Moranoline

Other Names

(2R,3R,4R,5S)-2-(Hydroxymethyl)-3,4,5-piperidinetriol(2R,3R,4R,5S)-2-(Hydroxymethyl)piperidine-3,4,5-triol(2R,3R,4R,5S)-2-Hydroxymethyl-3,4,5-trihydroxypiperidine(2R,3R,4R,5S)-2-methylolpiperidine-3,4,5-triol1,5-Dideoxy-1,5-imino-D-glucitol1,5-imino-1,5-dideoxy-D-glucitol1-deoxy-nojirimycin1-Deoxynojirimicin1-Deoxynojirimycin1-DNJ1-dNM3,4,5-Piperidinetriol, 2-(hydroxymethyl)-, (2R,3R,4R,5S)-5-Amino-1,5-dideoxy-D-glucopyranoseBAY-h-5595BAY-n-5595D-1-DeoxynojirimycinD-5-Amino-1,5-dideoxyglucopyranoseDeoxynojirimycinDesoxynojirimycinDNJDNMDuvoglustatMoranolinnojirimycin, deoxy-S-GI[2R-(2a,3b,4a,5b)]-2-(Hydroxymethyl)-3,4,5-piperidinetriol

Synopsis

Moranoline (1-Deoxynojirimycin): A Comprehensive Reference

1. Identity and Chemical Characterisation

Moranoline is the botanical name assigned to the compound now most widely known in the scientific literature as 1-deoxynojirimycin (abbreviated DNJ or 1-DNJ). Also known as moranoline or duvoglustat, DNJ has a molecular formula of C₆H₁₃NO₄ and a molecular weight of 163 g/mol. The IUPAC name of DNJ is (2R,3R,4R,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol.

DNJ is a polyhydroxylated piperidine alkaloid azasugar or iminosugar commonly found in the leaves of Morus (mulberry) species, notably Morus alba. The chemical structure of DNJ resembles that of glucose except that the oxygen atom of the pyranose ring in glucose is replaced with an imino group (−NH−). The pyranose ring has a hydroxymethyl (−CH₂OH) moiety and three hydroxyl (−OH) groups.

DNJ belongs to the class of iminosugars, naturally occurring compounds that differ from carbohydrates because of the presence of a basic nitrogen atom in lieu of the endocyclic oxygen one; they act as inhibitors of α-glucosidase, β-glucosidase, and glucosylceramide synthase.

The name "moranoline" was coined by Japanese researchers. An unidentified piperidine alkaloid named moranoline was isolated from Mori Cortex and intact Morus species. The structure of moranoline was determined as (2R,3R,4R,5S)-2-hydroxymethyl-3,4,5-trihydroxypiperidine on the basis of its spectral data. The compound is also referred to by the pharmaceutical synonym duvoglustat (and its hydrochloride salt form, AT2220). Deoxynojirimycin (DNJ, moranoline) is one of the prospective active pharmaceutical ingredients due to its excellent biological activities. Sometimes it is also referred to as duvoglustat and/or duvoglustat HCl (AT2220).

1.1 Natural Sources

1-Deoxynojirimycin is a biologically active natural compound that exists in mulberry leaves and Commelina communis (dayflower) as well as from several bacterial strains such as Bacillus and Streptomyces species.

Originally, reduction of nojirimycin led to the chemical synthesis of DNJ; afterward, DNJ was found from natural sources, i.e., mulberry tree root and Bacillus species. This iminosugar has been reported in multiple tissues of M. alba, including leaves, seeds, and root bark.

The white mulberry (Morus alba L., family Moraceae) is the overwhelmingly dominant botanical source in both research and commercial use. DNJ is a widely used functional food constituent in China, Japan, Korea, Thailand and many other Asian countries. The DNJ content of mulberry leaves from 132 varieties of nine Morus species has been determined. The degree of maturity of the mulberry leaves affected the DNJ content significantly. The younger leaves contained higher DNJ concentrations than did the older leaves. DNJ concentrations in mature leaves varied among these 132 mulberry varieties from 0.1341 to 1.472 mg/g of dry leaves.

DNJ constitutes only approximately 0.11% (w/w) of mulberry leaf. Because of this low natural abundance, microbial fermentation has been investigated as an alternative production route. Although it can be obtained in small quantities by brewing an herbal tea from mulberry leaves, interest in commercial production has led to research on developing mulberry tea higher in DNJ, and on alternate routes of production, such as via Bacillus species.

