Rose hip as an underutilized functional food: Evidence-based review

Accepted Manuscript Rose hip as an underutilized functional food: Evidence-based review Seema Patel

PII:

S0924-2244(16)30427-7

DOI:

10.1016/j.tifs.2017.03.001

Reference:

TIFS 1976

To appear in:

Trends in Food Science & Technology

Received Date: 25 September 2016 Revised Date:

9 December 2016

Accepted Date: 4 March 2017

Please cite this article as: Patel, S., Rose hip as an underutilized functional food: Evidence-based review, Trends in Food Science & Technology (2017), doi: 10.1016/j.tifs.2017.03.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Water Methanol Petroleum ether Ethyl acetate Hexane Chloroform Butanol

Antioxidative Antiinflammatory

Neuroprotective

Rose hip

Antiarthritic

Cardioprotective

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Renoprotective

Immunomodulatory

Antidiabetic

Anticancer

Antiobesity

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Antispasmodic

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Dermatoprotective

Flavonoid Carotenoid Tocopherol Galactolipid Ascorbic acid Tiliroside

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Nitric oxide synthase (iNOS) Cyclo-oxygenase-2 (COX-2)

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Activated cells

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Inhibition of: NO and prostaglandin production Reduction in: TNF-α, IFN-γ, IL-1β, IL-6 secretion

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Rheumatoid arthritis

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Downregulation of: Cytokine production MMP expression Galactolipid

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R. canina hip powder

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Rose hip as an underutilized functional food: Evidence-based review

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Seema Patel Bioinformatics and Medical Informatics Research Center, San Diego State University, 92182, San Diego, CA USA

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Short running title: Functional food potential of rose hips

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Key words: Rose hip; Rosa canina; functional food; tocopherol; ascorbic acid; galactolipid

*Corresponding author and address for correspondence:

Dr. Seema Patel Bioinformatics and Medical Informatics Research Center San Diego State University 5500 Campanile Dr San Diego, CA 92182 Email: [email protected] 1

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Abstract The search for nutrient-dense food source is a top-priority in today’s food-challenged world of multi-billion population. Food insecurity has become especially critical in developing countries, though

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potential sources of functional foods are being wasted right before our eyes. Rose hips, the fruits of rose plants (Rosa sp.) have been discovered to be rich in polyphenols (triterpene acids, flavonoids, proanthocyanidins, catechin), essential fatty acids, galactolipid, folate, vitamin A, C and E, mineral (Ca,

antioxidant,

anti-inflammatory,

immunomodulation,

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Mg, K, S, Si, Se, Mn and Fe), among other bioactive components. The extracts have proven to possess anticancer,

cardioprotective,

antidiabetic,

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neuroprotective, and antimicrobial properties. The extracts have been validated beneficial against nonalcoholic fatty liver disease, osteoarthritis, rheumatoid arthritis, obesity, cancer, kidney stone, depression, dermal issues. The mechanisms of therapeutic actions involved intervention in COX-2, iNOS, NFkappaB, PPAR-γ, p38 MAPK, Bak, Caspase-3, Ca++ channel blockade pathways. Apart from the Rosaceae family-characteristic allergenicity due to LTPs, the rose hips are free of other side effects. This holistic

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review, based on recent findings is excited to report rose hips as an emerging ‘functional food’ that

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deserves to be integrated to food platter without delay.

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Introduction As world population rises and natural resources dwindle, availing sufficient nutritious food for all becomes a serious issue (Karhagomba et al., 2013). Chronic micronutrient deficiencies affect over two

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billion people worldwide (Burchi, Fanzo, & Frison, 2011). Scale-up of food production in sustainable manner is a major challenge. In this regard, prospecting on natural food sources from biodiversity is a solution (Patel, 2015a). It turns out that several candidates with functional food relevance have been left

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out back then when food was abundant. Over the years, many underutilized food sources have been recognized and their nutritional and safety assessment is being conducted. Functional food potentials of

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the emergent foods are being profiled. The term ‘functional food’ embraces the edible sources with potential to nourish as well as improve antioxidant, mutagen-combating, and immune status of body. These are foods that furnish health benefits when fortified to regular diet on a regular basis at sufficient levels (Hasler, 2000).

One such unexploited nutrition source is rose hip, the fleshy fruit of roses. Family Rosaceae

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comprising of about 100 genera and 3,000 species is well-known to encompass a huge number of nutritious, palatable fruits like apple, pear, plum, cherry, peach, apricot, nectarine, almond, strawberry, raspberry, blackberry (Jung & Main, 2014). This family also contains a wide variety of ornamental plants

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including rose, flowering cherry, crabapple, quince and flowering pear. The genus Rosa encompasses about 100 species, with geographical distribution predominantly spanning Europe, Asia, and North

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America (Czyzowska, Klewicka, Pogorzelski, & Nowak, 2014). This genus is cultivated for the ornate flowers, where the bulbous fruits (hypanthium/ haw) located below the petal corolla, known as rose hips are discarded (Fig 1). The fruits contain numerous hairy achene-like seeds, which contain oil of emollient value. Figure 1 shows the rose hips and the seeds, which contain the oils. In certain cultures, rose hips are relished as food and in some other they are used as medicines. Consumption of rose hips is popular in European countries such as Poland, Portugal, Germany, Finland, Romania and Sweden, though they are especially popular in Scandinavian countries. The hips are processed into dessert, cookies, cakes, bread, jelly, marmalade, ice cream, pudding, custard soup, pie, 3

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syrup, herbal tea, beverages etc. (Dobosch, Gomez Zavaglia, & Kuljich, 1995). R. canina hips are widely consumed in countryside Portugal (Barros, Carvalho, & Ferreira, 2011). Nyponsoppa is a rose hip soup popular in Swedish cuisine. Hagebuttem is a traditional German rose hip soup. Dzika Róza Zachowaniais

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is a Polish rose hip preserve. Many berries, including rose hip in Finnish diet has been analyzed to be rich in the hydrolyzable tannins ellagitannins (Koponen, Happonen, Mattila, & Törrönen, 2007). In Romania, Rosa varieties and rose hips are abundant. They use the fruits in myriad forms as support therapies to

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supplement their vitamin A and C intake (Oprica, Bucsa, & Zamfirache, 2015). Palinka is a traditional Hungarian brandy made of fruits, which includes rose hips too (Small, 2014). British too relish their rose

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hip tea. Rose hip is a major herbal remedy in Turkey (Nur, 2010). R. canina fruits are also used as snacks in Turkey (Gürbüz, Ustün, Yesilada, Sezik, & Kutsal, 2003). In the Tokat region of Anatolia, Turkey, rose hips are processed into marmalade, and juice (Günes, 2013). In this country, rose hips are wellappreciated or their aromatic and medicinal properties (Patel, 2012). Rose hip is consumed as herbal tea and used as folk medicine in Iran for common cold, gastric disorder, gallstones, constipation and dropsy

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(Montazeri, Baher, Mirzajani, Barami, & Yousefian, 2011). Even in the USA, foragers relish it as snacks, syrup and sauce (Small, 2014). The Chumash Native Indians consumed the hips of R. californica (California wild rose) raw, cooked or brewed, as food and health. Samish Indians in Washington State

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consumed the hips as jelly and wine. R. canina L. and R. corymbifera Borkh fruits are consumed or topically applied for relief from cold, influenza, infections, diarrhea, inflammations, pain (Barros,

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Carvalho, Morais, & Ferreira, 2010). Hips from R. roxburghii Tratt., native to China is used for nutritional and medicinal purposes (Yan, Zhang, Lu, He, & An, 2015). R. multiflora hips have been used as dietary supplements and remedies for illnesses like cold, flu, inflammation, osteoarthritis, rheumatoid arthritis and chronic pain in China. Rose hip seed-derived oil has immense popularity as skin emollient in Chile. However, global consumption of rose hip is sparse. Only recently, as the craze for health foods escalated, they have garnered attention. Ever since the high-end analytical and phytochemical analysis techniques were adopted, the hips have been validated to have edible ingredients like other Rosaceae fruits. Facts are emerging that they are nutrient-dense and ideal candidate for dietary incorporation, for direct consumption 4

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or as food additives. Nutritional analyses have suggested the usage of rose hips as functional food and natural colorants in food technology (Rosu et al., 2011). With interesting findings on their functional food relevance, several patents on rose hip processing have been filed, and they are either being evaluated for

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nutritional uses or have entered to mainstream food processing. R. rugosa and R. canina wines revealed high antioxidant activity as measured by ABTS, and DPPH assays. Wine from R. canina showed appreciable anti-mutagenic effect in vitro, as lowered the level of the mutagen N-methyl-N′-nitro-

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nitrosoguanidine in a dose-dependent manner (Czyzowska et al., 2014). R. laevigata Michx hip-derived wine was evaluated for its phenolic composition and antioxidant activities by standard assays. The

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beverage had higher contents of total phenolics, total flavonoids, and oligomeric proanthocyanidins than Cabernet Sauvignon wine, suggesting usage of the rose hip juice to wine (Meng et al., 2012). R. canina hip addition to frankfurters acted as a partial substitute of the antioxidant sodium nitrite (Vossen, Utrera, De Smet, Morcuende, & Estévez, 2012). Rose hip addition to broiler meat numerically decreased 2Thiobarbituric Acid Reactive Substances (TBARS) (indicator of lipid oxidation prevention) and enhanced

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carcass weight (Loetscher, Kreuzer, & Messikommer, 2013). In the coming times, more rose hipvalorized food products are expected. However, what makes these hitherto obscure Rosaceae fruits worthy of functional food have been discussed in the following sections.

