Nusrat Hussain

Acetyl and butyryl cholinesterase inhibitory sesquiterpene lactones from Amberboa ramosa

BackgroundAlzheimer’s disease (AD) is characterized by a progressive memory loss that leads to a profound emotional disturbance in later stages. As no safe and effective drug is yet available for the treatment of AD, secondary metabolites from plants may be instrumental in meeting this challenge. Keeping in view this point we evaluated sesquiterpenes of medicinal plant Amberboa ramosa for their cholinesterase inhibitory activity.ResultsFour sesquiterpene lactones have been isolated from the ethyl acetate soluble fraction of Amberboa ramosa. In which one compound Amberbin C (1) was found to be new while other three Amberin (2), Amberbin A (3), and Amberbin B (4) were previously reported ones. The structures of the isolated compounds were elucidated using different spectroscopic techniques. Isolated compounds were tested for their inhibitory potential against acetyl cholinesterase and butyryl cholinesterase enzymes. All compounds showed excellent inhibitory activities against acetyl cholinesterase and butyryl cholinesterase.ConclusionsA new sesquiterpene lactone has been isolated and fully characterized, the sesquiterpene lactones from Amberboa ramosa showed good inhibitory activities against acetyl cholinesterase and butyryl cholinesterase enzymes, this study indicated that sesquiterpene lactone can become interesting lead molecules in drug development against Alzheimer’s disease (AD).

Corniculatin A, a new flavonoidal glucoside from Oxalis corniculata

Oxalis corniculata L. (creeping wood sorrel) is medicinally important member of family Oxalidaceae, and is distributed in the tropical and subtropical regions of the world. It has been used in different systems of traditional medications for different diseases. Corniculatin A, a new flavonoid glucoside, was isolated from the ethyl acetate soluble fraction of the whole plant along with luteolin, luteolin-7-O-β-D-glucoside and β-sitosterol-3-O-β-D-glucoside, This is the first report of these compounds from this species. Their structures were elucidated on the basis of spectral data including mass and 2D NMR experiments.

Two new prenylated flavonoids from the roots of Berberis thunbergii DC.

Abstract Two new prenylated flavonoids, thunbergiols A (1) and B (2), along with three known compounds, chrysin (3), quercetin (4) and berberine (5) were obtained from the methanolic extract of roots of Berberis thunbergii DC. MS, NMR and other spectroscopic techniques were employed for their structural characterisation.

Eriodictyol stimulates insulin secretion through cAMP/PKA signaling pathway in mice islets

ABSTRACT Eriodictyol, a flavonoid isolated from Lyonia ovalifolia, was found to be the most potent insulin secretagogue in our preliminary studies. Here, we explored mechanism(s) of insulin secretory activity of eriodictyol in vitro and in vivo. Mice islets and MIN6 cells were incubated in basal and stimulatory glucose containing eriodictyol with or without agonist/antagonist. Secreted insulin and cAMP contents were measured using ELISA kits. K+‐ and Ca2+‐channels currents were recorded with patch‐clamp technique. Oral glucose tolerance test and plasma insulin was evaluated in non‐diabetic and diabetic rats. Eriodictyol stimulated insulin secretion from mice islets and MIN6 cells only at stimulatory glucose concentrations with maximum effect at 200 &mgr;M. Eriodictyol showed no pronounced effect on inward rectifying K+ and Ca2+ currents. Furthermore, in KCl depolarized islets, in the presence of diazoxide, insulin secretory ability of eriodictyol was enhanced. IBMX, a phosphodiesterase inhibitor, significantly (P<0.001) enhanced eriodictyol‐induced insulin secretion at 16.7 mM glucose in comparison to eriodictyol or IBMX alone. The cAMP content after eriodictyol exposure was also increased. Eriodictyol‐induced insulin secretion was partially inhibited by adenylate cyclase inhibitor (SQ22536) and completely inhibited by PKA inhibitor (H‐89), suggesting that the eriodictyol effect is more on PKA. Molecular docking studies showed the best binding affinities of eriodictyol with PKA. Eriodictyol improved glucose tolerance and enhanced plasma insulin in non‐diabetic and diabetic rats. Eriodictyol also lowered blood glucose in diabetic rats upon chronic treatment. Taken together, it can be concluded that eriodictyol, a novel insulin secretagogue, exerts an exclusive glucose‐dependent insulinotropic effect through cAMP/PKA pathway.

