Evaluation of Aster bakerianus Burtt Davy ex C.A. Sm. Crude Root Extract for Acute Antiinflammatory Activity in Rats

Author(s): Sibusisiwe Magama, Asita Okorie Asita, Teboho Derrick Skundla

The crude extract of Aster bakerianus roots used for treatment of a variety of ailments in Lesotho was evaluated for anti-inflammatory activity and phytochemical content. Extract was first tested for toxicity at oral dosages of 0 (negative control), 1000, 2000, 3000 and 5000 mg/kg bw with five groups of female mice, each group having four mice. Negative control group received sterile distilled water (1.0 ml/kg bw). Mice were observed for general symptoms of toxicity for 24 hours and left for a further 14 days for any delayed toxicity. None of the extract doses induced toxicity. Anti-inflammatory activity of A. bakerianus was determined using the carrageenan-induced rat paw oedema assay. Five groups of six mice each were orally pre-treated as follows: Negative control group (group 1) received sterile distilled water (1.0 ml/kg bw). Positive control group (group 2) received indomethacin (10mg/kg bw). Three test groups (group 3, 4 and 5) received A. bakerianus extract, 100, 200 and 400 mg/kg bw respectively. After one hour of pre-treatment, all test groups and controls were injected with 0.1 ml carrageenan subcutaneously in the right hind paw and paw thicknesses recorded at the following time intervals: 0, 1, 2, 3, 4, 5, 6, and 24 hours. Statistically (p<0.05) there was no difference observed in the antiinflammatory activity profile of A. bakerianus and that of the drug indomethacin at the different time intervals of the study, implying same efficacy. The anti-inflammatory activity of extract was attributed to presence of terpenoids, saponins, sterols, simple phenols, coumarins, polyphenols, flavonoids, tannins, phlobatannins, anthocyanins, alkaloids, glycosides and amino acids. The results of this study justified the documented use of this plant by Basotho for treatment of inflammatory disorders.

Eicosanoids, Cyclooxygenase, Phytochemicals, Indomethacin, Rat Paw Diameter

1. Agnihotri S, Kakode S, Agnihotri A. 2010. An overview on antinflammatory properties and chemo-profiles of plants used in traditional medicine. Indian Journal of Natural Products and Resources. 1 (2): 150-167.
2. Ahad A, Ganai AA, Mujeeb M, Siddiqui WA. 2014. Ellagic acid, an NF-ĸB inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chemico- Biological Interactions. 219 (5): 64–75. https://doi.org/10.1016/j.cbi.2014.05.011
3. Akamatsu H, Miyachi Y, Asada Y, Niwa Y. 1991. Effects of azelastine on neutrophil chemotaxis, phagocytosis and oxygen radical generation. The Japanese Journal of Pharmacology. 57(4):583–589. https://doi.org/10.1254/jjp.57.583.
4. Amala Hazel AM, Pattarayan R, Banumathi V. 2018. Acute Anti-inflammatory activity of Eraippu Noi Chooranam on carrageenan induced paw edema in wistar albino rats. International Journal of Current Research in Medical Sciences. 4(1): 170-175. https://dx.doi.org/10.22192/ijcrms.2018.04.01.021
5. Ambriz-Pérez DL, Leyva-López L, Gutierrez-Grijalva EP, Heredia JB. 2016. Phenolic compounds: Natural alternative in inflammation treatment. A review. Cogent Food and Agriculture. 2(1): 1–14. https://doi.org/10.1080/23311932.2015.1131412
6. Aquila S, Giner RM, Recio MC, Spegazzini ED, Rios JL. 2009. Anti-inflammatory
7. activity of flavonoids from Cayaponia tuyuya roots. Journal of Ethnopharmacology. 121, 333–337.
8. Arulselvan P, Fard MT, Tan WS, Gothai S, Fakurazi S, Norhaizan ME, Kumar SS. 2016. Role of antioxidants and natural products in inflammation. Oxidative Medicine and Cellular Longevity. 1:1-16. https://doi.org/10.1155/2016/5276130.
