White Mulberry

Generic name: Morus Alba L.
Brand names: Common Mulberry, Mulberry, Pawi Bush, Silkworm Mulberry, White Mulberry

Usage of White Mulberry

Allergic Reactions

In vitro data

Pretreatment with a white mulberry root bark extract inhibited induced mast cell degranulation and Histamine release in rat peritoneal mast cells.(Chai 2005)

Antibacterial activity

In vitro data

Antibacterial activity is associated with kuwanon C, mulberrofuran G, and albanol B from mulberry leaves, with minimum inhibitory concentrations (MICs) ranging from 5 to 30 mg/mL.(Butt 2008, Kumar 2008) Chloroform mulberry extracts have antibacterial activity against Bacillus subtilis, and acetic acid extracts have activity against Staphylococcus aureus and Escherichia coli. Chemical constituents (eg, morusin, kuwanon C, sanggenon B and D) from the bark have activity against S. aureus, Streptococcus faecalis, B. subtilis, Mycobacterium smegmatis, and mold species. Kuwanon G from a leaf methanol extract HAD an MIC (8 mg/mL) against the oral pathogen Streptococcus mUTAns; the cariogenic bacteria Streptococcus sobrinus; Streptococcus sanguis; and Porpyromonas gingivalis, which causes periodontitis.(Park 2003) At a concentration of 20 mcg/mL, kuwanon G completely iNACtivated S. mutans in 1 minute. Similar studies of other isolated leaf compounds showed antibacterial activity against S. mutans.(Islam 2008)

Anti-inflammatory activity

Animal and in vitro data

Reduction in carrageenin-induced paw edema in rats via anti-inflammatory activity of mulberroside A and oxyresveratrol from the root bark has been documented.(Chung 2003) A white mulberry leaf methanol extract and its fractions inhibited the inflammatory mediators nitric oxide, prostaglandin E2, and cytokines in a mouse macrophage cell line.(Choi 2005) In a study in immobilized rats, antioxidants in white mulberry leaf extracts protected rat organ tissues (eg, liver, adrenal glands, kidneys, spleen) against inflammation and peroxidation induced by stress; the antioxidants were more effective than pure rutin, with adrenal glands appearing to be the primary target organs of the antioxidants.(Lee 2007)

Antioxidant activity

In vitro data

The numerous flavonoids(Kim 1999b) from mulberry leaves and the phenols(Chon 2009) from the roots, branches, and fruits all have free radical–scavenging properties. Mulberroside A and oxyresveratrol show inhibitory activity against induced lipid peroxidation in rat microsomes and free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical.(Butt 2008) The DPPH scavenging activity is associated with caffeoylquinic acids in immature white mulberry fruits and with anthocyanins in mature white mulberry fruits.(Oki 2006) In a study examining the cardioprotective effect of plant extracts, a white mulberry water extract increased the concentration that inhibits 50% (IC50) of doxorubicin (P<0.05 vs control) in a dose-Dependent manner.(Wattanapitayakul 2005)

Antiviral data

In vitro data

Leachianone G from the root bark showed potent antiviral activity (IC50, 1.6 mcg/mL) against herpes simplex type 1 virus.(Du 2003) Kuwanon H has been reported to exhibit activity against HIV, and other Morus species flavonoids have inhibited respiratory syncytial virus and adenoviruses.(Thabti 2020) Antiviral activity of extracts from the stem bark of M. alba var. alba, M. alba var. rosea, and Morus rubra ranged from 34% to 45% against human coronavirus 229E, while inhibitory effects of the leaf extract ranged from 67% to 100%. However, no significant inhibition was found against 4 nonenveloped human viruses (ie, poliovirus 1, parechovirus 1 and 3, echovirus 11). Kuwanon G at a concentration of 10 mcg/mL reduced the coronavirus 229E cytopathic effect to 2%.(Thabti 2020)

Anxiety

Animal data

In various animal models of anxiety, white mulberry leaf extracts showed anxiolytic and muscle relaxant activities based on exploratory behavior.(Yadav 2008a)