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Phytonutrients

Analytical studies have unveiled the presence of several nutrients in rose hips. The most

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significant are ascorbic acid (vitamin C), proanthocyanidins, galactolipids, and folate. Health benefits of these components and key findings pertaining to rose hips have been discussed below. Ascorbic acid as an adjunct therapy to cancer, cardiovascular ailments and cataract have been well-documented (Hoffer et al., 2015; Ohno, Ohno, Suzuki, Soma, & Inoue, 2009; Ravindran et al., 2011). Dual, antagonistic response of ascorbic acid towards cancer has been a bone of contention among researchers (Cabanillas, 2010; Carr, Vissers, & Cook, 2014; Ohno et al., 2009). Like most nutrients, the dosage determines therapeutic effect, which however cannot be fixed for a heterogeneous disease like cancer, which depends on age, gender, co-morbidities, among a range of other factors. Also, the dichotomous results regarding the function of 5

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ascorbic acid is likely to be due to the diverse study models. For in vitro condition, this vitamin in high concentration can reduce viability of cancer cell line; however; for in vivo condition, intravenous injection of this acid can or cannot reduce hypoxic extracellular acidic milieu, the characteristic of cancer,

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depending on numerous other variables (Ohno et al., 2009). Irrespective of these two contradictory schools of inferences, inclusion of this vitamin in diet is likely to improve redox status and health. Beneficial impact of this vitamin on cognitive decline and Alzheimer's disease has been verified

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(Harrison, 2012). The above health-promoting roles justify the supplementation of diet with ascorbic acid. The concentration of this vitamin were found to be 1,200 mg/L in R. rugosa and 600 mg/L for R. canina

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hips (Czyzowska et al., 2014). Phenolic acids, the prominent triterpene acids in rose hips have been identified as oleanolic acid, betulinic acid and ursolic acid (Saaby, Jäger, Moesby, Hansen, & Christensen, 2011). Flavonoids too abound in these Rosaceae fruits. Quercetin and ellagic acid are common flavonoids in them. Galactolipids, namely monogalactosyldiacylglycerols and digalactosyldiacylglycerol are accumulated in plant plasma membranes (Gaude et al., 2004). Isolation of these compounds in many

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green vegetables explains their abundance in chloroplasts and role in photosynthetic apparatus integrity (Christensen, 2009a). Some galactolipids have shown anti-inflammatory and antitumor roles (Lopes, Daletos, Proksch, Andrade, & Valentão, 2014). The galactolipid, 1,2-di-O-alpha-linolenoyl-3-O-beta-D-

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galactopyranosyl-sn-glycerol has been isolated from R. canina hips (Christensen, 2009b). A study revealed that galactolipid inhibited both mRNA and protein expression of inducible NO synthase and

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cyclooxygenase-2 (COX-2) in murine macrophages. Also, it prevented NF-kappaB/DNA complex formation and suppressed B16 melanoma growth in C57BL/6J mice (Hou et al., 2007). A galactolipid ((2S)-1,2-di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-β-d-galactopyranosyl glycerol) from R. canina with anti-inflammatory property has been identified (Cohen, 2012; Erik Larsen, Arsalan Kharazmi, Lars P. Christensen, & Christensen§, 2003). Lipophilic antioxidants like tocopherols and total carotenoid have immense health benefits. Rose hips have carotenoids as chlorophyll a and lycopene (Andersson, Rumpunen, Johansson, & Olsson, 2011). Seed oils recovered from R. canina L. hips were analyzed for their tocopherol and carotenoid contents using HPLC-DAD-MS (Fromm, Bayha, Kammerer, 6

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& Carle, 2012). Tocopherols and total carotenoid contents were quantified to be high (Fromm et al., 2012). Folates are essential for human health, as they serve as cofactors for many enzymatic reactions (Hanson & Gregory, 2011). Though animal-based foods are major sources of folate, some plants are rich

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reserves of the vitamin B as well, which includes Moringa oleifera (Saini, Manoj, Shetty, Srinivasan, & Giridhar, 2016). Rose hips have been shown to be a rich reserve of folate. The content ranges from 400600 mg/100 g based on dry matter and 160-185 mg/100 g based on the fresh weight (Strålsjö, Alklint,

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Olsson, & Sjöholm, 2003). Tiliroside (kaempferol 3-β-D-(6"-p-coumaroyl)-glucopyranoside), a glycosidic flavonoid contained in several dietary plants such as strawberry and raspberry also occurs in rose hips

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(Goto et al., 2012). Proanthocyanidins are oligomeric and polymeric end products of the flavonoid biosynthetic pathway (Dixon, Xie, & Sharma, 2005). These condensed tannins provide astringency to many plant parts. The flavan-3-ols catechin and epicatechin belonging to this group and have been implicated in biological roles (Dixon et al., 2005). Catechin, the most abundant flavan-3-ol in R. canina and R. micrantha have been measured to be 3.59 mg/100g) and 2.90 mg/100g, respectively (Guimarães et

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al., 2013). Apart from the above-mentioned phytochemicals the rose hip has been reviewed to contain flavonoid (rutin, quercetin), pectin, Vitamin A, vitamin B complex, vitamin E, also minerals like Ca, Mg K, S, Si, Fe, Se and Mn (Dubtsova et al., 2012; Patel, 2012). Anthocyanins, and dihydrochalcones are

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some other detected phenomic compounds (Ogah, Watkins, Ubi, & Oraguzie, 2014). A range of health roles have been assigned to these phytochemicals such as antioxidant, anti-inflammatory, anticancer,

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antidiabetic, and antimicrobial (de la Iglesia et al 2010). Berries and fruits are generally the best sources of proanthocyanidins, and a study found that rose hip have high concentration of proanthocyanidins as in cocoa derivatives (Hellström, Törrönen, & Mattila, 2009). The intervention of these phenolic compounds in apoptosis (up-regulation of pro-apoptotic mediators as TRAIL-DR4/-DR5 receptors), gene expression and transcription factors such as NF-kappaB have been investigated in recent times (Cos et al., 2004; Maldonado, Bousserouel, Gossé, Lobstein, & Raul, 2010).

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Validated biological roles of rose hips In vitro, in vivo and clinical case as well as cohort studies has validated pharmacological properties or rose hip derivatives. The sections below outline the key components and mechanisms responsible for

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these functions. Table 1. presents this data. Antioxidative

Oxidative stress is the underlying cause of a gamut of physical disorders cancer, allergy, diabetes,

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depression and others. Antioxidants to eliminate the stressors are necessary for health restoration. ABTS radical scavenging, cupric ion reduction, inhibition of lipid peroxidation are some of the standard assays

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to determine antioxidant properties. Oxidation ameliorative effect of freeze-dried powder of rose hips was investigated on erythrocytes in vitro. The fact that all sequentially eluted extracts contributed to protective effects on the erythrocytes indicates that rose hips contain a promising level of clinically-relevant antioxidant protection (Widén, Ekholm, Coleman, Renvert, & Rumpunen, 2012). R. laevigata Michx hip flavonoids could reverse induced hepatotoxicity in mice model. The

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flavonoid pretreatment attenuated serum aspartate transaminase (AST) and alanine transaminase (ALT) activities. Liver injury was healed and the level of antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH)) was improved. Malondialdehyde (MDA)

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content was decreased. DNA fragmentation and mitochondrial modification was attenuated. Downregulation of the protein expressions of CYP2E1, iNOS, NF-κB, Bak and Caspase-3 was observed

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(Zhang, Lu, et al., 2013). The effect of total flavonoids from R. laevigata Michx fruit on high-fat dietinduced non-alcoholic fatty liver disease was investigated. Gavage administration significantly decreased the relative liver weight, serum AST and ALT activities, the levels of serum lipid, LDL, blood glucose and insulin; suppressed lipid accumulation in liver; and increased serum HDL level (Zhang, Zheng, et al., 2013). Also, it enhanced SOD and GSH activity while decreasing the concentration of MDA and CYP2E1 expression. Mitochondrial membrane potential perturbation and ultra structural alterations was prevented. It inhibited hepatic lipid accumulation by suppressing the expressions of some key molecules in fatty acid

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synthesis pathway and promoting fatty acid β-oxidation (Zhang, Zheng, et al., 2013). The total flavonoids dose of 500mg/kg/day was selected as the safe level (Zhang et al., 2012). Oral administration of the flavonoid-rich extract from R. laevigata Michx fruit might help manage

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ischemic stroke due to its antioxidant, anti-apoptosis and anti-inflammatory properties (Zhang, Qi, et al., 2013). The healing mechanism was found to be the decreased DNA fragmentation, downregulation of p53, Apaf1, Fas, FasL, Bax, Bid, cytochrome C and active Caspase-3, -9 and -8; downregulation of NF-

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κB, iNOS, MMP-9, COX-2, TNF-α, IL-1β, IL-4, IL-6, p-JNK, p-ERK and p-p38 in MAPK pathways. On the other hand, upregulation of Bcl-2 was observed (Zhang, Qi, et al., 2013). Chronic mild stress-induced

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depression rat models were exposed to Rosa × damascena Mill. rose hip oil vapor at a dose of 0.15 ml/kg for 28 days. Histological analysis showed that the treatment with the oil vapor induced protective effects on oxidative stress in depression (Nazıroğlu, Kozlu, Yorgancıgil, Uğuz, & Karakuş, 2013). Tiliroside reduced neuro-inflammation in BV2 microglia by suppressing TNF-α, IL-6, nitrite and prostaglandin (PGE2) production, as well as iNOS and COX-2 protein expression (Velagapudi, Aderogba, & Olajide,

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2014).

Excess calcium oxalate causes nephrolithiasis or kidney stone (Finkielstein & Goldfarb, 2006). R. canina extracts proved effective as a preventive agent against the formation of the renal stones.

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Supplementation of the rose hip extract reduced the kidney and liver lipid peroxide levels to normalcy in rats (Tayefi-Nasrabadi, Sadigh-Eteghad, & Aghdam, 2012). The extract also lowered renal and urinary

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calcium contents, decreased the size and number of oxalate calculi in the kidneys, and significantly increased citrate excretion without changing the volume, pH, or urinary concentrations of oxalate in comparison with the control group (Tayefi-Nasrabadi et al., 2012). In another study, R. canina fruit extract exerted protective effects towards kidney when exposed to oxidative stress (Changizi Ashtiyani, Najafi, Jalalvandi, & Hosseinei, 2013). Ischemia and reperfusion were induced on the kidneys of anesthetized male Sprague-Dawley rats. Blood creatinine and urea concentrations were significantly lower in the R. canina hip-fed group. In this group, the degree of histological damage and the level of MDA were lower than the reperfusion group, while ferric reducing/antioxidant power level was 9

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significantly higher (Changizi Ashtiyani et al., 2013). R. canina hip extract reduced ROS production in oxidative-stressed colon cancer Caco-2 cell lines (Jiménez et al., 2016).

