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Biomedical subjects

K C Srivastava

Publications and source records attributed to K C Srivastava.

At least 19 recordsLinked to original sources

Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease.

Thirty patients with coronary artery disease (CAD) were administered garlic (study group) while another 30 patients received the placebo (control group). Various risk parameters were determined at 1.5 and 3 months of garlic administration. Garlic, administered in a daily dose of 2 x 2 capsules (each capsule containing ethyl acetate extract from 1 g peeled and crushed raw garlic), reduced significantly total serum cholesterol and triglycerides, and increased significantly HDL-cholesterol and fibrinolytic activity. There was no effect on the fibrinogen and glucose levels. In vitro effects of the garlic oil on platelet aggregation (PAg) and eicosanoid metabolism were examined; it inhibited PAg induced by several platelet agonists, and also platelet thromboxane formation. Two important paraffinic polysulphides - diallyl disulphide (DADS) and diallyl trisulphide (DATS) - derived from garlic and are usual constituents of garlic oil, showed antiplatelet activity, and also inhibited platelet thromboxane formation. In this respect DATS was more potent than DADS. The nature of inhibition of PAg by DATS was found to be reversible.

Allyl Compounds↗

Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease.

In a placebo-controlled study the effect of ginger and fenugreek was examined on blood lipids, blood sugar, platelet aggregation, fibrinogen and fibrinolytic activity. The subjects included in this study were healthy individuals, patients with coronary artery disease (CAD), and patients with non-insulin-dependent diabetes mellitus (NIDDM) who either had CAD or were without CAD. In patients with CAD powdered ginger administered in a dose of 4 g daily for 3 months did not affect ADP- and epinephrine-induced platelet aggregation. Also, no change in the fibrinolytic activity and fibrinogen level was observed. However, a single dose of 10 g powdered ginger administered to CAD patients produced a significant reduction in platelet aggregation induced by the two agonists. Ginger did not affect the blood lipids and blood sugar. Fenugreek given in a dose of 2.5 g twice daily for 3 months to healthy individuals did not affect the blood lipids and blood sugar (fasting and post prandial). However, administered in the same daily dose for the same duration to CAD patients also with NIDDM, fenugreek decreased significantly the blood lipids (total cholesterol and triglycerides) without affecting the HDL-c. When administered in the same daily dose to NIDDM (non-CAD) patients (mild cases), fenugreek reduced significantly the blood sugar (fasting and post prandial). In severe NIDDM cases, blood sugar (both fasting and post prandial) was only slightly reduced. The changes were not significant. Fenugreek administration did not affect platelet aggregation, fibrinolytic activity and fibrinogen.

Arachidonic Acids↗

Effect of garlic on platelet aggregation in humans: a study in healthy subjects and patients with coronary artery disease.

Garlic's value in preventing cardiovascular disease has been reported by several research groups. Garlic and its components are known to possess antiplatelet activity which has been demonstrated mostly in vitro. It was found that garlic oil administration to healthy subjects and patients with coronary artery disease (CAD) inhibited platelet aggregation ex vivo. Though garlic components leave the body quickly, a slow build-up of the active ingredients may take place. This was evident from the observation that though a 2-3 fold higher dose was not effective in inhibiting platelet aggregation when administered once, a lower dose became effective in long-term administration.

Adult↗

Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets.

In traditional medicine, Ayurveda, several spices and herbs are held to possess medicinal properties. Earlier we have reported that extracts from several spices, including turmeric, inhibit platelet aggregation and modulate eicosanoid biosynthesis. Due to their eicosanoid-modulating property, it was suggested that the spices may serve to provide clues to drugs directed to arachidonic acid (AA) pathway enzymes as pharmacological targets. Curcumin, a major component of turmeric, inhibited platelet aggregation induced by arachidonate, adrenaline and collagen. This compound inhibited thromboxane B2 (TXB2) production from exogenous [14C] arachidonate in washed platelets with a concomitant increase in the formation of 12-lipoxygenase products. Moreover, curcumin inhibited the incorporation of [14C]AA into platelet phospholipids and inhibited the deacylation of AA-labelled phospholipids (liberation of free AA) on stimulation with calcium ionophore A23187. Curcumin's anti-inflammatory property may, in part, be explained by its effects on eicosanoid biosynthesis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Suppressive effects of eugenol and ginger oil on arthritic rats.

