Bark Of Myrica Rubra Research Articles

Myricanol improves metabolic profiles in dexamethasone induced lipid and protein metabolism disorders in mice

Myricanol (MY) is one of the main active components from bark of Myrica Rubra. It is demonstrated that MY rescues dexamethasone (DEX)-induced muscle dysfunction via activating silent information regulator 1 (SIRT1) and increasing adenosine 5’-monophosphate-activated protein kinase (AMPK) phosphorylation. Since SIRT1 and AMPK are widely involved in the metabolism of nutrients, we speculated that MY may exert beneficial effects on DEX-induced metabolic disorders. This study for the first time applied widely targeted metabolomics to investigate the beneficial effects of MY on glucose, lipids, and protein metabolism in DEX-induced metabolic abnormality in mice. The results showed that MY significantly reversed DEX-induced soleus and gastrocnemius muscle weight loss, muscle fiber damage, and muscle strength loss. MY alleviated DEX-induced metabolic disorders by increasing SIRT1 and glucose transporter type 4 (GLUT4) expressions. Additionally, myricanol prevented muscle cell apoptosis and atrophy by inhibiting caspase 3 cleavages and muscle ring-finger protein-1 (MuRF1) expression. Metabolomics showed that MY treatment reversed the serum content of carnitine ph-C1, palmitoleic acid, PS (16:0_17:0), PC (14:0_20:5), PE (P-18:1_16:1), Cer (t18:2/38:1(2OH)), four amino acids and their metabolites, and 16 glycerolipids in DEX mice. Kyoto encyclopedia of genes and genomes (KEGG) and metabolic set enrichment analysis (MSEA) analysis revealed that MY mainly affected metabolic pathways, glycerolipid metabolism, lipolysis, fat digestion and absorption, lipid and atherosclerosis, and cholesterol metabolism pathways through regulation of metabolites involved in glutathione, butanoate, vitamin B6, glycine, serine and threonine, arachidonic acid, and riboflavin metabolism. Collectively, MY can be used as an attractive therapeutic agent for DEX-induced metabolic abnormalities.

Myricanol Inhibits Platelet Derived Growth Factor-BB-Induced Vascular Smooth Muscle Cells Proliferation and Migration in vitro and Intimal Hyperplasia in vivo by Targeting the Platelet-Derived Growth Factor Receptor-β and NF-κB Signaling.

The abnormal proliferation and migration of Vascular smooth muscle cells (VSMCs) are related to many cardiovascular diseases, including atherosclerosis, restenosis after balloon angioplasty, hypertension, etc. Myricanol is a diarylheptanoid that can be separated from the bark of Myrica rubra. It has been reported that myricanol can anti-inflammatory, anti-cancer, anti-neurodegenerative, promote autophagic clearance of tau and prevent muscle atrophy. But its potential role in the cardiovascular field remains unknown. In this study, we investigated the effect of myricanol on the proliferation and migration of VSMCs in vitro and on the intimal hyperplasia in vivo. In vitro experiments, we found myricanol can inhibit the proliferation and migration of VSMCs induced by PDGF-BB. In terms of mechanism, the preincubation of myricanol can suppress the PDGF-BB induced phosphorylation of PDGFRβ and its downstream such as PLCγ1, Src, and MAPKs. In addition, NF-kB p65 translocation was also suppressed by myricanol. In vivo experiments, we found myricanol can suppress the intimal hyperplasia after wire ligation of the carotid artery in mice. These results may provide a new strategy for the prevention and treatment of coronary atherosclerosis and post-stent stenosis in the future.

Hypolipidemic effects of Myrica rubra extracts and main compounds in C57BL/6j mice.

The present study evaluated the antihyperlipidemic activity of myricetin, myricetrin, the alcohol fraction (AF) and the ethyl acetate fraction (EF) obtained from the bark of Myrica rubra (MR) in high-fat and high-cholesterol (HFHC) induced hyperlipidemic C57BL/6j mice. Mice were treated with myricetin, myricetrin, AF and EF with a dose of 130 mg per kg per day for 35 days. After treatment, serum parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA), etc., were examined. The results revealed that EF showed the highest weight lowering activity (P < 0.01). All tested samples decreased the levels of the TC, TG, LDL-C, TBA and LPS (lipopolysaccharide) content in the serum of mice to different extents. Liver fat deposition was significantly reduced after myricetin, myricetrin, AF and EF therapy (P < 0.01). Additionally, the cell size of epididymal adipose tissue was also decreased in myricetin, AF and EF groups (P < 0.05). The antihyperlipidemic activity of these samples may be attributed to the inhibition of lipid synthesis via suppressing the expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and ACC1 (acetyl-CoA carboxylase), promoting the metabolism and excretion of lipids via up-regulating the expression of SREBP2 (sterol regulatory element binding proteins), LDLR (low density lipoprotein receptor), UCP2 (uncoupling protein 2) and CYP7A1 (cholesterol 7α-hydroxylase). These results may provide a powerful foundation for seeking and utilizing Myrica rubra bio-active compounds for the treatment of hyperlipidemia and cardiovascular diseases.

Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway.

Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark of Myrica rubra, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway.

Growth-inhibiting and apoptosis-inducing activities of Myricanol from the bark of Myrica rubra in human lung adenocarcinoma A549 cells

Myrica rubra (Lour.) Sieb. Et Zucc. is a myricaceae Myrica plant. It is a subtropical fruit tree in China and other Asian countries. The bark of M. rubra is used in Chinese folk medicine because of its antibacterial, antioxidant, anti-inflammatory, and anticancer activities. However, the mechanisms underlying such activities remain unclear.This study investigated whether or not Myricanol extracted from M. rubra bark elicits anti-cancer effects on human lung adenocarcinoma A549 cells by inducing apoptosis in vivo.Myricanol was extracted from M. rubra bark through system solvent extraction and silica gel layer column separation. The results of tritiated thymidine assay, colony formation assay, and flow cytometry indicated that Myricanol inhibited the growth of A549 cells. The effects of Myricanol on the expression of key apoptosis-related genes in A549 cells were evaluated by quantitative PCR and Western blot analyses.Myricanol significantly inhibited the growth of A549 cells in a dose-dependent manner, with a half maximal inhibitory concentration of 4.85μg/ml. Myricanol significantly decreased colony formation and induced A549 cell apoptosis. Myricanol upregulated the expression of Caspase-3, Caspase-9, Bax, and p21 and downregulated the expression of Bcl-2 at the mRNA and protein levels. These changes were associated with apoptosis.Based on these results, we propose that Myricanol elicits growth inhibitory and cytotoxic effects on lung cancer cells. Therefore, Myricanol may be a clinical candidate for the prevention and treatment of lung cancer.

Diarylheptanoid Sulfates and Related Compounds from Myrica rubra Bark

Three new diarylheptanoids, myricanol 11-sulfate (1), juglanin B 11-sulfate (2), and myricanone 5-O-(6'-O-galloyl)glucoside (3), were isolated from the bark of Myrica rubra. Compounds 1 and 2 were characterized as diarylheptanoid sulfates on the basis of spectroscopic analyses. The antioxidative activities of the fractionated extracts and isolated compounds were estimated by the oxygen radical absorbance capacity (ORAC) and superoxide dismutase (SOD)-like activity assays. The major isolate, myricitrin (4), displayed a high ORAC value and moderate SOD-like activity (13,198 μmol TE (Trolox equivalent)/g and IC₅₀ 127.5 μg/mL, respectively), which might explain the potent antioxidative activity of this material.

Three New Cyclic Diarylheptanoids and Other Phenolic Compounds from the Bark of Myrica rubra and Their Melanogenesis Inhibitory and Radical Scavenging Activities

Ten cyclic diarylheptanoids (1-10), including three new compounds: myricanone 5-O-alpha-L-arabinofuranosyl-(1-->6)-beta-D-glucopyranoside (7), myricanone 17-O-beta-D-(6'-O-galloyl)-glucopyranoside (8), and 16-methoxy acerogenin B 9-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (10), along with two flavonoids (11, 12), were isolated from the extracts of Myrica rubra (Myricaceae) bark. The structures of new compounds were determined on the basis of spectroscopic methods. On evaluation of compounds 1-12 against the melanogenesis in the B16 melanoma cells, six compounds, 3, 5, 7, 8, 10, and 12, exhibited inhibitory effects with 30-56% reduction of melanin content at 25 microg/mL with no or very weak toxicity to the cells (82-103% of cell viability at 25 microg/mL). In addition, upon evaluation of compounds 1-12 against the scavenging activities of free radicals [against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical], seven compounds, 1, 3, 5, 6, 8, 11, and 12, showed potent scavenging activity [IC(50) 2-21 microM (0.6-7.3 microg/mL)].

ChemInform Abstract: A New Diarylheptanoid from the Bark of Myrica rubra

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A new diarylheptanoid from the bark of Myrica rubra

A new diarylheptanoid, 3,5-dimethoxyl-17-hydroxyl-4,11,19-triketo-[7,0]meta-cyclophane, named as rubanone 1, was isolated from the bark of Myrica rubra along with four known compounds 2– 5. Their structures were elucidated by various spectroscopic methods including 2D-NMR techniques or comparison with authentic samples.

A new diaryheptanoid from the bark of Myrica rubra

A new diarylheptanoid, (11ξ)-3,5-dimethoxy-11,17-dihydroxy-4,19-diketo-[7,0]-metacyc- lophane, named as rubanol 1, was isolated from the bark of Myrica rubra along with four known compounds (2–5). Their structures were determined by spectroscopic methods including 1D, 2D NMR or comparison with authentic samples. Compound 1 exhibited cytotoxicity against Lun-06, Neu-04, and Bre-04 cell lines with GI50 values of 16.03–32.58 µg mL−1.

