acids (PUFA), minerals (magnesium, phosphorous, copper and potassium, iron, zinc, manganese), carotenoids, b-carotene, and g-tocopherol. Vitamin E or g-tocopherol content is particularly high [8]. C. maxima seed had oil content of 11 to 31%, of which 73.1 to 80.5% was total unsaturated fatty acid [9]. Total tocopherol content in pumpkin seeds was measured to be 15.9 mg/100 g [10]. Higher tocopherol content was determined in the extracts of C. pepo (15 mg/100 g) compared to that of C. maxima (12 mg/100 g). In the total tocopherol extracts, g form was consistently higher over the a form [11]. Watermelon seed oils showed high total tocopherol and phenolic contents [12]. Watermelon seed meal has proteins like globulin, albumin and glutelin [13]. Major fatty acids of both pumpkin and watermelon include linoleic acid, followed by oleic, palmitic and stearic acid [8,14]. Phenolic acids in C. maxima seed oil included protocatechuic, caffeic, syringic, vanillic, p-coumaric and ferulic acid, of which syringic acid was predominant (8 mg/100 g) [15]. Quercetin and rutin were isolated from B. hispida seeds using High performance liquid chromatography (HPLC) [16]. Phytosterols like b-sitosterol (13–25 mg mg/100 g) have been detected in pumpkin seeds [10,17]. Squalene, a highly unsaturated hydrocarbon of triterpenoid family is present in the unsaponifiable fraction of pumpkin seeds (89 mg/100 g) [10,18]. Also, nitrogen-containing compounds (Cucurbitacin B and E, cucurbitin) [2,19], and glucosides (saponins) are present in the seeds. A water-soluble polysaccharide fraction from C. maxima exerted DPPH radical scavenging and superoxide dismutase-like activity [20]. Hot water

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extraction, ethanol precipitation and purification of pumpkin seeds led to the discovery of a protein-bound polysaccharide [21]. The contents of above phytochemicals vary based on the cultivar, season of harvest, soil and climates [22,23]. Further, the oil extraction method plays decisive role in antioxidant content. Microwave-assisted aqueous enzymatic [24] and ultrasoundassisted [25] oil extraction methods have been found more effective than other existing methods in retention of antioxidants in the oil. The content of trans fatty acids was higher in roasted seed oil (at most 0.39%) than in cold-pressed oil (at most 0.05%) [26]. It suggests that the cold-pressed oil extraction method is better as the trans fatty acids adversely affect cardiovascular health, causing coronary heart diseases [27]. Table 1 presents the components in pumpkin seeds, their nutrient value, and the percentage of Recommended Dietary Allowance (RDA). 1.2. Biological properties of the edible Cucurbitaceae seeds In vitro and in vivo assays have validated the multiple nutritional benefits of these seeds. Some major biological roles have been discussed below, along with the intervened mechanisms. Fig. 1 shows the nutrients conferring the biological benefits. 1.2.1. Antioxidant property The administration of pumpkin seed protein isolate to CCl4intoxicated rats exerted antiperoxidative properties, as determined from post euthanasia-tissue analysis [28]. Antioxidants of pumpkin seed oil resulted from phenolic compounds such as tyrosol (phenylethanoid), vanillic acid, vanillin, luteolin and sinapic acid [29]. Pumpkin seeds, when extracted with 50% Table 1 Bioactive components and their percentages in pumpkin seed (Nutrient value per 100 g). Courtesy: USDA National nutrient database. Principles

Nutrient value

Percentage of RDA

Energy Carbohydrates Protein Total fat Cholesterol Dietary fiber

559 Kcal 10.71 g 30.23 g 49.05 g 0 mg 6g

28% 8% 54% 164% 0% 16%

Vitamins Folate Niacin Pantothenic acid Pyridoxcine Riboflavin Thiamin Vitamin A Vitamin C Vitamin E

