Murad Ali Khan

Diverse compounds mimic Alzheimer disease–causing mutations by augmenting Aβ42 production

Increased Aβ42 production has been linked to the development of Alzheimer disease. We now identify a number of compounds that raise Aβ42. Among the more potent Aβ42-raising agents identified are fenofibrate, an antilipidemic agent, and celecoxib, a COX-2–selective NSAID. Many COX-2–selective NSAIDs tested raised Aβ42, including multiple COX-2–selective derivatives of two Aβ42-lowering NSAIDs. Compounds devoid of COX activity and the endogenous isoprenoids FPP and GGPP also raised Aβ42. These compounds seem to target the γ-secretase complex, increasing γ-secretase–catalyzed production of Aβ42 in vitro. Short-term in vivo studies show that two Aβ42-raising compounds increase Aβ42 levels in the brains of mice. The elevations in Aβ42 by these compounds are comparable to the increases in Aβ42 induced by Alzheimer disease–causing mutations in the genes encoding amyloid β protein precursor and presenilins, raising the possibility that exogenous compounds or naturally occurring isoprenoids might increase Aβ42 production in humans.

The antinociceptive activity of Polygonatum verticillatum rhizomes in pain models

AIM OF THE STUDY The current study was designed to establish the pharmacological rationale for the traditional use of the rhizomes of Polygonatum verticillatum in the treatment of painful conditions and as a plant diuretic. MATERIALS AND METHODS The crude methanolic extract of the rhizomes of Polygonatumverticillatum (PR) was tested in various established pain models in rodents at 50, 100 and 200mg/kg i.p. while the diuretic activity was assessed at 300 and 600 mg/kg p.o. in rats. RESULTS PR demonstrated significant reduction (14-72%) in the number of writhes induced by acetic acid in a dose-dependent manner. When nociceptive threshold was measured in the formalin test, PR strongly attenuated the formalin-induced flinching behaviour in both phases (6-30% in first phase while 12-72% in second phase). Central involvement in the analgesic profile of PR was confirmed by the hot plate test, in which PR elicited a significant (P<0.01) analgesic activity by increasing latency time. However, an opioid receptor antagonist, naloxone (2mg/kg s.c.) strongly antagonized the antinociceptive activity of PR. As a plant diuretic, PR showed mild but statistically insignificant diuretic activity at 300 mg/kg. The crude extract and solvent fractions of the plant contained reasonable quantity of total saponin and alkaloid contents. CONCLUSIONS The mechanisms underlying the analgesic action of PR shows that the opioid dependant central mediation has synergistic effect by enforcing the peripheral analgesic effects. Interestingly, our findings not only substantiated the folk use of the plant as an analgesic but also reported for the first time in the whole genus.

Antinociceptive Activity of Aerial Parts of Polygonatum verticillatum: Attenuation of Both Peripheral and Central Pain Mediators

Polygonatum verticillatum All. is used traditionally as an analgesic and plant diuretic. The methanol extract of aerial parts of Polygonatum verticillatum (PA) was assessed in various experimental paradigms. The pain threshold in the form of abdominal constriction induced by acetic acid was significantly (p < 0.01) inhibited by PA at test doses (50, 100 and 200 mg/kg). In the formalin test, PA elicited a significant (p < 0.01) analgesic activity in both phases and strongly attenuated the formalin‐induced flinching behaviour. The hot plate test was used to evaluate central involvement in the analgesic profile of PA. The PA significantly relieved thermal‐induced pain. From a mechanistic point of view, the central antihyperalgesic activity was tested for antagonism with naloxone, but no antagonism was observed. The current investigations suggest that the active constituent(s) in PA has an analgesic profile with predominant peripheral activity which is augmented by an opioid independent central effect. In the diuretic assay, PA (300 and 600 mg/kg) showed mild insignificant diuretic activity. Our study rationalized the traditional use of Polygonatum verticillatum in the treatment of painful conditions. Copyright

Anti-inflammatory, analgesic and antipyretic activities of Physalis minima Linn

In our present investigation, the crude methanol extract and chloroform fraction of the whole plant of Physalis minima Linn (Solanaceae) was investigated for anti-inflammatory, analgesic and antipyretic activities in NMRI mice and Wistar rats of either sex at 200 and 400 mg/kg, respectively. Various established in-vivo models were used during the study. Both crude extract and chloroform fraction showed marked anti-inflammatory and analgesic activities as compared to a control at tested doses. The antipyretic potential of the crude extract and chloroform were insignificant in the Brewers yeast fever model. Therefore, the whole plant of Physalis minima Linn could be considered as a potential candidate for bioactivity-guided isolation of natural anti-inflammatory and analgesic agents.

