Morinda citrifolia Inhibits Both Cytosolic Ca2+-dependent Phospholipase A2 and Secretory Ca2+-dependent Phospholipase A2

Ho Sun Song; Sung Hun Park; Myoung Soo Ko; Jae Min Jeong; Uy Dong Sohn; Sang Soo Sim

doi:10.4196/kjpp.2010.14.3.163

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Song, Park, Ko, Jeong, Sohn, and Sim: Morinda citrifolia Inhibits Both Cytosolic Ca2+-dependent Phospholipase A2 and Secretory Ca2+-dependent Phospholipase A2

Original Article

Korean J Physiol Pharmacol 2010;14(3):163-167.

Published online: 18 February 2010

DOI: https://doi.org/10.4196/kjpp.2010.14.3.163

Morinda citrifolia Inhibits Both Cytosolic Ca²⁺-dependent Phospholipase A₂ and Secretory Ca²⁺-dependent Phospholipase A₂

Ho Sun Song¹, Sung Hun Park¹, Myoung Soo Ko¹, Jae Min Jeong¹, Uy Dong Sohn², Sang Soo Sim^1,

¹Department of Pathophysiology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea

²Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea

Corresponding to: Sang Soo Sim, Department of Pathophysiology, College of Pharmacy, Chung-Ang University, 221, Huksuk-dong, Dongjak-gu, Seoul 156-756, Korea. (Tel) 82-2-820-5615, (Fax) 82-2-821-7680, (E-mail) simss@cau.ac.kr

Received 7 May 2010 Revised 8 June 2010 Accepted 18 June 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study investigated the effects of the methanol extracts of Morinda citrifolia containing numerous anthraquinone and iridoid on phospholipase A₂ (PLA₂) isozyme. PLA₂ activity was measured using various PLA₂ substrates, including 10-pyrene phosphatidylcholine, 1-palmitoyl-2-[¹⁴C]arachidonyl phosphatidylcholine ([¹⁴C]AA-PC), and [³H]arachidonic acid (AA). The methanol extracts suppressed melittin-induced [₃H]AA release in a concentration-dependent manner in RAW 264.7 cells, and inhibited cPLA₂/sPLA₂-induced hydrolysis of [¹⁴C]AA-PC in a concentration- and time-dependent manner. A Dixon plot showed that the inhibition by methanol extracts on cPLA₂ and sPLA₂ appeared to be competitive with inhibition constants (K_i) of 3.7μg/ml and 12.6μg/ml, respectively. These data suggest that methanol extracts of Morinda citrifolia inhibits both Ca²⁺-dependent PLA₂ such as, cPLA₂ and sPLA₂. Therefore, Morinda citrifolia may possess anti-inflammatory activity secondary to Ca²⁺-dependent PLA₂ inhibition.

Keywords: Morinda citrifolia, Phospholipase A₂, Arachidonic acid

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Fig. 1.

Effects of the methanol extracts on [³H]arachidonic acid (AA) release in RAW 264.7 cells stimulated by 0.5 μM melittin. Cells were incubated with the methanol extracts at 37°C for 10 min and AA release was induced by 0.5 μM melittin. Results are mean±S.D. values from 4 separate experiments. ^∗p<0.05 vs melittin.

Fig. 2.

Effects of methanol extracts on cPLA₂ activity. cPLA₂ activity was measured using 1-palmitoyl-2-[¹⁴C]arachidonyl phosphatidylcholine ([¹⁴C]AA-PC) as a substrate by previously methods. The methanol extracts inhibited cPLA₂-induced hydrolysis of [¹⁴C]AA-PC in a concentration (A)- and time (B)-dependent manner. A Dixon plot showed that cPLA₂ inhibition by methanol extracts appeared to be competitive with an inhibition constant (K_i) of 3.7 μg/ml (C). Results are mean±S.D. values from 4 separate experiments. ^∗p<0.05 vs control.

Fig. 3.

Effects of methanol extracts on sPLA₂ activity. sPLA₂ activity was measured using 1-palmitoyl-2-[¹⁴C]arachidonyl phosphatidylcholine ([¹⁴C]AA-PC) as a substrate by previously described methods. The methanol extracts inhibited sPLA₂-induced hydrolysis of [¹⁴C]AA-PC in a concentration (A)- and time (B)-dependent manner. A Dixon plot showed that the inhibition of sPLA₂ by methanol extracts appeared to be competitive with an inhibition constant (K_i) of 12.6 μg/ml (C). Results are mean±S.D. values from 4 separate experiments. ^∗p<0.05 vs control.

Fig. 4.

Effects of methanol extracts on bee venom sPLA₂ activity with 10-pyrene phosphatidylcholine (10-Pyrene PC). 10-Pyrene PC hydrolyzed by purified sPLA₂ was inhibited by the methanol extracts in a concentration-dependent manner. Results are mean± S.D. values from 4 separate experiments. ^∗p<0.05 vs control.

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