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Nutritional constituents of mulberry and their potential applications in food and pharmaceuticals: A review

March 2021
Saudi Journal of Biological Sciences 28(8)

DOI:10.1016/j.sjbs.2021.03.056

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CC BY 4.0

Authors:

Bisma Jan

Rabea Parveen

Jamia Hamdard

Sultan Zahiruddin

National Center for Natural Products Research

Mohammad Umar Khan

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Mulberry is a fast growing deciduous plant found in wide variety of climatic, topographical and soil conditions, and is widely distributed from temperate to subtropical regions. Due to presence of valuable phytochemical constituents, mulberry as a whole plant has been utilized as a functional food since long time. Mulberry fruits are difficult to preserve as they have relatively high water content. Therefore for proper utilization, different value-added products like syrups squashes, teas, pestil sand köme, pekmez (turkuish by-products), yogurts, jams, jellies, wines, vinegar, breads, biscuits, parathas, and many more are made. In overseas, these value-added products are commercially sold and easily available, though in India, this versatile medicinal plant is still missing its identity at commercial and industrial scale. Leaves of mulberry are economically viable due to their important role in the sericulture industry since ancient times. Mulberries or its extracts exhibit excellent anti-microbial, anti-hyperglycaemic, anti-hyperlipidemic, anti-inflammatory, and anti-cancer effects and is used to combat different acute and chronic diseases. Different parts of Morus species like fruits, leaves, twigs, and bark exhibit strong anti-tyrosinase inhibition activity that makes it a suitable candidate in cosmetic industries as a whitening agent. The current review provides a comprehensive discussion concerning the phytochemical constituents, functionality and nutraceutical potential of mulberry and as a common ingredient in various cosmetic products.

Diverse application of mulberries in multiple areas.

…

Scientific classification of mulberry.

…

Chemical structures of some important metabolites of mulberries.

…

Mechanism of anti-cancer activity of mulberry.

…

Physicochemical paramter of different varieties of mulberry.

…

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Available via license: CC BY 4.0

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Review

Nutritional constituents of mulberry and their potential applications in

food and pharmaceuticals: A review

Bisma Jan

a,c

, Rabea Parveen

a,b

, Sultan Zahiruddin

, Mohammad Umar Khan

a,c

, Sradhanjali Mohapatra

c,d

Sayeed Ahmad

⇑

Department of Food Technology School of Interdisciplinary Science & Technology, Jamia Hamdard, New Delhi, India

Department of Biosciences, Human Genetics and Laboratory, Jamia Milia Islamia, New Delhi, India

Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India

Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India

article info

Article history:

Received 6 January 2021

Revised 21 March 2021

Accepted 22 March 2021

Available online 31 March 2021

Keywords:

Mulberry

Cosmetics

Nutraceuticals

Functional food

Value addition

abstract

Mulberry is a fast growing deciduous plant found in wide variety of climatic, topographical and soil con-

ditions, and is widely distributed from temperate to subtropical regions. Due to presence of valuable phy-

tochemical constituents, mulberry as a whole plant has been utilized as a functional food since long time.

Mulberry fruits are difﬁcult to preserve as they have relatively high water content. Therefore for proper

utilization, different value-added products like syrups, squashes, teas, pestil sand köme, pekmez (turku-

ish by-products), yogurts, jams, jellies, wines, vinegar, breads, biscuits, parathas, and many more are

made. In overseas, these value-added products are commercially sold and easily available, though in

India, this versatile medicinal plant is still missing its identity at commercial and industrial scale.

Leaves of mulberry are economically viable due to their important role in the sericulture industry since

ancient times. Mulberries or its extracts exhibit excellent anti-microbial, anti-hyperglycaemic, anti-

hyperlipidemic, anti-inﬂammatory, anti-cancer effects and is used to combat different acute and chronic

diseases. Different parts of Morus species like fruits, leaves, twigs, and bark exhibit strong anti-tyrosinase

inhibition activity that makes it a suitable candidate in cosmetic industries as a whitening agent. The cur-

rent review provides a comprehensive discussion concerning the phytochemical constituents, function-

ality and nutraceutical potential of mulberry and as a common ingredient in various cosmetic products.

Ó2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access

article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Contents

1. Introduction . . . ..................................................................................................... 3910

2. Botanical description of Morus . . . . . . . .................................................................................. 3910

3. Dietary importance of Morus . . . . . . . . .................................................................................. 3910

4. Role of Morus in food industries . . . . . . .................................................................................. 3911

5. Anti-tyrosinase properties of Morus for cosmetic application . ............................................................... 3914

6. Nutraceutical applications of Morus . . . .................................................................................. 3914

6.1. Anti-microbial properties .......................................... .............................................. 3915

6.2. Anti-hyperglycaemic property . . . . . . . . . . . . .... .................................................................... 3915

6.3. Anti-hyperlipidemic activity. . . . . . . . . . . . . . ....................... ................................................. 3915

https://doi.org/10.1016/j.sjbs.2021.03.056

1319-562X/Ó2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

⇑

Corresponding author.

E-mail address: sahmad_jh@yahoo.co.in (S. Ahmad).

Peer review under responsibility of King Saud University.

Production and hosting by Elsevier

Saudi Journal of Biological Sciences 28 (2021) 3909–3921

Contents lists available at ScienceDirect

Saudi Journal of Biological Sciences

journal homepage: www.sciencedirect.com

6.4. Anti-inflammatory activity . . . . . . . . . . . . . . . ...................................................................... .. 3917

6.5. Anti-cancer action . . . . . . ............................. ........................................................... 3918

6.6. Neurodegenerative actions . . . . . . . . . . . . . . . ...................................................... .................. 3918

7. Miscellaneous activities of Morus species . . . . . . . . . . . . . . . . . ............................................................... 3918

8. Conclusion . . . . ..................................................................................................... 3919

Declaration of Competing Interest . . . . .................................................................................. 3919

Acknowledgement . . . . . . . . . . . . . . . . . .................................................................................. 3919

References . . . . ..................................................................................................... 3919

1. Introduction

Mulberry belongs to the Morus genus of Moraceae family and is

dispersed extensively in diverse climatic and environmental cir-

cumstances ranging from tropical to temperate. Moraceae, also

known as the mulberry or ﬁg family, is a family of ﬂowering plants

of more than twenty-four species with one subspecies and at the

minimum hundred identiﬁed varieties. The term Morus is derived

from the Latin word ‘mora’, which means delay, most likely

because of the slow development of its buds. It is an economical

and widespread woody plant and has an enormous economic value

other than sericulture leading to its several unique and special fea-

tures. Morus alba (white mulberry), Morus nigra (black mulberry)

and Morus rubra (red mulberry) are all commonly accepted world-

wide species of genus Morus as they exhibit maximum medicinal

properties. Amongst all the species, M. alba is a dominant species

(Ercisli and Orhan, 2007). Roots, leaves, bark, stem twigs, and fruits

of mulberry possess valuable bioactive constituents that can be

explored in food, health care, and cosmetic industries. Convention-

ally, it is believed that fruits of mulberry, particularly black and red

varieties are advantageous to the human body (Ercisli and Orhan,

2007). Almost all varieties of mulberry plant are traditionally rec-

ognized in Unani, Ayurveda, and Chinese systems of medicine with

several pharmacological properties. Fruits of M. nigra are among

the important constituents of Unani medicine known as Tutiaswad,

which is believed to have anti-cancerous activities (Nursalam,

2016). In India, mulberry is known as ‘‘KalpaVruksha” since all

parts of the plant are used for various purposes and its fruit is com-

monly named as toot and shahtoot (King’s or ‘‘superior” mulberry).

Chinese utilizes mulberry fruit as a natural medicine to strengthen

the joints, lower the blood pressure, treat fever, protect liver dam-

age, and assist discharge of urine. Its fruits, leaves, and barks in tra-

ditional Turkish folk medicine have been utilized as an anti-fever,

an expectorant, assists in the discharge of urine, to lower blood

pressure, as a folk remedy to treat dental diseases, in dysentery,

as a de-worming agent, laxative, anthelmintic, odontalgic, treat

diabetes, hypertension, arthritis, and anaemia (Özgen et al.,

2009). Azerbaijan people utilize M. nigra fruits in the treatment

of ailments like gall bladder, liver, and heart diseases (Farid

Alakbarli and Iskandar Aliyev, 2000). The presence of valuable con-

stituents in mulberry leaves and fruits makes the plant suitable to

be placed in the category of functional foods that are useful to

human health in addition to its basic nutritional function

(Kadam, 2019). Leaves of M. nigra are commonly used by women

during menopause as a replacement for the conventional hormonal

substitute therapy, with a similar effect to that obtained by estro-

genic use (de Queiroz et al., 2012). Furthermore, its fruits, roots,

and leaves extracts can be utilized in cosmetics globally and is a

commonly used constituent in many dermatological creams, bath

gels, and many more owing to its exceptionally high radical scav-

enging potential. As stated by the Ministry of Health of China in

1985, M. alba was recorded as the ﬁrst medicinal and edible fruit

(Yuan and Zhao, 2017), and its leaves and fruits were considered

not only food but also as drugs (Wang et al., 2014). Mulberry fruits

are soft and delicate, and harvesting season lasts for a month usu-

ally from May-June in most parts of the world and the best growing

temperature is between 24 and 28 °C(Sharma and Zote, 2010;

Dhiman et al., 2020). To properly utilize the mulberry or enhance

the storage life, maintain nutritional and organoleptic qualities,

and to minimize the waste, the possibility of introducing mulberry

as a functional food and nutraceutical is a need of the hour that

many researchers are looking forward to. Nonetheless, being

exceptionally good in nutrients and comparatively low in fats

can be considered a good choice for healthy consumers. An over-

view of multifunctional role of mulberry is shown in Fig. 1.

Based on the existing literature on the mulberry, it will be inter-

esting to review the effectiveness of this multifunctional plant in

attributing different functional properties, when being incorpo-

rated in several food products and to explore its nutraceutical

applications and dermatological role with special emphasis on

tyrosinase inhibition activity.

The current review attempted to provide a holistic insight into

the nutraceutical potential of Morus in preventing various health-

related issues and to investigate the possibilities of using mulberry

as a functional food with some formulations and as a common

ingredient in many cosmetics.

