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Licensed Unlicensed Requires Authentication Published by De Gruyter September 14, 2017

Anti-arthritic and gastroprotective activities of Ardisia crispa root partially mediated via its antioxidant effect

Roslida Abdul Hamid, Lau Moi Fong and Yeong Looi Ting



Ardisia crispa Thunb A.DC (Myrsinaceae), commonly known as “hen’s eyes”, has been traditionally used in treating various inflammatory diseases. The present study evaluated anti-arthritic, gastroprotective and antioxidant activities of Ardisia crispa root hexane extract (ACRH) in various animal models.


Anti-arthritic activity was evaluated in complete Freund adjuvant (CFA)-induced adjuvant arthritis and gastroprotective effect was studied in the ethanol-induced ulcer model in rats. ACRH was further isolated to yield quinone-rich fraction (QRF) and both were analyzed for their total phenolic content, total flavonoid content and antioxidant activities in various antioxidant assays. Both ACRH and QRF were also analyzed for the quinone composition via gas chromatography analysis.


ACRH exerted significant reduction of IL-1β and TNF-α at a lower dose range in CFA-induced arthritis, as well as exhibited its cytoprotective effect against ethanol-induced ulcer lesion via involvement of mucosal nonprotein sulfhydryl (NP-SH) groups. ACRH also showed higher phenolic and flavonoid contents, as well as better antioxidant activities than QRF.


These findings demonstrated the plant as a potential anti-inflammatory agent, with ACRH succeeded in inhibiting both arthritic and ulcerogenic effect, possibly mediated via its antioxidant effect.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was funded by Fundamental Research Grant Scheme (FRGS) (Project no : 04-02-14-1546FR) awarded by Ministry of Higher Education, Malaysia.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report or in the decision to submit the report for publication.


[1] Zhou J, Xie G, Yan X. Encyclopedia of Traditional Chinese Medicines - Molecular Structures, Pharmacological Activities, Natural Sources and Applications. Berlin: Springer-Verlag Berlin Heidelberg, 2011.10.1007/978-3-642-16738-6Search in Google Scholar

[2] Kobayashi H, De Mejía E. The genus Ardisia: A novel source of health-promoting compounds and phytopharmaceuticals. J Ethnopharmacol. 2005;96:347–354.10.1016/j.jep.2004.09.037Search in Google Scholar PubMed

[3] Jansakul C, Herbert B, Lennart K, Gunnar S. Ardisiacrispin A and B, two utero-contacting saponins from Ardisia crispa. Planta Med. 1987;53:405–409.10.1055/s-2006-962758Search in Google Scholar PubMed

[4] Muhammad Z, Mustafa AM. Traditional Malay Medicinal Plants, 2nd ed. Kuala Lumpur, Malaysia: Institut Terjemahan Negara Berhad, 2010:185.Search in Google Scholar

[5] Burkill IH. A Dictionary of the Economic Products of the Malay Peninsula (Volume 1). Kuala Lumpur, Malaysia: Ministry of Agriculture and Co-operative, 1966:218–223.Search in Google Scholar

[6] Yoshida K, Koma Y, Kikuchi H. Therapeutic substance FR-900359 from Ardisia crispa. Japan Kokkai Tokyo Kobo JP. 1987;283:917–920.Search in Google Scholar

[7] Kang YH, Kim WH, Park MK, Han BH. Antimetastatic and antitumor effects of benzoquuinonoid AC7-1 from Ardisia crispa. Int J Cancer. 2001;93:736–740.10.1002/ijc.1384Search in Google Scholar PubMed

[8] Roslida AH, Kim KH. Anti-inflammatory effect and anti-hyperalgesic effect of Ardisia crispa Thunb D C. Pharmacogn Mag. 2008;4:262–268.Search in Google Scholar

[9] Lau MF, Roslida AH, Sabrina S, Nhareet SM. Anti-inflammatory and anti-pyretic effects of hexane fraction of Ardisia crispa Thunb D.C. Pharmacologyonline. 2009;3:29–39.Search in Google Scholar

