Morus (Mulberry): A Comprehensive Reference Article
1. Identity and Taxonomy
Botanical and Nomenclatural Identity
Genus: Morus L. Family: Moraceae (the mulberry family, which also includes fig and breadfruit). Among Morus spp., Morus alba L. (white mulberry), Morus nigra L. (black mulberry), and Morus rubra L. (red mulberry) are the three main species that grow all over the world. Of these, Morus alba is by far the most extensively studied medicinally and pharmacologically. It is one of the most cultivated species of mulberry, widely distributed in the Asian subcontinent.
White mulberry (Morus alba) is native to China but can be found throughout the world in temperate and tropical climates. Common names include white mulberry, common mulberry, silkworm mulberry, Egyptian mulberry, and Russian mulberry. In Hindi, it is known as Tut.
Botanical Description
Morus alba is a fast-growing shrub or medium-sized tree with a straight, cylindrical trunk. The leaves of this plant serve as the primary food source for silkworms, making it a crucial component of the global silk industry. The nutrients and uses of mulberry differ across species (Morus alba L., Morus nigra L., and Morus rubra L.).
Pharmacopoeial and TCM Nomenclature
Morus alba L. is a common traditional Chinese medicine (TCM) with a centuries-old medicinal history; its various medicinal parts are known as Mori folium, Mori ramulus, Mori cortex, and Mori fructus. In China, the mulberry tree is considered a "treasure from root to crown": its leaf (Sang Ye), twig (Sang Zhi), fruit (Sang Shen), root bark (Sang Bai Pi), and even the parasitic mistletoe growing on it (Sang Ji Sheng) are all distinct and widely used medicines. These Pinyin names correspond to the pharmacopoeial designations Folium Mori, Ramulus Mori, Fructus Mori, and Cortex Mori, respectively, as listed in the Pharmacopoeia of the People's Republic of China.
Common Preparations and Dosage Forms
Medicinally, whole plants, leaves, fruits, branches, and roots have been employed. Modern commercial preparations include:
- Dried whole leaf powder (used in capsules or tablets)
- Standardized aqueous or hydroethanolic leaf extracts, often standardized to a percentage of 1-deoxynojirimycin (DNJ)
- Herbal decoctions (teas)
- Topical creams or serums (particularly for skin applications)
Reducose® (Phynova Group Limited) is a commercial water-soluble extract of M. alba leaves standardized to 5% 1-deoxynojirimycin (DNJ), an iminosugar with α-glucosidase inhibition properties. Mulberry leaf is widely distributed in China; clinically, it is used either in dried or processed (fried with honey) forms. Traditionally, mulberry leaf collected after the first frost (霜桑叶, Shuāng Sāng Yè) is considered therapeutically superior; classical texts from the Tu Jing Yan Yi Ben Cao onward specify frost-touched leaves, and this remains the standard in the modern Chinese Pharmacopoeia.
2. Traditional and Historical Use
Traditional Chinese Medicine (TCM)
China is the relatively early known country raising silkworms and growing M. alba L.; the presence of M. alba could be traced back to thousands of years ago, and many medical classics such as Shennong Ben Cao, Tang Ben Cao, and Ben Cao Gang Mu also recorded it. The source of the earliest record in TCM pharmacopoeia is the Shennong Bencao Jing.
Each part of the plant carried distinct indications in TCM. Mori folium (leaf) exhibited analgesic, anti-inflammatory, hypoglycemic, and lipid-regulation effects; Mori ramulus (twig) owned anti-bacterial, anti-asthmatic, and diuretic activities; Mori cortex (root bark) showed counteraction of pain, inflammation, bacteria, and platelet aggregation; and Mori fructus (fruit) was used to decompose fat, lower blood lipids, and prevent vascular sclerosis.
