Morus Root Research Articles

Morusin Protected Ruminal Epithelial Cells against Lipopolysaccharide-Induced Inflammation through Inhibiting EGFR-AKT/NF-κB Signaling and Improving Barrier Functions.

Using phytogenic extracts for preventing or treating rumen epithelial inflammatory injury is a potential alternative to antibiotic use due to their residue-free characteristics. In this study, the efficacy of Morus root bark extract Morusin on ruminal epithelial cells (RECs) against pathogenic stimulus was investigated for the first time. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and quantitative real-time polymerase chain reaction (qPCR) results showed that the Morusin did not affect the cell viability of RECs and exerted anti-inflammatory effects in a concentration-dependent manner. Transcriptome analysis further revealed that the Morusin significantly downregulated the inflammatory-response-related cell signaling, while it upregulated the cell-proliferation-inhibition- and barrier-function-related processes in RECs upon lipopolysaccharide (LPS) stimulation. The epidermal growth factor receptor (EGFR) blocking and immunoblotting analysis further confirmed that the Morusin suppressed LPS-induced inflammation in RECs by downregulating the phosphorylation of protein kinase B (AKT) and nuclear factor-kappaB (NF-κB) p65 protein via inhibiting the EGFR signaling. These findings demonstrate the protective roles of Morusin in LPS-induced inflammation in RECs.

Organ-Specific Analysis of Morus alba Using a Gel-Free/Label-Free Proteomic Technique.

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.

Protective Effects of Morus Root Extract (MRE) Against Lipopolysaccharide-Activated RAW264.7 Cells and CCl4-Induced Mouse Hepatic Damage

Background/Aims: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity. Methods: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl₄-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Results: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl₄-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl₄-induced hepatic iNOS and COX-2 expression, as well as CCl₄-induced hepatic inflammation and necrosis in mice. Conclusion: MRE exhibited antiinflammatory and hepatic protective activity.

Effects of Morus root bark extract and active constituents on blood lipids in hyperlipidemia rats

ObjectiveChinese crude drug Mori Cortex Radicis (the root cortex of Morus species) has been used as a folk medicine to treat hypertension, diabetes, as well as in expectorant, diuretic agents. This investigation aims to study the anti-hyperlipidemia effects of Mori Cortex Radicis (MCR) extracts in hyperlipidemic rat models and the potential therapeutic activities of compounds isolated from the extracts. Materials and methodsThe effects of MCR on hypolipidemic parameters were investigated using Wistar rats induced by high-lipid emulsion. Sixty healthy Wistar rats were randomly divided into 6 groups: normal group, hyperlipidaemia model group, simvastatin, and high-, medium- and low-dose MCR extracts. After four weeks, body weight, total cholesterol (TC), triglycerides (TG), high and low-density lipoproteins (HDL, LDL), as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured. To further investigation, four major active compounds were isolated from extracts through high performance liquid chromatography (HPLC) and their diacylglycerol acyltransferase 1 (DGAT1) inhibitory activity was evaluated. ResultsMCR dose-dependently reduced serum TC, TG, LDL-C, inhibited the activity of ALT, AST, and increased HDL-C. Furthermore, in vitro biochemistry tests revealed that four active isolates showed moderate inhibitory activity against DGAT1 with IC50 values ranging from 62.1±1.2 to 99.3±2.3µM. ConclusionsThe results demonstrated that MCR could effectively ameliorate hyperlipidaemia and inhibit DGAT1 that a key enzyme closely related to hyperlipidaemia and type 2 diabetes. It may provide a new pharmacological basis for treating hyperlipidaemia and related diseases using MCR.

상백피로부터 α-Glucosidase 저해제의 분리 및 동정

ABSTRACT Among the four different parts of mulberry ( Morus alba L.) tree, ethanol extract of Morus root bark showed the highest α-glucosidase inhibitory activity (IC 50 =12.01 μg/mL). Bioassay-guided fractionation of the ethanolic extract of root bark by Diaion HP-20, silica gel, ODS-A, and Sephadex LH-20 column chromatographies led to the isolation of four compounds, including Compound (Comp.) 1 (IC 50 =5.22 μg/mL), Comp. 2 (IC 50 =1.78 μg/mL), Comp. 3 (IC 50 =2.94 μg/mL), and Comp. 4 (IC 50 =1.54 μg/mL) with strong α-glucosidase inhibitory activities. Their chemical structures were elucidated as morusin (Comp. 1), kuwanon H (Comp. 2), chalcomoracin A (Comp. 3), and chalcomoracin B (Comp. 4) by UV and NMR spectral analyses. These results suggest that prenylflavonoid and mulberrofuran of Morus root bark may be useful as potential therapeutic agents for diabetes. Key words: Morus root bark, α-glucosidase inhibitors, morusin, kuwanon H, chalcomoracin A & BReceived 3 March 2015; Accepted 22 April 2015 Corresponding author: Sang Won Choi, Department of Food Science and Nutrition, Catholic University of Daegu, Gyeongsan,Gyeongbuk 712-702, Korea E-mail: swchoi@cu.ac.kr, Phone: +82-53-850-3525