DNJ also accumulates in the silkworm (Bombyx mori) as a consequence of the insect feeding on mulberry leaves. Polyhydroxylated alkaloids have been isolated from mulberry trees (Morus alba L.) and silkworms (Bombyx mori L.).

1.2 Common Forms and Preparations

White mulberry leaves are a source of 1-deoxynojirimycin (DNJ), which, due to its ability to inhibit α-glucosidase, can be used to regulate postprandial glucose concentration. In addition to consuming dried white mulberry leaves as herbal tea, many functional foods also contain this raw material.

Currently, mulberry leaves are processed as dry teas and commercially available as functional foods in China, Japan, Korea, Thailand and many other Asian countries. In research and clinical settings, moranoline is typically delivered as a standardised mulberry leaf extract in capsule or powder form, quantified by DNJ content. A proprietary extract known as Reducose® is a commercially available Morus alba leaf extract standardised to 5% 1-deoxynojirimycin. Reducose® is a proprietary Morus alba (white mulberry) leaf extract standardised to 5% 1-deoxynojirimycin.

Mulberry leaf products used in studies have included leaf powder mixed directly into food or beverages, aqueous extracts delivered in gelatin capsules, and highly purified DNJ isolate for pharmacological comparison. Microbially fermented DNJ preparations derived from Bacillus culture supernatants have also been studied as a source of moranoline.

2. Traditional and Historical Use

2.1 Traditional Chinese Medicine

White mulberry (Morus alba L.) is a plant that has been used in traditional Chinese medicine for thousands of years due to its many beneficial biological properties. All parts of Morus are used as TCM, including leaves (Sangye), twigs (Sangzhi), root barks (Sangbaipi), and fruits (Sangshen). All of the medicinal parts are recorded in the Chinese Pharmacopoeia 2010.

The formal documentation of mulberry leaf as medicine goes back to the Shennong Ben Cao Jing, or the Divine Farmer's Classic of Materia Medica. Compiled around 200 AD, this text catalogued hundreds of medicinal substances — and mulberry leaf, known as Sang Ye (桑葉), earned its place among them. According to the classical TCM framework, Sang Ye was used primarily for three purposes: cooling the lungs, clearing heat from the liver, and treating coughs and respiratory irritation.

In traditional Chinese medicine (TCM), the leaves are predominantly used to treat respiratory or metabolic complaints. In TCM, they are known as Sang Yè and are primarily associated with the lung and liver meridians. Sang Ye has been recorded in Chinese medical texts for over two thousand years and appears in classical formulas such as Sang Ju Yin, traditionally used to address wind-heat affecting the lungs. Historically, it has been valued for its ability to clear heat while gently moistening dryness, making it especially useful for respiratory patterns.

The root bark (Sang Bai Pi, Mori Cortex) has its own classical indications in TCM. Indications and properties of Mori Cortex as a traditional Chinese medicine include purging lungs to relieve dyspnea, inducing diuresis to alleviate edema; it is indicated for treating cough and dyspnea due to lung heat, face edema, and dysuria; and for decreasing blood pressure, relieving dyspnoea, calming and easing pain, anti-inflammation, anti-bacteria, and lowering blood sugar.

2.2 Silk Industry and Its Ethnobotanical Significance

Mulberry (Morus alba L. and other plants of the genus Morus) has traditionally been cultivated in China, Korea, and Japan to use its leaves to feed silkworms (Bombyx mori L.) or as Chinese herbal tea based on folklore. Mulberry (Morus alba L.), a perennial shrub belonging to the family Moraceae, represents an extremely important economic plant given that its foliage is used in sericulture as the sole diet for the monophagous silkworm (Bombyx mori). This sericulture context is historically significant: mulberry cultivation drove one of the most important trade networks in human history (the Silk Road), and the deep ethnobotanical familiarity with the plant supported its concurrent use in medicine.

The traditional preparation for dietary or medicinal use was typically as a tea or decoction of dried leaves. Mulberry (Morus alba L.) leaves have been used in traditional Chinese medicines for several centuries and have effects on diabetes therapy and its complications. It is important to note that the traditional Chinese use of Sang Ye was principally for lung and liver heat, not explicitly as an anti-diabetic agent as modern science frames it; the systematic evaluation of moranoline as the active anti-hyperglycaemic constituent within the leaf is a product of twentieth-century analytical chemistry.

