{"id":62204,"date":"2024-12-30T11:50:13","date_gmt":"2024-12-30T11:50:13","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=62204"},"modified":"2025-01-06T18:02:12","modified_gmt":"2025-01-06T18:02:12","slug":"phytochemistry-and-potential-pharmacological-properties-of-morus-alba-plant-for-health-benefits-a-comprehensive-review","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no4\/phytochemistry-and-potential-pharmacological-properties-of-morus-alba-plant-for-health-benefits-a-comprehensive-review\/","title":{"rendered":"Phytochemistry and Potential Pharmacological Properties of Morus alba Plant for Health Benefits: A Comprehensive Review"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><strong>Introduction<\/strong><em><\/em><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>Morus alba <\/em>(<em>M. alba<\/em>) is <em>known as<\/em>&nbsp;white mulberry, common mulberry, silkworm mulberry,\nand in Hindi Tut. <em>M. alba <\/em>is\nnative to Asian countries such as China and India. They are widely cultivated\nand naturalized everywhere across the world for the process of sericulture as a primary source of food. Furthermore, the leaves are\nsometimes consumed by humans as vegetables or utilized as cow fodder in many\nregions. The bark of <em>M. alba <\/em>can be\nused to make paper, and the fruits are primarily consumed either directly once\nripe or are used to make other items, mainly desserts such as jams, jellies,\npies, tarts, etc. The various components of the <em>M. alba <\/em>plant (bark, leaves, flowers, and fruits) have enormous\npotential medicinal properties. Furthermore, they have a lengthy history of use\nin Traditional Chinese Medicine (TCM) to treat a variety of internal illnesses\nand infections. It is because they have been found to contain a significant\namount of biologically active compounds or constituents that might have potential use in pharmacological activities that\nmight improve the health of human beings<sup>1,2<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Materials and\nMethods <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The phytochemistry and pharmacological properties of <em>Morus alba<\/em> Plant were searched online\ndatabases by using keywords like \u201c<em>Morus\nalba<\/em> Plant\u201d, \u201cPhytochemistry of <em>Morus\nalba\u201d, \u201cTaxonomy of&nbsp; Morus alba\u201d<\/em>,&nbsp;\u201cAntioxidant properties of <em>Morus alba\u201d, <\/em>\u201cAnticancerous effects of <em>Morus alba\u201d, <\/em>&nbsp;\u201cAntimicrobial properties of <em>Morus alba\u201d, <\/em>\u201cAnti-inflammatory\nproperties of <em>Morus alba\u201d, <\/em>\u201cAnti-hyperlipidemic\nproperties of <em>Morus alba\u201d, <\/em>\u201cAnti-atherosclerotic\nproperties of <em>Morus alba\u201d, <\/em>\u201cAnti-obesity\nproperties of <em>Morus alba\u201d, <\/em>\u201cHypocholesterolemic\nproperties of <em>Morus alba\u201d, <\/em>\u201cAnti-diabetic\nproperties of <em>Morus alba\u201d, etc. <\/em>in\norder to explore the pharmacological properties of <em>Morus alba.<\/em><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Plant Description<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">                                                                         <br> The <em>M. alba <\/em>is a medium-sized shrub or tree, growing 10 to 20 m in height. In young active stems, the leaves can grow up to 30 cm in length with well-rounded elaborate lobes, whereas in older trees, they typically measure 5-15 cm in length with no lobes. Catkins of the single sex are the blooms. Male catkins are 10 to 30 mm long and slender, and female catkins are 2 to 12 mm in length and ovoid. The male flowers do not have sepals and are broadly ovate, whereas the female flowers have suborbicular sepals and are as long as or slightly larger than male flowers.<\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-62210\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig1-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig1-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig1-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig1.jpg 509w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 1: Fruits and leaves of <em>Morus alba<\/em><\/strong><\/p>\n<\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig1.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\">In\nthe wild plant, the fruit is 1 to 1.5 cm long and deep purple color however in\nmany cultivated plants the fruit color change from white to pink hue (Figure 1).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Taxonomy<\/strong><em><\/em><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Kingdom: Plantae<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Division:\nTracheophyta<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Class:\nMagnoliopsida<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Order: Rosales<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Family: Moraceae<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Genus: Morus L.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Species: <em>M. alba <\/em>L.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Phytochemical Constituents of <em>M. alba<\/em><\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>M. alba <\/em>mainly\ncontains phenolic compounds and a balanced content of proteins and minerals.\nThe major bioactive phytochemicals found in <em>M.\nalba <\/em>are carotenoids, glycosides, saponins, polysaccharides, alkaloids,\nvitamins, fats (mainly linoleic acid, palmitic acid, and oleic acid), sugars,\nminerals, and phenolic compounds such as terpenoids, flavonoids (including\nchalcones and anthocyanins), anthocyanins, and tannins<sup>3<\/sup>. Other bioactive\nphytochemicals found in <em>M. alba <\/em>are\nantibacterial substances, lectins, digestive enzyme\ninhibitors, stilbene glycosides, coumarins, and unsaturated fatty acids. Leaves\nof the <em>M. alba<\/em> have the richest source of bioactive substances than the\nfruits, roots, and stems<sup>4<\/sup>. The following table shows the\ndistribution of the various biologically active components obtained from\ndifferent parts of the plant.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Table 1: Distribution of the biologically active components in <em>M. alba <\/em>plant\u2019s parts<\/strong><\/p>\n\n\n<table style=\"width: 95%; height: 1746px;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<thead>\n<tr style=\"height: 72px;\">\n<td style=\"height: 72px;\" width=\"79\">\n<p style=\"text-align: center;\"><strong>Parts<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center; height: 72px;\" width=\"124\">\n<p><strong>Substances<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center; height: 72px;\" width=\"346\">\n<p><strong>Phytochemicals<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center; height: 72px;\" width=\"225\">\n<p><strong>References<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 106px;\">\n<td style=\"height: 212px;\" rowspan=\"2\" width=\"79\">\n<p style=\"text-align: center;\">Bark<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"124\">\n<p style=\"text-align: center;\">Triterpenoids<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"346\">\n<p>Moruslanosteryl acetate, moruslupenoic acid A and B,<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"225\">\n<p style=\"text-align: center;\">5<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 106px;\">\n<td style=\"text-align: center; height: 106px;\" width=\"124\">\n<p>Phenolic compounds<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"346\">\n<p>Maklurein, rutin, isoquercetin, resveratrol, morin, apigenin<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"225\">\n<p