1-desoxinojirimicina

1-Deoxynojirimycin (DNJ): A Comprehensive Reference Article

1. Identity and Chemical Characterization

Names and Synonyms

1-Deoxynojirimycin (DNJ, molecular formula C₆H₁₃NO₄, molecular weight 163.17 g/mol) is an alkaloid azasugar, or iminosugar, classified as a biologically active natural compound. Its IUPAC name is (2R,3R,4R,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol. It is also known as moranoline. Additional synonyms include duvoglustat.

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. Mulberry DNJ is thus a glucose analog with an NH group substituting for the oxygen atom of the pyranose ring.

Classification

1-Deoxynojirimycin is a natural polyhydroxylated piperidine alkaloid that is attracting growing attention due to its important biological functions. 1-Deoxyiminosugars are chemically more stable than normal iminosugars because of the absence of a hydroxyl group at the C1 position. Among the iminosugars, naturally occurring 1-deoxyiminosugars such as DNJ are strong glycosidase inhibitors.

Notable Derivatives

Various derivatives of DNJ include N-azidopropyl-1-deoxynojirimycin, N-nonyl-1-deoxynojirimycin, 1-deoxynojirimycin-6-phosphate, and N-methyl-1-deoxynojirimycin-6-phosphate. DNJ, the most famous representative of polyhydroxylated alkaloids, shows both α- and β-glucosidase inhibition, and has been converted into two clinically approved drugs: Zavesca® and Glyset®, targeting type I Gaucher's disease and type II diabetes mellitus, respectively.

2. Natural Sources and Occurrence

Primary Plant Sources

DNJ is a biologically active natural compound that exists in mulberry leaves and Commelina communis (dayflower), as well as in several bacterial strains such as Bacillus and Streptomyces species. DNJ is an iminosugar with notable pharmacological properties, and mulberry (Morus spp.) represents the richest natural source of this compound, particularly in young leaves and roots.

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. 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.

DNJ Content in Mulberry Leaves

The degree of maturity of the mulberry leaves affects the DNJ content significantly. The younger leaves contain higher DNJ concentrations than the older leaves. DNJ concentrations in mature leaves vary among 132 mulberry varieties from 0.1341 to 1.472 mg/g of dry leaves. DNJ content in leaves is variety-dependent and has no obvious relationship with either the species or their place of origin. DNJ constitutes only approximately 0.11% (w/w) of mulberry leaf.

Microbial Sources

The possible intense demand for DNJ in the future has urged exploration of other sources of DNJ, including various bacterial strains such as Bacillus, Streptomyces, Actinoplanes, and Flavobacterium saccharophilium species. Glucose and lysine are two precursors of 1-DNJ biosynthesis in plants and microbes; however, the precise biosynthesis pathways have not yet been fully clarified.

Presence in Insects

DNJ naturally occurs in plants (especially Morus spp.), microbes, and insects, or it can be synthesized. Because silkworms (Bombyx mori) feed exclusively on mulberry leaves, DNJ has also been detected in silkworm-derived materials, and silkworm larvae are themselves noted as an ancillary biological source.

3. Traditional and Historical Use

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. 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 leaf extracts have been used possibly as far back as 4,000 years ago in ancient China, with modern research exploring effects on body weight and blood glucose. Mulberry (Morus alba L.), a perennial shrub belonging to the family Moraceae, is an extremely important economic plant given that its foliage is used in sericulture as the sole diet for the monophagous silkworm (Bombyx mori), and it has long been used in traditional Chinese medicine to treat disease. Because of its high nutritive value, rate of growth, and adaptability, mulberry is also used for other purposes, including as a nutritional fruit and food.

Historical Preparations and Purposes

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 addition to consuming dried white mulberry leaves as herbal tea, many functional foods also contain this raw material.

