Medicinal value of Black Mulberry

Medicinal value of Black Mulberry: Comparison

View Latest Version

Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Maria Valentina Ignat.

Roughly 100 species of

Morus

have been described, such as

Morus alba

(white mulberry),

Morus rubra

(red mulberry), and

Morus nigra

(black mulberry). The mulberry plant is monoecious or dioecious, reaching up to 10–12 m in height.

Morus nigra

(

Moraceae

family) is commonly distributed in Asia, Africa, Europe, and America. Given its therapeutic properties, the leaves, root barks, branches, and fruits are traditionally used in medicinal preparations to manage diabetes mellitus, atherosclerosis, hyperlipidemia, and hypertension. Various extracts of mulberry leaves were studied over the years, investigating their bioactive compounds’ pharmaceutical in public health concerns, such as diabetes, hepatic diseases, and cardiovascular diseases.

This entry is based on a

literature review

and highlights the beneficial and therapeutic action of black mulberry extracts and their confirmed or hypothesized mechanism of action in diabetes, hepatic disorders, and cardiovascular disease, as indicated by the results of

in vivo

and

in vitro

studies, on cell lines, human and animal models.

cardiovascular disease
diabetes
Black Mulberry
hepatic disorders
morus nigra

1. Mulberry Extracts and Their Natural Products Studied for Therapeutic Potential in Diabetes

Before 2010, the effect of black mulberry leaf extracts on diabetes was studied by two in vitro studies and two

in vivo

settings. However, more studies were published after 2010. As seen in

Table 1

, the extracts are accounted for reducing diabetic symptoms, neuropathy, hyperglycemia, and inhibiting the carbohydrate metabolism enzyme activities.

Table 1.

Mulberry in diabetes and their potentially responsible effective compounds.

Extract Type and Plant Part	Type of Study	Results	Responsible Functional Natural Products	References
Mulberry leaves decoction extract (5%, 10%, 15%)	in vivo, 38 women, 12 men; 25–60 years old, diabetes mellitus	- reduced diabetic symptoms and eliminated neuropathy, however, did not reduce fasting blood sugars	NA	^[1]
Mulberry leaves extract enriched with 1-deoxynojirimycin	in vivo, 76 human subjects with impaired glucose metabolism	- enhanced postprandial glycemic control	- polyphenols, 1-deoxynojirimycin	^[2]
Extract P-9801091 (mulberry leaves and other plant extracts among T. officinale root and

extract (4.38 mg/g). Given the elevated insulin serum levels measured in the rats treated, it was suggested that the black mulberry leaf extract might be boosting the endogenous insulin secretion. Moreover, it was advised that the amount of elevated polyphenols identified in

M. nigra

foliage extract might add to its antioxidant action in protecting the liver and kidneys from tissue injury linked to hyperglycemia

^[9]

In January 2020, a group of researchers explored a hexane fraction of black mulberry Brazilian foliage (Hex-Mn) and their action on carbohydrate digestion and absorption in diabetic mice. HPLC analysis revealed the presence of flavonoids isoquercitrin and kaempferol-3-O-rhamnoside. It was shown that administering Hex-Mn through an oral route to diabetic mice led to the delay of carbohydrate digestion but not to the glucose transport through a brush border membrane of the intestine, which contributed to the reduction of postprandial hyperglycemia. Moreover, it was suggested that Hex-Mn was more effective in suppressing the α-glucosidase enzyme than the a-amylase activity in vitro

^[10]

. Similarly, a later study concluded that the black mulberry leaf extract obtained through maceration acts as an α-glucosidase inhibitor. Their

M. nigra

extract inhibited the α-glucosidase enzyme with an IC

₅₀

value of 549.7 μg/mL

^[16].

Figure 1

shows some of the mechanisms of actions investigated regarding

M. nigra

’s effect in managing diabetes.

Figure 1.

Mechanisms of action regarding mulberry’s effect in managing diabetes.

2. Mulberry Extracts and Their Natural Products Studied for Therapeutic Potential in Hepatic Disorders

After checking the literature published before 2010, it was found that, before 2010, there are no relevant studies regarding black mulberry extracts and their potential benefits in treating or preventing hepatic diseases. However, in

Table 2

, there are summaries of the later studies conducted to assess mulberry’s action in managing hepatic disorders.

Table 2.

Mulberry extracts in hepatic disorders and their potentially responsible effective compounds.

