Entadamide A

Optimization, extraction, and purification of three bioactive compounds from Entada phaseoloides by high-speed countercurrent chromatography.[Pubmed:34424556]

Biomed Chromatogr. 2021 Dec;35(12):e5232.

The objective of this paper was to develop a preparative method for the separation and purification of phaseoloidin, Entadamide A, and Entadamide A-beta-D-glucopyranoside from the crude extract of Entada phaseoloides by high-speed countercurrent chromatography (HSCCC) for the first time. Optimized by orthogonal experiments, the extraction conditions were extraction temperature of 65 degrees C, solid-to-liquid ratio of 1:15 (g/mL), ethanol concentration of 40%, and extraction time of 2.5 h. Using n-butanol-acetic acid-water (4:1:5, v/v/v) as the two-phase solvent system, 38.79 mg phaseoloidin (the purity was 99.3% with a recovery of 98.1%), 34.85 mg Entadamide A (the purity was 96.4% with a recovery of 98.5%), and 33.97 mg Entadamide A-beta-D-glucopyranoside (the purity was 98.6% with a recovery of 97.7%) were obtained from 500 mg crude extract by HSCCC in head-to-tail elution mode. The retention ratio of stationary phase was 51.0%. According to the antioxidant activity assays, phaseoloidin, Entadamide A, and Entadamide A-beta-D-glucopyranoside had certain scavenging abilities on 1,1-diphenyl-2-picrylhydrazyl free radicals and hydroxyl free radicals.

Comparative Study of Onion (Allium cepa) and Leek (Allium ampeloprasum): Identification of Organosulphur Compounds by UPLC-QTOF/MS and Anticancer Effect on MCF-7 Cells.[Pubmed:31696379]

Plant Foods Hum Nutr. 2019 Dec;74(4):525-530.

Onion (Allium cepa) and leek (Allium ampeloprasum var. porrum) are common herbs and vegetables found in our daily life. It belongs to the genus Allium, which is usually known for their high antioxidant and anticancer properties. Medical researchers highly recommend the exploitation of herbs and plants as alternative ways in the treatment of cancer. This research was designed to study the anticancer effects of onion and leek extracts on MCF-7 human breast cancer cell. Crude extracts of ethanol, methanol, and water of onion and leek were obtained by maceration. MCF-7 cells were cultured in complete media at 37 degrees C and subjected to different treatments that involved varying concentrations (10, 50, and 100 mug/mL) of onion and leek extracts for 24, 48, and 72 h of incubation. The percentage of cell viability and the concentration of extracts on MCF-7 cells were determined using MTT assay. The water leek extract proved to be the most effective extract at 50 mug/mL, whereby it showed a significant inhibition ability due to the presence of Entadamide A-beta-D-glucopyranoside as identified by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF/MS). Further studies about the mechanism of both extracts in causing cell death and the determination of the presence of other bioactive compounds in the extracts are needed.

Effect of seeds of Entada phaseoloides on chronic restrain stress in mice.[Pubmed:30635249]

J Ayurveda Integr Med. 2020 Oct-Dec;11(4):464-470.

BACKGROUND: Entada phaseoloides is a well-known medicinal plant traditionally used in Ayurvedic medicine for centuries. OBJECTIVE: To evaluate the anti-stress activity of seeds of E. phaseoloides in endoplasmic reticulum stress during chronic restrain stress in mice, based on our preliminary screening. MATERIALS AND METHODS: Mice (n = 6/group) were restrained daily for 6 h in 50 ml polystyrene tubes for 28 days. Methanolic extract of E. phaseoloides (MEEP) (100 and 200 mg/kg, p.o.) and standard drug, imipramine (10 mg/kg i.p.) were administered daily 45 min prior to restrain from day 22-28. Then, forced swim test (FST) was performed to assess despair behavior. Lipid peroxidation (LPO) and antioxidant enzymes Reduced glutathione (GSH), Superoxide dismutase (SOD) were measured in the hippocampus of mice. 78 kDa Glucose-regulated Protein, 94 kDa Glucose-regulated Protein, C/EBP homologous protein, Caspase-12 expression were quantified by Real Time PCR. RESULTS: MEEP significantly reduced the immobility time in FST (P < 0.001). Significant reduction of LPO (P < 0.05) level and restored antioxidant enzymes viz. GSH (P < 0.001) and SOD towards vehicle control group were observed. Down-regulation of genes GRP 78, GRP 94 (P < 0.001), CHOP and Caspase-12 (P < 0.001) as compared to the chronic restrain stress group was evident, which were upregulated following treatment. Isolation of the active components of the seeds revealed the presence of Oleic acid (1), Entadamide A (2), Entadamide A-beta-d-glucopyranoside (3) and 1-O-protocatechuoyl-beta-d-glucose. CONCLUSION: MEEP altered endoplasmic reticulum stress in chronic restrain stressed mice; however, as an antidepressant it showed a weaker response.

