Progress in Research of Roses in Diabetes Treatment

2021-01-03 14:04XuBAIYanruiCHEN
农业生物技术(英文版) 2021年6期

Xu BAI Yanrui CHEN

Abstract Diabetes is a common endocrine and metabolic disease, which is mainly caused by insufficient insulin secretion and improper secretion of glucagon by the pancreas. The mortality of diabetes and its complications is only second to tumors and cardiovascular diseases. At present, the research on natural drugs related to diabetes attracts much attention, and roses, as a traditional Chinese medicine that can be used as both medicine and food, are considered to be a new therapeutic agent for diabetes research in the future. In this paper, progress in research on the treatment of diabetes by rose was reviewed from the aspects of chemical constituents, pharmacological effects and their relationship with diabetes. The review includes  Rosa rugosa  Thunb., Branchlets  R. rugosa  Thunb.,  R. damascena  Miller and  R. damascena  ‘Hetian’. It can be seen that roses are rich in polyphenols, flavonoids, pectic bee pollen polysaccharide, quercetin, tannins, organic acids and other hypoglycemic chemical components. Modern pharmacological studies show that roses have hypoglycemic effects. It has been reported in animal experiments that rose extract can reduce blood sugar and improve diabetes symptoms. However, the clinical hypoglycemic effect and hypoglycemic mechanism of rose have yet to be clarified, and the comparative study of hypoglycemic effects of different rose varieties has not been published.

Key words Roses; Hypoglycemic effect; Diabetes; Research progress

Received: August 23, 2021  Accepted: October 26, 2021

Supported by Newly Introduced Doctor Scientific Research Start-up Project of Guilin Medical University (20501019030).

Xu BAI (1977-), male, P. R. China, senior engineer, master, devoted to basic medical research.

*Corresponding author. E-mail: 442660048@qq.com.

Diabetes is a metabolic disease characterized by persistent hyperglycemia and having a mortality rate second only to tumors and cardiovascular diseases. It is a common chronic non-communicable disease and has become a serious global public health problem. Diabetes and its complications seriously affect human health and their prevention and treatment are a major research topic worldwide. The development of drugs for the treatment of diabetes is highly valued. At present, the clinical treatment of diabetes mainly relies on insulin injections and oral hypoglycemic drugs, but they produce many side effects, and the treatment cost is very high, which brings a heavy economic burden[1]. The latest research shows that traditional Chinese medicine can improve glucose metabolism and reduce blood sugar, which provides a new method for the prevention and treatment of diabetes[2]. Therefore, finding safe effective natural medicines with less adverse reactions from plant resources to treat diabetes and its complications is still the focus and hotspot of the world’s medical workers[3-4].

Chemical Constituents and Pharmacological Effects of Roses

Roses refer to the dried petals of  Rosa rugosa  Thunb., which are used as traditional Chinese medicine and foodstuff. They are widely used and have a high medicinal value. Yao Kecheng’s  Food Materia Medica  recorded: "It mainly benefits the lungs and spleen, benefits the liver and gallbladder, wards off evil spirits, and has a sweet and refreshing fragrance when being eaten as a food". A large number of domestic and foreign studies have shown that roses contain ingredients such as polyphenols, flavonoids, sugars, volatile oils, terpenes, tannins and phenylpropanoids, as well as vitamins, amino acids, proteins, pigments and fats[5-6], which are the material basis for good pharmacological effects of roses. Modern pharmacological studies have shown that roses have a wide range of pharmacological activity, such as myocardial ischemia-improving[7], oxygen free radical-eliminating, anti-oxidation[8], antibacterial and antiviral[9] and antitumor activity[10]. Rose varieties with hypoglycemic active ingredients or hypoglycemic effects reported in the literature mainly include  Rosa rugosa  Thunb., Branchlets  R. rugosa  Thunb.,  R. damascena  Miller, and  R. damascena  ‘Hetian’. The chemical composition and pharmacological functions of these 4 rose varieties are shown in Table 1 below.