DNJ from mulberry is a widely used functional food constituent in China, Japan, Korea, Thailand, and many other Asian countries. The traditional applications of mulberry in East Asian medicine encompassed uses described for the leaf (to clear heat, expel wind, and cool the blood), the fruit (as a tonic for liver and kidney), and the root bark (for respiratory complaints). Sedative effects of mulberry fruits and anti-inflammatory, diuretic, antitussive, and antipyretic properties of mulberry root bark have been studied.

Discovery of DNJ as a Specific Constituent

In the modern era, health benefits from mulberry products have been scientifically verified, and naturally occurring DNJ, a kind of azasugar, was first isolated from its roots by Yagi et al. in 1976. This isolation of what was then termed "moraoline" from Morus species marked the transition from traditional empirical use to targeted phytochemical research on DNJ specifically.

4. Key Constituents and Mechanisms of Action

DNJ as the Principal Active Compound

1-Deoxynojirimycin (DNJ), which is a well-known anti-diabetic agent because of its α-glucosidase inhibition activity, is the most-abundant phytochemical and bioactive compound in mulberry leaves. In addition to DNJ, many other bioactive compounds including flavonoids, alkaloids, steroids, and coumarins also exist in mulberry leaves.

Mechanism 1: α-Glucosidase Inhibition

DNJ has attracted remarkable interest because of its effective and specific inhibition of different carbohydrate-degrading enzymes involved in a wide range of important biological processes, including hepatic glycogen breakdown, lysosomal catabolism of glycoconjugates, intestinal digestion, and maturation of the sugar chains in glycoproteins.

DNJ is an α-glucosidase inhibitor which acts as an antihyperglycemic agent by slowing the rate of carbohydrate degradation to monosaccharides; it can delay glucose absorption and significantly reduce postprandial blood glucose levels. 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.

Structurally similar to monosaccharides, iminosugars have unique mechanisms of action that regulate glucose metabolism through competitive inhibition of various glycosidases and enzymes vital for carbohydrate digestion. The competitive inhibition arises because DNJ's structural similarity to glucose allows it to bind at the active site of α-glucosidase enzymes in the intestinal brush border membrane, blocking the hydrolysis of disaccharides and complex oligosaccharides into absorbable monosaccharides.

Mechanism 2: Glycoprotein Processing Inhibition

DNJ and its N-alkyl derivatives behave as host-targeted glucomimetics that inhibit endoplasmic reticulum α-glucosidase I and II (GluI and GluII, respectively) enzymes, resulting in improper glycosylation and misfolding of viral glycoproteins; this underlies their antiviral potential. This mechanism is distinct from intestinal glucosidase inhibition and operates systemically after absorption.

Mechanism 3: Effects on Lipid Metabolism

DNJ has been found to beneficially influence lipid metabolism and mitochondrial function in the liver, in addition to its anti-obesity properties. Animal studies have indicated that the high-fat diet group showed greater expression of C/EBPα and CD36 mRNA in the liver, while mRNA expressions of ACC and FAS were lower and mRNA expression of PGC-1β was higher in the liver of the DNJ-treated group compared to the high-fat group.

Mechanism 4: Anti-inflammatory Pathways

DNJ, a unique polyhydroxy alkaloid and the main active component in mulberry leaves, may exhibit protective properties in the prevention of stable angina pectoris in patients with coronary heart disease by affecting the NF-κB pathway. In clinical context, DNJ's anti-inflammatory activity has been associated with reductions in pro-inflammatory cytokines (CRP, IL-6, TNF-α) and changes in oxidative stress markers.

Mechanism 5: Insulin Sensitization

In addition to its impact on glucose metabolism, DNJ has been observed to enhance insulin sensitivity, potentially improving glucose uptake and reducing insulin resistance in peripheral tissues.