Extract Type and Plant Part	Type of Study	Results	Responsible Functional Natural Products	References
Mulberry leaves MeOH-H₂O extract	in vivo, paracetamol-induced hepatic lesions in rats	- hepatoprotective action	- quercetin, luteolin, and isorhamnetin	- reduce TC and low-density lipids (LDL )serum levels^[17]
NA	^[	²³	^]	Mulberry leaves ethanolic extract	in vivo, methotrexate-induced hepatotoxicity in rats, in vitro, in HepG2 cells	- antioxidant and cytoprotective action
Mulberry leaves aqueous extracts (infusion and decoction)	in vivo, in hyperlipidemic murine models	- flavonoids	^[	^18]	- hypolipidemic and antioxidant action, beneficial in dyslipidemia	- quercetin, chlorogenic acid	^[24]C. intybus root)	in vivo, on non-obese diabetic mice	- influenced lipid peroxidation and increased the antioxidative action of Glutathione S-transferases in the liver, probably via a reduction in hyperglycemia	NA
Mulberry hydroalcoholic leaves extract	in vivo, in alloxan-induced diabetic rats	^[	- attenuate levels of liver damage markers, hepatoprotective	^3]
- caffeoylquinic acids	^[	¹⁹	^]
Fresh mulberry leaves (integrated into diet)	in vivo, in swine fattening models	- obesity preventive action	NA	^[25]	Mulberry leaves extract (powder)	in vivo, in STZ–induced diabetes in rats	- suppress blood sugar levels	NA	^[4]
Mulberry leaves lyophilized extracts	in vivo, in CCI₄-induced hepatic injury in rats	- antioxidant action, controls the activity of SOD and GPx	NA	^[20]	Mulberry leaves aqueous extract	in vivo, in STZ-induced diabetic and non-diabetic Wistar rats	- antioxidant action and reduced occurrence of skeletal and visceral abnormalities	NA	^[5]
Mulberry leaves EtOH extract	in vivo, in female and male rats	- protective and cholesterol-lowering actions	- quercetin, caffeic acid	^[21]	Mulberry leaves ethanolic extract	in vivo, in diabetes rat models induced by high-fat diet and STZ	- antioxidant action, modulate fasting blood glucose	- 1-deoxynojirimycin, flavonoids, polyphenols, and polysaccharides	^[6]^[7
Mulberry leaves MeOH extract	in vivo, in rat models of APAP-induced liver damage	- genetic protection and for the treatment of organotoxicity	^]
- polyphenols and flavonoids (gallic acid, chlorogenic acid, catechin, rutin)	^[	²²	^]	Mulberry leaves fractions	in vivo, in alloxan-induced diabetic mice	- reduce postprandial blood glucose and alleviate toxicity	- hybrid of 1-deoxynojirimycin and polysaccharides	^[8]
Mulberry leaves extract	in vivo, STZ-induced diabetic murine model	- boost endogenous insulin secretion, have antioxidant action	- quercitrin	^[9]
Mulberry leaves Hex-Mn fraction	in vivo, in diabetic mice models	- delay of carbohydrate digestion	- isoquercitrin and kaempferol-3-O-rhamnoside	^[10]
Fresh and freeze-dried mulberry leaves	in vitro, on inhibition of alpha-glucosidase	- lowered blood glucose, inhibited alpha-glucosidase	NA	^[11]
Mulberry (n-hexane, chloroform, ethyl acetate fractions)	in vitro, on the starch breakdown of alpha-amylase activity	- dose-dependent inhibitory effects on alpha-amylase activity [IC50 = 13.26 (12.86–13.66) mg/mL]	NA	^[12]
Mulberry leaves fractions	in vitro, in Caco-2 cell lines	- impede glucose absorption	- chlorogenic acid, rutin, benzoic acid, and hyperoside	^[13]

Diabetes mellitus is a chronic disease defined by the overproduction of ROS, which affects the lysosomal membrane integrity, and, as a metabolic disorder, diabetes is also described by enzymatic alterations

^[14]

. In 2015, a study investigated the catalytic characters and gene expression of hepatic arylsulfatase B (ASB) in streptozotocin-induced diabetic rats treated with black mulberry leaf extract. The results indicated that the black mulberry leaf and fruit extract administered as a powder managed to suppress the blood sugar levels in diabetic rats and substantially diminished hepatic ASB activity. The study’s published data revealed that the daily supplementation of