Taraxacin, a new guaianolide from Taraxacum wallichii.

A new guaianolide, taraxacin (1), and a known sesquiterpene ketolactone (2) have been isolated from an ethyl acetate-soluble part of a methanolic extract of Taraxacum wallichii. The structure of 1 was established using NMR, MS, and X-ray crystallographic methods. The (13)C NMR data of 2 is also being reported for the first time.

Phytotoxic, insecticidal and leishmanicidal activities of aerial parts of Polygonatum verticillatum

The aim of the present study was to explore the aerial parts of the Polygonatum verticillatum for various biological activities such as phytotoxic, insecticidal and leishmanicidal properties. Outstanding phytotoxicity was observed for the crude extract and its subsequent solvent fractions against Lemna acquinoctialis Welv at tested doses of 5, 50 and 500 ig/ml. Complete growth inhibition (100%) was demonstrated by the crude extract and aqueous fraction at maximum tested dose (500 ig/ml). Among the tested insects, moderate insecticidal activity was recorded against Rhyzopertha dominica. However, neither crude extract nor its solvent fraction registered any significant (> 100 ig/ml) leishmanicidal activity against Leishmania major. Based on the phytotoxicity, the aerial parts of the plant could be a significant source of natural herbicidal for sustainable weed control.

Antibacterial Activities of Dodonaea viscosa using Contact Bioautography Technique

The crude ethanolic extract and n-hexane, dichloromethane, ethyl acetate, n-butanol and aqueous fractions of Dodonaea viscosa were analyzed for antibacterial potential against four Gram positive bacteria: Bacillus subtilis, Bacillus cereus, Micrococcus luteus, Staphylococcus aureus, and three Gram negative bacteria: Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa. Preliminary screening showed inhibition against Staphylococcus aureus, Micrococcus luteus, Escherichia coli and Pseudomonas aeruginosa. The thin layer chromatograms of the fractions were then subjected to contact bioautography, which showed inhibition zone at different Rf values against Bacillus subtilis, Micrococcus luteus, Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa, indicating the presence of antibacterial components. The MIC of each fraction was determined through a 96-well micro-titer plate method. The non-viability of the organisms was ascertained by determining the MBC of the fractions.

Antibacterial, antioxidant and cytotoxic studies of total saponin, alkaloid and sterols contents of decoction of Joshanda: identification of components through thin layer chromatography.

The current study was aimed to assess antibacterial, antioxidant and cytotoxic activity of total saponin, alkaloid and sterol contents of Joshanda decoction followed by its constituent’s analysis via thin layer chromatography (TLC). Saponins and alkaloids showed prominent antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klebsiella pneumoniae whereas sterols only against S. aureus. Saponin and alkaloid contents of 97 and 108 µg/ml, respectively, showed prominent free radical scavenging activity against 1,1-diphenyl-2-picrylhidrazyl, with mild cytotoxicity in brine shrimp cytotoxic test. Under ultraviolet light at 254 nm, TLC of total saponins showed eight different compounds, total sterols comprising three while total alkaloids two compounds of various polarities. It is concluded that the various contents of Joshanda decoction possess outstanding susceptibility against bacteria implicating primarily upper respiratory tract infections augmented by strong antioxidant activity.

Antimicrobial activities of Gloriosa superba Linn (Colchicaceae) extracts

The methanol extract of the rhizomes of Gloriosa superba Linn (Colchicaceae) and its subsequent fractions in different solvent systems were screened for antibacterial and antifungal activities. Excellent antifungal sensitivity was expressed by the n-butanol fraction against Candida albicans and Candida glaberata (up to 90%) and against Trichophyton longifusus (78%) followed by the chloroform fraction against Microsporum canis (80%). In the antibacterial bioassay, the crude extract and subsequent fractions showed mild to moderate antibacterial activities. Chloroform fraction displayed highest antibacterial sensitivity against Staphylococcus aureous (88%) followed by the crude extract (59%). The total phenol content of the crude extract and fractions of the plant expressed no significant correlation with the antimicrobial activities.

SANTOFLAVONE, A 5-DEOXYFLAVONOID FROM ACHILLEA SANTOLINA

Abstract Two methoxylated flavones isolated from the aerial parts of Achillea santolina were identified as 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone and the new compound, 7-hydroxy-3,6,3′,4′-tetramethoxyflavone. Their 1 H and 13 C assignments and structural characterization were achieved through analysis of the BB, DEPT, 1 H 1 H, COSY-45, HMQC and HMBC spectra.