3. Key Constituents and Active Compounds

While the mulberry leaf contains numerous bioactive constituents — white mulberry leaves contain various beneficial components to health such as flavonoids, alkaloids, phenolics, amino acids, and polysaccharides — moranoline (DNJ) is specifically the alkaloid most extensively studied for its glycaemic properties.

The active constituents of mulberry leaves are flavonoids, alkaloids, steroids, and coumarins. Among these constituents, the antihyperglycemic effect is attributed mainly to alkaloids whose main compound is 1-Deoxynojirimycin (DNJ).

In addition to DNJ itself, mulberry extracts contain related iminosugars. Although DNJ is largely responsible for postprandial glucose reduction, other components of mulberry fruit extract, particularly 2-O-alpha-D-galactopyranosyl-deoxynojirimycin (GAL-DNJ) as a precursor of DNJ, may contribute to its observed efficacy for reducing postprandial blood glucose and insulin. Mulberry extracts contain relevant concentrations of iminosugars, particularly 1-deoxynojirimycin (DNJ) and also 2-O-alpha-D-galactopyranosyl-deoxynojirimycin (GAL-DNJ), which are known as α-glucosidase inhibitors.

Research has also shown that flavonoid constituents of mulberry leaves may act synergistically with DNJ. The addition of flavonoid components (5,6,7-trihydroxyflavone sapogenins) to 1-DNJ-containing diets can have a synergistic effect by increasing the inhibition of α-glucosidase by 1-DNJ, probably due to the fact that flavonoid sapogenins can act as an inhibitor that can bind to the non-competitive position of maltosidase-glucoamylase, allowing 1-DNJ to interact with α-glucoamylase.

4. Mechanisms of Action

4.1 Intestinal α-Glucosidase Inhibition

The most thoroughly characterised mechanism of moranoline is competitive inhibition of intestinal α-glucosidases. DNJ is a competitive inhibitor of α-glucosidase, inhibiting the digestion and glucose absorption of disaccharides and thereby lowering blood glucose levels. DNJ is a potent α-glucosidase inhibitor with strong affinity toward α-glucosidase. DNJ can competitively inhibit the binding of maltose, sucrose and other disaccharides to α-glucosidase and prevent the breakdown of disaccharides to form glucose. Thus, these disaccharides cannot be digested and absorbed and are passed into the large intestine and eventually excreted into faeces. DNJ reduces glucose absorption and lowers blood sugar levels.

These findings align with DNJ's role as an inhibitor of α-glucosidase and sucrase, delaying carbohydrate digestion and glucose absorption in the small intestine. Among iminosugars, DNJ is one of the most potent α-glucosidase inhibitors, exhibiting stronger inhibition of sucrase and maltase enzymes compared to synthetic analogs like miglitol and voglibose (noting that this characterisation derives from in vitro comparative studies).

DNJ shows α- and β-glucosidase inhibition, as well as α-amylase inhibition.

4.2 Insulin Signalling and Peripheral Insulin Sensitivity

Beyond its gut lumen action, evidence from animal studies indicates that DNJ can improve insulin sensitivity through activation of intracellular signalling pathways. GLUT4 translocation and phosphorylation of Ser473-AKT, p85-PI3K, Tyr1361-IR-β and Tyr612-IRS1 were significantly increased by DNJ treatment. These results indicate that DNJ significantly improved insulin sensitivity via activating insulin signalling PI3K/AKT pathway in skeletal muscle of db/db mice. These findings are from animal experiments and have not yet been confirmed in controlled human trials.

4.3 Anti-Obesity and Lipid-Lowering Mechanisms

Studies using Bacillus subtilis-based DNJ examined its influence on hepatic lipid metabolism and mitochondrial status of model mice fed a fat-rich diet for twelve weeks. By week 12, mice receiving DNJ in addition to the fat-rich diet did not show weight gain, unlike the high-fat group. The hepatic C/EBPα and CD36 mRNA of the high-fat group was highly expressed, whereas the DNJ group showed higher expression of hepatic p-AMPK/AMPK and PGC-1β mRNA. These results give explanation for the proposed use of DNJ as a dietary supplement to avoid obesity and its consequences. Again, these data are from animal (murine) models.