Roses are rich in polyphenols, such as gallic acid, ellagic acid, quercetin, isoquercetin, kaempferol, rutin, chlorogenic acid, catechin, apigenin, proanthocyanidin and its glycoside compounds,  etc. , and can inhibit the activity of α-glucosidase and improve insulin sensitivity, thereby improving the symptoms of diabetes[5,25]. Jiao[26] pointed out that quercetin extracted from roses could effectively reduce postprandial blood glucose in mice[26]. Rose flavonoids have a hypoglycemic effect on alloxan-induced diabetic mice[8]. There is also a large number of carbohydrates in roses, among which glycoprotein complexes and soluble rose polysaccharides are important active ingredients. Li  et al. [27] isolated pectic bee pollen polysaccharide (RBPP-P) from roses, which promotes autophagy through the AMPK/mTOR-mediated signaling pathway, which significantly alleviates the conditions of poor glucose intolerance and insulin resistance in obese mice induced by high-fat diet. They suggested that RBPP-P could be a novel therapeutic agent used for the treatment of obesity and diabetes. Research reports have confirmed that flowers and roots of rose have hypoglycemic effects. In the ethnic medicine of South Korea[9-10], Japan[28] and China[29], it has been found that roses can be used to treat diabetes and its complications.

Relationship between Roses and Diabetes

In recent years, the research on the effect of roses on lowering blood sugar has attracted more and more attention[29-30]. Feng  et al. [7] used a high-throughput assay to evaluate the activity of 92 traditional Chinese herbal medicines on α-glucosidase and α-amylase. They found that rose flower extract had a great inhibitory effect on α-glucosidase and α-amylase, indicating that roses are an effective natural hypoglycemic agent, which can be used in the production of hypoglycemic food or Chinese herbal formulae for controlling hyperglycemia. Cho  et al. [31] reported that roses could improve abnormal glucose metabolism that causes oxidative stress, reduce the production of free radicals related to diabetes, and reduce the oxidative stress related to the disease by inhibiting lipid peroxidation. The results provide a theoretical basis for the use of roses in the treatment of diabetes. The hypoglycemic effects of these four rose varieties are shown in Table 2 below.

CHO  et al. [31] experimentally studied the hypoglycemic effect of rose water extract on SD rats induced by streptozotocin. After administration treatment, they found that it could significantly reduce the levels of blood sugar, triglycerides, total cholesterol, alanine aminotransferase and aspartate aminotransferase in diabetic rats, while increasing serum insulin and high-density lipoprotein levels. Zhang  et al. [38] pointed out that rose flower extract could promote glucose consumption and has potential hypoglycemic activity. It activates the PIEK/AKT insulin signaling pathway by increasing the phosphorylation levels of IRS-1 and downstream signaling molecules PDK1, AKT and GSK-3β protein, thereby promoting insulin signaling and glycogen synthesis, and achieving the effect of lowering blood sugar. Guo  et al. [36] revealed that the blood sugar-lowering active ingredients of Xinjiang Branchlets  R. rugosa  Thunb. were contained in its alcohol extract, and the hypoglycemic mechanism might be related to the inhibition of α-glucosidase activity, which in turn inhibits the increase of blood sugar. Gholamhoseinian  et al. [37] pointed out that rose flowers are anti-diabetic and could reduce postprandial hyperglycemia with glucosidase inhibitor acarbose as a control. It can be seen that the effect of rose water extract in improving diabetes may be achieved by lowering the blood sugar level of diabetic rats, promoting secretion of insulin by pancreatic β cells and improving the liver function of rats. Liu  et al. [24] carried out research on the separation of chemical components of  R. damascena  ‘Hetian’ and its hypoglycemic activity, and the results showed that the concentrated polyphenol extract of  R. damascena  ‘Hetian’ had hypoglycemic activity.  R. damascena  ‘Hetian’ has no toxic side effects and is of great significance for delaying the progression of diabetes and relieving diabetic constipation.

Summarizing literature reports, roses have played an excellent role in the treatment of diabetes, and they may be considered a new type of therapeutic agents for diabetes research in the future. The literature mainly reported the hypoglycemic active ingredients in  R. rugosa  Thunb., Branchlets  R. rugosa  Thunb.,  R. damascena  Miller,  R. damascene  ‘Hetian’, or the hypoglycemic effect of certain components, and the overall hypoglycemic effects of roses as a Chinese medicinal material, the hypoglycemic efficacy of roses, and the comparative study on the hypoglycemic effects of different rose varieties have not been reported yet.

Branchlets R. rugosa Different extracts of roses had a certain α-glucosidase inhibitory activity, and the  IC 50 values of Ms and Mc were 23.14 and 11.35 μg/ml, respectively; multiple administrations of Mc could significantly reduce the blood glucose of normal mice, and showed a certain dose-effect relationship, and medium and high doses of Mc had better blood glucose lowering effects than acarbose[36].