9. Bamgbose SO, Noamesi BK. 1981. Studies on cryptolepine II: inhibition of carrageenan-induced edema by cryptolepine. Planta Medica. 41(4): 392–396. https://doi.org/10.1055/s-2007-971733.
10. Bandaranayake WM. 2006. Quality control, screening, toxicity and regulation of herbal drugs. pp 25-55. In: Modern Phytomedicine: Turning Medicinal Plants into Drugs 2006. Editors: Iqbal Ahmad, Farrukh Aqil, Mohammad Owais. Copyright © 2006 Wiley‐VCH Verlag GmbH & Co. KgaA. https://doi.org/10.1002/9783527609987.ch2
11. Barik BR, Bhowmik T, Dey AK, Patra A, Chatterjee, A, Joy S, Susan T, Alam M,
12. Kundu AB. 1992. Premnazole and isoxazole alkaloid of Premna integrifolia and Gmelina arborea with anti-inflammatory activity. Fitoterapia. 63(4):295–299.
13. Barragán-Zarate GS, Lagunez-Rivera L, Solano R, Pineda-Peña EA, Landa-Juárez AY, Chávez-Piña AE, Carranza-Álvarez C, Hernández-Benavides DM. 2020. Prosthechea karwinskii, an orchid used as traditional medicine, exerts anti-inflammatory activity and inhibits ROS. Journal of Ethnopharmacology. 253:112632. https://doi.org/10.1016/j.jep.2020.112632
14. Ben IO, Etim OE, Udo NM. 2016. Anti-inflammatory effects of Napoleona imperialis P. Beauv. (Lecythidaceae) on rat model of inflammation. Indian Journal of Health Sciences. 9:89-95. https://doi: 10.4103/2349-5006.18368.
15. Ben Saad LA, Kim KH, Quah CC, Kim WR, Shahimi M. 2017. Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum. BMC Complementary and Alternative Medicine. 17: 47-56. https://doi.org/10.1186/s12906-017-1555-0
16. Bharathi T, Udayakumar R. 2019. Phytochemical screening and nutrient content analysis of stem and root of Tridax procumbens Lin. International Journal of Research – Granthaalaya. 7(8): 470-477. https://doi.org/10.5281/zenodo.3401617
17. Birhane R, Shibeshi W, Asres K. 2014. Evaluation of analgesic and anti-inflammatory activities of the root extracts of Indigofera spicata F. in mice. Ethiopian Pharmaceutical Journal. 30: 65-76. http://dx.doi.org/10.4314/epj.v30i2.1
18. Bribi N, Algieri F, Rodriguez-Nogales A, Garrido-Mesa J,Vezza T, Maiza F, Utrilla MP, Rodriguez-Cabezas ME, Galvez, J. 2015. Antinociceptive and anti-inflammatory effects of total alkaloid extract from Fumaria capreolata. Evidence- Based Complementary and Alternative Medicine. https://doi.org/10.1155/2015/736895
19. Calixto JB, Campos MM, Otuki MF, Santos ARS. 2004. Anti-inflammatory compounds of plant origin. Part II. Modulation of pro-inflammatory cytokines, chemokines and adhesion molecules. Planta Medica.70(2): 93–103. doi: 10.1055/s-2004-815483
20. Cheng D, ShaoY. 1993.Terpenoid glycosides from the roots of Aster tataricus. Phytochemistry. 35(1):173-176. https://doi.org/10.1016/S0031-9422(00)90528-4
21. Danya U. 2017. In vivo anti-inflammatory activity of the endemic medicinal plant Caralluma sarkariae R.Br. using carrageenan induced paw oedema in swiss albino mice. Journal of Medicinal Plants Studies. 5(2):133-135.