[Quality standard study on Entadae Semen].[Pubmed:26390638]

Zhongguo Zhong Yao Za Zhi. 2015 May;40(10):1860-4.

OBJECTIVE: To establish the quality standard of Entadae Semen, and provide scientific basis for its quality control. METHOD: TLC and HPLC were used for qualitative identification and quantitative analysis of phaseoloidin and Entadamide A-O-beta-D-glucopyranoside in Entadae Semen. The test of water content, ash and ethanol-soluble extractives of Entadae Semen was carried out according to the methods recorded in appendix of Chinese Pharmacopeia (2010 edition). RESULT: The TLC was well separated with clear spots. The linear range of phaseoloidin was between 0.014 to 2.747 g x L(-1) (r = 0.999 6, n = 9) with an average recovery rate of 101.06% (RSD 0.90%, n = 6); the linear range of Entadamide A-O-beta-D-glucopyranoside was between 0.002 to 0.452 g x L(-1) (r = 0.999 7, n = 9) withan average recovery rate of 101.52% (RSD 1.09%, n = 6). The content of phaseoloidin in sample is between 5.12% to 9.24%, Entadamide A-O-beta-D-glucopyranoside is between 0.55% to 2.17%, alcohol-soluble extracts is between 30.9% to 45.2%, water is between 6.6% to 8.6%, and total ash is between 2.4% to 2.9%. CONCLUSION: The established standard is acceptable for quality control of Entadae Semen.

Chemical constituents and bioactivities of Clinacanthus nutans aerial parts.[Pubmed:25490430]

Molecules. 2014 Dec 5;19(12):20382-90.

Four new sulfur-containing compounds, named clinamides A-C (1-3), and 2-cis-Entadamide A (4), were isolated together with three known compounds from the bioactive ethanol extract of the aerial parts of Clinacanthus nutans. These secondary metabolites possess sulfur atoms and acrylamide functionalities. The structures of the isolated components were established by interpretation of their spectroscopic data, especially 1D and 2D NMR.

Intestinal bacterial metabolism and anti-complement activities of three major components of the seeds of Entada phaseoloides.[Pubmed:25398297]

J Nat Med. 2015 Apr;69(2):171-7.

The present study aimed to investigate the metabolism of Entadae Semen by human fecal bacteria to clarify the relationship between its pharmacological activities and intestinal metabolism. Three major components (phaseoloidin, Entadamide A-beta-D-glucopyranoside and Entadamide A) were isolated and identified from Entadae Semen and then incubated with human fecal microflora in vitro to investigate the metabolic processes. The metabolites were analyzed with high-performance liquid chromatography (HPLC). The anti-complement activities of the three components and their metabolites produced by human fecal microflora were evaluated in vitro using a hemolysis assay. Phaseoloidin and Entadamide A-beta-D-glucopyranoside were metabolized into their respective aglycones during the incubation process, which enhanced their anti-complement effects. These results indicated that the presence of intestinal bacteria likely plays an important role and that the pharmacological effects of Entadae Semen may be dependent on intestinal bacterial metabolism.

Two new tryptophan derivatives from the seed kernels of Entada rheedei: effects on cell viability and HIV infectivity.[Pubmed:23537889]

Fitoterapia. 2013 Jun;87:37-42.

Two new tryptophan derivatives, N-sulfonyl-L-tryptophan (tryptorheedei A) (1) and 3-(N-sulfonylindolyl)-D-lactic acid (tryptorheedei B) (2) together with the known 5-O-beta-D-glucopyranosyl-2-hydroxyphenylacetic acid (3), 1-O-methylglucopyranoside, Entadamide A, homogentisic acid and 3-O-beta-D-glucopyranosyl-beta-sitosterol, were isolated from the seed kernels of Entada rheedei (Mimosaceae). Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry and by comparison with spectroscopic data reported in the literature. Compounds 1 and 2 showed no toxicity to TZM and Human PBMC cells. Both compounds 1 and 2 were found to promote early infection events in HIV, likely by inhibiting the enzyme indolamine 2,3-dioxygenase (IDO) and preventing tryptophan depletion. Inhibition of IDO acutely in HIV infection inhibits viral replication, but chronic activation of IDO leads to immune impairment in AIDS. IDO is also the gatekeeper enzyme for kynurenine metabolism, a pathway involved in serotonin and melatonin biosynthesis and the regulation of glutamate and dopamine levels in the brain. Therefore inhibition of IDO might explain both the reported medicinal and neuropsychiatric effects of E. rheedei.