style=\"text-align: center;\">6, 7, 8<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 140px;\">\n<td style=\"height: 386px;\" rowspan=\"3\" width=\"79\">\n<p style=\"text-align: center;\">Fruits<\/p>\n<\/td>\n<td style=\"height: 140px;\" width=\"124\">\n<p style=\"text-align: center;\">Saturated and unsaturated Fatty acids<\/p>\n<\/td>\n<td style=\"text-align: center; height: 140px;\" width=\"346\">\n<p>Saturated: Palmitic acid<\/p>\n<p>Unsaturated: Oleic acid, linoleic acid<\/p>\n<\/td>\n<td style=\"text-align: center; height: 140px;\" width=\"225\">\n<p>8<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 174px;\">\n<td style=\"text-align: center; height: 174px;\" width=\"124\">\n<p>Phenolic compounds<\/p>\n<\/td>\n<td style=\"text-align: center; height: 174px;\" width=\"346\">\n<p>Quercetin, chlorogenic acid, kaempferol, rutin, gallic acid, caffeic acid, hydroxybenzoic acid, protocatechuic acid, p-coumaric acid, ferulic acid<\/p>\n<\/td>\n<td style=\"height: 174px;\" width=\"225\">\n<p style=\"text-align: center;\">8, 9, 10, 11, 12<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 72px;\">\n<td style=\"height: 72px;\" width=\"124\">\n<p style=\"text-align: center;\">Glucosides<\/p>\n<\/td>\n<td style=\"text-align: center; height: 72px;\" width=\"346\">\n<p>Rutinoside cyanine, cyanine glucoside<\/p>\n<\/td>\n<td style=\"height: 72px;\" width=\"225\">\n<p style=\"text-align: center;\">13<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 106px;\">\n<td style=\"height: 580px;\" rowspan=\"4\" width=\"79\">\n<p style=\"text-align: center;\">Leaves<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"124\">\n<p style=\"text-align: center;\">Enzyme inhibitors<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"346\">\n<p>Moranoline, 1-deoxynojirimycin<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"225\">\n<p style=\"text-align: center;\">14<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 106px;\">\n<td style=\"height: 106px;\" width=\"124\">\n<p style=\"text-align: center;\">Lectins<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"346\">\n<p>Hemagglutinin, phytosins,\u00a0 phytohemagglutinin and phytoagglutinin<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"225\">\n<p>14, 15<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 159px;\">\n<td style=\"text-align: center; height: 159px;\" width=\"124\">\n<p>Saturated and unsaturated Fatty acids<\/p>\n<\/td>\n<td style=\"text-align: center; height: 159px;\" width=\"346\">\n<p>Saturated: Palmitic acid<\/p>\n<p>Unsaturated: Oleic acid, linoleic acid, eicosanoids<\/p>\n<\/td>\n<td style=\"height: 159px;\" width=\"225\">\n<p style=\"text-align: center;\">9<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 209px;\">\n<td style=\"height: 209px;\" width=\"124\">\n<p style=\"text-align: center;\">Phenolic compounds<\/p>\n<\/td>\n<td style=\"text-align: center; height: 209px;\" width=\"346\">\n<p>Kaempferol, quercetin, coumaric acid, apigenin, syringic acid, morin, ferulic acid, luteolin, chlorogenic acid, gallic acid, rutin, caffeic acid, atalantoflavone, umbelliferone, morusin, cyclomorusin,<\/p>\n<\/td>\n<td style=\"height: 209px;\" width=\"225\">\n<p style=\"text-align: center;\">5, 7, 9, 12, 16, 17, 18<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 106px;\">\n<td style=\"height: 496px;\" rowspan=\"5\" width=\"79\">\n<p style=\"text-align: center;\">Root<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"124\">\n<p style=\"text-align: center;\">Glucosides<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"346\">\n<p>Cyanidin 3-O-\u03b2-D-glucopyranoside, moran, 1-deoxynojirimycin, glucoside, moracin<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"225\">\n<p style=\"text-align: center;\">19, 20<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 106px;\">\n<td style=\"height: 106px;\" width=\"124\">\n<p style=\"text-align: center;\">Enzyme inhibitors<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"346\">\n<p>Oxyresveratrol<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"225\">\n<p style=\"text-align: center;\">12<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 72px;\">\n<td style=\"height: 72px;\" width=\"124\">\n<p style=\"text-align: center;\">Lectins<\/p>\n<\/td>\n<td style=\"text-align: center; height: 72px;\" width=\"346\">\n<p>Albanol<\/p>\n<\/td>\n<td style=\"text-align: center; height: 72px;\" width=\"225\">\n<p>21<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 106px;\">\n<td style=\"text-align: center; height: 106px;\" width=\"124\">\n<p>Mulberry flavonoids<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"346\">\n<p>Sanggenols, kwanon, mulberrofuran<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"225\">\n<p style=\"text-align: center;\">17<\/p>\n<\/td>\n<\/tr>\n<tr style=\"height: 106px;\">\n<td style=\"height: 106px;\" width=\"124\">\n<p style=\"text-align: center;\">Phenolic compounds<\/p>\n<\/td>\n<td style=\"text-align: center; height: 106px;\" width=\"346\">\n<p>Resveratrol, luteolin, sinapic acid, gallic acid<\/p>\n<\/td>\n<td style=\"height: 106px;\" width=\"225\">\n<p style=\"text-align: center;\">7, 9<\/p>\n<\/td>\n<\/tr>\n<\/thead>\n<\/table>\n<p>\u00a0<\/p>\n\n\n<p class=\"wp-block-paragraph\"><strong>Results and\nDiscussion<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>M. alba <\/em>is\na pharmacologically important plant and has various phytochemicals and\nbiologically active phytocompounds. The leaves are rich in flavonoids and have\nantioxidant, anti-hyperlipidemic, antibacterial, anti-diabetic, skin whitening,\nanti-obesity, cardioprotective, and cytotoxic properties, whereas the fruits\nare rich in alkaloids and anthocyanins, which exhibit hepatoprotective\nproperties, anti-obesity, and anti-diabetic (Figure 2).\nThe root and the bark of <em>M. alba<\/em> have\nanti-inflammatory, antimicrobial, cytotoxic, skin-whitening, and\nanti-hyperlipidemic properties<sup>22<\/sup>. The detail pharmacological\nproperties of <em>M. alba<\/em> plant\u2019s parts\nare as follows:<\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-62211\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig2-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig2-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig2-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig2.jpg 780w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 2: Pharmacological properties present in different parts of <em>M. alba<\/em> plant<\/strong><\/p>\n<\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig2.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\"><strong>Antioxidant Properties <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The harmful impacts of xenobiotic\ncompounds on our biological systems are the generation\nof reactive oxygen species (ROS), causing\noxidative damage to several macromolecules. It has been found that natural\nantioxidants present in mulberry fruit play a significant role in neutralizing\nROS and are able to protect against oxidative\nstress induced by \u03b3-rays. A reported study suggests\nthat exposure of \u03b3-irradiated in rats causes a significant elevation in the\nxanthine oxidase activity, malondialdehyde (MDA), and liver enzymes concentrations which can be restored their levels by\nadministration of mulberry fruit powder (MFP)<sup>23<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Oxidative stress is a condition in which the concentration of antioxidants and production of free radicals in the body gets imbalanced. For the neutralization of ROS, the counteraction of the harmful effects is usually done with the help of antioxidants. It has been reported that plant\u2019s parts having high phenolic content are known to possess antioxidant properties. Many studies have been performed to investigate the relationship between phenolic contents and antioxidant properties. It has been reported that <em>M. alba <\/em>bark, leaves, flowers, and fruit parts possess antioxidant properties<sup>24<\/sup>. Bae and Suh<sup>25<\/sup>reported that the antioxidant activities of <em>M. alba <\/em>ethanol fruit extract vary significantly depending on the plant species used for the experiments.