M. nigra

foliage has a beneficial action in the correction of diabetes-stimulated ASB alteration

^[4]

Moreover, about four years before the above study, an aqueous black mulberry leaf extract (Botucatu, São Paulo State, Brazil) was evaluated for its effects on maternal reproductive results, lipid and oxidative stress outline, and fetal anomaly prevalence when orally administered to streptozotocin-induced diabetic and non-diabetic WR. The study concluded that administering a dose of 400 mg/kg/day of black mulberry leaf extract, by gavage, from day 0 until day 20 of pregnancy resulted in an antioxidant outcome contributive to a reduced occurrence of skeletal and visceral abnormalities in progenies from diabetic dams. However, it could not regulate maternal hyperglycemia, pregnancy rate, and placental–fetal development in diabetic rats

^[5]

Another study evaluated an ethanolic mulberry leaf extract’s properties in diabetes models induced by a high-fat diet and injection of 35 mg/kg STZ in male WR. The extract was administered to one of the four groups over the curse of four weeks. Kidney and blood samples were subjected to biochemical analysis such as fasting blood glucose level, albumin, creatinine, urea and uric acid concentrations, white blood cells, hemoglobin, hematocrit, and histological assessment. The results showed that fasting blood glucose, creatinine, urea, and uric acid displayed considerably lower levels in the extract-treated group than the group lacking mulberry leaf treatment. Moreover, histology evaluation proved that glycogen accumulation, fatty degeneration, and lymphocyte infiltration in the extract-treated group were only mild while they were moderate in the non-treated group

^[6]

. These results were associated with the contents of mulberry leaves in 1-deoxynojirimycin (1- DNJ), quercetin-3-O-βD-glucopyranoside, phytoalexins moracin C, moracin N, and chalcomoracin.

It was also indicated that mulberry leaf extracts, such as mulberry leaves tea, can be addressed to hyperuricemia and nephropathy in diabetes. Diabetic nephropathy results from overly increased oxidative stress and mulberry leaves contain antioxidant components such as 1-DNJ, flavonoids, polyphenols, and polysaccharides with beneficial therapeutic actions

^[7]

To explain the regulatory mechanism of mulberry in treating diabetes, in 2011, a study evaluated 1-DNJ and polysaccharides extracted from mulberry leaves on alloxan-induced diabetic mice. Administering a daily oral treatment with polysaccharides (150 mg/kg body weight) to diabetic mice for three months resulted in postprandial blood glucose reduction and lessened toxicity caused by prolonged supra-physiological glucose to pancreatic cells. Moreover, it was concluded that polysaccharides might control hepatic glucose metabolism and gluconeogenesis by up/down-regulating the expression of rate-limiting enzymes (glucokinase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase) in the liver and up-regulating the pancreatic and duodenal homeobox factor-1 (PDX-1), insulin-1, and insulin-2 expressions in the pancreas

^[8]

Mulberry foliage extract enriched with deoxynojirimycin (DNJ) was studied on postprandial hyperglycemia in patients with impaired glucose metabolism. After three months of supplementation with

M. nigra

extract (6 mg DNJ, t.i.d.) to 76 subjects with fasting plasma glucose varying between 110–140 mg/dL, it was determined that prolonged ingestion of

M. nigra

leaf extract with high DNJ contents can result in enhanced postprandial glycemic control, especially in cases of impaired glucose metabolism

^[2]

Another research investigated the coincubation of 0.1–10 μmol/L DNJ with mature 3T3-L1 adipocytes and established that the genes/proteins expression of the insulin receptor, phosphatidylinositol-3-kinase, protein kinase B, and adiponectin were amplified in a dose-dependent manner. However, it was concluded that further studies are needed to clarify the molecular mechanism of action

^[15]

In 2020, there was another attempt to assess the mechanism of action and bioactivity of mulberry foliage polyphenols in preventing T2D by inhibiting disaccharidase and glucose transport in Caco-2 cells. The mulberry leaves extract’s main composition consisted of chlorogenic acid, rutin, benzoic acid, and hyperoside. The results indicated that mulberry leaf polyphenols hindered glucose absorption by curbing the sodium-dependent glucose cotransporter-1–glucose transporter 2 pathway by downregulating phospholipase mRNA expression, protein kinase A, and protein kinase C

^[13]