Cancer

In vitro data

Anti-cancer activity via induction of apoptosis and inhibition of migration and invasion has been demonstrated with M. alba in various human cancer cell lines, including colorectal, lung, leukocytes.(Chen 2006, Park 2021, Skupień 2008) The anthocyanins cyanidin 3-rutinoside and cyanidin 3-glucoside from white mulberry inhibited the migration and invasion of highly metastatic A549 human lung carcinoma cells.(Chen 2006) Anticancer activity may be associated with decreased expression of matrix matalloprotinase-2 and Urokinase-plasminogen activator and enhanced expression of tissue inhibitor of matrix matalloprotinase-2 and plasminogen activator inhibitor. A prenylated flavanone isolated from an ethyl acetate extract of white mulberry root exerted cytotoxic activity against rat hepatoma cells, with an IC50 of 52.8 mg/mL.(Butt 2008) A white mulberry root bark extract exhibited cytotoxic activity by inducing apoptosis and inhibiting microtubule assembly on K-562, B380 human leukemia cells and B16 mouse melanoma cells.(Nam 2002) In another in vitro study, white mulberry leaf extracts inhibited the growth of HL60 human promyelocytic leukemia and multidrug-resistant HL60 cells (HL60/VINC and HL60/DOX).(Skupień 2008) The anthocyanins from the fruit controlled tumor metastasis and motility of a melanoma murine cancer cell line by inhibiting tumor cell migration and metastasis, as well as tissue invasion of tumor cells; by inhibiting signaling pathways; and by decreasing DNA binding to nuclear factor kappa-B and AP-1.(Huang 2008) Albanol A from the root bark of white mulberry induced apoptosis in HL60 cells. Albanol A showed potent DNA topoisOmerase II inhibitory activity (IC50, 22.8 mcM) similar to that of the control etoposide (IC50, 34.5 mcM), which may trigger apoptosis of HL60 cells.(Kikuchi 2010)

Cardiovascular disease

Several mechanisms of action may be involved with the effects of white mulberry leaf tablet therapy on lipid profiles, including the following: regulation of hepatic gene expression involved in lipid and lipoprotein metabolism; reduction of plasma glucose levels by 1-deoxynojirimycin (DNJ) (isolated from the leaves), resulting in decreased fatty acid influx to the liver from adipose tissue and decreased triglyceride and cholesterol levels; and anti-atherosclerotic effects of leaf flavonoids.(Chan 2016)

Animal and in vitro data

White mulberry leaf extracts suppressed gene expression of proinflammatory stimuli in vascular endothelial cells.(Shibata 2007) A leaf ethyl acetate extract exhibited dual vasoactive effects on rat aorta.(Xia 2008) Relaxation of the aorta was caused by inhibition of voltage- and receptor-dependent calcium channels in vascular smooth muscle cells and contraction of the aorta through activation of ryanodine receptors in the sarcoplasmic reticulum. The leaf extracts may also inhibit the activity of matrix metalloproteinases, protein expression and phosphorylation, and signaling pathways in rat thoracic aorta smooth muscle cells involved in the pathophysiology of atherosclerosis.(Chan 2009)

Dietary consumption of white mulberry leaf (containing Quercetin) reduced atherosclerotic lesion development in LDL receptor–deficient mice by increasing LDL resistance to oxidative modification.(Enkhmaa 2005) Supplementation of white mulberry methanol root bark extract (500 mg/kg/day for 15 days) in cholesterol-fed rats resulted in decreased total cholesterol, LDL cholesterol, very low–density lipoprotein cholesterol, and triglycerides, as well as improved HDL cholesterol.(El-Beshbishy 2006) White mulberry fruit extracts also improved the lipid profile in hyperlipidemic rats(Yang 2010a) and in hamsters fed a high-cholesterol diet.(Liu 2009) The hypolipidemic activity is associated with enhanced hepatic LDL receptor expression, which improves clearance of LDL and decreases lipid biosynthesis. Liver lipid accumulation was suppressed in rats administered either DNJ or white mulberry extract enriched in DNJ.(Tsuduki 2009) Similar results were observed with mulberry leaf extract in a nonalcoholic fatty liver disease rat model in which triglycerides and total cholesterol were significantly decreased compared with controls. Hepatic tissue morphology of the mulberry group was similar to that of the positive control, Fenofibrate.(Hu 2020)