22. de las Heras B, Hortelano S. 2009. Molecular basis of the anti-inflammatory effects of terpenoids. Inflammation & Allergy Drug Targets. 8(1):28-39. https://doi.org/10.2174/187152809787582534
23. Di Rosa M, Giroud JP, Willoughby DA. 1971. Studies on the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. The Journal of Pathology. 104:15–29. https://doi.org/10.1002/path.1711040103
24. Di Rosa M, Sorreatino L. 1968. The mechanism of the inflammatory effects of carrageenan. European Journal of Pharmacology. 4(3): 340-342. https://doi.org/10.1016/0014-2999(68)90103-9
25. El-Shitany NA, El-Bastawissy EA, El-desoky K. 2014. Ellagic acid protects against carrageenan-induced acute inflammation through inhibition of nuclear factor kappa B, inducible cyclooxygenase and proinflammatory cytokines and enhancement of interleukin-10 via an antioxidant mechanism. International Immunopharmacology 19(2): 290–299. https://doi.org/10.1016/j.intimp.2014.02.004.
26. Falodun A, Okunrobo LO, Uzoamaka N. 2006. Phytochemical screening and anti-inflammatory evaluation of methanolic and aqueous extracts of Euphorbia heterophylla Linn (Euphorbiaceae). African Journal of Biotechnology 5 (6):529-531.
27. Fernandes G, Banu J. 2012. Medicinal properties of plants from the genus Cissus: A review. Journal of Medicinal Plants Research 6(16):3080-3086.
28. Ganesh G, Saurabh M, Sarada NC. 2013. Antioxidant and anti-inflammatory activities of the methanolic leaf extract of traditionally used medicinal plant Mimusops elengi L. Journal of Pharmaceutical Science and Research. 5(6):125-130.
29. García MD, M T Sáenz MT, Gómez MA, Fernández MA. 1999. Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models. Phytotherapy Research. 13(1):78-80. https://doi.org/10.1002/(SICI)1099-1573(199902)13:1<78::AID-PTR384>3.0.CO;2-F
30. Ghorbanzadeh B, Mansouri M, Hemmati A, Naghizadeh B, Mard S, Rezaie A. 2015. A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats. Indian Journal of Pharmacology. 47, 292–298. https://doi.org/10.4103/0253-7613.157127
31. González R, Ballester I, López-Posadas R, Suárez MD, Zarzuelo A, Martínez-Augustin O, Sánchez De Medina F. 2011. Effects of flavonoids and other polyphenols on inflammation. Critical Reviews in Food Science and Nutrition. 51(4): 331-362, https://doi.org/10.1080/10408390903584094
32. Gul R, Jan SU, Faridullah S, Sherani S, Jahan N. 2017. Preliminary phytochemical screening, quantitative analysis of alkaloids, and antioxidant activity of crude plant extracts from Ephedra intermedia Indigenous to Balochistan. Hindawi The Scientific World Journal. Volume 2017: Article ID 5873648, 7 pages. Pp1-7. https://doi.org/10.1155/2017/5873648
33. Hassimotto NM, Moreira V, do Nascimento NG, Souto PC, Teixeira C, Lajolo FM. 2013. Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside. Biomedicine Research International. 2013(4):146716. https://doi:10.1155/2013/146716.
34. Hien TTT, Quang TH, Tai BH, Nhiem NX, Yen PH, Yen DTH, Cuong Le Canh V, Chul Kim Y-C, Oh H, Minh CV and Kiem PV. 2018. Iridoid glycosides and phenolic glycosides from Buddleja asiatica with anti-inflammatory and cytoprotective activities. Natural Product Communications 13(1):1-4.
35. Hussein SZ, Yusoff KM, Makpol S, Yusof YAM. 2012. Gelam honey inhibits the production of proinflammatory mediators NO, PGE2, TNF-α, and IL-6 in carrageenan-induced acute paw edema in rats. Evidence-based Complementary & Alternative Medicine. 2012: 109636. p 1-13. https://doi.org/ 10.1155/2012/109636
36. Hutchings A, van Staden J. 1994. Plants used for stress-related ailments in traditional Zulu, Xhosa, Sotho Medicine. Part1: Plants used for headaches. Journal of Ethnopharmacology. 43: 89-124.