[10] Roslida AH, Fezah O, Yeong LT. Suppression of DMBA/croton oil-induced mouse skin tumor promotion by Ardisia crispa root hexane extract. Asia Pac J Can. Prev. 2011;12:665–669.Search in Google Scholar

[11] Sulaiman H, Roslida AH, Fezah O, Yeong LT. Anti-tumor effect of Ardisia crispa hexane fraction on 7,12-dimethyl benz(α)anthracene-induced skin papillomagenesis. J Can Res Ther. 2012;8:404–410.10.4103/0973-1482.103521Search in Google Scholar PubMed

[12] Hamid RA, Othman F, Anthony JJ, Ting YL. Chemopreventive effect of Ardisia crispa hexane fraction on the peri-initiation phase of mouse skin tumorigenesis. Med Princ Pract. 2013;22:57–61.10.1159/000346622Search in Google Scholar PubMed PubMed Central

[13] Hamsin DE, Hamid RA, Yazan LS, Taib CNM, Ting YL. The hexane fraction of Ardisia crispa Thunb. A. DC. roots inhibits inflammation-induced angiogenesis. BMC Complement Altern Med. 2013;8 13:5.10.1186/1472-6882-13-5Search in Google Scholar PubMed PubMed Central

[14] Hamsin DE, Hamid RA, Yazan LS, Taib CN, Yeong LT. Ardisia crispa roots inhibit cyclooxygenase and suppress angiogenesis. BMC Complement Altern Med. 2014;19 14 :102.10.1186/1472-6882-14-102Search in Google Scholar PubMed PubMed Central

[15] Roslida AH, Teh YH, Kim KH. Evaluation of anti-ulcer activity of Ardisia crispa Thunb. D.C. Pharmacogn Res. 2009;1:250–255.Search in Google Scholar

[16] Yeong LT, Roslida AH, Latifah SY, Huzwah K, Hamsin DE. Synergistic action of compounds isolated from hexane extract of Ardisia crispa root against tumour promoting effect, in vitro. Nat Prod Res. 2014;28:2026–2030.10.1080/14786419.2014.917415Search in Google Scholar PubMed

[17] Roslida AH. Anti-inflammatory and analgesic effects of AC-2 isolated from Ardisia crispa are mediated via COX-2 inhibition. Kuala Lumpur: Universiti Malaya, , 2004. PhD thesis.Search in Google Scholar

[18] Pearson CM. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol Med. 1956;91:95–101.10.3181/00379727-91-22179Search in Google Scholar PubMed

[19] Arrieta J, Benitez J, Flores E, Castillo C, Navarrete A. Purification of gastroprotective triterpenoids from stem bark of Amphiterygium adstringens: Role of prostaglandins. Sulfhydryls, nitric oxide and capsaicin neurons. Planta Med. 2003;69:90.Search in Google Scholar

[20] Matsuda H, Yutana P, Toshio M, Akinobu K, Shinya K, Masayuki Y. Protective effects of steroid saponins from Paris polyphylla var. yunnanensis on ethanol- or indomethacin-induced gastric mucosal lesions in rats: Structural requirement for activity and mode of action. Bioorg Med Chem Lett. 1999;13:1101–1106.10.1016/S0960-894X(03)00052-0Search in Google Scholar

[21] Al-Bekairi AM, Qureshi S, Ahmed MM, Afzal M, Shah AH. A study of uric acid pretreatment for the protection of rat gastric mucosa against toxic damage. Food Chem Toxicol. 1992;30:525–531.10.1016/0278-6915(92)90105-TSearch in Google Scholar PubMed

[22] Ikram EHK, Eng KH, Jalil AMM, Ismail A, Idris S, Azlan A, et al. Antioxidant capacity and total phenolic content of Malaysian underutilized fruits. J Food Compos Anal. 2009;22:388–393.10.1016/j.jfca.2009.04.001Search in Google Scholar

[23] Quettier-Deleu C, Gressier B, Vasseur J, Dine T, Brunet C, Luyckx M, et al. Phenolic compounds and antioxidant activities of buckwheat (Fagopyrum sculentum Moench) hulls and flour. J Ethnopharmacol. 2000;72:35–42.10.1016/S0378-8741(00)00196-3Search in Google Scholar

