An everted intestinal sac technique has been used to extensively estimate the transport of regular human insulin in rats. As the preliminary experiments using an injectable vial of the insulin showed a considerable transport of insulin, this composition was used deliberately instead of combination of crystalline form of this substance and a permeation enhancer. Two series of experiments were performed with insulin concentrations of 12 and 3.4 u/ml and concentrations of transported insulin were determined with HPLC in serosal fluid of the sac. The results indicated that, in all experiments about 85% of insulin was transported across the medial jejunum segment of rat during an hour regardless of the insulin concentration used. Therefore, a number of factors such as the excipient incorporated with the insulin, pH, the nature of solvent and its ionic strength may play important role in enhancing insulin transport.

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The objective of the present study is the determination of the safety of use of some natural agents proved previously to have a remarkable anti-inflammatory activity. So screening of certain biochemical and nutritional changes that may occur on administration of the natural anti-inflammatory agents and two reference anti-inflammatory drugs was carried out in both adult and growing rats. The natural agents undertaken in this study were the petroleum ether and the alcoholic extracts of fenugreek seeds and liquorice roots and the whole powder of coriander fruits (200 mg/kg). The reference drugs used are indomethacin and urbason retard (5 mg/kg). In the first experiment, the natural or synthetic anti-inflammatory agents were given as daily oral dose to different groups of normal adult rats for a month. At the end of the experiment the serum total protein, albumin, ALP, AST, ALT, creatinine, BUN, glucose, cholesterol, Ca, P, Fe and TIBC were determined. Nutritional parameters (such as food intake, body weight changes and food efficiency ratio) were assessed. The biochemical and nutritional parameters were compared with control rats given no medications. Results showed non-significant changes of any of the studied biochemical parameters after the administration of the natural agents. However urbason retard produced significant increase of serum albumin and ALT and significant decrease of serum globulin. Concerning nutritional parameters, petroleum ether extract of liquorice and urbason retard produced significant reduction of body weight gain and total food intake. Food efficiency ratios were reduced significantly on the administration of urbason retard.
In the second experiment, nutritional status of growing rats fed balanced diet (10% casein) was assessed after 4 weeks of daily oral treatment with previously mentioned natural agents and reference drugs. Results showed significant increase of haematocrit on administration of either alcoholic or petroleum ether extract of liquorice. Alcoholic extract of fenugreek produced significant increase of haematocrit also while urbason retard produced significant increase in both haematocrit and haemoglobin. Serum total protein levels were significantly reduced on oral administration of urbason retard, indomethacin, petroleum ether or alcoholic extract of fenugreek, serum albumin was also significantly reduced on administration of the previous medication except in case of indomethacin. Urbason retard produced severe reduction of all the nutritional parameters including protein efficiency and food efficiency ratios. Petroleum ether extract of liquorice produced only significant reduction in protein and food efficiency ratios.
The third experiment was carried out aiming at improving the adverse effects occurring in serum protein of growing rats during the second experiment, through feeding high protein diet (20% casein). It was then observed that the serum protein levels in all the tested groups were maintained at normal levels.

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Glycyrrhizic acid (GCA) the active component of liquorice acts by inhibiting the enzyme 11-hydroxysteroid dehydrogenase (11HSD) which is a microsomal enzyme catalysing the reversible conversion of corticosterone to 11-dehydrocorticosterone. On repeated exposure to ether stress, there was a significant reduction in tail blood pressure during the second exposure followed by adaptation on the fifth to seventh exposure. This stress-induced hypotension was blocked by prior treatment with opioid antagonist Naloxone, mineralocorticoid deoxycorticosterone and GCA. It is not mediated by the -endorphins containing neurons at the paraventricular nucleus of the hypothalamus. The 11HSD type 1 bioactivity is reduced in the anterior pituitary of rats exposed to ether stress suggesting it could be involved in blocking stress-induced hypotension. Rats exposed to restraint stress demonstrated similar pattern, that is, a significant decrease in the locomotor activity on the second exposure and adaptation on the seventh exposure. This decrease in locomotor activity was partially blocked and adaptation to the repetitive stress was enhanced in rats given GCA. It thus appears that GCA acts in reducing stress by increasing the body's corticosterone level by blocking the enzyme which breaks it down.

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