2. Botanical description of Morus

Mulberry is typically a deciduous or medium sized woody

perennial tree having upright ﬁssured bark and cylindrical stem

with a milky sap growing upto 10–13 m tall (Singh et al., 2010,

Rahman and Khanom, 2013). Leaves of mulberry vary in shape

and size, usually range from 5 to 7.5 cm long and 6–10 cm wide

and are mostly deeply lobed, margins serrate, shortly acuminate,

apex acute or, base cordate or truncate; 3 basal nerves, lateral

nerves forked near the margins. Flowers are yellowish green in col-

our with chromosome number 2n = 28. Female spikes are ovoid

and stalked while as male spikes (catkins) are cylindrical and

broad. Male catkins tend to be longer than female catkins. Botani-

cally, mulberry fruit is precisely a cluster of small fruits that are

organised longitudinally around the central axis similar to that in

blackberry or loganberries. Its fruit or syncarp comprises of numer-

ous drupes that are enclosed in a ﬂeshy perianth, ovoid or sub glo-

bose, upto 5 cm long, white to pinkish white, purple or black when

ripe (Anonymous, 2001). In terms of morphology and growth

habits, mulberry ovary is unicellular with a biﬁd stigma and anal-

ogous to that of other ﬂeshy drupaceous fruits. Scientiﬁc classiﬁca-

tion of Morus species is given in Fig. 2.

3. Dietary importance of Morus

Fully ripened mulberry fruit has a wonderful mouth-watering

taste with a good aroma and ﬂavour. It is appreciated for direct

consumption and for making value-added products. Mulberry

fruits are recognized for the well-being of human beings due to

their high nutritional signiﬁcance (Sengül et al., 2005). Addition-

ally, mulberry fruits hold a diversity of nutrient elements that play

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3910

a vital function in human metabolism (Akbulut and Özcan, 2009).

M. alba fruit is a good resource of carbohydrate, lipid, protein, vita-

mins, minerals, and ﬁbers. The quantity of protein in fresh M. alba

fruit is greater than that of raspberries (Rao and Snyder, 2010)and

strawberries (Giampieri et al., 2012)and comparable to blackber-

ries, (Kaume et al., 2012)whereas the anthocyanin content is

higher than blackberry, blueberry, blackcurrant, and redcurrant

(Veberic et al., 2015). M. alba fruit contains both essential and

non-essential amino acids. Essential amino acid /total amino acid

ratio is 42 percent, which is almost equal to certain protein-rich

foods such as ﬁsh and milk (Jiang and Nie, 2015). Hence, can be

considered as an excellent protein source. Chemical structures of

some important metabolites are given in Fig. 3. Each variety of

Morus species contains a signiﬁcant amount of vitamin C, however

among all varieties M. nigra contains the maximum quantity. The

ascorbic acid content in M. alba and M. nigra is 15.81 and

12.81 mg/100g, respectively of fresh fruit weight (Eyduran et al.,

2015). Mulberries also contain some important alkaloids that acti-

vate macrophages by stimulating the immune system and hence

safe guard the human body against health threats (Kim et al.,

2013). The most important alkaloids isolated from mulberry leaves

are 1-deoxynojirimycin (DNJ),1,4-dideoxy-1,4-imino-D-ribitol, and

1,4-dideoxy-1,4-imino-D-arabinitol (Li et al., 2013; Sharma et al.,

2010; Li et al., 2011). Primary sugars present in mulberry are fruc-

tose and glucose, which increase with ripening (Gundogdu et al.,

2011; Mahmood et al., 2012; Eyduran et al., 2015). Amongst the

widely recognised varieties, M. alba has the maximum fat content

of 1.10% followed by M. nigra with0.95% and M. rubrawith0.85%.

Oleic acid, palmitic acid and linolenic acid are the major fatty acids

in mulberry fruit (Ercisli and Orhan, 2007). The sequence of fatty

acids in M. alba fruit is polyunsaturated fatty acids (PUFA) followed

by monounsaturated fatty acid (MUFA) and saturated fatty acids.

Among all fatty acids, PUFA is the main fatty acid in mulberry fruits

comprising at least 76.68%, which is even higher than that of

strawberries (Giampieri et al., 2012; San and Yildirim 2010). There

are many organic acids present in mulberry fruits viz citric acid,

tartaric acid, malic acid, succinic acid and fumaric acid however,

malic acid is primarily found organic acid in all the species

(Eyduran et al., 2015). Mulberry is also an excellent source of some

important minerals particularly calcium, phosphorus, potassium,

magnesium, and sodium. Nonetheless, the mineral content differs

among phenotypes (Gungor and Sengul, 2008). Although M. alba,

M. nigra and M. rubra belong to same genus however, there are still

some differences in their physiochemical parameters. A compara-

tive study of varied physiochemical parameters of mulberry vari-

eties (M. alba, M. nigra and M. rubra) is given in Table 1.

Fig. 1. Diverse application of mulberries in multiple areas.

Fig. 2. Scientiﬁc classiﬁcation of mulberry.

Fig. 3. Chemical structures of some important metabolites of mulberries.

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3911

4. Role of Morus in food industries

The understanding of the relationship between diet and health

by customers has now acquired a profound shift in eating pattern

and lifestyle transformation. The advent of this consumer

understanding has been one of the driving forces in production

of food products that can satisfy both basic dietary requirements

and health beneﬁts. Mulberry fruits are famous throughout the

world for their mouth-watering taste that makes it suitable to con-

sume either in fresh or as an ingredient in value-added products

and for culinary uses. It has gained popularity due to consumer

awareness and enthusiasm for healthy and low calories foods. This

has led to increased demand in food processing industries. The role

of mulberry in diverse food areas is mentioned in Table 2.Ripened

mulberry fruits are harvested by slightly shaking trees (Singhal

et al., 2010). Mulberry fruit is highly perishable making it underuti-

lized, however, there is the scope of value addition by various

means. It contains health-promoting polyphenols and is consumed

directly or in processed product forms such as juices, syrups,

liquors, molasses, jams, wines, and soft drinks. Mulberry fruits

are among the berries that can be called as superfood and can be

industrially explored for diverse commercially priceless valuable

edible products. Several patents have been ﬁled on Morus species

for multiple therapeutic applications such as hypoglycaemic, neu-

rodegenerative, hypolipidemic, compounds with anti-tyrosinase

inhibition and some formulated value-added products as enlisted

in Table 3.

Mulberry may be well exploited in fruit and vegetable indus-

tries for making, marmalade, fondant jams, jellies, cakes, breads,

parathas, fruit teas, fruit drink pulp, fruit wine, fruit sauce, fruit

powder, and chocolate, due to high sugar content. Moreover, these

fruits are either used in dried, frozen, or fresh forms in the food

industry to yield different syrups, amaretto or vermouth wine,

tonic wine, and vinegar. Mulberry seeds can also yield oil. ‘Pestil’

and ‘köme’ are the famous traditional Turkish foods, which are pre-

pared from a mulberry, walnut, hazelnut, honey, and ﬂour mixture

(Oktay, 2013; Sengül et al., 2005; Ercisli and Orhan 2007). Persian

utilize mulberries for making jellies, desserts and sauces. Unripe

and immature fruits are utilised for chutney preparations

(Jalikopa et al., 2011). Pure and fresh mulberry fruit juice under

cold storage environment remains fresh for a duration of three

months and bottled juice can stay fresh at ambient temperature

for a period of six months to a year. This mulberry juice aids in

keeping healthy and smooth skin, prevents irritations, inﬂamma-

tions and throat infections, and has also has laxative properties

(Buhroo et al., 2018). It is also used as medicine to reduce fever,

cold, diarrhoea, endemic, malaria, and amoebiosis (Kumar and

Chauhan, 2008). In China, mulberry is usually available in the form

of a paste famous as sangshengao. This paste is dissolved in warm

water to make tea that improves kidney and liver functions and

enhances the vision and hearing. Chinese people also take young

leaves and tender shoots of mulberry as vegetables in some speci-

ﬁed regions. Iranian people utilize dehydrated mulberries as a

sweetening agent in black tea.

Mulberry fruits can be used to make syrup due to their high

sugar content. Mulberry syrup is widely consumed as processed

mulberry products in Vietnam. In syrup production, usually fresh

mulberry fruit is mixed with cane sugar in a ceramic or glass bottle

and can be stored for at least 2 weeks (Quang Trung et al., 2018).

Mulberry fruit powder prevents aging of the skin by disturbing

the formation of free radicals in cells. It also manages good choles-

terol in the human body and balances the absorption of carbohy-

drates (Liu et al., 2009). Mulberry wine, which is sweet and sour

can be produced from over-ripened mulberry fruits (Feng et al.,

2015). This functional wine aids in removing unwanted faecal

impurities from the body and may help in making the body lean

and function as medication to tonify the masculine weakness after

diseases. Mulberry wine is well-known in Europe as a name lady’s

drink. In countries like Armenia, Azerbaijan, and Georgia, mulberry

is a famous liquor known as Tut araghi.This drink is placed among

the national Azerbaijani type of vodka and little quantity of it pro-

tects from stomach and cardiovascular diseases (Farid Alakbarli

Table 1

Physicochemical paramter of different varieties of mulberry.

Physiochemical Properties Morus alba Morus nigra Morus rubra Reference

Moisture (%) 71.5 72.6 74.6 Imran et al., 2010 Ercisli and Orhan, 2007

Protein (g

1

100 g DW) 1.55 0.96 1.2 Koca et al., 2008

Fat (%) 1.10 0.95 0.85 Ercisli and Orhan, 2007

Fiber g

1

100 g 1.47 11.75 – imran et al., 2010

Ash (g

1

100 g) 0.57 0.50 2.45 imran et al., 2010

Total dry weight 29.5 27. 24.4 Ercisli and Orhan, 2007

Ascorbic acid mg

1

100 g 22.4 21.8 19.4 Ercisli and Orhan, 2007

Total acidity (%) 0.25 1.40 1.37 Ercisli and Orhan, 2007

pH 5.60 3.52 4.04 Ercisli and Orhan, 2007, Koca et al., 2008

Calcium (mg

1

100 g) 152 132 132 Ercisli and Orhan, 2007

Mg (mg

1

100 g) 106 106 115 Ercisli and Orhan, 2007

K (mg

1

100 g) 1668 922 834 Ercisli and Orhan, 2007

Fe (mg

1

100 g) 4.2 4.2 4.5 Ercisli and Orhan, 2007

Nitrogen (%) 0.75 0.92 0.82 Ercisli and orhan 2007

FRAP (mmol TE

1

g fw) 4.494 12.9 6.4 Gundogdu et al., 2011

Total phenolics (mg QE

1

100 g fresh mass) 181 1422 1035 Ercisli and Orhan, 2007

Total ﬂavnoids (mg QE

1

100 g fresh mass 29 276 219 Ercisli and Orhan, 2007

Total anthocyanins content C3G mg

1

g frozen weight 911.8 719 109 Natic

´et al., 2015

Total antioxidant capacity (mol TE g

1

fw) 4.494 13.999 5.497 Gundogdu et al., 2011

Malic acid (g 100

g1

fw) 3.095 1.323 4.467 Gundogdu et al., 2011

Succinic acid (g 100

g1

fw) 0.168 0.342 0.132 Gundogdu et al., 2011

Citric acid (g 100 g

1

fw) 0.393 1.084 0.762 Gundogdu et al., 2011

Total organic acid (g 100 g

1

fw) 3.983 2.951 5.812 Gundogdu et al., 2011

Total soluble solids (%) 7.27 11.60 19.20 Aljane and Sdiri, 2016

Fructose (g 100 g

1

fw) 6.269 5.634 5.407 Gundogdu et al., 2011

Glucose (g 100 g

1

fw) 6.864 7.748 6.068 Gundogdu et al., 2011

Hunter L* 78.4 14.3 27.3 Ercisli and Orhan, 2007

Hunter a* 13.6 7.02 8.55 Ercisli and Orhan, 2007

Hunter b* 16.2 1.72 2.02 Ercisli and Orhan, 2007

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3912

Table 2

Role of mulberry in different food industries and major ﬁndings.