[24] Al-Saikhan MS, Howard LR, Miller JC. Antioxidant activity and total phenolics in different genotypes of potato (Solanum tuberosum, L.). J Food Sci. 1995;60:341–343.10.1111/j.1365-2621.1995.tb05668.xSearch in Google Scholar

[25] Rufino MSM, Alves RE, De Brito ES, Pérez-Jiménez J, Saura-Calixto F, Mancini-Filho J. Bioactive compounds and antioxidant capacities of 18 non-traditional tropical fruits from Brazil. Food Chem. 2000;121:996–1002.10.1016/j.foodchem.2010.01.037Search in Google Scholar

[26] Wootton-Beard PC, Moran A, Ryan L. Stability of the total antioxidant capacity and total polyphenol content of 23 commercially available vegetable juices before and after in vitro digestion measured by FRAP, DPPH, ABTS and Folin–Ciocalteu methods. Food Res Int. 2011;44:217–224.10.1016/j.foodres.2010.10.033Search in Google Scholar

[27] Newbould BB. Chemotherapy of arthritis induced in rats by Mycobacterial adjuvant. Brit J Pharmacol. 1963;21:127–136.10.1111/j.1476-5381.1963.tb01508.xSearch in Google Scholar PubMed PubMed Central

[28] Ahmed S, Anuntiyo J, Malemud CJ, Haqqi TM. Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: A review. Evid-Based Complement Altern Med. 2003;2:301–308.10.1093/ecam/neh117Search in Google Scholar PubMed PubMed Central

[29] Redlich K, Schett G, Steiner G, Hayer S, Wagner EF, Smolen S. Rheumatoid arthritis therapy after tumor necrosis factor and interleukin-1 blockade. Arthritis Rheum. 2003;48:3308–3319.10.1002/art.11358Search in Google Scholar PubMed

[30] Zhang JM, An J. Cytokines, Inflammation and Pain. Int Anesthesiol Clin. 2007;45:27–37.10.1097/AIA.0b013e318034194eSearch in Google Scholar PubMed PubMed Central

[31] Molto O, Olive A. Anti IL-1 molecules: Newcomers and new indications. Joint Bone Spine. 2010;77:102–107.10.1016/j.jbspin.2009.10.011Search in Google Scholar PubMed

[32] Lee YR, Lee JH, Noh EM, Kim EK, Song MY, Jung WS, et al. Guggulsterone blocks IL-1β-mediated inflammatory responses by suppressing NF-kB activation in fibroblast-like synoviocytes. Life Sci. 2008;8:1203–1209.10.1016/j.lfs.2008.04.006Search in Google Scholar PubMed

[33] Szekanecz Z, Koch AE. VEGF as an activity marker in rheumatoid arthritis. Int. J Clin Rheumatol. 2010;5:287–289.10.2217/ijr.10.24Search in Google Scholar

[34] Shibuya N, Tanaka M, Yoshida M, Ogasawara Y, Togawa T, Ishii K, et al. 3-mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid Redox Signal. 2009;11:703–714.10.1089/ars.2008.2253Search in Google Scholar PubMed

[35] Doan T, Masarotti E. Rheumatoid arthritis: An overview of new and emerging therapies. J Clin Pharmacol. 2005;45:751–762.10.1177/0091270005277938Search in Google Scholar PubMed

[36] Okamura M, Takano Y, Hiramitsu N, Hayakawa K, Yao J, Paton AW, et al. Suppression of cytokine responses by indomethacin in podocytes: A mechanism through induction of unfolded protein response. Am J Physiol. 2008;295:1495–1503.10.1152/ajprenal.00602.2007Search in Google Scholar PubMed

[37] Kaoru O, Fumio T, Masaki L, Shuichi F, Bin T, Takashi K, et al. Suppression of inflammation in rat autoimmune myocarditis by S100A8/A9 through modulation of the proinflammatory cytokine network. Eur J Heart Fail. 2009;11:229–237.10.1093/eurjhf/hfn049Search in Google Scholar PubMed PubMed Central

