{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T23:30:37Z","timestamp":1774999837132,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2016,8,20]],"date-time":"2016-08-20T00:00:00Z","timestamp":1471651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC50, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation.<\/jats:p>","DOI":"10.3390\/molecules21081095","type":"journal-article","created":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T10:40:33Z","timestamp":1471862433000},"page":"1095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0162-4478","authenticated-orcid":false,"given":"Shafiq","family":"Ur Rahman","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir (U)-18000, Pakistan"},{"name":"H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achyut","family":"Adhikari","sequence":"additional","affiliation":[{"name":"H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Raza Shah","sequence":"additional","affiliation":[{"name":"H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Khurram","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir (U)-18000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Shahid","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5730-7730","authenticated-orcid":false,"given":"Farman","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Shaheed Benazir Bhutto University, Sheringal, Dir (U)-18000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-5054","authenticated-orcid":false,"given":"Abdul","family":"Haseeb","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Umm Al Qura University, Makkah 21514, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fazal","family":"Akbar","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Microbiology, University of Swat, Swat 19200, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-1236","authenticated-orcid":false,"given":"Marcello","family":"Iriti","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Environmental Sciences, Milan State University, Milan 20133, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S2221-6189(13)60107-9","article-title":"A review on antimicrobial efficacy of some traditional medicinal plants in Tamilnadu","volume":"2","author":"Munuswamy","year":"2013","journal-title":"J. Acute Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/ecam\/neh140","article-title":"Ayurveda and traditional Chinese medicine: A comparative overview","volume":"2","author":"Patwardhan","year":"2005","journal-title":"Evid. Based. Complement. Altern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0378-8741(03)00009-6","article-title":"Inhibition of human pathogenic fungi by members of Zingiberaceae used by the Kenyah (Indonesian Borneo)","volume":"85","author":"Ficker","year":"2003","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/ptr.1335","article-title":"Bioassay guided isolation and identification of antifungal compounds from ginger","volume":"17","author":"Ficker","year":"2003","journal-title":"Phytother. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.phytol.2011.04.010","article-title":"Seven new triterpene glycosides from the pericarps of Stryphnodendron fissuratum","volume":"4","author":"Yokosuka","year":"2011","journal-title":"Phytochem. Lett."},{"key":"ref_6","first-page":"1","article-title":"Prospects and perspectives of natural plants products in medicine","volume":"26","author":"Gupta","year":"1994","journal-title":"Indian. J. Pharmacol."},{"key":"ref_7","first-page":"111","article-title":"Study of analgesic and anti-inflammatory activity from plant extracts of Lactuca scariola and Artemisia absinthium","volume":"5","author":"Ahmad","year":"1992","journal-title":"J. Islam. Acad. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1658-3655(12)60014-4","article-title":"Analgesic and anti-inflammatory properties of Argyreia argentea methanol extract in animal model","volume":"3","author":"Dina","year":"2010","journal-title":"J. Taibah Univ. Sci."},{"key":"ref_9","unstructured":"Muhammad, S.K. (2011). Diversity of Vascular Plants, Ethnobotany and Conservation Status of Ushairy Valley, District Dir, Upper NWFp Northern Pakistan. [Ph.D. Thesis, Quaid-i-Azam University]. Available online: http:\/\/eprints.hec.gov.pk\/7497\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.jep.2013.05.035","article-title":"Indigenous knowledge of medicinal plants from Gujranwala district, Pakistan","volume":"148","author":"Mahmood","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","first-page":"193","article-title":"Ethnobotanical observations in the Mornaula reserve forest of Komoun, West Himalaya, India","volume":"14","author":"Pant","year":"2010","journal-title":"Ethnobot. Leafl."},{"key":"ref_12","first-page":"3147","article-title":"Ethnomedicinal plants of Chamba district, Himachal Pradesh, India","volume":"7","author":"Rani","year":"2013","journal-title":"J. Med. Plant Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2307\/2990062","article-title":"A systematic study of the North American genus Trillium, its variability, and its relation to Paris and Medeola","volume":"4","author":"Gates","year":"1917","journal-title":"Ann. MI. Bot. Gard."