37. Ishola IO, Agbaje EO, Adeyemi OO, Shukla R. 2014. Analgesic and anti-inflammatory effects of the methanol root extracts of some selected Nigerian medicinal plants. Pharmaeutical Biology. 52 (9): 1208–1216. https://doi.org/10.3109/13880209.2014.880487
38. Iwueke AV, Nwodo OFC, Okoli CO. 2006. Evaluation of the anti-inflammatory and analgesic activities of Vitex doniana leaves. African Journal of Biotechnology. 5 (20): 1929-1935.
39. Karin M, Ben-Neriah, Y. 2000. Phosphorylation meets ubiquitination: the control of NF-kB Activity. Annual Review of Immunology.18: 621–663. https://doi.org/10.1146/annurev.immunol.18.1.621
40. Kaur S, Jaggi R. 2010. Antinociceptive activity of chronic administration of different extracts of Terminalia bellerica Roxb. and Terminalia chebula Retz. fruits. Indian Journal of Experimental Biology. 48:925-930.
41. Khakimov ZZ, Rakhmanov AK, Mavlanov SR. 2019. Study of the influence of dry extract of medicinal plants on the course of carrageenan-induced inflammation. American Journal of Medicine and Medical Sciences. 9(8): 307-310. https://doi.org/10.5923/j.ajmms.20190908.07
42. Khan S, Shehzad O, Cheng M-S, Li R-J, Kim YS. (2015). Pharmacological mechanism underlying anti-inflammatory properties of two structurally divergent coumarins through the inhibition of pro-inflammatory enzymes and cytokines. Journal of Inflammation. 12(47):1-11. https://doi.org/10.1186/s12950-015-0087-y
43. Kim SH, Jun CD, Suk K, Choi BJ, Lim H, Park S, Lee SH, Shin HY, Kim DK, Shin TY. 2006. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicological Sciences. 91(1):123–131. https://doi.org/10.1093/ toxsci/kfj063
44. Kim JY, Shin JS, Ryu JH, Kim SY, Cho YW, Choi JH, Lee KT. 2009. Anti-inflammatory effect of anemarsaponin B isolated from the rhizomes of Anemarrhena asphodeloides in LPS-induced RAW 264.7 macrophage is mediated by negative regulation of the nuclear factor-kappaB and p38 pathways. Food and Chemical Toxicology. 47(7):1610–7. https://doi.org/10.1016/j.fct.2009.04.009
45. Kosala K, Widodo MA, Santoso S, Karyono S. 2018. In vitro and in vivo anti-inflammatory activities of Coptosapelta flavescens Korth root’s methanol extract. Journal of Applied Pharmaceutical Science. 8(09): 042-048. https://doi.org/10.7324/JAPS.2018.8907
46. Kulinsky VI. 2007. Biochemical aspects of inflammation. Biochemistry Moscow. 72:595–607. https://doi.org/10.1134/S0006297907060028.
47. Kumar T, Jain V. 2014. Antinociceptive and anti-inflammatory activities of Bridelia retusa methanolic fruit extract in experimental animals. Scientific World Journal. 2014:890151. 12 pages. https://doi.org/10.1155/2014/890151
48. Kwon HC, Cho OR, Lee KC, Lee KR. 2003. Cerebrosides and terpene glycosides from the root of Aster scaber. Archives of Pharmacal Research. 26(2):132-137. https://doi.org/10.1007/BF02976658
49. Liu H, Li B, Jiang P, Zhong Y, Zhang D, Liu H, Wan P, Lai X, Liu B, Chen J. 2016. Anti-diabetes and anti-inflammatory activities of phenolic glycosides from Liparis odorata. Medicinal Chemistry. 6:500-505. https://doi.org/ 10.4172/2161-0444.1000390.
