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Tumour reducing and anticarcinogenic activity of selected spices.

Tumour reducing activity of extracts of eight commonly used spices in India were studied in mice transplanted intraperitoneally with Ehrlich ascites tumour. Oral administration of extracts of black pepper, asafoetida, pippali and garlic could increase the percentage of life span in these mice by 64.7%, 52.9%, 47% and 41.1%, respectively. However intraperitoneal administration of spice extracts did not produce any significant reduction in tumour growth except for sesame (38.8%). Garlic extract and asafoetida extracts also inhibited two stage chemical carcinogenesis induced by 7,12 dimethyl benzanthracene and croton oil on mice skin with significant reduction in papiloma formation. These results indicate the potential use of spices as anti-cancer agents as well as anti-tumour promoters.

9,10-Dimethyl-1,2-benzanthracene↗

Chemopreventive action of mace (Myristica fragrans, Houtt) on DMBA-induced papillomagenesis in the skin of mice.

The present paper reports the chemopreventive property of mace (aril covering the seed of Myristica fragrans) on DMBA-induced papillomagenesis in the skin of male Swiss albino mice. When a single topical application of DMBA (150 micrograms in 100 microliters of acetone) was followed, 2 weeks later, by repeated applications of croton oil (1% in acetone, three times/week) skin papillomas appeared in 100% animals and the average tumors per tumor-bearing animal was 5.67. On the other hand, when animals receiving similar treatments were put on a diet containing 1% mace during the periinitiational phase of tumorigenesis, the skin papilloma incidence was reduced to 50% and the average tumor per tumor-bearing mouse was only 1.75. This decline in papilloma was significant (P less than 0.05).

9,10-Dimethyl-1,2-benzanthracene↗

A model for the study of visceral pain states: chronic inflammation of the chronic decerebrate rat urinary bladder by irritant chemicals.

Normal healthy visceral tissue is largely insensitive to many kinds of tissue damaging stimuli, such as cutting, crushing or burning. When inflamed, however, visceral tissue frequently and easily elicits pain. Here we have produced inflammatory responses in urinary bladders of chronically decerebrated rats with irritant chemicals, as a model of a visceral pain state. The irritants used were 25% turpentine, 2.5% mustard oil, 2% croton oil. All produced a strong inflammatory response, as judged by protein extravasation and oedema, and invasion of the tissue with leucocytes, which started within hours of treatment. The inflammatory states were associated with hyperexcitable bladder reflexes; baseline pressures were larger at given volumes, and large micturition contractions occurred at lower volumes. These changes persisted for up to 48 h after a single treatment. The behaviour of the animals and their responsiveness to noxious stimulation were also assessed. In general animals were hypersensitive to noxious stimuli applied to the tail or caudal abdomen, with small or no changes in responses to hind limb or rostral abdominal stimulation. These irritants, particularly turpentine, applied to chronic decerebrate rats may thus provide useful models for studies of the neuronal processes which contribute to visceral nociception.

Animals↗

Ocimum sanctum: an experimental study evaluating its anti-inflammatory, analgesic and antipyretic activity in animals.

A methanol extract and an aqueous suspension of Ocimum sanctum inhibited acute as well as chronic inflammation in rats as tested by carrageenan-induced pedal edema and croton oil-induced granuloma and exudate, respectively. In both test procedures, the anti-inflammatory response of 500 mg/kg of methanol extract and aqueous suspension was comparable to the response observed with 300 mg/kg of sodium salicylate. Both the extract and suspension showed analgesic activity in the mouse hotplate procedure and the methanol extract caused an increase in the tail-withdrawal reaction time of a subanalgesic dose of morphine. Both preparations reduced typhoid-paratyphoid A/B vaccine-induced pyrexia. The antipyretic action of the methanol extract and aqueous suspension was weaker and of shorter duration than that of 300 mg/kg sodium salicylate. Oral premedication with the methanol extract and the aqueous suspension delayed castor oil-induced diarrhoea in rats.

