IngredientsMaclura tricuspidata (Carr.) Bur belongs to the Moraceae family and is a thorny deciduous tree distributed throughout the East Asian region, including Korea, China, and Japan. The plant was formerly classified under the genus Cudrania and is still widely referenced in scientific literature under the synonym Cudrania tricuspidata Bureau. The name Cudrania tricuspidata is consistently cited as the former accepted name, and both designations appear throughout peer-reviewed literature.
The name "Maclura" pays homage to the American botanist William Maclure, while "tricuspidata" stems from the Latin tri meaning three and cuspidata meaning pointed, aptly describing the shape of its leaves.
Among its common names are Chinese mulberry (not to be confused with Morus australis, also known by that name), storehousebush, mandarin melon berry, silkworm thorn, cudrang, kujibbong, zhe, or che (Chinese: 柘; pinyin: zhè).
Maclura tricuspidata is a deciduous shrub or small tree in the Moraceae family, typically reaching 1–7 meters in height with grayish-brown bark and thorny branchlets bearing spines 0.5–2 cm long. Its leaves are ovate to rhombic-ovate, measuring 5–14 cm long by 3–6 cm wide, with entire margins and occasionally three-lobed forms, while male flowers form capitulate inflorescences about 5 mm in diameter and female ones reach 1–1.5 cm, leading to syncarp fruits that are globose to oblong, 2.5–5 cm in diameter, with a distinctive bumpy, knobby, or lumpy exterior surface that ripen from green to shades of red, maroon, pinkish-red, or brownish-purple. The juicy flesh is red to pink, containing 3–6 small brown seeds, and has a mild, sweet flavor often compared to watermelon or cantaloupe.
The whole plant of C. tricuspidata, including the roots, leaves, bark, stems, and fruits, has been found to contain diverse phytochemicals with various bioactivities. Currently, the fruits are consumed fresh and in juices and jams, and further development as a dietary supplement and functional food ingredient has been actively accomplished in many fields. Both premature and fully mature fruits of M. tricuspidata have traditionally been used in Korea to make fresh juice, jam, wine, vinegar, and fermented alcoholic beverages.
In China, its leaves are fed to silkworms, its bark is used to make paper and a reddish-yellow dye, and its roots are used for medicinal purposes. The fruit is used for the production of drinks and food items, while its roots and bark are used as medicinal materials.
Cudrania tricuspidata is a perennial plant of the family Moraceae with numerous medicinal and nutritional applications. It has been widely used in East Asia as an important traditional folk medicine for the treatment of many ailments such as eczema, mumps, tuberculosis, contusions, insomnia, and acute arthritis.
In Korean traditional medical books such as the Donguibogam (1613 A.D., Joseon Dynasty), most parts of this plant were utilized as folk medicine for the treatment of various disorders such as neuritis, arthritis, mumps, tuberculosis, inflammation, jaundice, and hepatitis. The distinctive medical system of traditional Korean medicine was established shortly after the publication of Donguibogam by Dr. Heo Jun in 1613; in 2009, the United Nations Educational, Scientific and Cultural Organization registered the book on its cultural heritage list.
In the Korean classic Donguibogam, it was reported that the fruit, leaf, and root of C. tricuspidata were used for deafness due to "Pungheo" and malaria. In China, the roots have been used for the treatment of bruising, gonorrhea, boils, rheumatism, scabies, jaundice, and dysmenorrhea in traditional Chinese medicine under the name "Chuan-po-shi," and the root bark has been used for the treatment of hemoptysis, contusions, and lumbago.
In Korean traditional medicine, the plant has been used as a folk remedy for gastritis, liver damage, and hypertension. The leaves, root, stem, and fruit of this plant have also been used in traditional Korean herbal medicines to treat jaundice, hepatitis, neuritis, and inflammation.
Bark decoctions have been employed for ailments such as contusions, eczema, and acute arthritis, with historical records in traditional Chinese medicine documenting their application since the Tang Dynasty for lumbago and hemoptysis. Fruits and leaves have been utilized in folk remedies for rheumatoid arthritis and hepatitis, reflecting the plant's broad ethnomedicinal role in East Asia.
The leaves of M. tricuspidata are much used in China for feeding the silkworm, being considered as good for this purpose as the mulberry. The bark of M. tricuspidata yields a reddish-yellow dye derived from flavonoids like morin, historically used in China for coloring textiles such as imperial garments, while its fibers have been processed for papermaking. Its wood is also valuable, and has been used for the construction of bows.
The Tanzhe Temple west of Beijing, China is named for this tree.
Among bioactive phytochemicals, xanthones and flavonoids are representative ingredients that mainly possess anti-inflammatory, antioxidant, and antitumor activities. Seventeen new prenylated xanthones were isolated from an ethyl acetate-soluble extract of the root bark of Cudrania tricuspidata, together with 17 previously identified xanthones. Notable xanthones identified include cudratricusxanthone A (CTXA), cudraxanthone D, cudratricusxanthone F, macluraxanthone B, and cudratricusxanthone L.
