Research and Prospect of Mulberry (Morus alba L.)

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  Abstract Mulberry (Morus alba L.) is not only rich in nutrients, but also has medicinal value. As a drug and food, it is widely planted all over the country, with considerable yield and economic value. In recent years, it has attracted many scholars and been widely reported, and indepth research has already been conducted. Through reviewing the literatures on mulberry, this paper summarized the chemical composition, pharmacological effects and quality evaluation of mulberry, providing some reference for the further development and utilization of mulberry.
  Key words Morus alba L.; Chemical components; Pharmacology; Quality evaluation; Research progress
   Mulberry, also known as "Sangshenzi", refers to the dry ear of Morus alba L. which is a Moraceae plant[1]. Mulberry was recorded as early as in "Er Ya" and "Compendium of Materia Medica"[2-3]. The fresh fruit of mulberry can be eaten directly or dried for medicinal use, and it is a longestablished medicine and food. At present, the planting area of fruit mulberry has reached 53 300 hm2, and the output of mulberry has exceeded 790 000 t. It is planted in most parts of China and has abundant resources, most of which are sold as succulent seasonal fruits. When it is used as a medicine, it has the effects of nourishing yin and blood, moisturizing dryness and producing fluid, and is often used for treatment of yin deficiency of liver and kidney, dizziness, tinnitus, palpitations, premature graying of hair, and intestinal dryness with constipation[1]. As a medicine and food, mulberry is also very active in its research and development. This paper reviewed the research status of mulberry in the past decade.
  Chemical Composition of Mulberry
  The chemical composition of mulberry is complex. At present, nearly 400 compounds are isolated from mulberry plants, such as flavonoids, phenolic acids, polysaccharides, and various amino acids[4]. The moisture content of mulberry fruit is more than 80%, the sugar content is about 9%, and the organic acid content is about 2%, so the taste is sweet and sour. As a drug, it also contains effective medicinal ingredients, including crude fiber, protein, vitamins, resveratrol, and various flavonoids, minerals and anthocyanins[5].
  Flavonoids
  Flavonoids are widely found in nature, especially among plant secondary metabolites. They are a type of very common and strong antioxidants, which can effectively prevent cell aging and degradation, and have a certain disinfection effect[6]. The flavonoids in mulberry are mainly anthocyanins, rutin, quercetin, isoquercetin, dihydroquercetin, morin and kaempferol hexose glycoside[7].   Polysaccharides
  As a type of energy supply substances, polysaccharides are also good immune enhancers, which can lower blood fat, lower blood sugar and resist aging. Li[8]extracted the crude polysaccharide of mulberry by enzymeassisted water extraction, and then obtained six homogeneous polysaccharides through isolation and purification. They found that sulfated polysaccharides SulFMP6H and SulFMP6S2 can inhibit the lumen formation of HMEC1 cells in vitro and had an antiangiogenic effect. Jiang[9]obtained mulberry polysaccharide by water extractionalcohol precipitation and alkali extractionalcohol precipitation. Mulberry polysaccharides MFP50 and MFP90 had better effects in treating type 2 diabetes with low toxic and side effects, and better pharmacological activity in restoring pancreatic injury, improving liver function and resisting oxidation than metformin.
  Anthocyanins
  Anthocyanins exist in the form of glycosides in the natural state, which are the main active ingredients and color forming substances of mulberry. They have antioxidant and antitumor activities, and are also a type of natural watersoluble food coloring agents with very good health efficacy and medicinal value and broad application prospects[10-11]. Minh Anh Thu Phan et al.[12]mixed lycopene and anthocyanins, and found that the mixture achieved an optimal antioxidant capacity of cells at 1∶3 or 1∶1, laying a foundation for the further development and application of natural products.
  Resveratrol
  Resveratrol is a polyphenolic compound with high content in fresh mulberry. It is a toxin produced by plants, which has antibacterial, anticancer, antioxidation, platelet aggregation and vasodilation inhibiting, lipoprotein metabolism regulating, body immunity improving and other effects[13]. However, resveratrol is not stable. Zhu et al.[14]explored the change of resveratrol content after mulberry harvesting by HPLC. They pointed out that the resveratrol content increased slightly 1-4 h after picking, and then decreased rapidly, and after 18 h, resveratrol had decreased by about3/4, which had been converted into products such as pterostilbene and piceid. Therefore, as a traditional Chinese medicine after harvesting and processing, the resveratrol content is often low.