Immunomodulation and anti-inflammation

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Immune attacks to own body occur when homeostasis is broken by wrong lifestyle or age-related hormonal changes (Kuchroo, Ohashi, Sartor, & Vinuesa, 2012). Immune activation can be measured from the level of T-lymphocyte (CD3+, CD4+, CD8+), immunoglobulin (IgG, IgM, IgA) and complement (C3, C4) in blood and serum (Noris & Remuzzi, 2013). To overcome the adverse effects, modulation of the

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agitated immune system is required. Rose hips have shown promise in this regard. A standardized powder of R. canina L. hips exerted immunomodulatory effect in a study using human monocytic Mono Mac 6

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cells. The triterpene acid mixture (oleanolic, ursolic and betulinic acid) inhibited IL-6 and TNF- α release (Saaby & Nielsen, 2012). Urinary arsenic level is closely related to immune function suppression (Andrew et al., 2008). R. roxburghii tratt preparation, when ingested orally for one month can effectively improve immune function of arseniasis patients (Li et al., 2013).

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Inflammation is a form of immune perturbation, evoked to counteract pathogens, to heal injuries or the result of sensitization. Non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, and corticosteroids are commonly prescribed to heal osteoarthritic pain, which inhibits cyclooxygenase-2 (COX-2), reducing inflammation. Glucosamine sulfate taken orally at a daily dosage of 1,500 mg treats

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knee osteoarthritis symptoms (Herrero-Beaumont et al., 2007). However, the chemotherapeutics are

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expensive and exert side effects. To assuage the pain, stiffness and functional disability rose hip powder is commonly used as a remedy. Anti-inflammatory properties of rose hips have been well-studied. Among its parts, the seeds are the major contributors to the anti-inflammatory profile in the supplement preparations (Marstrand, Warholm, Kharazmi, & Winther, 2013). Anti-inflammation of rose hip extracts against bone and cartilage tissues have been well-investigated. Osteoarthritis is a degenerative, autoimmune disease in geriatrics, caused by the perturbation in the balance between formation and the destruction of cartilage due to wear and tear (Sinusas, 2012). Meta-analysis and randomized controlled trials indicate that R. canina hip powder reduce pain (Christensen, Bartels, Altman, Astrup, & Bliddal, 10

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2008). Standardized R. canina hip powder alleviated some pathologies (pain) of osteoarthritis (Saaby et al., 2011). A comparative study between glucosamine sulfate and rose hip powder in healing osteoarthritis was conducted. The former was used at a dose of 1,500 mg per day, while the latter was given at 4,500

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mg per day. Both the drug and rose hips could significantly reduce symptoms of knee pain and stiffness, after 3 weeks of treatment. By the end of the 8th week, rose hip showed better efficacy than glucosamine sulfate in term of total WOMAC (Western Ontario and McMaster Universities Arthritis Index) score

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reduction, and functional disability reduction, with less evidence and severity of adverse reactions (Petcharat & Wongsuphasawat, 2013).

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Rheumatoid arthritis is another type of arthritis caused by autoimmunity where activated cells release reactive oxygen substances. Standardized R. canina hip powder assuaged pain in rheumatoid arthritis as well (Willich et al., 2010). Intake of R. canina hip powder daily (Litozin®) at a dose of 10.5 g for 28 days improved antioxidant enzyme levels in rheumatoid arthritis patients (Kirkeskov et al., 2011). Rose hip powder and galactolipid GLGPG (galactolipid (2S)-1, 2-di-O-[(9Z, 12Z, 15Z)-octadeca-9, 12,

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15-trienoyl]-3-O-β-D-galactopyranosyl glycerol) attenuate inflammatory responses in different cellular systems (macrophages, PBLs (peripheral blood cells) and chondrocytes). The effects on cytokine production and matrix metalloproteinases (MMP) expression indicate that both forms of the extract down-

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regulate catabolic processes associated with osteoarthritis and rheumatoid arthritis (Schwager, Hoeller, Wolfram, & Richard, 2011). The mechanism of action was explained to be the inhibition of NO and

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prostaglandin production and reduced secretion of cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-12)/ chemokines (CCL5/RANTES, CXCL10/IP-10) (Schwager et al., 2011). In rat model of inflammation, R. multiflora hip powder had ameliorative effects. The bioactive components were unsaturated fatty acids, which acted by manipulating inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2). Inhibition of these enzymes reduced NO production and prevent inflammation (Guo et al., 2011). R. multiflora Thunb hip extract, given at a dose of 120mg/kg per day to rat models of rheumatoid arthritis improved antioxidative enzymes, reduced cartilage surface erosion and inhibited the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 (J. Wu et al., 2014). The chondroprotective effect of rose hip 11

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was reported to be concentrated in the lipophilic fraction (Chrubasik-Hausmann, Chrubasik, Neumann, & Müller-Ladner, 2014). Figure 2 shows the mechanism of arthritic anti-inflammation by rose hip ingestion. The gastroprotective effects of the alcoholic crude extract of R. canina fruits were evaluated in rat

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model. The extract inhibited the development of edema and prevented gastric lesions (Lattanzio et al., 2011). Oral administration of R. multiflora Thunb. hip exerted anti-inflammation by down-regulating the COX-2 expression and reducing NO production via inhibition of iNOS activity (Guo et al., 2011). R.

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moschata hips are used as a relief for abdominal spasm and diarrhea. The hydro-methanolic extract of the fruits showed antispasmodic effects in rabbit jejunal preparations. Also, in mice models, anti-diarrheal effect was observed, mediated through voltage-gated Ca++ channel blockade (Ali et al., 2014). The extract

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is suggested to possess Ca++ antagonist-like components, playing role in gut motility (Ali et al., 2014). Cardiovascular

Total flavonoids from R. laevigata Michx fruit proved effective in healing cardiovascular and cerebro-vascular diseases in a H2O2-induced damage in human umbilical vein endothelial cells (HUVECs)

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(Jia et al., 2012). The underlying mechanism was detected to be by lowering nuclear morphological damage, inhibiting the collapse of mitochondrial membrane potentials, reducing excessive reactive oxygen species generation, restoring glutathione level, decreasing caspase-3, -9 activities, and retarding

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DNA fragmentation (Jia et al., 2012). Daily consumption of 40 g of rose hip powder for 6 weeks significantly reduced the cardiovascular risks in obese individuals by lowering of systolic blood pressure,

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plasma cholesterol levels and low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio (Andersson, Berger, Högberg, Landin-Olsson, & Holm, 2012). Anti-obesity and anti-diabetic Dietary supplement (10-20 weeks) of rose hip prevented the development of diabetes in mouse. Down-regulation of the hepatic lipogenic proteins by the rose hip was implicated as the mechanism (Ulrika Andersson et al., 2011). Another study too reports that R. canina L. and its seed component tiliroside exhibit anti-obesity and anti-diabetic activities (Nagatomo, Nishida, Matsuura, & Shibata, 2013). The mechanism has been unraveled to be via the enhancement of fatty acid oxidation in the liver and 12

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skeletal muscle. The extract and tiliroside inhibited lipid accumulation in a dose-dependent manner in mouse T3-L1 cells (fibroblast-like cells capable of differentiating into adipocytes). Rose hip extract down-regulated peroxisome proliferator-activated receptor gamma (PPARγ) expression and suppressed

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lipid accumulation in white adipose tissue in high-fat diet-induced obesity mice model (Nagatomo et al., 2015, 2013). In another mice model study, it was found that tiliroside inhibits obesity-induced hepatic and muscular triglyceride accumulation. It enhances fatty acid oxidation by enhancing the adiponectin

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signaling associated with the activation of both AMP-activated protein kinase and PPARα and ameliorates obesity-induced metabolic disorders, such as hyperinsulinemia and hyperlipidemia (Goto et al., 2012).

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The hypoglycemic effect was observed which supported the traditional usage of rose hips as a folk remedy of diabetes in various cultures (Patel, 2012). Anticancer and antimicrobial

Cancer has emerged as a dominant cause of morbidity and mortality in recent times (Siegel et al., 2016). Plant phenolics are well known to build resistance towards carcinogenesis. In this regard, rose hip

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extracts have shown ample promise. R. canina hip-extracted polyphenols, dominated by quercetin and ellagic acid contribute to its anti-proliferative activity of HeLa, MCF7 and HT-29 cell lines (Tumbas et al., 2012). The cancer preventive action can be explained by the abundance of the carotenoid lycopene,

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known to scavenge ROS (Gupta et al., 2012). The findings above suggest that standardized rosehip supplements may be beneficial for cancer patients or survivors. Following 72h incubation, R. canina hip extract exerted cytotoxicity on colon cancer Caco-2 cell lines. This effect was explained to be via redox modulation,

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perturbation in cell cycling and apoptosis. This result can be a framework for further exploration of the efficacy of the extract on colorectal carcinoma. (Jiménez et al., 2016).

Bacteria can contaminate food and lead to multiple health issues. Rather than using chemical

additives, it is preferable to use natural ingredients to curb these pathogens. The antimicrobial activity of R. nutkana, and R. woodsii hip extracts were assayed using disc diffusion assays. Both the pericarp extracts showed yeast and Gram-positive bacteria-inhibitory effects, which was attributed to the phenolic contents (Yi, Jovel, Towers, Wahbe, & Cho, 2007a). The mechanism of pathogen eradication is likely to

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be the same as that of plant essential oils (Patel, 2015b). The rose oil components as citrenellol, geraniol and nerol are identified to mediate the antibacterial effects (Boskabady, Shafei, Saberi, & Amini, 2011). Cosmetics

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Cosmetology research has proven the benefits of rose hip oil in skin care. It has been shown to reduce skin pigmentation, manage acnes, heal scars and stretches, rehydrate skin, delaying wrinkling, among other dermatological benefits (Binic, Lazarevic, Ljubenovic, Mojsa, & Sokolovic, 2013; Datta,

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Mitra, Paramesh, & Patwardhan, 2011; Fujii, Ikeda, & Saito, 2011; Korać & Khambholja, 2011; Phetcharat, Wongsuphasawat, & Winther, 2015; Schagen, Zampeli, Makrantonaki, & Zouboulis, 2012).