50. Liu K-Y, Zhang T-J, Gao W-Y, Liu H-J. (2007). Phenolic compounds isolated from root and rhizoma of Aster tataricus. Chinese Traditional and Herbal Drugs. 38(12):1793-1795.
51. Lucas S. 2016. The pharmacology of indomethacin. Headache-The Journal of Head and Face Pain. 56(2): 436-446. https://doi.org/10.1111/head.12769
52. Lucetti DL, Lucetti ECP, Bandeira MM, Veras HNH, Silva AH, Leal LAM, Lopes AA, Alves VCC, Silva GS, Brito GA, Viana GB. 2010. Anti-inflammation effects and possible mechanism of action of lupeol acetate isolated from Himatanthus drasticus (Mart.) plumel. Journal of Inflammation. 7:60-70. https://doi.org/10.1186/1476-9255-7-60
53. Magama S, Asita OA. 2017. Evaluation of Chenopodium album Linn. crude methanolic leaf extract for central antinociceptive activity in albino mice using the hot plate test. International Journal of Sciences. 6(6):36-44. https://doi.org/10.18483/ijSci.1310.
54. Mansouri MT, Hemmati AA, Naghizadeh B, Mard SA, Rezaie A, Ghorbanzadeh B. 2015. A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats. Indian Journal of Pharmacology. 47(3):292-298. https://doi.org/10.4103/0253-7613.157127
55. Middleton E. 1998. Effect of plant flavonoids on immune and inflammatory cell function. In: Manthey J.A., Buslig B.S. (eds) Flavonoids in the Living System. Advances in Experimental Medicine and Biology. 439:175-182. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5335-9_13
56. Moteetee A, Seleteng-Kose L. 2017. A review of medicinal plants used by the Basotho for treatment of skin disorders: their phytochemical, antimicrobial, and anti-inflammatory potential. African Journal of Traditional, Complementary and Alternative Medicines. 14 (5): 121-137 https://doi.org/10.21010/ajtcam.v14i5.16
57. Nathan C. 2002. Points of control in inflammation. Nature. 420(6917):846–852.
58. N’Goka V, Nsonde Ntandou GF, N’Goka V, Boumba SL, Abena A.A. 2018. Chemical screening, acute toxicity and analgesic effect of the aqueous extracts of Vitex madiensis Oliv. (Lamiaceae-Viticoïdeae) and Phytolacca dodecandra L’Hérit. (Phytolaccaceae) leaves. International Journal of Sciences. 7(1):1-9. https://doi.org/10.18483/ijSci.1261
59. Nguyen TH, Nachtergael A, Nguyen TM, Cornet V, Duez P, Mullere M, Huong DTL, Kestemonta P. 2020. Anti-inflammatory properties of the ethanol extract from Clerodendrum cyrtophyllum Turcz based on in vitro and in vivo studies. Journal of Ethnopharmacology 254: 112739. https://doi.org/10.1016/j.jep.2020.112739
60. Nsonde Ntandou GF, Bassoueka DJ, Banzouzi JT , Etou Ossibi AW, Elion Itou RDG., Makambila MC, Ramos S, Benoit-Vical F, Abena AA, Ouamba JM. 2015. Assessment of Cassia siamea stem bark extracts toxicity and stability in time of aqueous extract analgesic activity. African Journal of Pharmacy and Pharmacology 9(41): 988-994. DOI: 10.5897/AJPP2009.138.
61. OECD. 2002. Test No. 423: Acute Oral toxicity - Acute Toxic Class Method, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264071001-en
62. Oguntibeju OO. 2018. Medicinal plants with anti-inflammatory activities from selected countries and regions of Africa. Journal of Inflammation Research. 11: 307–317. https://doi.org/10.2147/JIR.S167789.