4.4 Antiviral Mechanism via Endoplasmic Reticulum α-Glucosidase Inhibition

Moranoline and particularly its N-alkyl derivatives exert antiviral activity through a distinct mechanism operating in the endoplasmic reticulum (ER). The antiviral effects were associated with the inhibitory action of DNJ-containing iminosugar derivatives on enzymes in the endoplasmic reticulum (ER), α-glucosidases I and II. DNJ, a ring-nitrogen-containing and unmetabolizable glucose analogue, competitively binds to these enzymes and prevents them from performing the stepwise removal of three glucose residues attached to the N-linked glycans carried by newly synthesized polypeptides. This in turn prevents these polypeptides from interacting with the ER chaperones calnexin and calreticulin, which bind to monoglucosylated glycoproteins.

Mechanistically, iminosugars act as competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of protein folding than most host glycoproteins. Therefore, extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents.

4.5 Anti-Inflammatory Mechanism

DNJ has been shown in animal studies to modulate inflammatory cytokine production. To explore the effects of DNJ on inflammation, ELISA experiments analysed hepatic tumour necrosis factor α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) levels in the liver tissue of db/db mice. The hepatic TNF-α, IL-1, and IL-6 content of db/db groups were significantly higher than those of the normal control group. However, DNJ treatment notably decreased the levels of TNF-α, IL-1, and IL-6 in liver tissue in a dose-dependent manner.

In the cardiovascular context, DNJ, which is a unique polyhydroxy alkaloid, is the main active component in mulberry (Morus indica L.) leaves and may exhibit protective properties in the prevention of stable angina pectoris (SAP) in patients with coronary heart disease (CHD) by affecting the NF-κB pathway.

5. Scientific Evidence by Health Area

5.1 Glycaemic Control and Diabetes

5.1.1 Postprandial Blood Glucose — Human Evidence

The most robustly supported human use for moranoline is reduction of postprandial blood glucose (PPG). A 2024 systematic review and meta-analysis examined this evidence base. This meta-analysis investigated the effects of 1-Deoxynojirimycin (DNJ), derived from mulberry leaves, on glycaemic control in individuals with impaired glucose tolerance and type 2 diabetes. DNJ significantly reduced postprandial plasma glucose (PPG) at 30 min, postprandial plasma insulin (PPI) at 30 min, and both glucose and insulin incremental area under the curve (iAUC) at 120 min, with substantial heterogeneity across studies. However, the effects were short-lived, indicating DNJ's limited prolonged efficacy due to low bioavailability and rapid clearance.

A pivotal randomised, double-blind, dose-finding study followed by a long-term randomised controlled trial established key human clinical findings. The aims of the study were to examine the optimal dose of 1-deoxynojirimycin (DNJ) in mulberry leaves and to determine the efficacy and safety of mulberry leaves in glycaemic control in obese persons with borderline diabetes. First, healthy adults were recruited into the dose-finding study and randomly allocated to ingest sucrose solution concurrently with mulberry leaf powder at weights equivalent to 0 (control), 6, 12, and 18 mg of DNJ. Twelve mg of mulberry DNJ was the minimum effective dose attenuating postprandial hyperglycaemia. Mulberry leaves decreased fasting plasma glucose (FPG) by 3.86 ± 5.99 mg/dL (p = 0.002) and glycated haemoglobin (HbA1c) by 0.11 ± 0.22% (p = 0.011) when compared with the baseline levels. Improvement in glucose tolerance was not observed. Furthermore, mulberry leaves tended to ameliorate insulin resistance (p = 0.057).

A separate randomised, double-blind, crossover trial by Asai et al. assessed single and long-term administration of standardised mulberry leaf extract. In study 1, a randomised, 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 (FPG) in the range of 100–140 mg/dL. Study 2 was a randomised, double-blind, placebo-controlled trial to assess the efficacy of 12-week extract supplementation (6 mg DNJ, three times daily) for long-term glycaemic control in 76 subjects with FPG in the range of 110–140 mg/dL. The long-term study found that FPG and insulin concentrations were not significantly changed over the study period in both groups. HbA1c and glycated albumin concentrations were reduced during the study period in both groups; however, there were no significant differences at any time-point between the groups. This trial did not demonstrate superiority of the extract over placebo for long-term markers, highlighting limitations of existing evidence.