Application Major ﬁndings Reference

Natural colorant in

yogurt

Colouring potential of M. rubra was studied in yogurt and the colour developed by adding mulberry

anthocyanins was similar to commercial brand strawberry yogurt

Byamukama et al., 2014

Antioxidant

component in

museli

M. alba fruit was incorporated in museli that resulted in signiﬁcant increase in its antioxidant, and

nutritional value

Kobus-Cisowska et al., 2013

Ready to serve juice Cloudy dark purple mulberry juice containing 0.5% xanthan gum as the stabiliser had the highest levels of

acceptance after storage without precipitation

Akkarachaneeyakorn and Tinrat,

2015

Wine M. alba fruit was used as raw material to brew fruit wine. Phenolics present in the wines were detected by

HPLC

Wang et al., 2015; Yadav et al.,

2017; Kim et al., 2008

Sake Mulberry leaves were utilized for the production of sake orrice wine by fermentation with Mauri yeast and

product was rich in nutrients, amino acids, and polyphenolics

Tan and Li, 2013

Vinegar Vinegar produced from M. alba exhibited powerful antioxidant potential and showed anti-microbial effects Karaagac et al., 2016

Jelly Anthocyanin-rich jelly was developed by adding M. alba fruit containing anthocyanins. The consumption of

formulated functional product resulted in a signiﬁcant decrease in fasting blood cholesterol and LDL in

dyslipidemia patients

On-Nom et al., 2020

Syrup M. alba fruit was utilized for the development of syrup and when packed in PET bottles can be stored for six

months under ambient and refrigerated conditions

Thakur and Abhimanyu Thakur,

2017

Squash M. alba fruit can be utilized to develop appetizer or spiced squash after optimization and when stored in

PET bottles can retain better quality attributes

Hamid and Thakur, 2017

Mixed fruit jam Mixed fruits jam based on rosella and mulberry in the ratios of 70/30 was selected based on overall

acceptability

Wongchalat and Chatthongpisut,

2016

Alcoholic beverage M. alba fruit can be utilized to produce alcoholic beverages. However, it is not possible to make wine from

fresh black mulberry juice due to the low alcohol level that the beverage showed after fermentation

Darias-Martín et al., 2003

Chocolate Chocolate can be fortiﬁed with encapsulated anthocyanins from spray-dried M. nigra fruit waste hence, can

be utilized in a better way in food and pharmaceutical industry

Gültekin-Özgüven et al., 2016

Probiotics M. alba silage is a potential source for the isolation of lactic acid bacteria. In a study 38, lactic acid bacteria

were isolated from mulberry silage however only four strains were capable to survive in the

gastrointestinal tract

Shokryazdan et al., 2015

Pastry M. alba extract along with buckwheat ﬂour, buckwheat hulls, chokeberry, and inulin can be utilized to

produce pastry with lower energy level and higher ﬁbre content.

Komolka et al., 2016

Pasta Enriched pasta by different formulations of M. nigra extract exhibited hypoglycaemic effect by decreasing

the glycemic index and inhibiting

-amylase and

-glucosidase activity.

Yazdankhah et al., 2019

Minced meat Methanolic extract of mulberry leaves increased the shelf life of minced meat Yazdankhah et al., 2019

Cupcake Cupcakes were prepared from concentrated paste of M. alba fruits with accepable and sugar beet root

production while maintaining satisfactory organoleptic and physico-chemical parameters

Jabborova et al., 2020

Table 3

List of patents published from on mulberry with emphasis on therapeutic, cosmetic and functional applications 2011–2020.

Patent no. Publication

date

Title Purpose

US 2011/0064866 A1 17-Mar-11 Black mulberry ﬂavoured composition and method of

preparation

M. nigra ﬂavoured composition was prepared from water, tagette

essence, blueberry essence, grape essence apple juice concentrate,

blackberry juice concentrate, blue berry juice concentrate, and

raspberry added at different times and mixing the ingredients at

various times during the process

US 2013/0108567 A1 2-May-13 Skin-whitening composition for priority data external

application on skin containing extracts from paper

mulberry ﬂowers and fruits

An extract of the ﬂower and fruit of paper mulberry inhibits

melanin production, therefore, has an excellent skin whitening

effect

US 2014/0356468 A1 4-Dec- 2014 Composition containing paper mulberry extracts Paper mulberry extract possessing cosmetic composition has an

important role in many skin related functions like enhancement of

skin moisturization, inhibition of skin aging, alleviation of

inﬂammation, antibacterial activity, pore size reduction, sebum

control, skin complexion improvement, decomposition of

subcutaneous fat, stimulation of melanin synthesis, and gray hair

prevention

US 9,040,106 B2 26-May-15 Pharmaceutical composition for preventing or

treating diabetic erectile dysfunction comprising C3g

or extract of mulberry containing C3g

Cyanidin-3-O-3-d-glucopyranoside present in mulberry has an

ameliorating effect particularly for preventing or treating diabetic

erectile dysfunction

US 9,066,960 B2 30-Jun-15 Use of the effective fraction of alkaloids from

mulberry twig in preparing hypoglycaemic agents

Alkaloids present in mulberry twig are 50% or more by weight in

the effective fraction and are said to have hypoglycaemic agents

US 2018/0139966 24-May-18 Method for treatment of mulberry leaves and for anti

-bacterial silk production

Development of intrinsically antibacterial silk directly from the

silkworm, by feeding the worm on mulberry leaves or silver

treated feedstuff

US 2019 / 0,314,439 A1 17-Oct- 2019 Method for suppressing obesity or development of

obesity

Fermented Indian mulberry comprised of appetite-suppressing

composition resulting in prevention and amelioration of obesity

and other health problems as a result of reduced food intake

US 10, 588, 927, B2 17-Mar-20 Composition containing mixed extract of mulberry

and Poria cocus peel

Treating or improving neurodegenerative disorders

US 2020/0178585 A1 11-Jun-20 Savoury concentrate with mulberry fruit extract Signiﬁcantly be used in the preparation of starch rich food like

pasta

US 2020/0197429 A1 25-Jun-20 Dietary supplement for glycemic control and diabetes

prevention

Formulation containing root extract of mulberry along with some

other functional extracts of astragalus root, phlorizin has glucose-

lowering effect

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3913

and Iskandar Aliyev, 2000). Mulberry fruit is a concentrated source

of anthocyanins mainly cyanidin-3-glucoside (C3G) and cyanidin-

3-rutinoside (C3R)that can be utilized as a natural colorant in food

industries (Du et al., 2008; Aramwit et al., 2010; Zhang et al., 2011).

Recently, the effect of polyphenols in mulberry juice on the

oxidation stability and functional properties of myoﬁbrillary and

sarcoplasmic proteins in dried minced pork slices during storage

and processing was studied. Structural stability was improved to

a greater extent by reducing protein aggregation, carbonyl accu-

mulation, and transformation of SH group into S-S group in pork

slices (Cheng et al., 2020). Similarly, mulberry extracts demon-

strated a protective effect on protein oxidation of dried-minced

pork slices (Cheng et al., 2018). Mulberry leaves can be incorpo-

rated into wheat ﬂour to make paratha with different mix ratios.

The optimized mix has storage stability of two weeks at room tem-

perature and does not exert any adverse effect on the growth of

visceral organs of rats (Srivastava et al., 2003).

One of the special caffeine-free teas made from mulberry leaves

is mulberry tea. It is popular in China, Thailand, Japan, and Korea,

where it has been used in conventional medicine since ages. Itis

famous for enhancing liver and kidney functions, sharpening hear-

ing, and brightening the eyes. This tea also relieves cough, cold, and

throat infections, and also inhibits cholesterol oxidation, thereby

freeing the arteries from fat deposition, hence avoiding artery

hardening (Yu et al., 2018). Because of its anti-diabetic and

cholesterol-lowering properties, this functional tea is a very popu-

lar drink. In case of a throat infection, a decoction of leaves is often

used as a gargle (Buhroo et al., 2018).

Nutritionists and health experts have recently placed M. alba

tea in the list of superfoods especially in European countries

(Natic

´et al., 2015; Krishna et al., 2020). Mulberry tea, particularly

from M. alba, health beneﬁts are largely due to its naturally occur-

ring ingredient, DNJ. It holds anti-diabetic effects, due to its ability

to decrease carbohydrate absorption and helps to regulate the level

of blood sugar in diabetes. However, it is necessary to steep it for a

suitable period to obtain as many of the beneﬁts of mulberry tea as

possible. Brewing of one gram of mulberry leaves in 100 ml of

water for 3–5 min at 98 °C will lead to effective inhibitory activity

against certain enzymes such as maltase (Hansawasdi and

Kawabata, 2006).

Thus, it is evident from the above studies that mulberry can be

effectively used in the food and beverage industries as an interest-

ing raw material being exceptionally rich in antioxidants with a

strong nutritional proﬁle.

5. Anti-tyrosinase properties of Morus for cosmetic application

Use of tyrosinase inhibitors is becoming increasingly important

in the cosmetic industry due to their skin-whitening effects.

Tyrosinase is a copper-containing primary regulatory multifunc-

tional enzyme that is responsible for melanin biosynthesis and

determines the colour of the skin and hence it can be used as a

whitening agent. Excessive melanin deposition induces numerous

dermatological disorders, such as melasma and age spots

(Mukherjee et al., 2018). Roots and twigs of Morus could be uti-

lized as promising natural agents to counteract tyrosinase activity

in cosmetics given in Table4.

