Academia.eduAcademia.edu

Anti-Inflammatory Activity of Piperine

1990, Japanese Journal of Medical Science and Biology

Piperine (1-peperoyl piperidine) was isolated from Piper nigrum Linn for the evaluation of anti-inflammatory activity in rats. Different acute and chronic experimental models like carrageenin-induced rat paw edema , cotton pellet granuloma, and croton oil-induced granuloma pouch, were employed. Simultaneously, biochemical estimations were made to elucidate the underlying mechanism of the action. Piperine acted significantly on early acute changes in inflammatory processes and chronic granulative changes. It also acted partially through stimulation of pituitary adrenal axis. Exudative changes in both acute and chronic models, however, were insignificant.

Jpn. J. Med. Short Sci. Biol., 43, 95-100 Communication ANTI-INFLAMMATORY Arvind Manohar Vinaykumar and , 1990. Suresh ACTIVITY MUJUMDAR, Keshav Ramnath OF Jayant DESHMUKH PIPERINE Nilkanth , Palghat DHULEY Hariharan , RAMAN NAIK Pharmacology & Toxicology ndustan Antibiotics Limited, Section, Research & Development Pimpri , Pune 411 018, India Division (Received March 19, 1990. Accepted June 28, 1990) SUMMARY: Piperine (1-peperoyl piperidine) was isolated from Piper nigrum Linn for the evaluation of anti-inflammatory activity in rats . Different acute and chronic experimental models like carrageenin-induced rat paw edema , cotton pellet granuloma, and croton oil-induced granuloma pouch, were employed. Simultaneously, biochemical estimations were made to elucidate the underlying mechanism of the action. Piperine acted significantly on early acute changes in inflammatory processes and chronic granulative changes . It also acted partially through stimulation of pituitary adrenal axis. Exudative changes in both acute and chronic models, however, were insignificant. Piperine (1-peperoyl piperidine) is a major alkaloid of Piper sp . It was investigated for various interesting pharmacological activities viz , antifertility (1) and increase in bioavailability of various drugs (2-5). In routine screening , antipyretic, analgesic and anti-inflammatory activities in the acute rat paw model were reported by Lee et al (6). In the present communication , antiinflammatory activity was investigated in various acute and chronic models to elucidate the probable mechanism of the action. 95 , Hi Piperine Henery (pip) (7). butazone It were light 50 and 14 hr Effect of pip adrenalectomized half hour to induce and then to sc local inflammation and (9). Pip was the lowest (Table I). This dose studies. OPB at than the dose histamine-, in expressed compared as with the Histamine solution the in bradykinin-induced region of the treatment the 28.3% •} in effect Formaline saline were and and OPB of normal 0.30 normal and 40 the hind measured the mg/kg initially and upto this was in paw plethysmographic in pip 10 240 model lower min and than for that adrenalectomized phleogestic edema. mean (% ml region of of rats In were agents these like models, calculated mean and anti-inflammatory saline) was (11). PGE1 paw a of the normal histamine- 4.2 values count of edema changes the of activity, various paw (0.1 plantar paw; in results activity) as volume 1 rat mg/ml paw injected (10). was was Formaline into (5 ƒÊg) was solution) the rat injected measured half (0.05 paw into an injected hour ml to the of study plantar after PGE1 (10). In no rat hr (10). phosphate into 3.5% group in 20 activity activity error of (10 libitum studied 10, was by animals PGE1-induced inhibition control acid subcutaneously a % volume of with standard ad g insignificant. further and 5, significant lower cycle region injection was 100-125 water was in plantar paw produce was difference and volume the activity extended and edema adrenalectomized There this was paw The weighing anti-inflammatory to in used. formaline- increase (8). anti-inflammatory level study in Oxyphenyl- used. orally carrageenin required used paw following a light-dark diet were administered rats after on HA rats pepper drug. strain kept on 10 dose-dependent was however, This were min dose The normal; were rat was Black a standard of carrageenin showed mg/kg further Pip in 240 oral (HA) rats treatment, injection administration. as carrageenin-induced prior for maintained each rats. 45,120 method on used The and For Linn Antibiotics study. cycle) nigrum oil was Hindustan this dark Piper coconut orally, of quarters. and from in mg/kg rats throughout animal isolated suspended albino used our was (OPB), Male was pip and 32.8% •} groups 5.6 were treatment ascites after ml •} 6.1 induced in pip The (12). and 38.1% •} 6.8 model, pip showed respectively. respectively. These There was changes. by treatment. edema activity, and PGE1-induced accurately 0.38 paw anti-inflammatory 32.8% •} on were pip measured 2.10 formaline-induced OPB ip injection ascitic The ascitic groups, 96 of a 0.1 fluid ml volume fluid respectively, of and volumes and 1.5% total solution in leukocyte were 2.25 2.60 ml •} ml •} 0.42 Table I. *Not Effect of piperine significant significant **Insignificant in control 12,500 as compared as compared difference group. This Cmm •} 10,300 1,000 Cmm •} activity Effect of for the method weighing 10 mg were The pellets were determine the control 20.4 group; mg •} dry 6.2, pip- and values migration of pip et in on al. treatment (12). this dissected out weight. The and respectively. of and These for granuloma weight OPB pip pip, are in dried weights significantly was each pellets the count Cmm •} were less was rats and were 60 C 36.21 22.60 than studied pellets of axilla at and noted. cotton were was 780 Thus, granuloma days was cotton leukocyte sterilized seven . respectively. model Four are 10,800 pellet one