Abstract
Rosa roxbughii Tratt (RRT) is a welcome medicinal and edible fruit with unique functions and nutrients in China. In the past decades, extensive research including chemical constituents and bioactivities of RRT were reported. A total of small 78 small molecules, such as flavonoids, organic acid, triterpenes, etc. and 11 polysaccharides have been isolated from RRT. Its antioxidant, anti-tumor and other pharmacological effects were also discovered. This paper reviews the progress of those information for the R&D of RRT in the future.
Keywords: Rosa roxburghii Tratt; chemical constituents; biological activities
1 Introduction
In recent years, the research and development of functional fruit juice or beverage products made from fruits and vegetables has attracted increasing attention (Coronado-Reyes et al., 2022; Köten & Ünsal, 2022; Ruiz-Cisneros et al., 2022; Yin et al., 2022). Rosa roxbughii Tratt (RRT) is a perennial deciduous tufted shrub of the genus Rosa in the rose family. RRT is an important fruit in China due to its nutritional and medicinal values (Wang et al., 2021). The traditional efficacy of this plant was described as early as in the book “Compendium of Materia Medica” in the Ming Dynasty, and it is believed that RRT has the efficacy of eliminating food and strengthening the spleen, astringent, and stopping diarrhea, mainly used for treating accumulated food and bloating, diarrhea and pain. RRT fruits are rich in nutrients, including sugars, organic acids, proteins, amino acids, fatty acids, vitamins and inorganic salts, especially vitamin C, which is much higher than other fruits and vegetables, and is known as the “King of Vitamin C” (Kuhn et al., 2018). Moreover, RRT fruit exhibits a marked extent of functional activities against aging (Luo et al., 2002; Ma et al., 1997), anti-tumor, atherosclerosis (Jian et al., 2015b; Zhang et al., 2001), reduce blood lipid and blood sugar (Chen et al., 2019b), and can also control intestinal flora disorders caused by diabetes (Wang et al., 2020). In order to offer a more comprehensive understanding of RRT and to conduct more in-depth research on their edible and medicinal values, this paper reviews the progress of research on its chemical constituents and biological activities.
2 Chemical constituents
The phytochemical constituents in edible plants play a vital role in human health. Previous phytochemical composition investigation has found that RRT in addition to rich containing vitamin C, also contains flavonoids, triterpenes, organic acids, tannins, polysaccharides and other chemical components. Their structures and names are listed below.
2.1 Flavonoids
Flavonoids are omnipresent natural products in the plant kingdom, having comprehensive biological activities including anti-free radical, anti-oxidative, anti-inflammatory, anti-microbial, anti-cancer and anti-glycating activities. RRT is rich in flavonoids, which are the primary active substances. To date, a total of 24 flavonoids (1-24) have been isolated from RRT (Table 1). Their structures are presented in Figure 1.
2.2 Triterpenes
Triterpenes are a cluster of polymers that possess isoprene as the basic unit, and are existed in vegetables, fruits and whole-wheat foods. Triterpenes are other core active constituents in RRT fruit with α-glucosidase inhibitory activity. 21 triterpenes were reported in RRT dominated by pentacyclic triterpenes. The triterpenes present RRT are summarised in Table 2. Their structure is shown in Figure 2.
2.3 Organic acids
Organic acids are not only delicious substances but also crucial medicinal ingredients in fruits that can boost digestion and sustain the acid-base balance in the human body. The composition and content of accumulated organic acids vary highly in diverse fruits. RRT fruits involve a certain percentage of organic acids, especially its ascorbic acid (Vitamin C, ~1300 mg) content is higher than most common fruits, such as tomato (~20 mg), strawberry (~50 mg), and kiwifruit (~100 mg). In addition to ascorbic acid, RRT also contains many other organic acids, such as lactic acid, malic acid, citric acid, succinic acid, oxalic acid, tartaric acid, etc. In Table 3, the Organic acids in RRT are summarized. Their structures are presented in Figure 3.
2.4 Tannins
Tannins are the main component of unripe fruits with an astringent taste. RRT also contains a large number of tannins, mainly condensed tannins with proanthocyanidins as the basic unit. Tannins have a variety of biological activities, including antioxidant and anti-inflammatory effects, and prevention of neurological, cardiovascular and chronic intestinal disease function (Westfall & Pasinetti, 2019). Up to date, about 13 kinds of tannins have been found in RRT. The composition and structure are shown in Table 4 and Figure 4.