The leaves of black mulberry were studied compared to the leaves of

Bauhinia variegate

L., which is a species of flowering plant in the legume family

Fabaceae

. The study evaluated the impact of administering these plants’ extracts orally on hyperglycemia, insulin activity, and renal and hepatic function in an STZ-induced diabetic murine model. The HPLC with a diode-array detection analysis of the extracts highlighted major flavonoids being rutin, quercitrin, quercetin, and hesperidin, and phenolic acids as chlorogenic and p-coumaric acids. Quercitrin was found as the key flavonoid in

M. nigra

foliage extract (2.75 mg/g), and rutin was the main one in

B. variegate

As in the case of dandelion leaf extracts, black mulberry leaves have a potentially beneficial and partly proven impact in cases of hepatic lesions induced by excessive or chronic drug administration. In 2014, a MeOH- H

₂

O extract of

M. nigra

foliage was dispensed in doses of 250 mg/kg and 500 mg/kg through an oral route to mice suffering from paracetamol-induced hepatic damage, and it resulted in lower hepatic enzymes and total bilirubin levels. These hepatoprotective properties were attributed to the high contents of quercetin, luteolin, and isorhamnetin

^[17]

The antioxidant actions of

Morus

leaf ethanolic extracts were also examined in other cases of drug-induced hepatotoxicity.

In vivo

and

in vitro

studies were performed on methotrexate-induced hepatotoxicity models of male rats and on human HepG2 cells. The results indicated that the administration of

M. nigra

leaves extract is advised simultaneously with the anti-rheumatic drug therapy given the extract’s antioxidant and cytoprotective characteristics, which likely resulted from the plant’s flavonoid content

^[18]

Black mulberry leaves and pulp were also evaluated in what concerns their impact on the glycemic response and redox profile on a hepatic level in alloxan-induced diabetic rats. The findings indicated that the hydroalcoholic foliage extracts diminished the SOD-CAT ratio and carbonylated protein levels by decreasing oxidative stress. Finally, it was suggested that black mulberry leaves could be used to control hyperglycemia as they increased the serum insulin level and present hepatoprotective action given the attenuated liver damage markers

^[19]

. The authors concluded as well that the black mulberry leaves extract contained more phenolic compounds than the fruit extract, and that the therapeutic results are most likely triggered by caffeoylquinic acid contents, which were identified in the leaves but not in the fruits.

The effect of lyophilized black mulberry leaf extracts on CCI

₄

-induced hepatic injury in a rat model was investigated. The leaf extracts at doses ranging from 150 to 300 mg/kg were administered to rats by i.p. injection for eight weeks. Black mulberry extracts counteracted protein oxidation caused by CCI

₄

and exhibited the capability to control the activity of SOD and GPx. Moreover, the extracts counteracted the CCI

₄

-induced rise in AST and gamma-glutamyl transferase levels. Finally, leaf extracts offered substantial protection from CCl

₄

-induced hepatic injury, and it was suggested that they might also represent a novel approach for treating hepatic diseases

^[20]

In what concerns the

M. nigra

’s toxicity, a study published in 2018 aimed to identify the chemical profile of EtOH leaves extract and perform a toxicological study in rats of both genders. In the acute exposure group, 2000 mg/kg of the extract was orally administered, and signs of toxicity and mortality were observed. The extract was orally dispensed for 28 days in doses of 500, 750, and 1000 mg/kg in the sub-acute exposure group. The extract’s chemical profile was determined through HPLC/DAD analysis and the findings indicated that quercetin and caffeic acid were the main compounds. After evaluating its action following acute administration, the EtOH

M. nigra

leaf extract was graded as a safe product (category 5), according to the protocol. Moreover, in the subacute exposure group, the researchers noted a reduction in AST in males (750 and 1000 mg/kg) and females (1000 mg/kg) and a decrease in TC in females (750 and 1000 mg/kg). Finally, the ethanolic

M. nigra

leaf extracts were marked as safe when administered orally. They exhibited protective action of organs along with cholesterol-lowering actions, likely due to the extract’s content of quercetin and caffeic acid, which are known as the mulberry leaf’s major compounds

^[21]