This study examined the effect of eugenol and ginger oil on severe chronic adjuvant arthritis in rats. Severe arthritis was induced in the right knee and right paw of male Sprague-Dawley rats by injecting 0.05 ml of a fine suspension of dead Mycobacterium tuberculosis bacilli in liquid paraffin (5 mg/ml). Eugenol (33 mg/kg) and ginger oil (33 mg/kg), given orally for 26 days, caused a significant suppression of both paw and joint swelling. These findings suggest that eugenol and ginger oil have potent antiinflammatory and/or antirheumatic properties.

Animals↗

Properties of thermostable hemicellulolytic enzymes from Thermomonospora strain 29 grown in solid state fermentation on coffee processing solid waste.

During decaffeination of Coffee Processing Plant Solid Wastes (CPSW) by actinomycetes, Thermomonospora, Strain 29 exhibited high titers of cellulase and xylanase. This organism, originally isolated on soybean seed coat was grown in solid state fermentation on CPSW supplemented with mineral salts. Enzymes recovered were arabinosidase, xylanase, and beta-D-xylosidase. Higher activity of the former two enzymes was in the extracellular broth, whereas the beta-D-xylosidase activity was highest in the cell fraction. The enzymes were characterized after precipitation with (NH(4))(2)SO(4), dialysis, and gel filtration. Production of all three enzymes was inhibited by monomeric sugars and sugar alcohols but not by arabinoxylan, xylans, or xylan containing water insoluble carbohydrates. The optimum pH for the activity was 6.5, 7.0, and 7.5 for beta-xylosidase, xylanase and arabinosidase (alpha-L-arabinofuranosidase, alpha-arabinosidase, alpha-L-arabinosidase) respectively. These enzymes were stable in the pH range of 6.5 to 8.0. All three enzymes were thermostable up to 80 degrees C. At 55 degrees C, arabinosidase had the longest half life of 120 h. However, at 40 degrees C, xylanase had the longest half life (504 h). At either temperature, beta-D-xylosidase had the shortest half life. The molecular weights (kDa), and Kms (mM) were estimated to be 95, 0.27; 45, 12.4; and 106, 0.67 for arbinosidase, xylanase, and beta-xylosidase respectively. Step wise addition of the three enzymes showed higher saccharification of lignocellulosics.

Journal Article↗

Antiplatelet principles from a food spice clove (Syzygium aromaticum L) [corrected].

In continuation of our studies on the oil of cloves--a common kitchen spice and a drug for home medicine--we have isolated and identified two antiplatelet components, eugenol and acetyl eugenol. They inhibited arachidonate-, adrenaline- and collagen-induced platelet aggregation; they were more potent in inhibiting aggregation by the first two agonists. Their inhibitory effect was reversible. These components were antiaggregatory by a combination of at least two effects: (i) inhibition of platelet thromboxane formation, and (ii) increased formation of 12-lipoxygenase products (12-HPETE). Though the presence of plasma proteins would reduce the effective concentration of these substances due to binding, the relatively lower amounts of these components which inhibited arachidonate-induced aggregation when compared to their effects on thromboxane production was intriguing. The answer might partly lie in an increased formation of 12-HPETE facilitated by albumin which acts as a 'conduit' to divert free arachadonic acid (AA) from the platelet cyclooxygenase (CO) to the lipoxygenase pathway (22). Based on their IC50 values, it was found that both eugenol and acetyl eugenol were more potent than aspirin in inhibiting platelet aggregation induced by arachidonate, adrenaline and collagen. In arachidonate-induced aggregation eugenol was on a par with indomethacin. It was found that eugenol and acetyl eugenol when used in combination potentiated inhibition of platelet aggregation induced by arachidonate, adrenaline and collagen. This effect was, however, not evident from the metabolism of AA in platelets; when used in combination the two compounds produced an additive effect.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Effects of a garlic-derived principle (ajoene) on aggregation and arachidonic acid metabolism in human blood platelets.