Microbial transformation of mestanolone by Macrophomina phaseolina and Cunninghamella blakesleeana and anticancer activities of the transformed products

The microbial transformation of anabolic androgenic steroid mestanolone (1) with Macrophomina phaseolina and Cunninghamella blakesleeana has afforded seven metabolites. The structures of these metabolites were characterized as 17β-hydroxy-17α-methyl-5α-androsta-1-ene-3,11-dione (2), 14α,17β-dihydroxy-17α-methyl-5α-androstan-3,11-dione (3), 17β-hydroxy-17α-methyl-5α-androstan-1,14-diene-3,11-dione (4), 17β-hydroxy-17α-methyl-5α-androstan-3,11-dione (5), 11β,17β-dihydroxy-17α-methyl-5α-androstan-1-ene-3-one (6), 9α,11β,17β-trihydroxy-17α-methyl-5α-androstan-3-one (7), and 1β,11α,17β-trihydroxy-17α-methyl-5α-androstan-3-one (8). All the metabolites, except 5 and 6, were identified as new compounds. Substrate 1 (IC50 = 27.6 ± 1.1 μM), and its metabolites 2 (IC50 = 19.2 ± 2.9 μM) and 6 (IC50 = 12.8 ± 0.6 μM) exhibited moderate cytotoxicity against the HeLa cancer cell line (human cervical carcinoma). All metabolites were noncytotoxic to 3T3 (mouse fibroblast) and H460 (human lung carcinoma) cell lines. The metabolites were also evaluated for immunomodulatory activity, and all were found to be inactive.

Lignans from Tujia Ethnomedicine Heilaohu: Chemical Characterization and Evaluation of Their Cytotoxicity and Antioxidant Activities

Heilaohu, the roots of Kadsura coccinea, has a long history of use in Tujia ethnomedicine for the treatment of rheumatoid arthritis and gastroenteric disorders, and a lot of work has been done in order to know the material basis of its pharmacological activities. The chemical investigation led to the isolation and characterization of three new (1–3) and twenty known (4–23) lignans. Three new heilaohulignans A-C (1–3) and seventeen known (4–20) lignans possessed dibenzocyclooctadiene skeletons. Similarly, one was a diarylbutane (21) and two were spirobenzofuranoid dibenzocyclooctadiene (22–23) lignans. Among the known compounds, 4–5, 7, 13–15 and 17–22 were isolated from this species for the first time. The structures were established, using IR, UV, MS and NMR data. The absolute configurations of the new compounds were determined by circular dichroism (CD) spectra. The isolated lignans were further evaluated for their cytotoxicity and antioxidant activities. Compound 3 demonstrated strong cytotoxic activity with an IC50 value of 9.92 µM, compounds 9 and 13 revealed weak cytotoxicity with IC50 values of 21.72 µM and 18.72 µM, respectively in the HepG-2 human liver cancer cell line. Compound 3 also showed weak cytotoxicity against the BGC-823 human gastric cancer cell line and the HCT-116 human colon cancer cell line with IC50 values of 16.75 µM and 16.59 µM, respectively. A chemiluminescence assay for antioxidant status of isolated compounds implied compounds 11 and 20, which showed weak activity with IC50 values of 25.56 µM and 21.20 µM, respectively.

