Mahendra Sahai

Osteogenic activity of constituents from Butea monosperma.

Phytochemical investigation from the stem bark of Butea monosperma, led to the isolation and identification of three new compounds named buteaspermin A (1), buteaspermin B (2) and buteaspermanol (3), along with 19 known compounds. The structure of compounds 1-22 were established on the basis of their spectroscopic data. The isolated compounds 2-17 were evaluated using neonatal (1-3 day old) rat calvaria derived primary osteoblast cultures. Five of these compounds 7, 10-13 showed promising osteogenic activity, attributed to increased osteoblast proliferation, differentiation and mineralization as evidenced by marked increase in expression of alkaline phosphatase, an early phase differentiation marker, and alizarin Red S staining of osteoblasts cultured for 48 h and von Kossa silver staining of nodules formed 15 days after culture with these compounds. Quantification of mineralization by optical density measurement of Alizarin Red S extracted from stained osteoblasts cultured for 7 days in presence of these compounds showed significant (P<0.05, vs corresponding vehicle control group) increase in mineralization. On the basis of biological results, structure-activity relationships are discussed.

Anti-ulcer constituents of Annona squamosa twigs.

Phytochemical investigation of Annona squamosa twigs, resulted in isolation and identification of twelve known (1-12) compounds among them one 1-(4-β-D-glucopyranosyloxyphenyl)-2-(β-D-glucopyranosyloxy)-ethane (11) is synthetically known but first time isolated from natural sources. Their structures were elucidated using 1D and 2D NMR spectroscopic analysis. The isolated compounds (2-8, 11) were evaluated for H(+) K(+)-ATPase activity. Three of these compounds (+)-O-methylarmepavine (2), N-methylcorydaldine (3), isocorydine (6) showed promising anti-secretory activity. Activity of these compounds, comparable to the standard drug omeprazole is novel to our finding. Moreover, there is no information accessible regarding the pharmacological effect of A. squamosa on the gastrointestinal system. This study is the first of its kind to show the significant anti-ulcer effect of A. squamosa. The present study aimed to evaluate the gastroprotective effect of A. squamosa (AS) and to identify its active constituents. Anti-ulcer activity was evaluated against cold restraint (CRU), pyloric ligation (PL), aspirin (ASP), alcohol (AL) induced gastric ulcer and histamine (HA) induced duodenal ulcer model and further confirmed through in vitro assay of H(+) K(+)-ATPase activity and plasma gastrin level. AS and its chloroform and hexane fraction attenuated ulcer formation in CRU, PL, HA model and displayed anti-secretory activity in vivo through reduced free, total acidity and pepsin in PL, confirmed by in vitro inhibition of H(+) K(+)-ATPase activity with corresponding decrease in plasma gastrin level. Cytoprotection of AS was apparent with protection in AL, ASP models and enhanced mucin level in PL.

Synthetic analogs of daidzein, having more potent osteoblast stimulating effect.

A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of osteoblasts. Further, these three compounds did not show any estrogen agonistic activity, however had mild estrogen antagonistic effect. Out of the three compounds, 3c was found to maximally increase the mineralization of bone marrow osteoprogenitor cells. Compound 3c also robustly increased the mRNA levels of osteogenic genes including bone morphogenetic protein-2 and osteocalcin in osteoblasts. Unlike daidzein, 3c did not inhibit osteoclastogenesis. Collectively, we demonstrate osteogenic activity of daidzein analogs at significantly lower concentrations than daidzein.

Withaperuvins F and G, two withanolides of Physalis peruviana roots

Abstract Withaperuvins F and G, the minor constituents of the roots of Physalis peruviana , have been formulated respectively, as (3 R ,6 S ,17 S ,20 S ,22 R )-4β,5β,17β,20α F ,-tetrahydroxy-3α,6α-oxido-l-oxoergosta-14,24-dien-22,26-olide and (17 S ,20 S ,22 R )-2β,3β:5β,6β-diepoxy-14α,17β,20α F -trihydroxy-1-oxoergosta-24-en-22,26-olide.

A new kaempferol diglycoside from Datura suaveolens Humb. & Bonpl. ex. Willd.

A new flavonol glycoside, kaempferol 3-O-α-L-arabinopyranosyl-7-O-β-D-glucopyranoside (1), has been isolated from methanol extract of leaves of Datura suaveolens (Solanaceae), along with six other known compounds, which include kaempferol 3-O-α-L-arabinopyranoside (2), 3-phenyl lactic acid, 3-(3-indolyl) lactic acid, and its methyl ester, physalindicanol A and physalindicanol B. The structural elucidation of 1 and characterization of the known compounds are based on detailed spectral analysis (ESI-FTICR-MS and 2D-NMR). This is the first report of isolation of these compounds from this plant.

