226 Planta Med. 58(1992)
Curcumin: A Potent Inhibitor of Leukotriene B4 Formation in Rat Peritoneal Polymorphonuclear Neutrophils (PMNL)
Letters
LTB4 production (% of control)
100
80
H. P. T. Ammon'3, M. I. Anazodo'. H. Safayhi1, B. N. Dhawan2, and B. C. Srimal2 60
Department of Pharmacology, Institute of Pharmacy, University of Tiibingen, D(W)-7400 Tubingen, Federal Republic of Germany 2 Division of Pharmacology, Central Drug Research Institute, Lucknow,
India
40
Address for correspondence Received: April 5, 1991
Extracts of Curcuma longa L. (Zingiberaceae), a medicinal plant in Asia and a constituent of the spice "curry" used for imparting colour and flavour to food, have been shown to exhibit anti-inflammatory activity in standard animal models (1, 2). Current traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism, and sinusitis (2—4). The mechanism of this action is, however, unknown. Important mediators of inflammation are products of the arachidonic acid cascade i.e. prostaglandins and leukotrienes. Here we have studied the effect of durcumin, an active principle of Curcuma longa, on leukotriene formation using PMNL.
0.001
0.01
0.1
1
10
100
1000
log (pM) Curcumin
NDGA
Hydrocortisone
Fig. 1 Effects of curcumin (—•—), NDGA (—A—), and hydrocortisone (—•—) on LTB4-production in stimulated rat peritoneal PMNL (mean SD; n = 4).
cium/calcium ionophore-stimulated formation of LTB4 with an EC50 of27 x iO M was observed (Fig. 1). In contrast, the
steroidal anti-inflammatory agent hydrocortisone did not show any effect on this system. However, when nordihy-
Curcumin was isolated from rhizomes of
droguaiaretic acid (NDGA), a classical inhibitor of 5-
Curcuina longa as a chrome/orange yellow, odourless crystalline compound. It is soluble in alkalies, ethanol, acetone,
lipoxygenase was used as a reference compound, an EC50 of
3 x iO M was observed.
acetic acid, and chloroform but insoluble in water. Rhizomes were finely powdered and extracted with petroleum ether. Defatted powder was extracted with ethanol. Ethanol was evaporated to give a brown resinous product which was titrated with benzene, benzene/ethanol mixture (9: 1) and filtered. The curcumin obtained has a melting
point of 176—177°C and was identified by thin layer chromatography. The purity of the sample was 91 %.
Since leukotrienes, for which the 5lipoxygenase is the key enzyme, are considered to be involved in the initiation and the maintenance of a variety of inflammatory diseases (6—7), it may be reasonable to state that the inhibition of leukotriene synthesis may at least in part be responsible for the anti-inflammatory action of curcumin/Curcuma longa.
References
Suspensions of PMNL elicited with glycogen
were stimulated by calcium and calcium ionophore A 23187 to produce LTB4 and 5-HETE from endogenous arachidonic acid (5). These products were quantified using a reversed-phase HPLC method (Shimadzu HPLC equipped with rp-HPLC column: Nova Pak C-18, 3.9 mm x 15 cm).
1
2
kashan, Bombay, p. 414—417. Chopra, H. N., Chopra, I. C., Handa, K. L., Kapur, L. D. (1958) Indigenous Drugs of India, 2nd Edn., U. N. Dhar and Sons Private Ltd., Calcutta, p. 325—327. Safayhi, H.. Tiegs, G., Wendel, A. (1985) Biochem. Pharmacol. 34,
methanol:water:acetic acid (67:33:0.2), pH 4.75; flow rate 1 mi/mm. Detection wavelength was 280 nm for 15 mm after which it was switched over to 235 nm in order to allow
products.
Curcumin exhibited no cytolytic effect on PMNL within the concentration used in this study as assessed with the trypan blue exclusion test (data not shown). However, a concentration-dependent inhibition of the cal-
452. Ammon, H. PT., Wahl, A. W. (1991) Planta Med. 57, 1—7.
Nadkarni, K. M. (1976) In: Indian Materia Medica, Popular Pre-
Analysis was performed by isocratic elution with
the detection of the monohydroxylated arachidonic acid
Srimal, R. C., Dhawan, B. N. (1973) J. Pharm. Pharmacol. 25, 447—
6
2691— 2694. Samuelsson, B. (1983) Science 220. 568—575. HammarstrOm, S. (1983) Ann. Rev. Biochem. 52, 355—377.
Downloaded by: National University of Singapore. Copyrighted material.