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Even the skin specialists are recommending rose hip oil as natural skin-vitalizer. Natural, mild, sideeffect-free skin whitening agents are sought-after for cosmetic as well as clinical (melasma, hyperpigmentation etc.) purposes (Smit, Vicanova, & Pavel, 2009). The R. canina hip extract exerted melanogenesis-inhibiting effect on mouse melanoma B16 cells. Also, the pigment reduction ability of rose hips extract was observed in guinea pig skin (Binic et al., 2013; Fujii et al., 2011). Proanthocyanidins

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were implicated in the skin fairness induction. A common cellular targets for depigmentation is the enzyme tyrosinase and allied melanogenic enzymes (Ebanks, Wickett, & Boissy, 2009). Apart from that, regulation of melanocyte homeostasis, alteration of constitutive and facultative pigmentation and down-

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regulation of melanosome transfer to the keratinocytes can influence pigment formation (Ebanks et al., 2009). Rosaceae family member peach was verified to exert anti-melanogenesis effect and the mechanism

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was identified as the suppression of tyrosinase which acts by controlling the inhibition of phosphorylation of p38 MAPK (Murata, Takahashi, Nakamura, Itoh, & Matsuda, 2014). Safety of rose hips

While evaluating and recommending the food potential of a candidate, its health risks need to be emphasized. In this regard, several studies have assessed the threats associated with rose hips. Though the family Rosaceae encompasses a huge number of food plants, they are often linked to allergic reactions. Rosaceae fruit (strawberry, apple, pear, peach, plum, apricot, almond etc.) allergy includes oral symptoms, systemic inflammation, even anaphylaxis (Cianferoni & Muraro, 2012). Respiratory and 14

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dermal symptoms following occupational exposure to rose hips powder has been reported (Kwaselow, Rowe, Sears-Ewald, & Ownby, 1990). The sensitization has been found to be IgE-mediated (Demir, Karakaya, & Kalyoncu, 2002; Kwaselow et al., 1990).The Rosaceae species allergens show cross-

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reactivity among themselves and with other plants (Fernández-Rivas, van Ree, & Cuevas, 1997; Rodriguez et al., 2000). The allergens in Rosaceaee family members have been identified as lipid transfer protein (LTP) as in peach Pru p 3 (Novembre, Mori, Contestabile, Rossi, & Pucci, 2012). Rosaceae fruits

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as peaches, apricots, almonds are also reservoirs of cyanogenic glucosides (such as amygdalin, prunasin) (Chaouali et al., 2013; Sánchez-Pérez, Jørgensen, Olsen, Dicenta, & Møller, 2008). Upon hydrolysis these

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glycosides release hydrogen cyanide, which has been proven harmful to consumers. The cyanide inhibits mitochondrial electron transport chain (ETC), which leads to hypoxia, dizziness, nausea, diarrhea, convulsions, even coma and death (Chaouali et al., 2013). Rose hip being a member of this cyanogenesiscausing family deserves stringent profiling, though no literature in this aspect is available as of now. Also, while purchasing the rose hip oil-based cosmetics, consumers should be aware that the products also

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contain a number of chemicals, in the form of fixative, preservatives, dye, emulsifier, mineral pigments, etc. Even if the rose oil is harmless and emollient, the chemicals can cause skin inflammations or other systemic hypersensitivity. Many herbal products have been labeled as detrimental in recent times

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(Kaličanin & Velimirović, 2016).

Hurdles and Scopes of rose hip usage

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The above-cited findings are testimony to the fact that rose hips are nutrition-rich food candidates that ought to be included into food platter. However, some awareness needs to be generated and hurdles overcome for optimal efficacy, from health, economic and ecological perspective. It has been observed that the rose plant variety, ripening state and harvesting time play decisive role in the bioactive profile of rose hips (Demir, Yildiz, Alpaslan, & Hayaloglu, 2014; Roman, Stănilă, & Stănilă, 2013). Ripe hips have the highest tocopherols and β-carotene contents, whereas unripe hips have the highest levels of ascorbic acid (Barros et al., 2011). Also, altitude, water level, frost, other ecological/edaphological factors and interactions among them do play significant part (S. C. Andersson et 15

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al., 2011; Oprica et al., 2015; Roman et al., 2013). The components influenced by the above condition variability includes chlorophyll a and lycopene (S. C. Andersson, Olsson, Gustavsson, Johansson, & Rumpunen, 2012; Cunja, Mikulic-Petkovsek, Zupan, Stampar, & Schmitzer, 2015). Ornamental Rosa

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cultivars Repandia and Bonica have high β-carotene and lycopene content, respectively (Cunja et al., 2016).

The red, pink, purple-colored ripe rose hips are harvested during autumn (September and

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October) season (Oprica et al., 2015). So, it requires effective preservation strategies. Sun drying is a common way to store the hips, but they tend to render the product moldy in wet, cloudy climate. Thin

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layer hot air drying is another method for rose hip dehydration (Erenturk, Gulaboglu, & Gultekin, 2004). However, air drying has been known to deplete ascorbic acid of fruits. Freeze-drying is the opted method for commercial preservation and subsequent nutrient extraction (Widén et al., 2012). Optimal recovery of bioactive components from the rose hip extracts is paramount for high-quality supplements. Hexane, chloroform, ethyl acetate, and butanol are commonly-used organic solvents for the

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extraction. Traditional solvent extraction, ultrasound, microwave, subcritical and supercritical fluid extraction methods are some of the used methods for recovery of fatty acids. Counter-current chromatography is often paired with the above extraction techniques (Li, Guo, Liu, & Zhang, 2013).

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Ultrasound-assisted extraction of polyphenols from R. canina was carried out (Ilbay, Sahin, & Kırbaşlar, 2013). Optimization of the parameters by response surface methodology (RSM) revealed that ethanol

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concentration, extraction time and temperature played significant role in the yield. A 47.23 mg gallic acid equivalent/g dry matter was predicted at 40% ethanol composition, 50°C temperature, and 81.23 min of extraction time (Ilbay et al., 2013). Supercritical fluid extraction coupled with high-speed counter-current chromatography could be used to isolate formononetin, delphinidin, cyanidin, 5,6,4'-trihydroxy-7,8dimethoxy flavone, 5,3'-dihydroxy-7,8-dimethoxy flavone, and 5-hydroxy-6,7,8,3',4'-pentamethoxy flavone from R. damascene (S. Li et al., 2013). The analytical tools used for the bioactive (fatty acids, tocopherols, phenolics, flavonoids, carotenoids, gallic acid, cymosic acid, catechins, procyanidin-B2, hydroxycinnamic acid derivatives (chlorogenic, t-caffeic, p-coumaric, ferulic and sinapic acids), volatile 16

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compounds (alcohols, aldehydes, monoterpenes, sesquiterpenes), chlorophylls, ascorbic acid extraction include spectroscopic and fluorescence techniques like HPLC-RI, GC-FID, HPLC-ESI-MS (highperformance liquid chromatography-electrospray ionisation mass spectrometry), RP-HPLC-DAD, HPLC-

COSY, HSQC, HMBC, NOESY (X.-P. Wu et al., 2014).

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DAD-APCI(+)-MS (Zhong et al., 2016), SPME/GC-MS (N. Demir et al., 2014),¹H and ¹³C NMR, ¹H-¹H

Rosa species are varied, distributed globally. Till now, R. canina, R. rugosa are the most-studied,

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most-consumed species (Roman et al., 2013). Some other well-known species include R. multiflora, R. micrantha, R. cymosa Tratt., R. dumalis, R. eglanteria, R. laevigata. A plethora of other species specific

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to geographical regions as British Columbia (R. nutkana, R. pisocarpa, R. woodsii) (Yi, Jovel, Towers, Wahbe, & Cho, 2007b); South China (R. laevigata Michx.) (Meng et al., 2012); Turkey (R. gallica, R. hirtissima) (Demir et al., 2014)have been identified as well. R. foitida, R. pisiformis, R. rubiginosa, R. vosagiaca, R. subcanina, R. villosa, R. damascena, R. sericea, R. soulieana, R. pulverulenta, and R. caryophyllacea are some other studied species. It has been validated that non-hybrid roses yield more

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nutritious hips than the ornamentally cultivated ones. A study found the R. canina hips to have maximum antioxidant and R. dumalis subsp. boissieri hips to have the highest fat content (Ercisli 2007). These nutritious berries can be collected from sea shores, woodlands, meadows, chaparral canyons, homestead

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gardens. Figure 3, 4 and 5 show ripe rose hips growing wild in different parts of the USA. While people are showing interest to consume exotic functional foods like acai berry, quinoa etc., letting locally-grown

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nutrient reserves to go waste is unreasonable. If popularity of rose hips as food and dietary supplement picks up, the plants might be over-exploited. It requires species conservation efforts in the form of germplasm conservation. Conclusions

A myriad of, multi-paradigm studies have supported the nutraceutical potency of rose hips, attributing them to their due to their ample polyphenol, flavonoids, galactolipids, vitamins and other bioactive components. In fact, studies report that rose hips have higher vitamin C content than most edible berries. Even if rose hip extract cannot alleviate complex metabolic, auto-immune, degenerative diseases, 17

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it can promote healthy redox status of the body. While consumers are willing to pay exorbitant price for dietary supplements, a natural source of multi-nutrients going to waste is paradoxical. However, to ensure no adverse health effects on consumption of the rose hips, additional empirical analyses on the nutrient

expected to inspire investigations on rose hips as functional foods. Conflict of interest statement

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profile of rose hips need to be determined by randomized controlled trials (RCTs). This review is

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The author declares no conflict of interest in submission of this manuscript.

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References Ali, N., Alam, H., Khan, A., Ahmed, G., Shah, W. A., Nabi, M., & Junaid, M. (2014). Antispasmodic and antidiarrhoeal activity of the fruit of Rosa moschata (J). BMC Complementary and Alternative

RI PT

Medicine, 14, 485. http://doi.org/10.1186/1472-6882-14-485 Andersson, S. C., Olsson, M. E., Gustavsson, K.-E., Johansson, E., & Rumpunen, K. (2012). Tocopherols in rose hips (Rosa spp.) during ripening. Journal of the Science of Food and Agriculture, 92(10),

SC

2116–21. http://doi.org/10.1002/jsfa.5594

Andersson, S. C., Rumpunen, K., Johansson, E., & Olsson, M. E. (2011). Carotenoid content and

implications for

M AN U

composition in rose hips (Rosa spp.) during ripening, determination of suitable maturity marker and health promoting food products.

