Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964

International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 8 Number 04 (2019) Journal homepage: http://www.ijcmas.com

Review Article https://doi.org/10.20546/ijcmas.2019.804.341

The Mulberry, Morus alba (L.): The Medicinal Herbal Source for Human Health

Rutuja Ashok Kadam1*, Nivedita Dattatray Dhumal1 and Vitthalrao Bhimasha Khyade2,3,4

1Department of Home Science, Shardabai Pawar Mahila Mahavidyalaya, Shardanagar Tal. Baramati District, Pune – 413115, India 2A Sericulture Unit, Malegaon Sheti Farm, Agricultural Development Trust Baramati, Shardanagar, (Malegaon Khurd) Post Box No - 35, Baramati, Pune 413 115, Maharashtra, India 3Department of Zoology, Baramati Dist. Pune – 413115 (India Shardabai Pawar Mahila Mahavidyalaya, Shardanagar Tal), India 4Dr. APIS, Shrikrupa Residence, Teachers Society, Malegaon Colony (Baramati) Dist. Pune – 413115, India

*Corresponding author

ABSTRACT

Nutrient contents in the leaves of mulberry, Morus alba (L) made it to occupy the pace making place in the sericultural practices. The mulberry, Morus alba (L.) is native to eastern and central China. It became naturalized in Europe centuries ago. The tree was

introduced into America for silkworm culture in early colonial times and naturalized and K e yw or ds hybridized with the native red mulberry. The red or American mulberry is native to eastern United States from Massachusetts to Kansas and down to the Gulf coast. The black Antioxidants, mulberry is native to western Asia and has been grown for its fruits in Europe since before Mulberry, Morus Roman times. It is a flowering, fast growing, woody and perennial plant. Taxonomically, it alba (L.), Cancer, belongs to the family: Moraceae. Mulberry, Morus alba (L.) gained attention since time diabetes, immemorial. This is due to its pharmacological and economic value. Use of mulberry Deoxynojirimycin leaves in sericulture has been reported in the ancient Chinese literature and therefore well

recognized. Therapeutic Significance of Mulberry, Morus alba (L.) have been depicted in Article Info the ancient literature through Ayurveda. Some of the ayurvedic therapeutic preparations

Accepted: use fruits, leaves, roots, bark or latex of mulberry, Morus alba (L.) to administer against 20 March 2019 various human diseases. The raw mulberry fruits, of about 100 g are able to provide 180 kJ Available Online: (43 kcal), 44% of the Daily Value (DV) for vitamin C, and 14% of the DV for iron; and 10 April 2019 other nutrients. The health benefits of mulberry, Morus alba (L.) include their ability to improve digestion, lower cholesterol, help in weight loss, increase blood circulation, build bone tissues, and boost the immune system. The fruits of mulberry, Morus alba (L.) also helps prevent certain cancers, slow down the aging process, lower blood pressure, protect eyes, and improve the overall body metabolism. The present attempt is a overview

of the major pharmacological properties of Mulberry, Morus alba (L.) along with major applications of phytochemicals purified from it. 2941

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Introduction these berries ideal for sherbets, jams, jellies, fruit tarts, pies, wines, teas, and cordials. In Herbal contents are serving a lot to certain areas of the world, the flavors of the orchestrate the progression of development of mulberry varieties differ, but the American faculty of Medicine. Human being trusts mulberry and the black mulberry are effective and time-tested home remedies that considered to have the most powerful flavor have survived for several generations. Human and are widely sought after. Interestingly, the being is turning towards the herbal mulberry tree has another important resource, supplements than ever before. The person besides providing people with delicious living in a medicated nation does not like to berries and that is its leaves. The mulberry take the risk of side effect induced leaves are also the only known food source prescription drugs. The society is now looking for silkworms. for alternative ways of preventing any diseases or ailments. The herbal preparation The mulberry, Morus alba (L.) is also from medicinal plants is the one of the recognized as white mulberry. It is a fast- humanity’s oldest and wealthy health care growing, small to medium-sized mulberry tools. The herbal formulations are serving as tree which grows to 10–20 m tall. The the basis of modern medicines, Ancient species, Morus alba (L.) is native to northern civilizations relied on herbs and medicinal China. It is widely cultivated and naturalized plants for healing, as do many contemporary elsewhere (United States, Mexico, Australia, culture throughout the world. According to Kyrgyzstan, Argentina, etc.). The genus the World Health Organization, near about Morus contains more than 15 species of eighty percent of the population of the world deciduous plants commonly called mulberry. continues to use complimentary therapies, a The major ones include Morus alba, Morus major part of which are derived from the nigra, Morus rubra, Morus australis, Morus plants like, mulberry, Morus alba (L.). The atropurpurea, Morus cathayana, Morus mulberries are the sweet, hanging fruits from notabilis and Morus mesozygia. These are a genus of deciduous trees that grow in a economically important plant because the variety of temperate areas around the world. leaves are extensively used in sericulture. Thought to possibly have originated in China, Mulberries are filled with nutrients that are they have spread throughout the world and are important for our body, including iron, highly praised for their unique flavor and riboflavin, vitamin C, vitamin K, potassium, impressive composition of nutrients. In fact, phosphorous, and calcium. They also contain most varieties found in different parts of the a significant amount of dietary fiber and a world are considered to be ―native‖ from wide range of organic compounds, including those areas, as they are widespread. The phytonutrients, zeaxanthin, resveratrol, scientific name of mulberries varies anthocyanins, lutein, and various depending on which species you are looking polyphenolic compounds. Apart from this, at, the most common types are Morus many nutritional benefits and medicinal australis and Morus nigra, but there are other values are attributed to this plant. The leaves delicious varieties as well. In terms of contain high amount of protein and the appearance, the berries grow very fast when nutritional scientists in India suggested the they are young but gradually slow as their use of dry leaf powder for making parathas, color changes from white or green to pink or one of the most popular Indian food items. In red, and eventually settling on dark purple or Korea and Japan the mulberry leaves and even black. The sweet or tart flavor makes fruits are included in their functional foods,