A recent study attempted to assess the mechanism through which the MeOH extract of black mulberry foliage curbs the damage caused by APAP in various murine tissues, including hepatic tissues. APAP (500 mg/kg) was administered orally with or without black mulberry leaf extract (150, 300, and 500 mg/kg) over the course of four days. It was, thus, indicated that the crude extract had powerful antioxidant activity (EC50 = 42.97 µg extract/mL) given the significant contents of polyphenols and flavonoids, such as gallic acid, chlorogenic acid, catechin, and rutin. Furthermore, the initially modified levels of glutathione S transferase activity, lipid peroxidation, and liver and kidney functions were radically overturned when black mulberry MeOH extract was administered to the APAP group. Finally, it was indicated that

M. nigra

leaves’ natural products including potential candidates for genetic protection and the treatment of organotoxicity was caused by heightened oxidative stress

^[22]

Figure 2

shows some of the mechanisms of actions investigated regarding

M. nigra

’s effect in managing hepatic disorders.

Figure 2.

Mechanisms of action regarding mulberry’s effect in managing hepatic disorders.

3. Mulberry Extracts and Their Natural Products Evaluated for Therapeutic Potential in Cardiovascular Disease

After checking the literature published before 2010, it was found that there are no relevant studies regarding

M. nigra

leaf extracts and their potential benefits in treating or preventing cardiovascular disorders. However, in

Table 3

, there are some summaries of the later studies conducted to assess mulberry’s action in managing cardiovascular disease.

Table 3.

Mulberry extracts in cardiovascular disease and their potentially responsible effective compounds.

Extract Type and Plant Part	Type of Study	Results	Responsible Functional Natural Products	References
Mulberry leaves extract	in vivo, in hyperlipidemic murine models

Black mulberry leaves were traditionally used to remedy ailments connected with various hepatic disorders and heart diseases. Currently, their extracts are studied for pharmacological and nutraceutical applications due to the reported bioactive compounds. Over the last 10 years, a few

in vivo

and

in vitro

studies were published on the

M. nigra

’s leaves' therapeutic properties on a cardiovascular level, attributed mainly to its antioxidant properties.

In 2016, a black mulberry leaf extract at a dose of 200 mg/kg combined with binahong (

Anredera cordifolia

[Ten.] Stennis) leaf extract was administered to hyperlipidemic-induced rats for 21 days. Powdered crude herb of binahong and mulberry leaves were extracted by ethanol 70% and ethanol 95%, following the reflux method for 3 h with three repetitions. The combination of extracts showed superior effectiveness in a dose-dependent manner than that of the reference drug simvastatin in reducing TC and LDL serum levels

^[23]

Two black mulberry leaves’ aqueous solutions obtained through infusion and decoction and a hydromethanolic extract of black mulberry leaves was compared to fenofibrate-based therapy to highlight their hypolipidemic abilities. Fenofibrate treatment is usually recommended for lowering cholesterol and for preventing cardiovascular complications. However, in what concerns the extracts, it was determined that the infusion extract of black mulberry leaves had superior contents of antioxidant polyphenols like chlorogenic acid and quercetin, while decoction extract offered a greater ascorbic acid content. The hyperlipidemic rats were treated with 100, 200, or 400 mg/kg of black mulberry extracts and showed diminished serum cholesterol, triglycerides, and regulated lipoproteins. Moreover, black mulberry leaves infusion reduced lipid peroxidation in the liver, kidney, and brain. It also resulted in a stronger hypolipidemic effect where high-density lipoprotein (HDL) improved, and LDL dropped. Finally, the potential therapeutic effect attributed to the high contents of quercetin and chlorogenic acid of the black mulberry leaf infusion was indicated as beneficial in dyslipidemia and related oxidative stress

^[24]

Although some studies are exploring the action of white mulberry leaves and black mulberry fruits over triggering conditions of cardiovascular diseases, obesity, and diabetes

^[26][27]

, there is very little preclinical information given over the last 20 years on the therapeutic effects of black mulberry leaves on cardiovascular disease, with the fruits being mainly studied for their content of anthocyanins, proven to be effective in managing cardiovascular disease and triggering factors such as hyperlipidemia

^[28][29]

As mentioned in the previous chapters, cardiovascular ailments are often triggered by diabetes and obesity. In these regards, a study published in 2020 investigated the impact and the action mechanism of dietary black mulberry leaf powder on fat deposition in fattening pigs. The animals were randomly allotted to a normal diet or a 5% (

w/w

) mulberry leaf supplemented diet. Changes in backfat thickness were assessed with blood triglycerides, cholesterol, serum hormones, and leptin-related signaling activity. The mulberry leaf supplemented diet reduced serum triglycerides and free cholesterol concentrations while it increased the ratio of HDL to LDL. Finally, it was indicated that administering black mulberry leaves as diet supplements in fattening pigs have potent obesity preventive action, offering a promising start for developing mulberry leaves-based products as anti-obesity agents

