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.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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.
Employment or leadership: None declared.
Honorarium: None declared.
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.
 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
 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
 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
 Muhammad Z, Mustafa AM. Traditional Malay Medicinal Plants, 2nd ed. Kuala Lumpur, Malaysia: Institut Terjemahan Negara Berhad, 2010:185.Search in Google Scholar
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
© 2018 Walter de Gruyter GmbH, Berlin/Boston