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 used in the preparation of tea (Fig. 1 and 2) potential of mulberry, Morus alba (L.). The and ice creams. This plant has remarkable fruits of mulberry, Morus alba (L.) are effects in lowering serum glucose and blood considered as nutritious food. This is because, cholesterol levels enabling their use in the fruits of mulberry, Morus alba (L.) traditional Chinese herbal and folk medicines. contain flavonoids and polyphenols. The most These properties are due to the presence of important flavonoids and polyphenols many bioactive components such as identified from mulberry, Morus alba (L.) are flavonoids, polyphenols, alkaloids, apigenin, luteolin, quercetin, morin, caffeic terpenoids, steroids etc. in this plant acid, gallic acid, rutin, umbelliferone, (Scrivastava, et al., 2003; Andallu and chlorogenic acid and kaempferol (Arfan, et Varadacharyulu, 2003; Asano, et al., 2001). al., 2012 and Chu, et al., 2006). The Different parts (root bark, stem bark, leaves compounds like maclurin, rutin, isoquercitrin, and fruits) of the mulberry, Morus alba (L.) resveratrol and morin belong to the twigs and have been extensively investigated for their root bark of mulberry, Morus alba (L.) various health benefits, including (Chang, et al., 2011). The fruits of mulberry, antioxidative, hypolipidemic, Morus alba (L.) contains essential fatty acids antihyperglycemic, and antiatherogenic like palmitic, oleic and linoleic acids which effects (Harauma et al., 2007). The present are important for cell membrane formation, review focuses on the antioxidant activity and proper development and functioning of medicinal properties of mulberry, Morus alba nervous system, production of eicosanoids (L.) responsible for its therapeutic utilization, and many inflammatory responses (Ercisli with special emphasis on major bioactive and Orhan, 2007). Morus cathayana (L.) is principles from its different parts. The one more species of mulberry. This Morus parameters considered for the present attempt cathayana (L.) is a deciduous tree usually of review on therapeutic Significance of found in secondary forest and scrubland. The Mulberry, Morus alba (L.) include: tree of mulberry, Morus cathayana (L.) Antioxidative Potentials of mulberry, Morus reaches a height of up to 15 metres (49 feet). alba (L.); Antidiabetic Significance of It use to flower from May to June. It produces mulberry, Morus alba (L.); The mulberry, edible berries and its leaves are made into a Morus alba (L.) for cardiovascular diseases; tea. The phytochemical investigation of the Anticancer effects of mulberry, Morus alba stem bark of mulberry, Morus cathayana (L.) (L.); Anti-inflammatory effects of mulberry, led to the isolation and identification of Morus alba (L.); The mulberry, Morus alba cathayanin and various cathayanons (Ni, et (L.) for neurological disorders; The mulberry, al., 2010). Few arylbenzofurans with Morus alba (L.) for skin diseases; antioxidant and anti-inflammatory activities Hepatoprotective Potentials of mulberry, were reported form M. wittiorum (Tan, et al., Morus alba (L.); The mulberry, Morus alba 2010). HPLC coupled with UV absorption (L.) for gastrointestinal disorders and detection lead to the identification of five Antimicrobial effects of mulberry, Morus important stilbene glycosides from mulberry, alba (L.). Morus alba (L.) (Piao, et al., 2011). Benzokuwanon E, hydroxymorusin, Antioxidative potentials of mulberry, dicyclokuwanon EA, and dicyclokuwanon EB Morus alba (L.) are the important flavonoids isolated from Morus australis (L.) and their structures were Presence of wide array of phytochemicals in elucidated on the basis of UV, IR, MS, NMR, different parts accounts for the antioxidative and CD spectral data (Zheng, et al., 2012).

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The aqueous extractives the leaves of Moracin. The fibroblasts pre-incubated with mulberry, Morus alba (L.), prepared at high Moracin had significantly lower levels of temperature was reported to contain four catalase; lactate dehydrogenase and important flavonols, quercetin-3-ß-D-glucose, malondialdehyde activity when compared to quercetin-3-O-glucose-6?-acetate, rutin and untreated ones. The acetone-soluble (and quercetin (Kim and Jang, 2011). The lupeol water soluble too) Moracin, from a natural type pentacyclic triterpenoids separated from source, the fruits of mulberry, Morus alba the stem bark of mulberry, Morus alba (L.) (L), serve as ideal molecule to prevent include: moruslupenoic acid A, oxidative stress. moruslupenoic acid B and moruslanosteryl acetate (Ali and Ali, 2012). The aqueous Antidiabetic significance of mulberry, methanolic extract of the root bark of Morus alba (L.) mulberry, Morus alba (L.) yields the compound ―Moran 20K‖. The Moran 20K is a The Diabetes mellitus is a group of metabolic glycoprotein with antioxidant antidiabetic disorders. It is characterized by high blood activity (Kim, 1999). 1-deoxynojirimycin sugar (glucose) levels. This high blood sugar (DNJ), resveratrol, oxyresveratrol, cyanidin- (glucose) levels is in response to the defects 3-O-betaglucoside (Cy-3-glu), cyanidin-3-O- in insulin secretion, or its action, or both. The beta-rutinoside (Cy-3-rut), and rutin were also disease diabetes mellitus was first identified reported in different species of mulberry as a disease associated with "sweet urine," (Song, et al., 2009). The compounds like and excessive muscle loss in the ancient sanggenol, kuwanon, moracin, mulberrofuran, world. Increased levels of blood glucose mulberroside, 1-deoxynojirimycin, 2-O- (which may also called as hyperglycemia) alpha-Dgalactopyranosyl- 1- lead to spillage of glucose into the urine, deoxynojirimycin, fagomine, betulinic acid, hence the term sweet urine. Normally, in ursolic acid and beta-sitosterol are the healthy body, the blood glucose levels are important chemical constituents of the root tightly controlled by insulin, a hormone bark of mulberry, Morus atropurpurea (L.). produced by the pancreas. Insulin lowers the Kumar, et al., 2008 and Butt, et al., (2008) the blood glucose level. When the blood glucose literature on the major pharmacologically elevates (for example, after eating food), important compounds from mulberry, Morus insulin is released from the pancreas to alba (L.) and other species of mulberry. normalize the glucose level by promoting the Vitthalrao B. Khyade, et al., (2013, 2014. uptake of glucose into body cells. In diabetic 2015, 2015, 2018) assed the capabilities of patients, the absence of insufficient moracin as antioxidant and reported it as ideal production of or lack of response to insulin herbal compound to prevent oxidative stress. causes hyperglycemia. The Diabetes mellitus The potential regarding antioxidant activity of is thus characterized by sustained Moracin, the novel compound belong to hyperglycemia. It is associated with many mulberry was assessed through the use of secondary complications in the body hydrogen peroxide induced stress in skin metabolism. The secondary complications fibroblast cell line culture (AH927) by through diabetes mellitus include: formation Vitthalrao B. Khyade et al., (2018). The of free radicals and non enzymatic results of this attempt showed that the glycosylated end products. This situation is Moracin offers protection against oxidative responsible for higher oxidative stress and stress. And cell viability was found restored vascular complications (Ahmed, 2000; to that of control on pre-incubation with the Baynes and Thorpe, 2000). Naowaboot et al.,

