Isolation, structure elucidation and in vivo hepatoprotective potential of trans-tetracos-15-enoic acid from Indigofera tinctoria Linn.

The bioassay guided fractionation of the dried aerial part of Indigofera tinctoria Linn. led to the identification of an active fraction labelled as indigotin. On further chemical analysis, a compound isolated from indigotin was identified and characterized as trans-tetracos-15-enoic acid (TCA). The chemical structure of this compound was established on the basis of physical properties and spectral data, including NMR. It afforded significant hepatoprotection against carbon tetrachloride and paracetamol induced hepatotoxicity in experimental models. Silymarin, a well known plant based hepatoprotective agent, and N-acetylcysteine, which has proven efficacy as a replenisher of sulfhydryls, were used for relative efficacy. TCA was found to reverse the altered hepatic parameters in experimental liver damage. In the safety evaluation study the oral LD50 was found to be more than 2000 mg/kg, with no signs of abnormalities or any mortality for the 15 day period of observation after administration of a single dose of drug in mice. The studies revealed significant and concentration dependent hepatoprotective potential of TCA as it reversed the majority of the altered hepatic parameters in experimental liver damage in rats and mice and may be useful in the management of liver disorders.

Hepatoprotective activity of indigtone--a bioactive fraction from Indigofera tinctoria Linn.

A bioactive fraction, indigtone (FA), obtained by fractionation of a petroleum ether extract of the aerial parts of Indigofera tinctoria, showed significant dose related hepatoprotective activity against CCl(4) induced liver injury in rats and mice. Hexobarbitone induced 'sleeptime', zoxazolamine induced 'paralysis time', levels of transaminases, bilirubin and total protein in serum were employed as indices of liver injury. Pre and post treatment with FA significantly reversed the majority of the parameters altered by the hepatotoxin. This indicated the preventive and restorative effect of FA in the process of CCl(4) induced liver damage. The fraction possessed a high therapeutic ratio, as no mortality was observed up to a dose of 2 g/kg p.o. in mice.

3,4,5-Trihydroxy benzoic acid (gallic acid), the hepatoprotective principle in the fruits of Terminalia belerica-bioassay guided activity.

Compound I isolated from fraction TB5 of Terminalia belerica and finally identified as 3,4,5-trihydroxy benzoic acid (gallic acid) was evaluated for its hepatoprotective activity against carbon tetrachloride (CCl4)-induced physiological and biochemical alterations in the liver. The main parameters studied were hexobarbitone-induced sleep, zoxazolamine induced paralysis, serum levels of transaminases and bilirubin. The hepatic markers assessed were lipid peroxidation, drug metabolising enzymes, glucose-6-phosphatase and triglycerides. Administration of Compound I led to significant reversal of majority of the altered parameters. Our results confirm the presence of hepatoprotective activity in altered parameters. Our results confirm the presence of hepatoprotective activity in Compound I.

Structure and hepatoprotective activity of a biflavonoid from Canarium manii.

Canarium manii (Burseraceae) was chemically investigated and the presence of the biflavonoid agathisflavone is reported for the first time from this plant. Pharmacologically, this biflavonoid in doses 50.0 mg and 100.0 mg given orally exhibited dose-dependent hepatoprotective activity against experimentally-induced carbon tetrachloride-hepatotoxicity in rats and mice.

Effect of Zizyphus sativa leaves on blood glucose levels in normal and alloxan-diabetic rats.

An alcoholic extract of Zizyphus sativa leaves was tested for hypoglycemic activity in normal and alloxan-diabetic rats. Single (100-400 mg/kg) oral doses of extract to normal animals showed a dose-dependent statistically significant lowering of blood glucose 2, 4 and 6 h later. The effect was most pronounced at 6 h with blood glucose returning to control values at 24 h. In alloxan-diabetic rats, no significant effect was observed with extract and tolbutamide. The minimum lethal dose was greater than 3000 mg/kg, orally in mice.

Morphine-like effects of clonidine on the EEG, slow wave sleep and behavior in the dog.

EEG, behavioral and autonomic effects of morphine and clonidine were compared in the unrestrained beagle dog placed in a dimly-lit, sound-attenuated chamber equipped with video monitors. Intravenous (i.v.) morphine (0.5, 1 and 2 mg/kg) and clonidine (11, 33 and 100 microgram/kg) caused parallel dose-related increases in NREM sleep with clonidine being 43 times more potent than morphine. Other similar effects were: an initial transient EEG-behavioral dissociation; increases in spectral power (8-16 Hz); decreases in temperature and heart and respiratory rates; emesis, miosis and salivation. Intraventricular (i.v.t.) morphine (33, 100 and 300 microgram) and clonidine (10 and 30 microgram) caused qualitatively similar EEG, sleep and behavioral effects. Naloxone (30 microgram/kg i.v.) prevented EEG synchrony and behavioral effects of i.v. morphine (1 mg/kg) but not those of i.v. clonidine (100 microgram/kg). Yohimbine pretreatment (0.1 mg/kg i.v.) was more effective in antagonizing clonidine than morphine. These results suggest that morphine and clonidine induce similar EEG, behavioral and autonomic effects through actions upon different receptors on the same or parallel neural pathways. The results further emphasize the importance of an alpha 2-adrenergic-opioid interaction to regulate sleep in the dog.

Ultrasonic characterization of acute renal failure.

The attenuation coefficient, propagation velocity and backscattering coefficient were measured in vitro, on freshly excised and functionally impaired rabbit kidneys. subcutaneous glycerol treatment was used to introduce acute renal failure. Elevated plasma creatinine levels, measured prior to the excision of kidneys, were used as an index of the degree of renal functional impairment. Propagation velocity for the ten kidneys ranged between 1538-1575 m/s with that for the normals being 1540 +/- 4 m/s. Velocity was found to increase with increasing renal damage. The attenuation coefficient for all ten kidneys exhibited a linear frequency dependence over the range 3.5-6.5 MHz. The slope of the attenuation coefficient for the glycerol treated kidneys (0.723 dB/cm/MHz) was found to be higher than the slope for the normals (0.499 dB/cm/MHz). The frequency dependence of the backscattering coefficient was not altered by glycerol treatment leading to the postulate that modification of frequency dependent behavior of the attenuation coefficient in this experimental model is primarily due to absorption.

Microprocessor-base system for ultrasonic tissue characterization.

A microprocessor-based ultrasonic data acquisiton and analysis system has been developed for measuring acoustic parameters of biologic media in a controlled environment. The system consists of commercially available pulse-echo electronics and both minicomputers and microcomputers. Measurements were made on various biologic tissues, both freshly excised and formalin fixed. Propagation velocity measurements were made using the substitution technique. Peak amplitude and log power spectra difference methods were used for attenuation measurements. Measured results indicate that propagation velocity in the soft tissues was in the range of 1530-1580 m/sec at 20 degrees C. Velocity variation among tissues at any given frequency was less than 2%; dispersion in the frequency range 1-10 MHz was approximately 1.5%. Attenuation coefficients showed a marked dependence on frequency increasing in a linear fashion. The slope of the attenuation frequency curve varied with tissue type and could be used for tissue characterization.