A 2025 randomised, double-blind, placebo-controlled study using mulberry fruit extract (MFE) tested bioequivalence between the extract and isolated DNJ. Healthy adults (n = 84) participated in a balanced-order, double-blind, placebo-controlled study assessing PPG and PPI following the addition of MFE (0.75 g, containing 2.90 mg DNJ), pure DNJ (2.90 mg) or placebo to a rice meal. This study confirmed the bioequivalence of DNJ and MFE for reducing PPG responses in humans. Although DNJ is largely responsible for this effect, other components of MFE, particularly 2-O-alpha-D-galactopyranosyl-deoxynojirimycin as a precursor of DNJ, may contribute to its observed efficacy for reducing PPG and PPI.

A previous randomised controlled clinical study of mulberry DNJ revealed that 12 mg of mulberry DNJ was an optimal dose to reduce postprandial hyperglycaemia, and there were no side effects.

Evidence strength — postprandial glucose: Multiple human RCTs and a meta-analysis consistently demonstrate statistically significant acute reductions in postprandial glucose and insulin. Evidence for this acute effect is moderately strong. Evidence for long-term HbA1c reduction is weaker and inconsistent across trials, with some studies showing trends but not significant between-group differences vs. placebo.

5.1.2 Long-Term Glycaemic Control — Human Evidence

A previous study demonstrated that mulberry leaf powder with 12 mg of DNJ improves postprandial hyperglycaemia, fasting plasma glucose, and glycated haemoglobin. Moreover, long-term ingestion of mulberry leaves showed a decrease in fasting plasma glucose (FPG). Mulberry leaves supplementation had no effect in persons without diabetes. Mulberry leaves powder enriched with DNJ at the dose of 18 mg/meal did not cause a significant change in FPG among healthy volunteers throughout 38 days of the treatment period.

A 24-week active-controlled clinical trial compared a mulberry twig alkaloid tablet (Sangzhi alkaloid, SZ-A) with acarbose in patients with type 2 diabetes. This clinical trial enrolled 38 patients who were randomised into two groups (SZ-A: 23; acarbose: 15) and were treated for 24 weeks. Patients and clinical trial staffs were masked to treatment assignment throughout the study. The primary outcome measures were glycated haemoglobin (HbA1c) and 1-hour and 2-hour postprandial and fasting plasma glucose levels from baseline to the end of treatment. By the end of this study, HbA1c level in the SZ-A group was decreased from baseline significantly (p < 0.001). No significant difference was found when compared with acarbose group (p = 0.652). Similarly, 1-hour and 2-hour postprandial plasma glucose levels in the SZ-A group were decreased from baseline statistically (p < 0.05), without any significant differences compared with acarbose group. The fasting plasma glucose levels were not significantly changed in both groups. This trial compared a mulberry-derived alkaloid preparation against a pharmaceutical α-glucosidase inhibitor and found comparable glycaemic effects, though it was small and limited to 38 patients.

5.1.3 Pre-clinical (Animal) Evidence

The alpha-glucosidase inhibitor DNJ is one of the simplest naturally occurring carbohydrate mimics, with promising biological activity in vivo. Although there is considerable interest in the pharmacological effects of DNJ, the antidiabetic effects of DNJ in type 2 diabetes mellitus have received limited attention. DNJ was isolated from the silkworm (Bombyx mori), and its antidiabetic effects were evaluated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established animal model of human type 2 diabetes mellitus. DNJ treatment showed significant antidiabetic effects in OLETF rats, with significant improvements in fasting blood glucose levels and glucose tolerance and, especially, increased insulin sensitivity. DNJ also showed significant antihyperglycaemic effects in streptozotocin- and high-fat-diet-induced hyperglycaemic rats. Its efficacy and dose profiles were better than those of acarbose, a typical alpha-glucosidase inhibitor in clinical use.

Preclinical studies on diabetic rodents have demonstrated that DNJ, primarily derived from mulberry root extract, can significantly reduce blood glucose levels, lower HbA1c, and improve insulin sensitivity. These animal studies also indicate that DNJ's inhibition of α-glucosidase effectively delays carbohydrate digestion, reducing postprandial blood sugar spikes.

5.2 Blood Lipid Profiles

Human evidence for lipid-lowering effects comes primarily from a single open-label study. An open-label, single-group study was conducted in 10 subjects with initial serum triglyceride (TG) level ≥200 mg/dl. Subjects ingested capsules containing DNJ-rich mulberry leaf extract at 12 mg three times daily before meals for 12 weeks. The findings showed a modest decrease in serum TG level and beneficial changes in the lipoprotein profile following 12-week administration of DNJ-rich mulberry leaf extract. No significant changes in haematological or biochemical parameters were observed during the study period; no adverse events associated with DNJ-rich mulberry leaf extract occurred.