Regarding the leaf specifically, it is characterized in TCM as sweet, bitter, and cold in flavor, acting on the lung and liver meridians. Its TCM functions include expelling wind and clearing heat, and clearing heat in the liver to benefit the eyes. A classical formulation, Sang Ju Yin (Mulberry and Chrysanthemum Drink), combined mulberry leaf with chrysanthemum, platycodon, mentha, and forsythia for wind-heat syndromes characterized by fever, headache, sore throat, and cough. This formula was derived from the classical work Wen Bing Tiao Bian (Analysis of Warm Diseases) by Wu Jutong in the Qing Dynasty (1798 AD).
The root bark of Morus alba was used traditionally as a diuretic, antipyretic, antitussive, and expectorant agent. Indications and properties of Mori Cortex as a traditional Chinese medicine included purging the lungs to relieve dyspnea, inducing diuresis to alleviate edema, and treating cough and dyspnea due to lung heat, face edema, and dysuria.
Japanese Tradition
The use of Morus alba was first recorded around 500 AD and has been used for more than 750 years in Japan as an infusion tea. Mulberry leaves have been widely cultivated for sericulture from ancient times, and the leaves are also consumed as herbal tea in Asian countries. In Japan, Mori folium is used as an anti-hyperglycemic supplement for the treatment of diabetes.
Ayurvedic and South/Southeast Asian Tradition
Morus alba L. is a member of the family Moraceae that has been traditionally used to cure various ailments in many Asian, South African, and European countries. M. alba is native to Asian countries such as China and India; they are widely cultivated and naturalized everywhere across the world for sericulture. In Ayurvedic traditions, it is recognized as a medicinal plant. The fruits of Morus alba have traditionally been used as an analgesic, anthelmintic, antibacterial, anti-rheumatic, diuretic, hypotensive, hypoglycemic, purgative, restorative, sedative tonic, and blood stimulant; various plant parts were used as a cooling, sedating, diuretic, tonic, and astringent agent to treat nerve disorders.
Traditional Food Use
In parts of Asia, mulberry leaves have been used for tea, wine, bean curd, and noodles. The mulberry foliage has remained the primary food for silkworms for centuries; its leaves have also been used as animal feed for livestock, and its fruits have been made into a variety of food products.
3. Key Constituents and Active Compounds
Overview of Phytochemical Classes
The main chemical components in Morus alba L. cover flavonoids, phenolic compounds, alkaloids, and amino acids. The plant also contains tannins, steroids, phytosterols, sitosterol, glycosides, carbohydrates, proteins, saponins, triterpenes, benzofuran derivatives, anthocyanins, and anthraquinones.
Flavonoids
Flavonoids such as rutin, quercetin, and kaempferol are produced via the phenylpropanoid and flavonoid biosynthetic pathways. Mulberry contains polyphenol compounds, including flavonoids such as quercetin 3-(6-malonylglycoside), kaempferol 3-(6-malonylglycoside), rutin, isoquercetin, astragalin, and moracetin derivatives and other glycosides. Flavonoids such as rutin and quercetin in the mulberry tree have potential biological activities including antioxidant, anti-inflammatory, and neuroprotective effects.
A particularly notable flavonoid is morusin, a prenylated flavone. One of the most important compounds found in the bark of white mulberry is morusin, a prenylated flavone with interesting pro-health properties; research has revealed that morusin has antioxidant, antitumor, anti-inflammatory, and anti-allergic activity, with neuroprotective and antihyperglycemic properties also confirmed.
Alkaloids / Iminosugars
Deoxynojirimycin (DNJ), the first isolated iminosugar, is a natural alkaloid acting as a potent inhibitor of α-glucosidase with high nutritional value; it naturally occurs in plants (especially Morus spp.), microbes, and insects, or can be synthesized. The leaves of Morus alba are known to contain a diverse array of bioactive constituents, including flavonoids, alkaloids, and imino sugars, including compounds like 2-O-α-D-galactopyranosyl deoxynojirimycin, fagomine, and DNJ (1-deoxynojirimycin). Mulberry leaves are rich in amino group-containing sugar analogs, termed iminosugars.