^[25]

M. nigra

leaf extract’s therapeutic action was also studied on symptoms and quality of life among climacteric women. Women go through various hormonal modifications during the menopausal transition that heightens the probability of developing certain diseases and deteriorate women’s quality of life. This study is included in this chapter given that the most frequently met symptoms of hormonal changes also comprise cardiovascular affections among palpitations, headaches, depression, irritability, and fatigue. Furthermore, 250 mg of black mulberry leaf powder, 1 mg of estradiol, or placebo were administered for 60 days to 62 climacteric women. The conclusion was that climacteric symptoms and the women’s quality of life improved after administrating

M. nigra

leaf powder, similarly to the estradiol outcome

^[30]

Figure 3

, there are some mechanisms of actions investigated regarding

M. nigra

’s effect in managing cardiovascular disease.

Figure 3.

Mechanisms of action regarding mulberry’s effect in managing cardiovascular disease.

4. Conclusions

In what concerns the

Morus

species, it seems like black mulberry leaves and some of their natural products are mainly proven to be effective in managing diabetes due to their antioxidant action and reported the capacity of increasing a serum insulin level. These therapeutic properties in managing diabetes are thought to be attributed to mulberry leaf compounds such as 1-deoxynojirimycin, chlorogenic acid, quercetin, and polysaccharides. In hepatic ailments, black mulberry leaves present antioxidant action and cytoprotective characteristics, have a hypolipidemic effect, and are beneficial in dyslipidemia due to compounds such as gallic and chlorogenic acid, rutin, and catechin, quercetin, luteolin, and isorhamnetin. In cardiovascular diseases and associated disorders, white mulberry and black mulberry fruits are studied more than the leaves because anthocyanins present in mulberry fruits are already validated for their beneficial action in cardiovascular disease prevention. Nevertheless, anthocyanins often interact with other phytochemicals, showing synergistic biological effects while making contributions from individual components that are difficult to decipher.