5. Pharmacokinetics

Absorption and Peak Plasma Levels

DNJ, a potent glucosidase inhibitor, is a characteristic constituent of the mulberry leaf. Dietary mulberry DNJ may be beneficial for the suppression of abnormally high blood glucose levels, thereby preventing diabetes mellitus. Although there has been considerable interest in the effects of mulberry DNJ, the intestinal absorption and pharmacokinetic profile of orally administered mulberry DNJ had not been characterized until recently.

It has been reported that there is a proportional increase in plasma DNJ level with increase in mulberry-derived DNJ dose (1.1, 11, and 110 mg/kg of body weight), a dose-dependent phenomenon. An improved bioavailability was observed for pure DNJ versus the mulberry leaf extract administered to rats. Plasma levels of mulberry-derived DNJ after single oral administration (110 mg/kg of body weight) rapidly increased to a maximum level of 15 µg/mL, followed by a quick decline in level due to rapid excretion from the body, with a T_max (time to reach maximum plasma drug concentration) value of 30 min.

Metabolism and Excretion

No DNJ metabolites were detected in the plasma. These findings indicate that orally administered mulberry DNJ is absorbed as an intact form from the alimentary tract and then is quickly excreted from the body. Orally administered DNJ is absorbed into the blood and then excreted into the urine.

Implications of Rapid Clearance

These pharmacokinetic findings align with DNJ's role as an inhibitor of α-glucosidase and sucrase, delaying carbohydrate digestion and glucose absorption in the small intestine. However, the effects are short-lived, indicating DNJ's limited prolonged efficacy due to low bioavailability and rapid clearance. Research into the bioavailability and pharmacokinetics of DNJ indicates that, although it has moderate oral absorption, advances in formulation methods, such as encapsulation and sustained-release delivery systems, are currently being explored to improve its absorption and effectiveness.

Human Pharmacokinetic Data

DNJ is a potent α-glucosidase inhibitor. Although it is useful for the treatment of diabetes, the human absorption and metabolism of DNJ had never been fully characterized prior to the development of specialized mass spectrometric methods. Evidence has suggested that mulberry leaf iminosugars possess relatively good uptake and safety profiles, which support their prospective use for oral intake.

6. Scientific Evidence by Health Area

6.1 Glycemic Control and Diabetes

Overview

A 2024 meta-analysis investigated the effects of DNJ derived from mulberry leaves on glycemic 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.

Key Clinical Trials

One 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 hours after a carbohydrate challenge (200 g boiled white rice) in 12 subjects with fasting plasma glucose (FPG) in the range of 100–140 mg/dL. A second study 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 FPG in the range of 110–140 mg/dL.

One clinical study demonstrated that mulberry leaf powder with 12 mg of DNJ improves postprandial hyperglycemia, fasting plasma glucose, and glycated hemoglobin. Another study investigated the effect of long-term (12-week) supplementation of mulberry leaves in obese people with prediabetes and patients with early-stage type 2 diabetes.

Lipid Profiles in Humans

A published open-label human study examined the effects of DNJ-rich mulberry leaf extract on plasma lipid profiles. 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.

Strength of Evidence

The evidence for acute postprandial glucose lowering by DNJ-containing mulberry preparations in humans is supported by multiple randomized controlled trials and a 2024 meta-analysis. Evidence for longer-term HbA1c reduction is more limited in scope, with smaller sample sizes and shorter durations. Future research is needed to further investigate its long-term effects and improve its therapeutic potential. Most clinical studies of DNJ are focused on its anti-diabetic and related activities.

6.2 Lipid-Lowering and Anti-Obesity Effects

Preclinical Evidence

In a controlled animal study, male C57BL/6 mice were randomly assigned to normal control diet, high-fat diet, or high-fat diet supplemented with DNJ groups. After 12 weeks, the high-fat diet group exhibited higher overall weight gain, liver weight, and weight of various fat pads than the control and DNJ groups.

Proposed Mechanisms (Preclinical)

The high-fat diet group also showed greater expression of C/EBPα and CD36 mRNA in the liver than the control and/or DNJ groups. mRNA expressions of ACC and FAS were lower, while mRNA expression of PGC-1β was higher in the liver of the DNJ group compared to the high-fat diet group.

