1,721,012 research outputs found
Validation of ethnopharmacological uses of Heliotropium strigosum Willd. as spasmolytic, bronchodilator and vasorelaxant remedy
No full textBackground: Heliotropium strigosum is used in traditional medicine to manage gastrointestinal pain, respiratory distress and vascular disorders. The present study was undertaken to provide scientific evidences for these folkloric uses by in vitro experimental settings. Methods: A crude methanol extract of the Heliotropium strigosum (Hs.Cr) was tested in vitro on isolated rabbit jejunum preparations to detect the possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Results: The Hs.Cr exhibited relaxant effects in rabbit jejunum in a concentration dependent manner (0.01-3.0 mg/ml). The Hs.Cr also relaxed K+ (80 mM)-induced spastic contractions in rabbit jejunum and shifted the Ca2+ concentration response curves towards right. The extract relaxed carbachol (1 μM)- as well as K+ (80 mM)-induced contractions in rabbit trachea at concentrations ranging from 0.01 to 10 mg/ml. Moreover, Hs.Cr. also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta. Conclusions: The Hs.Cr was found to exhibit spasmolytic, bronchodilator and vasorelaxant activities on isolated rabbit jejunum, trachea and aorta preparations, likely mediated through Ca2+ channel blockade. This finding may provide a scientific basis for the folkloric uses of the plant
Ameliorative effect of water spinach, Ipomea aquatica (Convolvulaceae), against experimentally induced arsenic toxicity
Full text linkBackground: Ipomea aquatica (Convolvulaceae) is traditionally used against Arsenic (As) poisoning in folk medicines in India. The present study was designed to explore the therapeutic role of aqueous extract of I. aquatica (AEIA) against As-intoxication.
Methods: AEIA was chemically standardized by spectroscopic and chromatographic analysis. The cytoprotective role of AEIA was measured on isolated murine hepatocytes. The effect on redox status were measured after incubating the hepatocytes with NaAsO2 (10 mu M) + AEIA (400 mu g/ml). The protective effect of AEIA (400 mu g/ml) in expressions of apoptotic proteins were estimated in vitro. The protective role of AEIA was measured by in vivo assay in mice. Haematological, biochemical, As bioaccumulation and histological parameters were evaluated to ensure the protective role of AEIA (100 mg/kg) against NaAsO2 (10 mg/kg) intoxication.
Results: Phytochemical analysis revealed presence of substantial quantities of phenolics, flavonoids, saponins and ascorbic acid in AEIA. Incubation of murine hepatocytes with AEIA (0-400 mu g/ml) + NaAsO2 (10 mu M) exerted a concentration dependent cytoprotective effect. Incubation of murine hepatocytes with NaAsO2 (10 mu M, similar to IC50) induced apoptosis via augmenting oxidative stress. NaAsO2 treated hepatocytes exhibited significantly (p < 0.01) enhanced levels of ROS production, lipid peroxidation and protein carbonylation with concomitant depletion of antioxidant enzymes (p < 0.05-0.01) and GSH (p < 0.01) levels. However, AEIA (400 mu g/ml) + NaAsO2 (10 mu M) could significantly (p < 0.05-0.01) reinstate the aforementioned parameters to near-normal status. Besides, AEIA (400 mu g/ml) could significantly counteract (p < 0.05-0.01) ROS mediated alteration in the expressions of apoptotic proteins viz. Bcl-2, BAD, Cyt C, Apaf 1, caspases, Fas and Bid. In in vivo bioassay, NaAsO2 (10 mg/kg) treatment in mice caused significantly (p < 0.05-0.01) elevated As bioaccumulation, ATP levels, DNA fragmentations and oxidative stress in the liver, kidney, heart, brain and testes along with alteration in cytoarchitecture of these organs. In addition, the serum biochemical and haematological parameters were significantly (p < 0.05-0.01) altered in the NaAsO2-treated animals. However, concurrent administration of AEIA (100 mg/ml) could significantly reinstate the NaAsO2-induced pathogenesis
Pharmacological basis of the use of the root bark of Zizyphus nummularia Aubrev. (Rhamnaceae) as anti-inflammatory agent
No full textBackground: The root bark of Zizyphus nummularia (Rhamnaceae) is traditionally used as an anti-inflammatory agent. The current study aimed to explore the anti-inflammatory activity (in vivo) of a crude ethanolic extract (EE) and the pure identified octadecahydro-picene-2,3,14,15-tetranone (IC) in the root bark of Z. nummularia. IC was further subjected to suitable in vitro and in silico studies to find out the mechanistic pharmacology.