58 mg 4.987 mg 0.750 mg 0.143 mg 0.153 mg 0.27 mg 16IU 1.9 mg 35.10 mg

15% 31% 15% 11% 12% 23% 0.5% 3% 237%

Electrolytes Sodium Potassium

7 mg 809 mg

0.5% 17%

Minerals Calcium Copper Iron Magnesium Manganese Phosphorus Selenium Zinc

46 mg 1.343 mg 8.82 mg 592 mg 4.543 mg 1233 mg 9.4 mg 7.81 mg

4.5% 159% 110% 148% 198% 176% 17% 71%

Phyto-nutrients Carotene-b Crypto-xanthin-b Lutein-zeaxanthin

9 mg 1 mg 74 mg

– – –

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Fig. 1. Cucurbitaceae family seed nutrients and their biological roles.

ethanol, have high antioxidant activity [30]. Pumpkin seed oil (1.5 mL/kg/day for 21 days) when administered to mice stressed with aflatoxin, lowered the toxic effects of the mycotoxin [31]. Sacrificing followed by tissue analysis revealed the increased content of antioxidative parameters (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)), and declined oxidative (malondialdehyde (MDA)) activities. On hydrolysis of the protein isolates of pumpkin seeds, antioxidative peptides were obtained. At optimal hydrolytic conditions of temperature 50  C, pH 2.5, substrate concentration of 0.05 g/ml and hydrolyzing period of 5 h, the scavenging activity of DPPH radical was the highest (92.82%) [32]. Pumpkin seed oil supplementation attenuated the cytotoxicity and genotoxicity of the immunosuppressive agent azathioprine, as observed from the plasma lipids and blood pressure profile. Restoration of glutathione content and DNA integrity was also noticed following the supplementation [33]. 1.2.2. Anti-inflammation and immunomodulation property Inflammation, hallmarks of which include calor (heat), dolor (pain), rubor (redness), and tumour, is a necessity for survival, which however, becomes detrimental when the homeostasis is broken [34,35]. Allergies, auto-immune and geriatric degenerative ailments are the self-damaging facets of inflammation. A study found that the consumption of dietary milled sesame/pumpkin/ flax seed mixture by hemodialysis patients lowers the inflammation markers as triglyceride, CRP (C-reactive protein), TNF-a, and IL-6 levels [36]. Immune-potentiation property of pumpkin seeds at a dose of 7.6 g/kg in mice model was observed. The extract when supplemented for 7 days, increased lymphocyte counts and enhanced phagocytic activity was noticed [37]. Pumpkin seed oil was incorporated into nanoemulsion system, and tested for therapeutic potential. At 10% ratio of the system, it inhibited the progression of fatty liver to steatohepatitis, as determined from low MDA and TNF-a content [38]. 1.2.3. Hypolipidemic, antihypertensive and cardioprotective effect Pumpkin seed oil supplementation (40 mg/kg for 5 days/week for 12 weeks) to female rats prevented the adverse plasma lipids

and blood pressure profiles associated with estrogen deficiency [39]. In a randomized, double-blinded study, pumpkin seed oil when administered to postmenopausal women at a dose of 2 g/day for a 12 week duration led to increased concentration of high density lipoprotein (HDL) cholesterol and decreased diastolic blood pressure [40]. Also, perimenopausal symptoms as hot flushes, headaches and joint pains subsided following the supplementation [40]. The effect of treatment with pumpkin seed oil on hypertension model of rats was studied. Oral administration of pumpkin seed oil (40–100 mg/kg) for 6 weeks was followed by haematological and histological profiling. The treatment reduced blood pressure, and MDA level [41]. Pumpkin seed oil when substituted for saturated dietary oil, led to the amelioration of metabolic and cardiovascular disease [42]. 1.2.4. Hypoglycemic effect Diabetes mellitus is a chronic, metabolic disease, afflicting mankind like an epidemic. A mixture of pumpkin seed and flaxseed (Linum usitatissimum) when fed to diabetic rats, the level of plasma enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) caused by liver lesions lowered [43]. Also, the level of antioxidant enzymes (CAT, SOD, and GSH-Px) were restored [43]. The antidiabetic activities of the tocopherol fraction of C. pepo raw seeds in diabetic rat model were investigated. The extract (108 mg/100 g) reduced oxidative markers. Also, the caecum and pancreases tissue morphology was found to be improved [44]. Pumpkin seed extracts have components as trigonelline (an alkaloid formed from niacin), nicotinic acid, and D-chiro-inositol which were found to be the hypoglycaemiaexerting compounds [45]. 1.2.5. Anticancer property A novel ribosome-inactivating protein (RIP) moschatin from the mature seeds of pumpkin (C. moschata) was isolated [46]. This rRNA N-glycosidase when conjugated with anti-human melanoma monoclonal antibody (McAb) Ng76, a novel compound moschatinNg76 was developed. This immunotoxin could inhibit the growth of targeted melanoma cells M21 [46]. Oral administration of pumpkin seed oil (2–4 mg/100 g for 20 days) inhibited the

