Sabina Shrestha

Potential neuroprotective flavonoid-based inhibitors of CDK5/p25 from Rhus parviflora

Rhus parviflora (Anacardiaceae) is an indigenous medicinal shrub found in South Asia with flavonoid rich edible fruit. This study examined flavonoid derivatives of R. parviflora fruit with CDK5/p25 inhibition activity. Evaluation by in vitro assay and docking simulations for CDK5/p25 revealed that the aurones, sulfuretin (1) and aureusidin (2), the aurone glycoside, aureusidin-6-O-β-D-glucopyranoside (3) and hovetrichoside C (4), the flavonoid glycoside, quercetin-3-O-β-D-galactopyranoside (5), and the biflavonoid, cupressuflavone (6), had the potential to inhibit CDK5/p25, which could be useful in the treatment of neurodegenerative disorders such as Alzheimers disease. Compound2 showed the significant in vitro inhibition capacity (IC50 value of 4.81 μM) as well as binding affinity with docking energy of -8.73 (kcal/mol) for active sites CYS83 and GLN130 of CDK5/p25 enzyme in comparison to reference compound R-roscovitine.

Flavonoid glycosides from cowpea seeds (Vigna sinensis K.) inhibit LDL oxidation

Six flavonoid glycosides were isolated from the n-butanol fraction of cowpea seeds (Vigna sinensis K.) through silica gel (SiO2) and octadecyl silica gel (ODS) column chromatographies. Based on their chemical structures determined via interpretation of spectroscopic data including NMR, MS, and IR, the compounds were identified as kaempferol 3-O-β-d-sophoroside (1), quercetin 3-O-β-d-sophoroside (2), isoquercitrin (3), hyperin (4), catechin 7-O-β-d-glucopyranoside (5), and quercetin 3-O-β-Dglucopyranosyl( 1→6)-O-β-d-galactopyranoside (6). This is the first report of the isolation of these flavonoids from this plant. Among these flavonoids, compound 2, 5, and 6 significantly inhibited LDL oxidation exhibiting 96.0±0.1 (IC50: 3.9 μM), 96.8±1.7 (IC50: 2.9 μM), and 97.4±0.1% (IC50: 3.5 μM) inhibition, respectively, at a concentration of 40 μM.

Cytotoxic and Neuroprotective Biflavonoids from the Fruit of Rhus parviflora

Six biflavonoids, succedaneaflavanone (1), mesuaferrone B (2), rhusflavanone (3), rhusflavone (4), agathisflavone (5), and cupressuflavone (6), were isolated from the fruits of Rhus parviflora. The chemical structures of the compounds were determined based on NMR, fast atom bombardment mass spectrometry, and IR. Biflavonoid compounds were evaluated for cytotoxicity against human cancer cell lines, including human colon carcinoma (HCT-116), human breast carcinoma (MCF-7), and human cervical carcinoma (HeLa). Biflavonoids 2, 3, and 5 showed significant cytotoxicity with IC50 values of 17.25 μM (mesuaferrone B against HCT-116), 17.50 μM (rhusflavone against MCF-7), and 15.20 μM (agathisflavone against HeLa). Compound 5 showed inhibition of β-secretase activity at a 10 μM concentration. Compound 6 showed inhibition of cyclin-dependent kinases (CDK2 and CDK5) with IC50 values of 18.58 and 9.29 μM, respectively.

Flavonoids from the fruits of Nepalese sumac (Rhus parviflora) attenuate glutamate-induced neurotoxicity in HT22 cells

Nepalese sumac (Rhus parviflora) is a wild edible fruit used for the treatment of various ailments including neurological complications and stomach disorders in the traditional medicinal system of south Asia (Ayurveda). Four flavonoids were isolated from ethyl acetate (EtOAc) fraction of Nepalese sumac fruits and their chemical structures were determined on the basis of NMR, fast atom bombardment mass spectrometry (FAB/MS), and IR. The efficiency of isolated compounds in attenuating glutamateinduced cell death in an immortalized mouse hippocampal cell line (HT-22) and inhibition of cycline dependent kinase 5 (Cdk5) were investigated. Among the compounds, flavanols, fustin (1) and taxifolin (2), an aurone, aureusidin (3), and a biflavonoid, agathisflavone (4) were found to have protective effect against glutamate induced oxidative injury in HT22 cells. Aureusidin (3), a Cdk5/p25 inhibitor (IC50 3.5 μM), was the most potent neuroprotector with an EC50 value of 11.90 μM.

New diarylpropanoids from Lindera glauca Bl. heartwood

Abstract From the heartwood of Lindera glauca Blume three new diarylpropanoids have been isolated and identified, which were named lindeglaucol, lindeglaucone, and lindeglaucoside A. Chipped heartwood was extracted repeatedly with 80% aqueous methanol (MeOH) at room temperature, and the concentrated methanolic extract was successively partitioned with ethyl acetate (EtOAc), n-butanol, and H2O. From the EtOAc fraction, three new diarylpropanoids and a known chalconoid were isolated through repeated column chromatography with silica gel, octadecyl silica gel, and Sephadex LH-20. The chemical structures of the compounds were elucidated by interpretation of extensive spectroscopic data such as nuclear magnetic resonance, fast atom bombardment mass spectroscopy, and infrared. In addition, a known chalconoid, cilicicone B, was isolated for the first time from the heartwood of L. glauca.