References

Khazaei, M.; Hosseinzadeh, H.; Kazemi, L.; Clinical trial of antidiabetic effect of Morus Nigra leave extracts. Iran. J. Basic Med. Sci. 2002, 5, 27–34.
Akira Asai; Kiyotaka Nakagawa; Ohki Higuchi; Toshiyuki Kimura; Yoshihiro Kojima; Jun Kariya; Teruo Miyazawa; Shinichi Oikawa; Effect of mulberry leaf extract with enriched 1-deoxynojirimycin content on postprandial glycemic control in subjects with impaired glucose metabolism. Journal of Diabetes Investigation 2011, 2, 318-323, 10.1111/j.2040-1124.2011.00101.x.
R. Petlevski; M. Hadzija; M. Slijepčević; D. Juretic; J. Petrik; Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091. Phytotherapy Research 2003, 17, 311-314, 10.1002/ptr.1128.
Al-awar, A.; Attieh, Z.; Balbaa, M.; Mulberry leaves lower the enzymatic activity and expression of hepatic arylsulfatase B in streptozotocin-induced diabetic rats. Curr. Top. Nutraceutical Res. 2015, 13, 121–128.
G.T. Volpato; I.M.P. Calderon; S. Sinzato; K.E. Campos; M.V.C. Rudge; D.C. Damasceno; Effect of Morus nigra aqueous extract treatment on the maternal–fetal outcome, oxidative stress status and lipid profile of streptozotocin-induced diabetic rats. Journal of Ethnopharmacology 2011, 138, 691-696, 10.1016/j.jep.2011.09.044.
Hassanalilou, T.; Payahoo, L.; Shahabi, P.; Abbasi, M.M.; Jafar-Abadi, M.A.; Bishak, Y.K.; Khordadmehr, M.; Esnaashari, S.; Barzegar, A.; The protective effects of Morus nigra L. leaves on the kidney function tests and histological structures in streptozotocin-induced diabetic rats. Biomed. Res. 2017, 28, 6113–6118.
Yao Sheng; Shujuan Zheng; Chuanhai Zhang; Changhui Zhao; Xiaoyun He; Wentao Xu; Kunlun Huang; Mulberry leaf tea alleviates diabetic nephropathy by inhibiting PKC signaling and modulating intestinal flora. Journal of Functional Foods 2018, 46, 118-127, 10.1016/j.jff.2018.04.040.
Li, Y.G.; Ji, D.F.; Zhong, S.; Lv, Z.-Q.; Lin, T.; Chen, S.; Hu, G.-Y.; Hybrid of 1-deoxynojirimycin and polysaccharide from mulberry leaves treat diabetes mellitus by activating PDX-1/insulin-1 signaling pathway and regulating the expression of glucokinase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in allox. J. Ethnopharmacol. 2011, 134, 961–970.
Salma Hago; Engy A. Mahrous; Mohamed Moawad; Samia Abdel-Wahab; Essam Abdel-Sattar; Evaluation of antidiabetic activity of Morus nigra L. and Bauhinia variegata L. leaves as Egyptian remedies used for the treatment of diabetes. Natural Product Research 2019, 35, 829-835, 10.1080/14786419.2019.1601094.
Dionísio Henrique Amaral Da Silva; Humberto De Moura Barbosa; Raphaelle Lima De Almeida Beltrão; Clarissa De França Oliveira Silva; Celuane Alves Moura; Rosane Nora Castro; Jackson Roberto Guedes Da Silva Almeida; Dayane Aparecida Gomes; Eduardo Carvalho Lira; Hexane fraction from Brazilian Morus nigra leaves improved oral carbohydrate tolerance and inhibits α-amylase and α-glucosidase activities in diabetic mice.. Natural Product Research 2020, ., 1-4, 10.1080/14786419.2020.1723087.
Wang, L.-L.; Zhou, Z.-Y.; Effect of extracts of mulberry leaves processed differently on the activity of α-glucosidase. J. Food Agric. Environ. 2008, 6, 86–89.
Nickavar, B.; Mosazadeh, G.; Influence of three Morus species extracts on α-Amylase activity. IJPR 2009, 8, 115–119.
Qian Li; Chen Wang; Fan Liu; Tenggen Hu; Weizhi Shen; Erna Li; Sentai Liao; Yuxiao Zou; Mulberry leaf polyphenols attenuated postprandial glucose absorption via inhibition of disaccharidases activity and glucose transport in Caco-2 cells. Food & Function 2020, 11, 1835-1844, 10.1039/c9fo01345h.
Ann-Charlotte Johansson; Hanna Appelqvist; Cathrine Nilsson; Katarina Kågedal; Karin Roberg; Karin Öllinger; Regulation of apoptosis-associated lysosomal membrane permeabilization. Apoptosis 2010, 15, 527-540, 10.1007/s10495-009-0452-5.
Qian Li; Yiguo Wang; Yanli Dai; Weizhi Shen; Sentai Liao; Yuxiao Zou; 1-Deoxynojirimycin modulates glucose homeostasis by regulating the combination of IR-GlUT4 and ADIPO-GLUT4 pathways in 3T3-L1 adipocytes. Molecular Biology Reports 2019, 46, 6277-6285, 10.1007/s11033-019-05069-y.
Arif Budiman; Ferry F Sofian; Ni Made W S Santi; Diah L Aulifa; The formulation of lozenge using black mulberries (Morus nigra L.) leaf extract as an α-glucosidase inhibitor. Journal of Pharmacy And Bioallied Sciences 2020, 12, 171-176, 10.4103/jpbs.jpbs_219_19.
