Korean J Physiol Pharmacol.  2015 Jan;19(1):21-27. 10.4196/kjpp.2015.19.1.21.

Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.

Affiliations
  • 1Department of Periodontology, College of Dentistry, Wonkwang University, Iksan 570-749, Korea.
  • 2Department of Microbiology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea. kimwy@cau.ac.kr
  • 3Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
  • 4Asia Pacific International School, Seoul 139-852, Korea.
  • 5DOSIS M&M, Seoul 143-891, Korea.

Abstract

The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin derived from water, methanol, ethanol, or acetone extracts of Artemisia annua L. were evaluated. All 4 artemisinin-containing extracts had anti-inflammatory effects. Of these, the acetone extract had the greatest inhibitory effect on lipopolysaccharide-induced nitric oxide (NO), prostaglandin E2 (PGE2), and proinflammatory cytokine (IL-1beta , IL-6, and IL-10) production. Antioxidant activity evaluations revealed that the ethanol extract had the highest free radical scavenging activity, (91.0+/-3.2%), similar to alpha-tocopherol (99.9%). The extracts had antimicrobial activity against the periodontopathic microorganisms Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum subsp. animalis, Fusobacterium nucleatum subsp. polymorphum, and Prevotella intermedia. This study shows that Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases.

Keyword

Anti-inflammatory effect; Anti-microbial activity; Antioxidant activity; Artemisinin

MeSH Terms

Acetone
Aggregatibacter actinomycetemcomitans
alpha-Tocopherol
Artemisia annua*
Dinoprostone
Ethanol
Fusobacterium nucleatum
Interleukin-6
Methanol
Nitric Oxide
Pharmaceutical Preparations
Prevotella intermedia
Stomatognathic Diseases
Water
Acetone
Dinoprostone
Ethanol
Interleukin-6
Methanol
Nitric Oxide
Pharmaceutical Preparations
Water
alpha-Tocopherol

Figure

  • Fig. 1 The structure of artemisinin.

  • Fig. 2 HPLC chromatography peak area against the concentration. HPLC chromatogram showing peaks of artemisinin-containing solution (ACS). A: Water extract, B: methanol extract, C: ethanol extract, D: acetone extract. Examples of HPLC traces with the artemisinin peak labelled (*).

  • Fig. 3 The cell viability of RAW 264.7 cells with the artemisinin at different concentrations. Cells were treated for 24 hr with 0, 1, 5, 10, 50 or 100 µg/ml of artemisinin-containing solution (ACS). The normal group was treated with media only. The results are expressed as the mean±SE from three independent experiments. *p<0.01 indicates significant differences from the cells.

  • Fig. 4 Suppression of LPS-induced NO and PGE2 production in RAW 264.7 cells by the artemisinin. Cells were treated for 18 hr with 0, 1, 5, 10, 50, or 100 µg/ml of artemisinincontaining solution (ACS) in the presence of 0.1 µg/ml LPS. The results are expressed as the mean±SE from three independent experiments. *p< 0.01 indicates significant differences from the LPS treated cells. A: NO, B: PGE2.

  • Fig. 5 Suppression of LPS-induced cytokine production (IL-1β and IL-10) in RAW264.7 cells by the artemisinin. RAW 264.7 cells were treated for 18 hr with 0, 1, 5, 10, 50 or 100 µg/ml of artemisinin-containing solution (ACS) in the presence of 0.1 µg/ml LPS. The results are expressed as the mean±SE from three independent experiments. *p<0.01 indicates significant differences from the LPS treated cells. A: IL-1β, B: IL-10.