of total were cotton model animals groups subcutaneously After in The these OPB-treated leukocyte implanted however, . All rest of the values is insignificant. of D'Arcy rats. rat paw edema and adrenalectomized while treatment to anesthetized to control. in normal controls, in chronic according an to control difference in 980 insignificant on carrageenin-induced those each groin in sacrificed. overnight mg •} mg •} to 5.6 6.2 of the in and control group. A injecting granuloma 25 ml pouch air and was croton prepared oil [0.5 on ml of 97 shaven 1% (v/v) skin prepared on dorsal in cotton side of seed rats oil] by Table II. Effect of piperine on croton oil-induced granuloma in rats *P <0 .01 Significant as compared to control. **Not significant as compared to control . was injected fifth day, the volume. the tissues. rats was control but Pip the cortisone levels and mg •} 8.20 acute acute the was seven 1.34 per for g of study chronic pip models carrageenin-induced action support of of pip this inflammation. mediated edema on observation. This through prostaglandin-induced It indicates histamine local not serotonin inflammatory show C less till a Table than than acid pip 12.20 and pg •} in on but mg •} 2.10 14.91 Lee et al (6). both results early no are in PGE1-induced phases action of Further, inflammation against pg levels. activity The and groups, and at P < 0.05 with (14) control 2.80 employed. action changes. 98 60 groups were were in 19.93 agreement does and record in pip ascorbic animals formaline-induced pip at anti-inflammatory in of the extraneous presented volumes on to from and significant and action are OPB acid were were in drying values significant are histamine- and II). ascorbic inflammation after adrenal values days aspirated free in These differences showed of rats. for these was fluid four made studies (Table adrenals cortisone, fluid less subsequently in for and of these exudative and given recorded insignificant These present and results determined g, respectively. the out significantly the days were exudative was The was difference was dissected however, While per In granuloma obtained. (15) respectively. •} 1.8 of granuloma given treatment The were animals; was Pip pouches weight of control (13). sacrificed. the dry weight of pouch were weight The that in the Then, The constant II. into of on inflammation later phase of In granuloma the acute pouch, in support capillary pellet of formaline exudative are not significant also model and granuloma It shows, pouch In carrageenin-induced in adrenalectomized not significant. With cortisone were action levels through to control. observation, permeability. activity fluid volumes as compared of this chronic rat The results edema, than treatment, of pituitary than adrenal tissue formation. was less in both the adrenal with of they count are action on the cotton anti-inflammatory animals. axis groups; leukocyte action in control. model significant there however, higher no in normal chronic in pip-treated significant on granular animals as the of total indicating however, paw as well were lesser thus, model significantly stimulation ascites This This difference ascorbic indicates pip chronic is acid and partial treatment only. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. Piyachaturawat, P., Glinsukon, T, and Peugvicha, P. (1982): Postcoital antifertility effect of piperine. Contraception, 26, 625-633. Atal, C. K., Zutschi, U. and Rao, P. G. (1981): Scientific evidence on the role of Ayurvedic herbals on bioavailability of drug. J. Ethnopharrnacol., 4, 229232. Atal, C. K., Dubey, R. K. and Singh, J. (1985): Biochemical basis of enhanced drug bioavailability by piperine-evidence that piperine is a potent inhibitor of drug metabolism. J. Pharmacol. Exptl. Therap., 232, 258-263. Singh, J., Dubey, R. K, and Atal, C. K. (1986): Piperine mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea pig small intestine-evidence that piperine lowers the endogenous UDP-glucuronic acid contents. J. Pharmacol. Exptl. Therap., 236,488-493. Mujumdar, A. M., Dhuley, J. N., Deshmukh, V. K., Raman, P. H., Thorat, S. L, and Naik, S. R. (1990): Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J. Exptl. Biol., 28,486-487. Lee, E. B., Shin, K. H, and Woo, W. S. (1984): Central nervous system depressant and antiinflammatory activity of piperine. Arch. Pharmac. Res., 7, 127-132. Henery, T. A. (1949): The plant alkaloids, Churchill, London, p.1-2. Winter, C. A., Risley, E. A, and Nuss, G. W. (1962): Carrageenin induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc. Soc. Exptl. Biol. Med., 111,544-547. 99 9. Harris, J. M. apparatus Pharmacol., 10. 11. Spencer, G. actions of 37, B., Leach, U. M., of 13. G. D. H. Friz, A in modified the plethysmographic rat paw. and Atal, C. K. (1987): J. Pharm. Anti-inflammatory ketones. L. F., Howard, Gandini, J. M., A, and Drug. Della Bella, D. 12, W. of Thio Chem., and 6,248-250. P. W. griseofulvin and in Townsend, S. experimental B. (1960): animals. J. 659-665. (1961): and Med. (1963): Synthesis Muggleton, action Pharmacol., Hydrocortisone J. E. antiinflammatory Fisher, P., 2,3-dihydro-4H-1,3-benzoxazin-4-one. properties. P. Pharm. (1962): changes phenyl-3-methoxy-4-hydroxy-styryl pharmacological The J. 435-440. Teotino, D'Arcy, S. volume methyl-and derivatives 12. P. recording 14,464-466. Singh, Res., and for Adrenocortical cobaltous chloride. activities J. of Pharmacol. Exptl. 20 cobalto -1 Therap., 132, 232-239. 14. Roe, J. H., Kuether, Spectrophotometric C. A., assay of Oesterling, vitamin •eC' M. in J. and tissue. J. Mills, Biol. M. B. Chem., (1943): 147, 399- 407. 15. Porter, cortisone C. C. in and rat Silber, adrenals. R. J. H. (1950): Biol. Chem., 100 Spectrophotometric 185, 201-207. determination of