Prodelphinidin B-2 3,3′-di- O-gallate from Myrica rubra inhibits proliferation of A549 carcinoma cells via blocking cell cycle progression and inducing apoptosis

In this study, the antiproliferative activity of prodelphinidin B-2 3, 3′-di- O-gallate (PB233′OG) isolated from the bark of Myrica rubra (Myricaceae) was investigated. The results showed that PB233′OG inhibited the proliferation of A549 by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. Enzyme-linked immunosorbent assay (ELISA) showed that the G0/G1 phase arrest is due to increase the expression of p21/WAF1. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the apoptotic effect induced by PB233′OG. Our study reports here for the first time that the induction of p21/WAF1 and activity of the Fas/Fas ligand apoptotic system may participate in the anti-proliferative activity of PB233′OG in A549 cells.

In vitro antiviral activity of prodelphinidin B-2 3,3'-di-O-gallate from Myrica rubra.

In this study, the in vitro antiviral properties of prodelphinidin B-2 3,3'-di- O-gallate (PB233'OG) isolated from the bark of Myrica rubra (Myricaceae) was investigated. Results showed that PB233'OG exhibited anti-herpes simplex virus type 2 (HSV-2) activity with IC (50) values of 5.3 +/- 0.1 and 0.4 +/- 0.04 microM for XTT and plaque reduction assays, respectively. The IC (50) value increased with increasing MOI (multiplicity of infection). PB233'OG did not show a cellular cytotoxic effect at concentrations that possessed antiviral activity. Mechanistic studies demonstrated that PB233'OG inhibited HSV-2 attachment to the Vero cell, interfered with the penetration of HSV-2 into the Vero cell, affected the late stage(s) of the HSV-2 infection cycle, and also reduced the viral infectivity at high concentrations. It is concluded that PB233'OG exhibits various modes of action in its anti-HSV-2 effects.

Inhibitors of nitric oxide production from the bark of Myrica rubra: structures of new biphenyl type diarylheptanoid glycosides and taraxerane type triterpene

Three new biphenyl type diarylheptanoid glycosides, myricanol 11- O-β- d-glucopyranoside, myricanone 5- O-β- d-glucopyranoside, and neomyricanone 5- O-β- d-glucopyranoside, and a new taraxerane type triterpene, myricetrione, were isolated from the bark of Chinese Myrica rubra. Their structures were elucidated on the basis of chemical and physicochemical evidence. Biphenyl type diarylheptanoids, triterpene, and their polyphenols showed potent inhibitory effects on nitric oxide production in lipopolysaccharide-activated macrophages. Furthermore, diarylheptanoids, myricanol and myricanone, were found to inhibit induction of inducible nitric oxide synthase.

ChemInform Abstract: Bioactive Constituents of Chinese Natural Medicines. Part 7. Inhibitors of Degranulation in RBL‐2H3 Cells and Absolute Stereostructures of Three New Diarylheptanoid Glycosides (I)—(III) from the Bark of Myrica rubra.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Bioactive constituents of Chinese natural medicines. VII. Inhibitors of degranulation in RBL-2H3 cells and absolute stereostructures of three new diarylheptanoid glycosides from the bark of Myrica rubra.

Three new diarylheptanoid glycosides, named (+)-S-myricanol 5-0-beta-D-glucopyranoside, myricanene A 5-O-alpha-L-arabinofuranosyl(1-->6)-beta-D-glucopyranoside, and myricanene B 5-0-alpha-L-arabinofuranosyl(1-->6)-beta-D-glucopyranoside, were isolated from the bark of Chinese Myrica rubra, together with twenty known compounds. The absolute stereostructures of the new diarylheptanoid glycosides were elucidated on the basis of chemical and physicochemical evidence, including the application of the modified Mosher's method. The inhibitory effects of isolated constituents on the release of beta-hexosaminidase from RBL-2H3 cells were examined, and several diarylheptanoids, myricanol, (+)-S-myricanol, myricanone, and myricanenes A and B, and a flavonol, myricetin, were found to show the inhibitory activity.

Studies of cuticle drugs from natural sources. III. Inhibitory effect of Myrica rubra on melanin biosynthesis.

The inhibitory effect of a 50% ethanolic extract obtained from the dried leaves and the bark of Myrica rubra, was investigated in vitro on melanin biosynthesis which is closely related to hyperpigmentation. These extracts inhibited tyrosinase activity which converts dopa to dopachrome in the biosynthetic process. Furthermore, the extracts inhibited the production of melanin from dopachrome by autoxidation and also showed superoxide dismutase (SOD)-like activity. After bioassay-guided fractionation, quercetin, myricetin and myricetin 3-O-rhamnoside were isolated from the leaves. As they showed the inhibitory effect on tyrosinase activity, the activity is partially attributable to them in the extract of M. rubra. These results suggested that the leaves or the bark of M. rubra might be used as a whitening agent for the skin.