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(2009) reported the antihyperglycemic, isolated rat islet cells. In patients with type 2 antioxidant and antiglycation activities of diabetes, mulberry treatment caused an extractives of leaves of mulberry, Morus alba improvement in glycemic control and fall in (L.) in streptozotocin induced chronic diabetic VLDL production. Also it decreased the lipid rats. The leaves of mulberry, Morus alba (L.) peroxidation in blood, urine and RBC are one of the important herbal medicines membrane (Andallu et al., 2001). The used for the treatment of hyperglycemia. It moracin M; steppogenin-4'-O-ß-D-glucosiade was proved by experiments in animal models and mullberroside-A were also isolated from that mulberry leaf extract possess the root bark of mulberry, Morus alba (L.). antihyperglycemic, antioxidant and All the three flavones (moracin M; antiglycation activities (Naowaboot, et al., steppogenin-4'-O-ß-D-glucosiade and 2009). The extractive of the leaves of mullberroside-A) exhibited hypoglycemic mulberry, Morus alba (L.) is reported as effect in alloxan induced diabetic mice effective in modulating the nitric oxide (Zhang, et al., 2009). There is important role synthase expression in the hypothalamus of of a-amylase, the key enzyme catalyzes the streptazotocin treated rats (Jang, et al., 2002). initial step in the hydrolysis of starch to The red mulberry, Morus rubra (L.) is a smaller oligosaccharides. Retardation of species of mulberry native to eastern and starch digestion by inhibition of a-amylase, central North America. The leaf extractives of the key enzyme catalyzes the initial step in this red mulberry, Morus rubra (L.) exerts its the hydrolysis of starch to smaller antidiabetic activity in streptazotocin induced oligosaccharides plays a key role in the diabetic rats by decreasing the fasting glucose control of diabetes. The extractives of leaves levels, glycosylated haemoglobin and of mulberry, Morus alba (L.) rich in tannins, increasing the plasma insulin and C-peptide flavonoids, cardiac glycosides and saponins levels Sharma, et al., 2010). The credit of exhibit significant a-amylase inhibitory antidiabetic activity of mulberry, Morus alba activity (Sudha et al., 2011). (L.) goes to its novel compound: 1- Deoxynojirimycin (DNJ). This 1- The insulin resistance and low grade chronic Deoxynojirimycin (DNJ) has been shown to inflammatory status are the distinguishing inhibit intestinal a-glucosidases, which results features of type 2 diabetes. The secondary in reduction of blood glucose (Hansawasdi, et complication associated with type 2 diabetes al., 2006). According to Li, et al., (2011), a is the development of cardiovascular diseases. hybrid of 1- Deoxynojirimycin (DNJ) and a Type 2 diabetic related resistance of insulin polysaccharide helps in regulating the depends both on glucose metabolism and fatty expression of the hepatic gluconeogenic acid metabolism (Haffner, 1991). enzymes, glucokinase, PEP carboxykinase Improvement in insulin resistance has been and glucose 6-phosphatse. The polysaccharide suggested as an effective way to prevent life in this mixture is able to protect pancreatic style related type 2 diabetes and vascular islets from alloxan induced damge, repair the complications. Repeated ingestion of destroyed pancreatic islets, upregulate the extractives of leaves of mulberry, Morus alba PDX-1, insulin-1 and insulin-2 expression in (L.) reduces the insulin resistance in high fat pancreas and normal secretion of insulin in fed KK-Ay mice (Tanabe, et al., 2011). Kim, serum. Taniguchi, et al., (1998) fagomine et al., (2012) reported improvement in the contents in the leaves of mulberry, Morus markers of inflammation and insulin alba (L.). Fagomine of mulberry leaves is resistance in experimental animal models capable of inducing insulin secretion in through the long term provision of extractives

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 of leaves of mulberry, Morus alba (L.). The Reduction in the fasting blood sugar, circulating oxidized low density lipoproteins normalization of liver enzymes level and (LDL) was also improved in the treated improvement in the lipid profile are reported group, which is often elevated in type 2 in the diabetic rats treated with the extractives diabetes. The extractives of leaves of of leaves of mulberry, Morus alba (L.) mulberry, Morus alba (L.) increases the rate (Vitthalrao B. Khyade, 2014). of glucose uptake by a direct enhancement of insulin independent glucose transport in The treatment of diabetic rats using the skeletal muscle. 5’- AMP-activated protein decoction leaves of Mulberry, Morus alba kinase (AMPK) is the major signaling (L.) (20 g/L) is reported to decrease the blood intermediary in the exercise-stimulated glucose levels, to inhibit hepatic glycogen insulin independent glucose transport in loss, and to prevent potential skeletal muscle (Musi, et al., 2006). The histopathological alterations in the pancreas skeletal muscle AMPK is also implicated in a and kidneys. The provision of leaf decoction variety of antidiabetic properties of exercise, of Mulberry, Morus alba (L.) (20 g/L) was including glucose transporter 4 (GLUT4) found to be able to regulate the altered expression, glycogen regulation, fatty acid metabolic processes. The results suggest that oxidation and enhanced insulin sensitivity. Mulberry, Morus alba (L.) leaf decoction Mulberry leaf extract increases the activity of (20g/L) is useful for diabetes mellitus both AMPK a 1 and 2 in skeletal muscles and management (Vitthalrao B. Khyade, 2018). is associated with insulin independent glucose Mulberry, Morus alba (L.) should be explored transport without change in the energy status as medicinal plant to be used to control the of the muscle and reduces the risk of type 2 diabetes. Given a reasonable likelihood that diabetes (Ma, et al., 2009). Decrease in medicinal plants with a long history of human adipogenesis lead to limited storage sites for use will ultimately yield novel drug free fatty acids cause increase in plasma free prototypes, systematic and intensive search in fatty acids. This increase in circulating free plants for new drugs to treat Type 2 diabetes fatty acids result in fat deposition in muscle mellitus seem to be of a great utility. This and liver causing insulin resistance and type 2 approach seems likely to increase the chances diabetes mellitus. Adiponectin is a member of for discovering new drugs for the the adipokine family is induced during management of diabetes mellitus. adipocyte differentiation. Circulating levels of adiponectin will be low in patients having The mulberry, Morus alba (L.) for obesity and type 2 diabetes (Nadler, et al., cardiovascular diseases 2000). The mulberry, Morus alba (L.) has been The extractives of leaves of mulberry, Morus widely used to prevent and to treat symptoms alba (L.) stimulates differentiation of 3T3-L1 associated with cardiovascular disease for preadipocytes into adipocytes by increasing over a millennium in eastern countries. the expression of adipogenic genes and Aqueous preparations of mulberry, Morus improve the secretion of adiponectin and alba (L.) were used in the herbal prescriptions insulin sensitivity. This mechanism of action by Chinese people to reduce blood pressure. is similar to that of the thiazolidinediones, a The leaf extractives of the mulberry, Morus class of insulin sensitizing drugs used to treat alba (L.) shown to reduce hypertension in type 2 diabetes (Naowaboot et al., 2012). rodents and decreases serum cholesterol and prevent atherosclerosis (Doi, et al., 2000 and

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Oh, et al., 2007). The ethyl acetate extractives bearberry shrub, cranberry, blueberry, some of mulberry, Morus alba (L) has dual mushrooms, and most types of pears. Morus vasoactive effects. The relaxation was Bombycis' arbutin can potentially prevent mediated by inhibition of voltage- and melanin production, Therefore, naturally receptor dependent Ca2+ channels in vascular lightening skin and creating a more youthful smooth muscle cells, while the contraction appearance (Source). Morus bombycis is also occurred via activation of ryanodine receptors high in antioxidants, and although this in the sarcoplasmic reticulum (Xia, et al., property has made it a popular inclusion in 2008). The deoxyribonucleic acid (DNA) the treatment of liver disease and other micro array analysis were used to investigate internal ailments, it is also an effective free gene expression in the livers of radical scavenger. M. bombycis root extract hypertriglyceridemic rats treated with exhibited strong anti-lipase activity, with an mulberry leaves to elucidate the mechanism IC50 value of 2.07μg/ ml in fully behind the lipid lowering effect of mulberry. differentiated 3T3-L1 adipocytes and adipose Dietary supplementation increased protein tissues. The extract increased lipolytic effects expression of the Carnitine such as decreased intracellular triglyceride Palmitoyltransferase 1A (CPT1A); Acyl-CoA and the release of glycerol. Moreover it Oxidase 2 (ACOX2); phytanoyl-CoA inhibited phosphodiesterase activity in a dose hydroxylase (PHYH) and the activity of acyl- dependent manner (Kim et al., 2010). So it CoA oxidase / dehydrgenase, the rate limiting does have pharmacological applications in enzymes of fatty acid oxidation. The genes metabolic disorders such as obesity. DNJ upregulated by mulberry included the present in mulberry leaf extract helps in following peroxisome proliferator-activated increasing serum adiponectin level, stimulated receptor alpha (PPAR alpha) and or AMP activated protein kinase to activate ß- peroxisome proliferator-activated receptor oxidation which inhibits lipid accumulation in delta (PPAR delta) targets and many of them liver (Kim, et al., 2010). Mulberry water are involved in fatty acid oxidation. extract inhibited acetyl coenzyme A Angiopoietin-like 3 (also known as carboxylase activities by stimulating AMPK ANGPTL3), is a protein that in humans is and attenuated the expression of sterol encoded by the ANGPTL3 gene (Conklin, et regulatory element binding protein 1 and its al., 1999). Mulberry induced down regulation target molecules such as fatty acid synthase. of this ANGPTL3 results in the activation of In contrast, the lipolytic enzyme expressions lipoprotein lipase and enhanced triglyceride of PPAR gamma and carnitine hydrolysis. Mulberry administration also palmitoyltransferase1 were increased (Ou, et upregulated the Glycerol Kinase gene (Gyk al., 2011) (Fig. 3). gene) and caused a reduction in the plasma non esterified fatty acid level. The Stearoyl- Continuous for 12 weeks of provision of the CoA desaturase gene (Scd gene) is the gene herbal capsules of 1- Deoxynojirimycin involved in lipogenesis and this gene was (DNJ) rich mulberry leaf extractives for down regulated after treatment with mulberry humans reported a modest decrease in serum which inhibits lipogenesis and facilitates fatty triglyceride levels and beneficial changes in acid oxidation (Kobayashi, et al., 2010). lipid profile without any side effects (Kojima, Morus Bombycis is an extract found in et al., 2010). Administration of freeze dried mulberries that is often used in cosmetics due powder of fruits of the mulberry, Morus alba to the presence of arbutin, a hydroquinone (L.) to rats resulted in a significant decrease in derivative isolated from the leaves of the serum and liver triglyceride, total cholesterol,