Most Asian countries use M. alba (leaves, fruits, root bark and

branches) as an ingredient in cosmetics (Li et al., 2018). In a study,

ethanolic extract of M. alba fruit was utilized to develop an

emulsion-based cream to study its clinical effect on skin melanin,

erythema, and moisture content for eight weeks. The formulated

cream signiﬁcantly decreased melanin content without causing

any type of skin irritation (Akhtar et al., 2012). In other research,

betulinic acid (C

) was isolated from M. alba (hexane extract

of stem and root bark)which can be utilized as a whitening agent

owing to its tyrosinase inhibitory activity (Nattapong and

Omboon, 2008). Ethanolic extract of M. nigra exhibits excellent

tyrosinase inhibition activity and also be utilised for the formula-

tion of peel-off mask and for acne treatment (Budiman et al.,

2017a; Budiman et al., 2019).

Mulberries can help to mitigate skin problems such as reduc-

tion in spots and blemishes appearing with age and inhibition of

free radical linked oxidative activity thereby bestowing a healthier

and shiny appearance to skin and hair. Hence from the above dis-

course, it is clear that different parts of Morus exhibit excellent

tyrosinase inhibition activity, and hence can be included as a nec-

Table 4

Reported tyrosinase inhibitory phytoconstituents in mulberry.

Species/part Compound Extract Salient ﬁndings Reference

M. nigra/roots Moracin N, kuwanon H, morachalcone A,

mulberrofuran G, 5

-geranyl-5

,20

tetrahydroxyﬂavone, steppogenin-7-O-b-D-

glucoside.

Ethanol IC

of Isolated compounds showed better

tyrosinase inhibitory activities than kojic acid

Zheng et al., 2010

M. alba/ twig Morusone, steppogenin, 2, 2,2

tetrahydroxychalcone, morachalcone,

oxyresveratrol and moracin

Ethanol Potential natural tyrosinase inhibitors in cosmetics

as skin-whitening agents

Zhang et al., 2016

M. alba/twigs/roots Maclurin and morin Ethanol The anti-tyrosinae activity of twigs was better than

roots

Chang et al., 2011

M. alba/leave Mulberroside F Hydroalcoholic Isolated compound showed inhibitory effects on

tyrosinase activity and on the melanin formation of

melan-a cells

Lee et al., 2002

M. alba/leave Moracin J Ethanol The isolated compound could be utilized to inhibit

melanin production through the regulation of

melanogenesis-related protein expression

Li et al., 2018

M. alba/root Oxyresveratrol, oxyresveratrol-3-O-glucoside, and

mulberroside

Ethanol Inhibited the pigmentation in guinea pig skin when

applied topically without causing any eye irritation

and skin sensitization

Park et al., 2011

M. alba/wood Oxyresveratrol, trans-dihydromorin, and 2,4,3

trihydroxydihydrostilbene

Methanol Suppressed melanogenesis in the zebraﬁsh model

hence can be used in treating the disorders

associated with melanin pigment

Chaita et al., 2017

M. australis/stem Austraone Ethanol Isolated new compound exhibited moderate

tyrosinase inhibitory activity

Zheng et al., 2012

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3914

essary component of cosmetic products and de-pigmentation

agents for the treatment of hyperpigmented disorders.

6. Nutraceutical applications of Morus

Nutraceuticals have various therapeutic properties that are pri-

marily due to their chemical structure, anti-oxidant, anti-diabetic,

anti-hypertensive, hypo-cholesterolemic, anti-microbial, hepato-

protective properties, and many more. Some of the traditional for-

mulations containing mulberry as an ingredient are listed in

Table 5 and Table 6 summarizes some ﬁndings on nutraceutical

applications of Morus plant. The current available literature on

the nutraceutical ability of Morus species to improve human health

and well-being is presented in this section.

6.1. Anti-microbial properties

To date, a signiﬁcant amount of research related to the anti-

microbial properties of natural plants and their associated compo-

nents is reported. Compound viz chalcomoracin with anti-

microbial activity against methicillin-resistant Staphylococcus aur-

eus (S. aureus) was isolated from M. alba leaves (Fukai et al., 2005).

In another study, hydro-methanolic extract of stem bark of M. alba

exhibited anti-microbial activity against Enterococcus faecalis, (E.

faecalis), Escherichia coli (E. coli)S. aureus, Staphylococcus epider-

midis (S. epidermidis) and Salmonella typhimurium (S.typhimurium)

(Thabti et al., 2014). Budiman et al. 2017b, reported that the

ethanolic extract of M. nigra was effective and inhibited the growth

of S. epidermidis and Propionibacterium acnes (P. acnes) bacteria.

Morin an anti-bacterial compound was isolated from M. alba fruits

by LH-20 column chromatography and the structure was eluci-

dated by

C NMR and

H NMR spectroscopy. The isolated com-

pound showed modest anti-bacterial activity against

Streptococcus mutans (S.mutans) at 5 and 2 mg/disc (Yang and

Lee, 2012).

Apart from leaves, fruits, stems, and bark of Morus varieties,

value-added products from them also exhibited potential

anti-microbial activities. M. nigra juice exhibited anti-microbial

potential against bacteria Bacillus spizizenii (B. spizizenii) and

Pseudomonas aeruginosa (P.aeruginosa) with an inhibition zone of

19.68 mm and 19.87 mm, respectively (Khalid et al., 2011). Vinegar

produced from M. alba showed antibacterial effect against S. aur-

eus, S. pyogenes,E. coli,E. faecalis, Erwinia carotovora (E. carotovora)

Klebsiella oxytoca (K. oxytoca), Bacillus cereus (B. cereus) and Bacillus

subtilis (B. subtilis),anti-fungal activities against Candida albicans

(C. albicans). Among all bacteria, S. aureus (28 mm) followed by S.

pyogenes (20.6 mm) exhibited the highest zone of inhibition while

E. coli showed the lowest zone of inhibition 5.3 mm and for C. albi-

cans 9.6 mm zone of inhibition was observed (Karaagac et al.,

2016).

6.2. Anti-hyperglycaemic property

Diabetes mellitus (DM) is now considered the third most life-

threatening metabolic condition in the world, characterized by

hyperglycaemia (high blood glucose levels) (Wang et al., 2013).

There are more than 170 million people affected by this chronic

disease globally and it is estimated to rise by 50 percent by the

year 2030, with the highest increase forecasted in developing

countries like Asia, Africa, and South America.

Various studies have reported the anti-diabetic properties of

mulberry. The leaves of M. alba have been included in Chinese tra-

ditional medicine since a long time for treatment and prevention of

diabetes due to the presence of functional chemical constituents

that suppress raised blood sugar levels following a carbohydrate-

rich meal (Miyahara et al., 2004). Polysaccharides in M. alba fruit

hold excellent potential for anti-diabetic activity. A signiﬁcant

reduction in fasting serum insulin, homeostasis model of

assessment-insulin resistance, fasting glucose level, glycated

serum protein, and repairment of impaired pancreatic tissues of

the diabetic rats was observed after seven weeks of treatment with

M. alba fruit polysaccharides (two fractions)in wister rats (Jiao

et al., 2017). Extracted DNJ appreciably decreased blood glucose

and insulin levels, reversed insulin resistance, and enhanced serum

lipid levels and in high fat diet-induced (HFD) diabetic Kunming

mice (Hu et al., 2019). A single dose of M. alba leaves extract with

a DNJ concentration of 3, 6, or 9 mg was given to subjects with fast-

ing glucose levelsof100-140 mg/dL. Meanwhile, 6 mg of DNJ for

twelve weeks was given to subjects with a fasting glucose level

of 110–140 mg/dL. Long-term ingestion of DNJ rich M. alba leaves

extract resulted in improved post-prandial glycemic control in

patients with damaged glucose metabolism (Asai et al., 2011).

Ingestion of diet containing M. alba extract repeatedly may main-

tain postprandial glucose levels. In a study after eight weeks of

repeated ingestion of M. alba extract in KK-Ay mice, fasting plasma

glucose (FPG) and insulin levels were measured and found an

Table 5

Available traditional formulation containing mulberry extract as one of ingredient.

Brand name Formulation name Composition Function

Green silk Green silk formula 1 M. alba extract, wolfberry extract, milk thistle extract, chicory root

extract, safﬂower extract, nettle extract, cayenne fruit extract

Lowers blood sugar, improves cholesterol

and weight loss

Hamdard Laboratories Sharbat Toot Siyah M. nigra with sugar An effective herbal remedy in swelling and

pain of throat (Pharyngitis)

Ahana Nutrition White mulberry leaf

extract

M. alba leaf extract, Garcinia cambogia, green coffee bean, african

mango extract, cinnamon

Slows down the build of cholesterol plaque

around arteries and minimizes the

progression of atherosclerosis

BioGanix White mulberry leaf

extract

M. alba, vegetable cellulose Maintains healthy blood sugar levels, curbs

appetite

Vox nutrition White mulberry leaf

pure

M. alba leaf extract standardized to 1% alkaloids, 15% quercetin and

isoquercetin and inactive ingredient cellulose

Weight loss and craving control

Immortalitea White mulberry leaf 100% M. alba leaf Caffeine-free weight loss tea

Nature’s Max slim white

mulberry blend

M. alba extract 500 mg with Garcinia cambogia, green coffee bean,

African mango

Sugar blocker and appetite suppressant

diet pill

Naturesque White mulberry leaf

extract

M. alba leaf extract 1000 mg, vegetable cellulose (capsule),

microcrystalline cellulose

Helps to reduce sugar and carb cravings,

help lower blood sugar, supports

cardiovascular health

Hamdard Laboratories Sualin M. nigra 50 mg, liquorice extract 8.571 mg, Adhatoda vasica extract

5.714 mg, Ocimum basilicum extract 5.714 mg, menthol 0.00171 mg,

oil anise 0.00054 ml, oil eucalyptus 0.00053 ml, oil pine 0.00043 ml,

oil cubeb 0.00016 ml and oil cinnamon 0.00011 ml

Sualin tablet is used to treat sore throat,

cold, cough and bronchitis

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3915

Table 6

Nutraceutical applications of mulberry.

Biological activity Extract Species/Part Salient ﬁndings Reference

Antioxidant Ethyl acetate M. alba/ fruit M. alba fruit extract showed excellent in vitro radical-scavenging activities

against DPPH and superoxide anion radicals and increase antioxidant

enzymatic activities like SOD, CAT, and GSH-Px in STZ-induced mice

Wang et al., 2013

Ethanol M. alba/leave Moracin extracted from M. alba leave exhibited antioxidant activity better

than resveratrol

Tu et al., 2019

Ethanol M. nigra/fruit Polysaccharides in M. nigra fruit exhibited the strongest protective effect on

-induced oxidative injury in PC12 cells

Wang et al., 2018

Ethanol M. alba/ stem M. alba stem extract increase superoxide and NO scavenging activity as well

as iron reducing capacity in vitro

Pham et al., 2017

Powdered leaves

mixed with diet.