2.5 Polysaccharides
Polysaccharides are a group of sugars with complex and large molecular structures, formed by the condensation and water loss of several monosaccharide molecules. Polysaccharides are the most abundant biopolymers in nature and are widely distributed in plants, animals, microorganisms and other living organisms. Plant polysaccharides have become the focus of recent research in medical and food functional chemistry. RRT polysaccharides have been reported to increase gastrointestinal health and immune function and have potential applications as functional beverages and foods. The monosaccharide composition and preparation method of Rosa roxburghii polysaccharide are shown in Table 5.
3 Bioactivities
3.1 Anti-tumour properties
Several kinds of literature have reported that RRT has antitumor activity. Huang et al. (2013) found that RRT has an anti-tumor effect in vitro, which may be related to down-regulating the expression of Bad mRNA and inducing the differentiation of tumor cells, but not related to apoptosis and cell proliferation cycle arrest (Huang et al., 2013). Yang et al. (2020) used MCF-7, MDA-MB-468 hominine breast cancer cells and HCT116 human colon cancer cells to research the anti-proliferative effect of an ethanol-water extract of RRT fruit (Yang et al., 2020). RRT inhibits the growth of gastric cancer SGC-7901 cells in vitro, but has no significant effect on the proliferation and differentiation of human cord blood CD34 (Xu et al., 2006) hematopoietic stem cells (Liu et al., 2006). Dai et al. by using the MTT reduction test to determine the cytotoxicity of RRT on gastric cancer SGC-7901 and MKN-45 cells. The results showed that the extract of RRT had a certain inhibitory effect on the growth of gastric cancer SGC-7901 and MKN-45 cells in vitro in a dose-dependent and time-dependent manner, which indicated that RRT extract had a certain antitumor effect in vitro (Dai et al., 2005). Liu et al. (2012) Combined the use of extracts from RRT and Fagopyrum cymosum, the proliferation and apoptosis of three cancer cell lines (human esophageal squamous cell carcinoma CaEs-17, human gastric cancer SGC-7901 and lung cancer A549) were evaluated by MTT assay and flow cytometry respectively. We found that the mRNA and protein expression levels of Ki-67 and Bcl-2 were greatly reduced, while the expression of Bax was significantly increased (Liu et al., 2012). Moreover, Chen et al. (2015) firstly discovered that RRT polysaccharides can effectively reduce the wound closure rate of A2780 cells. In addition, RRT could hinder the migration and infestation of ovarian cancer cells by decreasing MMP-9 expression (Chen et al., 2015). According to reports in the literature, RRT juice can obviously inhibit the proliferation of human leukemia K562 cells, and it can act at low concentrations, with the highest inhibition rate of 83.4% (Qiang et al., 2000). According to related reports, RRT juice can induce apoptosis of COC2 cells and inhibit the growth and proliferation of COC2 cells (Xu et al., 2006). Besides, flavonoids from RRT can play an important role in curbing autophagy by down-regulating the assay of LC3-II and up-regulating that of P62 (Yuan et al., 2020).
3.2 Antioxidant properties
More and more literature have been reported, that RRT polysaccharide has obvious antioxidant activity. In vitro antioxidant test showed that RRTP1-1 had the activity of scavenging free radicals against DPPH, hydroxyl and superoxide radicals. Antioxidant assays in vivo showed that RRTP1-1 could significantly enhance the activities of antioxidant enzymes (CAT, SOD, and GSH-Px), increase TAOC values, and reduce the LPO and MDA levels in the serum of D-Gal aging-induced mice. It is speculated that RRTP1-1 may be a new source of natural antioxidants for functional foods and dietary supplements (Chen & Kan, 2018a). According to reports RRTP can markedly improve the SOD, GSH-Px and CAT activities, and TAOC to some degree, and shorten the level of MDA in both serum and liver of D-Gal aging-induced mice (Chen & Kan, 2018b).
RRT polyphenol also has obvious antioxidant activity. Wang detected the antioxidant activity of 80% ethanol extract of RRT in vitro. The results showed that polyphenols might be the main antioxidant component in RRT. And ethyl acetate has the strongest activity (Wang, 2018). In addition, the free phenolic fraction and bound phenolic fraction were extracted from RRT pomace by solvent extraction method and alkaline hydrolysis method, separately. The results showed that RRT pomace could be a great and inexpensive source of natural antioxidants (Huang et al., 2022). Zhou et al. (2017) found that the total flavonoids of RRT had a strong DPPH free radical scavenging ability (Zhou et al., 2017). Li et al. (2020) optimized the extraction process of flavonoids from RRT seeds by ultrasonic-assisted extraction, and determined that flavonoids from Rosa roxburghii seeds had certain antioxidant activity (Li et al., 2020).