Animals↗

Bioactivity of certain medicinal latexes used by the Ese'ejas.

Latexes from Croton erythrochilus, Ficus inspidia and Sapium marmieri used traditionally as medicinal by the Ese'ejas were analyzed for bioactivity. The assays run were: the brine shrimp toxicity microplate bioassay, the wheat rootlet growth inhibition and the DNA-methyl green bioassay. The three latexes showed cytotoxicity to the brine shrimp and concentration-related growth inhibition. No interaction with the DNA-methyl green complex was observed with any of the three latex samples. The field bioassays described has demonstrated to be useful for supporting ethnobotanical information.

Animals↗

Repellency of essential oils of some plants from the Kenyan coast against Anopheles gambiae.

Volatile oils extracted by hydrodistillation from six plant species growing in the Kenyan coast, Croton pseudopulchellus Pax, Mkilua fragrans Verdc. (Annonaceae), Endostemon tereticaulis (poir.) Ashby, Ocimum forskolei Benth., Ocimum fischeri Guerke and Plectranthus longipes Baker (Labiateae), were evaluated for repellency on forearms of human volunteers against Anopheles gambiae sensu stricto. All oils were found to be more repellent (RC50 range = 0.67-9.21 x 10(-5) mg cm(-2)) than DEET (RC50 = 33 x 10(-5) mg cm(-2)). The individual components of the oils were identified by GC-MS and GC co-injections with authentic standards. The repellency of 15 of the main constituents of the different oils (which had not been previously assayed) was evaluated. Although some of these showed relatively high individual repellencies, none was comparable to the parent essential oils. Partial synthetic blends of selected constituents with moderate or relatively high individual repellency against the vector were also assayed. Four of these exhibited activities comparable to or higher than those of the corresponding parent oils, indicating interesting blend effects in the repellent action of the oils against the mosquito. The implication of these results in the utilization of the plants is discussed.

Animals↗

Synergistic effect of cigarette smoke and saliva on lymphocytes--the mediatory role of volatile aldehydes and redox active iron and the possible implications for oral cancer.

Oral squamous cell carcinoma (SCC) is most induced by exposure of the oral epithelial cells to tobacco products such as cigarette smoke. This exposure always occurs in the presence of saliva and presumably is induced by free radicals. To explore the effects of CS on cells in the presence of saliva, we used peripheral blood lymphocytes (PBL) and exposed them to CS, alone or in the presence of saliva. We discovered that after 80min, exposure of the lymphocytes to CS alone resulted in a time-dependent cellular loss with a survival rate of 56%, while following lymphocyte exposure to CS in the presence of saliva, less than 15% of the cells survived. This was accompanied by concomitant accumulation of cellular protein carbonyls which could be protected by the exogenous addition of uric acid or glutathione, but not by the addition of ascorbate (Asc), N-acetyl-l-cystein (NAC) or desferal (DES). Exposure of the lymphocytes to aldehydes present in CS, such as acrolein and croton-aldehyde, also resulted in the elevation of protein carbonyls, which was ameliorated primarily by the addition of glutathione. However, lymphocyte exposure to acroline in the presence of saliva did not show the same synergism in cell death observed as when the lymphocytes were exposed to CS and saliva. Thus, we postulated the existence of another mechanism and examined the role of redox active iron as an additional explanation for this synergism. In fact, it was found that in the presence of saliva and ascorbate there was a marked decrease in the lymphocyte survival rate; this was reversed by the addition of the iron chelator desferal. In light of these results, a comprehensive mechanism for the induction of oral cancer by cigarette smoke is suggested, stressing the role of a pivotal player in the process leading to oral cancer which has never been previously considered in this regard - the saliva.

Adult↗

The in vitro hydrolysis of poly(ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] and poly(ethylene glycol).