M. indica/leave M. indica leaf powder resulted in improvement of antioxidant enzymes viz.,

GPx glutathione reductase (GR), glutathione-S-transferase (GST) SOD in STZ

induced wistar rats

Andallu and

Varadacharyulu,

2003

Ethanol M. alba/ fruit Flavnoids extracted from M. alba fruit showed antioxidant activity both

in vitro DPPH scavenging activity and reducing power and in vivo hemolysis

induced by H

in mice was reduced

Raman et al., 2016

Freeze dried

powder

M. alba/fruit Freeze dried M. alba fruit resulted in increased activity of SOD and GSH-Px

activity and lipid peroxidation was reduced in HFD induced wistar rats

Yang et al., 2010

Methanol M. alba/leave Isolated astragalin showed strong prevention effect against free radical-

induced oxidative hemolysis of human red blood cells and GSH depletion in

RBCs

Choi et al., 2013

Aqueous M. alba/leaves Separated ﬂavonoids exhibited peroxyl radical-scavenging capacity and CAC

against 2, 2

-Azobis (2-amidinopropane) dihydrochloride (AAPH) and

induced oxidative stress in HepG2 cells

Kim and Jang, 2011

Anti-diabetic Ethyl acetate M. alba/fruit Soluble extract of M. alba fruit decrease fasting blood glucose (FBG) FBG and

glycosylated serum protein (GSP) in STZ-induced diabetic mice

Wang et al., 2013

Aqueous M. alba/leave M. alba leave decoction decreased blood glucose levels, inhibited hepatic

glycogen loss, and prevented potential histopathological alterations in the

pancreas and kidneys in STZ induced brown rat

Khyade and

Hershko, 2018

Ethanol M. alba/stem bark Signiﬁcant alterations in glutathione and insulin level and blood glucose level

was observed in STZ induced diabetic rats

S ALAnazi et al.,

2017

Hydroalcoholic M. alba/leave Chlorogenic acid and rutin responsible for anti-diabetic effect in STZ induced

newborn Sprague-Dawley rats

Hunyadi et al., 2012

Ethanol M. alba/branches Oxyresveratrol signiﬁcantly reduced FPG in STZ-induced diabetic ICR mouse Ahn et al., 2017

Ethanolic M. nigra/leave Ethanolic extract may aid in preventing liver and kidney tissue damage in STZ

induced rats

Hago et al., 2019

Powdered leaf

(mixed with diet)

M. indica/leave Decrease in lipid peroxidation and the activity of CAT in erythrocytes in STZ

induced albino rats

Andallu and

Varadacharyulu,

2003

Ethanol M. alba/fruit Polysaccharides like arabinose, galactose, and glucose exhibited excellent

invitro hypoglycaemic effects

Chen et al., 2016

Hydroalcoholic M. multicaulis/ branch

bark

Signiﬁcant inhibition in activity

-glycosidase was observed in vitro and

regulation of mRNA expression of glycometabolism genes including glucose-

6-phosphatase (G6Pase) and glucokinase (GCK) in STZ induced diabetic mice

Liu et al., 2014

Hydroalcoholic M. alba/fruit Anthocyanins have protection effect against b-cell damage in carboxy methyl

cellulose treated Zucker diabetic fatty rats

Sarikaphuti et al.,

2013

Anti-microbial Ethanol M. alba/leave Puriﬁed and isolated DNJ inhibited the overgrowth and bioﬁlm formation of S.

mutans

Islam et al., 2008

Methanol M. nigra/leave Signiﬁcant anti-microbial and antioxidant properties, by the ability to

increase antioxidant levels was observed against some pathogens.

Zhou et al., 2019

Ethanolic M. alba/leave Inhibition against large population of pathogens De Oliveira et al.,

2015

Ethanolic M. nigra/stem bark

and wood

Oxyreversterol, moracin, morusin, kuwanon isolated from wood and stem

bark exhibited anti-microbial against some pathogens

Mazimba et al.,

2011

Aqueous,

hydroalcoholic

and methanol

M. alba/fruit It showed inhibitory effect against some pathogens Dimitrijevic

´et al.,

2014

Methanol M. alba/root Kuwanon G possessed antibacterial activity against some oral pathogens Park et al., 2003

Methanol M. alba/root Kuwanon L, sanggenons B, C, D, G, moracin P, and sanggenol A, showed

potential anti-microbial activities against Bacillus subtilis and Escherichia coli

Ristivojevic

´et al,

2019

Ethyl acetate M. alba/twig Isolated oxyresveratrol exhibit inhibitory effect against Trichophyton rubrum

with the minimum inhibitory concentration of 1 mg/mL

Lu et al., 2017

Methanol M. alba/ leave Isolated compounds chalcomoracin and moracin C inhibited the growth of S.

aureus

Kim et al., 2012

Ethanol M. alba/leave M. alba possess excellent antibacterial activity against periodontal disease Gunjal et al., 2015

Hyperlipidemia Freeze-dried

powder

M. alba/fruit Signiﬁcant decrease in the atherogenic index and decrease in liver TG, TC and

LDL in wistar rats fed with HFD

Yang et al., 2010

Methanol M. alba/root bark Isolated compounds Albanol A and Albanol B signiﬁcantly reduce in

resistance towards major atherogenic modiﬁcations was observed in HFD fed

hypercholesterolemia wistar rats

El-Beshbishy et al.,

2006

Ethanol M. alba/root Puriﬁed stilbenoids decrease in serum lipids, coronary artery risk index, and

atherogenic index in high-cholesterol diet-induced hyperlipidemia Sprague

Dawley rats

Jo et al., 2014

Ethanol M. alba/fruit Signiﬁcantly ameliorated LXRa-mediated lipogenesis and hepatic ﬁbrosis

markers such as smooth muscle actin in HFD induced obesity in C57BL/6 mice

Ann et al., 2015

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3916

appreciable reduction in insulin resistance, and the onset time of

urinary glucose excretion was delayed (Tanabe et al., 2011).

6.3. Anti-hyperlipidemic activity

Obesity is deﬁned as an unusual deposition of fat that extents

risk to health. It is one of the serious concerns prevailing today

across the globe as it increases the risk of diabetes, heart disease,

and cancer. Beneﬁcial phytoconstituents in mulberry has increased

the attention of researchers to explore its best potential for anti-

obesity characteristics.

The effect of M. alba fruit on the lipid proﬁle of humans in the

age group of 30–60 years was studied. After consumption of M.

alba fruit for six weeks at a dose of 45 g per day, a signiﬁcant

decrease in the total cholesterol (TC) and low-density lipoprotein

(LDL) levels in blood was noted (Sirikanchanarod et al., 2016). Sim-

ilarly, in another study, on oral administration of DNJ rich M. alba

leaves extract at a dose of 12 mg three times per day before meals

reduced the level of serum triglycerides (ST) and lipoproteins. DNJ,

extracted from M. alba leaves when administered to diet-induced

obese mice, was found beneﬁcial for lowering down the levels of

plasma triacylglycerol besides activating the b-oxidation system

and reducing the lipid accumulation in the liver (Tsuduki et al.,

2013). It may also reduce hyperlipidemia by moderating feeding

behaviour and endoplasmic reticulum stress in the hypothalamus

of mice with HFD obesity in C57BL/6J mice (Kim et al., 2017). Mul-

berry juice in combination with blueberry juice may aid in decreas-

ing the blood cholesterol, resistance to insulin and leptin secretin

attenuated lipid accumulation in HFD-induced obesity C57BL/6

mice (Wu et al., 2013). Isolated oxyresveratrol from M. alba wood

monitored the degradation of fatty acids and hepatic lipogenesis

to ameliorate non-alcoholic fatty liver fat in HFD mice (Lee et al.,

2018). In another study, it was observed that administration of

aqueous extract of M. alba fruit for twelve weeks in male Syrian

golden hamsters resulted in lowered cholesterol, free fatty acid,

and hepatic lipids (Peng et al., 2011).

Recently extract of leaves of M. alba fermented with 10% of

Cordyceps militaris signiﬁcantly stimulated the lipolysis of primary

adipocytes at a suitable concentration and hence can be utilised as

lipolytic agents to treat obesity (Lee et al., 2020).

6.4. Anti-inﬂammatory activity

The presence of microorganisms (bacteria, viruses, and fungi)

in speciﬁc tissues and their circulation in the blood can cause

one of the complex vascular biological responses called inﬂam-

mation. It can damage the body if not regulated after a certain

period and may cause some chronic diseases like rheumatoid

arthritis, cardiovascular diseases, and cancers. Studies have high-

lighted that regular consumption of natural plants with anti-

inﬂammatory activities can help in the treatment of acute

chronic inﬂammation.

Recently novel extraction technique, high hydrostatic pressure

was employed as an extraction method in M. alba. High hydrostatic

pressure extracts inhibited in vitro release of nitric oxide (NO) and

messenger ribonucleic acid (mRNA) expression of nitric oxide syn-

thase 2(NOS2) and reduction of cytokines such as interleukin (IL)-6

and tumor necrosis factor (TNF)-

, which are associated with

inﬂammation in lipopolysaccharide (LPS)-induced RAW264.7 cells

(Jung et al., 2019). Similarly, methanolic extract of M. alba root bark

blocked NO production through suppressing inducible nitric oxide

synthase (iNOS)over-expression in LPS-stimulated RAW264.7 cells

(Eo et al., 2014).

Ethanolic extract of M. alba leaves effectively reduces pro-

inﬂammatory mediators and cytokine production by modulating

the LPS-induced activation of macrophage cells by suppressing

nuclear factor-

B (NF-

B) activation (Park et al., 2013). Ethanolic

extract of stem of M. alba at a concentration of 20 and 40 mg/ml

show anti-inﬂammatory activity in LPS-stimulated RAW264.7

macrophage cell line by inhibition of NO production via suppres-

sion of both the protein and iNOS mRNA.