63. Owolabi OO, James DB, Sani I, Andongma BT, Opeoluwa O, Fasanya OO, Kure B. 2018. Phytochemical analysis, antioxidant and anti-inflammatory potential of Feretia apodanthera root bark extracts. BMC Complementary and Alternative Medicine. 18(12):1-9. https://doi.org/10.1186/s12906-017-2070-z
64. Panthong A, Supraditaporn W, Kanjanapothi D, Taesotikul T, Reutrakul V. 2007. Analgesic, anti-inflammatory and venotonic effects of Cissus quadrangularis Linn. Journal of Ethnopharmacology. 110: 264–270.
65. Perez RM. 2001. Anti-inflammatory activity of compounds isolated from plants. Scientific World Journal. 1:713–84.
66. Ponmathi SA, Evanjaline M, Muthukumarasamy S, Mohan V. 2017. Evaluation of antiinflammatory activity of ethanol extracts of Barleria courtallica Nees (Acanthaceae). International Journal of Pharmacognosy and Phytochemical Research. 9(2): 245-247. https://doi.org/10.25258/phyto.v9i2.8070
67. Popoola TD, Awodelea O, Omisanyaa A, Obia N, Umezinwaa C, Fatoku AA. 2016. Three indigenous plants used in anti-cancer remedies, Garcinia kola Heckel (stem bark), Uvaria chamae P. Beauv. (root) and Olax subscorpioidea Oliv. (root) show analgesic and anti-inflammatory activities in animal models. Journal of Ethnopharmacology. 194: 440-449. https://doi.org/10.1016/j.jep.2016.09.046.
68. Prasad DMR, Izam A, Khan MR. 2012. Jatropha curcas: Plant of medical benefits. Journal of Medicinal Plants Research. Vol. 6(14): 2691-2699.
69. Rajanandhini M, Musthafa M. 2017. Pharmacological evaluation of antiinflammatory activity of Pancha Pashana Chendhuram against carrageenan induced paw edema in Rats. International Journal of Current Research in Medical Sciences. 3(8): 124-129. https://dx.doi.org/10.22192/ijcrms.2017.03.08.019
70. Rizvi, W, Fayazuddin M, Shariq S, Singh O, Moin S, Akhtar K, Kumar A. 2014. Anti-inflammatory activity of roots of Cichorium intybus due to its inhibitory effect on various cytokines and antioxidant activity. Ancient Science of Life. 34(1):44–49. https://doi:10.4103/0257-7941.150780
71. Rodrigues LB, Martins AOBPB, Cesário FRAS, e Castro FF, de Albuquerque TR, Fernandes MNM, da Silva BAF, Quintans Junior LJ, da Costa JGM, Coutinho HDM, Barbosa R, de Menezes IRA. 2016. Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models. Chemico-Biological Interactions. 257:14-25. http://dx.doi.org/10.1016/j.cbi.2016.07.026
72. Salvemini D, Wang ZQ, Wyatt PS, Bourdon DM, Marino MH, Manning PT, Currie, MG. 1996. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. British Journal of Pharmacology. 118(4): 829-838. https://doi.org/10.1111/j.1476-5381.1996.tb15475.x
73. Samad TA. 2001. Interleukin-1β-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature. 410:471–475. https://doi.org/10.1038/35068566
74. Santangelo C, Varì R, Scazzocchio B, Benedetto R Di, Filesi C, Masella R. 2007. Polyphenols, intracellular signalling and inflammation. Annali dell'Istituto Superiore di Sanità. 43(4):394–405.
75. Sarkhel S. 2016. Evaluation of the anti-inflammatory activities of Quillaja saponaria Mol. saponin extract in mice. Toxicology Reports. 3:1–3. https://doi.org/10.1016/j.toxrep.2015.11.006
76. Sarada K, Jothibai, RM, Mohan VR. 2012. Anti-inflammatory activity of ethanol extracts of leaf and bark of Naringi crenulata (Roxb.) Nicolson. International Journal of Pharmceutical Science and Research. 3(11): 4540-4544.