Strength of Evidence

Mulberry leaf iminosugars have been gaining increasing attention due to their health-promoting effects, including anti-diabetic, anti-obesity, anti-hyperglycemic, anti-hypercholesterolemic, anti-inflammatory, and gut microbiota-modulatory activities. Human evidence for anti-obesity effects specifically attributable to DNJ remains very limited; most evidence derives from animal models and mechanistic studies.

6.3 Antiviral Properties

Mechanisms (In Vitro and Preclinical)

N-butyl-DNJ (miglustat) inhibits endoplasmic reticulum α-glucosidase I and II enzymes, resulting in improper glycosylation and misfolding of viral glycoproteins; thus, it is a potential antiviral agent. It has been studied against a broad range of viruses in vitro and in vivo; however, its utility as an antiviral has not been fully explored.

Research has shown that DNJ and its derivatives have demonstrated in vitro inhibitory effects against various viral pathogens. N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, including antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine viral diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.

HIV (In Vitro)

Research has shown that the α-glucosidase inhibitor 1-deoxynojirimycin blocks human immunodeficiency virus envelope glycoprotein-mediated membrane fusion at the CXCR4 binding step. This is a mechanism identified in cell-culture studies.

Hepatitis B (In Vitro)

Treatment of hepatitis B virus-infected cells with α-glucosidase inhibitors results in production of virions with altered molecular composition and infectivity. These findings are from cell-based laboratory experiments and have not been replicated in clinical trials of DNJ itself.

Strength of Evidence

The antiviral evidence for DNJ itself is predominantly in vitro or derived from studies with N-alkyl derivatives (such as miglustat). Other N-alkylated congeners of DNJ are in preclinical and clinical studies for diverse viral infections. 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. No antiviral clinical trials have been completed with DNJ as the primary study compound.

6.4 Cardiovascular Health

Clinical Evidence

A clinical trial enrolled patients with stable angina pectoris (SAP) in the setting of coronary heart disease (CHD) and blood stasis syndrome. NF-κB signaling was cited as associated with angina pectoris. DNJ, purified from mulberry leaves using a pretreated cation exchange chromatography column, was studied. A total of 144 SAP patients were randomly and evenly divided into experimental (DNJ treatment) and control (conventional treatment) groups. Echocardiography and ascending aortic elasticity were evaluated.

The DNJ from mulberry leaves improved stable angina pectoris in patients with coronary heart disease and blood stasis syndrome by increasing their antioxidant and anti-inflammatory capacities. Specifically, it significantly lowered the levels of high-sensitivity C-reactive protein, IL-6, TNF-α, malondialdehyde, and SOD levels.

Strength of Evidence

The single published RCT on SAP and DNJ represents preliminary human evidence. It was conducted in a specific patient subgroup (CHD with blood stasis syndrome, a traditional Chinese medicine categorization) and has not been replicated in larger, multicenter trials. Other clinical studies of DNJ have included its effect on serum triglyceride, starch digestion and absorption, stable angina pectoris, and atherosclerotic lesion. This evidence base is limited.

6.5 Anti-Inflammatory and Antioxidant Activity

Mulberry DNJ shows high α-glucosidase inhibitory, antioxidant, antimicrobial, and anti-inflammatory activity. Diverse biological activities, such as antihyperglycemic, lipid-lowering, antitumor, antiviral, and anti-inflammatory, have been recognized for DNJ. The majority of anti-inflammatory evidence derives from in vitro and preclinical animal studies; human data on anti-inflammatory outcomes specifically attributed to DNJ supplementation remain sparse.