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 serum low-density lipoprotein (LDL) and (L.) helps in inhibiting the vascular smooth decrease in atherogenic index. Also an muscle proliferation by the upregulation of increase in serum high-density lipoprotein p53 and inhibition of cyclin dependent kinase (HDL) level, Red Blood Corpuscles (RBC) (Chan, et al., 2010). The high levels of iron and liver superoxide dismutase (SOD) level content in mulberries can significantly boost and blood glutathione peroxidase level was the production of red blood cells. This means observed. The thiobarbituric acid content of that the body will increase its distribution of serum and liver was reduced indicating the oxygen to important tissues and organs, low level of lipid peroxidation (Yang, et al., thereby helping to boost metabolism and 2010). Mulberry leaf powder can preserve the optimize the functionality of those systems. cardiac function in experimental autoimmune Resveratrol is a very important flavonoid that myocarditis by modulating oxidative stress directly affects the functioning of certain induced MAPK activation and further afford mechanisms in blood vessels, primarily protection against endoplasmic reticulum making them less prone to damage by stress mediated apoptosis. It significantly angiotensin, which can cause blood vessel decreased oxidative stress, myocyte constriction. In fact, resveratrol increases the apoptosis, cellular infiltration, cardiac production of nitric oxide, which is a fibrosis, mast cell density, myocardial levels vasodilator. This means that it relaxes blood of sarco/endo plasmic reticulum Ca2+ vessels and reduces chances of blood clot ATPase2, p22phox, receptor for advanced formation and subsequent heart issues like glycation end products, phosphor p38 strokes or heart attacks. Resveratrol is found mitogen activated protein kinase, phospho-c- in many dark-skinned berries like mulberries. Jun-NH2-terminal protein kinase, glucose Because mulberries are high in vitamin C and regulated protein78, caspase12 and flavanoids, they can also help prevent cold osteopontin levels (Arumugam, et al., 2013). and flu-like symptoms, and even treat Morusinol extracted from M.alba root bark hepatitis. They are a wonderful dietary significantly inhibited collagen and addition for post-operative patients, too, since arachidonic acid induced platelet aggregation they can speed up recovery via improved and TXB2 formation in cultured platelets. So blood circulation. it is effective in inhibiting arterial thrombosis in vivo due to antiplatelet activity and exerts Anticancer effects of mulberry, Morus alba beneficial effects on transient ischemic (L.) attacks or stroke via modulation of platelet activation (Lee, et al., 2012). Some Cancer is a serious public health problem isoprenylated flavonoids with adipogenesis world wide. Most of the natural compounds promoting activity were purified from M. targets inflammatory pathways and immune nigra and M. notabilis (Hu, et al., 2011 and modulation for the prevention and treatment Hu, et al., 2011). The extractives of mulberry, of cancer. Mulberry also contains several Morus alba (L.) increases the vascular smooth anticancer compounds. M. fructus fruit extract muscle cell migration in a dose dependent induces cancer cell death in vitro and in vivo. manner by inhibiting the activities of MMP-2 The in vitro effect is due the cell death in an and 9, phosphorylation of FAK, protein ROS dependent mitochondrial apoptotic expression of small GTPases (c-Raf, Ras, pathway (Jeong, et al., 2010). Phenolic Rac1, Cdc42, and RhoA) and NF-kappaB compounds from mulberry, Morus alba (L.) expression (Chan, et al., 2009). Also the induces in vitro anticancer activity in extractives of leaves of mulberry, Morus alba hepatoma cells by cell cycle arrest at G2-M

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 phase and inhibition of topoisomerase II potent among them. The morusin is with an activity (Naowaratwattana, et al., 2010). IC50 value of 0.64 μM against HeLa cells Albanol A (also called as Mulberrofuran G) is (Dat et al., 2010). New 2-arylbenzofuran the bio-active compound isolated from the derivatives (namely moracins of different root bark of mulberry, Morus alba (L.). This structure from mulberry, Morus alba (L.) and Albanol A was found inducing potent wittifurans from Morus wittiorum) with cytotoxicity (IC50 1.7mM) in HL60 cells potent cytotoxic activity against different (Human Leucamia Cell line) through human cancer cell lines were identified inhibition of topoisomerase II activity (IC50 recently (Yang, et al., 2010 and Tan, et al., 22.8mM). In addition, it induced early 2012). A new galactose binding lectin was apoptosis through cell death receptor pathway also purified from M. alba leaves with and mitochondrial pathway, observed by cytotoxic activity on human breast cancer membrane phospholipid exposure, reduced (IC50-8.5 μg) and colon cancer cells (IC50-16 levels of pro caspase3, 8 and 9 and increased μg) (Deepa and Priya, 2012) (Fig. 4). levels of cleaved caspase 3, 8 and 9 and increased bax/BCl2 ratio (Kikuchi, et al., The anthocyanins are a group of phenolic 2010). The anticancer activity of the essential compounds with beneficial effects in reducing oil separated from mulberry, Morus the risk of cardiovascular diseases and cancer rotunbiloba Koidz was studied in human because of its antioxidant, anti-inflammatory larynx epidermoid carcinoma (Hep2) and and chemopreventive properties (Middleton, human colon adenocarcinoma (SW620) cell et al., 2000). Cyanidin 3-rutinoside and lines with African green monkey kidney cyanidin 3-glucoside are the two anthocyanins (Vero) cell line as a control. The oil at 0.1- present in mulberry, Morus alba (L.). They 100 μg/ml had no effect on Vero cell have strong anticancer properties. They have viability. The median lethal concentration shown to be inhibiting the invasion and (LC50) of the oil on the cytotoxicity of Hep2, migration of human lung cancer A549 cells SW620 and Vero were 70, 120 and 280 μg/ml by downregulating the expression of MMP-2 respectively (Patharakorn, et al., 2010). and urokinase plasminogen activator and Resveratrol, purified from the methanol enhances the expression of TIMP-2 and extract of M. alba showed heparinase plasminogen activator inhibitor. Also an inhibition and antimetastatic effects on inhibition of the activation of NF-kappa B and murine B16 melanoma cells (Ahn, 2006). The c-jun was also observed in this case (Chen, et mulberry, Morus alba (L.) is a rich source of al., 2006). The osajin is a prenylated prenylated cytotoxic flavonoids such as isoflavone isolated from the fruit of Maclura sanggenon J and K, cyclomorusin, morusin, pomifera (L.). The tree of Maclura pomifera atalantoflavone, kaempferol etc. Henrietta (L.) and a tree of mulberry, Morus alba (L.), Lacks (August 1, 1920 – October 4, 1951) both belong to one and the same family was an African-American woman whose (Moraceae). It exerts multiple effects such as cancer cells are the source of the HeLa cell loss of mitochondrial transmembrane line, the first immortalized cell line and one of potential, release of cytochrome C, expression the most important cell lines in medical of Fas ligand, suprresion of glucose regulated research. An immortalized cell line will protein 78 and activation of various caspsses reproduce indefinitely under specific and propaoptotic proteins in human conditions, and the HeLa cell line continues nasopharyngeal carcinoma cells. So osajin to be a source of invaluable medical data to induced apoptosis include extrinsic death the present day. The morusin is the most receptor pathway and intrinsic pathways

