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  1. Zhong Z, Zhu W, Liu S, Guan Q, Chen X, Huang W, et al.
    Plant Cell Physiol, 2018 Nov 01;59(11):2214-2227.
    PMID: 30020500 DOI: 10.1093/pcp/pcy138
    Pharmaceutically active compounds from medical plants are attractive as a major source for new drug development. Prenylated stilbenoids with increased lipophilicity are valuable secondary metabolites which possess a wide range of biological activities. So far, many prenylated stilbenoids have been isolated from Morus alba but the enzyme responsible for the crucial prenyl modification remains unknown. In the present study, a stilbenoid-specific prenyltransferase (PT), termed Morus alba oxyresveratrol geranyltransferase (MaOGT), was identified and functionally characterized in vitro. MaOGT recognized oxyresveratrol and geranyl diphosphate (GPP) as natural substrates, and catalyzed oxyresveratrol prenylation. Our results indicated that MaOGT shared common features with other aromatic PTs, e.g. multiple transmembrane regions, conserved functional domains and targeting to plant plastids. This distinct PT represents the first stilbenoid-specific PT accepting GPP as a natural prenyl donor, and could help identify additional functionally varied PTs in moraceous plants. Furthermore, MaOGT might be applied for high-efficiency and large-scale prenylation of oxyresveratrol to produce bioactive compounds for potential therapeutic applications.
    Matched MeSH terms: Morus/enzymology*; Morus/genetics; Morus/metabolism
  2. Zhu W, Zhong Z, Liu S, Yang B, Komatsu S, Ge Z, et al.
    Int J Mol Sci, 2019 Jan 16;20(2).
    PMID: 30654535 DOI: 10.3390/ijms20020365
    Morus alba is an important medicinal plant that is used to treat human diseases. The leaf, branch, and root of Morus can be applied as antidiabetic, antioxidant, and anti-inflammatory medicines, respectively. To explore the molecular mechanisms underlying the various pharmacological functions within different parts of Morus, organ-specific proteomics were performed. Protein profiles of the Morus leaf, branch, and root were determined using a gel-free/label-free proteomic technique. In the Morus leaf, branch, and root, a total of 492, 414, and 355 proteins were identified, respectively, including 84 common proteins. In leaf, the main function was related to protein degradation, photosynthesis, and redox ascorbate/glutathione metabolism. In branch, the main function was related to protein synthesis/degradation, stress, and redox ascorbate/glutathione metabolism. In root, the main function was related to protein synthesis/degradation, stress, and cell wall. Additionally, organ-specific metabolites and antioxidant activities were analyzed. These results revealed that flavonoids were highly accumulated in Morus root compared with the branch and leaf. Accordingly, two root-specific proteins named chalcone flavanone isomerase and flavonoid 3,5-hydroxylase were accumulated in the flavonoid pathway. Consistent with this finding, the content of the total flavonoids was higher in root compared to those detected in branch and leaf. These results suggest that the flavonoids in Morus root might be responsible for its biological activity and the root is the main part for flavonoid biosynthesis in Morus.
    Matched MeSH terms: Morus/genetics; Morus/metabolism*
  3. Liu J, Niu YF, Ni SB, Liu ZY, Zheng C, Shi C
    Mitochondrial DNA B Resour, 2017 Dec 12;3(1):13-14.
    PMID: 33474051 DOI: 10.1080/23802359.2017.1413317
    The Artocarpus heterophyllus, native to Western Ghats of India, Malaysia and south-eastern Asia, is a tree member of the mulberry family (Moraceae). Chloroplast genome sequences play a significant role in the development of molecular markers in plant phylogenetic and population genetic studies. In this study, we report the complete chloroplast genome sequence of A. heterophyllus for the first time. The chloroplast genome is 160,387 bp long and includes 113 genes. Its LSC, SSC and IR regions are 88,422, 18,869 and 26,548 bp long, respectively. Phylogenetic tree analysis exhibited that A. heterophyllus was clustered with other Moraceae species with high bootstrap values.