3.3 Anti-atherogenic properties
Lipid metabolism disorder is the pathological basis of atherosclerosis. And Hyperlipemia is a major risk element of atherosclerosis, so improving lipid metabolism disorder is deemed an important strategy to hold back cardiovascular disease (Juźwiak et al., 2005). RRT has been known as a dietary supplement for its wealthy alimentation and bioactive products, which can perfect dyslipidemia and reduce the risk of atherosclerosis (Song & Shen, 2021). Jian et al. (2015b) reported that RRT has a remarkable anti-atherosclerosis effect, which may be due to its ability to reduce blood lipid levels, LDL-C level and prevent its aggregation in cells, reduce LDL damage caused by lipid peroxide, improve SOD activity of red blood cells, prevent the damage caused by lipid peroxidation and LDL damage, and prevent foam cells from aggregation, thus inhibiting the occurrence of atherosclerosis (Jian et al., 2015b). Zhang et al. (2001) researched the outcomes of RRT juice on in vitro oxidative revision of LDL and on LDL-induced macrophage growth and cellular cholesteryl ester CE amassing (Zhang et al., 2001). Research results manifested that RRT juice uncased its antiatherogenic effectiveness largely because of its competence to restrain the oxidative modification of LDL and to control the constitution of foam cells. It was found that RRT juice can obviously prolong the oxidation delay time of HDL and HDL-3, significantly weaken their oxidation susceptibility and reduce their TBARS value, suggesting that RRT juice contains effective anti-HDL oxidation components (Feng et al., 2000). In addition, some studies (Jian et al., 2015a) have found that RRT juice can reduce blood lipid content, cell deposition, LPO to reduce LDL damage and effectively prevent foam cells from forming in the early stage of atherosclerosis. Wang et al. (2001) by establishing an experimental model of atherosclerosis in golden hamsters, it was found that RRT can be used as an antioxidant to improve the oxidative susceptibility of low density lipoprotein and reduce the occurrence of atherosclerosis (Wang et al., 2001).
3.4 Hypoglycemic properties
The chronic presence of hyperglycemia leads to chronic damage and dysfunction of various tissues, especially the eyes, kidneys, heart, blood vessels and nerves. Chen et al. (2019c) revealed that the RRT formula beverage efficiently modified the polydipsia and polyphagia symptoms of diabetic mice, restrained body loss, expressively improved liver glycogen content, significantly lessened FGB, GSP concentration and GHb relative content, and enhanced insulin sensitivity, reflecting that the formula beverage had an assistant hypoglycemic influence on diabetic mice (Chen et al., 2019c). An et al. through the STZ-induced type 1 diabetic rat model, the hypoglycemic effect of RRT fruit wine on diabetic rats and its possible mechanism were studied from physiological and biochemical indexes and mRNA levels. The results showed that the high, middle and low dose groups of RRT fruit wine could reduce the blood sugar level of diabetic mice to different degrees compared with the model group, especially the high and middle dose groups had significant differences from the model group. Zhang et al. (2004) found that flavonoids from RRT can effectively protect the pancreas from oxidative damage caused by alloxan and prevent diabetes (Zhang et al., 2004). Chen et al. (2021) reported the effect of RRT, RRT total polysaccharide extract (RP), and RRT total flavonoid extract (RF) on glucose and lipid metabolism disorders in type 2 diabetic mice (T2DM). RRT, RP, and RF can all build up the turmoil of glucose and lipid metabolism of T2DM mice. The effect of RP and RF is meaningfully better than that of RRT (P < 0.05), and the impact of RF is expressively better than that of RP and positive (Chen et al., 2021). In addition, T2DM is an acute chronic metabolic disorder characterized by senior BG and lipid metabolism disorders (Cao et al., 2018). Wang et al. (2019) reported that db/db mice were selected as model mice to value the anti-hyperglycemia and anti-hyperlipidemia activities of RTFP. The results manifest that the oral administration of RTFP could markedly reduce the body weight, fat, and liver hypertrophy and the extents of fasting blood glucose, serum insulin, and serum lipids of the db/db mice. Selenium nanoparticles functionalized with a novel polysaccharide could meaningfully inhibit H2O2-induced INS-1 cell apoptosis by attenuating oxidative stress and down-regulation expression of UCP-2. Their findings broadly prove that RP3-SeNPs can function as a promising candidate for the treatment of ROS-mediated diabetes (Wang et al., 2019). These findings suggest that RTFP can be used as a promising functional supplement to prevent and treat type 2 diabetes (Wang et al., 2020).