Food Chemistry,

128(3),

689–696.

http://doi.org/10.1016/j.foodchem.2011.03.088

Andersson, U., Berger, K., Högberg, A., Landin-Olsson, M., & Holm, C. (2012). Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind,

TE D

cross-over investigation in obese persons. European Journal of Clinical Nutrition, 66(5), 585–90. http://doi.org/10.1038/ejcn.2011.203

Andersson, U., Henriksson, E., Ström, K., Alenfall, J., Göransson, O., & Holm, C. (2011). Rose hip exerts

American

EP

antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program. Journal

of

Physiology.

Endocrinology

and

Metabolism,

300(1),

E111-21.

AC C

http://doi.org/10.1152/ajpendo.00268.2010 Andrew, A. S., Jewell, D. A., Mason, R. A., Whitfield, M. L., Moore, J. H., & Karagas, M. R. (2008). Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environmental Health Perspectives, 116(4), 524–31. http://doi.org/10.1289/ehp.10861 Barros, L., Carvalho, A. M., & Ferreira, I. C. F. R. (2011). Exotic fruits as a source of important phytochemicals: Improving the traditional use of Rosa canina fruits in Portugal. Food Research International, 44(7), 2233–2236. http://doi.org/10.1016/j.foodres.2010.10.005 Barros, L., Carvalho, A. M., Morais, J. S., & Ferreira, I. C. F. R. (2010). Strawberry-tree, blackthorn and 19

ACCEPTED MANUSCRIPT

rose fruits: Detailed characterisation in nutrients and phytochemicals with antioxidant properties. Food Chemistry, 120(1), 247–254. http://doi.org/10.1016/j.foodchem.2009.10.016 Binic, I., Lazarevic, V., Ljubenovic, M., Mojsa, J., & Sokolovic, D. (2013). Skin ageing: natural weapons

RI PT

and strategies. Evidence-Based Complementary and Alternative Medicine : eCAM, 2013, 827248. http://doi.org/10.1155/2013/827248

Boskabady, M. H., Shafei, M. N., Saberi, Z., & Amini, S. (2011). Pharmacological effects of rosa

SC

damascena. Iranian Journal of Basic Medical Sciences, 14(4), 295–307. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23493250

M AN U

Burchi, F., Fanzo, J., & Frison, E. (2011). The role of food and nutrition system approaches in tackling hidden hunger. International Journal of Environmental Research and Public Health, 8(2), 358–73. http://doi.org/10.3390/ijerph8020358

Cabanillas, F. (2010). Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later? Puerto

Rico

Health

Sciences

Journal,

29(3),

215–7.

Retrieved

from

TE D

http://www.ncbi.nlm.nih.gov/pubmed/20799507

Carr, A. C., Vissers, M. C. M., & Cook, J. S. (2014). The effect of intravenous vitamin C on cancer- and chemotherapy-related

fatigue

and

quality

of

life.

Frontiers

in

Oncology,

4,

283.

EP

http://doi.org/10.3389/fonc.2014.00283

Changizi Ashtiyani, S., Najafi, H., Jalalvandi, S., & Hosseinei, F. (2013). Protective effects of Rosa

AC C

canina L fruit extracts on renal disturbances induced by reperfusion injury in rats. Iranian Journal of Kidney Diseases, 7(4), 290–8. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23880806 Chaouali, N., Gana, I., Dorra, A., Khelifi, F., Nouioui, A., Masri, W., … Hedhili, A. (2013). Potential Toxic Levels of Cyanide in Almonds (Prunus amygdalus), Apricot Kernels (Prunus armeniaca), and Almond Syrup. ISRN Toxicology, 2013, 610648. http://doi.org/10.1155/2013/610648 Christensen, L. P. (2009a). Galactolipids as potential health promoting compounds in vegetable foods. Recent

Patents

on

Food,

Nutrition

&

http://www.ncbi.nlm.nih.gov/pubmed/20653526 20

Agriculture,

1(1),

50–8.

Retrieved

from

ACCEPTED MANUSCRIPT

Christensen, L. P. (2009b). Galactolipids as potential health promoting compounds in vegetable foods. Recent

Patents

on

Food,

Nutrition

&

Agriculture,

1(1),

50–8.

Retrieved

from

http://www.ncbi.nlm.nih.gov/pubmed/20653526

RI PT

Christensen, R., Bartels, E. M., Altman, R. D., Astrup, A., & Bliddal, H. (2008). Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?--a meta-analysis of randomized controlled trials. Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society, 16(9), 965–

SC

72. http://doi.org/10.1016/j.joca.2008.03.001

Chrubasik-Hausmann, S., Chrubasik, C., Neumann, E., & Müller-Ladner, U. (2014). A pilot study on the

M AN U

effectiveness of a rose hip shell powder in patients suffering from chronic musculoskeletal pain. Phytotherapy Research : PTR, 28(11), 1720–6. http://doi.org/10.1002/ptr.5192 Cianferoni, A., & Muraro, A. (2012). Food-induced anaphylaxis. Immunology and Allergy Clinics of North America, 32(1), 165–95. http://doi.org/10.1016/j.iac.2011.10.002 Cohen, M. (2012). Rosehip - an evidence based herbal medicine for inflammation and arthritis. Australian

TE D

Family Physician, 41(7), 495–8. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22762068 Cos, P., De Bruyne, T., Hermans, N., Apers, S., Berghe, D. Vanden, & Vlietinck, A. J. (2004). Proanthocyanidins in health care: current and new trends. Current Medicinal Chemistry, 11(10),

EP

1345–59. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15134524 Cunja, V., Mikulic-Petkovsek, M., Weber, N., Jakopic, J., Zupan, A., Veberic, R., … Schmitzer, V.

AC C

(2016). Fresh from the Ornamental Garden: Hips of Selected Rose Cultivars Rich in Phytonutrients. Journal of Food Science, 81(2), C369-79. http://doi.org/10.1111/1750-3841.13220 Cunja, V., Mikulic-Petkovsek, M., Zupan, A., Stampar, F., & Schmitzer, V. (2015). Frost decreases content of sugars, ascorbic acid and some quercetin glycosides but stimulates selected carotenes in Rosa

canina

hips.

Journal

of

Plant

Physiology,

178,

55–63.

http://doi.org/10.1016/j.jplph.2015.01.014 Czyzowska, A., Klewicka, E., Pogorzelski, E., & Nowak, A. (2014). Polyphenols, vitamin C and antioxidant activity in wines from Rosa canina L. and Rosa rugosa Thunb. Journal of Food 21

ACCEPTED MANUSCRIPT

Composition and Analysis. http://doi.org/10.1016/j.jfca.2014.11.009 Datta, H. S., Mitra, S. K., Paramesh, R., & Patwardhan, B. (2011). Theories and management of aging: modern and ayurveda perspectives. Evidence-Based Complementary and Alternative Medicine :

RI PT

eCAM, 2011, 528527. http://doi.org/10.1093/ecam/nep005 de la Iglesia, R., Milagro, F. I., Campión, J., Boqué, N., & Martínez, J. A. Healthy properties of proanthocyanidins. BioFactors (Oxford, England), 36(3), 159–68. http://doi.org/10.1002/biof.79

SC

Demir, A. U., Karakaya, G., & Kalyoncu, A. F. (2002). Allergy symptoms and IgE immune response to rose: an occupational and an environmental disease. Allergy, 57(10), 936–9. Retrieved from

M AN U

http://www.ncbi.nlm.nih.gov/pubmed/12269941

Demir, N., Yildiz, O., Alpaslan, M., & Hayaloglu, A. A. (2014). Evaluation of volatiles, phenolic compounds and antioxidant activities of rose hip (Rosa L.) fruits in Turkey. LWT - Food Science and Technology, 57(1), 126–133. http://doi.org/10.1016/j.lwt.2013.12.038 Dixon, R. A., Xie, D.-Y., & Sharma, S. B. (2005). Proanthocyanidins--a final frontier in flavonoid

TE D

research? The New Phytologist, 165(1), 9–28. http://doi.org/10.1111/j.1469-8137.2004.01217.x Dobosch, D., Gomez Zavaglia, A., & Kuljich, A. (1995). [The role of food in cholera transmission]. Medicina, 55(1), 28–32. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7565031

EP

Dubtsova, G. N., Negmatulloeva, R. N., Bessonov, V. V, Baĭkov, V. G., Sheviakova, L. V, Makhova, N. N., … Baĭgarin, E. K. (2012). [Composition and content of biologically active substances in rose Voprosy

Pitaniia,

81(6),

84–8.

Retrieved

from

AC C

hips].

http://www.ncbi.nlm.nih.gov/pubmed/23530442 Ebanks, J. P., Wickett, R. R., & Boissy, R. E. (2009). Mechanisms Regulating Skin Pigmentation: The Rise and Fall of Complexion Coloration. International Journal of Molecular Sciences, 10(9), 4066– 4087. http://doi.org/10.3390/ijms10094066 Ercisli, S. (2007). Chemical composition of fruits in some rose (Rosa spp.) species. Food Chemistry, 104(4), 1379–1384. http://doi.org/10.1016/j.foodchem.2007.01.053 Erenturk, S., Gulaboglu, M. S., & Gultekin, S. (2004). The Thin-layer Drying Characteristics of Rosehip. 22

ACCEPTED MANUSCRIPT

Biosystems Engineering, 89(2), 159–166. http://doi.org/10.1016/j.biosystemseng.2004.06.002 Fernández-Rivas, M., van Ree, R., & Cuevas, M. (1997). Allergy to Rosaceae fruits without related pollinosis. The Journal of Allergy and Clinical Immunology, 100(6 Pt 1), 728–33. Retrieved from

RI PT

http://www.ncbi.nlm.nih.gov/pubmed/9438478 Finkielstein, V. A., & Goldfarb, D. S. (2006). Strategies for preventing calcium oxalate stones. CMAJ : Canadian Medical Association Journal = Journal de l’Association Medicale Canadienne, 174(10),

SC

1407–9. http://doi.org/10.1503/cmaj.051517

Fromm, M., Bayha, S., Kammerer, D. R., & Carle, R. (2012). Identification and quantitation of

M AN U

carotenoids and tocopherols in seed oils recovered from different Rosaceae species. Journal of Agricultural and Food Chemistry, 60(43), 10733–42. http://doi.org/10.1021/jf3028446 Fujii, T., Ikeda, K., & Saito, M. (2011). Inhibitory effect of rose hip (Rosa canina L.) on melanogenesis in mouse melanoma cells and on pigmentation in brown guinea pigs. Bioscience, Biotechnology, and Biochemistry, 75(3), 489–95. http://doi.org/10.1271/bbb.100702

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Gaude, N., Tippmann, H., Flemetakis, E., Katinakis, P., Udvardi, M., & Dörmann, P. (2004). The galactolipid digalactosyldiacylglycerol accumulates in the peribacteroid membrane of nitrogenfixing nodules of soybean and Lotus. The Journal of Biological Chemistry, 279(33), 34624–30.