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testosterone-induced hyperplasia of the prostate, which is expected to be beneficial for the management of benign prostatic hyperplasia [47]. In a randomized, double-blind study, the combination of pumpkin seed oil (320 mg/day) and saw palmetto (Serenoa repens) oil (320 mg/day) was effective against benign prostatic hyperplasia [48]. Referring to another study, the efficacy on benign prostatic hyperplasia might be due to b-sitosterol [49]. A 12 month treatment of benign prostatic hyperplasia patients with pumpkin seed diminished the pathological symptoms [50]. The hydroethanolic extract of C. pepo seeds reduced viability of the cell lines of prostate cancer (LNCaP (androgen sensitive) and DU145 (androgen insensitive)), breast cancer (MCF-7 (ERa positive)), and colorectal adenocarcinoma (Caco-2) [6]. B. hispida seed oil (20 and 40 mg/kg) exhibited inhibition of 5a-reductase activity in in vitro studies. Ethanolic extract did not exhibit significant inhibitory potential in vitro. Further in vivo study showed that B hispida seed oil can inhibit testosterone-induced hyperplasia of the prostate in the test rats [51]. A study was carried out to evaluate the antiangiogenic effect of the seed extract of B. hispida Cogniaux. It was found that the seed extract decreased bFGF (basic fibroblast growth factor), the angiogenic factor found in tumors. Inhibition of angiogenesis in vivo was observed. Further, the seed extract showed no cytotoxicity on HUVECs (Human Umbilical Vein Endothelial Cells) and normal fibroblast cells [52]. Antiproliferative ability of the oxidized tetracyclic triterpenoid cucurbitacin B and E has been validated through the cancer cell lines such as bladder cancer, hepatocellular carcinoma, pancreatic cancer, breast cancer, and leukemia, among others [19]. 1.2.6. Effect on urinary health Urinary disorders can occur due to multiple malfunctions such as bladder and urinary tract infections, thyroid perturbations, other hormonal imbalance, chronic kidney disease etc. [53]. Oral intake of pumpkin (C. maxima) seed oil extracts at a dosage of 10 g of oil/day for 6–12 weeks reduced the bladder over-activity in patients [54]. The combination of pumpkin seed and soy (Glycine max) germ extract, when administered for 12 weeks led to reduction in urination, and incontinence frequency [55]. Bladder stone formation is debilitating. Pumpkin seeds consumption has been claimed to prevent crystal formation (oxalcrystalluria) and to avert bladder stones, owing to its abundance in phosphorus, though it remains to be validated. 1.2.7. Gender-specific issues and their amelioration Androgenetic alopecia or common baldness is a condition of progressive scalp hair loss, more frequent in males [56]. Receding hair density is the resultant of testosterone metabolite dehydrotestosterone (DHT) on the hair follicles [57]. The enzyme 5-a reductase has been found responsible for excess DHT generation [56]. A randomized, placebo-controlled study showed that the treatment with pumpkin seed oil (400 mg/day) for 24 weeks increased hair counts [58]. Pumpkin seed oil sterols are likely to be blocking the activity of 5-a reductase and slowing down the progressive alopecia [58,59]. 1.2.8. Anthelmintic effect Pumpkin (C. maxima) seed extracts exerted anthelmintic effect on rat models of infection. The inhibitory mechanism of the extract was by the impairment of the nematode tegument and affecting their motility [60]. The administration of pumpkin seed meal (1 g/ kg) could control gastrointestinal nematodes in infected ostriches [61]. A combination of pumpkin seeds and areca nut (Areca catechu) extract inhibited the taeniasis-causing Taenia spp. [62]. A case study reports that Taenia solium infection might be treated using pumpkin seed extracts [63]. Pumpkin seed ethanolic extracts could inhibit the nematode Heligmosoides bakeri egg hatching,