1-deoxynojirimycin (DNJ), fagomine (FA), and N-methyl-1-deoxynojirimycin are the primary active ingredients of the root bark fraction and target carbohydrate metabolism, regulating alpha-glucosidase activity to produce a potent anti-diabetic effect.
Stilbenoids and Phenolic Compounds
Phenolic compounds like resveratrol and oxyresveratrol are produced via the phenylpropanoid pathway using phenylalanine as a precursor. Among them, the stilbenes oxyresveratrol and resveratrol were reported present in the Morus plants and demonstrated antioxidant activity.
Oxyresveratrol is a particularly important stilbene. Oxyresveratrol (OXY) is one of the natural resorcinol-type polyphenols obtained from mulberry twigs with anti-melanogenesis effects. Oxyresveratrol inhibited nitrogen oxide (NO) production, inducible NO synthase (iNOS) expression, prostaglandin E2 (PGE2) production, and activation of nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) in macrophages.
Mulberroside A, a glycosylated stilbene, is also significant. Mulberroside A (MsA), a glycosylated stilbene from Morus alba L., has garnered attention for its antioxidative, anti-inflammatory, and neuroprotective capacities across disease models.
M. alba leaves contain various bioactive phenolic compounds, in particular chlorogenic acid (CGA), which is a major bioactive ingredient. The presence of numerous phenolic acids (chlorogenic acid, caffeic acid, hydroxybenzoic acid, and ferulic acid) was determined in mulberry leaves and fruits.
Anthocyanins (Fruit)
Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. Phenolic compounds are prominent among the biologically active ingredients in mulberry, especially flavonoids, anthocyanins, and phenolic acids.
Kuwanon-Type Compounds
From different parts of Morus alba, constituents such as prenylated flavonoid (moralbanone), stilbene glucoside (oxyresveratrol 3′-O-beta-glucopyranoside), mulberroside A, cis-mulberroside A, oxyresveratrol, kuwanon A, B, C, E, G, J, R, S, and T, mulberroside C, and cyclomorus have been successfully isolated.
4. Mechanisms of Action
Alpha-Glucosidase Inhibition (Glycemic Control)
White mulberry (Morus alba L.) leaf extracts have been widely investigated for their content of 1-deoxynojirimycin (DNJ), an iminosugar that competitively inhibits intestinal α-glucosidases and attenuates postprandial glucose rises following carbohydrate ingestion. Mulberry extracts can reduce postprandial blood glucose (PPG) and insulin (PPI) responses by slowing rates of glucose uptake following carbohydrate-rich meals; the presumed mechanism is the inhibition of intestinal alpha-glucosidase, mainly attributed to 1-deoxynojirimycin (DNJ) in the extracts.
Insulin Signaling Pathway Activation
Animal model research (not human clinical evidence) indicates further mechanisms beyond simple enzyme inhibition. MLE and 1-DNJ positively raised the protein expression related to glucose uptake and increased the translocation of glucose transporter type 4 (GLUT4) to the membrane; furthermore, MLE and 1-DNJ activated the IRS-1/PI3K/Akt pathway in the skeletal muscle and subsequently modulated the protein levels of glycogen synthase kinase-3beta (GSK-3β) and glycogen synthase (GS), leading to elevated muscle glycogen content.
Network pharmacology analysis revealed that morusin, kuwanon C, and morusyunnansin L are the main active compounds of the mulberry leaf flavonoid fraction and that they amend insulin resistance and glycemia via the PI3K-Akt signaling pathway, lipid and atherosclerosis pathways, and the AGE-RAGE signaling pathway.
Anti-Inflammatory Mechanisms
Oxyresveratrol inhibited nitrogen oxide (NO) production, inducible NO synthase (iNOS) expression, prostaglandin E2 (PGE2) production, and activation of NFκB in macrophages. The root bark was found to inhibit bronchitis-like symptoms, determined by TNF-α production, inflammatory cell infiltration, and histological observation; several flavonoid components (kuwanone E, kuwanone G, and norartocarpanone) also inhibited IL-6 in lung epithelial cells and nitric oxide production in lung macrophages.