This paper reports the study of the complete degradation process for a series of newly synthesized multi-block poly(ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] (PHB) as hard and hydrophobic block and poly(ethylene glycol) (PEG) as soft and hydrophilic segment. The initial stages of degradation of the poly(PHB/PEG urethane)s were monitored by carrying out the degradation experiments at pH 7.4 and 37 degrees C. The weight loss of the copolymer films was traced, and the degraded copolymer films were characterized by GPC, (1)H NMR, TGA, and SEM. The induction phase of the polymer degradation was characterized by a random chain scission of the ester backbone bonds of the PHB segments and an insignificant decline in the weight of the polymer films. An accelerated degradation process was carried out at pH 11.5 and 37 degrees C to investigate the long-term degradation behaviour. The characterization of the degraded polymer films was similar to that for the experiment at pH 7.4. In addition, the water-soluble degradation products were characterized by GPC, (1)H NMR, and FTIR. The main components of the water-soluble degradation products were found to be PEG blocks (monomeric up to quadmeric), 3-hydroxybutyric acid, and crotonic acid. It was found that the copolymer incorporating the highest amount of PEG degraded at the highest rate of all the copolymers studied. The complete degradation of the poly(PHB/PEG urethane)s was monitored using a combination of the physiological and accelerated hydrolytic degradation.

Biocompatible Materials↗

Synthesis and anti-inflammatory activity of natural and semisynthetic geranyloxycoumarins.

Nine new 7-geranyloxycoumarin derivatives differently substituted at position 8 were semi-synthesised. Their topical anti-inflammatory activity was evaluated using the Croton oil ear test in mice as a model of acute inflammation. Auraptene (7-geranyloxycoumarin), its 8-methoxy (collinin, 1) and 8-acetoxy derivatives (5) (1 micromol/cm(2)) provoked 50% oedema reduction, similarly to 0.25 micromol/cm(2) of the reference drug indomethacin, a nonsteroidal anti-inflammatory drug.

Animals↗

Synthesis of a novel plant growth promoter from gallic acid.

Gallic acid has been modified to naphthophenone derivatives with esterified fatty acid side chain. Compound 12, an ethyl crotonate ester of naphthophenone derivative has shown potent auxin like growth promoter activity. This is the first example of naphthophenone derivatives with plant growth promoting activity.

Bacopa↗

Cytotoxic and proapoptotic activity of ent-16beta-17alpha-dihydroxykaurane on human mammary carcinoma cell line MCF-7.

Here we describe the cytotoxic and proapoptotic effect of an ent-kaurane (ent-16beta-17alpha-dihydroxykaurane), compound isolated from Croton malambo barks, on malignant cell growth. When MCF-7 mammary carcinoma cells were treated with increasing concentrations of the ent-kauranoid, its cytotoxic activity showed an IC50 of 12.5microg/ml, dose that is 2.66-fold lower than the corresponding value for non-malignant cells. At this growth inhibitory dose, both mRNA and protein levels for Bcl-2 as well as mRNA for hTERT were significantly reduced. The observed preapoptotic activity seemed to be triggered by a mechanism that is not directly affecting NF-(kappa)B binding ability. The potential use of this plant-derived compound as a cancer chemotherapy agent is discussed.

Apoptosis↗

Synthesis of new iso-C-nucleoside analogues from 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)ethanal.

Treatment of 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)ethanal with malononitrile, cyanoacetamide and 2-cyano-N-(4-methoxyphenyl)acetamide, respectively, in the presence of aluminium oxide yielded 2-cyano-4-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)crotonic acid derivatives. Cyclization with sulfur and triethylamine was performed to synthesize the 2-amino-5-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)thiophene-3-carbonic acid derivatives, which were treated with triethyl orthoformate/ammonia and triethyl orthoformate, respectively, to furnish 6-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)thieno[2.3-d]pyrimidine derivatives. Deprotection in two steps afforded 2-amino-5-(1,6-anhydro-3-deoxy-beta-D-altropyranos-3-yl)thiophene-3-carbonitrile and 6-(1,6-anhydro-3-deoxy-beta-D-altropyranos-3-yl)thieno[2.3-d]pyrimidine derivatives, respectively.