New iridoids from Lyonia ovalifolia and their anti-hyperglycemic effects in mice pancreatic islets

Phytochemical investigation on the aerial parts of Lyonia ovalifolia (Wall.) Drude led to the isolation of three new iridoids, lyonofolin A (1), lyonofolin B (2), and lyonofolin C (3), and a known iridoid, gelsemiol (4). Structures of compounds 1-4 were determined by extensive spectroscopic analyses, including EI-MS, HREI-MS, UV, IR, and 1D- and 2D-NMR (HMBC, HSQC, COSY, NOESY) spectroscopic methods. The effect of insulin secretion of compounds 1, 2, and 4 were evaluated in mice pancreatic islets cellular model. This insulin secretory assay demonstrated that compound 2 potentiates glucose-induced insulin secretion, and thus can serve as a new insulin secretagogue for the treatment of diabetes. The newly isolated compounds were further evaluated against normal 3 T3 cell lines for cytotoxicity, where they did not show any cytotoxicity.

Amberinone, a new guaianolide from Amberboa ramosa

The Amberboa is a medicinally important genus present in the family Asteraceae; members of this genus are mainly distributed in Pakistan and India. It has been used in different systems of traditional medicines for different diseases. Amberinone (1), a new sesquiterpene lactone, has been isolated from the ethyl acetate (EtOAc) soluble fraction of Amberboa ramosa together with chrysin (2), quercitine (3), eriodictyol (4) and keamferol (5). This is the first report of these compounds from this species. The structures of the isolated compounds have been elucidated by 1D and 2D 1H 13C NMR spectroscopy.

Ficusonic acid: a new cytotoxic triterpene isolated from Maytenus royleanus (Wall. ex M. A. Lawson) cufodontis

Phytochemical investigation of the roots of Maytenus royleanus resulted into the isolation of a new cytotoxic triterpene ficusonic acid, 3β,21β-dihydroxyolean-12-en-29-oic acid, together with three known compounds, 3α,22β-dihydroxyolean-12-en-29-oic acid, salaspermic acid and orthosphenic acid, reported for the first time from this source. Their structures were established on the basis of extensive spectroscopic techniques. The cytotoxic activity of compound 3β,21β-dihydroxyolean-12-en-29-oic acid was evaluated against two cancer cell lines, PC-3 prostate and HeLa cervical cancer lines. 3β,21β-dihydroxyolean-12-en-29-oic acid showed weak activity against PC-3 (IC50 = 35.42 µmol L-1) however against HeLa (IC50 = 20.47 µmol L-1), its activity was moderate.

Bioassay-guided Isolation of New Antitumor Agent from Ficus faveolata (Wall. ex Miq.)

Ficus species have been used in both Ayurvedic and Traditional Chinese Medicine (TCM); however the medicinal uses of these species are widely found and originated in Middle East. The phytochemical study of Ficus foveolata was under taken with small scale extraction of stem (300 g) for cytotoxic screening and dereplication purpose. The crude methanolic extract of Ficus was partitioned into different fractions of hexane, dichloromethane and methanol. All the five fractions FA, FB, FC, FD and FE were screened for their anti-proliferative effect in the disk diffusion assay (In vitro) against six cancer cell lines. The bioassay-guided isolation of a new antitumor agent (Ficusonolide; 3α-hydroxylean-12-en-29, 19α-olide (1)) was carried out from the methanolic extract (FB) of Ficus faveolata. Its structure was elucidated on the basis of extensive spectroscopic techniques (IR, MS and NMR). The pure compound 1 was evaluated against twelve cell cancer lines for the determination of its antiproliferative potency. In disk diffusion assay the dichloromethane fraction (FB) showed excellent activity at very low concentration. The compound 1 exhibited strong and selective activity against two cancer cell lines: H116 (Human colon adenocarcinoma) and H125 (Human lung adenocarcinoma) with the IC 50 =7.8 μg/ml and 11.0 μg/ ml respectively. The selectivity and potency of the pure compound 1 was in concordance with the activity profile of the fraction FB and ethno-medicinal uses of this plant. This small project on local medicinal plants has opened new vista for future research work on indigenous medicinal plants. The compound 1 can be used a template compound for further studies, as a chemotherapeutic agents against cancer.