    Matched MeSH terms: Morus
  4. Niu YF, Ni SB, Liu ZY, Zheng C, Mao CL, Shi C, et al.
    Mitochondrial DNA B Resour, 2018 Apr 03;3(1):440-441.
    PMID: 33490512 DOI: 10.1080/23802359.2018.1457995
    The Lucuma nervosa, native to Western Ghats of India, Malaysia and south-eastern Asia, is a tree member of the mulberry family (Sapotaceae). Chloroplast genome sequences play an significant role in the development of molecular markers in plant phylogenetic and population genetic studies. In this study, we report the complete chloroplast genome sequence of L. nervosa for the first time. The chloroplast genome is 157,920 bp long and includes 113 genes. Its LSC, SSC, and IR regions are 88,123, 18,861, and 25,468 bp long, respectively. Phylogenetic tree analysis exhibited that L. nervosa was clustered with other Sapotaceae species with high bootstrap values.
    Matched MeSH terms: Morus
  5. Guan Q, Yu J, Zhu W, Yang B, Li Y, Zhang L, et al.
    Gene, 2018 Mar 01;645:60-68.
    PMID: 29274907 DOI: 10.1016/j.gene.2017.12.045
    Ultraviolet-B (UVB) irradiation induces oxidative stress in plant cells due to the generation of excessive reactive oxygen species. Morus alba L. (M. abla) is an important medicinal plant used for the treatment of human diseases. Also, its leaves are widely used as food for silkworms. In our previous research, we found that a high level of UVB irradiation with dark incubation led to the accumulation of secondary metabolites in M. abla leaf. The aim of the present study was to describe and compare M. alba leaf transcriptomics with different treatments (control, UVB, UVB+dark). Leaf transcripts from M. alba were sequenced using an Illumina Hiseq 2000 system, which produced 14.27Gb of data including 153,204,462 paired-end reads among the three libraries. We de novo assembled 133,002 transcripts with an average length of 1270bp and filtered 69,728 non-redundant unigenes. A similarity search was performed against the non-redundant National Center of Biotechnology Information (NCBI) protein database, which returned 41.08% hits. Among the 20,040 unigenes annotated in UniProtKB/SwissProt database, 16,683 unigenes were assigned 102,232 gene ontology terms and 6667 unigenes were identified in 287 known metabolic pathways. Results of differential gene expression analysis together with real-time quantitative PCR tests indicated that UVB irradiation with dark incubation enhanced the flavonoid biosynthesis in M. alba leaf. Our findings provided a valuable proof for a better understanding of the metabolic mechanism under abiotic stresses in M. alba leaf.
    Matched MeSH terms: Morus/genetics; Morus/metabolism; Morus/radiation effects*
  6. Yulistiani D, Jelan ZA, Liang JB, Yaakub H, Abdullah N
    Asian-Australas J Anim Sci, 2015 Apr;28(4):494-501.