R. rugosa  extract could significantly reduce the blood sugar of diabetic mice and improve their glucose tolerance, showing that it had an antagonistic effect on the increase in blood sugar caused by exogenous glucose[21].It inhibited α-glucosidase activity, thereby inhibiting the increase in blood sugar.

The hypoglycemic active ingredients of Branchlets  R. rugosa  were contained in its alcohol extract, and the hypoglycemic mechanism might be related to the inhibition of α-glucosidase activity, which further results in inhibition of the increase in blood sugar[36].[21, 36]

R. damascena The rose flowers have anti-diabetic properties and reduce postprandial hyperglycemia[37].The effect of rose water extract in improving diabetes might be achieved by reducing the blood sugar level of diabetic rats, promoting the secretion of insulin by pancreatic β cells and improving the liver function of rats[37] .[37]

R. damascena ‘Hetian’Polyphenol concentrate extract (RPE) of  R. damascene  ‘Hetian’ could significantly reduce the blood sugar level of diabetic rats, improve impaired glucose tolerance and insulin resistance, increase muscle glycogen content by about 3 times, and improve activity of hexokinase and antioxidant enzymes (SOD, CAT, GSH-PX, MDA). It has hypoglycemic activity and excellent antioxidant capacity[24].Its polyphenol extract has the effect of promoting cellular glucose consumption, and could act synergistically with insulin to significantly increase glucose consumption[24].[24]

Conclusions

Diabetes belongs to the category of consumptive thirst in Chinese medicine, and its causes are complicated, mainly due to insufficient congenital endowment, yin deficiency in the body, as well as improper diet, emotional imbalance, and excessive exertion, which lead to visceral dysfunction, abnormal circulation of qi and blood, yin deficiency and dryness, finally leading to the occurrence of the disease. Being diagnosed with diabetes, individual patients vary greatly, and their response and prognosis to the disease are also worlds apart, so the main object of observation by medical researchers is "people" instead of "disease." As a result, different diabetic patients should be treated differently due to their etiology, disease progression and characteristics, and their treatment and prevention methods are also different from person to person. According to "the same source of medicine and food", roses, and other good products (such as mulberry leaves, kudzuvine root and hawthorn) that have been studied by modern pharmacological studies and have been found to have the effects of regulating blood sugar and lowering blood sugar, can be used as a supplementary treatment in different medicated diet prescriptions, based on syndrome differentiation which takes conventional treatment as the mainstay and varies from person to person.

Because different patients with diabetes and its complications consume foods that are different in the type, proportion and amount and their food absorption conditions are also different, their course of disease development and results are also different. Both the AHS-2 study in California, USA, and related studies in Taiwan, China, have shown that a vegetarian diet can significantly reduce the incidence of fasting blood sugar and diabetes (RR: 0.38-0.49)[39-40], and changing from a non-vegetarian to a vegetarian can reduce the risk of diabetes by 53% (HR: 0.47, 0.30-0.71)[41]. In India, vegetarians who eat fish but do not eat other meats may increase the risk of diabetes, and the odds ratio (OR) is 1.15 (95%  CI  0.85-1.54)[42]. Therefore, diabetic patients should carry out reasonable diet control based on syndrome differentiation while accepting medication, so that medication can play a better role.

References

[1] ZHANG B. Hypoglycemic active ingredients and synergetic effect of alpha-glucoside inhibitor from Ramulus Mori (RM)[D]. Chongqing: Southwest University, 2013. (in Chinese)

[2] TANG MT, XIAO BQ, LIU ZH,  et al.  Progress in the understanding of the roles and mechanisms of Traditional Chinese Medicine in lowering blood glucose by regulating gut microbiota[J]. Chinese Journal of Comparative Medicine, 2020, 30(5): 120-126. (in Chinese)

[3] DIAO YL, JIANG W, ZHU T,  et al.  Antidiabetic activities of natural plant polysaccharides and their advances[J]. Journal of International Pharmaceutical Research, 2011, 38(4): 275-279. (in Chinese)

[4] JIANG Z, HU TJ, LI JP. Research progress of Chinese medicine rose[J]. Diabetes New World, 2015(11): 229-230. (in Chinese)

[5] MANSUR S, ABDULLA R, AYUPBEC A,  et al.  Chemical fingerprint analysis and quantitative analysis of  Rosa rugosa  by UPLC-DAD[J]. Molecules, 2016, 21(12): 53-56

[6] SARANGOWA O, KANAZAWA T, NISHIZAWA M,  et al.  Flavonol glycosides in the petal of Rosa species as chemotaxonomic markers[J]. Phytochemistry, 2014(107): 61-68.