3.5 Immunoregulatory properties
For the non-specific immune function of animals, RRT can have a significant impact on it, for example, it can enhance the phagocytosis of macrophages, promote the level of serum lysozyme, increase the number of B lymphocytes, promote the body's ability to secrete antibodies, and enhance the peripheral blood T lymphocytes of mice (Wang, 2019). Zhang et al. (1998) fed the mice with RRT juice (0. 5 mL/d/mouse) for 5 days, the NK activity and the levels of IL-2, TNF-β and IFN-γ in the spleen cells of mice were significantly enhanced, indicating that the cellular immune function of mice was improved (Zhang et al.,1998). Li et al. (2019) by injecting 0.6 mL RRT extract into the stomach of mice, the spleen index and thymus index were significantly increased, and the immune function was improved (Li et al., 2019). According to a report, total triterpenes from RRT can improve the immune function inhibition induced by CTX, enhance the body's antioxidant capacity, proliferate macrophages of RAW264.7, inhibit the secretion of NO by macrophages induced by LPS, and have potential anti-inflammatory and immune activity (Tian et al., 2022). It has been reported RRT polysaccharides can significantly improve the ability of mice to resist fatigue, hypoxia, high temperature and low temperature, and improve the immunity of mice (Lu & Bao, 2002). Dietary antioxidants, especially polyphenols, have been proved to increase the expression of HO-1 in different in vitro systems. The potential use of these natural substances in regulating immune response should be carefully studied (Brambilla et al., 2008). Furthermore, Urine arsenic level in patients with arsenism caused by coal burning is closely related to the suppression of immune function. RRT preparation can efficiently build up the immune function of patients with arsenism (Li et al., 2013).
3.6 Radioprotection properties
Xu et al. (2014) by detecting the cell survival rate, the radiation protection of flavonoids from RRT was studied, the 30-day survival rate of mice and the number of colony forming units in spleen (CFU-S) after Co60 irradiation. Pretreatment with FRT before irradiation resulted in a significant increase in the cell survival rate at 24 h after 5 Gy irradiation, the 30-day survival rate of mice exposed to 8 Gy potentially lethal dose, and the CFU- sulfur content of mice exposed to 6 Gy dose. All these results indicate that FRT is an effective radio protective agent (Xu et al., 2014). Xu et al. (2016) investigate the radiation protective effect of RRT flavonoids and to explore the role of the Bcl- 2(Ca2+)/Caspase-3/PARP-1 pathway in radiation-induced apoptosis (Xu et al., 2016). And Flavonoids from RRT reduced radiation damage through PARP-1 in vivo and in vitro (Xu et al., 2020). Xu et al. (2017) conclude that FRT enhanced radioprotection at least partially by regulating PARP-1/AIF to reduce apoptosis (Xu et al., 2017). Other research suggested that FRT reinforced radioprotection at the lowest half by adjusting caspase 3/8-10, AIF, and PARP-1 to reduce apoptosis and by regulating ICAM-1, IL-1α/IL-6, TNF-α/NF-κB to weaken inflammation (Xu et al., 2018). Besides, using ultraviolet radiation to damage the cell model of skin inflammation caused by releasing self RNA from epidermal cells, it was found that the 50% aqueous extract of RRT inhibited interleukin-8 mRNA expression in normal human epidermal keratinocytes stimulated with polyinosinic: polycytidylic acid, a ligand of toll-like receptor-3 (Takayama et al., 2021). Hao et al. (2016) investigated the effect of prickly pear flavonoids on the cell cycle of radiation-injured bone marrow. The results showed that prickly pear flavonoid could reduce the G2 phase of bone marrow cells after the radiation phase and increase the proportion of cells in G1 and S phases after radiation, and had a protective effect on γ-radiation-induced bone marrow cell damage. Radiation-induced bone marrow cell injury, and showed a protective effect to a certain extent, and the protective effect was concentration-dependent within a certain concentration range (Hao et al., 2016). RRT extract has an anti-Violet radiation effect. It is hypothesized that RRT extract could be used as a novel anti-inflammatory anti-inflammatory agent for the prevention of inflammation and anti-photoaging.
