Thirty five rats with biliary obstruction induced by double ligation and section of the common bile duct were randomly and blindly assigned to receive piperine (20, 40 or 80 mg/kg), silymarin (25 mg/kg) or saline once a day orally, starting one day after surgery and continued for one month. At the end of the treatment period, rats were killed and analyzed for blood biochemistry, liver and bone histopathology. Piperine administered at 20, 40 or 80 mg/kg to bile duct-ligated (BDL) rats reduced elevated plasma ALT by 16.2-37.5%, AST by 15.4-26.8%, ALP by 60.5-72.7% and bilirubin by 28.4-46.3%, respectively. On histology, liver fibrosis was reduced by piperine in a dose-dependent manner. Piperine also increased the amount of collagenous fibers in the matrix of bone tissue and areas of regeneration. It is concluded that in the model of bile duct ligation, piperine protects against hepatocellular injury and fibrosis and improves bone alterations. Introduction Spices are widely used in human food due to their taste and burning sensations caused by their pungent principles. Black pepper (family Piperaceae) alone accounts for about 35% of the world's total spice trade. Piperine is the active principle of black pepper (Piper nigrum L.) and long pepper (Piper longum L.). It is also the principal alkaloid of these plants.(1) The piperine content is 3-9% and 3-5% (on dry weight basis) in P. nigrum and P. longum respectively. The average daily consumption of black pepper in food in the U.S. is 446 mg, while the average human consumption of chemical piperine is 21.0 mg. (2) Apart from being used as for its food flavoring properties, the pungent piperine has important pharmacological actions. Capsaicin as well as piperine act as legends for the vanilloid receptor (TRPV1, formerly VR1)(3), a member of the transient receptor potential (TRP) family of ion channels, a large group of proteins involved in the detection and integration of sensory stimuli.(4) TRPV1 is a cation channel that is highly expressed in peripheral and central terminals of a subset of primary afferent neurons (with unmyelinated C fiber or thinly myelinated A δ fibers) and is directly activated by a wide range of stimuli including noxious heat, protons, endogenous lipoxygenase products and fatty acid amides as well as capsaicin, gingerols, eugenol, resiniferatoxin, piperine and camphor.(5,6,7,8) Piperine in addition, exhibits a number of pharmacological effects. It has been shown to possess antioxidant properties(9), protect against AFB1-induced cytotoxicity(10) and to inhibit enzymatic drug biotransforming reactions in the liver(11). In the digestive tract, piperine exerted gastric protective effects(12) (Szolcsányi , 1990) and delayed gastrointestinal motility(13). Piperine also exerts antidepressant like effects in mice.(14) Contradictory data, however, has been reported as regards the effect of piperine in models of hepatic injury. Piperine pretreatment has been reported to inhibit(15) or potentiate(16) the hepatotoxicity of CCl4 in rodents. The present study was therefore designed to examine the effect of piperine treatment on liver damage caused in rats by ligation of the common bile duct. This model closely mimics the situation of surgical obstruction of the common bile duct in man such as that occurring due to stricture or malignant growth etc... The effect of piperine was compared with that of silymarin, a standardized extract, derived from the milk thistle plant and is used as a hepatoprotective agent worldwide(17). We also aimed to bone changes and the possible effect of piperine in this model of obstructive jaundice. Materials and methods DrugsThe following drugs were used: Piperine (Sigma, USA), silymarin (SEDICO, ARE).AnimalsSprague–Dawley rats of either sex, weighing 130–150 g of body weight were used. They were housed under standard laboratory conditions with free access to standard laboratory chow and water. Seven rats were used in each group. Animal procedure
展开▼