77. Sathiyabalan G, Evanjaline MR, Muthukumarasamy S, Mohan VR. 2018. Anti-inflammatory activity of whole plant of Beloperone plumbaginifolia (Acanthaceae). International Journal of Pharmaceutical Sciences and Research. 9(1): 328-331. https://doi: 10.13040/IJPSR.0975-8232.9(1).328-31
78. Sayyah M, Hadidi N, Kamalinejad M,. 2004. Analgesic and anti-inflammatory
79. activity of Lactuca sativa seed extract in rat. Journal of Ethnopharmacology. 92(2-3):325–329. https://doi.org/10.1016/j.jep.2004.03.016
80. Schmide D, Gruber M, Woehs F, Prinz S, Etzlstorfer B, Prucker C, Fuzzati N, Kopp B, Moeslinger T. 2009. Inhibition of inducible nitric oxide synthesis by Cimifuga racemosa (Actaea racemosa, black cohosh) extracts in LPS stimulated RAW 264.7 macrophages. Journal of Pharmacy and Pharmacology. 61(8):1089–1096. https://doi: 10.1211/jpp/61.08.0013.
81. Seleteng-Kose, L, Moteetee A, Van Vuuren S. 2019. Medicinal plants used for the treatment of sexually transmitted infections in the Maseru District, Lesotho: Antimicrobial validation, phytochemical and cytotoxicity studies. South African Journal of Botany. 122:457-466. https://doi.org/10.1016/j.sajb.2019.01.035
82. Senguttuvan J, Paulsamy S, Karthika K. 2014. Phytochemical analysis and evaluation of leaf and root parts of the medicinal herb, Hypochaeris radicata L. for in vitro antioxidant activities. Asian Pacific Journal of Tropical Biomedicine. 4(1): S359-S36. https://doi.org/10.12980/APJTB.4.2014C1030.
83. Shale TL, Stirk WA, van Staden J. 1999. Screening of medicinal plants used in Lesotho for anti-bacterial and anti-inflammatory activity. Journal of Ethnopharmacology. 67(3):347–354. https://doi.org/10.1016/S0378-8741(99)00035-5
84. Sidhapuriwala J, Li L, Sparatore A, Bhatia M, Moore PK. 2007. Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on carrageenan induced hind paw oedema formation in the rat. European Journal of Pharmacology. 569(1-2): 149–154. https://doi.org/ 10.1016/j.ejphar.2007.05.003
85. Street RA, Sidana J, Prinsloo G. 2013. Cichorium intybus: Traditional uses, phytochemistry, pharmacology, and toxicology. Evidence-Based Complementary and Alternative Medicine. 2013: 579319. https://doi.org/10.1155/2013/579319.
86. Su X-D, Jang H-J, Wang C-Y, Lee SW, Rho M-C, Kim YH, Yang SY. 2019. Anti-inflammatory potential of saponins from Aster tataricus via NF-κB/MAPK activation. Journal of Natural Products 82 (5): 1139-1148. https://doi.org/ 10.1021/acs.jnatprod.8b00856
87. Talluri MR, Rao BG, Rao YV. 2016. Anti-Inflammatory Activity of Chrozophora rottleri extracts on carrageenan-induced rat paw edema. International Journal of Pharmacology, Phytochemistry and Ethnomedicine. 3:20-26. https://doi:10.18052/www.scipress.com/IJPPE.3.20
88. Thilagavathi T, Arvindganth R, Vidhya D, Dhivya R. 2015. Preliminary phytochemical screening of different solvent mediated medicinal plant extracts evaluated. International Research Journal of Pharmacy. 6(4):246-248. http://dx.doi.org/10.7897/2230-8407.06455
89. Ugwoke CEC, Orji J, Anze SPG, Ilodibia CV. 2017. Quantitative Phytochemical Analysis and Antimicrobial Potential of the Ethanol and Aqueous Extracts of the Leaf, Stem and Root of Chromolaena odorata (Asteraceae). International Journal of Pharmacognosy and Phytochemical Research. 9(2); 207-214. DOI: 10.25258/phyto.v9i2.8064
90. Ullah HM, Zaman S, Juhara F, Akter L, Tareq SM, Masum EH, Bhattacharjee R. 2014. Evaluation of antinociceptive, in-vivo & in-vitro anti-inflammatory activity of ethanolic extract of Curcuma zedoaria rhizome. BMC Complementary and Alternative Medicine. 22(14):346. https://doi: 10.1186/1472-6882-14-346.