Lipid Metabolism
Research in animal models demonstrated that low-density lipoprotein receptor (LDLR) gene expression and the uptake ability of LDL in HepG2 cells were upregulated by addition of mulberry water extracts; mulberry water extracts also decreased the gene expressions of enzymes involved in triglyceride and total cholesterol biosyntheses, suggesting that hypolipidemic effects are via an enhancement of LDLR gene expression, clearance ability of LDL, and a decrease in lipid biosynthesis.
Neuroprotective Mechanisms
The polyphenols and alkaloids present in mulberry leaves enhance cognition and slow down the process of neurodegeneration; substances extracted from mulberry leaves can be employed in neurogenesis for neurodegenerative diseases including Alzheimer's disease, as they prevent the aggregation of amyloid β-peptide (91–42) and reduce neurotoxic effects attributable to amyloid β-peptide (1–42).
In vivo studies on mulberroside A showed it significantly ameliorated cognitive deficits and neuronal loss, concurrently enhancing cholinergic neurotransmission through increased acetylcholine levels and inhibited acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) activities; it also upregulated neurotrophic factors (BDNF, CREB) in critical brain regions.
Skin Depigmentation (Tyrosinase Inhibition)
DPPH radical scavenging and tyrosinase inhibition assays showed that oxyresveratrol (OXY) exhibited potent antioxidant and tyrosinase inhibitory activities; in human melanocytes, OXY significantly down-regulated protein expression related to melanin synthesis and transport. Out of the three stilbenoids tested, oxyresveratrol was found to exhibit the highest anti-melanogenesis effect and mulberroside A the lowest; it was suggested that the compounds extracted from M. alba have the potential to be used as a skin whitening agent as they successfully reduced pigmentation.
5. Scientific Evidence by Area of Use
5.1 Glycemic Control and Diabetes
This is the most extensively studied clinical application of Morus alba. M. alba leaves and their constituents, particularly iminosugars (or azasugars), have garnered attention for their ability to maintain normal blood glucose concentrations, an effect identified in both animal studies and human clinical trials.
Key clinical study (2014, PMC4014974): A randomized, double-blind, crossover trial assessed the effects of single ingestion of mulberry leaf extract (3, 6, or 9 mg DNJ) or placebo on blood glucose and insulin concentrations during 2 h after a carbohydrate (200 g boiled white rice) challenge in 12 subjects with fasting plasma glucose in the range of 100–140 mg/dL; a subsequent study 2 was a randomized, double-blind, placebo-controlled trial assessing the efficacy of 12-week extract supplementation (6 mg DNJ, three times daily) for long-term glycemic control in 76 subjects with fasting plasma glucose in the range of 110–140 mg/dL.
Bioequivalence trial (2025): Healthy adults (n = 84) participated in a balanced-order, double-blind, placebo-controlled study assessing postprandial blood glucose and postprandial insulin following the addition of mulberry fruit extract (0.75 g, containing 2.90 mg DNJ), pure DNJ (2.90 mg), or placebo to a rice meal; although DNJ is largely responsible for the effect, other components of the mulberry fruit extract, particularly 2-O-alpha-D-galactopyranosyl-deoxynojirimycin as a precursor of DNJ, may contribute to its observed efficacy for reducing postprandial blood glucose and postprandial insulin.
Systematic review and meta-analysis (2022): A systematic review of RCTs published up to May 2025 comparing mulberry extract to placebo or standard care in adults with metabolic disorders included 15 trials with 1,202 participants; the primary outcomes were fasting glucose, fasting insulin, liver enzyme levels, lipid profiles, and inflammatory markers; the pooled results indicated that mulberry supplementation improved blood sugar control and lowered total cholesterol, LDL, triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and inflammatory markers.