&nbsp; Mature fruits have a high content of anthocyanins, which have strong free radical scavenging activity than vitamin C<sup>26<\/sup>.&nbsp; In addition to the above studies, another experiment was designed to see the cytoprotective effect of <em>M. alba <\/em>root extract (MARE) on neuroblastoma with the help of flow cytometry along with immunoblot analysis. It was observed that MARE induced down-regulation of protein kinase B (Akt) and FOXO3, a phosphorylation, and an up regulation of caspase-3 activity. In neuroblastoma-B103 cells, it results in the inhibition of growth inductive signals, the generation of ROS, a decrease in the mitochondrial membrane potential, and a fast apoptotic response<sup>27<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Anticancerous Effects<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>M. alba <\/em>and\n<em>M. nigra <\/em>leaf\nextracts and their mixture showed anticancerous effects against mutation induced\nby radiation in the plant and animal cells. A water-ethanol leaf extract and their mixture composition were administered in a concentration-dependent manner.\nIt was observed that extracts and mixture composition\nextracts exhibited genoprotective properties. The mutation induced in the\nanimal and plant cells due to the gamma rays and chemical mutagens was successfully\ninhibited by the extracts and the mixture. The results also demonstrated that they\nhave huge potential to be used as a source of antimutagenicity in food industry\nproducts<sup>28<\/sup>.The\nvarious components of the <em>M. alba <\/em>tree\nexhibit cytotoxic effects, or they are found to possess the ability to combat\ncytotoxic activity. Several experiments have been performed to determine\nwhether the phytochemicals obtained from <em>M.\nalba <\/em>can exhibit cytotoxic effects on harmful cells or whether they can\nprotect against cytotoxic responses. In a study, flavonoids\nquercetin-3,7-di-O-\u03b2-D-glucopyranoside and quercetin-3-O-\u03b2-D-glucopyranoside\nwere extracted from the aqueous methanolic leaf\nof <em>M. alba <\/em>and reduced the growth of the human promyelocytic leukemia cell line (HL-60)<sup>29,30<\/sup>. In another\nstudy, a flavanone glycoside compound isolated\nfrom root bark also showed significant anti-cancerous properties against human\novarian cancer HO-8910 cells<sup>22,31<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Another\nstudy was conducted to evaluate the cytotoxic and apoptosis-enhancing\nactivities of albanol A, compound isolated from <em>M. alba <\/em>root bark by using human leukemia cells (HL-60). The\nfinding of this research paper showed that albanol A exhibited strong cytotoxic\naction and induced early apoptosis. It was postulated that the compound albanol\nA induced apoptosis in HL-60 cells death by the mechanism of caspase-2\nactivation and cell death receptor pathway. &nbsp;Hence, albanol A could be a source of drug for\neffectively treating leukemia<sup>21<\/sup><sup>,22<\/sup>.\nThe methanolic root and bark extracts of <em>M.\nalba <\/em>against human colorectal cancer SW480 cells also showed that extracts arrest cell division and induce apoptosis in colorectal cancerous SW480 cells<sup>22,32<\/sup>.&nbsp; In another study, a mixture of morusinol,\nisolated from <em>M. alba <\/em>root bark, and\ndoxorubicin, a chemotherapy medication, exerted anti-cancerous properties on\nthe human colon adenocarcinoma cell line (HT-29)\nby activation of apoptosis and suppression of nuclear\nfactor-kappa B (NF-\u03baB)<sup>33<\/sup>. Flavonoids morusin, 8-geranyl apigenin,\nand sanggenon K, isolated from <em>M. alba <\/em>showed\nanticancerous effects against HeLa cells, MCF-7\ncells and Hep-3B cells, respectively <sup>17<\/sup>. Water and aqueous\nmethanolic extracts also inhibited the growth of human hepatocellular carcinoma\nHepG2 cells<sup>34<\/sup>. A study was conducted to\nunderstand the basic molecular mechanism for immune system activation and the chemotherapeutic effect of the phytochemicals\nobtained from <em>M. alba, <\/em>showed\nincreased levels of cytokines, nitric oxide (NO)\nand tumor necrosis factor-\u03b1 (TNF-\u03b1) and\ntumoricidal properties of macrophages (Figure 3). Though it was found that\nphytochemicals never directly triggered on tumor cells, it did display\ncytotoxicity through activated macrophages. The following flowchart shows the\nmechanism of how phytochemicals obtained from <em>M. alba <\/em>affect the tumor cells indirectly<sup>35<\/sup>.<\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-62212\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig3-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig3-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig3-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig3.jpg 749w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 3: Summary of the effects of <em>M. alba <\/em>fruit extract against cancer development. TNF-\u03b1: tumor necrosis factor alpha; IFN-\u03b3: interferon\u2010gamma;<\/strong><\/p>\n<\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig3.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\"><strong>Antimicrobial Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A\nphytochemical compound, kuwanon G, isolated from <em>M. alba<\/em> methanolic extract showed antimicrobial potential against <em>Streptococcus sobrinus, Streptococcus\nsanguis, Porphyromonas gingivalis, <\/em>and<em>\nStreptococcus mutans<\/em><sup>36<\/sup>. Mulberrofuran G and albanol B isolated\nfrom the root bark strongly inhibit <em>Staphylococcus\naureus, Staphylococcus epidermidis, <\/em>and<em>\nSalmonella typhimurium<\/em><sup>37<\/sup>.&nbsp;\nA study involving chloroform, petroleum\nether, and methanolic leaf extracts of <em>M.\nalba <\/em>was conducted to determine antimicrobial activity against <em>Candida albicans <\/em>and<em> Aspergillus niger<\/em>. It was observed that all the extracts exhibit\nnoticeable antimicrobial activity against these microorganisms depending on the\ndose<sup>38<\/sup>. It was found that the flavonoids leachianone G and\nmulberroside C, which were separated from the root bark of <em>Morus alba<\/em>, have strong antiviral properties against the herpes\nsimplex type 1 virus (HSV-1)<sup>39<\/sup>.\nChalcomoracin, a mulberry tree phytoalexin, was isolated from <em>M. alba, <\/em>has\nantibacterial properties against methicillin-resistant <em>S. aureus<\/em> (MRSA) bacteria<sup>40<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Anti-inflammatory Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\ndifferent parts of <em>M. alba <\/em>plant\nshowed strong anti-inflammatory properties. Kuwanons C and G, isolated from <em>M. alba, <\/em>activate extracellular signal-regulated kinase (ERK) 1\/2 and\ninhibit NF-\u03baB pathway mediated anti-inflammatory effect<sup>41<\/sup>. In the\nsame way, oxyresveratrol, which is the active compound obtained from <em>M. alba <\/em>also\nshows anti-inflammatory activity<sup>42<\/sup>. Cyclooxygenase 2 (COX-2) gene\nexpression was inhibited by cudraflavone B flavonoid extracted from the roots\nof <em>Morus alba<\/em>. It blocks the translocation of NF-kB and has properties as a potent inhibitor of tumor necrosis factor-alpha\n(TNF alpha)<sup>43<\/sup>. In lipopolysaccharide (LPS)-induced THP-1 cells, a\nmonocyte derived from peripheral blood, resveratrol from <em>M. alba<\/em> was found to decrease interleukin-8\n(IL-8) release via preventing mitogen-activated protein kinase (MAPK)\nphosphorylation and activation of NF-kappaB<sup>44<\/sup>. Inhibition of\nphosphodiesterase-4 (PDE4) enzymes causes the accumulation of cAMP and\nconsiderably reduces the inflammatory responses. Moracin M obtained from <em>M. alba <\/em>is responsible for the\ninhibition of PDE-4 enzyme, which is related to anti-inflammatory activity<sup>45<\/sup>.