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 relying on mitochondria and endoplasmic anti-inflammatory properties (Hong, et al., reticulum (Huang, et al., 2011). Chalcones, a 2002). It exerts antiasthmatic effect in group of aromatic enones from plants, form experimental mouse model via enhancement the central core of a number of biologically of CD4+CD25+Foxp3+ regulatory T cells important compounds. Investigation on and inhibition of Th2 cytokines (Kim, et al., ethanol extract of the leaves of M. alba L. 2011). The extract of M. bombycis has yielded two new chalcone derivatives, antiiflammatory and inhibitory effect on morachalcone B and C with potent cytotoxic collagen induced arthritis. It acts by effects (Yang, et al., 2010). Flavonids such as decreasing the infiltration of immune cells, sanggenol L, sanggenol M and different types synovial hyperplasia, cartilage destruction and of mulberrofurans with cytotoxic effects were bone erosion. The mRNA levels of MMP1/3, also purified from M. mongolica (Shi, et al., inflammatory cytokines and chemokines were 2001). Between the high content of significantly suppressed, number of anthocyanins, vitamin C, vitamin A, and osteoclasts were reduced and activation of various other polyphenolic and phytonutrient NF-kappaB and Ap-1 were observed on compounds, mulberries are absolutely packed treatment with the extract (Kim, et al., 2011). with antioxidants. Antioxidants are the main The extractives of leaves of mulberry, Morus line of defense against free radicals, which nigra (L.) and extractives of fruits of form a dangerous by-product of cellular mulberry, Morus ihou Koidz are reported for metabolism and can damage healthy cells, capable of reducing the carrageenan-induced causing them to mutate into cancerous ones. paw edema as well as fibrovascular tissue The diverse range of antioxidants found in growth induced by s.c. cotton pellet mulberries means that they can neutralize implantation in animal models indicating its these free radicals quickly before too much anti-inflammatory property (Kim, et al., 2006 damage is done. and Padilha, et al., 2010). The cudraflavone B is a prenylated flavonoid found in large Anti-inflammatory effects of mulberry, amounts in the roots of mulberry, Morus alba Morus alba (L.) (Fig. 5) (L.) is reported to cause a significant inhibition of inflammatory mediators in Mulberry plants have a long history in selected in vitro models. It was a potent traditional medicine as anti-inflammatory inhibitor of Tumor Necrosis Factor – alpha agents. The root epidermis of mulberry, (TNF alpha) by blocking the translocation of Morus alba (L.) shown to have anti- nuclear factor kappa-light-chain-enhancer of inflammatory effects (Wang, et al., 2002). activated B cells (NF-kB) from the cytoplasm The leaves of mulberry, Morus alba (L.) have to the nucleus. The nuclear factor kappa-light- diaphoretic and emollient effects and are used chain-enhancer of activated B cells NF-kB for making a decoction that can be used as a activity reduction resulted in the inhibition of gargle that throat inflammation. Butanol cyclooxygenase 2 (COX-2) gene expression extract of mulberry, Morus alba (L.) also [74]. (Hosek, et al., 2011). The anti- significantly reduced LPS-induced PGE2 inflammatory compound wittifuran I was production, TNF-alpha and COX-2 purified from the ethanolic extract of stem expression in RAW264.7 macrophages (Choi, bark of mulberry, Morus wittiorum (L.) (Tan, et al., 2005). Methanol extract of mulberry, et al., 2012). Another compound resveratrol Morus alba (L.) contains compounds with from M. alba inhibits IL-8 secretion by inducible nitric oxide synthase (iNOS) blocking mitogen-activated protein kinase inhibitory activity which can attribute to its (MAPK) phosphorylation and nuclear factor

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 kappa-light-chain-enhancer of activated B such kaempferol -3-O-glucoside, and cells (NF-kappaB) activation in kaempferol -3-O-(6-malonyl) glucoside which lipopolysaccharide (LPS) induced human inhibits the formation of amyloid beta-peptide monocytic cell line THP-1 (Oh, et al., 2009). fibrils in vitro, and protects hippocampal Sanggenon C and O, two Diels-Alder type neurons from amyloid beta-peptide induced adducts isolated from M. alba, inhibit NO cell death (Niidome, et al., 2007 and production through the iNOS induction and Khaengkhan, et al., 2009). The amyloid activation of nuclear factor (NF-kB) in LPS- plaques are formed by the proteolysis of induced RAW264.7 cells indicating its anti- amyloid precursor protein by the by a, ß or d inflammatory potential (Dat, et al., 2012). secretase enzyme. Therapeutic efforts to Several arybenzofurans (moracins and target AD have now focused on the disruption mulberrofurans of different types), prenylated of this cascade by blocking these enzymes. flavonoids (kuwanons, morusin, sanggenon F, Many flavones are identified from M. ihou betunilic acid etc.) from M. alba var. with ß-secretase inhibitory activity (Cho, et multicaulis Perro showed significant al., 2011). Cholinesterases are key enzymes inhibitory activity towards the differentiation that play important roles in cholinergic of 3T3-L1 adipocytes and inhibition in NO transmission. Eight flavonoids including production in RAW264.7 cells (Yang, et al., kuwanon U, kuwanon E, kuwanon C morusin, 2011). Phytochemical fractionation of the morusinol displaying cholinesterase inhibitory methanol extract of M. alba root bark lead to (both acetylcholine and butyrylcholine the identification of two chalcone derived esterase) activity were isolated from the root Diels Alder adducts, kuwanon J trimethylester bark of M. lhou L. (Kim, et al., 2011). The and kuwanon R with inhibitory effect on neuroprotective effect of oxyresveratrol was NFkB with IC50 value of 4.65 and 7.38 μM studied in in vitro model of stretch-induced respectively (Fung, et al., 2012). Inhibitors of trauma in co-cultures of neurons and glia, or phosphodiesterase -4 (PDE4) enzymes have by exposing cultures to high levels of therapeutic applications as anti-inflammatory glutamate. Trauma produced marked neuronal agent because inhibition of PDE-4 will lead to death and oxyresveratrol significantly the accumulation of cAMP and thus inhibited this death. Microscopic examination attenuated inflammatory responses in various of glia suggested signs of toxicity in cultures cell types. Molecular docking studies have treated with 100 μM oxyresveratrol, as shown that moracin M from M. alba can demonstrated by elevated S-100B protein inhibit the activity of a variety of PDE-4 release and a high proportion of cells with enzymes (Chen, et al., 2012). condensed nuclei. Cultures exposed to glutamate for 24 h exhibited ~ 37% neuronal The mulberry, Morus alba (L.) for loss, which was not inhibited by neurological disorders oxyresveratrol (Weber, et al., 2012). Studies have demonstrated the beneficial effects of Unlike beneficial effect of mulberry in mulberry on the induction of an antioxidant treating diabetes, cardiovascular disease, defense system and improvement of memory cancer etc., but its effects on neurological deterioration in ageing animals (Shih, et al., disorders are less studied. The neurotoxicity 2010). The neuroprotective effect of in Alzheimers disease (AD) is associated with cyanidine- 3-glucoside (C3G) fraction from the accumulation of amyloid beta-peptides M. alba was studied in oxygen deprivation that forms as a plaque in brain. The methanol and glutamate induced cell death in rat extract of mulberry leaves contain compounds primary cortical neurons. C3G did not provide