    PMID: 25656207 DOI: 10.5713/ajas.14.0406
    A digestibility study was conducted to evaluate the effects of supplementing mulberry foliage and urea rice-bran as a source of fermentable energy and protein to 12 sheep fed diets based on urea-treated rice straw (TRS). The three dietary treatments were: T1, TRS with mulberry; T2, TRS with 50% mulberry replaced with rice bran and urea; and T3, TRS with rice bran and urea. The study was arranged in a completely randomized design with four replications for each treatment. The sheep were fed one of the three diets and the supplements were offered at 1.2% of the body weight (BW) and the TRS was provided ad libitum. There were no differences (p>0.05) among the three treatment groups with respect to dry matter (DM) intake (76.8±4.2 g/kg BW(0.75)) and DM, organic matter (OM), and crude protein (CP) digestibility (55.3±1.22; 69.9±0.85; 46.3±1.65% respectively for DM, OM, and CP). The digestibility of fiber (neutral detergent fiber [NDF] and acid detergent fiber) was significantly lower (p<0.05) for T3 (46.2 and 46.6 respectively) compared to T1 (55.8 and 53.7 respectively) and T2 (54.1 and 52.8 respectively). Nitrogen (N) intake by sheep on diet T3 was significantly (p<0.05) higher than sheep fed diet T1. However, N balance did not differ among the three diets (3.0±0.32 g/d). In contrast, the rumen ammonia (NH3-N) concentrations in sheep fed T2 and T3 were significantly (p<0.05) higher than in sheep fed T1. The NH3-N concentrations for all three diets were above the critical value required for optimum rumen microbial growth and synthesis. Total volatile fatty acid concentrations were highest (p<0.05) in T1 (120.3 mM), whilst the molar proportion of propionic acid was highest in T3 (36.9%). However, the microbial N supply in sheep fed T1 and T3 was similar but was significantly (p<0.05) higher than for sheep fed T2. It was concluded that mulberry foliage is a potential supplement of fermentable energy and protein for sheep fed TRS based diet. The suggested level of supplementation is 1.2% of BW or 32% of the total diet since it resulted in similar effects on the intake of DM, OM, and NDF, digestibility of DM, OM, and CP, N utilization and microbial supply when compared to rice bran and urea supplementation.
    Matched MeSH terms: Morus
  7. Chen C, Mohamad Razali UH, Saikim FH, Mahyudin A, Mohd Noor NQI
    Foods, 2021 Mar 23;10(3).
    PMID: 33807100 DOI: 10.3390/foods10030689
    Morus alba L. (M. alba) is a highly adaptable plant that is extensively incorporated in many traditional and Ayurveda medications. Various parts of the plant, such as leaves, fruits, and seeds, possess nutritional and medicinal value. M. alba has abundant phytochemicals, including phenolic acids, flavonoids, flavonols, anthocyanins, macronutrients, vitamins, minerals, and volatile aromatic compounds, indicating its excellent pharmacological abilities. M. alba also contains high nutraceutical values for protein, carbohydrates, fiber, organic acids, vitamins, and minerals, as well as a low lipid value. However, despite its excellent biological properties and nutritional value, M. alba has not been fully considered as a potential functional food ingredient. Therefore, this review reports on the nutrients and bioactive compounds available in M. alba leaves, fruit, and seeds; its nutraceutical properties, functional properties as an ingredient in foodstuffs, and a microencapsulation technique to enhance polyphenol stability. Finally, as scaling up to a bigger production plant is needed to accommodate industrial demand, the study and limitation on an M. alba upscaling process is reviewed.
    Matched MeSH terms: Morus
  8. Pandy V, Khan Y
    Exp Anim, 2016 Nov 1;65(4):437-445.
    PMID: 27333840
    Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings.
    Matched MeSH terms: Morus
  9. Sheikhlar A, Alimon AR, Daud H, Saad CR, Webster CD, Meng GY, et al.
    ScientificWorldJournal, 2014;2014:592709.
    PMID: 25574488 DOI: 10.1155/2014/592709
    Two experiments were simultaneously conducted with Morus alba (white mulberry) foliage extract (MFE) as a growth promoter and treatment of Aeromonas hydrophila infection in separate 60 and 30 days trail (Experiments 1 and 2, resp.) in African catfish (Clarias gariepinus). In Experiment 1, four diets, control and control supplemented with 2, 5, or 7 g MFE/kg dry matter (DM) of diet, were used. In Experiment 2, fish were intraperitoneally infected with Aeromonas hydrophila and fed the same diets as experiment 1 plus additional two diets with or without antibiotic. Results of experiment 1 showed that growth was unaffected by dietary levels of MFE. Treatments with the inclusion of MFE at the levels of 5 and 7 g/Kg DM had no mortality. Red blood cells (RBC), albumin, and total protein were all higher for the treatments fed MFE (5 and 7 g/Kg DM). Results of experiment 2 showed RBC, hemoglobin, hematocrit, globulin, albumin, and total protein improved with the increase in MFE in the infected fish. The dietary MFE at the level of 7 g/kg DM reduced mortality rate. In conclusion, MFE at the level of 7 g/kg DM could be a valuable dietary supplement to cure the infected fish.