[7] FENG L, CHEN C, LI T,  et al.  Flowery odor formation revealed by differential expression of monoterpene biosynthetic genes and monoterpene accumulation in rose ( Rosa rugosa  Thunb.)[J]. Plant Physiology and Biochemistry, 2014(75): 80-88.

[8] ZHANG J, RUI X, WANG L,  et al.  Polyphenolic extract from  Rosa rugosa  tea inhibits bacterial quorum sensing and biofilm formation[J]. Food Control, 2014(42): 125-131.

[9] SEO E, YOU Y, YOON HG,  et al.   Rosa rugosa  aqueous extract alleviates endurance exercise-induced stress[J]. Journal of Medicinal Foo, 2015, 18(6): 711-713.

[10] LEE YH, JUNG MG, KANG HB,  et al.  Effect of anti-histone acetyltransferase activity from  Rosa rugosa  Thunb. (Rosaceae) extracts on androgen receptor-mediated transcriptional regulation[J]. Journal of Ethnopharmacology, 2008, 118(3): 412-417.

[11] FU M, NING TB, JIANG Y,  et al.  Compounds from rose ( Rosa rugosa ) flowers with human immunodeficiency virus type 1 reverse transcriptase inhibitory activity[J]. J Pharma Pharmacol, 2006(58): 1275-1280.

[12] LI M, LI YF, SUN YC,  et al.  Research progress of Chinese medicine rose[J]. Health Vocational Education, 2007, 8(25): 145. (in Chinese)

[13] LIU HY, WANG Y, YAN WP,  et al.  Study on extraction process of total flavones in branchlet rose[J]. Journal of Xinjiang Medical University, 2018, 41(8): 1016-1018. (in Chinese)

[14] JIANG JJ. Activity screening and determining the component content of branchlets roses[D]. Urumqi: Xinjiang Medical University, 2016. (in Chinese)

[15] LAN W, WANG Y, HAO YW,  et al.  Effects of uygur medicine branchlets roses extracts on blood glucose and glucose tolerance in diabetes mice induced by alloxan[J]. Drug Evaluation Research, 2017, 40(4): 492-495. (in Chinese)

[16] State Administration of Traditional Chinese Medicine Chinese Materia Medica Committee. Chinese materia medica: Uyghur medicine sub-volume[M]. Shanghai: Shanghai Scientific & Technical Publishers,2005: 209-211. (in Chinese)

[17] Pharmacopoeia Committee of the Ministry of Health of the People’s Republic of China. Drug standards of the Ministry of Health of the People’s Republic of China: Uyghur medicine fascicule[M]. Urumqi: Xinjiang Science and Technology Medical Publishing House, 1999: 152-153. (in Chinese)

[18] JIANG JJ, GUO YT, SHI Y,  et al.  Determination of gallic acid content in the Uyghur medicine branchlets rose[J]. Journal of Xinjiang Medical University, 2016, 39(12): 1563-1565. (in Chinese)

[19] VENKATESAN B, SUBRAMANIAN V, TUMALA A,  et al.  Rapid synthesis of biocompatible silver nanoparticles using aqueous extract of Rosa damascena petals and evaluation of their anticancer activity[J]. Asian Pacific Journal of Tropical Medicine, 2014, 7(S): 294-300.

[20] MAHBOUBI M. Rosa damascena as holy ancient herb with novel applications[J]. Journal of Traditional and Complementary Medicine, 2016, 6(1): 10-16.

[21] MUHAMMAD A, MUHAMMAD R, NAVEED M. Chemical constituents, experimental and clinical pharmacology of Rosa damascena: A literature review[J]. Journal of Pharmacy and Pharmacology, 2020, 72(2): 161-174.

[22] MAHMOOD N, PIACENTE S, PIZZA C. The Anti-HIV activity and mechanisms of action of pure compounds isolated from Rosa damascene[J]. Biochem Biophys Res Commun, 1996, 229(1): 73-79.

[23] MANSUR SANAWAR. Study on the composition analysis and quality standards of three Uyghur medicines based on LC-MS/MS technology[D]. Beijing: University of Chinese Academy of Sciences, 2017. (in Chinese)

[24] LIU L. Study on pharmacological effects of  Rosa rugosa  Thunb. and  Chrysanthemum×morifolium  Ramat prescriptions on improving insulin resistance[D]. Beijing: University of Chinese Academy of Sciences, 2019. (in Chinese)

[25] GU D, YANG Y, BAKRI M,  et al.  A LC/QTOF-MS/MS application to investigate chemical compositions in a fraction with protein tyrosine phosphatase 1B inhibitory activity from  Rosa rugosa  flowers[J]. Phytochemical Analysis: PCA. 2013, 24(6): 661-670.