  Amino acids
  LYU et al.[15]determined five new varieties of mulberry produced in the hilly area of Sichuan. The five mulberry varieties all contained 17 kinds of amino acids such as threonine, glutamic acid, glycine, cystine, valine, methionine, leucine, isoleucine, tyrosine, histidine and arginine, including eight kinds of essential amino acids. Wu et al.[16]found in the study of the nutritional composition of mulberry, the lysine content was 0.2 mg/100 g, the arginine content reached 9.15 mg/100 g, and the aspartic acid and glutamic acid contents were also higher. These amino acids play an important role in the metabolism and growth and development of the human body. They also found that the ratio of essential amino acids to nonessential amino acids in mulberry was 0.22, and the essential amino acid content reached the international reference protein model value, which is in line with the international standard of natural green food. So mulberry is considered to be an excellent fruit.   Pharmacological Effect
  Antioxidant effect
  The theory of aging free radicals believes that free radicals attack cell components and cause a series of damages of aging. There is a strong correlation between free radicals and the life of organisms[17]. Mulberry contains a large amount of flavonoids, polysaccharides and anthocyanins, and its antioxidant capacity is strong. Therefore, research on antioxidants such as mulberry has been paid with more and more attention in recent years. Zhang et al.[18]investigated the antioxidant capacity of mulberry juice in five different ways, and found that it had good effects in scavenging hydroxyl radicals, superoxide anion radicals and DPPH free radicals and inhibiting the oxidative activity of linoleic acid. Xu[19]extracted mulberry with 75% ethanol and performed purification with macroporous resin to obtain anthocyanins. It was found that mulberry anthocyanins showed a strong absorption capacity of oxidative free radicals and had certain anticancer effect. Fan et al.[20]determined the DPPH free radical scavenging ability, ABTS+·clearing ability and ferrous reduction ability of mulberry extract, respectively, and found that its antioxidant capacity and antiglycationcapacity were in a significant regression relationships with total anthocyanin and total phenolic contents, respectively.
  Antiinflammatory effect
  Zhu[21]studied the effect of mulberry extract on the secretion of RAW264.7 in mouse peritoneal macrophages induced by LPS and its mechanism. The results showed that the extract of mulberry has a good antiinflammatory effect, and its mechanism may be related to the promotion of RAW264.7 cell activation and inflammatory factor production. According to another study, mulberry flavonoids can inhibit xyleneinduced ear swelling in mice and formalininduced toe pain in mice, reduce serum TNFα and NO levels, and have antiinflammatory and analgesic effects[22].
  Enhancing immunity
  Mulberry suspension can enhance the lymphocyte proliferation ability, IL 2 deceptive life and NK cell killing rate in yin deficiency mice, thereby enhancing immune function[23]. Lu[24]found that mulberry had an inhibitory effect on trypsin activity which is a noncompetitive inhibition and anticompetitive inhibition mixed type, and it can promote hematopoietic function and immune enhancement.
  Lowering blood sugar, lowering uric acid and lowering blood fat
  Wang[25]found that mulberry flavonoids can significantly reduce blood glucose levels in hyperglycemic rats, and can reduce uric acid levels in hyperuricemia rats, and had a positive preventive effect on adenineinduced hyperuricemia in rats with kidney injury. Wang et al.[26]used New Zealand purebred white rabbits as research animals, and found that mulberry extract can inhibit the expression of ICAM1 and the formation of AS, thereby reducing blood lipids.   Protecting liver
  Deng[27]developed a model of alcoholic liver injury in mice and carried out research on the antialcoholic liver injury effect of FMPS. It was found that the highdose group had a good effect, and clarified the pharmacodynamic material basis of mulberrys antialcoholic liver injury effect. Mulberry anthocyanins can increase the glucose consumption and uptake and glycogen content of hepatocytes, inhibit the expression of gluconeogenesis related proteins, and promote the expression of glycogen synthesis related proteins[28], indicating certain liver protection effects.
  Resisting tumors
  According to the principle that after cleaving the substrate with enzymes, the fluorophore and quenching groups at both ends of the enzymes are separated to produce fluoresce, Jin[29]found that the water extract of mulberry can inhibit the overexpression of tumor MMP in vivo, and this inhibition increased as the concentration of the drug increased. Wang et al.[30]obtained the crude anthocyanin extract of mulberry by ethanol extraction, and found that mulberry anthocyanin significantly inhibited the proliferation of human breast cancer cell line MDAMB453 in vitro and in vivo, and significantly inhibited the growth of transplanted tumor of breast cancer, exhibiting a remarkable antibreast cancer effect.