6.6 Oncology (Preclinical Only)

Major pharmacological properties of DNJ from mulberry include anti-diabetic, anti-obesity, cardioprotective, and anti-cancer activities. Other properties of DNJ are hepatoprotective, neuroprotective, antimicrobial, anti-inflammatory, hypolipidemic, and nephroprotective activities. These are designations drawn from preclinical investigations. No clinical trials have established efficacy for DNJ in cancer treatment or prevention in humans.

6.7 Lysosomal Storage Disorders (Pharmacological Derivatives)

While DNJ itself has not been approved for any clinical indication, its synthetic derivatives have achieved regulatory approval. Miglustat (also known as N-butyldeoxynojirimycin, brand name Zavesca®) is a clinically approved drug for the treatment of Niemann–Pick disease type C and Gaucher disease type I. Miglitol (N-hydroxyethyl-DNJ, Glyset®) is an approved anti-diabetic drug for the treatment of type 2 diabetes mellitus. It prevents hyperglycemia by reducing the rate of complex carbohydrate digestion. In addition, migalastat (1-deoxygalactonojirimycin), an orphan drug, is used for the treatment of Fabry disease.

7. Body Systems and Health Areas Associated with DNJ

• Endocrine / Metabolic: DNJ acts as an inhibitor of α-glucosidase and sucrase, delaying carbohydrate digestion and glucose absorption in the small intestine — the primary and best-evidenced application.
• Gastrointestinal: Enzyme inhibition occurs at the level of the small intestinal brush border; this is the primary site of DNJ's acute pharmacological action.
• Hepatic: DNJ has been found to beneficially influence lipid metabolism and mitochondrial function in the liver.
• Cardiovascular: DNJ may exhibit protective properties in the prevention of stable angina pectoris in patients with coronary heart disease by affecting the NF-κB pathway.
• Immune / Antiviral: DNJ and its derivatives inhibit endoplasmic reticulum glucosidases involved in glycoprotein processing, with demonstrated effects against multiple viruses in vitro.
• Lysosomal / Neurological: Approved derivatives of DNJ (miglustat, migalastat) are used in lysosomal storage diseases including Gaucher disease, Niemann–Pick type C disease, and Fabry disease.

8. Dosage Forms and Dosages Reported in Studies

Forms Available

DNJ is found in and delivered through the following forms, as documented in the scientific literature:

• Mulberry leaf tea: Consumed as dried white mulberry leaves in herbal tea form.
• Standardized mulberry leaf extract capsules: Used in multiple clinical trials, standardized to a specified quantity of DNJ.
• Food-grade mulberry powder: Enriched with DNJ for functional food applications.
• Purified DNJ: Used in some research and clinical investigations.

Dosages Reported in Human Studies

• Single-dose crossover: 3 mg, 6 mg, or 9 mg DNJ from mulberry leaf extract, administered with a carbohydrate challenge (200 g boiled white rice) in 12 subjects with fasting plasma glucose 100–140 mg/dL.
• Long-term trial: 6 mg DNJ three times daily for 12 weeks, in 76 subjects with fasting plasma glucose 110–140 mg/dL.
• Lipid study: Capsules containing DNJ-rich mulberry leaf extract at 12 mg three times daily before meals for 12 weeks, in 10 subjects with initial serum triglyceride ≥200 mg/dL.
• One study used mulberry leaf powder with 12 mg of DNJ per dose.

Regulatory Status

DNJ has not been approved as a food supplement as of the current literature. Mulberry leaf products containing DNJ are sold as dietary supplements and functional foods in various jurisdictions, but DNJ as an isolated compound does not hold a specific regulatory classification as a food ingredient or supplement in most Western regulatory frameworks.

9. Safety Considerations and Drug Interactions

Gastrointestinal Adverse Effects

Adverse events reported in some studies include primarily mild gastrointestinal symptoms such as bloating, flatulence, and discomfort. Gastrointestinal symptoms, such as abdominal distension, diarrhea, and flatulence, are the most frequent adverse events of α-glucosidase inhibitor agents. These symptoms contributed to the high withdrawal rate of acarbose in the STOP-NIDDM Trial. The lack of such symptoms in some DNJ trials suggests a potentially better-tolerated profile.