3.7 Regulate the digestive system
Dyspepsia is a systemic disease of the gastrointestinal tract caused by a decrease of digestive efficiency and internal flocculation. With the improvement of people's quality of life and the change in lifestyle, its incidence is also increasing. Tu et al. (2020) made animal experiments on 15th day mice and 28th day rats, and measured indexes to evaluate the efficacy of promoting digestion. Research proves that RRT juice has the function of promoting digestion, such as RRT juice developed into food with digestive effects, which will greatly promote the development of new products in the field of food therapy (Tu et al., 2020). RTFP-3 could significantly increase the yield of total short-chain fatty acids from 23.49 to 44.29 mM, and 60.28% of total carbohydrate was consumed after 48 hours of fermentation. In addition, RTFP-3 could significantly regulate the microbial structure, reducing the ratio of scleroderma to bacteroides from 14.89 to 4.68 mM after 48 h of fermentation, and increasing the relative abundance of some beneficial intestinal microflora. RTFP treatment reversed gut symbiosis by lowering the Firmicutes-to-Bacteroidetes ratio and enhancing the relative abundances of beneficial bacteria including Bacteroidaceae, Bacteroidaceae S24-7 group, and Lactobacillaceae (Wang et al., 2020). Tu et al. (2021) study the effect of RRT on gastrointestinal motility in mice with dyspepsia, some studies have shown that RRT oral liquid has a good effect on promoting digestion and effectively promoting gastrointestinal motility (Tu et al., 2021). RRT juice has a definite therapeutic effect on acetic acid-induced gastric ulcer model rats. Zheng et al. (2017) shows that RRT juice can increase the acidity of gastric juice in rats, reduce the activity of pepsin and the number of gastric ulcer, increase the activity of SOD in gastric tissue, and at the same time reduce the content of MDA and increase the content of PGE2 in serum. The mechanism of action may be related to the fact that RRT juice promotes the increase of TFF-2, EGF and NO content, thus improving the protection and repair of gastric mucosa (Zheng et al., 2017).
3.8 Other functions
In addition to the above pharmacological activities, RRT and its extracts also have anti-stress (van der Westhuizen et al., 2008), organ protection (liver, kidney and heart) and tyrosinase inhibition activities. The research shows that RRT lyophilized powder can effectively prevent renal fibrosis and injury in rats, which is related to inhibiting oxidative stress and TGF-β1/Smads signal transduction (Zhan et al., 2019). And a study found that RRT is rich in phenolic acid in hyperlipidemic rats have a hypolipidemic effect (Wu et al., 2020b). Furthermore, it has been shown that RRT has an ameliorative effect on ether-induced psychomotor alterations (Peña et al., 2014). One finding indicates that the protective effects of a polysaccharide from RRT can be used as a natural anti-inflammatory agent to reduce chronic obesity induced colitis (Wang et al., 2022). Moreover, the compound of RRT extract can alleviate liver injury caused by alcohol, liver lipopolysaccharide signal and intestinal barrier dysfunction (Li et al., 2015). Side effects of RRT have not been reported.
4 Conclusion
In recent years, RRT has received increasing attention in China and extensive research has been conducted on its chemical composition and its pharmacological activity. At least 78 small molecular compounds including flavonoids, organic acids, tannins and 11 polysaccharide components have been isolated from RRT, and it has been found that RRT has various effects such as antioxidant, antitumor, hypoglycemic, immune modulation and anti-radiation. This will also provide more ideas for the development of functional foods for this ancient fruit.
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Practical Application: The review provides a comprehensive information for consumers and researchers to understand RRT Chemical constituents and bioactivities.
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Funding
This work was supported by the Department of Science and Technology of Guizhou Province (Nos. QKHZC [2021] normal 476, QKHPTRC [2019]5657, QKHZC [2019]2953, QKHZC [2020]4Y072, QKHPTRC [2018]5772-001), Department of Education of Guizhou Province (QJHKY[2021]049) and Guizhou Engineering Research Center of Industrial Key-technology for Dendrobium Nobile (QJJ[2022]048 and QJJ[2022]006), Chongqing Science and Health Joint Chinese Medicine Research Project (2019ZY023205), Chongqing Key Specialties in Clinical Pharmacy Construction Project (No. YWBF[2020]68).
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Publication Dates
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Publication in this collection
29 Aug 2022 -
Date of issue
2022
History
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Received
20 June 2022 -
Accepted
01 Aug 2022