  Others
  Sangshen Shouwu Bunao Granules can promote the recovery of learning and memory function by downregulating the expression of βamyloid in brain tissue, increasing SOD level and decreasing the expression of amyloid β in hippocampus[31]. Resveratrol in mulberry has a significant effect on Parkinsons and Alzheimers disease[32]. Teng et al.[33]used the ICR male mouse swimming method to observe the antifatigue effect of the drug. The highdose group significantly increased the activity of SOD and CAT in mice, and decreased the levels of MDA, BUN and lactic acid (LD), indicating that the water extract of mulberry has a good antifatigue effect.
  Agricultural Biotechnology2019
  Quality Evaluation
  Mulberry is widely distributed in China, but uneven in quality. In the 2015 edition of Chinese Pharmacopoeia, only the items of moisture, ash and extract in mulberry were examined. Therefore, in recent years, various mulberry quality evaluation methods have been studied.
  Quality evaluation of mulberry medicinal materials
  Cao[34]extracted the active constituents of Sangshen Ziyin Granules, and used the total flavonoid, total triterpenoid saponin and total polysaccharide contents as indicators to optimize the extraction process. He or she also optimized the preparation process of Sangshen Ziyin Granules by studying the molding process and investigating the effects of extract density, accessory types and dosages, and established the quality evaluation standard of Sangshen Ziyin Granules. Ren et al.[35]measured the chemical constituents of 80 batches of Zhenqi Fuzheng Granules from different manufacturers, and found that the contents and components of different manufacturers were consistent, but the contents were quite different. It is recommended to strictly control the feeding process and the production process to improve product stability.   Quality evaluation of mulberry foods
  Zhao et al.[36]carried out horizontal analysis, correlation analysis and factor analysis on the ten indicators including mulberry soluble solids, polyphenols and proteins in 38 varieties. It was found that the comprehensive flavor factor and functional factor had a great effect on the quality of mulberry, but according to different products, it is recommended to establish different mulberry quality evaluation systems. Zhang et al.[37]developed preserved mulberry fruit with natural color with sensory and physical and chemical data as indicators through the selection of mulberry color protection agent, selection of hardener, selection of concentration and time, optimization of vacuum infiltration condition and optimization of taste adjustment. On May 1, 2018, China Food Industry Association released the first mulberry wine standard T/CNFIA 1042018 "Mulberry (Fruit) Wine", putting forward clear requirements for sensory quality, physicochemical indexes, food additives, net content and related testing methods of mulberry wine[38].
  Development and Application
  Mulberry is widely used in medicinal applications. Xinmeng Granules, Sangshen Bunao Paste and Compound Jiangtangning Granules have already been better used in clinic, and have good curative effect in soothing the nerves, helping sleep and lowering blood sugar. For example, Xinmeng Granules, a new Chinese medicine product, can significantly reduce the contents of sleeprelated substances (the monoamine neurotransmitters 5HT, NE, and DA) in mice, and has obvious sedative and hypnotic effects on mice through central nervous system inhibition[39]. As a food, the development and utilization of mulberry is more extensive, and mulberry wine, preserved fruit, jam, yoghurt and beverage[40]are favored by consumers and have broad economic prospects. The application of mulberry extract has also been continuously developed, and its health care products are constantly emerging.
  Conclusions and Prospect
  Mulberry has been planted in China for thousands of years. The planting area of fruit mulberry has reached 53 300 hm2. In 2012, the industrial output value was over 3 billion yuan. With the continuous advancement of technology, its development and utilization and the deep processing industry continue to develop, and the output value keeps growing. However, the short harvesting period, the difficulty in storage and the uneven quality have become important reasons restricting the development of the mulberry industry, and are also key issues to be solved urgently. Processed mulberry products are abundant, and there is still much room for development in medicinal research. As one of the substances released by the National Health and Family Planning Commission, which is both food and Chinese herbal medicines, further deepening the medicinal value of mulberry in the field of food and health care research can further enhance the comprehensive utilization value of mulberry. In addition, the material basis for the pharmacological activity of mulberry has not been clarified, and the correlation between chemical composition and mulberry quality and efficacy needs to be further studied.   References
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  Editor: Yingzhi GUANG Proofreader: Xinxiu ZHU
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