Aluminum Oxide↗

Antiinflammatory effects of genipin, an active principle of gardenia.

Genipin, the aglycone of geniposide, is metabolically produced from the geniposide in body tissues. The purpose of this study is to clarify some pharmacological actions of genipin. Genipin showed concentration-dependent inhibition on lipid peroxidation induced by Fe++/ascorbate in rat brain homogenate. Genipin exhibited significant topical antiinflammatory effect shown as an inhibition of croton oil-induced ear edema in mice. Nitric oxide (NO) synthesis by inducible nitric oxide synthase (iNOS) is increased in inflammatory diseases and leads to cellular injury. Genipin concentration-dependently (50-300 microM) inhibited NO production and iNOS expression upon stimulation by lipopolysaccharide/interferon-gamma (IFN-gamma) in RAW 264.7, a murine macrophage cell line. Genipin markedly blocked lipopolysaccharide-evoked degradation of inhibitor-kappaB-beta (IkappaB-beta), indicating that it exhibits inhibitory effect on NO production through the inhibition of nuclear factor-kappaB (NF-kappaB) activation. It was also shown to contain potent antiangiogenic activity in a dose-dependent manner, which was detected by chick embryo chorioallantoic membrane assay. In summary, we demonstrate that genipin possesses antiinflammatory and is a specific hydroxyl radical scavenger. Its antiangiogenic and NO production-inhibitory properties are also presented.

Angiogenesis Inhibitors↗

Evolution of the theory of circulation.

The first known descriptions regarding the basic aspects of circulation was probably in 500 B.C., by the Greek thinker Alcmaeon of Croton who observed arteries and veins to be dissimilar in animal dissection, and this was followed by the description of the human heart as a three chambered organ by Aristotle in 350 B.C. Herophilus of Chalcedon, a Greek anatomist, confirmed the findings of dissimilarity between arteries and veins in human cadaver dissections in 300 B.C., and determines that arteries were thicker than veins and contained blood. The advancement by far in the learning of human circulation was made possible first by significant contribution of Galen followed by observations of Ibn al-Nafis, Servetus, Colombo, Cesalpino, Vesalius and Fabricius. In 17th century William Harvey, an English physician, made important advancements into the understanding of this important area of medicine, advancements that continued with the observations of Malpighi.

Blood Circulation↗

Up-regulation of cell surface Toll-like receptor 4-MD2 expression on dendritic epidermal T cells after the emigration from epidermis during cutaneous inflammation.

BACKGROUND: Mouse epidermis contains a population of gammadelta T cells, termed dendritic epidermal T cells (DETCs), which uniformly express the invariant Vgamma3 T cell receptor. Certain DETC lines were reported to respond to Gram-negative bacteria in the presence of immobilized anti-CD3 monoclonal antibody or to lipopolysaccharide (LPS) in the presence of B cell lines. OBJECTIVE: To determine whether DETCs express the primary signaling receptor for LPS, Toll-like receptor (TLR) 4-MD2. METHODS: We analyzed expression of TLR4-MD2 in three independent DETC lines as well as in freshly isolated DETCs. RESULTS: All DETC lines expressed TLR4 and MD2 transcripts and TLR4-MD2 protein complex intracellularly, but none expressed TLR4-MD2 on the cell surface. By immunoblotting, only the immature form of TLR4 protein was detected in the DETC lines. The DETC lines did not respond to LPS even in the presence of immobilized anti-CD3 monoclonal antibody. Freshly isolated DETCs and their fetal thymic precursors also lacked cell surface expression of TLR4-MD2, but a small subpopulation of dermal Vgamma3 T cells isolated from croton oil-painted skin expressed TLR4-MD2 on the cell surface. Similarly, Vgamma3 T cells emigrated from organ-cultured epidermis expressed cell surface TLR4-MD2. CONCLUSIONS: These results demonstrate that DETCs do not constitutively express cell surface TLR4-MD2, but TLR4-MD2 expression may be up-regulated when DETCs emigrate from epidermis during cutaneous inflammation.