N-methyl-6, 7-dimethoxyisoquinolone in Annona squamosa twigs is the major immune modifier to elicit polarized Th1 immune response in BALB/c mice

Annona squamosa (AS) has traditionally been used as ethnomedicine. We have earlier extracted and fractionated the twigs of AS based upon its bioactivity and observed its immune potentiating activity that was localized in its three fractions. Present communication deals with the phytochemical analysis and pharmacological investigation of the most active chloroform fraction that led to isolation and identification of a number of compounds whose structures were elucidated using 1D and 2D NMR spectroscopic analysis. Amongst the twelve pure compounds isolated, five compounds Lanuginosine (1), (+)-O-methylarmepavine (2), (+)-anomuricine (3), Isocorydine (4), and N-methyl-6, 7-dimethoxyisoquinolone (5) were evaluated in vivo for their immune modifier activities in BALB/c mice after oral administration at three log doses of 0.3, 1.0 and 3.0mg/kg for 14 consecutive days. Of these, three compounds (1, 2 and 5) showed dose dependent immune stimulating activity. However, the uppermost activity was noted in the compound N-methyl-6, 7-dimethoxyisoquinolone at the 3.0mg/kg oral dose. The activity was assessed in the form of increased splenic T and B cellular proliferation, up-regulated CD4+, CD8+ and CD19+ cell population and accentuation in the peritoneal macrophage function. The compound possibly acted modifying the expression of Th1- and Th2- cytokines via stimulation of pro-inflammatory Th1 cytokines IL-2 and IFN-γ. These results warrant the use of the above compounds as an efficient immune-stimulant or immune-adjuvant against diseases with immune suppression. The analogs of the compound may further be chemically synthesized to achieve desired immune modifying activity.

Coumarinolignans from the seeds of Annona squamosa Linn.

Phytochemical investigations of Annona squamosa seeds have led to the isolation of three lignans consisting of coumarin moiety, cleomiscosin A (1), cleomiscosin B (2) and cleomiscosin C (3). Their structures were arrived at by detailed spectroscopic analysis. Cleomiscosin A and cleomiscosin B are position isomer.

Coptisine-induced cell cycle arrest at G2/M phase and reactive oxygen species–dependent mitochondria-mediated apoptosis in non-small-cell lung cancer A549 cells

This study aimed to explore the effect of coptisine on non-small-cell lung cancer and its mechanism through various in vitro cellular models (A549). Results claimed significant inhibition of proliferation by coptisine against A549, H460, and H2170 cells with IC50 values of 18.09, 29.50, and 21.60 µM, respectively. Also, coptisine exhibited upregulation of pH2AX, cell cycle arrest at G2/M phase, and downregulation of the expression of cyclin B1, cdc2, and cdc25C and upregulation of p21 dose dependently. Furthermore, induction of apoptosis in A549 cells by coptisine was characterized by the activation of caspase 9, caspase 8, and caspase 3, and cleavage of poly adenosine diphosphate ribose polymerase. In addition, coptisine was found to increase reactive oxygen species generation, upregulate Bax/Bcl-2 ratio, disrupt mitochondrial membrane potential, and cause cytochrome c release into the cytosol. Besides, treatment with a reactive oxygen species inhibitor (N-acetyl cysteine) abrogated coptisine-induced growth inhibition, apoptosis, reactive oxygen species generation, and mitochondrial dysfunction. Thus, the mediation of reactive oxygen species in the apoptosis-induced effect of coptisine in A549 cells was corroborated. These findings have offered new insights into the effect and mechanisms of action of coptisine against non-small-cell lung cancer.

Three new acyltyramines from Anisodus luridus Link et Otto (Solanaceae)

Abstract Three new acyltyramines, N-[2-(4-hydroxyphenyl)ethyl]hentriacontanamide (1), N-[2-(4-hydroxyphenyl)ethyl]nonacosanamide (2) and N-[2-(4-hydroxyphenyl)ethyl]heneicosanamide (3) have been isolated from n-hexane extract of leaves of Anisodus luridus (Solanaceae). Successive extraction of defatted leaves of A. luridus with methanol afforded a residue on removal of solvent under reduced pressure. Residue was partitioned by means of chloroform and n-butanol. Chromatographic resolution of n-BuOH extract afforded six known compounds, apigenin (4), luteolin (5), quercetin (6), quercetin 3-O-α-l-rhamnoside (7), kaempferol 3-O-α-rhamnoside (8) and quercetin 3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (9). The structures of the isolated compounds were assigned with the help of spectroscopic techniques. This is the first report of isolation of these compounds from this plant.

New lignan glycosides from Cissus quadrangularis stems

Abstract Phytochemical investigation of Cissus quadrangularis stems led to the isolation of one new phenolic glycoside (1) and two new lignan glycosides (7 & 8) along with twelve known compounds (2–6 & 9–15). Their chemical structures were determined on the basis of extensive spectroscopic analysis using 1D, 2D NMR, and mass spectrometric analysis. Among the known compounds, 4–6, 9 and 12 were isolated for the first time from the genus Cissus whereas compounds 10, 11 and 13 for the first time from this plant.