Reference

1. Taixiang W, Munro AJ, Guanjian L. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients. Cochrane Database Syst Rev. 2005; (1):CD004540. PMID: 15674951.
2. Hien TT, White NJ. Qinghaosu. Lancet. 1993; 341:603–608. PMID: 8094838.
Article
3. Bhakuni RS, Jain DC, Sharma RP, Kumar S. Secondary metabolites of Artemisia annua and their biological activity. Curr Sci India. 2001; 80:35–48.
4. de Vries PJ, Dien TK. Clinical pharmacology and therapeutic potential of artemisinin and its derivatives in the treatment of malaria. Drugs. 1996; 52:818–836. PMID: 8957153.
Article
5. Efferth T. Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin--from bench to bedside. Planta Med. 2007; 73:299–309. PMID: 17354163.
6. Konkimalla VB, Blunder M, Korn B, Soomro SA, Jansen H, Chang W, Posner GH, Bauer R, Efferth T. Effect of artemisinins and other endoperoxides on nitric oxide-related signaling pathway in RAW 264.7 mouse macrophage cells. Nitric Oxide. 2008; 19:184–191. PMID: 18472018.
7. Ferreira JF, Luthria DL, Sasaki T, Heyerick A. Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. Molecules. 2010; 15:3135–3170. PMID: 20657468.
8. Lawrence T, Willoughby DA, Gilroy DW. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol. 2002; 2:787–795. PMID: 12360216.
Article
9. Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol. 2003; 24:25–29. PMID: 12495721.
Article
10. Boscá L, Zeini M, Través PG, Hortelano S. Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. Toxicology. 2005; 208:249–258. PMID: 15691589.
Article
11. Ware CF. Network communications: lymphotoxins, LIGHT, and TNF. Annu Rev Immunol. 2005; 23:787–819. PMID: 15771586.
Article
12. Halliwell B. Protection against tissue damage in vivo by desferrioxamine: what is its mechanism of action? Free Radic Biol Med. 1989; 7:645–651. PMID: 2695408.
Article
13. Morrissey PA, O'Brien NM. Dietary antioxidants in health and disease. Int Dairy J. 1998; 8:463–472.
Article
14. Alma MH, Mavi A, Yildirim A, Digrak M, Hirata T. Screening chemical composition and in vitro antioxidant and antimicrobial activities of the essential oils from Origanum syriacum L. growing in Turkey. Biol Pharm Bull. 2003; 26:1725–1729. PMID: 14646179.
15. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005; 366:1809–1820. PMID: 16298220.
Article
16. Slots J, Reynolds HS, Genco RJ. Actinobacillus actinomycetemcomitans in human periodontal disease: a cross-sectional microbiological investigation. Infect Immun. 1980; 29:1013–1020. PMID: 6968718.
17. Bolstad AI, Jensen HB, Bakken V. Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum. Clin Microbiol Rev. 1996; 9:55–71. PMID: 8665477.
Article
18. Slots J, Ting M. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontol 2000. 1999; 20:82–121. PMID: 10522224.
19. van Steenbergen TJ, Bosch-Tijhof CJ, Petit MD, Van der Velden U. Intra-familial transmission and distribution of Prevotella intermedia and Prevotella nigrescens. J Periodontal Res. 1997; 32:345–350. PMID: 9210087.
20. Folin O, Denis W. On phosphotungastic-phosphomo-lybdic compounds as color ragents. J Biol Chem. 1912; 12:239–243.
21. Dhingra V, Rajoli C, Narasu ML. Partial purification of proteins involved in the bioconversion of arteannuin B to artemisinin. Bioresource Technol. 2000; 73:279–282.
Article
22. Ferrari M, Fornasiero MC, Isetta AM. MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. J Immunol Methods. 1990; 131:165–172. PMID: 2391427.
23. Hatano T, Kagawa H, Yasuhara T, Okuda T. Two new flavonoids and other constituents in licorice root: their relative astringency and radical scavenging effects. Chem Pharm Bull (Tokyo). 1988; 36:2090–2097. PMID: 3240445.
Article
24. Wikler MA. Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. 8th ed. Wayne, Pa: Clinical and Laboratory Standards Institute;2009.
25. Scannapieco FA. Periodontal inflammation: from gingivitis to systemic disease? Compend Contin Educ Dent. 2004; 25(7 Suppl 1):16–25. PMID: 15645883.
26. Tredwin CJ, Scully C, Bagan-Sebastian JV. Drug-induced disorders of teeth. J Dent Res. 2005; 84:596–602. PMID: 15972585.
Article
27. Spencer AJ, Do LG. Changing risk factors for fluorosis among South Australian children. Community Dent Oral Epidemiol. 2008; 36:210–218. PMID: 18474053.
Article
28. Ishiguro Y. Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. J Gastroenterol. 1999; 34:66–74. PMID: 10204613.
Article
29. Ponchel F, Morgan AW, Bingham SJ, Quinn M, Buch M, Verburg RJ, Henwood J, Douglas SH, Masurel A, Conaghan P, Gesinde M, Taylor J, Markham AF, Emery P, van Laar JM, Isaacs JD. Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood. 2002; 100:4550–4556. PMID: 12393721.
Article
30. Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003; 3:521–533. PMID: 12876555.
Article
31. Klotz L, Schmidt M, Giese T, Sastre M, Knolle P, Klockgether T, Heneka MT. Proinflammatory stimulation and pioglitazone treatment regulate peroxisome proliferator-activated receptor gamma levels in peripheral blood mononuclear cells from healthy controls and multiple sclerosis patients. J Immunol. 2005; 175:4948–4955. PMID: 16210596.
32. Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006; 83(6 Suppl):1505S–1519S. PMID: 16841861.
Article
33. Kawasaki T, Fujimi S, Lederer JA, Hubbard WJ, Choudhry MA, Schwacha MG, Bland KI, Chaudry IH. Trauma-hemorrhage induces depressed splenic dendritic cell functions in mice. J Immunol. 2006; 177:4514–4520. PMID: 16982888.
Article
34. Kovatcheva EG, Koleva II, Ilieva M, Pavlov A, Mincheva M, Konushlieva M. Antioxidant activity of extracts from Lavandula vera MM cell cultures. Food Chem. 2001; 72:295–300.
35. Ruberto G, Baratta MT, Biondi DM, Amico V. Antioxidant activity of extracts of the marine algal genus Cystoseira in a micellar model system. J Appl Phycol. 2001; 13:403–407.
36. Juteau F, Masotti V, Bessière JM, Dherbomez M, Viano J. Antibacterial and antioxidant activities of Artemisia annua essential oil. Fitoterapia. 2002; 73:532–535. PMID: 12385883.
37. Cavar S, Maksimovic M, Vidic D, Paric A. Chemical composition and antioxidant and antimicrobial activity of essential oil of Artemisia annua L. from Bosnia. Ind Crop Prod. 2012; 37:479–485.
38. Kwamin F, Gref R, Haubek D, Johansson A. Interactions of extracts from selected chewing stick sources with Aggregatibacter actinomycetemcomitans. BMC Res Notes. 2012; 5:203. PMID: 22537711.
Article
39. Kanokwiroon K, Teanpaisan R, Wititsuwannakul D, Hooper AB, Wititsuwannakul R. Antimicrobial activity of a protein purified from the latex of Hevea brasiliensis on oral microorganisms. Mycoses. 2008; 51:301–307. PMID: 18924261.
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