Piperine modulation of carcinogen induced oxidative stress in intestinal mucosa

The plasma-borne long-chain free fatty acids (FFA) enter skeletal muscle cells. Upon entering they are oxidized or esterified and a fraction remains free (non-esterified). The data on free fatty acids in skeletal muscles remain highly controversial. Furthermore, the composition of individual fatty acids in various lipid fractions including free fatty acids, monoglyceride and diglyceride in muscles has not been characterized. Also data on the composition of fatty acids esterified into muscle triglycerides and phospholipids are incomplete. The present study was undertaken to examine a composition of fatty acids in lipid fractions of different skeletal muscle types. For this purpose, samples of the rat soleus, red and white portions of gastrocnemius were excised, trimmed of visible fat and fascias and immediately frozen in liquid nitrogen. Samples were then pulverized and, lipids were extracted and fractionated by thin-layer chromatography. Individual long-chain fatty acids in different fractions were identified, characterized and quantitated by gas-liquid chromatography. FFA composition in the plasma was also determined. The total FFA content in the soleus, red and white gastrocnemius was 69.1 ± 10.8, 49.0 ± 13.6 and 22.7 ± 8.6 nmol/g, respectively. Palmitic and oleic acids were the major fatty acids in the muscles FFA fraction. Monoglyceride fraction of each muscle contained palmitic, stearic and linoleic acid as the major fatty acids, Diglyceride fraction contained mostly palmitic and oleic acid whereas triglyceride fraction mostly palmitic and linoleic acid.. The fraction of phospholipids was composed mostly of palmitic and linoleic acid but contained also considerable percentage of archidonic acid. Total plasma FFA/muscle FFA ratio depended on a muscle type and was: 2.4 in the soleus, 3.5 in the red and 7.4 in the white gastrocnemius. This assured transport of FFA to the myocytes. However, there were great differences in the ratio between particular FFA within the same muscle as well between the muscles. It indicates that individual FFA are either selectively transported from the plasma to the muscles or selectively used within the myocytes or both.     

Piperine modulates permeability characteristics of intestine by inducing alterations in membrane dynamics: Influence on brush border membrane fluidity, ultrastructure and enzyme kinetics

Piperine (1-Piperoyl piperidine) is a major alkaloid of Piper nigrum Linn. and Piper longum Linn. It is shown to possess bioavailability-enhancing activity with various structurally and therapeutically diverse drugs. The mechanism of enhancing the bioavailability, is, however, not understood. We hypothesize that piperine's bioavailability-enhancing property may be attributed to increased absorption, which may be due to alteration in membrane lipid dynamics and change in the conformation of enzymes in the intestine. Results of membrane fluidity studies using an apolar fluorescent probe, pyrene (which measures the fluid properties of hydrocarbon core), showed an increase in intestinal brush border membrane (BBM) fluidity. Piperine also stimulated Leucine amino peptidase and Glycyl-glycine dipeptidase activity, due to the alteration in enzyme kinetics. This suggests that piperine could modulate the membrane dynamics due to its apolar nature by interacting with surrounding lipids and hydrophobic portions in the protein vicinity, which may decrease the tendency of membrane lipids to act as stearic constrains to enzyme proteins and thus modify enzyme conformation. Ultra structural studies with piperine showed an increase in microvilli length with a prominent increase in free ribosomes and ribosomes on the endoplasmic reticulum in enterocytes, suggesting that synthesis or turnover of cytoskeletal components or membrane proteins may be involved in the observed effect. In conclusion, it is suggested that piperine may be inducing alterations in membrane dynamics and permeation characteristics, along with induction in the synthesis of proteins associated with cytoskeletal function, resulting in an increase in the small intestine absorptive surface, thus assisting efficient permeation through the epithelial barrier.     

gamma-Glutamyl transpeptidase activity in mice: age dependent changes and effect of cortisol.

gamma-Glutamyl transpeptidase (gamma-GT) activity in various organs of mice during ontogenesis has been determined. The activity profile in foetus, neonates and the adult animal were compared to ascertain the functional significance of the enzyme. In addition, the effect of cortisol on gamma-GT activity in adult kidney is presented.