When garlic cloves are chopped or crushed several dialkyl thiosulfinates are rapidly formed by the action of the enzyme alliin lyase or alliinase (EC 4.4.1.4) on S(+)-alkyl-L-cysteine sulfoxides. Allicin (diallyl thiosulfinate or allyl 2-propene thiosulfinate) is the dominant thiosulfinate released. A variety of sulfur containing compounds are formed from allicin and other thiosulfinates depending on the way in which garlic is handled. One such compound identified recently is ajoene which has been reported to possess antithrombotic properties. We present here data on the antiplatelet properties of ajoene together with its effects on the metabolism of arachidonic acid (AA) in intact platelets. Thus, ajoene was found to inhibit platelet aggregation induced by AA, adrenaline, collagen, adenosine diphosphate (ADP) and calcium ionophore A23187; the nature of the inhibition was irreversible. In washed platelets stimulated by labelled arachidonate, ajoene inhibited the formation of thromboxane A2; 12-lipoxygenase product(s) were reduced at higher ajoene concentrations. This garlic-derived substance inhibited the incorporation of labelled AA into platelet phospholipids at higher concentration. In labelled platelets, on stimulation with either calcium ionophore A23187 or collagen, reduced amounts of thromboxane and 12-HETE (12-hydroxyeicosatetraenoic acid) were produced in ajoene-treated platelets compared to control platelets. This substance had no effect on the deacylation of platelet phospholipids. The results suggest that at least one of the mechanisms by which ajoene shows antiplatelet effects could be related to altered metabolism of AA.

Arachidonic Acid↗

Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders.

One of the features of inflammation is increased oxygenation of arachidonic acid which is metabolized by two enzymic pathways--the cyclooxygenase (CO) and the 5-lipoxygenase (5-LO)--leading to the production of prostaglandins and leukotrienes respectively. Amongst the CO products, PGE2 and amongst the 5-LO products, LTB4 are considered important mediators of inflammation. More than 200 potential drugs ranging from non-steroidal anti-inflammatory drugs, corticosteroids, gold salts, disease modifying anti-rheumatic drugs, methotrexate, cyclosporine are being tested. None of the drugs has been found safe; all are known to produce from mild to serious side-effects. Ginger is described in Ayurvedic and Tibb systems of medicine to be useful in inflammation and rheumatism. In all 56 patients (28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular discomfort) used powdered ginger against their afflictions. Amongst the arthritis patients more than three-quarters experienced, to varying degrees, relief in pain and swelling. All the patients with muscular discomfort experienced relief in pain. None of the patients reported adverse effects during the period of ginger consumption which ranged from 3 months to 2.5 years. It is suggested that at least one of the mechanisms by which ginger shows its ameliorative effects could be related to inhibition of prostaglandin and leukotriene biosynthesis, i.e. it works as a dual inhibitor of eicosanoid biosynthesis.

Aged↗

Acetyl eugenol, a component of oil of cloves (Syzygium aromaticum L.) inhibits aggregation and alters arachidonic acid metabolism in human blood platelets.