Anthocyanins in M. nigra fruits have been reported to have anti-

inﬂammatory activity. C3G and C3R exert an anti-inﬂammatory

Table 6 (continued)

Biological activity Extract Species/Part Salient ﬁndings Reference

Aqueous M. alba leaves M. alba (1%) for twelve weeks might help prevent atherosclerosis involving

the underlying mechanism of its anti-oxidative activity

Harauma et al.,

2007

Ethanol M. alba/leave M. alba resulted in a decrease in TG, TC, and LDL in triton WR-1339 induced

hyperlipidemic ICR mice

Chen and Li, 2007

Aqueous M. alba/leave Decrease in body weight and adipose tissue mass in HFD fed mice was

observed

Lee et al., 2008

Anti-inﬂammatory Hydroalcoholic M. nigra/fruit Secondary metabolites signiﬁcantly decreased the number of leukocytes in

the bronchoalveolar lavage ﬂuid and serum levels of TNF

De Pádua Lúcio

et al., 2018

Methanol M. alba root bark Puriﬁed compounds albanol B, sanggenon B and sanggenon D exhibited

inhibitory effects on NO production in LPS-stimulated RAW264.7

Wu et al., 2020

Ethanol M. alba fruit M. alba fruit at a dose of 100 mg/kg body weight improves the learning and

spatial memory in APP/PS1 transgenic mice

Liu and Du, 2020

Ethanol M. alba fruit Phenolic compound has a positive effect on neuroprotection in AD Qiao et al., 2015

Ethanol M. alba/stem Morus in at a dose of 5 and 10 mg/kg delayed onset of convulsion and

signiﬁcantly increased level of brain GABA

Gupta et al., 2014

Methanol M. atropurpurea,M.

bombycis and M. alba/

branch

Bioactive constituent oxyresveratrol, is involved in the inhibition of CXCR-4-

mediated chemotaxis and MEK/ERK pathway in T cells

Chen et al., 2013

Methanol M. alba/twig Isolated compounds apigenin, albanin D, morachalcone A and mulberranol

reduced the expression of reduced LPS iNOS and LPS-induced expression of

COX-2 protein

Tran et al., 2017

Ethanol M. alba/stem M. alba stem at a particular concentration may signiﬁcantly suppress P.

gingivalis LPS-induced IL-6 and IL-8 mRNA and protein expression

Yiemwattana et al.,

2018

Ethanol M. alba/stem Inhibition of the expression of COX- 2 mRNA and iNOS protein expression

using RTPCR in LPS-induced RAW264.7cells

(Yiemwattana

et al., 2018)

Anti-cancerous Methanol M. alba/leave Morin extracted from methanolic extract of mulberry leaves exert an anti-

cancerous potential in HeLa with an IC

of 214.28

Zhang et al., 2018

Ethanol M. fructus/leave Oral administration of ethanolic extract in Balb/c nude mouse with

subcutaneous U87MG glioma cells reduced tumor volume

Jeong et al., 2010

Aqueous M. alba leave Preventive effect on obesity-mediated liver cancer in HepG2 cell proliferation Chang et al., 2018

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3917

effect through inhibition of pro-inﬂammatory cytokine in xylene-

induced ear edema and carrageenan-induced paw edema in mice

(Chen et al., 2016). Aqueous extract of M. alba root has strong

anti-histamine and anti-allergic activity by inhibiting compound

48/80-induced systemic allergic reaction and histamine release

in vitro and in vivo. Mast cell-mediated type allergic reactions are

also inhibited by the root extract of M. alba (Chai et al., 2005).

Hence, Morus species can be a budding natural source of anti-

inﬂammatory drugs.

6.5. Anti-cancer action

Cancer, with different forms, is believed as one of the primary

fatal diseases prevailing globally and the rate is surpassing with

a good number. Recently, many types of cancers have been consid-

ered to be among the group of diseases that are common reason for

death. Many medications are available in the market to treat differ-

ent forms of cancer, but successful and safe drugs are rarely avail-

able. As compared to synthetic and semi-synthetic compounds,

naturally occurring bioactive compounds particularly phenolic

compounds are less toxic and safer (Habauzit and Morand, 2012).

Many naturally occurring substances exert their anti-cancer

activity through apoptosis of tumor cells and by arresting the cell

cycle, which is thought to be the best way to avoid or ﬁght irregular

cell growth (Dewanjee et al., 2017). Detailed mechanism of anti-

cancer activity of Morus species is mentioned in Fig. 4.Traditionally,

medicine value of the mulberry plant is known to humans from the

earliest ages. Clinically, mulberry plant has the potential of inhibi-

tion of cell proliferation most likely due to the presence of ﬂavonoids

that are highly effective against certain types of cancers. Some stud-

ies reported the role of mulberry in cancer prevention in animal

models. Puriﬁed anti-proliferative lectin from M. alba leaves induced

cell death through apoptosis in human breast cancer (MCF-7) and

colon cancer (HCT-15) cells by inducing essential morphological

changes and DNA fragmentation related to apoptosis (Deepa et al.,

2012). The root bark of M. alba contains ﬂavanone glycoside, 5,2

-d

i-hydroxyﬂavanone-7,4

-di-O-b-D-glucoside (steppogenin-7,4

-di-

O-b-D-glucoside) has anti-proliferation activity against HO-8910

cells in human ovarian cancer (Zhang et al., 2009).

6.6. Neurodegenerative actions

Plants play an important role in treating cognitive disorders.

Many medicinal plants exhibit an essential role in the treatment

and prevention of numerous neuronal dysfunctions and neurode-

generative diseases. There are numerous studies reported on natu-

ral medicinal plants where the isolated bioactive constituents such

as polyphenolics and alkaloids can considerably delay neurodegen-

eration and may improve cognitive function and memory

(Mohebbati et al., 2017). Lyophilised ethanolic extract of mulberry

fruit protects neuronal cells against oxidative stress-induced

apoptosis through the enhancement of production of antioxidant

enzymes and brain-derived neurotrophic factor formation by

stabilizing the activation of the TrkB/Akt pathway in swiss CD-1

mice (Shin et al., 2019).

The role of antioxidants in M. alba fruits is well documented in

many studies. Non-anthocyanins in M. alba fruit like rutin and

quercetin have neuroprotective effects besides having multi-

bioactive functions (Shih et al., 2010; Isabelle et al., 2008; Zhang

et al., 2009). These non-anthocyanins have an impact on Parkin-

son’s disease (PD) models. Effect of ethanolic extract of M. alba fruit

in in vitro and in vivo models of PD was studied on dopaminergic

neuron protection using the SH-SY5Y neuroblastoma stressed with

6-hydroxydopamine (6-OHDA) and mesencephalic dopamine neu-

rons stressed with 6-OHDA and 1-methyl-4-phenylpyridinium

(MPPþ). The effect of the same extract was also studied on

in vivo models, where PD was induced by 1-methyl-4-phenyl-1,2,

3,6-tetra-hydropyridine (MPTP). Symptoms of PD like bradykinesia

and MPTP-induced dopaminergic neuronal damage in an immuno-

cytochemical analysis of the substantia nigra pars compacta (SNpc)

and striatum (ST) was prevented (Kim et al., 2010).

Fig. 4. Mechanism of anti-cancer activity of mulberry.

B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3918

7. Miscellaneous activities of Morus species

In traditional medicine, the usage of M. alba is credited toits

excellent diuretic properties, which are mainly owed to the free

radical scavenging attribute. A mixture made of M. alba fruit

(ethanolic extract) and gentamicin with a dosage of 200 mg/kg/day

and 80 mg/kg/day, respectively for three weeks controlled the

serum uric acid, creatinine, blood urea nitrogen content in rabbits

(Ullah et al., 2016). Mulberroside A (stilbene glycoside) from twigs

of M. alba at 10, 20, and 40 mg/kg signiﬁcantly treated renal dys-

function by suppressing the elevated protein and mRNA levels of

renal glucose transporter 9(mGLUT9) and urate transporter 1

(mURAT1) in hyperuricemia mice (Wang et al., 2011). Morusinol

a ﬂavonoid extracted from the root bark of M. alba may signiﬁ-

cantly inhibit arterial thrombosis that was recently studied for car-

diovascular potential (Lee et al., 2012). The alcoholic extract of M.

alba leaves showed hepatoprotective effect against hepatotoxicity

induced by carbon tetrachloride and paracetamol in Swiss albino

mice (Hogade et al., 2010). M. alba juice is helpful in the prevention

of food-borne viral infection (norovirus infection) by inhibiting the

internalization and replication of murine norovirus-1 (MNV-1),

wherein it may affect the adherence or internalization of feline

calicivirus-F9 (FCV-F9) virions (Lee et al., 2014). M. alba juice

may also induce anti-stress activity in Balb/c mice through a mech-

anism of radical scavenging activity (Sakagami et al., 2006).

From current scientiﬁc studies, it can therefore be inferred that

mulberry exhibits substantial antioxidant capacity in vitro and

in vivo, making them promising nutraceuticals.

8. Conclusion

Natural products are now being re-emphasized in order to

address a variety of health issues. The correlation between health

and diet is well established, and consumers are becoming more con-

scious of their eating habits. Investigating these connections has

resulted in the creation of functional, nutraceuticals, and pharma

foods, which are now dominating the global nutrition market. The

current review intended to highlight the signiﬁcance and applica-

tion of Morus species in different areas and it becomes amply clear

from the above discourse that mulberry is a versatile medicinal plant

with enormous vitality. Recent approaches regarding the functional

applications revealed that Morus species and their bioactive phyto-

chemicals display a wide variety of biomedical activities, including

antioxidants, anti-diabetic, hypo-lipidemic, anti-obesity, anti-

hypertensive, and anti-atherosclerosis, etc. Morus extracts or their

constituents particularly ﬂavonoids like chlorogenic acid, quercetin,

rutin and isoquercitrin scavenge free radicals exhibiting potential

against oxidative stress. Alkaloids like DNJ and fagomine present

in M. alba exhibit potential glucosidase inhibition. Compounds like

moracin, morusin, kuwanon isolated from wood and stem bark of

M. nigra exhibit anti-microbial activity. Tyrosinase inhibition prop-

erties of Morus species are comparable to kojic acid that makes it a

wonderful ingredient in cosmetics. Chemical compounds like

maclurin and morin, mulberroside F, oxyresveratrol and austraone

isolated from different parts of M. alba exhibit potential tyrosinase

inhibition activity. In addition to its exceptional usage as a nutraceu-

tical in the pharmaceutical industry, it is often used in food indus-

tries because of the power source of anthocyanins that exhibit

strong antioxidant properties and are used as a natural colouring

agent. Being low in calories, this plant can be utilised in the formu-

lation of hypocaloric foodstuffs and can be added as a novel ingredi-

ent to enhance the functional properties of existing foods. Value

added products like jam, jelly, wine, vinegar, tea, syrup, squash

and many more are formulated from Morus that aids industrialists

for effective utilization of its fruits and leaves. Additionally mulberry

is among the major ingredients in many traditional formulations

sold worldwide. Chemical composition of mulberry is already exten-

sively studied, there are still some unidentiﬁed biological com-

pounds that require proper exploration. It is necessary, however,

to investigate the metabolites produced in vivo and how they exert

their biological effects in future studies.