Previous phytochemical studies on the stems or root barks of Cudrania tricuspidata resulted in the isolation of various isoprenylated xanthones and flavonoids, some of which have anti-cancer, hepatoprotective, anti-inflammatory, and anti-oxidant activities.
Various types of flavonoids, including isoflavones, along with xanthones are considered as the major bioactive constituents of M. tricuspidata, exhibiting antioxidant, antiatherosclerotic, anti-inflammatory, cytotoxic, hepatoprotective, and neuroprotective activities. Cudraisoflavone L–T (11 compounds), cudradihydrochalcone A, and cudrabibenzyl A, together with 41 known constituents, have been isolated from the fruits of Maclura tricuspidata.
Several parts of C. tricuspidata have been studied regarding their phytochemical characterization, standing out for their abundance of phenolic compounds, especially flavonoids. Flavanone, flavonol, flavonol glycoside, flavanone glycoside, and xanthone have been reported in multiple studies highlighting the antioxidant potential of phenolic-rich extracts.
The fruits, leaves, and roots of Cudrania tricuspidata have been reported to contain large amounts of vitamin B, vitamin C, and flavonoids. Specific flavonoids characterized in the plant include steppogenin, cudraflavone C, cudraflavanone B, kaempferol, quercetin, rutin, taxifolin, and eriodictyol glycosides.
Parishin compounds are rare polyphenolic glucosides mainly found in the rhizome of the traditional Chinese medicinal plant Gastrodia elata; these constituents are reported to have several biological and pharmacological activities. Two novel parishin derivatives not previously reported as plant-based phytochemicals were identified from a twig of Maclura tricuspidata: macluraparishin E and macluraparishin C, elucidated by UV–Vis spectroscopy, HPLC-QTOF-MS, and NMR spectroscopy.
Among 18 polyphenolic compounds identified in the fruit, five parishin derivatives (gastrodin, parishin A, B, C, E) were positively identified for the first time in this plant and validated against authentic standards. Parishin A was the most abundant component, followed by chlorogenic acid, gastrodin, eriodictyol glucoside, parishin C, parishin E, and parishin B.
The compositions and contents of these constituents vary depending on the different parts of the plant. In particular, the contents of parishin A, parishin B, macluraparishin C, and macluraparishin E were higher in the twig, bark, and root than in the leaves, xylem, and fruit.
Protocatechuic acid (PA), isovanillic acid (IVA), and p-hydroxybenzoic acid (4-HA) have been isolated from M. tricuspidata. These compounds were found to attenuate the formation of fibrin polymers/clots and degrade blood clots. These compounds inhibited the activities of procoagulant proteases and fibrinoligase, and prolonged coagulation time.
The pharmacological effects of different parts of M. tricuspidata are attributed to the presence of high phenolic compounds, flavonoids, diterpenoids, terpenoids, and alkaloids. Sterol-class compounds such as butyrospermol, lupeol, and β-sitosterol have been identified in fruit extracts, along with the bibenzyl compound cudrabibenzyl A.
In research involving TNF-α + IFN-γ-treated HaCaT cells (a human keratinocyte line), 16 compounds from C. tricuspidata were evaluated: 11 decreased IL-6 production and 15 decreased IL-8 production. The six most effective compounds—steppogenin, cudraflavone C, macluraxanthone B, 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone, cudraflavanone B, and cudratricusxanthone L—were selected for further study, and five of these significantly inhibited NF-κB p65 translocation to the nucleus.
C. tricuspidata extracts have demonstrated effects including inhibition of pancreatic lipase, lipopolysaccharide-induced nitric oxide production, prostaglandin E2 production in macrophages, IL-1β-induced rheumatoid synovial fibroblast proliferation, and matrix metalloproteinase production.
The cytoprotective effects of C. tricuspidata leaf extract (CTE) are linked to the activation of the NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, as demonstrated in HepG2 cells. CTE upregulated nuclear translocation of Nrf2 and its target gene expression; it also inhibited the generation of reactive oxygen species (ROS) and cell death induced by arachidonic acid and iron treatment. The cytoprotective effects of CTE against oxidative stress were attributed in part to kaempferol, the major flavonoid present in the extract.
In SH-SY5Y neuroblastoma cell studies, M. tricuspidata fruit extract ameliorated H₂O₂-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release, and promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT).
C. tricuspidata leaf extract (CTe) exhibited a strong inhibitory effect on PTP1B (protein tyrosine phosphatase 1B) activity and substantially inhibited fat accumulation in 3T3-L1 cells. When orally administered to diet-induced obesity mice once daily for 3 weeks, hepatic enzyme markers (AST and ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, while CTe increased the phosphorylation of IRS-1 and Akt in liver tissue.