Tauqeer Hussain Mallhi; M. Imran Qadir; Yusra Habib Khan; Muhammad Ali; Hepatoprotective activity of aqueous methanolic extract of Morus nigra against paracetamol-induced hepatotoxicity in mice. Bangladesh Journal of Pharmacology 2014, 9, 60-66, 10.3329/bjp.v9i1.17337.
Hend M. Tag; Hepatoprotective effect of mulberry (Morus nigra) leaves extract against methotrexate induced hepatotoxicity in male albino rat. BMC Complementary and Alternative Medicine 2015, 15, 252, 10.1186/s12906-015-0744-y.
Carolina Morais Araujo; Karine De Pádua Lúcio; Marcelo Eustáquio Silva; Mauro César Isoldi; Gustavo Henrique Bianco De Souza; Geraldo Célio Brandão; Richard Schulz; Daniela Caldeira Costa; Morus nigra leaf extract improves glycemic response and redox profile in the liver of diabetic rats. Food & Function 2015, 6, 3490-3499, 10.1039/c5fo00474h.
Gulsah Deniz; Esra Laloglu; Kübra Koç; Hayrünnisa Nadaroğlu; Fatime Geyikoğlu; The effect of black mulberry (Morus nigra) extract on carbon tetrachloride-induced liver damage. Archives of Biological Sciences 2018, 70, 371-378, 10.2298/abs171009055d.
Kássia Caroline Figueredo; Camille Gaube Guex; Fernanda Ziegler Reginato; Andreia Regina Haas Da Silva; Gabriela Buzatti Cassanego; Cibele Lima Lhamas; Aline Augusti Boligon; Gilberti Helena Hübscher Lopes; Liliane De Freitas Bauermann; Safety assessment of Morus nigra L. leaves: Acute and subacute oral toxicity studies in Wistar rats. Journal of Ethnopharmacology 2018, 224, 290-296, 10.1016/j.jep.2018.05.013.
Kawthar A. Diab; Maha A. Fahmy; Emad M. Hassan; Zeinab M. Hassan; Enayat A. Omara; Negm S. Abdel-Samie; Inhibitory activity of black mulberry (Morus nigra) extract against testicular, liver and kidney toxicity induced by paracetamol in mice. Molecular Biology Reports 2020, 47, 1733-1749, 10.1007/s11033-020-05265-1.
Sukandar, E.Y.; Safitri, D.; Aini, N.N.; The study of ethanolic extract of binahong leaves (Anredera cordifolia [Ten.] Steenis) and mulberry leaves (Morus nigra L.) in combination on hyperlipidemic-induced rats. AJPCR 2016, 9, 288–292.
Ana Lúcia B. Zeni; Tatianne D. Moreira; Ana Paula Dalmagro; Anderson Camargo; Larissa A. Bini; Edésio L. Simionatto; Dilamara R. Scharf; Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra leaves extract. Anais da Academia Brasileira de Ciências 2017, 89, 2805-2815, 10.1590/0001-3765201720160660.
Lujie Fan; Ying Peng; Dan Wu; Jianhong Hu; Xin'e Shi; Gongshe Yang; Xiao Li; Dietary supplementation of Morus nigra L. leaves decrease fat mass partially through elevating leptin-stimulated lipolysis in pig model. Journal of Ethnopharmacology 2020, 249, 112416, 10.1016/j.jep.2019.112416.
Yan Jiang; Min Dai; Wen-Jing Nie; Xiao-Rong Yang; Xian-Chun Zeng; Effects of the ethanol extract of black mulberry ( Morus nigra L.) fruit on experimental atherosclerosis in rats. Journal of Ethnopharmacology 2017, 200, 228-235, 10.1016/j.jep.2017.02.037.
Thaipitakwong, T.; Numhom, S.; Aramwit, P.; Mulberry leaves and their potential effects against cardiometabolic risks: A review of chemical compositions, biological properties and clinical efficacy. Pharm. Biol. 2018, 56, 109–118.
Jia-Jen Chang; Man-Jung Hsu; Hui-Pei Huang; Dai-Jung Chung; Yun-Ching Chang; Chau-Jong Wang; Mulberry Anthocyanins Inhibit Oleic Acid Induced Lipid Accumulation by Reduction of Lipogenesis and Promotion of Hepatic Lipid Clearance. Journal of Agricultural and Food Chemistry 2013, 61, 6069-6076, 10.1021/jf401171k.
Zhong-Zheng Gui; Palanigounder Ganeshan Ajay Krishna; Thasma Raman Sivakumar; Chao Jin; Shao-Hu Li; Yu-Jie Weng; Juan Yin; Jun-Qiang Jia; Chu-Yan Wang; Antioxidant and Hemolysis Protective Effects of Polyphenol-Rich Extract from Mulberry Fruits. Pharmacognosy Magazine 2018, 14, 103-109, 10.4103/pm.pm_491_16.
Joyce P.L. Costa; Haissa O. Brito; Leonardo V. Galvão‐Moreira; Luiz G.O. Brito; Lucia Costa‐Paiva; Luciane M.O. Brito; Randomized double-blind placebo-controlled trial of the effect of Morus nigra L. (black mulberry) leaf powder on symptoms and quality of life among climacteric women.. International Journal of Gynecology & Obstetrics 2019, 148, 243-252, 10.1002/ijgo.13057.