In a separate study, the plasma lipid profile in humans following the administration of mulberry leaf extract revealed that serum triglyceride levels decreased and lipoprotein levels were positively altered.

In animal models, animals treated with mulberry leaves experienced marked reductions in total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) and an increase in high-density lipoprotein cholesterol (HDL-C) in blood circulation. In addition to blood lipid profiles, hepatic lipid accumulation was attenuated by mulberry leaves.

Evidence strength — lipids: Preliminary in humans; a single small open-label study (n = 10) with no placebo control limits conclusions. Animal data are supportive but cannot substitute for adequately powered human RCTs.

5.3 Cardiovascular / Anti-Atherosclerotic Effects

A placebo-controlled, double-blind clinical trial examined the effect of mulberry leaf deoxynojirimycin (MLD) on atherosclerotic lesions. Serum levels of DNJ had a strong negative relationship with IMT (intima-media thickness) values. MLD treatment attenuates atherosclerotic lesions possibly via DNJ. MLD treatment improved antioxidant and anti-inflammatory properties and serum lipid profile in heart disease patients. MLD reduces carotid intima-media thickness (IMT) and serum levels of DNJ (the main ingredient of mulberry leaf) had a strong relationship with IMT values.

A further human clinical study in stable angina pectoris patients reported that oral administration of 10 mg of 1-DNJ daily for 4 weeks in stable angina pectoris (SAP) patients improved coronary outcomes, with the mechanism attributed to effects on the NF-κB inflammatory pathway. Most clinical studies of DNJ are focused on its anti-diabetic and related activities. Other clinical studies of DNJ included its effect on serum triglyceride, starch digestion and absorption, stable angina pectoris, and atherosclerotic lesion.

Evidence strength — cardiovascular: Preliminary human evidence from small trials. The anti-atherosclerotic and angina data are interesting but come from limited, often single-centre studies requiring replication in larger independent trials.

5.4 Body Weight and Anti-Obesity Effects

DNJ treatment showed significant antidiabetic effects in OLETF rats, with significant improvements in fasting blood glucose levels and glucose tolerance and, especially, increased insulin sensitivity. Furthermore, there was significant loss of body weight in both groups. These findings suggest that its postprandial hypoglycaemic effect in the gastrointestinal tract is a possible but insufficient mechanism of action underlying the antidiabetic effects of DNJ. Its anti-obesity effect and improvement of insulin sensitivity are other possible antidiabetic effects of DNJ.

Mulberry leaves also tended to improve insulin resistance. The anti-obesity effects of DNJ in humans have not been demonstrated in dedicated clinical trials. Evidence remains at the pre-clinical stage. Evidence strength — anti-obesity: Preclinical (animal) only. No dedicated human clinical trial has specifically and convincingly demonstrated weight loss with moranoline or DNJ-rich mulberry extract as a primary endpoint.

5.5 Antiviral Activity

The antiviral potential of the DNJ iminosugar scaffold — and particularly its N-alkylated derivatives rather than the free base moranoline — has been investigated across numerous pre-clinical studies. Iminosugar derivatives containing the glucose analogue deoxynojirimycin (DNJ) exert antiviral effects against viruses of different families, including Human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Woodchuck hepatitis virus, Bovine viral diarrhea virus (BVDV), and Dengue virus.

N-Alkyl deoxynojirimycin-derived drugs, belonging to the class of iminosugars, are well-known for their α-glucosidase inhibitory activity. N-Butyl-deoxynojirimycin (N-butyl-DNJ; NB-DNJ; also known as miglustat or UV-1) has been developed for the treatment of type 1 Gaucher disease and Niemann–Pick disease type C as Zavesca®. Furthermore, it behaves as a host-targeted glucomimetic that inhibits endoplasmic reticulum α-glucosidase I and II (GluI and GluII, respectively) enzymes, resulting in improper glycosylation and misfolding of viral glycoproteins; thus, it is a potential antiviral agent.

The iminosugar N-9′-methoxynonyl-1-deoxynojirimycin (MON-DNJ or UV-4) is probably the most studied and potent inhibitor of α-Glu I and α-Glu II in clinical trials. It is often studied in the form of its hydrochloride salt (UV-4B) and has broad-spectrum activity against diverse viruses, including dengue and influenza. In clinical trials, it was found to be safe at all doses tested up to 1000 mg.