The First Total Synthesis Of Morusin And Himanimide D As Arachidonate 5-lipoxygenase Inhibitor In Automated Docking

Our research group has exhibited a long-standing interest in the synthesis and bioassay study of a number of unique natural products containing flavonoids, camphorataimides, and benzofurans. In previous works, we have shown that tumor suppressor protein p53 and p38 MAPK (mitogen activated protein kinase) play a prominent role in the caffaic acid phenethyl ester (CAPE) induced-apoptosis of C6 glioma cells. In addition, studies on the constituents of the Chinese crude drug “Sang-bai-pi” (Morus root bark) have been recorded in books of traditional Chinese herbal medicines, which are used as an antiphlogistic, a diuretic, an expectorant, and anti-hepatitis B activity. Herein, we present the first total synthesis of morusin and himanimide D, and then show the development of the COX/LOX inhibitors by an automated docking method. Morusin, which can be isolated from Chinese herbal medicine, is achieved in which the longest linear sequence is only 13 steps in 12% overall yield from commercially available phloroglucinol. In addition, to probe accessibility of the active sites of proteins, particular COXs/LOXs, the binding affinity of protein-ligand complexes were examined by an automated docking method. Consequently, the rationally optimized LEE-BNOHDM was identified as a potent inhibitor of the arachidonate 5-lipoxygenase.

Constituents from Morus root bark against Venturia inaequalis – the causal agent of apple scab

Constituents from Morus root bark against Venturia inaequalis – the causal agent of apple scab

Venturia inaequalis-Inhibiting Diels−Alder Adducts from Morus Root Bark

In organic apple orcharding there is a continuous need for natural fungicides effective against Venturia inaequalis (Cooke) Winter, the causal agent of apple scab. In this study an in vitro assay is presented for determining the germination inhibitory potential of extracts and pure compounds. From a screening of plant extracts, the methanol extract of Morus root bark revealed distinct V. inaequalis inhibiting qualities, which were subjected to a bioguided fractionation. Among the isolated metabolites [moracins M (1), O/P (2), kuwanon L (3), and sanggenons D (4), B (5), G (6), O (7), E (8), and C (9)] all the Diels-Alder adducts (3-9) showed an antifungal activity with IC50 values between 10 and 123 microM. The in vitro activity of the most active fraction (A5, IC50 39.0 +/- 4.2 microg/mL) was evaluated in vivo, confirming a distinct antifungal activity against V. inaequalis for the tested natural material.

Protein tyrosine phosphatase 1B inhibitors from Morus root bark

An organic layer prepared from the Chinese crude drug ‘Sang-Bai-Pi’ ( Morus root bark) was studied in order to identify the inhibitory compounds for protein tyrosine phosphatase 1B (PTP1B). Bioassay-guided fractionation resulted in the isolation of sanggenon C ( 1), sanggenon G ( 2), mulberrofuran C ( 3) and kuwanon L ( 4) as PTP1B inhibitors, along with moracin O ( 5) and moracin P ( 6). Compounds 1– 4 inhibited PTP1B with IC 50 values ranging from 1.6 ± 0.3 μM to 16.9 ± 1.1 μM.

Discovering COX-Inhibiting Constituents ofMorusRoot Bark: Activity-Guided versus Computer-Aided Methods

The aim of this study was to compare the efficiency of two well known approaches for the discovery of the bioactive principle/s in medicinal plants, namely the activity-guided isolation versus the computer-aided drug discovery by means of virtual screening (VS) techniques. Morus root bark of Morus sp. L. (Moraceae) was selected as application example for the discovery of compounds with anti-inflammatory activity. The two cyclooxygenase isoenzymes COX-1 and COX-2 were chosen as targets and the corresponding pharmacophore models were generated by our research. The activity-guided fractionation of the methanol extract of the root bark resulted in the isolation of nine compounds. Their structures were elucidated by mass spectrometry, 1- and 2-dimensional NMR experiments and identified as moracins B, M, the regioisomers O/P as a mixture, and sanggenons B, C, D, E and O. The COX-1 and COX-2 inhibiting activities of these compounds were established in an enzyme assay and compared with the predicted hits obtained from the VS. Sanggenons C, E, and O, that were tested the first time for an inhibitory effect on COX-1 and -2, showed IC50 values of 10-14 microM, and 40-50 microM, respectively. The results show that the COX activities obtained for the sanggenons are correctly predicted by the in silico filtering experiment. In the case of the isolated moracins, however, it failed because the COX inhibiting activities of moracins M and P/O were not retrieved by the VS. Structure-activity relationships of the isolated compounds are discussed as well as potential pitfalls and advantages of the applied strategies.

