Samir Kumar Sadhu

Lignan glycosides and flavonoids from Saraca asoca with antioxidant activity

Five lignan glycosides, lyoniside, nudiposide, 5-methoxy-9-β-xylopyranosyl-(−)-isolariciresinol, icariside E3, and schizandriside, and three flavonoids, (−)-epicatechin, epiafzelechin-(4β→8)-epicatechin and procyanidin B2, together with β-sitosterol glucoside, were isolated from a methyl alcohol (MeOH) extract of Saraca asoca dried bark. Their structures were determined by 1D and 2D nuclear magnetic resonance (NMR) and mass spectroscopic analysis. Antioxidant activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay.

Antioxidant, antinociceptive activity and general toxicity study of Dendrophthoe falcata and isolation of quercitrin as the major component

Plants have been used in traditional medicinal system for centuries. Bangladeshi medicinal plants have received considerable attention from the researchers for evaluation of their bioactivity. As a part of our ongoing research of screening the Bangladeshi medicinal plants, the ethanolic extract of Dendrophthoe falcata have been chosen for the present study. The ethanolic extract of the leaves of the plant have been assessed for their antioxidant, antinociceptive, and general toxicity. The extract showed potent antioxidant activity (IC50 5.1 μg/ml) using DPPH radical scavenging assay, which is comparable to the standard ascorbic acid (IC50 4.6 μg/ml). The extract significantly and dose dependently inhibited the acetic acid induced writhing in mice (71.2%, P < 0.001 and 28.0%, P < 0.05 for 500 and 250 mg/kg body weight, respectively). A general toxicity was assessed by a simple and low cost assay using brine shrimp lethality as an indicator. The extract showed low level of toxicity (LC50 100 μg/ml). Using different chromatographic techniques, quercitrin (quercetin 3-O-α-rhamnoside) was separated as the major component from the extract. The structure was elucidated by detailed 1D and 2D NMR and mass spectral analysis.

A new lignan from Aphanamixis polystachya

A new lignan, polystachyol (1), two lignan glycosides, lyoniside (2) and nudiposide (3), and a sterol, ergosta-4,6,8(14),22-tetraen-3-one (4), with stigmasterol, and oleic and linoleic acids, have been isolated from an MeOH extract of the dried bark of Aphanamixis polystachya. The structures of the isolated compounds were elucidated by analysis of 1D and 2D NMR and mass spectroscopic data. The compounds did not have growth inhibitory activity against HeLa cells.

New Hedgehog/GLI signaling inhibitors from Excoecaria agallocha.

The inhibition of the Hedgehog (Hh) signaling pathway has emerged as an anti-cancer strategy. Three flavonoid glycosides including 2 new compounds (1-2) were isolated from Excoecaria agallocha as Hedgehog/GLI1-mediated transcriptional inhibitors and exhibited cytotoxicity against human pancreatic (PANC1) and prostate (DU145) cancer cells. Our data revealed that compound 1 clearly inhibited the expression of GLI-related proteins (PTCH and BCL-2) and blocked the translocation of GLI1 transcription factors into the nucleus in PANC1. Deleting the Smoothened (Smo) function in PANC1 treated with 1 led to downregulation of the mRNA expression of Ptch. This study describes the first Hh signaling inhibitor which blocks GLI1 movement into the nucleus without interfering with Smo.

Flavonoids from Sonneratia caseolaris

According to the traditional medicinal usage of Sonneratia caseolaris, we tested the extract of S. caseolaris for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect on thin-layer chromatography. Following activity-oriented separation, two flavonoids, luteolin (1) and luteolin 7-O-β-glucoside (2), were isolated. Both of the compounds were found to possess antioxidant activity.

Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2–3). Compound 1 showed strong activity in overcoming TRAIL‐resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL‐induced apoptosis at the aforementioned concentrations. Copyright

Constituents of Amoora cucullata with TRAIL resistance-overcoming activity

In search of bioactive natural products for overcoming TRAIL resistance from natural resources, we previously reported a number of active compounds. Bioassay-guided fractionation of mangrove, Amoora cucullata, collected from Sundarbans Mangrove Forest, Bangladesh, led to the isolation of four new compounds (1-4), along with seven known compounds (5-11). Of the isolates, compounds 1, 5, 8, and 9 showed TRAIL resistance-overcoming activity, among which 8 showed the most potent activity and enhanced TRAIL-induced apoptosis in TRAIL-resistant human gastric adenocarcinoma (AGS) cells through the activation of caspase-3/7, enhancing the expression of DR4 and DR5 mRNA in AGS cells. Cell death caused by the combined treatment of 8 and TRAIL was inhibited by human recombinant DR5/Fc and DR4/Fc chimera proteins, indicating that 8 sensitizes TRAIL-resistant AGS cells to TRAIL through the induction of DR4 and DR5.

Calotropin: A Cardenolide from Calotropis gigantea that Inhibits Wnt Signaling by Increasing Casein Kinase 1α in Colon Cancer Cells

Wnt signaling plays key roles in embryonic development and various human diseases. Activity‐guided testing to isolate Wnt signaling inhibitors from the methanol extract of Calotropis gigantea (Asclepiadaceae) exudutes identified six Wnt inhibitory cardenolides (1–6), of which 1, 3, 5, and 6 exhibited potent TCF/β‐catenin inhibitory activities (IC50 0.7–3.6 nM). Calotropin (1) inhibited Wnt signaling by decreasing both nuclear and cytosolic β‐catenin in a dose‐dependent manner, and promoted degradation of β‐catenin by increasing the phosphorylation of β‐catenin at Ser45 through casein kinase 1α (CK1α). Moreover, 1 significantly increased CK1α protein and mRNA levels. The results suggest that 1 inhibits the Wnt signaling pathway by increasing CK1α protein levels. To the best of our knowledge, calotropin is the first small molecule to increase CK1α levels.

Xylogranin B: A Potent Wnt Signal Inhibitory Limonoid from Xylocarpus granatum

Xylogranin B (2) was isolated from Xylocarpus granatum (Meliaceae) leaves, by use of a cell-based luciferase screening system targeting a Wnt signaling pathway. Compound 2 inhibited TCF/β-catenin transcriptional activity (IC50 48.9 nM) and exhibited strong cytotoxicity against colon cancer cell lines. Compound 2 significantly decreased β-catenin protein levels in nuclei but not in the cytosol. These results indicated that a decrease in β-catenin levels in nuclei by 2 resulted in the Wnt signal inhibitory effects of 2.

GLYCOSIDES FROM VALLARIS SOLANACEAE WITH TRAIL-RESISTANCE-OVERCOMING ACTIVITY

A new cardenolide glycoside, vallarisoside (1), and a known one, 3β-O-(α-acofriosyl)-16-anhydrogitoxigenin (2) along with a new glycoside, benzyl 2-O-β-apiofuranosyl-(1→2)-β-D-glucopyranosyl-2, 6-dihydroxy-benzoate (3) were isolated from Vallaris solanaceae. Structures of the isolates were elucidated by ID and 2D NMR and mass spectroscopic analysis. Of the isolates, vallarisoside (1) showed potent TRAIL-resistance-overcoming activity in human gastric adenocarcinoma (AGS) cells and cell-growth-inhibitory activity against HeLa and SW480 cells.