Extract, fractions, and ethyl-p-methoxycinnamate isolate from Kaempferia galanga Elicit anti-inflammatory activity by limiting leukotriene B4 (LTB4) production

10.1016/j.jtcme.2021.06.004

Lusi Putri Dwita；Ni Putu Ermi Hikmawanti；Yeni；Supandi

Lipoxygenase ； Anti-inflammation ； Pleurisy ； Granuloma-air pouch

Journal of Traditional and Complementary Medicine

11卷6期（2021 / 11 / 01）

563 - 569

英文

Background and aim: Kaempferia galanga, also known as aromatic Ginger (kencur) in Indonesia, has been widely explored and shows potential as an anti-inflammatory agent. However, there has been limited research to show a possible mechanism by which aromatic ginger inhibits lipoxygenase (LOX). Therefore, this study aims to determine the anti-inflammatory activity of aromatic ginger by comparing extract, fractions, and ethyl-p-methoxycinnamate (EPMC) isolate, as well as possible LOX inhibition activity, by reducing the production of leukotriene B4 (LTB4). Experimental procedure: Two animal models were used, namely, the carrageenan-induced granuloma air pouch model and the pleurisy model. The test substance was administered 1 h before carrageenan induction, which was performed orally for each animal model. The number of leukocytes and the malondialdehyde (MDA) levels, leukotriene B4 (LTB4) levels, and histology were observed. GC-MS and LC-MS were used for analysis of the chemical compounds in the test samples. Results and conclusion: The results of GC-MS analysis showed that aromatic ginger rhizome extract and fractions were dominated by ethyl-trans-p-methoxycinnamate, with the highest level found in the extract. K. galanga showed significant anti-inflammatory activity compared to the control (p ＜ 0.01) in both the granuloma air pouch and pleurisy models. The results of examining the LTB4 concentration showed comparable activity between K. galanga extract, fractions and EMPC isolate, these results were not better than those of zileuton. Overall, this study shows that aromatic ginger extract, fractions and EPMC isolate have anti-inflammatory properties and have the potential to inhibit LOX, thereby reducing LTB4 levels.