Declaration of Competing Interest

The authors declare that they have no known competing ﬁnan-

cial interests or personal relationships that could have appeared

to inﬂuence the work reported in this paper.

Acknowledgement

Authors would like to acknowledge Indian Council of Medical

Research (ICMR), New Delhi, India for providing scholarship to

the author (Sanction No. 3/1/2/161/2019) to carry out the present

work.

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B. Jan, R. Parveen, S. Zahiruddin et al. Saudi Journal of Biological Sciences 28 (2021) 3909–3921

3920

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Prolonging mulberry leaf longevity with silver-doped copper oxide nanoparticles: a postharvest approach

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Full-text available

Feb 2025

Mulberry is crucial in silkworm rearing as it provides the primary food source for silkworms, directly impacting the quality and quantity of silk production. This, in turn, supports the global silk industry, which significantly contributes to the economies of many countries through the production of textiles and garments. Postharvest mulberry leaf preservation is required to ensure a continuous and reliable food supply for silkworms, especially during the rainy season when fresh dry leaves are not readily available. Proper preservation techniques will ensure the leaves' nutritional quality, which is essential for the health and productivity of silkworms, ultimately enhancing the efficiency and profitability of silk production. Due to their potent antimicrobial properties, silver-doped copper oxide nanoparticles (Ag-CuO NPs) are explored as preservatives. When used for preservation, Ag-CuO NPs effectively retained primary metabolites, chlorophyll, proteins, and carbohydrates, preserving the leaves' texture and nutritional value. Additionally, the synergistic action of enzymatic antioxidants and carotenoids with Ag-CuO NPs mitigated reactive oxygen species (ROS) damage, delayed senescence, and maintained cellular integrity. Postharvest leaves treated with Ag-CuO NPs supported optimal silkworm larval growth, resulting in higher growth indices, cocoon weights, and silk yields, comparable to fresh leaves. This nanoparticle-based approach extends leaf viability up to seven days, offering a sustainable and non-toxic preservation method with reduced environmental impact, enhancing the efficiency of sericulture practices.

Comparative Metabolomic Analysis of Phenolic Compounds in Different Ramulus Mori (Sangzhi) Based on UPLC‐ESI‐MS/MS

Article

Full-text available

Mar 2025

In traditional Chinese medicine, Ramulus mori (Sangzhi) is used to lower blood sugar and treat diseases such as diabetes, and its therapeutic effects are attributed to an abundance of bioactive compounds. This study employed a comparative analysis of Ramulus mori (Sangzhi) from three geographical regions within China. The samples included Morus atropurpurea Roxb from Guangdong (GDS), Morus australis Poir from Jiangsu (JS), and Morus nigra Linn, which is native to Xinjiang (XJYS). The study discovered significant differences in total polyphenol and flavonoid content among various Ramulus mori (Sangzhi), with those from XJYS showing the highest levels. Utilizing UPLC‐ESI‐MS/MS technology, a total of 128 phenolic metabolites were identified, from which 17 differential metabolites were screened. In Comparison to GDS, JS, and XJYS exhibited 12 and 10 different metabolites, respectively, with 8 differential metabolites observed between JS and XJYS. Furthermore, XJYS exhibited a higher polyphenol and flavonoid content than the other two varieties. Additionally, some of the upregulated differential metabolites have been confirmed to possess a variety of pharmacological effects and health benefits. Kyoto Encyclopedia of Genes and Genomes analysis linked these to flavonoid biosynthesis, and qRT‐PCR confirmed corresponding gene expression patterns. These findings provided a theoretical basis for the use of Ramulus mori (Sangzhi) in the pharmaceutical and food industries.

Determination of the effect of chitosan treatment before storage on the storage of mulberry fruits

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Full-text available

Feb 2025

The study of the preservation of the quality of berry raw materials is becoming relevant due to the value of berries as a food product for dessert and technological purposes in the processing industry. The solution to this issue is the use of edible films and coatings. The problem being solved is to determine safer and more effective technologies for post-harvest treatment of mulberry fruit with chitosan solutions, which will reduce product losses during storage and extend the duration of its consumption. The object of the study is the technology of pre-treatment of mulberry fruit using edible coatings based on chitosan. The subject of the study is mulberry fruit and protective coatings with 0.2 % 0.4 % 0.6 % concentration of chitosan and 0.5 % ascorbic acid. The minimum weight loss of mulberry fruit (2.72 %) and daily losses (0.84 %) during storage were observed after pretreatment with 0.6 % chitosan dissolved in 0.5 % ascorbic acid. The addition of ascorbic acid inhibited the development of Botrytis cinerea by 1.5–2.1 times. There is a close inverse relationship between the yield of marketable products and the concentration of the chitosan solution. An increase in the concentration of chitosan from 0.2 % to 0.6 % reduces natural weight loss, physiological disorders of fruit, and absolute shortage of products. The yield of marketable products increases from 91.7 to 95.1 %. The dry matter content during the storage period decreased by 3.0–6.6 % when treated with an aqueous solution of chitosan and a 2.0–3.5 % solution with ascorbic acid. The lowest losses were observed when treated with 0.6 % chitosan solution and 0.5 % ascorbic acid. A similar pattern was observed for the content of dry soluble substances

Effect of mixed fermentation of compound grapes on organic acids and volatiles in mulberry wine

Article

Mar 2025
J Food Sci Biotechnol

The main objective of this study was to investigate the effect of mixed fermentation of blended grapes on the organic acid and volatile content of mulberry fruit wines before and after fermentation. Rose-scented grapes and blackberry grapes were chosen to produce fruit wines through mixed fermentation with mulberries, respectively. HPLC was employed for the content of organic acids, whereas the concentrations of volatile compounds in the mulberry wines were determined using HS–SPME–GC–MS. The results showed that yeast fermentation could effectively reduce the content of malic acid and citric acid while generating rich aroma substances. During compound grape blend fermentation, the organic acid content decreases, and more volatile compounds are produced. Among them, mulberry rosé grapefruit wine exhibits a more complex array of volatile compounds, including phenylethanol, ethyl caprylate, and ethyl caprate, alongside recently discovered compounds like isobutanol, (+)-3-methyl-2-butanol, and α-pinitol. These compounds contribute to the enhanced flavor of mulberry wine.

Differential analysis of metabolites from mulberry (Morus abla L. cv. Longsang 1) juices fermented with Pichia kudriavzevii and Weissella confusa alone or in combination

Article

Mar 2025

Preparation and health benefits of herbal tea from mulberry leaves

Article

Jan 2025

Transcriptome sequencing and metabolome analysis to reveal renewal evidence for drought adaptation in mulberry

Article

Full-text available

Feb 2025

As an economically important tree species, mulberry (Morus spp.) has exhibited a remarkable tolerance for salinity, drought and heavy metals. However, the precise mechanism of metabolome‐mediated drought adaptation is unclear. In this study, two new mulberry varieties—‘drought‐sensitive guisangyou62 (GSY62) and highly drought‐tolerant guiyou2024 (GY2024)’—after three days (62F or 2024F) and six days (62B or 2024B) of drought–stress conditions were subjected to transcriptome and metabolome analyses. The enrichment analysis demonstrated that the differentially expressed genes (DEGs) were mainly enriched in carbohydrate metabolism, amino acid metabolism, energy metabolism and secondary metabolite biosynthesis under drought–stress conditions. Notably, compared with the CK group (without drought treatment), 60 and 70 DEGs in GY2024 and GSY62 were involved in sucrose and starch biosynthesis, respectively. The genes encoding sucrose phosphate synthase 2 and 4 were downregulated in GY2024, with a lower expression. The genes encoding key enzymes in starch biosynthesis were upregulated in GY2024 and the transcriptional abundance was significantly higher than in GSY62. These results indicated that drought stress reduced sucrose synthesis but accelerated starch synthesis in mulberry.

Integrative Analysis of the Fermentation Mechanisms, Antioxidant Properties, and Potential Health Benefits of Mulberry Wine Using Multiple Bioinformatics Approaches

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Feb 2025

Identification and Antidiabetic Activity of Peptides in Protein Morus alba Leaf Proteolytic Hydrolysates: A Novel Functional Food Ingredient for Ameliorating Type 2 Diabetes Mellitus

Article

Feb 2025

Impact of Picking Time on Leaf Quality Parameters of Three Varieties of Honeysuckle (Lonicera caerulea L.)

Article

Full-text available

Jan 2025

Lonicera caerulea is a nutrient-rich plant of significant importance. Its chemical composition is influenced by various intrinsic properties and external factors, which change with the seasons. This study aimed to evaluate the effects of different picking times on the proximate composition and the contents of pigments, macroelements, bioactive compounds and antioxidant activity in honeysuckle leaves. Seasonal changes in the contents of fiber, ash, proteins, nitrogen (N), potassium (K), magnesium (Mg), phosphorus (P), calcium (Ca), chlorophylls, total carotenoids, total flavonoids and total phenolics were analyzed. The results revealed that picking time and plant variety significantly affected the chemical composition of honeysuckle leaves. The first picking yielded the highest levels of protein, N, P, K, chlorophyll a and b, total chlorophyll and total carotenoids. Conversely, the third picking showed the highest levels of Ca and Mg. Specifically, the third picking of ‘Indigo Yum’ leaves had the highest Ca and Mg contents, while the second picking of ‘Zojka’ leaves (116.67 mg 100 g−1 DM) and the third picking of ‘Wojtek’ leaves (115 mg 100 g−1 DM) contained the most total flavonoids. The first picking of ‘Wojtek’ leaves recorded the highest levels of protein, N, P and total carotenoids, whereas the third picking showed the highest fiber and ash contents. These findings provide valuable insights for farmers, enabling them to select appropriate cultivars and optimal picking times to produce high-quality honeysuckle leaves for use as food or medicinal supplements.

