Murrayanine

Murrayanine exerts antiproliferative effects on human oral cancer cells through inhibition of AKT/mTOR and Raf/MEK/ERK signalling pathways in vitro and inhibits tumor growth in vivo.[Pubmed:31983115]

J BUON. 2019 Nov-Dec;24(6):2423-2428.

PURPOSE: Oral cancer ranks as the 6th most prevalent type of cancer accounting for significant mortality around the world and studies are being directed to develop efficient chemotherapy for oral cancer. In this study the anticancer effects of a carbazole alkaloid Murrayanine were investigated in vitro and in vivo. METHODS: Cell counting assay and colony formation assay were used to examine cell viability. DAPI and propidium iodide (PI) staining were used to detect apoptosis. Western blotting was used to examine protein expression. Xenografted mice were used for in vivo study. RESULTS: The results showed that Murrayanine decreased the viability of the oral cancer SCC-25 cells and exhibited an IC50 of 15 microM. The cytotoxicity of Murrayanine was also investigated on the normal hTERT-OME cells and it was found that this molecule exerted very low toxic effects on these cells exhibiting an IC50 of 92 microM. Murrayanine also caused considerable changes in the morphology of the SCC-25 cells and inhibited their colony forming potential. PI and DAPI staining revealed that Murrayanine prompted apoptosis of the SCC-25 cells. The apoptotic cells from 2.2% in the control increased to around 35% at 30 microM concentration. Moreover, Murrayanine caused increase in the Bax/Bcl-2 ratio and also increased the expression of Caspase-3. Murrayanine also deactivated the AKT/mTOR and Raf/MEK/ERK signalling pathways and suppressed the growth of the xenografted tumors in vivo. CONCLUSION: The findings of the present investigation suggest that Murrayanine may prove essential in the development of systemic therapy for oral cancers.

[Chemical constituents from stems and leaves of Clausena emarginata].[Pubmed:31355567]

Zhongguo Zhong Yao Za Zhi. 2019 May;44(10):2096-2101.

The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),Murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.

Murrayanine Induces Cell Cycle Arrest, Oxidative Stress, and Inhibition of Phosphorylated p38 Expression in A549 Lung Adenocarcinoma Cells.[Pubmed:30879017]

Med Sci Monit. 2019 Mar 17;25:2002-2008.

BACKGROUND Murrayanine is a carbazole alkaloid derived from Murraya koenigii, which has been used in traditional Chinese medicine in the treatment of cancer. This study aimed to investigate the effects of Murrayanine on human lung adenocarcinoma cells in vitro and to investigate the mechanisms of its action. MATERIAL AND METHODS A549 human lung adenocarcinoma cells and MRC-5 human lung fibroblasts were grown in culture, and an MTT assay determined cell viability. Cells were treated for 24 h with increasing doses of Murrayanine (0, 9, 18, and 36 microM). Fluorescence, using 4', 6-diamidino-2-phenylindole (DAPI), acridine orange, ethidium bromide, and propidium iodide (PI), were used for the detection of apoptosis. The cell cycle was studied with fluorescence-activated cell sorting (FACS), and Western blot evaluated protein expression. RESULTS Murrayanine treatment resulted in significant dose-dependent inhibition of the growth of A549 cells (p<0.05), with an IC(5)(0) of 9 microM, and arrested the cells at the G2/M phase of the cell cycle, reduced the expression of cyclin D and E, CDK2, 4, and 6, and increased the expression of p21 and p27. Murrayanine treatment increased apoptosis of the A549 cells and increased cleaved of caspase-3 and caspase-9, and the Bax/Bcl-2 ratio. Murrayanine treatment increased levels of reactive oxygen species (ROS), disrupted the mitochondrial membrane potential, inhibited invasion, and inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK) of the A549 cells. CONCLUSIONS Murrayanine induced cell cycle arrest, oxidative stress, and inhibited the expression of phosphorylated p38 in A549 adenocarcinoma cells.