\nSo that compounds which exhibit such properties can be used as\nanti-inflammatory agents. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Anti-hyperlipidemic Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Hyperlipidemia\nis a condition in which the levels of lipids or lipoproteins get abnormally high and show\nthe most prevalent risk factors for the\ndevelopment of atherosclerosis and cardiovascular disease.&nbsp; Rats that consumed cholesterol were\nadministered extracts from the root bark fractions of <em>M. alba<\/em> in order to test the plant&#8217;s hypolipidemic and antioxidant\nproperties. The formation of lipid peroxides and inhibition of low density lipoprotein (LDL) atherogenic\nmodifications suggests that the extract obtained from the root bark can exhibit\nstrong anti-hyperlipidemic nature, and it has the potential to act as a\nhypocholesterolemic nutrient implying that it possesses\nhypolipidemic properties<sup>46<\/sup>.&nbsp; In\na different investigation, hyperlipidemic rats received an oral aqueous extract\nfrom <em>M. alba<\/em> leaves for two weeks\nshowed a reduction in plasma triglycerides levels by 55.01%. In addition to the\ndecrease of the plasma level of triglycerides, hepatic enzymes were also positively\nrestored to the normal level, thus showing the\nhyper triglyceridemic effects of the leaves of mulberry<sup>47<\/sup>. The\nresults of both of the above studies were further supported by another study in\nwhich phytochemicals mulberroside A and oxyresveratrol isolated from <em>M. alba <\/em>were examined for anti-hyperlipidemic\nproperties in <em>in vivo<\/em> models which\nexplored that mulberroside A and oxyresveratrol reduce serum lipid levels in\nhyperlipidemic rats. Results also indicate that oxyresveratrol has strong\nlipid-lowering potential than mulberroside A<sup>48<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Anti-atherosclerotic Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It\nhas been reported in many studies that the fruits and leaf\nextracts of <em>M. alba <\/em>are known\nto exhibit anti-atherosclerotic effects in rodents. An experiment involved the\nadministration of 1% mulberry leaf powder as a dietary supplement to see the\neffects on atherogenesis in apolipoprotein E-deficient mice. After 12 weeks of\ntherapy, there was a noticeable increase in the mulberry leaf group&#8217;s\nlipoprotein oxidation lag time when compared to the control group. Furthermore,\na 40% decrease in the size of the aortic atherosclerotic lesion was seen in the\nmulberry leaf group. This could be attributed to the presence of antioxidant\nsubstances that have potent inhibitors of lipoprotein oxidation and free\nradical scavenging<sup>49<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">An\nexperiment was conducted in which New Zealand white rats were administered with\n<em>M. alba <\/em>water extract (MWE) in\naddition to a high cholesterol diet (HCD) to determine the hypolipidemic and\nanti-atherosclerotic properties of <em>M.alba<\/em>.\nIt was observed that the levels of low-density lipoprotein cholesterol (LDL-C),\ncholesterol and triglyceride were lower in the serum of rabbits administered\nwith MWE than control group. By including the\nextract in the rabbits&#8217; diets, the amount of atherosclerosis in the aorta was\nsignificantly reduced. There was a reduction in the aortic atherosclerotic\nlesion in the blood vessels of rabbits as observed in the histopathological\nexamination. In addition to the inhibition of LDL-oxidation, previously existing\ndata and findings from the experiment suggest that the extract directly affects\nthe antihyperlipidemic effect in animals. Administration of freezer-dried\nmulberry fruit powder (5% to 10%) to rats on a high-fat diet lowered the\ntriglyceride content, total cholesterol, increased the levels of antioxidant\nenzyme and inhibited malondialdehyde (MDA), a\nproduct of lipid peroxidation. This suppressed the growth of atherosclerosis in\nthe rats<sup>50<\/sup>. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Anti-obesity Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In\ndiet-induced obese mice, the effects of <em>M.\nalba<\/em> ethanol leaf extract on obesity were investigated. It was found that\nthe extract had a strong anti-obesity impact and reduced body weight and\nadiposity. Additionally, it controlled the mice&#8217;s hepatic lipid accumulation.\nIt has been suggested that receptor antagonism may be the cause of the\nextract&#8217;s anti-obesity effects<sup>51<\/sup>. Aqueous mulberry leaf extract was\ngiven to male hamsters on a high-fat diet as part of a study. This led to a\nsignificant a reduction in body weight, reduction in the cholesterol, serum\ntriacylglycerol, and free fatty acid concentrations, and in addition to that\nthe HDL\/LDL ratios were elevated<sup>52<\/sup>. There was another recent study\nconducted in which obese mice were administered with a combined mixture of the\nleaf and fruit extract of <em>M. alba <\/em>for\n12 weeks. This was because the combination mixture reduced the oxidative stress\nand, in addition to that, ameliorated the cholesterol transfer proteins<sup>53<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Hypocholesterolemic Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Rats\nthat were fed cholesterol were given methanolic extracts from the root bark\nfractions as part of an experiment. Three distinct <em>M. alba<\/em> fractions (MRBF-1, MRBF-2, and MRBF-3 fractions) were given\norally to the hypercholesterolemic rats for a period of 15 days in order to\nmonitor any hypocholesterolemic effects. The findings indicated that taking\nMRBF-2 and, to a limited extent, MRBF-3 portions of <em>M. alba<\/em> root bark possesses potential\ntendency to act as a powerful antioxidant and a hypocholesterolemic activity by\nthe formation of lipid peroxides and inhibition of LDL atherogenic\nmodifications in hypercholesterolemic rats<sup>46<\/sup>. In another experiment,\nanalysis of various bioactive components of Polish <em>M.alba<\/em>, especially the ethanol-water extract obtained from the\nleaves, showed hypocholesterolemic properties. It was mainly conducted to\nexamine the effect of the extract on plasma antioxidant capacity and plasma\nlipids in rats that have been fed a high-fat diet for 6 weeks. Additionally,\nthe extract was also added as a supplement to the diet of hyperlipidemic wistar\nrats. It was observed that both the antioxidant activity and LDL cholesterol\nlevels were found to have significantly decreased. It was postulated that\naqueous ethanolic extract from the leaves of <em>M. alba <\/em>was an excellent source as a supplement to the diets for hypercholesterolemic\nindividuals<sup>54<\/sup>. The\nphytochemicals present in <em>M. alba <\/em>have\nbeen known to contain various biologically active compounds that could prevent\natherosclerosis development caused by high cholesterol consumption. It was\npostulated that <em>M. alba <\/em>leaves\nprevented abnormal blood vessel reactivity caused by hypercholesterolemia<sup>55<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Anti-diabetic Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">An\ninvestigation was carried out on streptozotocin-induced diabetic rats to\nexamine the effects of mulberry leaf ethanolic extract by measuring blood\nglucose, oxidative damage, and glycation levels. The experiment involved the\ndaily administration of 1g\/kg <em>M. alba <\/em>for\nsix weeks. From this experiment, it has been found that both 4U\/kg insulin and 1g\/kg<em>M. alba <\/em>extract decrease blood glucose\nlevel in the same extent. Results suggest that\nlong-term <em>M. alba<\/em> treatment has\nantihyperglycemic, antiglycemia, and antioxidant benefits in chronic diabetic\nrats. Thus, they can be considered a beneficial food supplement for people\nsuffering from diabetes<sup>56<\/sup>. An additional investigation exploring the\npotential anti-diabetic effects of <em>M.