EP

http://doi.org/10.1074/jbc.M404098200

Goto, T., Teraminami, A., Lee, J.-Y., Ohyama, K., Funakoshi, K., Kim, Y.-I., … Kawada, T. (2012).

AC C

Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in

obese-diabetic

mice.

The

Journal

of

Nutritional

Biochemistry,

23(7),

768–76.

http://doi.org/10.1016/j.jnutbio.2011.04.001 Guimarães, R., Barros, L., Dueñas, M., Carvalho, A. M., Queiroz, M. J. R. P., Santos-Buelga, C., & Ferreira, I. C. F. R. (2013). Characterisation of phenolic compounds in wild fruits from Northeastern Portugal. Food Chemistry, 141(4), 3721–30. http://doi.org/10.1016/j.foodchem.2013.06.071 Günes, M. (2013, August 13). Pomological and phenological characteristics of promising rose hip (Rosa) 23

ACCEPTED MANUSCRIPT

genotypes.

African

Journal

of

Biotechnology.

Academic

Journals

(Kenya).

http://doi.org/10.4314/ajb.v9i38. Guo, D., Xu, L., Cao, X., Guo, Y., Ye, Y., Chan, C.-O., … Chen, S. (2011). Anti-inflammatory activities

RI PT

and mechanisms of action of the petroleum ether fraction of Rosa multiflora Thunb. hips. Journal of Ethnopharmacology, 138(3), 717–22. http://doi.org/10.1016/j.jep.2011.10.010

Gupta, S. C., Hevia, D., Patchva, S., Park, B., Koh, W., & Aggarwal, B. B. (2012). Upsides and

SC

downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxidants & Redox Signaling, 16(11), 1295–322.

M AN U

http://doi.org/10.1089/ars.2011.4414

Gürbüz, I., Ustün, O., Yesilada, E., Sezik, E., & Kutsal, O. (2003). Anti-ulcerogenic activity of some plants used as folk remedy in Turkey. Journal of Ethnopharmacology, 88(1), 93–7. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12902057

Hanson, A. D., & Gregory, J. F. (2011). Folate biosynthesis, turnover, and transport in plants. Annual

TE D

Review of Plant Biology, 62, 105–25. http://doi.org/10.1146/annurev-arplant-042110-103819 Harrison, F. E. (2012). A critical review of vitamin C for the prevention of age-related cognitive decline and

Alzheimer’s

disease.

Journal

of

Alzheimer’s

Disease :

JAD,

29(4),

711–26.

EP

http://doi.org/10.3233/JAD-2012-111853

Hasler, C. M. (2000). The changing face of functional foods. Journal of the American College of

AC C

Nutrition, 19(5 Suppl), 499S–506S. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11022999 Hellström, J. K., Törrönen, A. R., & Mattila, P. H. (2009). Proanthocyanidins in common food products of

plant

origin.

Journal

of

Agricultural

and

Food

Chemistry,

57(17),

7899–906.

http://doi.org/10.1021/jf901434d Herrero-Beaumont, G., Ivorra, J. A. R., Del Carmen Trabado, M., Blanco, F. J., Benito, P., Martín-Mola, E., … Branco, J. (2007). Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis and Rheumatism, 56(2), 555–67. http://doi.org/10.1002/art.22371 24

ACCEPTED MANUSCRIPT

Hoffer, L. J., Robitaille, L., Zakarian, R., Melnychuk, D., Kavan, P., Agulnik, J., … Jr. (2015). High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PloS One, 10(4), e0120228. http://doi.org/10.1371/journal.pone.0120228

RI PT

Hou, C.-C., Chen, Y.-P., Wu, J.-H., Huang, C.-C., Wang, S.-Y., Yang, N.-S., & Shyur, L.-F. (2007). A galactolipid possesses novel cancer chemopreventive effects by suppressing inflammatory mediators and mouse B16 melanoma. Cancer Research, 67(14), 6907–15. http://doi.org/10.1158/0008-

SC

5472.CAN-07-0158

Ilbay, Z., Sahin, S., & Kırbaşlar, S. İ. (2013). Optimisation of ultrasound-assisted extraction of rosehip

M AN U

(Rosa canina L.) with response surface methodology. Journal of the Science of Food and Agriculture, 93(11), 2804–9. http://doi.org/10.1002/jsfa.6104

Jia, Y., Ji, L., Zhang, S., Xu, L., Yin, L., Li, L., … Peng, J. (2012). Total flavonoids from Rosa Laevigata Michx fruit attenuates hydrogen peroxide induced injury in human umbilical vein endothelial cells. Food and Chemical Toxicology : An International Journal Published for the British Industrial

TE D

Biological Research Association, 50(9), 3133–41. http://doi.org/10.1016/j.fct.2012.06.047 Jiménez, S., Gascón, S., Luquin, A., Laguna, M., Ancin-Azpilicueta, C., Rodríguez-Yoldi, M. J., … Huang, P. (2016). Rosa canina Extracts Have Antiproliferative and Antioxidant Effects on Caco-2

EP

Human Colon Cancer. PLOS ONE, 11(7), e0159136. http://doi.org/10.1371/journal.pone.0159136 Jung, S., & Main, D. (2014). Genomics and bioinformatics resources for translational science in

AC C

Rosaceae. Plant Biotechnology Reports, 8, 49–64. http://doi.org/10.1007/s11816-013-0282-3 Kaličanin, B., & Velimirović, D. (2016). A Study of the Possible Harmful Effects of Cosmetic Beauty Products

on

Human

Health.

Biological

Trace

Element

Research,

170(2),

476–84.

http://doi.org/10.1007/s12011-015-0477-2 Karhagomba, I. B., Mirindi T, A., Mushagalusa, T. B., Nabino, V. B., Koh, K., & Kim, H. S. (2013). The cultivation of wild food and medicinal plants for improving community livelihood: The case of the Buhozi

site,

DR

Congo.

Nutrition

http://doi.org/10.4162/nrp.2013.7.6.510 25

Research

and

Practice,

7(6),

510–8.

ACCEPTED MANUSCRIPT

Kirkeskov, B., Christensen, R., Bügel, S., Bliddal, H., Danneskiold-Samsøe, B., Christensen, L. P., & Andersen, J. R. (2011). The effects of rose hip (Rosa canina) on plasma antioxidative activity and Creactive protein in patients with rheumatoid arthritis and normal controls: a prospective cohort study.

RI PT

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 18(11), 953–8. http://doi.org/10.1016/j.phymed.2011.02.008

Koponen, J. M., Happonen, A. M., Mattila, P. H., & Törrönen, A. R. (2007). Contents of anthocyanins

SC

and ellagitannins in selected foods consumed in Finland. Journal of Agricultural and Food Chemistry, 55(4), 1612–9. http://doi.org/10.1021/jf062897a

M AN U

Korać, R. R., & Khambholja, K. M. (2011). Potential of herbs in skin protection from ultraviolet radiation. Pharmacognosy Reviews, 5(10), 164–73. http://doi.org/10.4103/0973-7847.91114 Kuchroo, V. K., Ohashi, P. S., Sartor, R. B., & Vinuesa, C. G. (2012). Dysregulation of immune homeostasis in autoimmune diseases. Nature Medicine, 18(1), 42–7. http://doi.org/10.1038/nm.2621 Kwaselow, A., Rowe, M., Sears-Ewald, D., & Ownby, D. (1990). Rose hips: a new occupational allergen. Journal

of

Allergy

and

Clinical

Immunology,

85(4),

704–8.

Retrieved

from

TE D

The

http://www.ncbi.nlm.nih.gov/pubmed/2324410

Larsen, E., Kharazmi, K., Christensen, L. P., & Christensen, S.B. (2003). An Antiinflammatory

EP

Galactolipid from Rose Hip (Rosa canina) that Inhibits Chemotaxis of Human Peripheral Blood Neutrophils in Vitro. http://doi.org/10.1021/NP0300636

AC C

Lattanzio, F., Greco, E., Carretta, D., Cervellati, R., Govoni, P., & Speroni, E. (2011). In vivo antiinflammatory effect of Rosa canina L. extract. Journal of Ethnopharmacology, 137(1), 880–5. http://doi.org/10.1016/j.jep.2011.07.006 Li, J., Zhang, A., Ren, Y., Liu, Z., Huang, X., & Yang, D. (2013). [Regulating effects of Rosa roxburghii tratt preparation on immune function in arseniasis patients caused by coal burning]. Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine], 47(9), 783–7. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24351556 Li, S., Guo, L., Liu, C., & Zhang, Y. (2013). Application of supercritical fluid extraction coupled with 26

ACCEPTED MANUSCRIPT

counter-current chromatography for extraction and online isolation of unstable chemical components from

Rosa

damascena.

Journal

of

Separation

Science,

36(13),

2104–13.

http://doi.org/10.1002/jssc.201300324

RI PT

Loetscher, Y., Kreuzer, M., & Messikommer, R. E. (2013). Oxidative stability of the meat of broilers supplemented with rosemary leaves, rosehip fruits, chokeberry pomace, and entire nettle, and effects on performance and meat quality. Poultry Science, 92(11), 2938–48. http://doi.org/10.3382/ps.2013-

SC

03258

Lopes, G., Daletos, G., Proksch, P., Andrade, P. B., & Valentão, P. (2014). Anti-inflammatory potential of

M AN U

monogalactosyl diacylglycerols and a monoacylglycerol from the edible brown seaweed Fucus spiralis Linnaeus. Marine Drugs, 12(3), 1406–18. http://doi.org/10.3390/md12031406 Maldonado, M. E., Bousserouel, S., Gossé, F., Lobstein, A., & Raul, F. (n.d.). Implication of NF-κB and p53 in the expression of TRAIL-death receptors and apoptosis by apple procyanidins in human metastatic SW620 cells. Biomédica : Revista Del Instituto Nacional de Salud, 30(4), 577–86.