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 a protective effect against glutamate induced important enzyme in melanin production and cell death, but provide protection against in mammals the skin pigmentation results oxygen deprived cell death by maintaining the from the transfer of melanosomes from mitochondrial membrane potential (Bhuiyan, melanocytes to keratinocytes in the epidermis. et al., 2011) (Fig. 6). M. alba L. leaf extract exhibited potent inhibitory effects on mushroom tyrosinase, The mulberry, Morus alba (L.) for skin mammalian tyrosinase, and melanin synthesis diseases in Melan-a cells (Lee, et al., 2002). 2, 4, 2′, 4′-Tetrahydroxy-3-(3-methyl-2-butenyl)- Melanin is a broad term for a group of natural chalcone (TMBC), obtained from the stem pigments found in most organisms. Melanin is bark of mulberry, Morus nigra (L.) modulated produced by the oxidation of the amino acid melanogenesis by inhibiting tyrosinase. It tyrosine, followed by polymerization. The inhibited the L-dopa oxidase activity of melanin pigments are produced in a mushroom tyrosinase which was more potent specialized group of cells known as than kojic acid a well-known tyrosinase melanocytes. There are three basic types of inhibitor (Zhang, et al., 2009). Topical melanin: eumelanin, pheomelanin, and applications of mulberroside A, neuromelanin. The most common type is oxyresveratrol, and oxyresveratrol-3-O- eumelanin, of which there are two types— glucoside clearly caused depigmentation, brown eumelanin and black eumelanin. reduced melanin indices, inhibited tyrosinase Pheomelanin is a cysteine-derivative that activity, and decreased melanin content in UV contains polybenzothiazine portions that are induced hyperpigmentation in guinea pig largely responsible for the color of red hair, skin. Oxyresveratrol and oxyresveratrol-3-O- among other pigmentation. Neuromelanin is glucoside more potently inhibited found in the brain, though its function melanogenesis than mulberroside A. This remains obscure. In the human skin, treatment decreased the expression of MITF melanogenesis is initiated by exposure to UV gene, that are regulating the transcription of radiation, causing the skin to darken. Melanin proteins involved in melanocyte pigmentation is an effective absorbent of light; the pigment (Park, et al., 2011). Mulberries also boast a is able to dissipate over 99.9% of absorbed high level of vitamin A and vitamin E, along UV radiation. Because of this property, with a range of carotenoid components like melanin is thought to protect skin cells from lutein, beta-carotene, zeaxanthin, and alpha- UVB radiation damage, reducing the risk of carotene. All of these elements act as cancer, and it is considered that exposure to antioxidants that specifically affect the skin, UV radiation is associated with increased risk tissue, hair, and other areas of the body where of malignant melanoma, a cancer of free radicals strike. Mulberries can aid in skin melanocytes (melanin cells). Studies have care, reduce the appearance of blemishes and shown a lower incidence for skin cancer in age spots, and keep hair shiny and healthy by individuals with more concentrated melanin, preventing the oxidative actions of free i.e. darker skin tone. However; the radicals (Fig. 7). relationship between skin pigmentation and photoprotection is still being investigated. Hepatoprotective potentials of mulberry, Morus alba (L.) Melanin present in the skin protects from UV induced hyper pigmentation, wrinkling, The chemical investigation of the twigs of M. melasma and cancer. Tyrosinase is an mesozygia resulted in the isolation of several

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 compounds and few of them exhibited serving. Dietary fiber can help to improve heaptoprotective activities (Kapche, et al., digestion by bulking up the stool, thereby 2011). A glycoprotein (MIL) purified from M. speeding up the movement of food through indica protects againt CCl4 induced liver the digestive tract, while also reducing damage. MIL significantly reduced the occurrences of constipation, bloating, and activity of alanine aminotransferase (ALT), cramping. Furthermore, fiber helps to regulate lactate dehydrogenase (LDH), and cholesterol levels and can improve heart thiobarbituric acid-reactive substances health when regularly added to the diet. Like (TBARS) in CCl4 treated mice. It reduced the the majority of fruits and vegetables, activity of COX-2 and expression of TNF-a mulberries contain dietary fiber, which makes and IL-1 beta in liver from CCl4- treated approximately 10% of your daily mice. Moreover, supplementation of MIL requirements in a single serving. Dietary fiber suppressed stress-activated protein kinase/c- can help to improve digestion by bulking up jun N-terminal kinase phosphorylation and the stool, thereby speeding up the movement activator protein-1 transcriptional activation of food through the digestive tract, while also in livers of CCl4 treated mice (Oh, et al., reducing occurrences of constipation, 2010). M. alba extract significantly reduced bloating, and cramping. Furthermore, fiber the gastric mucosal injury in experimental rats helps to regulate cholesterol levels and can induced by tween 20 and absolute ethanol improve heart health when regularly added to with marked reduction in the leucocytes the diet. infiltration to submucosal layer (Abdulla, et al., 2009) (Fig. 8). Exploring and evaluating new and cheap feedstuffs as sources of protein for livestock The mulberry, Morus alba (L.) for and other farm animals is an important target gastrointestinal disorders for nutritionists to pursue. Competition between man and animal for the same food The health benefits of mulberries include their and the search for alternatives to feed ability to improve digestion, lower livestock are increasing. The increasing costs cholesterol, aid in weight loss, increase of conventional feedstuffs like corn, soybean circulation, build bone tissues, and boost the meal and fish meal for poultry diets is immune system. The fruit also helps prevent pushing to find less expensive alternatives. certain cancers, slow down the aging process, One possible feed alternative is tree fodder lower blood pressure, protect eyes, and mulberry leaves (Morus alba). Mulberry improve the overall metabolism of the body. grows well in the tropics and subtropics, and Mulberries are filled with nutrients that are is reported to have excellent nutritional value. important for our body, including iron, Mulberry leaves are very rich in protein (15- riboflavin, vitamin C, vitamin K, potassium, 35%), minerals [2.42-4.71% calcium (Ca); phosphorous, and calcium. They also contain 0.23-0.97% phosphorus (P)] and a significant amount of dietary fiber and a metabolizable energy (1130- 2240 kcal/kg) wide range of organic compounds, including with absence of or negligible anti-nutritional phytonutrients, zeaxanthin, resveratrol, factors (Omar et al., 1999; Sanchez, 2002; anthocyanins, lutein, and various Saddul et al., 2004; Sarita et al., 2006; Wang polyphenolic compounds. Like the majority et al., 2011). The amino acids composition of of fruits and vegetables, mulberries contain mulberry leaf meal indicates it is a good dietary fiber, which makes approximately source of essential amino acids especially 10% of your daily requirements in a single lysine 1.80% and leucine 2.58% (Al-Kirshi et