Murrayanine Attenuates Lipopolysaccharide-induced Inflammation and Protects Mice from Sepsis-associated Organ Failure.[Pubmed:29719125]

Basic Clin Pharmacol Toxicol. 2019 Apr;124(4):351-359.

Murrayanine (MK) is the main compound isolated from Murraya koenigii, an aromatic plant belonging to the Rutaceae family, also known as curry leaf tree. Murrayanine was reported to possess potential antioxidant, antimycobacterial and antifungal effects. However, its effect in sepsis remains unclear. This study was designed to investigate the anti-inflammatory effect of MK using both in vitro and in vivo assay. Results of this study indicated that MK decreased NO, TNF-alpha and IL-6 production in both lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and murine peritoneal macrophages. Moreover, iNOS and COX-2 protein expression as well as their downstream product, PGE2, was also decreased effectively in RAW 264.7 cells. Furthermore, MK decreased the phosphorylation of IKB and repressed NF-kB activity in LPS-activated RAW 264.7 cells. Additionally, we evaluated MK efficacy in vivo using LPS-induced sepsis, a systemic inflammation model in mice. Administration of MK inhibits pro-inflammatory cytokines (TNF-alpha and IL-6) secretion; decreases AST, ALT, BUN and CRE level in mouse sera; mitigates lung, liver and kidney injuries; and also increases LPS-challenged mice survival rate. Collectively, our results suggest that MK exerts potential as a new anti-inflammatory and immunosuppressive drug in sepsis treatment.

Four new carbazole alkaloids from Murraya koenigii that display anti-inflammatory and anti-microbial activities.[Pubmed:26947457]

Org Biomol Chem. 2016 Mar 28;14(12):3322-32.

In our present study, four new, designated as murrayakonine A-D (), along with 18 known carbazole alkaloids were isolated from CHCl3 : MeOH (1 : 1) crude extracts of the stems and leaves of Murraya koenigii (Linn.) Spreng. The structures of the all isolated compounds were characterized by analysis of HR-ESI-MS and NMR (1D and 2D spectroscopy) results, and comparison of their data with the literature data. For the first time, all the isolates were evaluated for their anti-inflammatory activities, using both in vitro and in vivo experiments, against the key inflammatory mediators TNF-alpha and IL-6. The new compound murrayakonine A (), O-methylmurrayamine A () and Murrayanine () were proven to be the most active, efficiently inhibiting TNF-alpha and IL-6 release in a dose-dependent manner and showing decreased LPS induced TNF-alpha and IL-6 production in human PBMCs [corrected]. Furthermore, all the isolates were screened for their antimicrobial potential, and the compounds girinimbine () (IC50 3.4 muM) and 1-hydroxy-7-methoxy-8-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carbaldehyde () (IC50 10.9 muM) displayed potent inhibitory effects against Bacillus cereus. Furthermore, compounds murrayamine J () (IC50 11.7 muM) and koenimbine () (IC50 17.0 muM) were active against Staphylococcus aureus. However, none of the compounds were found to be active against Escherichia coli or Candida albicans.

[Chemical constituents from stems of Clausena excavata].[Pubmed:26027123]

Zhong Yao Cai. 2014 Nov;37(11):2012-5.

OBJECTIVE: To study the chemical constituents from the stems of Clausena excavata. METHODS: The constituents were isolated by various chromatographic techniques(silica gel, RP-MPLC and PHPLC) and their structures were determined on the basis of their spectroscopic data, as well as literatures. RESULTS: Eleven compounds were separated and identified as adicardin(1),7-[O-alpha-L-rh-amnopyranosyl-(1-->6)-O-beta-D-glucopyranosyloxy]cou marin(2), 6-methoxy-7-[O-alpha-L-rhamnopyranosyl-(1-->6)-O-beta-D-glucopyranosyloxy] coumarin (3), alloisoimperatorin (4), isopentenoyloxypsoralen (5), nordentatin (6), xanthyletin (7), 7-hydroxycoumarin (8), 3-formylcarbazole(9), 3-formyl-6-methoxy carbazole(10), and Murrayanine(11). CONCLUSION: compounds 2-4 and 10 are isolated from this plant for the first time, and compounds 1 and 5 are isolated from Clausena genus for the first time.