\nalba<\/em> fruits and leaves in rat models revealed that the leaf extract\nsignificantly reduces postprandial glucose levels by blocking the transit of\nglucose and \u03b1-glucosidase<sup>57<\/sup>. Mulberry root bark extract was given to\ndiabetic rats that had been induced with streptozotocin (STZ) for ten days. The\nresults of this investigation indicate that serum glucose and lipid peroxides\nwere significantly reduced, and that this was followed by an increase in\ninsulin levels<sup>58<\/sup>. Research has also\nshown that the pancreas of diabetic rats benefited from the use of <em>M. alba<\/em> leaf extract. Different doses of\nmulberry leaf extract were given to diabetic rats for 35 days<sup>59<\/sup>.&nbsp; The findings suggested that this plant&#8217;s\nextract could lower blood sugar levels by regenerating \u03b2 cells, restoring\nnormal islet diameter, and balancing the pancreatic weight.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In a study, the alpha-glucosidase inhibitory components obtained from mulberry tea were studied. There is a significant observable difference in the inhibitory activity of different tea products against both sucrase and maltase. It was observed that during the preparation of the tea, if they were allowed to be brewed for 3-5 minutes, they proved to be the most effective in the inhibition of enzymes. On a Caco-2 cell culture experiment, the amount of glucose on the apical and basal sides of the cell monolayers decreased. It was shown that plant extracts can be consumed as an antidiabetic herb tea and have an inhibitory impact on the enzymes maltase, sucrase, and alpha-glucosidases<sup>60<\/sup>.&nbsp;&nbsp; According to a study by Hunyadi<sup>61<\/sup>, type II diabetic rats&#8217; blood glucose levels decreased after taking an 11-day dose of <em>M. alba<\/em> leaf extract in aqueous ethanol. They postulated that the extract&#8217;s anti-diabetic properties took place in the presence of rutin and chlorogenic acid.&nbsp; When Zucker diabetic fatty rats were given mulberry fruit extract, their blood glucose levels were found to be much lower than those of the control group. At the maximum dosage, there was no observable decline in the insulin levels, and no discernible changes were observed in the histology of the pancreatic \u03b2-cells<sup>62<\/sup>.&nbsp; An investigation was carried out to ascertain the cellular mechanisms by which white mulberry mitigates diabetic retinopathy (Figure 4). The mechanism examined the preventive impact of <em>M. alba<\/em> leaf ethanolic extract on angiogenesis, oxidative stress, inflammation, and apoptosis in diabetic retinopathy. <em>M. alba<\/em> extract (100 mg\/kg) was given daily to diabetic rats triggered by streptozotocin (STZ) for duration of 16 weeks. The findings suggest that <em>M. alba<\/em> may be susceptible to developing diabetic retinopathy<sup>63<\/sup>.<\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-62213\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig4-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig4-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig4-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig4.jpg 738w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 4: Protective mechanisms of <em>M. alba <\/em>extract against hyperglycemia-induced retinal damage<sup>63<\/sup><sub>.<\/sub><\/strong><\/p>\n<\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig4.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\"><strong>Effect on Cardiovascular Diseases<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">According\nto Lee<sup>64<\/sup>, morusinol obtained from <em>M. alba&#8217;s<\/em> root bark prevents the production of thromboxane B2 (TXB2) in cultured platelets. It also\ninhibited the induced platelet aggregation. Because of its antiplatelet action,\nit is highly efficient in vivo in preventing arterial thrombosis. It also has\nbeneficial effects on stroke through platelet activation modulation. Chan<sup>65<\/sup> explored\nthat the leaf extract of <em>M. alba <\/em>inhibits the migration of the vascular smooth muscle cell\n(VSMC). It was found that phosphorylation of focal\nadhesion kinase (FAK) and Akt, suppression of NF-kappaB, guanosine triphosphatase expression, and reduction of MMP-2,\nMMP-9, and metalloproteinases (MMPs) activities, increase\nvascular smooth muscle cell (VSMC) migration.\nA study was conducted to examine the effects of <em>M. alba<\/em> leaf extracts on aortic VSMC in rabbits fed a\nhigh-cholesterol diet. It was found that the\nmulberry leaf polyphenol extract inhibits VSMC proliferation and migration, and\nin addition to that, they also reduce the atheroma burden in the vascular wall<sup>66<\/sup>.&nbsp; <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Cardioprotective Effects<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">To\ninvestigate the cardioprotective effect of mulberry leaf powder in autoimmune\nmyocarditis rats, and results suggested that a diet having mulberry as a\nsupplement has the potential to preserve cardiac functions in experimental\nautoimmune myocarditis<sup>67<\/sup>. The mechanism by which cardiac functions were retained against oxidative stress due to\nactivation of MAPK pathways. This also enables\nprotection against endoplasmic reticulum stress-mediated apoptosis. There is a\nsignificant reduction in the mast cell density, cardiac fibrosis, myocyte\napoptosis, and myocardial levels of\nSarco\/endoplasmic reticulum Ca<sup>2+<\/sup>\nATPase2, caspase12 cellular infiltration, and phosphor p38 mitogen-activated\nprotein kinase with supplementation of mulberry leaf. An experiment was\nconducted <em>in vivo<\/em> using male wistar rats\nto assess the cardioprotective effect of the\nextract obtained from the leaves of <em>M. alba\n<\/em>against isoprenaline-induced myocardial infarction. The findings of this\nstudy indicate that the leaf extract of <em>M. alba <\/em>exhibits a cardioprotective\neffect by increasing antioxidant defense system and lowering lipid peroxidation during\nisoprenaline-induced myocardial infarction in rats<sup>68<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Neuroprotective Effects<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The accumulation of \u03b2-peptides leads to\nthe formation of plaque in individuals suffering from Alzheimer\u2019s disease.