91. Van Wyk BE, van Oudtshourch B, Gericke N. 1997. Medicinal Plants of South Africa, 1st Edition, Briza Publications, South Africa, pp 50.
92. Wang G-Y, Wu T, Lin P-C, Chou G-X, Wang Z-T. 2003. Phenolic compounds isolated from rhizoma of Aster tataricus. China Journal of Chinese Materia Medica. 28(10):946-8.
93. Winter CA, Risley EA, Nuss GW. 1962. Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proceedings of the Society for Experimental Biology and Medicine. 111(3), 544–547. https://doi.org/10.3181/00379727-111-27849
94. Wu Y, Zhou C, Song L, Li X, Shi S, Mo J, Chen H, Bai H, Wu X, Zhao J, Zhang R, Hao X, Sun H, Zhao Y. 2006. Effect of total phenolics from Laggera alata on acute and chronic inflammation models. Journal of Ethnopharmacology. 108(2): 243-250. https://doi.org/10.1016/j.jep.2006.05.017
95. Xiong Q, Tezuka Y, Kaneko T, Li H, Tran LQ, Hase K, Namba T, Kadota S. 2000. Inhibition of nitric oxide by phenylethanoids in activated macrophages. European Journal of Pharmacology. 400 (1): 137–144. https://doi.org/10.1016/s0014-2999(00)00354-x
96. Yamamoto Y, Gaynor RB. 2001. Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. The Journal of Clinical Investigation. 107(2): 135-142. https://doi.org/10.1172/JCI11914
97. Yoon J-H, Baek SJ. 2005. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Medical Journal. 46(5):585–596. https://doi.org/10.3349/ymj.2005.46.5.585
98. Yuan L, Zhang F, Shen M, Jia S, Xie J. 2019. Phytosterols suppress phagocytosis and inhibit inflammatory mediators via ERK Pathway on LPS-triggered inflammatory responses in RAW264.7 macrophages and the correlation with their structure. Foods. 8(11):582. https://doi.org/10.3390/foods8110582
99. Zahra Z, Khan MR, Shah SA, Maryam S, Majid M, Younisa T, Sajid M. 2020. Vincetoxicum arnottianum ameliorate inflammation by suppressing oxidative stress and pro-inflammatory mediators in rat. Journal of Ethnopharmacology 252: 112565. https://doi.org/10.1016/j.jep.2020.112565
100. Zelice da Cruz de Moraes S, Shan A, Oliveira Melo MA, Pereira da Silva J, Rocha Santos Passos F, de Souza Graça A, Araújo BS, Quintans J, Quintans Júnior LJ, Oliveira Barreto E, Brandão GC, Estevam C. 2020. Antinociceptive and anti-inflammatory effect of Poincianella pyramidalis (Tul.) L.P. Queiroz. Journal of Ethnopharmacology. 254: 112563. https://doi.org/10.1016/j.jep.2020.112563
101. Zhang T-T, Hu T, Jiang J-G, Zhao J-W , Zhu W. 2018. Antioxidant and anti-inflammatory effects of polyphenols extracted from Ilex latifolia Thunb. Royal Society of Chemistry Advances. 8: 7134-7141. https://doi.org/10.1039/C7RA13569F.