    Matched MeSH terms: Morus/chemistry*
  10. Lee CY, Sim SM, Cheng HM
    Nutr Res, 2008 Aug;28(8):555-63.
    PMID: 19083460 DOI: 10.1016/j.nutres.2008.05.001
    The use of a high quercetin dose to demonstrate its absorption and bioavailability does not reflect the real dietary situation because quercetin glycosides are usually present in small amounts in the human diet. This study aimed to demonstrate the absorption and bioavailability of quercetin in mulberry leaves that represents a more physiologic dietary situation. Mulberry leaf ethanol extract was prepared similar to tea infusion, which is the way the tea leaves are generally prepared for consumption. Accordingly, rats were fed by oral intubation the mulberry leaf ethanol extract (15 g%/rat per day) or pure rutin (135 microg/rat per day) for 2 weeks. The control group received a similar volume of the vehicle, 10% ethanol. There was a significant increase in total antioxidant activity (TAA) in the urine and feces of the antioxidants-fed rats. Phenylacetic acid, a microbial metabolite of quercetin, was detected in the urine of the test animals, and quercetin was present in the fecal samples. By using an in situ intestinal preparation, 3-hydroxyphenylacetic acid, another microbial metabolite of quercetin, was detected in the plasma when the duodenal segment was instilled with 2 mg of rutin. This microbial metabolite retained 50% of the TAA of quercetin. The results of this study indicate that in a more realistic dietary situation, an increase in TAA in the body after consumption of quercetin-containing foods is contributed mainly by the microbial metabolites.
    Matched MeSH terms: Morus/chemistry*
  11. Lee CY, Cheng HM, Sim SM
    Biofactors, 2007;31(1):25-33.
    PMID: 18806306
    The ability of the antioxidants in the mulberry leaves to protect Sprague-Dawley rats from injuries caused by immobilization stress was studied as an indicator of the tissue bioavailability of antioxidants. Nitrite level, lipid peroxidation and total antioxidant activity (TAA) in the plasma and tissues were measured. There were hypertrophy of the adrenal glands and kidneys, significant increased levels of nitrite in the plasma and adrenal glands, elevated thiobarbituric acid reactive substances (TBARS) in the plasma, kidneys and spleen, and a reduction of TAA in the plasma, liver, adrenal glands, kidneys and spleen of the immobilized rats. Antioxidants in the mulberry leaf extract suppressed the increase of nitrite and TBARS. Adrenal glands appeared to be the target organ of the antioxidants in the leaf extract. The low dose mulberry antioxidants were more effective than pure rutin (4 mg/day) to protect the cells against inflammation and peroxidation induced by stress.
    Matched MeSH terms: Morus/chemistry*
  12. Jahromi MF, Liang JB, Ebrahimi R, Soleimani AF, Rezaeizadeh A, Abdullah N, et al.
    Animal, 2017 May;11(5):755-761.
    PMID: 27804905 DOI: 10.1017/S175173111600224X
    To alleviate adverse effects of heavy metal toxicity, diverse range of removing methods have been suggested, that is usage of algae, agricultural by-products and microorganisms. Here, we investigated lead (Pb) biosorption efficacy by two lactic acid bacteria species (LABs) in broiler chickens. In an in vitro study, Pb was added to culture medium of LABs (Lactobacillus pentosus ITA23 and Lactobacillus acidipiscis ITA44) in the form of lead acetate. Results showed that these LABs were able to absorb more than 90% of Pb from the culture medium. In follow-up in vivo study, LABs mixture was added to diet of broiler chickens contained lead acetate (200 mg/kg). Pb exposure significantly increased lipid peroxidation and decreased antioxidant activity in liver. The changes were recovered back to normal level upon LABs supplementation. Moreover, addition of LABs eliminated the liver tissue lesion and the suppressed performance in Pb-exposed chicks. Analysis of liver and serum samples indicated 48% and 28% reduction in Pb accumulation, respectively. In conclusion, results of this study showed that L. pentosus ITA23 and L. acidipiscis ITA44 effectively biosorb and expel dietary Pb from gastrointestinal tract of chickens.