A new dimeric carbazole alkaloid from Glycosmis stenocarpa roots.[Pubmed:15467229]

Chem Pharm Bull (Tokyo). 2004 Oct;52(10):1175-8.

A new dimeric pyranocarbazole alkaloid, bisisomahanine (1), was isolated from the roots of Glycosmis stenocarpa (DRAKE) TAN., along with two known monomeric carbazole alkaloids, murrayafoline-A (2) and Murrayanine (3). The planar structure of bisisomahanine was determined to be 9,9''-dihydroxy-3,3'',8,8''-tetramethyl-3,3''-bis-(4-methyl-3-pentenyl)-3,3'',11, 11''-tetrahydro-10,10''-(bipyrano[3,2-a]carbazole) from the combination of spectroscopic and chemical evidence. Bisisomahanine is the first dimeric prenylated pyranocarbazole alkaloid with a 1,1' type of linkage; the NMR and CD spectroscopic data indicated it to be a mixture of diastereomers having a dominant configuration at the axis of chirality. (1)H- and (13)C-NMR assignments of murrayafoline-A were made on the basis of 2D-experiments.

Two new carbazole alkaloids from Murraya koenigii.[Pubmed:12662104]

J Nat Prod. 2003 Mar;66(3):416-8.

Two new carbazole alkaloids named Murrayanine (1) and 8,8' '-biskoenigine (2) were isolated from Murraya koenigii. The structure elucidations for 1 and 2 were carried out on the basis of 1D and 2D NMR experiments. Compound 1 was a novel carbazole alkaloid with a rare phenylpropanyl substitution. Compound 2 was a symmetrical dimer of the carbazole alkaloid koenigine and showed antiosteoporotic activity in the CAT-B model with IC(50) 1.3 microg/mL. The synthesis of 2 from koenigine was carried out through oxidative coupling using a solid state reaction.

Coumarins and carbazoles from Clausena excavata exhibited antimycobacterial and antifungal activities.[Pubmed:12624822]

Planta Med. 2003 Feb;69(2):155-7.

Four known coumarins, dentatin (1), nor-dentatin (2), clausenidin (3) and xanthoxyletin (5), and six known carbazole derivatives, 3-formylcarbazole (6), mukonal (7), 3-methoxycarbonylcarbazole (8), Murrayanine (9), 2-hydroxy-3-formyl-7-methoxycarbazole (10) and clauszoline J (11) were isolated from Clausena excavata. Compounds 1 and 6 were first isolated from the crude chloroform extract of the rhizomes. Compounds 1, 2, 3, 6, 7, 8, 10 and 11 showed antimycobacterial activity at a minimum inhibitory concentration (MIC) of 50, 100, 200, 100, 200, 50, 100 and 100 microg/mL, respectively. O-Methylated clausenidin ( 4), prepared from 3, exhibited antimycobacterial activity at MIC 50 microg/mL. Compounds 6, 7, 8 and 10 showed antifungal activity with IC 50 values of 13.6, 29.3, 9.5 and 2.8 microg/mL, respectively. All compounds demonstrated no cytotoxicity against KB and BC-1 cell lines.

[Studies on the chemical constituents of Murraya kwangsiensis].[Pubmed:11218858]

Yao Xue Xue Bao. 2000 Nov;35(11):826-8.

AIM: To investigate the chemical constituents of Murraya kwangsiensis. METHODS: Compounds were isolated by silica gel column chromatography and TLC method, respectively. Structures of compounds were elucidated by spectral (UV, IR, MS, 1HNMR and 13CNMR) analysis. RESULTS: Five carbazole alkaloids and two other compounds were isolated and identified. Six of them are known compounds: murrayafoline A, Murrayanine, koenine, isomahanine, palmitic acid and beta-sitosterol. One is a new alkaloid, named kwangsine. CONCLUSION: A new alkaloid, named kwangsine, was isolated from Murraya kwangsiensis Var. Six known compounds were isolated from this plant for the first time.