An assessment of Yarsagumba (Ophiocordyceps sinensis) collection in Dhorpatan Hunting Reserve, Nepal

Yarsagumba (Ophiocordyceps sinensis), an endemic species to the Himalayas and Tibetan Plateau, is one of the most valuable medicinal mushrooms in the world. In Nepal, it is distributed largely in isolated patches of alpine grasslands of 3,000-5,000 m elevation. Although it is reported from 27 northernmost districts of Nepal, the local distribution pattern of this species is largely unknown. Furthermore, the collection system and local management regime of this species are not well documented. We conducted a field survey at Dhorpatan Hunting Reserve (DHR) among the different stakeholders in January-June 2012 to assess collection sites, patterns and trends and to understand the management regime. We estimated that about 75 kg of Yarsagumba is collected every year from DHR and the amount has been declining since 2008. To manage the resource, locals have initiated regulating the collection by issuing permits, taxing to the collectors, and monitoring the activities of harvesters with the help of park authorities. The revenue generated at local level from the permits has been used for community developmental activities.

Flavonoid glycosides from the fruit of Rhus parviflora and inhibition of cyclin dependent kinases by hyperin

Chrysoeriol-7-O-β-d-glucopyranoside (1), luteolin-7-O-β-d-glucopyranoside (2), quercetin-3-O-β-d-glucopyranoside (3), quercetin-3-O-β-d-galactopyranoside (4), and quercetin-3-O-α-l-rhamnopyranoside (5) were isolated for the first time from the fruits of Rhus parviflora. The chemical structures of the compounds were determined using nuclear magnetic resonance, fast atom bombardment mass spectrometry, and infrared spectroscopy. Compound 4 (hyperin) inhibited cyclin dependent kinases (CDK2 and CDK5) in vitro with IC50 values of 21.02 and 10.28 μM, respectively.

Neolignans from the Fruits of Magnolia obovata and Their Inhibition Effect on NO Production in LPS-Induced RAW 264.7 Cells

Three new neolignans, named 9-methoxyobovatol (6), magnobovatol (7), and 2-hydroxyobovaaldehyde (9), along with six known ones, magnolol (1), honokiol (2), isomagnolol (3), obovatol (4), obovatal (5), and obovaaldehyde (8), were isolated from the fruits of Magnolia obovata using silica gel and ODS column chromatography. From the results of spectroscopic data including EIMS, IR, 1H- and 13C-NMR, DEPT, and 2D-NMR (gCOSY, gHSQC, gHMBC), the chemical structures were determined. All isolated compounds were evaluated for inhibition activity on nitric oxide production in LPS-induced RAW 264.7 cells, and compounds 1-4, 6, 7, and 9 showed significant activity with IC50 values of 15.8 ± 0.3, 3.3 ± 1.2, 14.1 ± 0.9, 6.2 ± 1.2, 14.8 ± 2.3, 14.2 ± 1.2, and 14.8 ± 3.2 µM, respectively, without any visible toxic effect.

Quality evaluation of Panax ginseng roots using a rapid resolution LC-QTOF/MS-based metabolomics approach.

Korean ginseng (Panax ginseng C.A. Meyer) contains several types of ginsenosides, which are considered the major active medicinal components of ginseng. The types and quantities of ginsenosides found in ginseng may differ, depending on the location of cultivation, making it necessary to establish a reliable method for distinguishing cultivation locations of ginseng roots. P. ginseng roots produced in different regions of Korea, China, and Japan have been unintentionally confused in herbal markets owing to their complicated plant sources. PCA and PLS-DA using RRLC-QTOF/MS data was able to differentiate between ginsengs cultivated in Korea, China, and Japan. The chemical markers accountable for such variations were identified through a PCA loadings plot, tentatively identified by RRLC-QTOF/MS and partially verified by available reference standards. The classification result can be used to identify P. ginseng origin.

Inhibition effect of phenyl compounds from the Oryza sativa roots on melanin production in murine B16-F10 melanoma cells

Five phenyl compounds, vanillin (1), methyl trans-ferulate (2), trans-p-coumaric acid methyl ester (3), N-benzoyltryptamine (4), and N-(trans-cinnamoyl)tryptamine (5), were isolated from the roots of Oryza sativa L. and identified on the basis of spectroscopic data. Compounds 3 and 5 showed strong inhibition effect on melanin production in murine B16-F10 melanoma cells and tyrosinase activity. Also, the quantitative analysis of the compounds was carried out using LC/MS/MS experiment. Compounds 3 and 5 could be used as skin-whitening agents.