{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:47:55Z","timestamp":1785163675036,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["R.G.P.1 \/ 119 \/ 40"],"award-info":[{"award-number":["R.G.P.1 \/ 119 \/ 40"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Kleinia pendula (Forssk.) DC. is a prostrate or pendent dark green succulent herb found in the southwestern mountain regions of Saudi Arabia. The literature survey of the plant reveals a lack of phytochemical and pharmacological studies, although traditional uses have been noted. The objective of the present work was to assess the in vivo analgesic and anti-inflammatory activities, as well as, the in vitro cytotoxic potential of the fractions of Kleinia pendula, and correlate these activities to the plant metabolites. The methanolic extract of Kleinia pendula was subjected to fractionation with n-hexane, ethyl acetate, chloroform, n-butanol, and water. The fractions were screened for their analgesic and anti-inflammatory activities, as well as cytotoxic activity against breast, liver, and colon cancer cell lines. The n-hexane and chloroform fractions of Kleinia pendula showed significant cytotoxic activity against all three cancer cell lines tested. The ethyl acetate and chloroform fractions showed significant analgesic and anti-inflammatory activities. The metabolites in these three active fractions were determined using UPLC-PDA-ESI-MS. Thus, the analgesic and anti-inflammatory activities of the plant were attributed to its phenolic acids (caffeoylquinic acid derivatives, protocatechuic, and chlorogenic acids). While fatty acids and triterpenoids such as (tormentic acid) in the hexane fraction are responsible for the cytotoxic activity; thus, these fractions of Kleinia pendula may be a novel source for the development of new plant-based analgesic, anti-inflammatory, and anticancer drugs.<\/jats:p>","DOI":"10.3390\/molecules25020418","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T03:04:43Z","timestamp":1579575883000},"page":"418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Analgesic, Anti-Inflammatory, Cytotoxic Activity Screening and UPLC-PDA-ESI-MS Metabolites Determination of Bioactive Fractions of Kleinia pendula"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4310-3539","authenticated-orcid":false,"given":"Mohammad","family":"Alfaifi","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrhman","family":"Alsayari","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-1354","authenticated-orcid":false,"given":"Narasimman","family":"Gurusamy","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Louis","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4680-3215","authenticated-orcid":false,"given":"Serag","family":"Eldin Elbehairi","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-9380","authenticated-orcid":false,"given":"Kumar","family":"Venkatesan","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivakumar","family":"Annadurai","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahya","family":"I. Asiri","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Shati","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmi","family":"Alboushnak","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Handoussa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9742-3573","authenticated-orcid":false,"given":"Abdullatif","family":"Bin Muhsinah","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Abdel Motaal","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Khalid University, Abha 9004, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural Products as Sources of New Drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd4510","article-title":"The re-emergence of natural products for drug discovery in the genomics era","volume":"14","author":"Harvey","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3109\/13880209.2010.512295","article-title":"Assessment of Yemeni medicinal plants for their in vitro antimicrobial, anticancer and antioxidant activities","volume":"49","author":"Mothana","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1467-8748.1989.tb00646.x","article-title":"Kleinia saginata Compositae","volume":"6","author":"Halliday","year":"1989","journal-title":"Curtis\u2019s Bot. Mag."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/j.1756-1051.2002.tb01394.x","article-title":"New species and combinations in Kleinia (Asteraceae) from the Horn of Africa","volume":"22","author":"Hulin","year":"2002","journal-title":"Nord. J. Bot."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"817","DOI":"10.2307\/4107755","article-title":"The genus Kleinia (Compositae) in Arabia","volume":"39","author":"Halliday","year":"1983","journal-title":"Kew Bull."},{"key":"ref_7","unstructured":"Collenette, S. (1985). An Illustrated Guide to the Flowers of Saudi Arabia, Scorpion Publishing Ltd."