DNJ and its derivatives can effectively inhibit infection by HIV, HCV, and other viruses.

Evidence strength — antiviral: The antiviral evidence is predominantly pre-clinical (cell culture, animal models) and pertains specifically to N-alkyl DNJ derivatives rather than to the parent compound moranoline itself. Unmodified DNJ has lower antiviral potency than its alkylated derivatives. No large-scale human clinical trial has established an antiviral indication for moranoline per se.

5.6 Hepatoprotective Effects

Hepatoprotective activity has been demonstrated in diabetic mouse models. DNJ treatment reduced hepatic inflammatory cytokines (TNF-α, IL-1, IL-6) dose-dependently in db/db mice as noted above. DNJ has demonstrated diverse biological activities such as hypoglycaemic, anti-inflammatory, antitumour, antioxidant, antiviral, lipid-lowering, cardioprotective, antimicrobial, and antiobesity activities. These observations are primarily from animal studies and await confirmation in well-designed human trials.

5.7 Neuroprotective and Other Activities

Major pharmacological properties of DNJ from mulberry are anti-diabetic, anti-obesity, cardioprotective, and anti-cancer activities. Other properties of DNJ are hepatoprotective, neuroprotective, antimicrobial, anti-inflammatory, hypolipidaemic, and nephroprotective activities. These properties are principally based on in vitro and animal evidence and have not been established in human clinical trials.

6. Body Systems and Health Areas Associated with Moranoline

Digestive / Carbohydrate Metabolism: Inhibition of intestinal α-glucosidase and sucrase, reducing postprandial glucose excursions. This is the best-evidenced action in humans.
Endocrine / Metabolic: Modulation of insulin secretion (reduced postprandial insulin response), possible improvement of peripheral insulin sensitivity via PI3K/AKT signalling (animal evidence).
Cardiovascular: Preliminary human evidence for lipid-lowering, anti-atherosclerotic effects (carotid IMT reduction), and amelioration of stable angina pectoris; mechanisms proposed to involve NF-κB inhibition and antioxidant activity.
Immune / Antiviral: ER α-glucosidase inhibition disrupting viral glycoprotein maturation; principally relevant to N-alkyl derivatives. Pre-clinical only for unmodified DNJ.
Hepatic: Reduction of hepatic lipid accumulation and inflammatory cytokines in animal models.
Adipose / Body Weight: Anti-obesity effects demonstrated in rodent models; mechanism involves AMPK-mediated lipid oxidation pathways.

7. Dosage Forms and Dosages Reported in Studies

The following dosages are those reported specifically in the cited studies and are not recommendations.

Minimum effective dose for postprandial glucose attenuation: 12 mg of mulberry DNJ was found to be the minimum effective dose.
Optimal dose for postprandial hyperglycaemia reduction: 12 mg of mulberry DNJ administered before meals, with no side effects reported in that trial.
Lipid study dose: Capsules containing DNJ-rich mulberry leaf extract at 12 mg three times daily before meals for 12 weeks.
Alternative lipid study dose: A dose of 3 capsules three times daily before each meal (9 capsules, equivalent to 36 mg of DNJ, per day) for 12 weeks.
Dose-ranging study: Single ingestion of mulberry leaf extract providing 3, 6, or 9 mg DNJ was assessed in a crossover trial; long-term supplementation used 6 mg DNJ three times daily for 12 weeks in 76 subjects.
Postprandial glucose reduction range: Mulberry fruit extract in doses of 0.37–1.5 g (containing approximately 2–8 mg DNJ) reduced PPG and PPI responses to test meals containing approximately 50 g of available carbohydrates.
Angina pectoris study: Oral administration of 10 mg of 1-DNJ daily for 4 weeks in stable angina pectoris patients.
Bioequivalence study dose: MFE (0.75 g, containing 2.90 mg DNJ) or pure DNJ (2.90 mg) added to a rice meal in 84 healthy adults.
Long-term low-dose observation: Daily supplementation with 6 mg/meal of mulberry DNJ for 12 weeks resulted in a significant improvement in 1,5-anhydroglucitol (1,5-AG), a marker of postprandial glycaemia, in participants with impaired glucose metabolism.
Animal study dosing (intravenous, for mechanistic reference): DNJ was shown to decrease glucose and insulin levels in a dose-dependent manner in the range of 20–80 mg·kg⁻¹·day⁻¹ in mouse experiments.