20
Curcumin: A Potent Inhibitor of Leukotriene B4 Formation in Rat Peritoneal Polymorphonuclear Neutrophils (PMNL)
Letters
LTB4 production (% of control)
100
80
H. P. T. Ammon'3, M. I. Anazodo'. H. Safayhi1, B. N. Dhawan2, and B. C. Srimal2 60
Department of Pharmacology, Institute of Pharmacy, University of Tiibingen, D(W)-7400 Tubingen, Federal Republic of Germany 2 Division of Pharmacology, Central Drug Research Institute, Lucknow,
India
40
Address for correspondence Received: April 5, 1991
Extracts of Curcuma longa L. (Zingiberaceae), a medicinal plant in Asia and a constituent of the spice "curry" used for imparting colour and flavour to food, have been shown to exhibit anti-inflammatory activity in standard animal models (1, 2). Current traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism, and sinusitis (2—4). The mechanism of this action is, however, unknown. Important mediators of inflammation are products of the arachidonic acid cascade i.e. prostaglandins and leukotrienes. Here we have studied the effect of durcumin, an active principle of Curcuma longa, on leukotriene formation using PMNL.
0.001
0.01
0.1
1
10
100
1000
log (pM) Curcumin
NDGA
Hydrocortisone
Fig. 1 Effects of curcumin (—•—), NDGA (—A—), and hydrocortisone (—•—) on LTB4-production in stimulated rat peritoneal PMNL (mean SD; n = 4).
cium/calcium ionophore-stimulated formation of LTB4 with an EC50 of27 x iO M was observed (Fig. 1). In contrast, the
steroidal anti-inflammatory agent hydrocortisone did not show any effect on this system. However, when nordihy-
Curcumin was isolated from rhizomes of
droguaiaretic acid (NDGA), a classical inhibitor of 5-
Curcuina longa as a chrome/orange yellow, odourless crystalline compound. It is soluble in alkalies, ethanol, acetone,
lipoxygenase was used as a reference compound, an EC50 of
3 x iO M was observed.
acetic acid, and chloroform but insoluble in water. Rhizomes were finely powdered and extracted with petroleum ether. Defatted powder was extracted with ethanol. Ethanol was evaporated to give a brown resinous product which was titrated with benzene, benzene/ethanol mixture (9: 1) and filtered. The curcumin obtained has a melting
point of 176—177°C and was identified by thin layer chromatography. The purity of the sample was 91 %.
Since leukotrienes, for which the 5lipoxygenase is the key enzyme, are considered to be involved in the initiation and the maintenance of a variety of inflammatory diseases (6—7), it may be reasonable to state that the inhibition of leukotriene synthesis may at least in part be responsible for the anti-inflammatory action of curcumin/Curcuma longa.
References
Suspensions of PMNL elicited with glycogen
were stimulated by calcium and calcium ionophore A 23187 to produce LTB4 and 5-HETE from endogenous arachidonic acid (5). These products were quantified using a reversed-phase HPLC method (Shimadzu HPLC equipped with rp-HPLC column: Nova Pak C-18, 3.9 mm x 15 cm).
1
2
kashan, Bombay, p. 414—417. Chopra, H. N., Chopra, I. C., Handa, K. L., Kapur, L. D. (1958) Indigenous Drugs of India, 2nd Edn., U. N. Dhar and Sons Private Ltd., Calcutta, p. 325—327. Safayhi, H.. Tiegs, G., Wendel, A. (1985) Biochem. Pharmacol. 34,
methanol:water:acetic acid (67:33:0.2), pH 4.75; flow rate 1 mi/mm. Detection wavelength was 280 nm for 15 mm after which it was switched over to 235 nm in order to allow
products.
Curcumin exhibited no cytolytic effect on PMNL within the concentration used in this study as assessed with the trypan blue exclusion test (data not shown). However, a concentration-dependent inhibition of the cal-
452. Ammon, H. PT., Wahl, A. W. (1991) Planta Med. 57, 1—7.
Nadkarni, K. M. (1976) In: Indian Materia Medica, Popular Pre-
Analysis was performed by isocratic elution with
the detection of the monohydroxylated arachidonic acid
Srimal, R. C., Dhawan, B. N. (1973) J. Pharm. Pharmacol. 25, 447—
6
2691— 2694. Samuelsson, B. (1983) Science 220. 568—575. HammarstrOm, S. (1983) Ann. Rev. Biochem. 52, 355—377.
Downloaded by: National University of Singapore. Copyrighted material.
20