},{"key":"ref_8","unstructured":"Migahid, A.M. (1988). Flora of Saudi Arabia, King Saud University Press. [3rd ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0031-9422(00)89395-4","article-title":"Zwei neue acylpyrrole aus Kleinia kleinioides","volume":"17","author":"Bohlmann","year":"1978","journal-title":"Phytochemistry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/0031-9422(80)87041-5","article-title":"Weitere abrotanifolon-derivate aus Kleinia tomentosa","volume":"19","author":"Bohlmann","year":"1980","journal-title":"Phytochemistry"},{"key":"ref_11","first-page":"201","article-title":"Sesquiterpenes from Kleinia species","volume":"20","author":"Bohlmann","year":"1981","journal-title":"Phytochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"905639","DOI":"10.1155\/2014\/905639","article-title":"Evaluation of the in vitro antiplasmoidal, antileishmanial and antitrypanasomal activity of medicinal plants used in Saudi and Yemeni traditional medicine","volume":"2014","author":"Mothana","year":"2014","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1746-4269-10-18","article-title":"Ethnomedicinal plants used to treat human ailments in the prehistoric place of Harla and Dengego valleys, eastern Ethiopia","volume":"10","author":"Belayneh","year":"2014","journal-title":"J. Ethnobiol. Ethnomed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1016\/S0031-9422(00)84596-3","article-title":"Volatile Mono and Sesquiterpenoids from Kleinia pendula","volume":"26","author":"Elmi","year":"1987","journal-title":"Phytochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11490","DOI":"10.3390\/molecules200611490","article-title":"Antioxidant capacities and analysis of phenolic compounds in three endemic Nolana species by HPLC-PDA-ESI-MS","volume":"20","author":"Simirgiotis","year":"2015","journal-title":"Molecules"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.foodchem.2016.05.052","article-title":"Identification and characterization of phenolic compounds in hydromethanolic extracts of sorghum wholegrains by LC-ESI-MSn","volume":"211","author":"Kang","year":"2016","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"679","DOI":"10.3390\/12030679","article-title":"Screening non-colored phenolics in red wines using liquid chromatography\/ultraviolet and mass spectrometry\/mass spectrometry libraries","volume":"12","author":"Sun","year":"2007","journal-title":"Molecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.bjp.2015.02.008","article-title":"HPLC-DAD-MS\/MS profiling of phenolics from Securigera securidaca flowers and its anti-hyperglycemic and anti-hyperlipidemic activities","volume":"25","author":"Ibrahim","year":"2015","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/rcm.2875","article-title":"Characterization of phenolic compounds in the fruits of Forsythia suspensa by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry","volume":"21","author":"Guo","year":"2007","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_20","first-page":"23","article-title":"Structural Characterization of Polyphenolics in Livistona chinensis Using HPLC-PDA-MS","volume":"3","author":"Ahmed","year":"2019","journal-title":"J. Adv. Pharm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.arabjc.2015.04.018","article-title":"Characterization of phenolic constituents and evaluation of antioxidant properties of leaves and stems of Eriocephalus africanus","volume":"11","author":"Catarino","year":"2018","journal-title":"Arab. J. Chem."},{"key":"ref_22","first-page":"4191","article-title":"Metabolic profiling of Shu-Yu capsule in rat serum based on metabolic fingerprinting analysis using HPLC-ESI-MSn","volume":"13","author":"Li","year":"2016","journal-title":"Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/chromsci\/bmw055","article-title":"Rapid identification and assignation of the active ingredients in fufang banbianlian injection using HPLC-DAD-ESI-IT-TOF-MS","volume":"54","author":"Li","year":"2016","journal-title":"J. Chromatogr. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ben Said, R., Hamed, A.I., Mahalel, U.A., Al-Ayed, A.S., Kowalczyk, M., Moldoch, J., Oleszek, W., and Stochmal, A. (2017). Tentative characterization of polyphenolic compounds in the male flowers of Phoenix dactylifera by liquid chromatography coupled with mass spectrometry and DFT. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030512"},{"key":"ref_25","first-page":"407","article-title":"Phenolic compounds in different barley varieties: Identification by tandem mass spectrometry (QStar) and NMR; quantification by liquid chromatography triple quadrupole-linear ion trap mass spectrometry (Q-Trap)","volume":"5","author":"Klausen","year":"2010","journal-title":"Nat. Prod. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1021\/jf904211q","article-title":"Antioxidant capacity, phenolic content, and profiling of phenolic compounds in the seeds, skin, and pulp of Vitis rotundifolia (muscadine grapes) as determined by HPLC-DAD-ESI-MS n","volume":"58","author":"Sandhu","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jpha.2011.09.009","article-title":"Characterization of flavonoids in Millettia nitida var. hirsutissima by HPLC\/DAD\/ESI-MSn","volume":"2","author":"Ye","year":"2012","journal-title":"J. Pharm. Anal."},{"key":"ref_28","first-page":"345465","article-title":"Characterization of the phytochemical constituents of Taif rose and its antioxidant and anticancer activities","volume":"2013","author":"Bazaid","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1590\/S0102-695X2013000600001","article-title":"Saponins, tannins and flavonols found in hydroethanolic extract from Periandra dulcis roots","volume":"23","author":"Negri","year":"2013","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xu, L.L., Guo, F.X., Chi, S.S., Wang, Z.J., Jiang, Y.Y., Liu, B., and Zhang, J.Y. (2017). Rapid screening and identification of diterpenoids in Tinospora sinensis based on high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry. Molecules, 22.","DOI":"10.3390\/molecules22060912"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1556\/AChrom.27.2015.4.9","article-title":"UPLC\/Q-TOF-MS analysis for identification of hydrophilic phenolics and lipophilic diterpenoids from Radix Salviae Miltiorrhizae","volume":"27","author":"Yang","year":"2015","journal-title":"Acta Chromatogr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/jms.1027","article-title":"Characterization of metabolites of tanshinone IIA in rats by liquid chromatography\/tandem mass spectrometry","volume":"41","author":"Li","year":"2006","journal-title":"J. Mass Spectrom."