[38] Yeong LT, Abdul Hamid R, Saiful Yazan L, Khaza’ai H, Mohtarrudin N. Low dose triterpene-quinone fraction from Ardisia crispa root precludes chemical-induced mouse skin tumor promotion. BMC Complement Altern Med. 2015;15:431.10.1186/s12906-015-0954-3Search in Google Scholar PubMed PubMed Central

[39] Liu Y, Tian X, Gou L, Fu X, Li S, Lan N, et al. Protective effect of l-citrulline against ethanol-induced gastric ulcer in rats. Environ Toxicol Pharmacol. 2012;34:280–287.10.1016/j.etap.2012.04.009Search in Google Scholar PubMed

[40] Wang D, Dubois RN, Richmond A. The role of chemokines in intestinal inflammation and cancer. Curr Opin Pharmacol. 2009;9:688–696.10.1016/j.coph.2009.08.003Search in Google Scholar PubMed

[41] Guslandi M. Effects of ethanol on the gastric mucosa. Dig Dis. 1987;5:21–32.10.1159/000171159Search in Google Scholar PubMed

[42] Al Batran R, Al-Bayaty F, Jamil Al-Obaidi MM, Abdulkader AM, Hadi HA, Ali HM, et al. In vivo antioxidant and antiulcer activity of Parkia speciosa ethanolic leaf extract against ethanol-induced gastric ulcer in rats. PLoS One. 2013;28:64751.10.1371/journal.pone.0064751Search in Google Scholar

[43] Hajrezaie M, Salehen N, Karimian H, Zahedifard M, Shams K, Batran RA, et al. Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats. PLoS One. 2015;10:0121529.10.1371/journal.pone.0121529Search in Google Scholar

[44] Szabo S, Vattay P. Experimental gastric and duodenal ulcers. Advances in pathogenesis. Gastroenterol Clin North Am. 1990;19:67–85.10.1016/S0889-8553(21)00457-XSearch in Google Scholar PubMed

[45] Ancha H, Ojeas H, Tedesco D, Ward A, Harty RF. Somatostatin-induced gastric protection against ethanol: Involvement of nitric oxide and effects on gastric mucosal blood flow. Regul Pept. 2003;110:107–110.10.1016/S0167-0115(02)00214-8Search in Google Scholar PubMed

[46] Banerjee D, Maity B, Nag S, Bandyopadhyay SK, Chattopadhyay S. Healing potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: A mechanistic exploration. BMC Complement Altern Med. 2008;8:3–16.10.1186/1472-6882-8-3Search in Google Scholar PubMed PubMed Central

[47] Bauerova K, Bezek A. Role of reactive oxygen and nitrogen species in ethiopathogenesis of rheumatoid arthritis. Gen Physiol Biophys. 1999;18:15–20.Search in Google Scholar

[48] Chew YL, Chan EWL, Tan PL, Lim Y, Stanslas J, Goh JK. Assessment of phytochemical content, polyphenolic composition, antioxidant and antibacterial activities of Leguminosae medicinal plants in Peninsular Malaysia. BMC Complement Altern Med. 2011;11:12.10.1186/1472-6882-11-12Search in Google Scholar PubMed PubMed Central

[49] Kogiannou DAA, Kalogeropoulos N, Kefalas P, Polissiou MG, Kaliora AC. Herbal infusions; their phenolic profile, antioxidant and anti-inflammatory effects in HT29 and PC3 cells. Food Chem Toxicol. 2013;61:152–159.10.1016/j.fct.2013.05.027Search in Google Scholar PubMed

[50] André CM, Oufir M, Hoffmann L, Hausman J, Rogez H, Larondelle Y, et al. Influence of environment and genotype on polyphenol compounds and in vitro antioxidant capacity of native Andean potatoes (Solanum tuberosum L.). J Food Comp Anal. 2009;22:517–524.10.1016/j.jfca.2008.11.010Search in Google Scholar

Received: 2017-2-2
Accepted: 2017-6-19
Published Online: 2017-9-14

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