Methods: EE (100 and 200 mg/kg, p.o.) and (IC) (400 and 600 mu g/kg, p.o.) were subjected to in vivo anti-inflammatory assays to evaluate the anti-inflammatory activity and predict the probable mechanism(s) of action. Suitable acute (carrageenan-induced paw edema, arachidonic acid-induced ear edema, xylene-induced ear edema) and chronic (cotton pellet granuloma) models were employed to investigate in vivo the anti-inflammatory activity. Based on in vivo observation, IC was further subjected to in vitro assays to estimate the inhibition of nitric oxide (NO), prostaglandin-E2 (PGE-2) and tumor necrosis factor-alpha (TNF-alpha) production in PBS stimulated RAW 264.7 cells. Based on the observation of in vitro studies, finally, ADME prediction and molecular docking studies of IC were performed for better understanding of interaction of IC with TNF-alpha.
Results: Oral administration of EE (100 and 200 mg/kg) exhibited significant inhibition of carrageenan (p < 0.05) and arachidonic acid (p < 0.05) induced oedema, and the reduced the granuloma tissue formation (p < 0.05) in experimental mice. IC (400 and 600 mu g/kg, p.o.) exhibited significant (p < 0.01) inhibition of carrageenan, xylene and arachidonic acid-induced edema, and reduced the granuloma tissue formation. In in vitro assays, IC caused a concentration-dependent inhibition of LPS stimulated NO (up to similar to 67.4 % at 50 mu M) and TNF-alpha (similar to 84.5 % at 50 mu M) production. However, the PGE-2 inhibition did not follow dose dependent pattern. Based on in vitro observations, the molecular docking has been performed on the basis of interaction with TNF-alpha. In in silico studies, it was observed that IC showed hydrogen bonding with GLN 47 amino acid residue of TNF-alpha protein.
Conclusions: IC possibly produces anti-inflammatory activity through inhibition of TNF-a and NO production
Zia-ul-Haq, Muhammad (1924-1988)
No full textIl contributo tratteggia sinteticamente la biografia politica di Muhammad Zia-ul-Haq, con particolare attenzione alle intersezioni fra dimensione religiosa e politica della sua azione
The effects of two common edible herbs, Ipomoea aquatica and Enhydra fluctuans, on cadmium-induced pathophysiology: A focus on oxidative defence and anti-apoptotic mechanism
Full text linkBackground: Ipomoea aquatica (Convolvulaceae) and Enhydra fluctuans (Asteraceae), two aquatic vegetables, are traditionally used against heavy metal toxicity in traditional medicines in India. The present study aimed to explore the protective role of edible (aqueous) extracts of I. aquatica (AEIA) and E. fluctuans (AEEF) against Cd-intoxication.
Methods: The extracts were chemically standardized by spectroscopic and HPLC analysis. The cytoprotective roles of AEIA and AEEF were measured on mouse hepatocytes. The effect on redox status were measured after incubating the hepatocytes with CdCl2 (30 mu M) along with AEIA or AEEF (400 mu g/ml). The effects on the expressions of apoptotic signal proteins were estimated. The protective roles of AEIA or AEEF were measured by in vivo assay in mice. Haematological, serum biochemical, tissue redox status, Cd bioaccumulation and histological parameters were evaluated to estimate the protective role of AEIA or AEEF (100 mg/kg) against CdCl2 (4 mg/kg) intoxication.