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larval stages and motility [64]. Alkaloids like berberine and palmatine were detected in the extract [64]. Both these alkaloids from diverse plant sources have been validated to exert antimicrobial effect and widely regarded as pharmaceutical candidates [65,66]. 1.2.9. Wound healing effect In rat model of wounds, the topical application of pumpkin seed oil (0.52 mL/mm2) could heal the lesions [4]. The mechanism was by the induction of re-epithelialization and organization of collagen fibers [4]. A legion of plant-derived oils have been proven to heal wounds on topical application, by promoting collagen synthesis, collagen cross-linking, differentiation of fibroblasts, neovascularization, up-regulation of TGF-b, tissue remodeling, and wound shrinkage [67,68]. 1.3. Risks of the Cucurbitaceae seed products No plant is altogether free of anti-nutrients. The plants from Cucurbitaceae family too have antimicrobial proteins for defense purposes, which if consumed in high amount or too regularly, can prove detrimental to the human body. High dosage ingestion of the pumpkin seeds can cause cramps and stomach pain [69]. Case studies of rectal seed bezoars (a mass of indigestible substance blocking the digestive system), following pumpkin seed consumption have come forth [69]. This problem might be due to the indigestible hull of the seed, which ought to be removed before consumption. Allergy to nuts, be that ground nuts (peanuts) or tree nuts (pine nuts, cashew, walnut etc.) is well-substantiated [70,71]. Lipid transfer protein (LTP) has been identified as the cause of the immune manipulation [70,71]. Allergic response to pumpkin nuts have also been noticed, though instances are rare, considering its regional popularity only. The IgE-mediated hypersensitivity in atopic people leads to itching, swelling, edema, and asthma [72]. The pumpkin oil forms foam, which is a negative aspect. Saponin has been detected in C. pepo seed extract [64]. So, saponin is likely to be the foaming component. Saponins are well-established as anti-nutrients, with their tissue necrosis and gut permeability alteration property proven adequately [73,74]. Also, other antinutritional compounds like raffinose family of oligosaccharides (RFOs) (stachyose, raffinose, verbascose etc.), trypsin inhibitor, phytic acid, and tannins have been detected in both the pumpkin and watermelon seed flours [75]. The RFOs are regarded responsible for flatulence, and bloating [76–78]. From brown pumpkin C. moschata seeds moschin proteins have been isolated, in their two isoforms (a and b). These proteins are homologs of insect programmed-cell death gene product and the storage protein 2S albumin. The moschins inhibited translation in the rabbit reticulocyte lysate system [79]. RIPs of plants are their ‘defense and offense components’ [80,81], and can exert toxicity on prolonged consumption. Though moschins have not been studied much, their homology to well-characterized allergens and toxins raises their safety risk. Cucurbitacins 1 and 2 extracted from the root of a flowering vine Trichosanthes kirilowii from Cucurbitaceae family had tyrosinase inhibitory activity [82]. This enzyme is critical for melanin synthesis as well as cancer cell metabolism [82]. Cucurbitacin does not occur in pumpkin seed itself, but is synthesized in the germinating seeds. 1.4. Future perspectives Pumpkin seeds also showed compatibility with other nutrients as flaxseed (Linum usitatissimum), sesame (Sesamum indicum) seed and purslane (Portulaca oleracea). Watermelon seeds has high content of protein [13]. Based on the nutritional benefits of these seeds, several food products have been formulated such as ready-