Preparations in human studies have included: standardised mulberry leaf powder mixed into beverages or foods, gelatin capsules containing DNJ-rich mulberry leaf extract, and isolated pure DNJ administered directly.

8. Pharmacokinetics

A substantial fraction of DNJ was absorbed into the bloodstream within a few minutes of oral administration. DNJ was also detected in the urine. The effects of DNJ on postprandial glucose were short-lived, indicating DNJ's limited prolonged efficacy due to low bioavailability and rapid clearance.

To determine its safety, the absorption and excretion of microorganism DNJ were evaluated using ¹⁵N labelling method. The recovery rate of ¹⁵N from DNJ reached 80% up to 48 hours after oral administration, suggesting rapid excretion.

No study has been reported on toxicity of DNJ despite its long-term use. Additional safety assessment on the pharmacokinetics, i.e., absorption, distribution, metabolism, and excretion of DNJ is needed prior to its utilisation as a useful food. This statement, from a 2016 review, reflects a gap in the literature that remains only partially addressed.

9. Safety Considerations and Interactions

9.1 Gastrointestinal Adverse Events

The most consistently reported adverse effects of moranoline and mulberry leaf preparations are gastrointestinal in nature, arising directly from the mechanism of action — undigested carbohydrates reaching the lower intestine. Adverse events of mulberry leaves commonly found in clinical studies were gastrointestinal symptoms including bloating, flatulence, and loose stools. Mulberry leaves possessed favourable effects on glycaemic profiles without serious side effects.

The most common adverse effects of α-glucosidase inhibitors (AGIs) are gastrointestinal disturbances from undigested carbohydrates reaching the hindgut.

9.2 General Tolerability

Clinical trials have focused on safety profiles, revealing that DNJ and mulberry extracts are generally well tolerated, with few adverse effects reported. In the 12-week lipid study, no significant changes in haematological or biochemical parameters were observed during the study period; no adverse events associated with DNJ-rich mulberry leaf extract occurred.

A study evaluating safety via stable isotope labelling found that the recovery rate of ¹⁵N from DNJ reached 80% up to 48 hours after oral administration, suggesting its rapid excretion and, by implication, its safety.

9.3 Dose-Related Considerations for N-Alkyl Derivatives

It is important to distinguish moranoline (unmodified DNJ) from its N-alkyl derivatives, some of which have an adverse event profile that does not necessarily apply to the parent compound. At higher doses of N-butyl-deoxynojirimycin, adverse events occur even more frequently. The poor specificity of N-butyl-deoxynojirimycin with respect to inhibition of glucosidases and glucosyltransferases contributes to these undesired side-effects. N-butyl-deoxynojirimycin is also a very potent inhibitor of intestinal glycosidases, and this inhibiting effect results in at least part of the intestinal complaints of patients. These data pertain to the pharmaceutical derivative miglustat/Zavesca, not to moranoline itself, but serve as a mechanistic caution.

9.4 Potential Interactions

Because moranoline acts as an α-glucosidase inhibitor — the same class of mechanism as pharmaceutical drugs such as acarbose — additive or potentiating effects on glucose lowering are pharmacologically plausible when co-administered with other anti-hyperglycaemic agents. Some studies have explored the potential of DNJ to enhance insulin sensitivity, further supporting its role in improving metabolic health. However, while the results are promising, the trials have highlighted the need for larger-scale studies to confirm the findings and to determine optimal dosing strategies.

Mulberry leaves supplementation had no effect on glycaemic markers in persons without diabetes, which suggests that the risk of hypoglycaemia in normoglycaemic individuals is low at the doses studied, consistent with the mechanism of action. Direct pharmacokinetic interaction data with specific pharmaceutical agents have not been characterised in published clinical literature.

9.5 Evidence Gaps

The trials have highlighted the need for larger-scale studies to confirm the findings and to determine optimal dosing strategies. Future research is needed to further investigate its long-term effects and improve its therapeutic potential. Long-term safety data beyond 12 weeks remain limited in humans, and standardised pharmacokinetic characterisation across different extract preparations and populations is lacking.

References

Health Conditions

Health conditions that Moranoline may help support.

No conditions available.

Body Systems

Body systems that Moranoline may help support.

No body systems available.