Animals↗

Anti-inflammatory activity of Sedum kamtschaticum.

Sedum kamtschaticum Fischer (Crassulaceae) has been used as a folk medicine in North-East Asia for treating inflammatory disorders. The present investigation was carried out to establish in vivo anti-inflammatory activity and cyclooxygenase-2 modulating activity of this plant material. The methanol extract of Sedum kamtschaticum significantly inhibited mouse croton oil-induced ear edema (24-47% inhibition at 50-400 mg/kg) and rat paw edema (24-30% inhibition at 400-800 mg/kg) by oral administration. Prednisolone (10 mg/kg) showed 54 and 36% inhibition in the same animal models, respectively. Sedum kamtschaticum also showed significant inhibitory activity against mouse ear edema induced by multiple treatment of phorbol ester for 3 days. In addition, Sedum kamtschaticum exhibited potent analgesic activity against mouse acetic acid-induced writhing (IC50=125 mg/kg), while aspirin (200 mg/kg) showed 57% inhibition. Using lipopolysaccharide-treated RAW 264.7 cells, down-regulation of cyclooxygenase-2 expression was found to be one of the cellular action mechanisms of anti-inflammation by Sedum kamtschaticum.

Animals↗

In vivo topical anti-inflammatory and in vitro antioxidant activities of two extracts of Thymus satureioides leaves.

Four extracts at increasing polarity were prepared from the leaves of Thymus satureioides Coss. (Labiatae) and assayed for the in vivo topical anti-inflammatory effect using the croton oil ear test in mice, and for in vitro both antioxidant (DPPH degrees test) and anti-bacterial (broth microdilution method) activities. The chloroform extract showed a topical anti-inflammatory activity (ID50=282 microg cm(-2)), only three times lower than that of the reference drug indomethacin (ID50=93 microg cm(-2)) and its active components were identified as ursolic and oleanolic acids. The methanol extract, showing a significant radical-scavenging effect (SC50=14.54 microg), was characterized by the isolation and identification of some flavonoids. On the contrary, the extracts did not show any anti-bacterial effect against four standard aerobial bacteria strains.

Administration, Topical↗

Evaluation of the antioedematogenic, free radical scavenging and antimicrobial activities of aerial parts of Tillandsiastreptocarpa Baker-Bromeliaceae.

The crude methanolic extract of the aerial parts of Tillandsiastreptocarpa was investigated for their acute toxicity and antioedematogenic, antioxidant and antimicrobial activities. Also, the antioedematogenic activity of the hexane fraction resulting from the partition of the crude methanolic extract was evaluated. The methanolic extract and the hexane fraction showed significant (P < 0.05) inhibition of ear oedema, observed at 2 mg/ear in the croton oil-induced mice ear oedema test. In the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging test, a high reactivity and potent antioxidant effect (IC(50) = 0.0056%, w/v) were observed for the methanolic extract. The antimicrobial activity assay showed that the crude methanolic extract was inactive toward Escherichiacoli, Staphylococcusaureus, Pseudomonasaeruginosa, Bacillussubtilis, Candidaalbicans, C. parapsilosis, C. krusei and C. tropicalis (MIC > 500 microg/ml). The methanolic extract showed no toxic effect on mice at a single dose of 2000 mg/kg (p.o). Common side effects including mild diarrhoea, loss of weight and depression were not recorded. The compounds cycloartenol, 4',5-dihydroxy-3',7-dimethoxyflavanone and a mixture of the steroids stigmasterol, beta-sitosterol and campesterol, were isolated from the hexane fraction and identified by spectroscopic methods.

Animals↗