プレニールフラボノイドの化学と生合成

Many isoprenylated flavonoids have been isolated from mulberry trees and related plants (Moraceae). Among them, kuwanons G (13) and H (14) were the first isolated active substances exhibiting a hypotensive effect from the Japanese Morus root bark. These compounds are considered to be formed through an enzymatic Diels-Alder reaction of a chalcone (15) and dehydro-kuwanon C (16) or its equivalent. Since that time, about forty kinds of Diels-Alder type adducts structurally similar to that of 13 have been isolated from the moraceous plants. Some strains of Morus alba as well as M. bombycis callus tissues have a high productivity of mulberry Diels-Alder type adducts, such as chalcomoracin (26) and kuwanon J (28). The biosynthesis of the mulberry Diels-Alder type adducts has been studied with the aid of the cell strain. Chalcomoracin (26) and kuwanon J (28) were proved to be enzymatic Diels-Alder type reaction products by the administration experiment with O-methylchalcone derivatives. Furthermore, for the isoprenoid biosynthesis of prenylflavonoids in Morus alba callus tissues, a novel way through the junction of glycolysis and pentose-phosphate cycle was proposed. The crude enzyme fraction catalyzing the Morus Diels-Alder type reaction could be isolated. Studies of phenolic constituents of licorice (Glycyrrhiza species) were carried out. On the course of the structure determination of the phenolic constituents of licorice, two new NMR structure determination methods for prenylflavonoids were found. Furthermore, the prenylphenols isolated from licorice were summarized according to the origin of the materials.

The chemistry and biosynthesis of isoprenylated flavonoids from moraceous plants

Abstract

Sanggenons R, S, and T, Three New Isoprentylated Phenoles from the Chinese Crude Drug "Sang-Bai-Pi" (Morus Root Bark)

Sanggenons R, S, and T, Three New Isoprentylated Phenoles from the Chinese Crude Drug "Sang-Bai-Pi" (Morus Root Bark)

Absolute Configuration of Natural Diels-Alder Type Adducts from the Morus Root Bark

Absolute Configuration of Natural Diels-Alder Type Adducts from the Morus Root Bark

Structures of Sanggenons E and P, Two New Diles-Alder Type Adducts from the Chinese Crude Drug "Sang-Bai-Pi" (Morus Root Bark)

Structures of Sanggenons E and P, Two New Diles-Alder Type Adducts from the Chinese Crude Drug "Sang-Bai-Pi" (Morus Root Bark)

Structure of Sanggenon O, a Natural Diels-Alder Type Adduct from Chinese Crude Drug "Sang-Bai-Pi" (Morus Root Bark)

Structure of Sanggenon O, a Natural Diels-Alder Type Adduct from Chinese Crude Drug "Sang-Bai-Pi" (Morus Root Bark)

Structures of three new 2-arylbenzofuran derivatives from the chinese crude drug "Sang-Bai-Pi" (morus root bark).

Three new 2-arylbenzofuran derivatives named mulberrofurans K, N, and O were isolated from the extract of the Chinese crude drug "Sang-Bai-Pi" (Japanese name "Sohakuhi"), the root bark of Morus sp. (Moraceae). The structures of mulberrofurans K, N and O were shown to be 1, 2, and 3, respectively, on the basis of spectral and chemical evidence. Mulberrofurans K and O are optically active and may be regarded biogenetically as Diels-Alder type adducts of chalcone derivatives and a dehydroprenyl-2-arylbenzofuran derivative. Furthermore, mulberrofuran K seems to be derived from the Diels-Alder type adduct by intramolecular ketalization.

Constituents of the Chinese Crude Drug "Sang-Bái-pí" (Morus Root Bark) V. Structures of Three New Flavanones, Sanggenons L, M, and N

Constituents of the Chinese Crude Drug "Sang-Bái-pí" (Morus Root Bark) V. Structures of Three New Flavanones, Sanggenons L, M, and N

Structure of mulberrofuran I, a novel 2-arylbenzofuran derivative from the cultivated mulberry tree (Morus bombycis Koidz.).

From an acetone extract of the reddish violet powder obtained from the surface of the Morus root bark (Morus bombycis Koidz.), a 2-arylbenzofuran derivative was isolated and named mulberrofuran I. Its structure was shown to be 1 on the basis of spectral evidence. Mulberrofuran I is regarded biogenetically as a variation of a Diels-Alder type adduct of a chalcone derivative and a dehydroprenyl-2-arylbenzofuran derivative.

Structure of Mulberrofuran K, an Optically Active Natiral Diels-Alder Type Adduct from Chinese Crude Drug "Sang-Bai-Pi" (Morus Root Bark)

Structure of Mulberrofuran K, an Optically Active Natiral Diels-Alder Type Adduct from Chinese Crude Drug "Sang-Bai-Pi" (Morus Root Bark)