General Tolerability from Available Studies

Evidence has suggested that mulberry leaf iminosugars possess relatively good uptake and safety profiles, which support their prospective use for oral intake. In the limited set of published human clinical trials, DNJ at doses of 6–12 mg per administration was generally well tolerated.

Additive Hypoglycemic Risk

Because DNJ inhibits intestinal α-glucosidase enzymes and reduces postprandial blood glucose, co-administration with other glucose-lowering agents — including sulfonylureas, insulin, or other α-glucosidase inhibitors such as acarbose or miglitol — could theoretically potentiate hypoglycemic effects. One study examined hypoglycemic effects of Morus alba leaf extract on postprandial glucose and insulin levels in patients with type 2 diabetes treated with sulfonylurea hypoglycemic agents. The potential for additive pharmacodynamic interaction in patients on existing antidiabetic medication is a documented concern in the literature.

Adverse Effects in DNJ Derivatives (Contextual Reference)

Information from studies on the N-butyl derivative (miglustat/Zavesca®) is illustrative of the class. 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 may contribute to these undesired side effects. N-butyl-deoxynojirimycin is also a potent inhibitor of intestinal glycosidases, and this inhibiting effect is postulated to result in at least part of the intestinal complaints of patients. These findings apply to a pharmaceutical derivative at therapeutic doses and are not directly transferable to food-grade DNJ.

Remaining Safety Unknowns

To understand the underlying mechanism responsible for DNJ's therapeutic effects, further study is needed to gain more insight into the distribution of DNJ and its metabolites in organs. The possible adverse effects resulting from disposition of DNJ in organs have also become a major concern; a more thorough safety evaluation on DNJ, referring to established guidelines such as Safety Pharmacology Studies for Human Pharmaceuticals, has been indicated. Long-term safety data from controlled human trials remain limited.

10. Relationship to Approved Pharmaceutical Agents

DNJ is a natural product that shows both α- and β-glucosidase inhibition. This molecule has been converted into two clinically approved drugs: Zavesca® and Glyset®, targeting type I Gaucher's disease and type II diabetes mellitus, respectively.

Miglustat (N-butyl-1-deoxynojirimycin; N-butyl DNJ or NB-DNJ, Zavesca®) is the first iminosugar-based drug, used to treat type I Gaucher's and Niemann–Pick type 2 diseases. Miglitol was designed from the natural product DNJ. These approved derivatives represent a chemical progression from the parent natural compound and demonstrate the pharmacological proof-of-concept established by DNJ. DNJ itself (sometimes referred to as duvoglustat or AT2220 in investigational contexts) is sometimes referred to as duvoglustat and/or duvoglustat HCl (AT2220).

11. Current Research Status and Evidence Gaps

DNJ is an iminosugar naturally present in mulberry and dayflower plants, as well as in several bacterial strains, and exerts a broad spectrum of biological activities. It has been reported to possess strong potential for combating diabetes mellitus and its complications. Research on the efficacy of DNJ in diabetes management has yielded promising results in both animal models and human trials.

Despite encouraging data, several evidence gaps persist:

• Most antiobesity, antiviral, anticancer, and anti-inflammatory effects have been demonstrated in cell culture or rodent models and have not been adequately tested in controlled human clinical trials.
• The effects of DNJ are short-lived, indicating limited prolonged efficacy due to low bioavailability and rapid clearance. Future research is needed to further investigate long-term effects and improve therapeutic potential.
• Despite tissue-specific distribution of DNJ in mulberry, the transcriptional regulatory mechanisms underlying its biosynthesis remain poorly understood.
• Advances in formulation methods, such as encapsulation and sustained-release delivery systems, are currently being explored to improve its absorption and effectiveness.

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