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 al., 2009). Excellent results have been of coumarins, flavonoids, tannins, and obtained with mulberry leaves as poultry feed triterpenes in the extract, which did not show (Chowdary et al., 2009; Al-Kirshi et al., toxicity to A. salina nauplii. No mortality and 2010; Olteanu et al., 2010). behavioral alterations were detected for mice treated with the extract (300 and 2000 mg/kg Antimicrobial effects of mulberry, Morus b.w.) for 14 days. However, animals that alba (L.) received the highest dose showed reduced MCV and MCHC as well as increased serum The methanolic extract of the bark of M. alkaline phosphatase activity. In treatments mesozygia as well as its constituents with the extract at both 300 and 2000 mg/kg, (cycloartocarpesin and different types of there was a reduction in number of moracins) are used for the treatment of leukocytes, with decrease in percentage of infections associated with microorganisms lymphocytes and increase in proportion of (Kuete, et al., 2009). Prenylated flavonoids segmented cells. Histopathological analysis of isolated from M. alba showed antibacterial, organs from mice treated with the extract at antifungal and antiviral activities (Du, et al., 2000 mg/kg revealed turgidity of contorted 2003 and Sohn et al., 2004). Kuwanon G was tubules in kidneys, presence of leukocyte isolated from the ethyl acetate fraction of infiltration around the liver centrilobular vein, methanol extract of M. alba is acting as an and high dispersion of the spleen white pulp. antibacterial agent against oral pathogens The extract showed antimicrobial activity (Park et al., 2003). Chalcomoracin, a leaf against Staphylococcus aureus, Pseudomonas phytoalexine of mulberry tree exhibited aeruginosa, Candida albicans, Candida considerable antibacterial activity against krusei, Candida tropicalis and Aspergillus methicillin-resistant Stapalococcus aureus flavus. In conclusion, the extract contains (Fukai et al., 2005). Alisson Macário de antimicrobial agents and was not lethal for Oliveira et al., (2015) evaluated an ethanolic mice when ingested; however, its use requires extractives of leaves of mulberry, Morus alba caution because it promoted biochemical, (L.) for toxicity to Artemia salina (L.), oral hematological, and histopathological toxicity to mice, and antimicrobial activity. alterations. Phytochemical analysis revealed the presence

Fig.1 Mulberry, the safe therapeutics for human health

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Fig.2 Herbal mulberry tea for keeping the diabetes away

Fig.3 The contents of mulberry, Morus alba (L.) serve to orchestrate the progression of Healthy heart

Fig.4 The cancer preventing bioactive compounds from Herbal Sources

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Fig.5 The mechanism of inflammation

Fig.6 The neurological disorders

Fig.7 Mulberry, Morus alba (L.) for skin diseases

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Fig.8 Mulberry, Morus alba (L.) for liver protection

Fig.9 Mulberry: The ancient super food of silkworms and now, for human being

In conclusion, the mulberry is the one among It is expected that in the 21st century more the most studied plants for pharmacological research will be focused on the natural source potential. Research over the years elucidated based compounds to treat various diseases the existence of a number of active molecules and mulberry is definitely be one of the in it. The mechanism included in the exciting species to be explored more extensively. One pharmacological effect has been studied with of the carotenoids found in mulberries is a significant number of compounds purified zeaxanthin, which has been connected from mulberry. The synthetic analogues of the directly to a reduction in oxidative stress on purified compounds are showed to be certain ocular cells, including the retinal effective in the treatment of various diseases. macula lutea. Furthermore, zeaxanthin More detailed studies in future with the functions as an antioxidant and prevents natural vs. synthetic compounds will clearly certain damage to the retina, including the show the potential of these compounds in the free radicals that can cause macular therapeutic field. degeneration and cataracts. Vitamin C is a

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Int.J.Curr.Microbiol.App.Sci (2019) 8(4): 2941-2964 powerful defensive weapon against any Antioxidant and antityrosinase activity of illness or foreign pathogens in the body that mulberry (Morus alba L.) twigs and root antioxidants don’t take care of. A single bark. Food Chem Toxicol 2011; 49: 785-90. Ercisli S, Orhan E. Chemical composition of white serving of mulberries is almost the entire (Morus alba), red (Morus rubra) and black requirement of vitamin C for the day, but (Morus nigra) mulberry fruits. Food Chem combine that with the minerals and vitamins 2007; 103: 1380–4. present in this fruit, and you have a true Ni G, Zhang QJ, Wang HY, Chen RY, Zheng FZ, weapon against illness. Add a few mulberries Yu DQ Chemical constituents of the stem to your morning meal and watch your bark of Morus cathayana. J Asian Nat Prod immune system soar. Res 2010; 12: 505–15. Tan XY, Gong T, Liu C, Chen RY, Yu DQ. Five New 2- Arylbenzofuran Derivatives from Acknowledgement Morus wittiorum. Chem. Pharm.Bull. 2010; 58: 579-81. Expertise support from Mulberry Garden of Piao SJ, Chen LX, Kang N, Qiu F. Simultaneous Sericulture Unit, Malegaon Sheti Farm, determination of five characteristic stilbene Agricultural Development Trust, Baramati glycosides in root bark of Morus alba L. (India) deserve appreciations and exert a (Cortex Mori) using high-performance liquid grand salutary influence. chromatography. Phytochem Anal 2011; 22: 230-5. Zheng ZF, Zhang QJ, Chen RY, Yu DQ. Four new References flavonoids from Morus australis. J Asian Nat Prod Res 2012;14: 263-9. Scrivastava S, Kapoor R, Thratola A, Scrivastava Kim GN, Jang HD. Flavonol content in the water RP. Mulberry (Morus alba) leaves as human extract of the mulberry (Morus L.)?alba leaf food: a new dimension in sericulture. Int J and their antioxidant capacities. J Food Sci Food Sci Nutr 2003; 338: 3-10. 2011; 76: C869-73. Andallu B, Varadacharyulu NC. Antioxidant role of Ali A, Ali M. New triterpenoids from Morus alba L. mulberry (Morus indica L. cv. Anantha) stem bark. Nat Prod Res. 2012 Apr 5. [Epub leaves in streptozotocin-diabetic rats. Clin ahead of print]. Chim Acta 2003; 338: 3-10. Kim ES, Park SJ, Lee EJ, Kim BK, Huh H, Lee BJ. Asano N, Yamashita T, Yasuda K, IkedaK, Kizu H, Purification and characterization of Moran Kameda Y, Kato A, Nash RJ, Lee HS, Ryu 20K from Morus alba. Arch Pharm Res 1999; KS. Polyhydroxylated alkaloids isolated from 22: 9-12. mulberry trees (Morus alba L.) and Song W, Wang HJ, Bucheli P, Zhang PF, Wei DZ, silkworms (Bombix mori L.). J Agric Food Lu YH. Phytochemical profiles of different Chem 2001; 49: 4208-13. mulberry (Morus sp.) species from China. J Harauma A, Murayama T, Ikeyama K, Sano H, Arai Agric Food Chem 2009; 57: 9133-40. H, Takano R, Kita T, Hara S, Kamei K, Wu D, Zhang X, Huang X, He X, Wang G, Ye W. Yokode M. Mulberry leaf powder prevents Chemical constituents from root barks of atherosclerosis in apolipoprotein E-deficient Morus atropurpurea. Zhongguo Zhong Yao mice. Biochem Biophys Res Commun 2007; Za Zhi 2010; 35: 1978-82. 358: 751-6. Kumar VR, Chauhan S. Mulberry: Life enhancer. J Arfan M, Khan R, Rybarczyk A, Amarowicz R. Med Plants Res 2008; 2: 271-8. Antioxidant Activity of Mulberry Fruit Butt MS, Nazir A, Sultan MT, Schroen K. Morus Extracts. Int J Mol Sci 2012; 13: 2472-80. alba L. nature’s functional tonic. Trends Food Chu Q, Lin M, Tian X, Ye J. Study on capillary Sci Tech 2008; 19: 505-12. electrophoresis amperometric detection Ahmed N. Advanced glycation end products-role in profiles of different parts of Morus alba L. J pathology of diabetic complications. Diabetes Chromatogr A 2006; 1116: 286-90. Res Clin Pract 2005; 67: 3-21. Chang LW, Juang LJ, Wang BS, Wang MY, Tai Baynes JW, Thorpe SR. Glycoxidation and HM, Hung WJ, Chen YJ, Huang MH. lipoxidation in atherogenesis. Free Radic Biol