Medicinal plants of Thailand. II: chemical studies on the seed kernels of Entada rheedei Sprengel.[Pubmed:22146972]

J Nat Med. 2012 Jul;66(3):552-7.

Chemical investigation of a methanolic extract of the seed kernels of Entada rheedei (Fabaceae), a Thai medicinal plant taken for stomachache, led to the isolation of five new compounds, 1-(3,4-dimethoxyphenyl)propan-9-ol O-(6''-O-alpha-L-arabinopyranosyl)-beta-D-glucopyranoside, 1-(3,4,5-trimethoxyphenyl)prop-7-en-9-ol O-(6''-O-alpha-L-arabinopyranosyl)-beta-D-glucopyranoside, and N-(2'-hydroxyethyl)-7-phenylacetamide 2'-O-beta-D-glucopyranoside, and Entadamide A 2'-O-(4''-O-beta-D-glucopyranosyl)-beta-D-glucopyranoside and 2'-O-(6''-O-beta-D-glucopyranosyl)-beta-D-glucopyranosides, together with one known compound, corchoionoside C. Their structures were elucidated on the basis of chemical and spectral evidence.

Medicinal plants of Thailand. I structures of rheedeiosides A-D and cis-entadamide A beta-D-glucopyranoside from the seed kernels of Entada rheedei.[Pubmed:21467675]

Chem Pharm Bull (Tokyo). 2011;59(4):466-71.

Four new oleanane-type triterpene oligoglycosides, named rheedeiosides A, B, C and D, and one new thioamide glycoside, cis-Entadamide A beta-D-glucopyranoside, were isolated from the seed kernels of a Thai medicinal plant, Entada rheedei SPRENGEL. The rheedeiosides were found to contain N-acetylglucosamine as a sugar component. Their structures were elucidated based on spectral and chemical evidence.

Sulfur-containing amides from Entada phaseoloides.[Pubmed:20931765]

Yao Xue Xue Bao. 2010 May;45(5):624-6.

To study the chemical constituents of the Entada phaseoloides (L.) Merr., seeds of Entada phaseoloides were extracted with 70% ethanol at room temperature. Isolation and purification were performed by silica gel, reversed-phase silica gel column chromatography and semi-preparative HPLC. Structures of the pure compounds were established on the basis of spectral analysis. Four sulfur-containing amide compounds were isolated from the n-BuOH-soluble fraction and identified as Entadamide A-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranoside (1), Entadamide A (2), Entadamide A-beta-D-glucopyranoside (3) and clinacoside C (4). Compound 1 is a new compound. Compound 4 is isolated from the genus Entada for the first time.

Sulfur-containing compounds from Clinacanthus siamensis.[Pubmed:14646322]

Chem Pharm Bull (Tokyo). 2003 Dec;51(12):1423-5.

Two new sulfur-containing compounds, trans-3-methylsulfonyl-2-propenol (1) and trans-3-methylsulfinyl-2-propenol (2) were isolated together with trans-3-methylthioacrylamide (3), Entadamide A (4) and entadamide C (5) from the leaves of Clinacanthus siamensis. The structures were established on the basis of the spectroscopic data. The compounds were tested for antimalarial and antimycobacterial activity.

Synthesis of entadamide A and entadamide B isolated from Entada phaseoloides and their inhibitory effects on 5-lipoxygenase.[Pubmed:2805174]

Chem Pharm Bull (Tokyo). 1989 Jul;37(7):1932-3.

Two new sulfur-containing amides, Entadamide A (1) and entadamide B (2), isolated from the seeds of Entada phaseoloides, were synthesized by the addition reaction of methanethiol to propiolic acid (5) followed by condensation with ethanolamine by the use of dicyclohexylcarbadiimide. These compounds inhibited the 5-lipoxygenase activity of RBL-1 cells at 10(-4) g/ml. This finding suggests that entadamides A and B may be examples of a new type of antiinflammatory drug.