TE D

Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21713362

Marstrand, C., Warholm, L., Kharazmi, A., & Winther, K. (2013). The anti-inflammatory capacity of Rose-hip is strongly dependent on the seeds - a comparison of animal and human studies.

EP

Osteoarthritis and Cartilage, 21, S216–S217. http://doi.org/10.1016/j.joca.2013.02.448 Meng, J., Fang, Y., Gao, J., Qiao, L., Zhang, A., Guo, Z., … Zhuang, X. (2012). Phenolics composition

AC C

and antioxidant activity of wine produced from spine grape (Vitis davidii Foex) and Cherokee rose (Rosa laevigata Michx.) fruits from South China. Journal of Food Science, 77(1), C8-14. http://doi.org/10.1111/j.1750-3841.2011.02499.x Montazeri, N., Baher, E., Mirzajani, F., Barami, Z., & Yousefian, S. (2011, September 16). Phytochemical contents and biological activities of Rosa canina fruit from Iran. Journal of Medicinal

Plants

Research.

Academic

Journals.

Retrieved

from

http://www.academicjournals.org/journal/JMPR/article-abstract/06F8FBE25511 Murata, K., Takahashi, K., Nakamura, H., Itoh, K., & Matsuda, H. (2014). Search for skin-whitening 27

ACCEPTED MANUSCRIPT

agent from Prunus plants and the molecular targets in melanogenesis pathway of active compounds. Natural

Product

Communications,

9(2),

185–8.

Retrieved

from

http://www.ncbi.nlm.nih.gov/pubmed/24689286

RI PT

Nagatomo, A., Nishida, N., Fukuhara, I., Noro, A., Kozai, Y., Sato, H., & Matsuura, Y. (2015). Daily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trial. Diabetes, Metabolic Syndrome and Obesity : Targets

SC

and Therapy, 8, 147–56. http://doi.org/10.2147/DMSO.S78623

Nagatomo, A., Nishida, N., Matsuura, Y., & Shibata, N. (2013). Rosehip Extract Inhibits Lipid

activated

Receptor

M AN U

Accumulation in White Adipose Tissue by Suppressing the Expression of Peroxisome ProliferatorGamma.

Preventive

Nutrition

and

Food

Science,

18(2),

85–91.

http://doi.org/10.3746/pnf.2013.18.2.085

Nazıroğlu, M., Kozlu, S., Yorgancıgil, E., Uğuz, A. C., & Karakuş, K. (2013). Rose oil (from Rosa × damascena Mill.) vapor attenuates depression-induced oxidative toxicity in rat brain. Journal of

TE D

Natural Medicines, 67(1), 152–8. http://doi.org/10.1007/s11418-012-0666-7 Noris, M., & Remuzzi, G. (2013). Overview of complement activation and regulation. Seminars in Nephrology, 33(6), 479–92. http://doi.org/10.1016/j.semnephrol.2013.08.001

EP

Novembre, E., Mori, F., Contestabile, S., Rossi, M. E., & Pucci, N. (2012). Correlation of anti-Pru p 3 IgE levels with severity of peach allergy reactions in children. Annals of Allergy, Asthma &

AC C

Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology, 108(4), 271–4. http://doi.org/10.1016/j.anai.2012.02.006 Nur, N. (2010). Knowledge and behaviours related to herbal remedies: a cross-sectional epidemiological study in adults in Middle Anatolia, Turkey. Health & Social Care in the Community, 18(4), 389– 395. http://doi.org/10.1111/j.1365-2524.2010.00911.x Ogah, O., Watkins, C. S., Ubi, B. E., & Oraguzie, N. C. (2014). Phenolic compounds in Rosaceae fruit and

nut

crops.

Journal

of

Agricultural

http://doi.org/10.1021/jf501574q 28

and

Food

Chemistry,

62(39),

9369–86.

ACCEPTED MANUSCRIPT

Ohno, S., Ohno, Y., Suzuki, N., Soma, G.-I., & Inoue, M. (2009). High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Anticancer Research, 29(3), 809–15. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19414313

on

Altitude.

Iranian

Journal

of

Public

RI PT

Oprica, L., Bucsa, C., & Zamfirache, M. M. (2015). Ascorbic Acid Content of Rose Hip Fruit Depending Health,

44(1),

http://www.ncbi.nlm.nih.gov/pubmed/26060787

138–9.

Retrieved

from

prospects.

Mediterranean

Journal

of

Nutrition

and

Metabolism,

M AN U

http://doi.org/10.1007/s12349-012-0118-7

SC

Patel, S. (2012). Rose hips as complementary and alternative medicine: overview of the present status and 6(2),

89–97.

Patel, S. (2015a). Emerging Bioresources with Nutraceutical and Pharmaceutical Prospects. Cham: Springer International Publishing. http://doi.org/10.1007/978-3-319-12847-4 Patel, S. (2015b). Plant essential oils and allied volatile fractions as multifunctional additives in meat and fish-based food products: a review. Food Additives & Contaminants. Part A, Chemistry, Analysis, Exposure

&

Risk

Assessment,

32(7),

1049–64.

TE D

Control,

http://doi.org/10.1080/19440049.2015.1040081

Petcharat, A., & Wongsuphasawat, K. (2013). The efficacy of a standardized Rose-hip powder containing

blinded,

EP

seeds and shells compared with glucosamine sulfate in patients with osteoarthritis of the knee - a parallel,

randomized

study.

Osteoarthritis

and

Cartilage,

21,

S216.

AC C

http://doi.org/10.1016/j.joca.2013.02.446 Phetcharat, L., Wongsuphasawat, K., & Winther, K. (2015). The effectiveness of a standardized rose hip powder, containing seeds and shells of Rosa canina, on cell longevity, skin wrinkles, moisture, and elasticity. Clinical Interventions in Aging, 10, 1849–56. http://doi.org/10.2147/CIA.S90092 Ravindran, R. D., Vashist, P., Gupta, S. K., Young, I. S., Maraini, G., Camparini, M., … Fletcher, A. E. (2011). Inverse association of vitamin C with cataract in older people in India. Ophthalmology, 118(10), 1958–1965.e2. http://doi.org/10.1016/j.ophtha.2011.03.016 Rodriguez, J., Crespo, J. F., Lopez-Rubio, A., De La Cruz-Bertolo, J., Ferrando-Vivas, P., Vives, R., & 29

ACCEPTED MANUSCRIPT

Daroca, P. (2000). Clinical cross-reactivity among foods of the Rosaceae family. The Journal of Allergy and Clinical Immunology, 106(1 Pt 1), 183–9. http://doi.org/10.1067/mai.2000.106927 Roman, I., Stănilă, A., & Stănilă, S. (2013). Bioactive compounds and antioxidant activity of Rosa canina

RI PT

L. biotypes from spontaneous flora of Transylvania. Chemistry Central Journal, 7(1), 73. http://doi.org/10.1186/1752-153X-7-73

Rosus, C. M., Manzu, C., Olteanu, Z., Oprica, L., Oprea, A., Ciornea, E., & Zamfirache, M. M. (2011,

SC

November 21). Several Fruit Characteristics of Rosa sp. Genotypes from the Northeastern Region of Romania. Notulae Botanicae Horti Agrobotanici Cluj-Napoca. http://doi.org/10.15835/nbha3926333

M AN U

Saaby, L., Jäger, A. K., Moesby, L., Hansen, E. W., & Christensen, S. B. (2011). Isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina L.). Phytotherapy Research : PTR, 25(2), 195–201. http://doi.org/10.1002/ptr.3241 Saaby, L., & Nielsen, C. H. (2012). Triterpene acids from rose hip powder inhibit self-antigen- and LPSinduced cytokine production and CD4+ T-cell proliferation in human mononuclear cell cultures.

TE D

Phytotherapy Research : PTR, 26(8), 1142–7. http://doi.org/10.1002/ptr.3713 Saini, R. K., Manoj, P., Shetty, N. P., Srinivasan, K., & Giridhar, P. (2016). Relative bioavailability of folate from the traditional food plant Moringa oleifera L. as evaluated in a rat model. Journal of

EP

Food Science and Technology, 53(1), 511–20. http://doi.org/10.1007/s13197-015-1828-x Sánchez-Pérez, R., Jørgensen, K., Olsen, C. E., Dicenta, F., & Møller, B. L. (2008). Bitterness in

AC C

almonds. Plant Physiology, 146(3), 1040–52. http://doi.org/10.1104/pp.107.112979 Schagen, S. K., Zampeli, V. A., Makrantonaki, E., & Zouboulis, C. C. (2012). Discovering the link between

nutrition

and

skin

aging.

Dermato-Endocrinology,

4(3),

298–307.

http://doi.org/10.4161/derm.22876 Schwager, J., Hoeller, U., Wolfram, S., & Richard, N. (2011). Rose hip and its constituent galactolipids confer cartilage protection by modulating cytokine, and chemokine expression. BMC Complementary and Alternative Medicine, 11, 105. http://doi.org/10.1186/1472-6882-11-105 Siegel, R. L., Miller, K. D., & Jemal, A. (n.d.). Cancer statistics, 2016. CA: A Cancer Journal for 30

ACCEPTED MANUSCRIPT

Clinicians, 66(1), 7–30. http://doi.org/10.3322/caac.21332 Sinusas, K. (2012). Osteoarthritis: diagnosis and treatment. American Family Physician, 85(1), 49–56. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22230308

RI PT

Small, E. (2014). North American cornucopia : top 100 indigenous food plants. CRC Press, Taylor & Francis Group.