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Med 2000; 28: 1708-16. diabetes mellitus. J Lab Clin Med 1991; 118: Naowaboot J, Pannangpetch P, Kukongviriyapan V, 109-10. Kongyingyoes B, Kukongviriyapan U. Tanabe K, Nakamura S, Omagari K, Oku T. Antihyperglycemic, antioxidant and Repeated ingestion of the leaf extract from antiglycation activities of mulberry leaf Morus alba reduces insulin resistance in extract in streptozotocin induced chronic KKAy mice. Nutr Res 2011; 31: 848-54. diabetic rats. Plant Foods Hum Nutr 2009; Kim HJ, Yoon KH, Kang MJ, Yim HW, Lee KS, 64: 116–21. Vuksan V, Sung MK. A six-month Jang MH, Kim H, Shin MC, Lim BV, Lee TH, Jung supplementation of mulberry, korean red SB, Kim CJ, Kim EH. Administration of ginseng, and banaba decreases biomarkers of Folium mori extract decreases nitric oxide systemic low-grade inflammation in subjects synthase expression in the hypothalamus of with impaired glucose tolerance and type 2 streptozotocin induced diabetic rats. Jpn J diabetes. Evid Based Complement Alternat Pharmacol 2002; 90: 189-92. Med 2012 Feb 28 [Epub ahead of print]. Sharma SB, Gupta S, Ac R, Singh UR, Rajpoot R, Musi N, Goodyear LJ. Insulin resistance and Shukla SK. Antidiabetogenic action of Morus improvements in signal transduction. rubra L. leaf extract in streptozotocin-induced Endocrine 2006; 29: 73–80. diabetic rats. J Pharm Pharmacol 2010; 62: Ma X, Iwanaka N, Masuda S, Karaike K, Egawa T, 247-55. Hamada T, Toyoda T, Miyamoto L, Nakao K, Hansawasdi C, Kawabata J. Alpha-glucosidase Hayashi T. Morus alba leaf extract stimulates inhibitory effect of mulberry (Morus alba) 5'-AMP-activated protein kinase in isolated leaves on Caco-2. Fitoterapia 2006; 77: 568- rat skeletal muscle. J Ethnopharmacol 2009; 73. 122: 54-9. Li YG, Ji DF, Zhong S, Lv ZQ, Lin TB, Chen S, Hu Nadler ST, Stoehr JP, Schueler KL, Tanimoto G, GY. Hybrid of 1-deoxynojirimycin and Yandell BS, Attie AD. The expression of polysaccharide from mulberry leaves treat adipogenic genes is decreased in obesity and diabetes mellitus by activating PDX- diabetes mellitus. Proc Natl Acad Sci U S A 1/insulin-1 signaling pathway and regulating 2000; 97: 11371-6. the expression of glucokinase, Naowaboot J, Chung CH, Pannangpetch P, Choi R, phosphoenolpyruvate carboxykinase and Kim BH, Lee MY, Kukongviriyappan U. glucose-6-phosphatase in alloxaninduced Mulberry leaf extract increases adiponectin in diabetic mice. J Ethnopharmacol 2011; 134: murine 3T3-L1 adipocytes. Nutr Res 2012; 961-70. 32: 39-44. Taniguchi S, Asano N, Tomino F, Miwa I. Oh KS, Han W, Wang MH, Lee BH. The effects of Potentiation of glucose induced insulin chronic treatment with Morus bombycis secretion by fagomine, a pseudosugar isolated KOIDZUMI in spontaneously hypertensive from mulberry leaves. Horm Metab Res 1998; rats. Biol Pharm Bull 2007; 30: 1278-83. 30: 679–83. Doi, K., Kojima, T., Fujimoto, Y. Mulberry leaf Andallu B, Suryakantham V, Lakshmi Srikanthi B, extract inhibits the oxidative modification of Reddy GK. Effect of mulberry (Morus indica rabbit and human low density lipoprotein. L.) therapy on plasma and erythrocyte Biol Pharm Bull 2000; 23: 1066-71. membrane lipids in patients with type 2 Xia M, Qian L, Zhou X, Gao Q, Bruce IC, Xia Q. diabetes. Clin Chim Acta 2001; 314: 47-53. Endothelium independent relaxation and Zhang M, Chen M, Zhang HQ, Sun S, Xia B, Wu contraction of rat aorta induced by ethyl FH. In vivo hypoglycemic effects of phenolics acetate extract from leaves of Morus alba from the root bark of Morus alba. (L.). J Ethnopharmacol 2008; 120: 442-6. Fitotherapia 2009a; 80: 475-7. Kobayashi Y, Miyazawa M, Kamei A, Abe K, Sudha P, Zinjarde SS, Bhargava SY, Kumar AR. Kojima T. Ameliorative effects of Mulberry Potent a-amylase inhibitory activity of Indian (Morus alba L.) leaves on hyperlipidemia in Ayurvedic medicinal plants. BMC Compl Alt rats fed a high fat diet: induction of fatty acid Med 2011; 11: 5-15. oxidation, inhibition of lipogenesis and Haffner SM. Compositional changes in lipoproteins suppression of oxidative stress. Biosci of subjects with non-insulin-dependent Biotechnol Biochem 2010; 74: 2385-95.

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Rutuja Ashok Kadam, Nivedita Dattatray Dhumal and Vitthalrao Bhimasha Khyade. 2019. The Mulberry, Morus alba (L.): The Medicinal Herbal Source for Human Health. Int.J.Curr.Microbiol.App.Sci. 8(04): 2941-2964. doi: https://doi.org/10.20546/ijcmas.2019.804.341

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