\nKaempferol-3-O-glucoside, and kaempferol-3-O-(6-malonyl) glucoside obtained\nfrom the methanolic extract of <em>M. alba <\/em>inhibit\nthe formation of amyloid beta-peptide (1-42) fibril. They also protected the\nhippocampal neurons against amyloid beta-peptide (1-42)-induced neurotoxicity. The\nresults indicated that there may be hope for treating Alzheimer&#8217;s disease with\nmethanolic extract derived from <em>M. alba<\/em>\nleaves; nevertheless, additional research is needed to confirm the extract&#8217;s\neffectiveness.<sup>69,70<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In\nan experiment, the neuroprotective effects of oxyresveratrol were tested on two\ndifferent pathologies. One is an <em>in vitro<\/em>\nmodel of co-cultures of glia and neurons with stretch-induced trauma, and the\nother is by exposing the culture to high levels of glutamate. The cultures were\ntreated with different concentrations of oxyresveratrol obtained from <em>M. alba<\/em>.\nIt was observed that oxyresveratrol significantly inhibited the neuronal death\ncaused by trauma. But in the case of the culture\nexposed to glutamate, it was not successful in inhibiting the neuronal loss\ncaused by extreme exposure. It was concluded that additional experiments to\nstudy the effect of oxyresveratrol in cases of traumatic injuries have to be\nconducted<sup>71<\/sup>. The effect of <em>M. alba\n<\/em>on glutamate and oxygen-glucose deprivation-induced cell death in cortical\nneurons of rats was observed.Cyanidin-3-glucoside (C3G) compound from the fruit\nof <em>M. alba<\/em> given to the rats and\nfound that the extract was able to preserve the mitochondrial function of the\nneurons and prevented the damage of the membrane in primary cortical neurons\nexposed to oxygen-glucose deprivation. But C3G didn\u2019t provide any sort of\nprotection in case of glutamate-induced cell death<sup>72<\/sup>.&nbsp; <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Hepatoprotective Effects<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">An\ninvestigation was carried out to ascertain the protective mechanism of mulberry\nwater extracts (MWE) in CCl<sub>4<\/sub>-induced hepatic wistar rats. The\nextract was administered orally, and it led to a reduction of lipid\nperoxidation and inhibition of liver fibrosis and lipid deposition. The findings\nof this experiment indicatethat the mulberry extract has hepatoprotective\neffects against fibrosis by inhibiting the proinflammatory gene expression and\ndecreasing the lipid peroxidation<sup>73<\/sup>. Rats were used in another\nexperiment to test the hepatoprotective effects of water, petroleum ether,\nalcohol-based <em>M. alba<\/em> extracts, and\nchloroform against paracetamol-induced hepatotoxicity. From this experiment, it\nwas observed that CCl<sub>4<\/sub> present in the paracetamol led to an increase\nin the levels of alanine phosphatase (ALP), serum\nglutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate\ntransaminase (SGPT), serum bilirubin, and caused\nsignificant damage to hepatocytes. According to the findings, pre-treating the\nrats with <em>M. alba<\/em> leaf water and\nalcoholic extracts minimized the hepatotoxicity\ncaused by paracetamol <sup>74<\/sup>. It was postulated that the hepatoprotective\nproperties of the alcohol-based extract occurred\nby the presence of carbohydrates, alkaloids, tannins, flavonoids, and steroids,\nwhereas the water extract possessed flavonoids, carbohydrates, and alkaloids. To\ntest <em>M. alba<\/em> hydroalcoholic extract\u2019s\nhepatoprotective properties in mice with CCl<sub>4<\/sub>-induced hepatic liver\ndamage, the findings of the experiment indicate that hydroalcoholic extract of <em>M. alba<\/em> leaves significantly reduced the\nlevels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST)\ncompared to the CCl<sub>4<\/sub> group<sup>75<\/sup>.&nbsp; <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Antihelmintic Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">An\nexperiment was conducted to determine the anthelmintic capacity by subjecting\nIndian earthworms to different concentrations of <em>M. alba<\/em>petroleum ether, chloroform, and methanolic leaf extract. The anthelmintic capacity was obtained\nby determining the time taken for paralysis and death of the earthworms. The\nanthelmintic capacity of the extracts at different dosages is quite comparable\nto that of the effect produced by albendazole, which is the standard antihelmintic drug. The study concluded that <em>M. alba <\/em>contains steroids,\ntriterpenoids, tannins, flavonoids, and alkaloids, hence having anantihelmintic effect<sup>38<\/sup>. The antihelmintic activity was further demonstrated by the\nexamination of alcohol, petroleum ether <em>M.\nalba<\/em> leaf aqueous extract. The time taken for paralysis and the death of\nthe worms at different concentrations of plant\u2019s extract was used to determine\nthe anthelmintic capacity. The results proved that petroleum ether, alcohol,\nand aqueous extract of <em>M. alba <\/em>leaf caused\nparalysis of the worms and at higher doses even led to their death<sup>76<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Research\nwas done to determine the anthelmintic potential of water extract prepared from\nthe leaves of <em>Azadirachta indica,\nDalbergia sisso<\/em>, and <em>M. alba<\/em>\nagainst the ova and adult worms of <em>Haemonchus\ncontortus<\/em>. Three different types of tests <em>i.e.<\/em> egg hatch test, the egg count reduction test and the adult\nmotility assay were carried out to determine the anthelmintic capacity of the\nplants. The findings of this study suggest that the extract obtained from the\nleaves of the mentioned plants possesses antihelmintic\nproperties as they can induce anti-parasitic activity in the test subject<sup>77<\/sup>.\nIn an experiment, <em>Pheretima posthuma<\/em>,\nan Indian earthworm, was subjected to aqueous, ethanolic and hydro-alcoholic extracts\nprepared from <em>M. alba <\/em>bark. The\nextracts were administered to the earthworms in a dose-dependent manner, and\nthe time taken for paralysis and death of the earthworms was recorded. Normal\nsaline was used as the control group and piperazine hydrate as a reference\nstandard. The anthelmintic capacity of the extracts depended on the dosage\nadministered to the earthworms. The results suggested that all the extracts\npossess anthelmintic properties. It was also found that the hydro-alcoholic\nextract is more potent than the other extracts,\nbut additional experiments need to be conducted to validate the efficacy and\nusage of <em>M. alba <\/em>as an anthelmintic\ndrug<sup>78<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Nephroprotective Activity<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nprotective effect of hydroalcoholic extract and flavonoid fraction from leaves\nof <em>M. alba<\/em> was evaluated against cisplatin-induced\nnephrotoxicity in male rats. It was observed that the hydroalcoholic extract\ndid not affect the increased serum levels of blood urea nitrogen (BUN) and creatinine\n(Cr) due to cisplatin, but on the other hand, the flavonoid fraction\nsignificantly decrease the serum concentration levels of Cr and BUN however, no\nsignificant effect was observed on serum nitric oxide levels. The findings\nsuggested that the flavonoid fraction obtained from the leaves of <em>M. alba <\/em>can be used as a nephroprotective\nagent against the cisplatin-induced nephrotoxicity<sup>79<\/sup>. In another\nexperiment, the hydroalcoholic extract from <em>M.