Clinical data

Twenty-three patients meeting National Cholesterol Education Program ATP III criteria guidelines for dyslipidemia received three 280 mg white mulberry leaf tablets (each containing 254.8 mg of mulberry leaf powder) 3 times a day before meals for 12 weeks. Lipid profiles and liver function tests were performed every 4 weeks. At 4 and 8 weeks, triglycerides were reduced by 10.2% and 12.5%, respectively, compared with baseline. At conclusion of the study, total cholesterol, triglycerides, and LDL had decreased by 4.9%, 14.1%, and 5.6%, respectively, and HDL increased by 19.7% when compared with baseline. Results suggest consumption of 1 g of white mulberry leaf tablets (1.3 mg of DNJ) 3 times a day before meals may be effective for mild dyslipidemia.(Aramwit 2011)

In a small study summarized in a review, mulberry leaf powder 3 g/day for 30 days significantly improved serum cholesterol, LDL, very low–density lipoprotein, and HDL in patients with type 2 diabetes, whereas these lipid parameters were not significantly changed in patients who received glibenclamide (glyburide) 5 mg/day.(Chan 2016)

In a systematic review and meta-analysis of 13 randomized, placebo-controlled trials evaluating effects of mulberry leaves (at any dose and formulation) on blood glucose and lipids, 2 of the 4 studies (n=158) that reported on lipids used mulberry in a combination product. Therefore, reported effects from the meta-analysis regarding LDL, HDL, total cholesterol, and triglycerides cannot be solely attributed to mulberry. Individual studies reporting on these outcomes showed equivocal results or no difference between treatment groups. No difference was found between groups in the relative risk of adverse events. Participants included both healthy individuals and those with dyslipidemia.(Phimarn 2017)

Diabetes

Animal and in vitro data

In rats with streptozotocin-induced diabetes, a dose of 600 mg/kg/day of 70% white mulberry alcohol bark extract over 10 consecutive days reduced serum glucose by 41% and increased serum insulin by 44%.(Singab 2005) The bark extract may reduce lipid peroxidation and oxidative stress in pancreatic beta cells. The glycoprotein moran 20K from a white mulberry aqueous methanolic root bark extract lowered blood glucose in streptozotocin-induced diabetic rats. The amino acid composition of moran 20K is similar to that of insulin, as it contains more than 20% serine and cysteine.(Kim 1999a) In vivo, hypoglycemic activity was documented for moracin M, steppogenin-4′-O-beta-D-glucosiade, and mullberroside A, which are common types of benzofurans, flavanones, and stilbene glycosides in white mulberry root bark.(Zhang 2009a)

In another study of rats with streptozotocin-induced diabetes, white mulberry aqueous leaf extract decreased nitric oxide synthase expression in the hypothalamus, suggesting a role in reducing the desire for food under diabetic conditions.(Jang 2002) DNJ from mulberry leaves has also competitively inhibited human and rat small intestinal disaccharidase activity of sucrase, maltase, and isomaltase.(Oku 2006) A white mulberry ethanol leaf extract reduced glucose levels in diabetic rats by increasing glucose uptake and glucose transporter 4 translocation in adipose tissue.(Naowaboot 2008) A similar study documented improved postprandial hyperglycemia with white mulberry leaf administration in rats, possibly by inhibiting glucose transport and alpha-glucosidase at the gut brush border.(Park 2009) Antioxidant activity of white mulberry leaf may restore free radical–induced vascular dysfunction in diabetic rats.(Naowaboot 2009) In rat skeleton muscle, a white mulberry leaf extract stimulated 5-adenosine monophosphate–activated protein kinase (AMPK), a major signaling pathway in exercise-stimulated, insulin-independent glucose transport in skeletal muscle.(Ma 2009) Dietary supplementation of purified quercetin from white mulberry leaves in obese mice led to improved plasma glucose levels and reduced oxidative stress in the liver.(Katsube 2010)