A study investigating the effect of water extract from Cudrania tricuspidata leaves (CTL) on hepatic insulin resistance in db/db mice found a marked decrease in ER stress response and insulin resistance in treated livers. Groups were given dietary supplements of 100 mg/kg and 300 mg/kg of CTL for 8 weeks.
Cudraflavanone A isolated from the root bark of C. tricuspidata was investigated for its ability to inhibit vascular smooth muscle cell (VSMC) growth under PDGF-BB-stimulated conditions. Cudraflavanone A at 0.1–1 µM significantly inhibited PDGF-BB-induced cell proliferation in a concentration-dependent manner. Cudraflavanone A suppressed PDGF-BB-stimulated Akt activation, which is involved in cell survival, and selective modification of Akt activation may suppress intimal thickening after angioplasty and plaque formation in atherosclerosis.
Xanthones and flavonoids as the main active constituents isolated from C. tricuspidata have been proven to possess notable anti-inflammatory, antioxidative, antitumor, hepatoprotective, neuroprotective, and anti-obesity effects.
The anti-inflammatory evidence is predominantly preclinical (in vitro and animal studies). Results from cell-based studies demonstrate that compounds from C. tricuspidata could be further developed as therapeutic agents that suppress inflammation in human keratinocytes. Six of the most effective isolated compounds decreased the expression levels of chemokines such as RANTES and TARC, and downregulated the protein expression levels of intercellular adhesion molecule-1. No large-scale human clinical trials on anti-inflammatory endpoints were identified in the peer-reviewed literature.
Different bioactive compounds from the fruit of M. tricuspidata have been identified via spectroscopic and chemical methods, showing neuroprotective effects against cell death induced by 6-hydroxydopamine (6-OHDA) in SH-SY5Y cells of human neuroblastoma.
In one study, six new prenylated xanthone compounds and six known compounds from the root bark showed neuroprotective effects against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells, with EC50 values of 0.7–16.6 µM. Isolated compounds from the fruit were also evaluated for neuroprotective effects against 6-OHDA-induced cell death in the same cell line, with six compounds exhibiting activities with EC50 values of 4.5–18.6 µM.
Maclura tricuspidata has been studied for its potential in the context of Alzheimer's and Parkinson's disease, with findings indicating that the plant decreases the damage caused by oxidative stress in cells and increases the expression of genes that encode the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), producing a protective and beneficial effect against neurodegeneration.
In cell viability studies, pretreatment with M. tricuspidata fruit extract at 5 to 50 µg/mL dramatically attenuated H₂O₂-induced cytotoxicity in SH-SY5Y cells, especially at the 50 µg/mL dose. Evidence strength: All neuroprotection evidence is currently in vitro or animal-based. There is limited scientific research directly linking Maclura tricuspidata to cognitive or neurological benefits in humans; these studies are mostly preclinical, and direct clinical evidence in humans is lacking.
In a screening of 115 herbal extracts for inhibition of pancreatic lipase activity in vitro, researchers verified the suppression of lipid absorption by C. tricuspidata leaves in vivo. The results suggest that C. tricuspidata leaves may be useful for the treatment of obesity.
Unripe fruits of C. tricuspidata, in accordance with their higher content of total phenolic compounds and flavonoids, exhibited stronger pancreatic lipase (PL)-inhibiting activity in comparison to ripe fruits. An isoflavone, namely cudracusisoflavone B, from unripe fruits exhibited strong PL-inhibiting activity, with an IC50 value of 16.8 µM, in a non-competitive manner.
The leaves of C. tricuspidata displayed a strong inhibitory effect against PTP1B and substantially inhibited fat accumulation in 3T3-L1 cells in a dose-dependent manner.
In a diet-induced obesity mouse model, CTe treatment effectively decreased blood glucose levels and increased insulin. Evidence strength: Evidence is predominantly from in vitro screens and animal models (rodents). Some preliminary clinical investigations suggest potential benefits in regulating blood sugar levels and supporting metabolic health, although sample sizes tend to be small and more robust, large-scale human trials are needed to confirm these effects.
The root bark of C. tricuspidata has demonstrated anti-atherosclerotic, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and cytotoxic activity in preclinical studies.
Researchers examined whether C. tricuspidata leaf extracts (CTEs) protect against oxidative stress-mediated liver injury in vitro and in vivo. The cytoprotective effects of CTE were presented through NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) activation, measured by biochemical analysis in HepG2 cells. To assess protective effects in vivo, mice were administered CTE at 250 and 500 mg/kg for 5 days before a single dose of acetaminophen (300 mg/kg). Kaempferol pretreatment blocked AA+Fe-induced ROS production and reversed glutathione depletion, leading to decreased cell death; protective effects of CTE against liver injury induced by excess acetaminophen in mice or primary hepatocytes were also observed.