Results: Phytochemical analysis revealed presence of substantial quantities of phenolics, flavonoids, saponins, carbohydrates and ascorbic acid in AEIA or AEEF. CdCl2 treated murine hepatocytes showed a gradual reduction of cell viability in a concentration dependent manner with an IC50 of similar to 30 mu M. CdCl2 treated hepatocytes exhibited significantly enhanced levels (p < 0.01) of ROS production, lipid peroxidation, protein carbonylation and NADPH oxidase with concomitant depletion (p < 0.01) of antioxidant enzymes and GSH. However, AEIA or AEEF treatment along with CdCl2 significantly restored the aforementioned parameters in murine hepatocytes near to normalcy. Besides, AEIA or AEEF significantly counteracted (p < 0.05-0.01) with ROS mediated alteration of transcription levels of signal proteins viz. Bcl-2, BAD, Cyt-C, Caspases, Fas and Bid. In in vivo bioassay, CdCl2 treatment caused significantly high Cd bioaccumulation and oxidative stress in the liver, kidney, heart, brain and testes in mice. In addition, the haematological and serum biochemical parameters were significantly altered in the CdCl2 treated animals. Simultaneous administration of AEIA or AEEF could significantly restore the tested parameters to the near-normal status
Pharmacological justification of use of Solena heterophylla Lour. in gastrointestinal, respiratory and vascular disorders
No full textBACKGROUND: Solena heterophylla Lour. has traditionally been used in the management of diseases pertaining to gastrointestinal, respiratory and vascular system and present study was undertaken to validate its traditional uses.
METHODS: The aqueous ethanolic extract of Solena heterophylla Lour (Sh.Cr) was tested in-vitro on isolated rabbit jejunum, tracheal and aorta preparations. The responses of tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system.
RESULTS: The aqueous ethanolic extract of Solena heterophylla Lour (Sh.Cr) (0.03-1.0 mg/ml) on application to spontaneous contractions in isolated rabbit jejunum preparation exerted relaxant effect through decrease in magnitude and frequency of contractions, caused relaxation of K(+)(80 mM)-induced contractions and shifted the Ca(2+) concentration response curves toward right in isolated rabbit jejunum preparations in a manner similar to verapamil (a standard Ca(2+) channel blocker), thus confirming its Ca(2+) channel blocking activity. The Sh.Cr also caused relaxation of carbachol (1 muM)- and K(+)(80 mM)-induced contractions in isolated rabbit tracheal preparations in a manner comparable to dicyclomine.
CONCLUSIONS: The observed relaxant effect may be outcome of anti-muscarinic and Ca(2+) channel blocking activities. The Sh.Cr (0.03-1.0 mg/ml) against phenyephrine (1 muM)- and K(+)(80 mM)-induced contractions in isolated rabbit aortic preparations exerted a relaxant effect, possibly through Ca(2+) channel blocking activity. These findings provide a rationale for the folkloric uses of the plant in the management of ailments pertaining to gastrointestinal, respiratory and vascular system
Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response
Full text linkBackground: Abroma augusta L. (Malvaceae) leaf is traditionally used to treat diabetes in India and Southern Asia. Therefore, current study was performed to evaluate the protective effect of defatted methanol extract of A. augusta leaves (AA) against type 2 diabetes mellitus (T2DM) and its associated nephropathy and cardiomyopathy in experimental rats.
Methods: Antidiabetic activity of AA extracts (100 and 200 mg/kg, p.o.) was measured in streptozotocin-nicotinamide induced type 2 diabetic (T2D) rat. Fasting blood glucose level (at specific interval) and serum biochemical markers (after sacrifice) were measured. Redox status, transcription levels of signal proteins (NF-kappa B and PKCs), mitochondria dependent apoptotic pathway (Bad, Bcl-2, caspase cascade) and histological studies were performed in kidneys and hearts of controls and AA treated diabetic rats.