In continuation of our studies with the oil of cloves--a common kitchen spice and a crude drug for home medicine--we have isolated yet another active component identified as acetyl eugenol (AE); the earlier reported active component being eugenol. The isolated material (IM) was found to be a potent platelet inhibitor; IM abolished arachidonate (AA)-induced aggregation at ca. 12 microM, a concentration needed to abolish the second phase of adrenaline-induced aggregation. Chemically synthesized acetyl eugenol showed similar effects on AA- and adrenaline-induced aggregation. A dose-dependent inhibition of collagen-induced aggregation was also observed. AE did not inhibit either calcium ionophore A23187- or thrombin-induced aggregation. Studies on aggregation and ATP release were done using whole blood (WB). AA-induced aggregation in WB was abolished at 3 micrograms/ml (14.6 microM) which persisted even after doubling the concentration of AA. ATP release was inhibited. Inhibition of aggregation appeared to be mediated by a combination of two effects: reduced formation of thromboxane and increased generation of 12-lipoxygenase product (12-HPETE). These effects were observed by exposing washed platelets to (14C)AA or by stimulating AA-labelled platelets with ionophore A23187. Acetyl eugenol inhibited (14C)TxB2 formation in AA-labelled platelets on stimulation with thrombin. AE showed no effect on the incorporation of AA into platelet phospholipids.

Acylation↗

Ginger (Zingiber officinale) in migraine headache.

Migraine is considered as a neurological disorder with little convincing evidence of the involvement of some vascular phenomenon. Recent understanding of the mechanisms behind migraine pain generation and perception have considerably helped the development of modern migraine drugs. Most migraine drugs in use, i.e., ergotamine and dihydroergotamine, iprazochrome, pizotifen and diazepam; and non-steroidal antiinflammatory drugs (i.e. aspirin, paracetamol, persantin, etc.) have side-effects and are prescribed with caution for a limited duration. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in neurological disorders. It is proposed that administration of ginger may exert abortive and prophylactic effects in migraine headache without any side-effects.

Adult↗

Isolation and effects of some garlic components on platelet aggregation and metabolism of arachidonic acid in human blood platelets.

Effects of aqueous extract of garlic, of materials extracted in two organic solvents, viz., ether and chloroform in succession, and of some fractions obtained after TLC of the aqueous extract were examined on platelet aggregation induced by several aggregating agents. Their effects were also investigated on the formation of thromboxane and lipoxygenase products from endogenous arachidonic acid in intact platelets. The aqueous extract inhibited aggregation induced by all aggregating agents and so did the materials extracted in two organic solvents. Only two fractions obtained from TLC of the aqueous garlic extract were examined for effects on epinephrine- and arachidonic acid (AA)-induced aggregation; they were found to be antiaggregatory. The material extracted in ether (MEE) inhibited the incorporation of labelled AA into platelets in platelet-rich plasma. Garlic extracts (MEE and material extracted in chloroform, MEC) at higher dosage inhibited the degradation of platelet phospholipids and reduced the formation of thromboxane (TxB2) and lipoxygenase-derived products from labelled platelets. The two organic extracts at low dosage, while not affecting the degradation of platelet phospholipids, inhibited the cyclooxygenase and lipoxygenase enzymes. A concomitant increase in the amount of released AA was observed in the treated platelets. Similar effects in relation to dosage were observed with the aqueous extract of garlic.

Arachidonic Acid↗

Ginger (Zingiber officinale) and rheumatic disorders.

Oxygenation of arachidonic acid is increased in inflamed tissues. In this condition products of two enzymic pathways--the cyclooxygenase and the 5-lipoxygenase producing respectively prostaglandins and leukotrienes--are elevated. Of the cyclooxygenase products, PGE2 and of the lipoxygenase products, LTB4 are the strongest candidates for mediating inflammation. Non-steroidal anti-inflammatory drugs which inhibit the cyclooxygenase, and corticosteroids are used to treat such disorders. Both types of drugs produce adverse side-effects on prolonged use. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in rheumatic disorders. Seven patients suffering from such disorders reported relief in pain and associated symptoms on ginger administration.

Aged↗

Effect of onion and ginger consumption on platelet thromboxane production in humans.