Overweight adults (2026): This mechanism helps blunt postprandial glycaemic peaks with favorable gastrointestinal tolerability; standardized aqueous MLE extracts have shown acute glycaemic benefits in both healthy and dysglycaemic individuals; preliminary evidence suggests broader metabolic actions that may extend beyond acute postprandial glucose attenuation.
Evidence strength: The alpha-glucosidase inhibitory effect on postprandial glucose is supported by multiple randomized controlled trials and a meta-analysis, representing moderate-to-good clinical evidence for acute postprandial glycemic attenuation. Evidence for long-term glycemic outcomes (HbA1c, fasting glucose) remains more limited and requires further large-scale trials. DNJ has not been approved as a food supplement as of the current literature.
5.2 Lipid Regulation (Dyslipidemia)
Clinical studies showed that mulberry leaf plays an important role in the treatment of metabolic diseases including dyslipidemia, alongside diabetes, obesity, atherosclerosis, and hypertension.
Small clinical study: In a small study of people with type 2 diabetes, white mulberry leaf, 1 gram taken 3 times daily for 4 weeks, reduced total cholesterol by 12%, LDL ("bad") cholesterol by 23%, and increased HDL ("good") cholesterol by 18%. This trial was small and should be interpreted cautiously.
Crossover trial in obese adults with metabolic risk: CMD (concentrated mulberry drink) consumption significantly reduced systolic and diastolic blood pressure and mean arterial pressure compared to baseline and placebo periods; while total cholesterol, LDL-C, and HDL-C remained unchanged, triglycerides were significantly lower during CMD consumption compared to placebo periods.
The meta-analysis cited above (pooled results from 15 trials, 1,202 participants) also indicated significant reductions in total cholesterol, LDL, and triglycerides. Animal data additionally support a mechanism of LDLR upregulation and reduced lipid biosynthesis, but these findings come from preclinical models.
Evidence strength: Preliminary to moderate. Human data exist but studies are heterogeneous in terms of formulation, dose, and population. Larger, well-controlled trials are needed to confirm lipid-lowering effects as a standalone indication.
5.3 Cardiovascular Effects
Morus alba L. is a traditional Chinese medicine known for its use in treating cardiovascular diseases and diabetes, exhibiting cardioprotective effects by inhibiting mechanisms of cardiomyopathy and alleviating hypertrophy, inflammation, and apoptosis in the heart. A randomized crossover trial reported that mulberry drink significantly reduced systolic and diastolic blood pressure and mean arterial pressure compared to baseline and placebo periods. C-reactive protein levels were also significantly lower during mulberry consumption compared to placebo periods.
Evidence strength: Preclinical evidence is substantial. Human clinical evidence for cardiovascular endpoints (blood pressure, CRP) is limited to small trials and requires replication.
5.4 Neuroprotection and Cognitive Function
Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. Phenolic compounds, anthocyanins, and flavonoids were identified to have neuroprotective properties; the polyphenols and alkaloids present in mulberry leaves enhance cognition and also slow down the process of neurodegeneration.
The stilbenoid mulberroside A has been studied for Alzheimer's disease in preclinical models. Natural bioactive compounds from Morus alba demonstrate diverse biological activities, significant efficacy, and low toxicity in preclinical studies; mulberroside A (MsA), a glycosylated stilbene from Morus alba L., has garnered attention for its antioxidative, anti-inflammatory, and neuroprotective capacities across disease models.
Evidence strength: Largely preclinical (in vitro and animal models). Human clinical trials specifically for cognitive endpoints are very limited. This is a promising but unconfirmed area of application.
5.5 Anti-Inflammatory Activity
M. alba, the most extensively studied species, has been reported to have anti-hyperlipidemic, anti-hypertensive, anti-hyperglycemic, anti-microbial, anti-allergic, anti-inflammatory, hepatoprotective, neuroprotective, immuno-modulatory, and anti-venom activities. The mechanisms by which oxyresveratrol suppresses inflammation at the molecular level have been characterized in in vitro systems, primarily via inhibition of NF-κB, iNOS, and COX-2 pathways, but robust human clinical anti-inflammatory trials are lacking.