Smit, N., Vicanova, J., & Pavel, S. (2009). The hunt for natural skin whitening agents. International

SC

Journal of Molecular Sciences, 10(12), 5326–49. http://doi.org/10.3390/ijms10125326

Strålsjö, L., Alklint, C., Olsson, M. E., & Sjöholm, I. (2003). Total folate content and retention in rosehips

http://doi.org/10.1021/jf034208q

M AN U

(Rosa ssp.) after drying. Journal of Agricultural and Food Chemistry, 51(15), 4291–5.

Tayefi-Nasrabadi, H., Sadigh-Eteghad, S., & Aghdam, Z. (2012). The effects of the hydroalcohol extract of Rosa canina L. fruit on experimentally nephrolithiasic Wistar rats. Phytotherapy Research : PTR, 26(1), 78–85. http://doi.org/10.1002/ptr.3519

TE D

Tumbas, V. T., Canadanović-Brunet, J. M., Cetojević-Simin, D. D., Cetković, G. S., Ethilas, S. M., & Gille, L. (2012). Effect of rosehip (Rosa canina L.) phytochemicals on stable free radicals and human cancer cells. Journal of the Science of Food and Agriculture, 92(6), 1273–81.

EP

http://doi.org/10.1002/jsfa.4695

Velagapudi, R., Aderogba, M., & Olajide, O. A. (2014). Tiliroside, a dietary glycosidic flavonoid, inhibits

AC C

TRAF-6/NF-κB/p38-mediated neuroinflammation in activated BV2 microglia. Biochimica et Biophysica Acta, 1840(12), 3311–9. http://doi.org/10.1016/j.bbagen.2014.08.008 Vossen, E., Utrera, M., De Smet, S., Morcuende, D., & Estévez, M. (2012). Dog rose (Rosa canina L.) as a functional ingredient in porcine frankfurters without added sodium ascorbate and sodium nitrite. Meat Science, 92(4), 451–7. http://doi.org/10.1016/j.meatsci.2012.05.010 Widén, C., Ekholm, A., Coleman, M. D., Renvert, S., & Rumpunen, K. (2012). Erythrocyte antioxidant protection of rose hips (Rosa spp.). Oxidative Medicine and Cellular Longevity, 2012, 621579. http://doi.org/10.1155/2012/621579 31

ACCEPTED MANUSCRIPT

Willich, S. N., Rossnagel, K., Roll, S., Wagner, A., Mune, O., Erlendson, J., … Winther, K. (2010). Rose hip herbal remedy in patients with rheumatoid arthritis - a randomised controlled trial. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 17(2), 87–93.

RI PT

http://doi.org/10.1016/j.phymed.2009.09.003 Wu, J., Liu, X., Chan, C., Mok, D. K. W., Chan, S., Yu, Z., & Chen, S. (2014). Petroleum ether extractive of the hips of Rosa multiflora ameliorates collagen-induced arthritis in rats. Journal of

SC

Ethnopharmacology, 157, 45–54. http://doi.org/10.1016/j.jep.2014.09.026

Wu, X.-P., Zhang, X.-P., Ma, G.-X., Han, M., Xu, M.-D., Wu, H.-F., … Zhong, X.-M. (2014). A new

M AN U

ursane-type triterpene, cymosic acid from Rosa cymosa. Journal of Asian Natural Products Research, 16(4), 422–5. http://doi.org/10.1080/10286020.2014.885507 Yan, X., Zhang, X., Lu, M., He, Y., & An, H. (2015). De novo sequencing analysis of the Rosa roxburghii fruit transcriptome reveals putative ascorbate biosynthetic genes and EST-SSR markers. Gene, 561(1), 54–62. http://doi.org/10.1016/j.gene.2015.02.054

TE D

Yi, O., Jovel, E. M., Towers, G. H. N., Wahbe, T. R., & Cho, D. (2007a). Antioxidant and antimicrobial activities of native Rosa sp. from British Columbia, Canada. International Journal of Food Sciences and Nutrition, 58(3), 178–89. http://doi.org/10.1080/09637480601121318

EP

Yi, O., Jovel, E. M., Towers, G. H. N., Wahbe, T. R., & Cho, D. (2007b). Antioxidant and antimicrobial activities of native Rosa sp. from British Columbia, Canada. International Journal of Food Sciences

AC C

and Nutrition, 58(3), 178–89. http://doi.org/10.1080/09637480601121318 Zhang, S., Lu, B., Han, X., Xu, L., Qi, Y., Yin, L., … Peng, J. (2013). Protection of the flavonoid fraction from Rosa laevigata Michx fruit against carbon tetrachloride-induced acute liver injury in mice. Food and Chemical Toxicology : An International Journal Published for the British Industrial Biological Research Association, 55, 60–9. http://doi.org/10.1016/j.fct.2012.12.041 Zhang, S., Qi, Y., Xu, Y., Han, X., Peng, J., Liu, K., & Sun, C. K. (2013). Protective effect of flavonoidrich extract from Rosa laevigata Michx on cerebral ischemia-reperfusion injury through suppression of

apoptosis

and

inflammation.

Neurochemistry 32

International,

63(5),

522–32.

ACCEPTED MANUSCRIPT

http://doi.org/10.1016/j.neuint.2013.08.008 Zhang, S., Zheng, L., Dong, D., Xu, L., Yin, L., Qi, Y., … Peng, J. (2013). Effects of flavonoids from Rosa laevigata Michx fruit against high-fat diet-induced non-alcoholic fatty liver disease in rats.

RI PT

Food Chemistry, 141(3), 2108–16. http://doi.org/10.1016/j.foodchem.2013.05.019 Zhang, S., Zheng, L., Xu, L., Sun, H., Li, H., Yao, J., … Peng, J. (2012). Subchronic toxicity study of the total flavonoids from Rosa laevigata Michx fruit in rats. Regulatory Toxicology and Pharmacology :

SC

RTP, 62(2), 221–30. http://doi.org/10.1016/j.yrtph.2011.12.009

Zhong, L., Gustavsson, K.-E., Oredsson, S., Głąb, B., Yilmaz, J. L., & Olsson, M. E. (2016).

M AN U

Determination of free and esterified carotenoid composition in rose hip fruit by HPLC-DAD-

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APCI+-MS. Food Chemistry, 210, 541–550. http://doi.org/10.1016/j.foodchem.2016.05.002

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Legends to the figures Figure 1. (A) Ripe rose hips (B) Fragmented rose hips (C) The seeds. The solvents used for extraction of bioactive fractions, the phytochemicals and the biological benefits.

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Figure 2. The mechanistic of arthritic anti-inflammation by rose hip extract Figure 3. (A) Rosa californica in California chaparral (Mission trails regional park, San Diego) (B) Rosa californica in High Sierra, California

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Figure 4. Rose hips ripening in autumn season in Pacific coast, Washington

Figure 5. Rosa species in Washington park arboretum, Seattle (A) Rosa rugosa (B) Rosa

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corymbulosa (C) Rosa nootkana

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As food security emerges as an urgent issue, rose hips appear to be a functional food candidate.

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Rich in polyphenols, essential fatty acids, vitamin A and C, minerals, these Rosaceae fruits have been evaluated nutritive.

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Biological properties of rose hip such as antioxidant, anti-inflammatory, immunomodulation, anticancer,

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This review can draw public and researcher interest, which will be contributing towards food security.

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cardioprotective, antidiabetic, neuroprotective, antimicrobial have been validated.

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Table 1. Rosa species, the phytochemicals in the rose hips, biological functions, and the pathways intervened for therapeutic roles Biological function Rosa species Phytochemicals Pathways manipulated References R. laevigata Flavonoids Lower serum AST and ALT activities (Zhang, Lu, et al., 2013) Antioxidative Tiliroside (Hepatoprotective, prevent Michx Improve SOD, CAT, GSH activities (Zhang, Zheng, et al., 2013) schemic stroke, anti- Rosa × Downregulate CYP2E1, iNOS, NF-κB, Bak and (Zhang, Qi, et al., 2013) depressant, prevent kidney damascena Mill. Caspase-3 (Nazıroğlu et al., 2013) stone) R. canina Downregulate p53, Apaf1, Fas, FasL, Bax, Bid, (Velagapudi et al., 2014) NF-κB, iNOS, MMP-9, COX-2, TNF-α, IL-1β, (Finkielstein & Goldfarb, 2006) IL-4, IL-6, p-JNK, p-ERK and p-p38 in MAPK (Tayefi-Nasrabadi et al., 2012) (Changizi Ashtiyani et al., 2013) Lower renal and urinary calcium contents Lower blood creatinine and urea concentrations Triterpene acid Inhibit IL-6 and TNF- α release (Saaby & Nielsen, 2012) Immunomodulation and R. canina R. roxburghii Galactolipid Facilitate detoxification of arsenic (Li et al., 2013) anti-inflammation (Prevent osteoarthritis and R. multiflora Unsaturated fatty Improve antioxidant enzyme levels (Christensen, Bartels, Altman, acids Inhibit NO and prostaglandin production rheumatoid arthritis pain; R. moschata Astrup, & Bliddal, 2008) Reduce inflammatory cytokines/ chemokines (Saaby et al., 2011) protect gut mucosa) secretion (Schwager et al., 2011) Downregulate iNOS and COX-2 (Guo et al., 2011) Block voltage-gated Ca++ channel and prevent (Ali et al., 2014) spasms R. laevigata Flavonoids Reduce ROS generation (Jia et al., 2012) Cardiovascular Michx Restore glutathione level (Andersson, Berger, Högberg, Decrease caspase activities Landin-Olsson, & Holm, 2012) Prevent DNA fragmentation (Ulrika Andersson et al., 2011) Tiliroside Downregulate hepatic lipogenic proteins Anti-obesity and anti- R. canina L. Downregulate PPARγ expression (Nagatomo et al., 2013) diabetic Enhance fatty acid oxidation via adiponectin (Goto et al., 2012) signaling Polyphenols (Tumbas et al., 2012) Scavenge ROS Anticancer and R. canina R. nutkana Phenolic contents Alcohols lyse bacterial membranes (Gupta et al., 2012) antimicrobial R. woodsii Lycopene (Yi et al., 2007a) (Boskabady et al., 2011) R. canina Proanthocyanidins Inhibit the phosphorylation of p38 MAPK (Binic et al., 2013; Fujii et al., 2011) Cosmetics Suppress tyrosinase (Ebanks et al., 2009) Prevent melanogenesis (Murata et al., 2014)