Results: Phytochemical screening of extracts revealed the presence of taraxerol, flavonoids and phenolic compounds in the AA. T2D rats showed significantly (p < 0.01) elevated fasting blood glucose level. Alteration in serum lipid profile and release of membrane bound enzymes like lactate dehydrogenase and creatine kinase, which ensured the participation of hyperlipidemia and cell membrane disintegration in diabetic pathophysiology. T2DM caused alteration in the serum biochemical markers related to diabetic complications. T2DM altered the redox status, decreased the intracellular NAD and ATP concentrations in renal and myocardial tissues of experimental rats. Investigating the molecular mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats also exhibited an up-regulation of NF-kappa B and increase in the concentrations of pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) in the renal and cardiac tissues. The activation of mitochondria dependent apoptotic pathway was observed in renal and myocardial tissues of the T2D rats. However, Oral administration of AA at the doses of 100 and 200 mg/kg body weight per day could reduce hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological studies also supported the protective characteristics of A
Preventive role of green tea catechins from obesity and related disorders especially hypercholesterolemia and hyperglycemia
Full text linkBACKGROUND: During the last few years, scientific investigations have proposed diet based regimens to prevent several health ailments including obesity, hypercholesterolemia and diabetes. In this regard, a promising tool is the use of functional foods/nutraceuticals. Present research project was an attempt to explore nutraceutical worth of locally grown green tea variety (Qi-Men) against lifestyle related disorders.
METHODS: Functional drinks (T2 and T3) were prepared by adding catechins and epigallocatechin gallate (EGCG) @ 550mg/500mL and compared with control (T1). These functional drinks were tested in experimental rats modeling (Sprague Dawley). Based on diets, four studies were conducted i.e. trial-I (normal diet), trial-II (high cholesterol diet), trial-III (high sucrose diet), trial-IV (high cholesterol+high sucrose diet). Rats were monitored daily for their feed and drink intake while body weight was measured on weekly basis. After period of 56days rats were sacrificed and evaluated their serum lipid (cholesterol, LDL and HDL), glucose and insulin levels.
RESULTS: Results for feed consumption by rats revealed that highest feed intake was recorded in group provided control drink than other groups. However, non significant differences were noted among all groups for drink consumption. Functional drinks resulted in significant reduction in body weight with maximum lowering noted in trial-II and III i.e. 10.73 to 8.49% and 10.12 to 10.49%, respectively. Likewise, cholesterol and LDL were substantially reduced with 14.42% decrease observed in trial-IV and 30.43% in trial-II, respectively. Furthermore, serum glucose and insulin levels were also lowered significantly in the trial-III and IV while in trial-I and II differences were non-significant. In contrast to lipid profile, experimental drink containing EGCG reduced the trait better than catechins based functional drink.
CONCLUSIONS: The drinks supplemented with catechins and EGCG are effective against obesity, hypercholesterolemia and hyperglycemia
Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition
No full textMultidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to P-glycoprotein (P-gp) and its down-regulation by natural bioactive molecules. P-gp, a unique ATP-dependent membrane transport protein, is one of those key regulators which are present in the lining of the colon, endothelial cells of the blood brain barrier (BBB), bile duct, adrenal gland, kidney tubules, small intestine, pancreatic ducts and in many other tissues like heart, lungs, spleen, skeletal muscles, etc. Due to its diverse tissue distribution, P-gp is a novel protective barrier to stop the intake of xenobiotics into the human body. Over-expression of P-gp leads to decreased intracellular accretion of many chemotherapeutic agents thus assisting in the development of MDR. Eventually, the effectiveness of these drugs is decreased. P-gp inhibitors act by altering intracellular ATP levels which are the source of energy and/or by affecting membrane contours to increase permeability. However, the use of synthetic inhibitors is known to cause serious toxicities. For this reason, the search for more potent and less toxic P-gp inhibitors of natural origin is underway. The present review aims to recapitulate the research findings on bioactive constituents of natural origin with P-gp inhibition characteristics. Natural bioactive constituents with P-gp modulating effects offer great potential for semi-synthetic modification to produce new scaffolds which could serve as valuable investigative tools to recognize the function of complex ABC transporters apart from evading the systemic toxicities shown by synthetic counterparts. Despite the many published scientific findings encompassing P-gp inhibitors, however, this article stand alones because it provides a vivid picture to the readers pertaining to Pgp inhibitors obtained from natural sources coupled with their mode of action and structures. It provides first-hand information to the scientists working in the field of drug discovery to further synthesise and discover new P-gp inhibitors with less toxicity and more efficacies
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