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1016\/j.phytochem.2008.08.004","article-title":"Steroidal glycosides from the underground parts of Trillium erectum and their cytotoxic activity","volume":"69","author":"Yokosuka","year":"2008","journal-title":"Phytochemistry"},{"key":"ref_15","first-page":"513","article-title":"Cytotoxicity of a plant steroidal saponin on human lung cancer cells","volume":"12","author":"Huang","year":"2011","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1248\/cpb.55.1093","article-title":"Three new steroid glycosides from the underground parts of Trillium kamtschaticum","volume":"55","author":"Ono","year":"2007","journal-title":"Chem. Pharm. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jep.2015.03.063","article-title":"Trillium tschonoskii steroidal saponins suppress the growth of colorectal cancer cells in vitro and in vivo","volume":"168","author":"Li","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1515\/znc-2011-9-1007","article-title":"The rhizome of Trillium tschonoskii Maxim. Extract induces apoptosis in human lung cancer cells","volume":"66","author":"Huang","year":"2011","journal-title":"Z. Naturforsch. A Phys. Sci."},{"key":"ref_19","unstructured":"Fu, L.K., and Jin, J.M. (1992). China Plant Red Data Book-Rare and Endangered Plants, Science Press."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1248\/cpb.55.679","article-title":"An 18-norspirostanol saponin with inhibitory action against COX-2 production from the underground part of Trillium tschonoskii","volume":"55","author":"Wang","year":"2007","journal-title":"Chem. Pharm. Bull."},{"key":"ref_21","first-page":"1178","article-title":"Study on the anti-inflammatory, analgesic and thrombosis effects of extract of Trillium tschonoskii Maxim","volume":"19","author":"Yu","year":"2008","journal-title":"Lishizhen Med. Mater. Med. Res."},{"key":"ref_22","first-page":"116","article-title":"The Royal Horticultural Society Encyclopedia of Herbs and Their Uses","volume":"424","author":"Deni","year":"1996","journal-title":"Dorling Kindersley B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.steroids.2015.10.013","article-title":"Govanoside A, a new steroidal saponin from rhizomes of Trillium govanianum","volume":"104","author":"Rahman","year":"2015","journal-title":"Steroids"},{"key":"ref_24","first-page":"187","article-title":"Pharmacognostic and ethnomedicinal studies on Trillium govanianum","volume":"47","author":"Rahman","year":"2015","journal-title":"Pak. J. Bot."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"577","DOI":"10.3329\/bjp.v10i3.23446","article-title":"GC\/MS analysis, free radical scavenging, anticancer and \u03b2-glucuronidase inhibitory activities of Trillium govanianum rhizomes","volume":"10","author":"Rahman","year":"2015","journal-title":"Bangladesh J. Pharmacol."},{"key":"ref_26","first-page":"493","article-title":"The role of radical oxygen species in airway inflammation","volume":"14","author":"Pawliczak","year":"2003","journal-title":"Pol. Merkur. Lekarski."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1096\/fj.00-0526hyp","article-title":"Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat","volume":"15","author":"Cuzzocrea","year":"2001","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0014-2999(96)00140-9","article-title":"Evidence of peroxynitrite involvement in the carrageenan-induced rat paw edema","volume":"303","author":"Salvemini","year":"1996","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18515","DOI":"10.1074\/jbc.272.30.18515","article-title":"Superoxide anion radical (O2), superoxide dismutases, and related matters","volume":"272","author":"Fridovich","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/157015909787602823","article-title":"Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options","volume":"7","author":"Uttara","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1752-153X-7-6","article-title":"Identification of anti-inflammatory and other biological activities of 3-carboxamide, 3-carbohydrazide and ester derivatives of gatifloxacin","volume":"7","author":"Sultana","year":"2013","journal-title":"Chem. Cent. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0378-8741(97)00155-4","article-title":"Heterotheca inuloides: Anti-inflammatory and analgesic effect","volume":"16","author":"Gene","year":"1998","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/j.1476-5381.1996.tb15475.x","article-title":"Nitric oxide: A key mediator in the early and late phase of carrageenan-induced rat paw inflammation","volume":"118","author":"Salvemini","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","first-page":"370","article-title":"A nitric oxide synthase inhibitor reduces inflammation, down-regulates inflammatory cytokines and enhances interleukin-10 production in carrageenin-induced oedema in