1. Naderi, Z,Mozaffari-Khosravi, H,Dehghan, A,Nadjarzadeh, A,Huseini, HF(2016).Effect of ginger powder supplementation on nitric oxide and C-reactive protein in elderly knee osteoarthritis patients: a 12-week double-blind randomized placebo-controlled clinical trial.J Tradit Complement Med.,6(3),199-203.
   連結：
2. Aryaeian, N,Shahram, F,Mahmoudi, M,Tavakoli, H,Yousefi, B(2018).The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis.Gene,698,179-185.
3. Busch, CJ,Binder, CJ(2017).Malondialdehyde epitopes as mediators of sterile inflammation.Biochim Biophys Acta Mol Cell Biol Lipids,1862(4),398-406.
4. Chatterjee, S.(2016).Oxidative Stress, Inflammation, and Disease.Elsevier Inc..
5. Cuzzocrea, S,Rossi, A,Serraino, I(2003).5-Lipoxygenase knockout mice exhibit a resistance to pleurisy and lung injury caused by carrageenan.Journal of Leukocyte Biology,73,739-746.
6. Duarte, DB,Vasko, MR,Fehrenbacher, JC(2016).Models of inflammation: carrageenan air pouch.Curr Protoc Pharmacol,2016
7. Dwita, LP,Supandi, Yeni(2020).In vitro study of Kaempferia galanga L. Compound, δ- 3- carene, against 5-lipoxygenase.Proceedings of the 4th International Conference on Sustainable Innovation 2020-Health Science and Nursing (ICoSIHSN 2020)
8. Gonçalves, S,Romano, A,Gonçalves, S,Romano, A.Gonçalves S, Romano A, Gonçalves S, Romano A. Inhibitory properties of phenolic compounds against inhibitory properties phenolic compounds against enzymes linked with of human diseases enzymes linked with human diseases..
9. Herebian, D,Choi, J-H,El-Aty, AMA,Shim, J-H,Spiteller, M(2009).Metabolite analysis in Curcuma domestica using various GC-MS and LC-MS separation and detection techniques.Biomed Chromatogr,23,951-965.
10. Hu, C,Ma, S(2018).Recent development of lipoxygenase inhibitors as anti-inflammatory agents.Medchemcomm,9(2),212-225.
11. Jagadish, PC,Latha, KP,Mudgal, J,Nampurath, GK(2016).Extraction, characterization and evaluation of Kaempferia galanga L. (Zingiberaceae) rhizome extracts against acute and chronic inflammation in rats.J Ethnopharmacol,194,434-439.
12. Jain, M,Singh, H.(2011).Evaluation of antioxidative and anti-inflammatory potential of hesperidin and naringin on the rat air pouch model of inflammation.Inflammation Research,483-491.
13. Jaismy Jacob, P,Manju, SL,Ethiraj Ge, KR(2018).Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: a structure-based approach.Eur J Pharmaceut Sci
14. Kumar, A(2020).Phytochemistry, pharmacological activities and uses of traditional medicinal plant Kaempferia galanga L .- an overview.J Ethnopharmacol,253,112667.
15. Leval, X,Julemont, F,Delarge, J,Pirotte, B,Dogne, J-M(2005).New trends in dual 5-LOX/COX inhibition.Curr Med Chem,9(9),941-962.
16. Mashima, R,Okuyama, T(2015).Redox Biology the role of lipoxygenases in patho-physiology ; new insights and future perspectives.Redox Biol,6,297-310.
17. Necas, J,Bartosikova, L(2013).Carrageenan. A review.Vet Med,58(4),187-205.
18. P, JJ,Manju, SL,Ethiraj, KR,Elias, G(2018).Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: a structure-based approach.Eur J Pharmaceut Sci.,121,356-381.
19. Rossi, A,Serraino, I,Dugo, P(2003).Protective effects of anthocyanins from blackberry in a rat model of acute lung inflammation.Free Radic Res,37(8),891-900.
20. Shariatpanahi, ZV,Mokhtari, M(2013).Effect of enteral feeding with ginger extract in acute respiratory distress syndrome.J Crit Care,28(2),217.e1-217.e6.
21. Subositi, D,Mujahid, R,Widiyastuti, Y(2020).Kaempferia galanga L. A Medicinal Plant Used By Indonesian Ethnic Groups: Genetic Diversity Based on Inter-Simple Sequence Repeats (ISSR).AGRIVITA Journal of Agricultural Science,42(1),44-52.
22. Sulaiman, MR,Zakaria, ZA,Daud, IA,Ng, FN,Ng, YC,Hidayat, MT(2008).Antinociceptive and anti-inflammatory activities of the aqueous extract of Kaempferia galanga leaves in animal models.J Nat Med
23. Tungcharoen, P,Wattanapiromsakul, C,Tansakul, P,Nakamura, S,Matsuda, H,Tewtrakul, S(2020).Anti-inflammatory effect of isopimarane diterpenoids from Kaempferia galanga.Phyther Res,34(3),612-623.
24. Umar, MI,Asmawi, MZ,Sadikun, A(2012).Bioactivity-guided isolation of ethyl-p-methoxycinnamate, an anti-inflammatory constituent, from Kaempferia galanga L. extracts.Molecules,17(7),8720-8734.
25. Vittalrao, AM,Shanbhag, T,Meena Kumari, K,Bairy, KL,Shenoy, S(2011).Evaluation of antiinflammatory and analgesic activities of alcoholic extract of Kaempferia galanga in rats.Indian J Physiol Pharmacol,55(1),13-24.
26. Wan, M,Tang, X,Stsiapanava, A,Haeggström, JZ(2017).Biosynthesis of leukotriene B 4.Semin Immunol,33,3-15.
27. Yao, F,Huang, Y,Wang, Y,He, X(2018).Anti-inflammatory diarylheptanoids and phenolics from the rhizomes of kencur (Kaempferia galanga L.).Ind Crop Prod,125,454-461.
28. Zhang, L,Liang, X,Ou, Z(2019).Industrial Crops & Products Screening of chemical composition , anti-arthritis , antitumor and antioxidant capacities of essential oils from four Zingiberaceae herbs.Ind Crop Prod,149,112342.
29. Zschaler, J,Arnhold, J(2016).Impact of simultaneous stimulation of 5-lipoxygenase and myeloperoxidase in human neutrophils.Prostaglandins Leukot Essent Fatty Acids.,107,12-21.