\nalba <\/em>on the isoniazid-induced nephrotoxicity in albino rabbits, a drug used\nfor the treatment of tuberculosis, explore that the hydroalcoholic\nextract had a significant nephroprotective effects against\nisoniazid induced nephrotoxicity in the rabbits. Histopathological analysis and\nthe HPLC analysis were also conducted, which indicate that isoniazid showed significant\ndecrease in the serum of rabbits that were treated with the hydroalcoholic\nextract of <em>M.alba<\/em>. Thus, it was\nsuggested that hydroalcoholic extract obtained from <em>M. alba <\/em>reduced the nephrotoxicity\ninduced by isoniazid and can potentially be used as an alternate drug<sup>80<\/sup>. Ullah<sup>81<\/sup>reported\nthe nephroprotective effects of ethanolic extract of <em>M. alba<\/em> in rabbits in which rabbits were administered with the\nethanolic extract along with gentamicin for three weeks. The findings indicate that\nthe plant extract inhibited the level of Cr, BUN and uric acid.\nHistopathological analysis also indicated that the extracts possess a\nprotective capacity. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Immunomodulatory Properties<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Immunoglobulins\n(Ig), also known as antibodies, are a \u2018Y\u2019- shaped protein molecule that is\nmainly produced by plasma cells. They are present in the blood, exocrine fluid,\nand tissue fluid. Amongst all of them, the body\u2019s humoral immunity, which\nconsists of IgG, IgA, and IgM in the serum of almost all mammals<sup>82<\/sup>.&nbsp; The immunomodulatory effect was tested by\nadministering oral doses of methanolic extract of <em>M. alba <\/em>both at high and low concentrations along with <em>Ocimum sanctum<\/em> as a standard drug. It\nwas observed that in both cases, the levels of immunoglobulins in serum were high.\nIt has been observed that an increase in antibody levels in the blood circulation, an increase\nin the phagocytic index, and increase in the adhesion of neutrophils led them\nto postulate that <em>M. alba <\/em>increases\nboth the cellular immunity as well as humoral immunity<sup>83<\/sup>. In\naddition to that, an experimental study was carried out on weanling pigs by\nadding mulberry (<em>M. alba<\/em>) leaves in\ntheir dietary supplements to test the effect on the immune parameters of the pigs.\nThe increase in the levels of immunoglobulin G (IgG)\nand immunoglobulin M (IgM) in the pigs indicated that an increase in the\nformation of antibodies. Such a rise in antibody and cytokine levels in the\nblood might indicate that the cellular and humoral immunity has improved in the\ntest animals&#8217;<sup>84<\/sup>.\nTo study the mechanisms of the immune response, a xenograft mouse was exposed\nto <em>M. alba <\/em>fruit extract (MFE). An\nimproved chemotherapeutic activity was obtained with a significant increase in\nthe IgG levels<sup>35<\/sup>. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Effect on Blood Coagulation<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Blood\ncoagulation is the process by which the blood converts itself from liquid to\ngel form, thus leading to the formation of a blood clot<sup>85<\/sup>.\nThrombosis is a process in which blood clotting takes\nplace within a blood vessel, known as a thrombus. It prevents blood flow within\nthe blood vessels. Thrombosis is caused by activation of platelet aggregation,\nadhesion, and induction of extrinsic and intrinsic blood clotting systems,\nwhich cause fibrin formation. So to prevent thrombosis, it is necessary to\ninhibit platelet function. The antiplatelet activity of <em>M. alba <\/em>leaf extract (MAE) was studied using rat platelets <em>i.e<\/em> an investigation\/experiment was\nconducted to determine whether <em>M. alba <\/em>leaf\nextract affects platelet aggregation or not. An arteriovenous shunt model of a\nrat was used to assess the formation of thrombus <em>in-vivo<\/em>. The following flowchart shows the mechanism of the\ninhibitory effect of MAE.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nresults obtained from the <em>in-vitro <\/em>experiment showed that the ethanol extract of <em>M. alba <\/em>leaf (MAE) has antiplatelet and\nantithrombotic properties because it inhibited the suppression of platelet\naggregation induced by collagen and reduced the thrombus formation<sup>86<\/sup>.\nAnother experiment was carried out by using an <em>in vitro<\/em> rabbit platelet aggregation to determine the antiplatelet\npotential of flavonoids morusinol from plant bark root against ferric chloride\ninduced thrombosis model. The results of this experiment signify that morusinol\nsignificantly suppresses platelet aggregation in a concentration-dependent\nmanner. In addition to that, it was observed that phytocompounds can\nsignificantly inhibit arterial thrombosis formation<sup>87<\/sup>. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Effect on Vasodilation<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Vasodilation\nmeans the widening of blood vessels, which usually occurs at the surface of the\nskin and it causes an increase in the blood flow and provides a feeling of\nwarmth<sup>88<\/sup>. The vasodilatory action of ethanolic extracts from <em>M. alba <\/em>leaves\nwas investigated on rats and rabbits. Result showed that mulberry leaf extract\nshowed dose dependent increase in the nitric oxide levels. When the rats were\ntreated with the lowest dosage of ethanolic mulberry leaf extract, at minute\n30, there was a marginally significant (P&lt;0.05) difference in the NO level\nas compared to the negative control. The highest concentration of NO in the\nserum was detected at 202.67 mg\/kg BW of mulberry extract. As a result, this\ndosage was selected for the rabbit ear vasodilatation test. At minute 60 following\nextract administration, it was found that the mulberry leaf ethanolic extract\ncould considerably widen the rabbit ears&#8217; large and small capillaries in\ncomparison to the negative control (P&lt;0.05). Thus, it can be claimed that\nmulberry leaf ethanolic extract has a vasodilator effect, most likely as a\nresult of raising serum NO levels<sup>89<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Effect on Cytokine <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In\na cytokine storm, it has to produce more and more cytokines, even if this is\ninsufficient to destroy the virus, and this cycle continues indefinitely. Now,\nbecause of this, the suppressor cells don&#8217;t receive the messages to turn off\nthe production. This potentially fatal systemic\ninflammatory syndrome is known as &#8220;cytokine storm&#8221; and caused a\nvariety of infections, malignancies, autoimmune diseases, and monogenic\ndisorders. They are characterized by high amounts of circulating cytokines and\nimmune cell hyperactivation<sup>90<\/sup>. So, there will be a barrage of\nimmune cells going to those places, thereby damaging any vulnerable organ.\nResearch was carried out to evaluate the impact of kuwanon-G isolated from the\nroot barks of <em>M. alba<\/em> to study the\ninfluence phytochemicals on the cytokine storm. In the asthmatic\nmice model, Kuwanon G compound reduces the levels of IgE, IL-4, IL-5, and IL-13\ncytokines in the bronchoalveolar lavage (BAL) fluids, which indicates that Kuwanon\nG has properties to inhibit the development of asthma by reducing the cytokines\nproduction<sup>91<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Effect on Sympathetic Responses <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A\nrat model of chronic stress (CS) was used in the study to assess the\nadaptogenic properties of the ethyl acetate soluble fraction of the methanol\nextract of <em>M. alba<\/em> roots. Chronic\nstress was shown to cause severe mental depression, cognitive impairment,\nelevated stomach ulcers, elevated blood cortisol levels, and hyperglycemia. The\nCS-induced problems were significantly reduced when the ethyl acetate soluble\nfraction of the methanol extract of <em>M. alba<\/em>\nroots was administered<sup>92<\/sup>. Thus the findings suggest that\nthe administration of <em>M. alba <\/em>has the\npotential of reducing the stress thereby, in turn, reducing the sympathetic\nresponses.