    Matched MeSH terms: Morus/microbiology
  13. Gupta G, Chellappan DK, Kikuchi IS, Pinto TJA, Pabreja K, Agrawal M, et al.
    J Environ Pathol Toxicol Oncol, 2017;36(2):113-119.
    PMID: 29199592 DOI: 10.1615/JEnvironPatholToxicolOncol.2017019457
    Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.
    Matched MeSH terms: Morus/chemistry*
  14. Wu YX, Kim YJ, Kwon TH, Tan CP, Son KH, Kim T
    Nat Prod Res, 2020 Jun;34(12):1786-1790.
    PMID: 30470128 DOI: 10.1080/14786419.2018.1527832
    Mulberry (Morus alba L.) root bark (MRB) was extracted using methanol and the extracts were subjected to tests of anti-inflammatory effects. The ethyl acetate fraction demonstrated the best anti-inflammatory effects. Purified compounds, sanggenon B, albanol B and sanggenon D, showed inhibitory effects on NO production in LPS-stimulated RAW264.7 cells and albanol B demonstrated the best anti-inflammatory effects. Regarding the underlying molecular mechanisms, further investigations showed that treatments with Albanol B reduced production of pro-inflammatory cytokines and decreased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results would contribute to development of novel anti-inflammatory drugs from MRB.
    Matched MeSH terms: Morus/chemistry*
  15. Gupta G, Chellappan DK, Agarwal M, Ashwathanarayana M, Nammi S, Pabreja K, et al.
    Cent Nerv Syst Agents Med Chem, 2017;17(3):196-200.
    PMID: 27834136 DOI: 10.2174/1871524917666161111095335
    BACKGROUND: Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action.

    METHODS: Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acid-reactive species (TBARS) and glutathione (GSH) levels.

    RESULTS: AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also produced a significant deterioration in brain AChE action and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Treatment with morusin (5.0 and 10.0 mg/kg, dose orally) significantly overturned AlCl3- induced learning and memory shortages along with diminution of AlCl3-induced rise in brain AChE activity and brain oxidative stress levels.

    CONCLUSION: It may be concluded that morusin exerts a memory-preservative outcome in mental discrepancies of rats feasibly through its various activities.

    Matched MeSH terms: Morus*
  16. Gao C, Sun X, Wu Z, Yuan H, Han H, Huang H, et al.
    Front Pharmacol, 2020;11:391.
    PMID: 32477104 DOI: 10.3389/fphar.2020.00391
    Introduction: The leaves of Morus alba L is a traditional Chinese medicine widely applied in lung diseases. Moracin N (MAN), a secondary metabolite extracted form the leaves of Morus alba L, is a potent anticancer agent. But its molecular mechanism remains unveiled.

    Objective: In this study, we aimed to examine the effect of MAN on human lung cancer and reveal the underlying molecular mechanism.

    Methods: MTT assay was conducted to measure cell viability. Annexin V-FITC/PI staining was used to detect cell apoptosis. Confocal microscope was performed to determine the formation of autophagosomes and autolysosomes. Flow cytometry was performed to quantify cell death. Western blotting was used to determine the related-signaling pathway.