Fermented mulberry (Morus alba) leaves suppress high fat diet-induced hepatic steatosis through amelioration of the inflammatory response and autophagy pathway

Article

Full-text available

Sep 2020

Background: A novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) is reported to exert anti-obesity activity, although their molecular mechanism during hepatic steatosis has not verified. Methods: To investigate the role of inflammation and autophagy during the anti-hepatic steatosis effects of EMfC, we measured alterations in the key parameters for inflammatory response and autophagy pathway in liver tissues of the high fat diet (HFD) treated C57BL/6N mice after exposure to EMfC for 12 weeks. Results: Significant anti-hepatic steatosis effects, including decreased number of lipid droplets and expression of Klf2 mRNA, were detected in the liver of the HFD + EMfC treated group. The levels of mast cell infiltration, expression of two inflammatory mediators (iNOS and COX-2), and the MAPK signaling pathway were remarkably decreased in the liver of HFD + EMfC treated group as compared to the HFD + Vehicle treated group. Furthermore, a similar inhibitory effect was measured for the expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and NF-κB. The expression level of members in the AKT/mTOR signaling pathway (a central regulator in autophagy) was recovered after treatment with EMfC, and autophagy-related proteins (Beclin and LC3-II) were remarkably decreased in the HFD + EMfC treated group compared to the HFD + Vehicle treated group. Moreover, the HFD + EMfC treated group showed decreased transcript levels of autophagy-regulated genes including Atg4b, Atg5, Atg7 and Atg12. Conclusions: Taken together, findings of the present study provide novel evidences that the anti-hepatic steatosis of EMfC is tightly linked to the regulation of the inflammatory response and autophagy pathway in the liver tissue of HFD-induced obesity mice.

Consumption of Anthocyanin-Rich Mulberry Fruit Jelly with a High-Fat Meal Decreases Postprandial Serum Cardiometabolic Risk Factors in Dyslipidemia Subjects

Article

Full-text available

Jul 2020
J Nutr Metab

Anthocyanin content in berries has been reported to promote antioxidant properties that mitigate the occurrence of noncommunicable diseases. However, only a few studies have investigated the benefits of anthocyanin-rich food products from mulberry fruit to reduce the cardiometabolic risk factor in dyslipidemia subjects. Anthocyanin-rich mulberry fruit jelly was formulated using mulberry fruit powder (MFP), and its activities on serum cardiometabolic risk factors in dyslipidemia subjects were studied. Morus alba var. Chiang Mai was used as the ingredient for MFP jelly containing 14 g MFP (191 mg anthocyanin) per serving size (170 g). To investigate the effect of MFP jelly on reduction of cardiometabolic risk factors, sixteen dyslipidemia subjects were given one serving of MFP jelly every day for seven days. After MFP jelly intervention, fasting blood cholesterol, low-density lipoprotein (LDL), and inflammatory markers including interleukin-6 levels of the subjects were significantly lower. Postprandial blood parameters were measured at 0–240 min after consuming a high-fat meal before and after MFP jelly intervention. Postprandial blood glucose at 30 min (p

Bioactive compounds, health benefits and utilisation of Morus spp .– a comprehensive review

Article

Full-text available

Aug 2019

Plants play an important role in the well-being of human beings and have been witnessed by their presence in the Rigveda and Ayurveda. Among those plants, Morus spp. is the one having versatile nature because of the presence of numerous phytochemicals in its different parts and also termed as ‘Kalpa Vruksha’. A wide range of the phytochemicals present in the leaves, fruit, root and wood of Morus because of which they possess wide range of biological functions (antidiabetic, antiobesity, antiinflammatory, anticancer, antibacterial, antioxidant, antiviral, cytoprotective and neuroprotective activities etc.). The plant is being utilised traditionally for development of different food products as well as treatment of various diseases. Recently, the researchers took a shift for the efficient utilisation of different parts of the plant for development of various value-added food products. The fruit-based products includes wine, vinegar, jelly, jam, biscuits, bread, squash, yoghurt, cosmetic cream, whereas, leaf-based products includes tea, toothpaste, pastry etc. However, the plant is still lacking its identity at the commercial scale. However, at commercial scale, a kind concern of the industrialists is required towards its effective and efficient utilisation as food, feed and value-added products with the aim to make it available throughout the year.

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

Article

Full-text available

Apr 2019

Anti-Inflammatory Effects of High Hydrostatic Pressure Extract of Mulberry (Morus alba) Fruit on LPS-Stimulated RAW264.7 Cells

Article

Full-text available

Apr 2019
MOLECULES

Mulberry fruit (Morus alba L.) contains abundant bioactive compounds, including anthocyanins and flavonols, and has been reported to possess potent beneficial properties including anticancer, antidiabetic, and anti-oxidant effects. High hydrostatic pressure (HHP) processing, a nonthermal food processing technology, is suitable for the extraction of bioactive compounds from plants. Nevertheless, the anti-inflammatory effects of HHP extract of mulberry fruit (HM) in RAW264.7 cells remain unclear. The present study aimed to investigate the anti-inflammatory effects of HM on lipopolysaccharide (LPS)-induced inflammation in vitro. RAW264.7 cells were treated with various concentrations (0.1–1 μg/mL) of HM in the presence or absence of LPS. HM inhibited the inflammatory mediator, nitric oxide (NO) release, and mRNA expression of nitric oxide synthase 2 (NOS2) in LPS-induced RAW264.7 cells. In addition, HM suppressed both mRNA and protein expressions of prostaglandin-endoperoxide synthase 2 (PTGS2). Moreover, it reduced the LPS-induced secretion of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α. These results revealed that HM exerts anti-inflammatory effects by inhibiting several mediators and cytokines involved in the inflammatory process.

A New Flavanone Glycoside with Anti-proliferation Activity from the Root Bark of Morus alba: A New Flavanone Glycoside with Anti-proliferation Activity from the Root Bark of Morus alba</I

Article

Jun 2009

Mulberry fruit improves memory in scopolamine-treated mice: role of cholinergic function, antioxidant system, and TrkB/Akt signaling

Article

Dec 2019

Objectives: Although mulberry fruit possesses some biological activities, it is not known how it protects neuronal cells in neurodegenerative diseases. Here, we examined whether mulberry fruit extract (MFE) protected neuronal cells against oxidative stress-induced neurodegeneration. Methods: In this experiments, glutamate challenged hippocampal neuronal HT-22 cell lines as an in vitro model and scopolamine-induced memoty-impairment mice model were used. Results: MFE improved cell viability and glutathione level as well as reducing reactive oxygen species level in glutamate-treated HT-22 cells. Additionally, MFE suppressed apoptotic bodies and mitochondrial depolarization through regulating expression of apoptosis-related proteins. Furthermore, MFE elevated expression of p-TrkB, p-Akt, p-CREB, BDNF, and antioxidant enzymes as well as nuclear translocation of Nrf2. In contrast, the inclusion of K252a, a TrkB inhibitor, or MK-2206, an Akt selective inhibitor, neutralized the neuroprotective actions of MFE. Separately, MFE attenuated scopolamine-induced amnesia via regulating the activities of enzymes related with cholinergic function and the antioxidant system in mice. Additionally, MFE protected neuronal cells in the hippocampal CA1 and CA3 regions in brain of mice. Conclusions: MFE protects neuronal cells against oxidative stress-induced apoptosis through upregulating the expression of BDNF and antioxidant enzymes by stabilizing the activation of the TrkB/Akt pathway. Such an effect of MFE, which includes rich polyphenols, may provide information for its application as a food supplement for the prevention and treatment of neurodegenerative diseases.

Effects of mulberry polyphenols on oxidation stability of sarcoplasmic and myofibrillar proteins in dried minced pork slices during processing and storage

Article

Oct 2019
MEAT SCI

This experiment was designed to evaluate the influence of mulberry polyphenols (MP) on oxidation stability of sarcoplasmic and myofibrillar proteins in dried minced pork slice during processing and storage. Composition, amino acid side chain modification, average particle size, hydrophobicity and solubility of proteins in the slices were investigated. MP displayed protective effects on oxidation stability of sarcoplasmic and myofibrillar proteins in slices, considering carbonyl formation and transformation from SH group to SS group were remarkably retarded by MP. Proteins in MP-treated slices possessed larger average particle size but lower aggregation during processing and storage. Meanwhile, the strengthened ionic bonds and weakened hydrogen, hydrophobic and disulfide bond could be responsible for the improved protein stability of slice with MP. All these results suggested that mulberry polyphenol could improve protein oxidation stability in meat products.

Effect of 1-Deoxynojirimycin Isolated from Mulberry Leaves on Glucose Metabolism and Gut Microbiota in a Streptozotocin-Induced Diabetic Mouse Model

Article

Aug 2019

1-Deoxynojirimycin (DNJ) exerts hypoglycemic effects. However, the traditional method for DNJ extraction is inefficient, and the hypoglycemic mechanism of DNJ remains unclear. In this study, the mixed fermentation by Lactobacillus fermentum and Saccharomyces cerevisiae was used to enhance DNJ extraction efficiency. It was found that this strategy was more efficient than the traditional method as the yield improved from the original 3.24 mg/g to 5.97 mg/g. The purified DNJ significantly decreased serum glucose (P < 0.01) and insulin levels (P < 0.05), improved serum lipid levels (P < 0.05), and reversed insulin resistance (P < 0.05) in diabetic mice. These changes were caused by up-regulating the protein expression of insulin receptor and glycolysis enzymes (GK, PK, and PFK) (P < 0.05) and down-regulating the protein expression of insulin receptor substrate-1 and gluconeogenesis enzymes (PCB, PEPCK, FBPase, and G-6-Pase) (P < 0.05), thus alleviating glucose tolerance. Additionally, DNJ treatment relieved gut dysbiosis in diabetic mice by promoting the growth of Lactobacillus, Lachnospiraceae NK4A136 group, Oscillibacter, norank Lachnospiraceae, Alistipes, and Bifidobacterium (P < 0.05) and suppressing the growth of Ruminococcaceae UCG-014, Weissella, Ruminococcus, Prevotellaceae Ga6A1 group, Anaerostipes, Klebsiella, Prevotellaceae UCG-001, and Bacteroidales S24-7 group (P < 0.05).

Identification of moracin N in mulberry leaf and evaluation of antioxidant activity

Article

Jul 2019
FOOD CHEM TOXICOL

Mulberry leaf is a newly accepted vegetable for daily diet. It tastes good and has multiple health benefits, including antioxidant and anti-inflammatory activities. However, the chemicals responsible for these health benefits remain unveiled. Prenylated phenolics are characteristic bioactive compounds in mulberry leaf, which are recognized as good antioxidants. In this work, moracin N was purified from mulberry leaf. It showed better antioxidant activities than resveratrol. The EC50 value of cellular antioxidant activity was 24.92 μM, and the IC50 value against DPPH radical was 40.00 μM. The prenyl group rendered the molecule more membrane affinity which improved the bioavailability. The furan ring was critical for the antioxidant behaviour. The cell viability test revealed that moracin N had a good safety. These results pointed out that moracin N contributed to the antioxidant activity of mulberry leaf.

Nutritional constituents of mulberry and their potential applications in food and pharmaceuticals: A review

Abstract and Figures

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