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Effect on Fibrosis<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Fibrosis is characterized by the unregulated development of\nextracellular matrix components in place of normal tissue, which results in\nsignificant tissue remodeling and the development of permanent scar tissue<sup>93<\/sup>.\nA study was conducted to ascertain whether or not administering <em>M. alba<\/em> leaves to mice on a high-fat\ndiet may mitigate the effects of obesity-induced hepatic lipogenesis, oxidative\nstress, and fibrosis. It was\nobserved that <em>M. alba<\/em> leaf extract treatment\nsignificantly reduced lipid biosynthesis and hepatic fibrosis markers. Therefore, supplementing with <em>M. alba<\/em> leaf extract may be a promising therapeutic agent for\nobesity-related fatty liver disease by controlling the synthesis of fibrosis, hepatic\nlipid metabolism, and the antioxidant defense system<sup>94<\/sup>. The effect of <em>M. alba <\/em>on other types of fibrosis is\nstill yet to be discovered, and more studies have to be made to determine\nwhether the phytochemicals present in the biologically active components of <em>M. alba <\/em>would have any effect or not. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Skin Whitening Effects<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Melanin\nis a natural skin pigment, and the amount of melanin in an individual decides\nthe color of hair, skin, and eyes. Melanin is\nproduced by melanocytes, and the process of creation is known as melanogenesis.\nTyrosine, an amino acid, undergoes oxidation in this complex chemical process,\nwhich is followed by polymerization. Melanin protects the cells of the skin\nfrom harmful UV radiation, thereby protecting the skin from melasma, skin\ncancer, hyper pigmentation, and wrinkling. Mulberroside F, which was derived\nfrom the methanolic extract of <em>M. alba<\/em>\nleaves, was found to have inhibitory effects on tyrosinase activity and the\nformation of melanin by melanocytes in a study.\nIt was also able to protect against auto-oxidation. The findings suggested that\nmulberroside F obtained from the leaves of <em>M.\nalba <\/em>can potentially be used as a skin protective agent<sup>19<\/sup>. A\nstudy involved the topical application of oxyresveratrol, mulberroside A and\noxyresveratrol-3-O-glucoside to brown-skinned guinea pigs to study the\npotential inhibitory effect on the harmful UV radiation. It was observed that\nall three of them successfully inhibited tyrosinase activity; significantly\nreduced the melanin content in the skin of guinea pigs exposed to the harmful\nUV rays and also caused depigmentation. Out of the three, oxyresveratrol was\nfound to exhibit the highest anti-melanogenesis effect and mulberroside A, the\nlowest. It was suggested that the compounds extracted from <em>M. alba <\/em>have the potential to be used as a skin whitening agent as\nthey successfully reduced the pigmentation (Figure 5)<sup>95<\/sup>. <\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-62214\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig5-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig5-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig5-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig5.jpg 825w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 5: Effect of resveratrol on melanogenesis and signaling pathways in elanocytes<sup>96<\/sup>.<\/strong><\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2024\/10\/Vol17No4_Phy_Anu_Fig5.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\"><strong>Conclusions<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nvarious bioactive compounds present in the extracts isolated from the different\nparts of <em>M. alba <\/em>plant have potential\npharmacological activities, which include antioxidant, anti-inflammatory,\nantimicrobial, hepatoprotective, antidiabetic, anti-atherosclerotic,\nneuroprotective, anthelmintic, anxiolytic, hypocholesterolemic, anti-obesity,\nantimutagenic, and nephroprotective properties, and also\nhave a positive impact on various parameters such as immunoglobulin\nlevels, blood coagulation factors, vasodilation, cytotoxic responses, cytokine\nstorming, sympathetic responses, oxidative stress, and fibrosis. Although the different extracts and isolated compounds from <em>M. alba <\/em>plant have many therapeutic implications,\nbut further research need to be conducted for the exploration of antiviral\nactivities of <em>M. alba <\/em>especially for\nSARS-CoV, Ebola, MERS-CoV, H1N1 pandemic, measles virus, and Nipah virus\ndiseases. The conclusions of review paper suggest that the various <em>M. alba<\/em> plant parts\u2019 extracts have\nsignificant pharmacological properties and can be used as potential source for\nthe preparation of various health care products and herbal formulation to treat\nvarious diseases.&nbsp; <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Acknowledgment<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Anuja\nMishra and Swaroop Kumar Pandey are thankful to Institute of Applied Science\n&amp; Humanities GLA University, Mathura, U.P., India; Rajeev Natesh Kumar is\nthankful to University of Michigan, Ann Arbor, MI, USA; Mamta Shukla is\nthankful to Khwaja Moinuddin Chishti Language University, Lucknow, Uttar\nPradesh, India and Pankaj Singh is thankful to Dr. Rammanohar Lohia Avadh\nUniversity, Ayodhya, Uttar Pradesh, India for providing a platform for this\nscientific contribution.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Funding Sources<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nauthor(s) received no financial support for the research, authorship, and\/or\npublication of this article.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Conflict of Interest<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The author(s) do not have any conflict of interest.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Data Availability<\/strong> <strong>Statement<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This\nstatement does not apply to this article.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Ethics Statement<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This\nresearch did not involve human participants, animal subjects, or any material\nthat requires ethical approval.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Informed Consent\nStatement<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This\nstudy did not involve human participants, and therefore, informed consent was\nnot required.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Clinical Trial Registration<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This\nresearch does not involve any clinical trials<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Authors\u2019 Contribution<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Pankaj\nSingh and Mamta Shukla: Conceptualization, writing, reviewing, and supervision;\nAnuja Mishra, Rajeev Natesh Kumar: Writing, review and editing; Swaroop Kumar\nPandey: Analysis, review and editing.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>References<\/strong><\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Zhang H, Ma ZF, Luo X, Li X. 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