The effects of onion and ginger consumption on platelet thromboxane production were examined. Volunteers, all Danish women, consumed either 70 g raw onion or 5 g raw ginger daily for a period of 7 days. Each participant in each (onion or ginger) group served as her own control. TxB2 determination was made in serum obtained after blood clotting. The following are the results. TxB2 (pmol/ml serum): (i) onion group--before consumption 910 +/- 327, after consumption 1005 +/- 713 (Mean +/- SD, N = 5); (ii) ginger consumption 782 +/- 482, after consumption 498 +/- 164 (Mean +/- SD, N = 7).

Adult↗

Extracts from two frequently consumed spices--cumin (Cuminum cyminum) and turmeric (Curcuma longa)--inhibit platelet aggregation and alter eicosanoid biosynthesis in human blood platelets.

In the traditional Indian system of medicine, Ayurveda, several spices and herbs are claimed to possess medicinal properties, such as being antithrombotic, antiatherosclerotic, hypolipidemic, anti-inflammatory etc. Earlier we have reported that extracts from several spices behave as antiaggregatory agents and inhibit eicosanoid synthesis. Similar studies with extracts prepared from cumin (Cuminum cyminum) and turmeric (Curcuma longa) were undertaken. Ethereal extract of both cumin and turmeric inhibited arachidonate-induced platelet aggregation. Extracts from these spices inhibited thromboxane B2 production from exogenous (14C) arachidonic acid (AA) in washed platelets; a simultaneous increase in the formation of lipoxygenase-derived products was observed. Less TxB2 was produced in blood samples treated with turmeric extract when they were allowed to clot. Turmeric extract inhibited incorporation of (14C)AA into platelet phospholipids and deacylation of AA-labelled phospholipids on stimulation with calcium ionophore A23187. Cumin extract was devoid of such effects. Extracts from the two spices reduced the formation of (14C)TxB2 from AA-labelled platelets when they were challenged with A23187. The anti-inflammatory property of turmeric may, in part, be explained by its effect on eicosanoid biosynthesis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Extract of a spice--omum (Trachyspermum ammi)-shows antiaggregatory effects and alters arachidonic acid metabolism in human platelets.

An ethereal extract of omum (Trachyspermum ammi; Hindustani: ajwan)--a frequently consumed spice--was found to inhibit platelet aggregation induced by arachidonic acid (AA), epinephrine and collagen; in this respect it was most effective against AA-induced aggregation. Inhibition of aggregation by omum could be explained by its effect on platelet thromboxane production as suggested by the following experimental observation. (i) Omum reduced TxB2 formation in intact platelet preparations from added arachidonate, and (ii) it reduced the formation of TxB2 from AA-labelled platelets after stimulation with Ca2+-ionophore A23187 by a direct action on cyclooxygenase as it did not affect the release of AA from labelled platelets. An increased formation of lipoxygenase-derived products from exogenous AA in omum-treated platelets was apparently due to redirection of AA from cyclooxygenase to the lipoxygenase pathway.

Arachidonic Acid↗

Inhibition of platelet aggregation and reduced formation of thromboxane and lipoxygenase products in platelets by oil of cloves.

Oil of cloves (OC) was found to be a potent inhibitor of platelet aggregation induced by arachidonic acid (AA), collagen and epinephrine; in this respect it was most effective against AA-induced aggregation. Inhibition of aggregation by OC seems to be mediated through a reduced formation of thromboxane as indicated by the following experimental evidence. (i) OC inhibited TxB2 formation in intact as well as lysed platelet preparations from added arachidonate, and (ii) it inhibited the formation of TxB2 from AA-labelled platelets after activation with Ca2+-ionophore A23187. The formation of lipoxygenase derived products was dependent on the concentration of OC used; at its lower concentration their amounts increased but this was found to be reversed at higher concentrations. At all concentrations thromboxane was decreased with a concomitant increase in unused AA.

Arachidonic Acid↗