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Fig. 2. Hormone receptor manipulation by Cucurbitaceae family seed phytoestrogens.

to-eat cereal, snack food, infant food, bakery products and ground meat formulations [75]. Watermelon seeds concentrates when fortified to wheat flour at 7.5% could be used to make cookies [83]. Formulations of bread with 5% pumpkin seeds (containing 31.48% dietary fibre) had good acceptability and sensory scores [84]. The replacement of wheat flour with 33% pumpkin seed flour increased the nutritional and gustatory value of muffins [85]. The gluten-free corn flour pasta containing 25% pumpkin flour garnered higher preference over unamended pasta as the former had better color, texture, and taste [86]. These products are likely to be helpful particularly for developing countries where nutritional deficiency is often inherent. Only a handful of countries like Slovenia, Hungary, Serbia, Austria etc. make use of these seeds in food formulations [8,87]. Other countries also should utilize the nutrients of the edible Cucurbitaceae seeds. Other research groups have also recommended the integration of these seed extracts in immunonutrient, cosmetics, pharmaceuticals preparations etc. [15,37]. The health benefits of pumpkin seeds are clearly exciting. However, it was noticed that a great deal of the biological intervention arises from the phytoestrogens. Phytoestrogens, the steroidal compounds from plants are ubiquitous in our diet [88– 90]. When consumed in higher dosages, these phytoestrogens manipulate human endocrine systems. Estrogen, the 17b-estradiol is a vital signaling molecule of the body; however, excess production of estrogen or exposure of the body to ‘estrogen mimics’ leads to the aberrant expression of estrogen receptors (ERs) [91], setting the stage for cancers [92], auto-immune diseases and neuropathologies. Phytoestrogens can bind to the ERs, fueling estrogen activity or the phytoestrogens can occupy the ER, preventing ligation with endogenous estrogen, thus exerting anti-estrogen effect [93,94]. Though it is still under dispute, phytoestrogen can act as selective estrogen receptor modulators (SERMs), and can influence endocrine signals [93,94]. Most phytoestrogens belong to lignan (diphenolic compounds) [95], isoflavone (a type of flavonoid) [96], or coumestan (polycyclic phenolics) [97] group. Antioxidant, cytotoxic, cardioprotective, neuroprotective, antiviral, anti-bacterial, immunosuppressive, and gyenic health-restorative properties of phytoestrogens have been

reported [98–101]. Fig. 2 shows the hormone receptor manipulation by phytoestrogens. While occasional consumption of these Cucurbitaceae seed products seems harmless, regular intake might have consequences. Studies ought to investigate it the phytoestrogens are carcinogenic. Also, assuming the above-discussed Cucurbitaceae seed nutrients to be panacea is over-simplification of the findings. Most diseases arise from persistent inflammation, and the underlying mechanisms are too intricate to resolve. Only, driving away the inflammatory agents can abrogate inflammation, which certainly is not easy. While therapeutic relevance is not yet adequately validated, the dietary importance of Cucurbitaceae seeds is proven. This review discusses the functional food relevance of only a few species from this family, because the usage of other seeds is either obscure or the seeds are too small to be economically harvested. The seeds of the vegetables like cucumber, zucchini, an bitter melon are consumed along with the vegetable, and not separated like that of pumpkin and watermelon. The food-challenged world ought to make the best possible use of these humble but wholesome seeds. 2. Conclusion The edible Cucurbitaceae seeds, which conventionally get discarded can be put to good use, for they are nutrient-dense and mostly anti-nutrient-free. They can be used in diverse forms to enrich food products. This review is expected to be a starting point for exploring these seeds-based food formulations. Also, this review is anticipated to stimulate research on other Cucurbitaceae seeds. Conflict of interest There is no conflict of interest in submitting this manuscript to this journal. References [1] S.S. Renner, A.K. Pandey, The Cucurbitaceae of India: accepted names, synonyms, geographic distribution, and information on images and DNA

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