Evidence strength: Well-characterized preclinical mechanisms; human clinical data on inflammation as a primary endpoint are sparse.
5.6 Antioxidant Activity
Phenolic compounds are prominent among the biologically active ingredients in mulberry, especially flavonoids, anthocyanins, and phenolic acids; epidemiologic studies suggest that mulberry contains a rich, effective chemical composition and a wide range of biological activity, including antioxidant and anti-inflammatory effects. Antioxidant activity is consistently demonstrated in in vitro assays across multiple mulberry extracts and isolated compounds. Reduced C-reactive protein in a human crossover trial provides indirect clinical support for in vivo anti-inflammatory/antioxidant activity.
Evidence strength: Strong in vitro; limited direct human clinical evidence for antioxidant endpoints per se.
5.7 Skin Depigmentation (Cosmetic and Topical Use)
The root bark of mulberry, containing flavonoids, alkaloids, and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Oxyresveratrol and mulberroside A are the primary compounds of interest for skin applications. As a traditional whitening agent, the skin benefits of various parts of mulberry extracts have been confirmed by multiple studies.
Evidence strength: In vitro evidence (cell culture with human melanocytes) is well-established for tyrosinase inhibition. Robust randomized controlled trials in human subjects for skin depigmentation are limited; most evidence supporting cosmetic use derives from preclinical models.
5.8 Antimicrobial Activity
The root bark, containing flavonoids, alkaloids, and stilbenoids, has demonstrated antimicrobial properties. Six compounds (five prenylated compounds and one simple phenol ester) have been found to suppress the replication of herpes simplex virus 1 (HSV1) and herpes simplex virus 2 (HSV2), with IC50 values ranging from 0.64 to 1.93 g/mL. One study found that Morus alba leaf water-ethanol extracts had an antiviral effect that was superior against enveloped human coronavirus than non-enveloped picornavirus, which was suggested to be due to the interaction of the constituents with the binding capacity of ligands on the envelope.
Evidence strength: Predominantly in vitro. No human clinical trials have been conducted for antimicrobial indications specifically.
5.9 Anti-Obesity Effects
With flavonoids as major constituents, mulberry leaves possess various biological activities including anti-obesity effects. Diverse biological activities, such as antihyperglycemic, lipid-lowering, antitumor, antiviral, and anti-inflammatory, have been recognized for DNJ. Evidence on body composition in human trials is preliminary; the crossover trial in obese adults found no significant changes in body composition despite improvements in blood pressure and triglycerides.
Evidence strength: Mostly preclinical. Human data on weight or fat mass reduction are weak.
5.10 Oral Mucositis (Cancer Supportive Care)
A systematic review evaluated the efficacy and safety of different black mulberry formulations in chemotherapy- and/or radiotherapy-induced oral mucositis; a systematic search was performed in PubMed, Embase, the Cochrane Library, and Web of Science; out of 30 articles retrieved, four articles with a cumulative sample size of N = 297 were included; mulberry formulations were compared with no intervention, grape molasses, chlorhexidine, and sodium bicarbonate; the reviewed studies included randomized controlled clinical trials, non-randomized controlled trials, and analytical cohort studies.
Evidence strength: Limited; only four small studies met inclusion criteria for the systematic review. Results are insufficient to draw definitive conclusions for clinical guidance.