mice","volume":"82","author":"Ianaro","year":"1994","journal-title":"Immunology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12013","DOI":"10.1073\/pnas.91.25.12013","article-title":"Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain","volume":"91","author":"Seibert","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","first-page":"395","article-title":"Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions","volume":"107","author":"Fantone","year":"1982","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1271\/bbb.50698","article-title":"Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI","volume":"70","author":"Huang","year":"2006","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_38","first-page":"76","article-title":"Anti-inflammatory Activity of Characterized Compound Diosgenin Isolated from Tinospora malabarica Miers in Ann. (Menispermaceae) in Animal Model","volume":"1","author":"Punitha","year":"2013","journal-title":"Int. J. Herb. Med."},{"key":"ref_39","unstructured":"Ferreira, S., Lorenzetti, B.B., Castro, M.S.A., and Correa, F. (1978). The Recognition of Anti-rheumatic Drugs, MTP Press Ltd."},{"key":"ref_40","unstructured":"Hosseinzadeh, H., and Younesi, H.M. (2002). Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol., 2."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1248\/bpb.31.643","article-title":"In vivo anti-inflammatory and analgesic activities of a purified saponin fraction derived from the root of Ilex pubescens","volume":"31","author":"Wang","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0024-3205(00)01019-5","article-title":"In vivo anti-inflammatory activity of saponins from Bupleurum rotundifolium","volume":"68","author":"Navarro","year":"2001","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.phytochem.2006.10.026","article-title":"Steroidal saponins from Smilax china and their anti-inflammatory activities","volume":"68","author":"Shao","year":"2007","journal-title":"Phytochemistry"},{"key":"ref_44","first-page":"150","article-title":"An overview on anti-inflammatory properties and chemo-profiles of plants used in traditional medicine","volume":"1","author":"Agnihotri","year":"2010","journal-title":"Indian J. Nat. Prod. Resour."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.4049\/jimmunol.1003335","article-title":"Endogenous opioid-mediated analgesia is dependent on adaptive T cell response in mice","volume":"186","author":"Blanpied","year":"2011","journal-title":"J. Immunol."},{"key":"ref_46","first-page":"16","article-title":"Central and peripheral analgesic action of non-acidic non-steroidal anti-inflammatory drugs in mice and rats","volume":"282","author":"Nakamura","year":"1986","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1476-5381.1968.tb00973.x","article-title":"The abdominal constriction response and its suppression by analgesic drugs in the mouse","volume":"32","author":"Collier","year":"1968","journal-title":"Br. J. Pharmacol. Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0160-5402(91)90014-V","article-title":"The increasing-temperature hot-plate test: An improved test of nociception in mice and rats","volume":"25","author":"Rosland","year":"1991","journal-title":"J. Pharmacol. Methods"},{"key":"ref_49","unstructured":"Thangaraj, P. (2016). Pharmacological Assays of Plant-Based Natural Products, Springe Nature."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jep.2009.10.003","article-title":"The antinociceptive activity of Polygonatum verticillatum rhizomes in pain models","volume":"127","author":"Khan","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Baydoun, E., Bibi, M., Iqbal, M.A., Atia-tul, W., Farran, D., Smith, C., Sattar, S.A., Rahman, A.U., and Choudhary, M.I. (2013). Microbial transformation of anticancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines. Chem. Cent. J., 7.","DOI":"10.1186\/1752-153X-7-57"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1385\/1-59259-374-7:115","article-title":"Carrageenan-induced paw edema in the rat and mouse","volume":"225","author":"Morris","year":"2003","journal-title":"Inflamm. Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1084\/jem.156.2.492","article-title":"Chemiluminescence response of human natural killer cells. I. The relationship between target cell binding, chemiluminescence, and cytolysis","volume":"156","author":"Helfand","year":"1982","journal-title":"J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0022-3565(25)30089-3","article-title":"Quantification of the analgesic activity of narcotic antagonists by a modified hot-plate procedure","volume":"192","author":"Holtzman","year":"1975","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/8\/1095\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:52Z","timestamp":1760210932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/8\/1095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,20]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8]]}},"alternative-id":["molecules21081095"],"URL":"https:\/\/doi.org\/10.3390\/molecules21081095","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,20]]}}}