[26] JIAO DL. Analysis and research progress of Chinese medicine rose[J]. Health Guide, 2019(32): 226. (in Chinese)

[27] LI X, GONG H, YANG S,  et al.  Pectic bee pollen polysaccharide from  Rosa rugosa  alleviates diet-induced hepatic steatosis and insulin resistance via induction of AMPK/mTOR-mediated autophagy[J]. Molecules 2017, 22(5): 55-63.

[28] CHEN T, LI J, CHEN J,  et al.  Anti-hyperplasia effects of  Rosa rugosa  polyphenols in rats with hyperplasia of mammary gland[J]. Environmental Toxicology and Pharmacology, 2015, 39(2): 990-996.

[29] ZHOU D, LU XX, LUO C. Anti-hyperglycemic effect of flavonoids of rose in vivo[J]. Science and Technology of Food Industry, 2011, 32(2): 319-321. (in Chinese)

[30] NA JR, OH DR, HAN S,  et al.  Antistress Effects of  Rosa rugosa  Thunb. on total sleep deprivation-induced anxiety-like behavior and cognitive dysfunction in rat: Possible mechanism of action of 5-HT6 receptor antagonist[J]. Journal of Medicinal Food, 2016, 19(9): 870-881.

[31] CHO EJ, YOKOZAWA T, KIM HY,  et al.   Rosa rugosa  attenuates diabetic oxidative stress in rats with treptozotocin-induced diabetes[J]. Am J Chin Med, 2004, 32(4): 487-496.

[32] CHEN RR, WANG CR, JIANG J,  et al.  Antihyperglycaemic actions of the antioxidant components from  Rosa rugosa  Thunb and  Pleurotus abalones [J]. Acta Scientiarum Naturalium Universitatis Nankaiensis, 2009, 42(2): 87-91. (in Chinese)

[33] CHEN RR, WANG CR, H J,  et al.  Study on the hypoglycemic mechanism of rose flower and abalone mushroom extracts[J]. Chinese Traditional and Herbal Drugs, 2009, 40(12): 1952-1955. (in Chinese)

[34] KIM EJ, KIM GY. Hypoglycemic and hypolipidemic effect of  Rosa rugosa  radix in Streptozotocineinduced diabetic rats[J]. Korean J Oriental Physiol Pathol, 2010, 24(5): 866-871.

[35] SHAO W, LIU ZK, LIU F. Studies on the anti-ageing actions of the extracts from  Rosa rugosa [J]. Acta Scientiarum  Naturalium  Universitatis Nankaiensis, 2008, 41(3): 64-68. (in Chinese)

[36] GUO YT, LAN W, TIAN SM,  et al.  The study on anti-diabetes and its mechanism of Xinjiang branchlets roses[J]. Journal of Xinjiang Medical University, 2015, 38(4): 452-454. (in Chinese)

[37] GHOLAMHOSEINIAN A, FALLAH H, SHARIFI FAR F. Inhibitory effect of methanol extract of Rosa damascena Mill[J]. Phytomedicine, 2009, 16(10): 935-941.

[38] ZHANG XC, TANG D, DOU J. Hypoglycemic activity of Xinjiang rose extracts in vitro[J]. Herald of Medicine, 2016; 35(7): 693-697. (in Chinese)

[39] TONSTAD S, STEWART K, OD K,  et al.  Vegetarian diets and incidence of diabetes in the adventist health study-2[J]. Nutr Metab Cardiovasc Dis, 2013, 23(4): 292-299.

[40] CHIU TH, HUANG HY, CHIU YF,  et al.  Taiwanese vegetarians and omnivores: dietary composition, prevalence of diabetes and IFG[J]. PlosOne, 2014, 9(2): 1-7.

[41] CHIU THT, PAN WH, LIN MN,  et al.  Vegetarian diet, change in dietary patterns, and diabetes risk: a prospective study[J]. Nutr Diabetes, 2018, 8(1): 12.

[42] AGRAWAL S, MILLETT CJ, DHILLON PK,  et al.  Type of vegetarian diet, obesity and diabetes in adult Indian population[J]. Nutr J, 2014(13): 89.