Clinical data

In a study in healthy volunteers, a single oral dose of DNJ-enriched powder 0.8 g or 1.2 g suppressed the elevation of postprandial blood glucose and the secretion of insulin.(Kimura 2007) A similar study documented a ratio of 1:10 white mulberry leaf extract to sucrose in suppressing postprandial blood glucose and insulin.(Nakamura 2009) A review of 2 small trials (N=20 in each) reported significant improvements in acute blood glucose in patients with type 2 diabetes after consumption of single doses of mulberry leaf extract 1 g or 3.3 g compared with controls.(Chan 2016) In obese patients with impaired glucose metabolism enrolled in a randomized controlled study (N=85), administration of 4.6 g of mulberry leaf powder (12 mg of DNJ) 3 times daily for 12 weeks in combination with nutritional counselling resulted in no significant difference in blood glucose compared with nutritional counselling alone. Mulberry supplementation did result in improvements from baseline for Fasting plasma glucose, glycated hemoglobin (HbA1c), and insulin resistance; however, no between-group statistics were provided.(Thaipitakwong 2020)

A systematic review and meta-analysis of randomized, placebo-controlled trials using mulberry leaves (at any dose and formulation) for managing blood glucose and lipids identified 13 studies (N=436) that met inclusion criteria. Pooled data from 7 studies (n=228) revealed significantly lower postprandial glucose levels for mulberry compared with controls at 30, 60, and 90 minutes (P<0.00001, P<0.0001, and P<0.001, respectively) but not at 120 minutes. Heterogeneity was high for all 4 time periods. Unfortunately, 3 of the 13 studies used multiherbal products and no subgroup analysis was conducted to exclude these studies; therefore, reported effects from the meta-analysis regarding fasting blood glucose, HbA1c, or insulin resistance cannot be solely attributed to mulberry. Individual studies reporting on these outcomes found equivocal results or no difference between treatment groups. No difference was found between groups in the relative risk of adverse events. Participants included healthy individuals and those with impaired glucose tolerance or type 2 diabetes.(Phimarn 2017)

Gout

Animal and in vitro data

In a study of rats with oxonate-induced hyperuricemia, morin from white mulberry (concentration of 80 mg/kg) exhibited a hypouricemic action and inhibited xanthine oxidase.(Yu 2006) The inhibitory activity on urate uptake in rat renal brush border membrane vesicles was more potent than that of the prescription agent probenecid. Morin exhibited similar activity on urate transport in human kidney cells.(Yu 2007)

Neurodegenerative diseases

Animal and in vitro data

In order to provide a pharmacological basis for neuroprotective actions of enhanced gamma-aminobutyric acid (GABA) accumulation in mulberry leaves against cerebral ischemia in vitro and in vivo, a process was developed to enhance the accumulation of GABA in mulberry leaves via various anaerobic treatments; results suggest that anaerobic treatment of mulberry leaves enhances neuroprotective effects against cerebral ischemia.(Kang 2006) in vivo and in vitro Parkinson disease models suggest protective effects of an ethanol extract of mulberry fruit against neurotoxicity.(Kim 2010) White mulberry leaf extracts have antidoPaminergic activity mediated through dopamine D2 receptors, as documented by reduced Haloperidol- and metoclopramide-induced catalepsy in mice, blocking of amphetamine-induced stereotyped behavior (such as schizophrenia), and increased sensitivity to barbiturates.(Nade 2010, Yadav 2008b) Metabolites of M. alba root bark, also known as Diels-Alder type adducts, have demonstrated not only modulation of dopaminergic receptors but also mild to moderate inhibition of both monoamine oxidase types A and B enzymes in vitro.(Paudel 2019)