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/bmc.1225","article-title":"Liquid chromatography mass spectrometry for the determination of salvianolic acid B, a natural compound from the herb Danshen in rat plasma and application to pharmacokinetic study","volume":"23","author":"Han","year":"2009","journal-title":"Biomed. Chromatogr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, H., Yao, W., Liu, Q., Xu, J., Bao, B., Shan, M., Cao, Y., Cheng, F., Ding, A., and Zhang, L. (2017). Application of UHPLC-ESI-Q-TOF-MS to identify multiple constituents in processed products of the herbal medicine Ligustri Lucidi Fructus. Molecules, 22.","DOI":"10.3390\/molecules22050689"},{"key":"ref_35","first-page":"229","article-title":"Pharmacological evaluation of abietane diterpenoids from Plectranthus bishopianus as potent antibacterial, antioxidant and their cytotoxic agents","volume":"9","author":"Vinodh","year":"2019","journal-title":"Nat. Prod. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/jms.3844","article-title":"LC-PDA-ESI-MSn analysis of phenolic and iridoid compounds from Globularia spp","volume":"51","author":"Bucar","year":"2016","journal-title":"J. Mass Spectrom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3389\/fchem.2018.00342","article-title":"UPLC-MS\/MS based identification of dietary steryl glucosides by investigation of corresponding free sterols","volume":"6","author":"Boulos","year":"2018","journal-title":"Front. Chem."},{"key":"ref_38","first-page":"385","article-title":"Synthetic analgesics. II, Dithenylbutenyl and dithienylbutylamines","volume":"107","author":"Eddy","year":"1953","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"410","DOI":"10.5530\/pj.2017.3.70","article-title":"Antimicrobial, Analgesic and Anti-inflammatory activity reported on Tamarindus indica Linn root extract","volume":"9","author":"Gupta","year":"2017","journal-title":"Pharmacogn. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ullah, H.M.A., Zaman, S., Fatematuj, J., Akter, L., Tareq, S.M., Masum, E.H., and Bhattacharjee, R. (2014). Evaluation of antinociceptive, in-vivo & in-vitro anti-inflammatory activity of ethanolic extract of Curcuma zedoaria rhizome. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-346"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3109\/14756366.2011.607446","article-title":"Anti-cancer characteristics of mevinolin against three different solid tumor cell lines was not solely p53-dependent","volume":"27","author":"Mahmoud","year":"2012","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.eujim.2018.10.005","article-title":"Anti-inflammatory activity of Kleinia odora","volume":"23","author":"Shehata","year":"2018","journal-title":"Eur. J. Integr. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1080\/13880209.2016.1190381","article-title":"In vivo anti-inflammatory activity of caffeoylquinic acid derivatives from Solidago virgaurea in rats","volume":"54","author":"Motaal","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s10787-011-0086-4","article-title":"Anti-inflammatory and analgesic activity of protocatechuic acid in rats and mice","volume":"19","author":"Lende","year":"2011","journal-title":"Inflammopharmacology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1248\/bpb.29.2236","article-title":"Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid","volume":"29","author":"Almeida","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4255\/mcpharmacol.09.05","article-title":"Anti-Inflammatory agents for cancer therapy","volume":"1","author":"Rayburn","year":"2009","journal-title":"Mol. Cell Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"768","DOI":"10.2174\/1871520611313050011","article-title":"Antiproliferative activities on renal, prostate and melanoma cancer cell lines of Sarcopoterium spinosum aerial parts and its major constituent tormentic acid","volume":"13","author":"Loizzo","year":"2013","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/BF01234480","article-title":"A new approach to practical acute toxicity testing","volume":"54","author":"Lorke","year":"1983","journal-title":"Arch. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3181\/00379727-111-27849","article-title":"Carrageenan-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs","volume":"111","author":"Winter","year":"1962","journal-title":"Proc. Soc. Exp. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Alahdal, A.M., Asfour, H.Z., Ahmed, S.A., Noor, A.O., Al-Abd, A.M., Elfaky, M.A., and Elhady, S.S. (2018). Anti-helicobacter, antitubercular and cytotoxic activities of Scalaranes from the Red Sea Sponge Hyrtios erectus. Molecules, 23.","DOI":"10.3390\/molecules23040978"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/2\/418\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:29:53Z","timestamp":1760362193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/2\/418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,20]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["molecules25020418"],"URL":"https:\/\/doi.org\/10.3390\/molecules25020418","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,20]]}}}