Evidence strength: Hepatoprotective evidence is derived from cell culture and rodent models. No controlled human clinical trials on hepatoprotective endpoints were identified.
Studies determined the antimetastatic properties of M. tricuspidata root, stem, leaf, and fruit extracts with high phenol and flavonoid content and antioxidant capacity in hepatocellular carcinoma cells, indicating that these extracts can be used in potential treatment for hepatocellular carcinoma with the possibility of improving therapeutic efficiency.
Researchers studied green-synthesized gold nanoparticles (GNPs) from M. tricuspidata root, stem, leaf, and fruit extracts and evaluated their anti-metastatic properties in hepatocellular carcinoma cells, quantifying phenolic and flavonoid contents, reducing capacity, and antioxidant activity of all four extracts.
Evidence strength: Anticancer evidence is entirely preclinical (in vitro cell culture studies). No human clinical trials were identified in the published literature.
Extracts and isolated compounds from M. tricuspidata exhibit antioxidant, antimicrobial, anticancer, and antihypertensive effects. Several studies have demonstrated protective effects on blood circulation and cardiovascular health, such as improving insulin resistance, plasma triglyceride levels, and platelet function.
Protocatechuic acid, isovanillic acid, and p-hydroxybenzoic acid isolated from M. tricuspidata attenuated the formation of fibrin polymers/clots and degraded blood clots in vitro; these compounds inhibited the activities of procoagulant proteases and fibrinoligase, and prolonged coagulation time.
In a study of the antiproliferative effect of cudratricusxanthone A isolated from the root bark against VSMCs, antiproliferative effects were examined by direct cell counting and [³H]-thymidine incorporation assays. Evidence strength: Cardiovascular evidence is exclusively preclinical (cell-based and animal). No human trials on cardiovascular endpoints were identified.
An ethanolic extract of C. tricuspidata has been investigated in the context of atopic dermatitis (AD), a chronic inflammatory skin disease characterized by elevated immunoglobulin E (IgE) levels, mast cell infiltration, and skin lesions including pruritus, erythema, and eczema. Published work cited in multiple peer-reviewed reviews (Phytother Res. 2012 Apr;26(4):594–9) showed that the fruits of C. tricuspidata suppress development of atopic dermatitis in an NC/Nga animal model, and the roots exhibit immunomodulatory and anti-oxidant activities in vitro.
Evidence strength: Skin-related evidence consists of in vitro studies on human keratinocytes and animal model studies. No controlled human clinical trials were found.
Accumulated studies have revealed that the extracts and components of C. tricuspidata exhibit a broad spectrum of pharmacological activities, including antimicrobial effects. Under optimized extraction conditions, M. tricuspidata ripe fruit extract showed potent antibacterial activity against fish pathogenic Streptococcus, with an MBC/MIC ratio of 2, suggesting a bactericidal action. The extract also exhibited disintegration of bacterial cytoplasmic membranes and cell disruption against S. iniae in scanning electron microscopy analysis.
No standardized human clinical dosage recommendations for Maclura tricuspidata have been established by major regulatory or pharmacopoeial bodies. The following dosages appear only in preclinical (animal or in vitro) research:
Recent research results have reported that MT extract has several beneficial health effects, including anticancer, anti-inflammatory, antioxidant, antiobesity, and antidiabetic effects, but none of the above dosing regimens have been validated in human subjects.
The safety profile of Maclura tricuspidata appears favorable in the doses traditionally consumed, with few adverse effects reported. However, rigorous human safety and toxicology trials are absent from the published literature.
A common perception of natural product safety and high consumer acceptance with a belief that "natural" equals "safe" is not only false, but also misleading. Formal preclinical toxicological profiling (LD50, chronic toxicity, genotoxicity) for M. tricuspidata has not been comprehensively published in accessible, peer-reviewed literature as of the available sources.
Given the antithrombotic and anticoagulant properties demonstrated in vitro—specifically that isolated compounds from M. tricuspidata attenuated fibrin clot formation, inhibited procoagulant proteases and fibrinoligase, and prolonged coagulation time—there is a theoretical basis for concern regarding interactions with anticoagulant or antiplatelet medications, although this has not been confirmed in human studies.
In the DIO mouse model, hepatic enzyme markers (AST and ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, suggesting no apparent hepatotoxicity at the doses studied. However, the implications for human liver safety are uncharacterized.
It is necessary to carry out more studies on these products' chemical composition, mechanism of action, and biological activity before robust safety conclusions can be drawn for human use. The absence of approved monographs from bodies such as the WHO, ESCOP, German Commission E, or EMA for this species reflects the early state of its evidence base.
Health conditions that Maclura tricuspidata may help support.
Body systems that Maclura tricuspidata may help support.
Go back