Obesity

Animal data

Melanin-concentrating hormone (MCH) is involved in feeding and energy metabolism. In a study in diet-induced obese mice, white mulberry leaf extract exhibited an MCH1 receptor antagonistic effect, resulting in decreases in body weight and adiposity, food intake, and hepatic lipid accumulation.(Oh 2009)

Osteoarthritis

Animal and in vitro data

In an osteoarthritis mouse model, administration of the flavonoid morusin, derived from the root bark of M. alba, reversed severe cartilage erosion and destruction. In vitro experiments pointed to attenuation of inducible nitric oxide synthase and cyclooxygenase 2 expression, protection against interleukin 1-beta–induced collagen degradation, and suppression of nuclear factor kappa-B signaling.(Jia 2020)

Skin tone

In vitro data

Because tyrosinase is a key enzyme involved in melanin biosynthesis, tyrosinase inhibitors may improve the appearance of skin by preventing the overproduction of melanin.(Butt 2008) Betulinic acid from white mulberry extracts showed anti-inflammatory and antityrosinase activities in vitro.(Nattapong 2008, Smit 2009) A white mulberry leaf methanol extract containing mulberroside F inhibited tyrosinase activity and exhibited superoxide scavenging activity.(Lee 2002)

Clinical data

In a single-blind, randomized, placebo-controlled study (N=50), administration of topical mulberry 75% extract (in coconut oil base) to hyperpigmented facial lesions appeared to be a safe and effective treatment in lightening melasma (P<0.05). The extract or placebo (coconut oil) was applied twice daily for 8 weeks, 30 minutes prior to applying SPF 30 sunscreen.(Alvin 2011)

In a randomized clinical trial, an over-the-counter cosmetic product containing white mulberry improved the appearance of facial wrinkles by restoring fibrillin-1.(Watson 2009)

Sleep

Animal data

M. alba leaf extract significantly reduced mean onset of sleep time and mean sleeping time in rats compared to controls (P<0.001) but was less effective than diazepam.(Rayam 2022)

Snake venom

In vitro data

White mulberry leaf extract completely blocked in vitro proteolytic and hyaluronolytic activities of Vipera/Daboia russelii venom, which protected against tissue degradation. The extract also Neutralized the edema, hemorrhage, and myonecrotic activities of the venom. Procoagulant activity was partially inhibited, while complete inhibition was attained against degradation of A-alpha chain of human Fibrinogen.(Chandrashekara 2009)

Stress

Animal data

An animal study reported that white mulberry root extract may have adaptogenic effects against induced neurological, behavioral, and biochemical changes due to long-term stress.(Nade 2009)

White Mulberry side effects

Avoid use in individuals hypersensitive to any component of white mulberry. The pollen extract may cause airborne contact urtIcaria.(Kumar 2008) Patients with nasobronchial allergies may be sensitive to the pollen extract.(Prasad 2009) One clinical study found that some patients experienced mild diarrhea, dizziness, constipation, and bloating.(Aramwit 2011)

Before taking White Mulberry

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

How to use White Mulberry

Results from a small study evaluating effects on mild dyslipidemia suggest a doSage of approximately 1 g of white mulberry leaf powder tablets (1.3 mg of DNJ) 3 times a day before meals.(Aramwit 2011) In a small study summarized in a review, encapsulated mulberry leaf powder at a dosage of 1 g 3 times a day (after meals) for 30 days was used to evaluate hypolipidemic effects of M. alba in patients with type 2 diabetes.(Chan 2016) White mulberry is available in numerous dose forms and is marketed as a product for maintaining healthy blood sugar levels and supporting cardiovascular health.

Warnings

No deaths were associated with 2 g/kg, 5 g/kg, or 10 g/kg doses in animal toxicity studies. High doses produced depression of locomotor activity, decreased alertness, passivity, and abnormal gait in mice.(Yamatake 1976)

What other drugs will affect White Mulberry

None well documented.

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