    Results: In the present study, we demonstrated for the first time that MAN inhibitd cell proliferation and induced cell apoptosis in human non-small-cell lung carcinoma (NSCLC) cells. We found that MAN treatment dysregulated mitochondrial function and led to mitochondrial apoptosis in A549 and PC9 cells. Meanwhile, MAN enhanced autophagy flux by the increase of autophagosome formation, the fusion of autophagsomes and lysosomes and lysosomal function. Moreover, mTOR signaling pathway, a classical pathway regualting autophagy, was inhibited by MAN in a time- and dose-dependent mannner, resulting in autophagy induction. Interestingly, autophagy inhibition by CQ or Atg5 knockdown attenuated cell apoptosis by MAN, indicating that autophagy serves as cell death. Furthermore, autophagy-mediated cell death by MAN can be blocked by reactive oxygen species (ROS) scavenger NAC, indicating that ROS accumulation is the inducing factor of apoptosis and autophagy. In summary, we revealed the molecular mechanism of MAN against lung cancer through apoptosis and autophagy, suggesting that MAN might be a novel therapeutic agent for NSCLC treatment.

    Matched MeSH terms: Morus
  17. Shu YH, Yuan HH, Xu MT, Hong YT, Gao CC, Wu ZP, et al.
    Acta Pharmacol Sin, 2021 May;42(5):780-790.
    PMID: 32814819 DOI: 10.1038/s41401-020-0492-5
    Guangsangon E (GSE) is a novel Diels-Alder adduct isolated from leaves of Morus alba L, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP-LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as "autophagy-mediated cell death." Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.
    Matched MeSH terms: Morus/chemistry*
  18. Ezzat MI, Hassan M, Abdelhalim MA, El-Desoky AM, Mohamed SO, Ezzat SM
    Food Funct, 2021 Mar 18.
    PMID: 33734250 DOI: 10.1039/d0fo03402a
    Morinda citrifolia L. is a plant of the family Rubiaceae and is known as Indian mulberry or Noni in India. It is a perennial herb native to Southeast Asia and has been used over the years as a food supplement and medicinal plant. Noni fruits are reported to possess anticancer, fungicidal, antiviral and antiarthritic effects. The objective of our study is the screening of the immunomodulatory activity of the total extract, fractions, and isolated compounds of Noni fruits to identify their bioactive compounds. To achieve our goal, an ethanol extract (EE) was prepared from Noni fruits. Fractionation and purification of the EE were accomplished. The cell-mediated immune (CMI) response in prednisolone-induced immunosuppression rats was evaluated. The toxicity of the EE, fractions and isolated compounds on the differentiated THP-1 macrophage was assessed using the MTT viability assay. Moreover, the inflammation-related immune responses in lipopolysaccharide (LPS)-induced THP-1 macrophage activation were evaluated. Fractionation of the EE gave three fractions, dichloromethane (DCMF), water (WF) and methanol (MF). Purification of DCMF yielded stigmast-7-ene-3-ol (M1), 28-hydroxy-3β-acetoxy-9-dehydrogramisterol (M2), 3β-acetoxy-taraxast-20(30)-ene-21-ol (M3), 22-dehydroclerosterol (M4) and 22-dehydroclerosterol-3-O-β-d-glucopyranoside (M5), while purification of MF yielded quercetin (M6), hesperidin (M7), naringin (M9) and gallic acid (M8). The results revealed that DCMF elicited an increase in paw edema to the extent of 35.8%. All the tested samples had no cytotoxic effect on THP-1 macrophages. Co-treatment of the LPS-induced macrophages with DCMF, M2, M3, and M6 decreased the production of TNF-α, IL-1β, and IL-6/IL-10. The expression of iNOS, COX-2, and NF-κB decreased to 0.14 ± 0.02, 0.15 ± 0.02, and 0.17 ± 0.03, respectively, after co-treatment with LPS and DCMF. M2 attenuated the expression of iNOS and NF-κB to 0.18 ± 0.03 and 0.17 ± 0.03, respectively. Additionally, M3 attenuated the expression of iNOS to 0.18 ± 0.03, and after co-treatment with M6 and LPS, the expression of COX-2 and NF-κB was down-regulated to 0.2 ± 0.03. Our study proves the immunomodulatory effect of Noni fruits and specifies for the first time the compounds responsible for their activity.
    Matched MeSH terms: Morus
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