6. Body Systems and Health Areas Associated with Morus
- Endocrine / Metabolic System: Glycemic control, insulin sensitivity, adiposity, obesity
- Cardiovascular System: Lipid profiles, blood pressure, atherosclerosis prevention, platelet aggregation inhibition
- Neurological System: Cognitive enhancement, neuroprotection, Alzheimer's disease models
- Respiratory System: Antitussive, expectorant, anti-asthmatic uses (traditional; root bark)
- Integumentary System: Skin whitening/depigmentation, anti-melanogenesis
- Hepatic System: Hepatoprotective effects (primarily preclinical)
- Immune System: Immunomodulatory, anti-inflammatory, antiviral activities
- Musculoskeletal System: Anti-rheumatic (traditional use; twigs)
7. Dosage Forms and Reported Dosages from Studies
Dosages used in clinical research vary considerably by preparation type, standardization, and indication. The following dosages are reported as stated in cited sources and should not be taken as recommendations:
- In a randomized, double-blind crossover trial, single ingestion of mulberry leaf extract at 3, 6, or 9 mg DNJ was compared to placebo for postprandial glucose and insulin response over 2 hours in 12 subjects with impaired fasting glucose.
- A 12-week supplementation regimen using 6 mg DNJ three times daily (t.i.d.) was used in a randomized, double-blind, placebo-controlled trial assessing long-term glycemic control in 76 subjects with fasting plasma glucose in the range of 110–140 mg/dL.
- A double-blind, placebo-controlled study used a dose of 0.75 g mulberry fruit extract (containing 2.90 mg DNJ) added to a rice meal.
- In a small study of people with type 2 diabetes, white mulberry leaf was administered at 1 gram taken 3 times daily for 4 weeks for lipid-lowering effects.
- Reducose®, a commercial standardized extract, is standardized to 5% 1-deoxynojirimycin (DNJ).
- White mulberry leaf has been used in studies lasting up to 12 weeks without serious harmful effects.
No universally established or regulatory-approved dosage range exists for Morus alba as a dietary supplement at the international level. Study protocols have employed different extract types, standardization levels, and formulations, making cross-study dose comparisons difficult.
8. Safety, Adverse Effects, and Drug Interactions
General Safety Profile
White mulberry leaf has been used in studies lasting up to 12 weeks without serious harmful effects; the most common side effect is digestive upset, including bloating, constipation, gas, and loose stools.
Hypoglycemia Risk
Given its established alpha-glucosidase inhibitory mechanism, co-administration with antidiabetic medications presents a documented pharmacodynamic interaction risk. NCCIH notes a potential low blood sugar risk when white mulberry leaf is taken with diabetes medications. The additive effect of mulberry leaf extract with insulin secretagogues or other glucose-lowering agents could theoretically produce hypoglycemia, particularly in susceptible individuals.
Herb–Drug Interactions via Drug-Metabolizing Enzymes
A dedicated in vitro investigation in HepG2 liver cells characterized potential metabolic interactions. When tested alone, M. alba significantly upregulated the expression of CYP1A2 and UDP-glucuronosyltransferase 1A6 (UGT1A6); co-treatment of HepG2 cells with acetaminophen, aspirin, simvastatin, or caffeine, and MA resulted in upregulation of CYP1A2 and N-acetyltransferase 1 expression and downregulation of ATP-binding cassette B1. Consequently, M. alba is recommended to be taken at a low dosage due to the feasibility of herb–drug interactions arising from concomitant use with acetaminophen, aspirin, simvastatin, or caffeine. These data are derived from an in vitro cell model; clinical significance in humans remains to be determined by pharmacokinetic studies.
Quality of Bias in Existing Clinical Trials
The risk of bias in included studies in a recent meta-analysis was evaluated using the Cochrane Risk of Bias 2.0 tool; of the thirteen studies assessed, five were rated as having a low overall risk of bias, five were classified as having some concerns, and three were judged to be at high risk. This unevenness in study quality limits the certainty of pooled estimates.
Limitations of Safety Data
Most safety data pertain to short-term use (up to 12 weeks). Long-term safety data in humans are not available from the current literature. Compared with other berries, there has been a lack of systematic research on mulberry, and this hinders its further expansion as a functional fruit. Safety in pregnancy, lactation, pediatric populations, and individuals with severe hepatic or renal impairment has not been established in clinical trials.
References
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