{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:28:08Z","timestamp":1789756088247,"version":"4.0.1"},"reference-count":96,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T00:00:00Z","timestamp":1726876800000},"content-version":"vor","delay-in-days":264,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019305","name":"Manipal Academy of Higher Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019305","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["3\/1\/2\/149\/Neuro\/2021-NCD-I"],"award-info":[{"award-number":["3\/1\/2\/149\/Neuro\/2021-NCD-I"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Sickness behaviour, a set of behavioural changes associated with neuroinflammation, is expressed as decreased mobility and depressed behaviour. Activation of AMP\u2010activated protein kinase (AMPK) is reported to regulate inflammation in conditions such as Alzheimer and traumatic brain injury. Metformin, an antidiabetic agent acting via AMPK activation, possesses anti\u2010inflammatory properties. Similarly, the reported anti\u2010inflammatory activities of berberine could be partially attributed to its ability to activate AMPK. In this study, we investigated the effects of metformin and berberine against lipopolysaccharide (LPS)\u2010induced sickness\u2010like behaviour, associated with neuroinflammation, impaired cognition, and oxidative stress. Swiss albino mice were divided into four groups, normal control, LPS control, metformin treatment, and berberine treatment. The control groups received saline for 7\u2009days. Groups 3 and 4 received metformin (200\u2009mg\/kg) and berberine (100\u2009mg\/kg), respectively, orally once daily for 7\u2009days. On day 7, 1\u2009h after the treatments, animals received LPS (1.5\u2009mg\/kg i.p.) to induce sickness\u2010like behaviour. Open field test (OFT) and forced swim test (FST), were performed within 2\u2009h of LPS administration. Then, proinflammatory cytokines (IL\u20101<jats:italic>\u03b2<\/jats:italic> and TNF\u2010<jats:italic>\u03b1<\/jats:italic>), acetylcholinesterase activity (AChE), and oxidative stress markers were estimated in the brain homogenate. In the LPS control group, immobility state, proinflammatory cytokines, AChE, and lipid peroxidation were significantly increased, whereas the glutathione levels were decreased. Pretreatment with metformin significantly improved immobility in the FST, with reduced IL\u20101<jats:italic>\u03b2<\/jats:italic>, oxidative stress markers, and AChE activity. However, no significant changes were observed in OFT. Berberine pretreatment exhibited only an apparent, statistically insignificant, improvement in sickness\u2010like behaviour assessed using FST and OFT, cytokine levels, oxidative markers, and AChE. Several factors affect treatment efficacy, such as treatment duration and administered dose. Considering these, berberine warrants elaborate preclinical evaluation for neuroinflammation. Nevertheless, based on the effects observed, AMPK activators could regulate neuroinflammation, cognition, and oxidative stress linked with sickness\u2010like behaviour.<\/jats:p>","DOI":"10.1155\/2024\/8599268","type":"journal-article","created":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T11:05:37Z","timestamp":1726916737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide\u2010Induced Sickness\u2010Like Behaviour in Mice"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7051-809X","authenticated-orcid":false,"given":"Triveni","family":"Kodi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4076-0186","authenticated-orcid":false,"given":"Sharanya","family":"Praveen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-5875","authenticated-orcid":false,"given":"Sravan Kumar","family":"Paka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-2856","authenticated-orcid":false,"given":"Runali","family":"Sankhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-3722","authenticated-orcid":false,"given":"Adarsh","family":"Gopinathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6653-4660","authenticated-orcid":false,"given":"Nandakumar","family":"Krishnadas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8116-8408","authenticated-orcid":false,"given":"Anoop","family":"Kishore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,21]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/271359"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.08.014"},{"key":"e_1_2_9_3_2","first-page":"227","article-title":"Childhood maltreatment and adult proinflammatory status in patients with major depression","volume":"25","author":"Zeugmann S.","year":"2013","journal-title":"Psychiatria Danubina"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2297"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0149-7634(88)80004-6"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169446"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.08.044"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2013.06.008"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2016.07.004"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0031-9384(00)00269-9"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2009.02.002"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.03.010"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4761-z"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4002148"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11862"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.08.013"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.3233\/jpd-171296"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m114.577908"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2018.0061"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.2174\/138955708786369546"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0982"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2012.696609"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.11124\/jbisrir-2017-003380"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.2174\/1872214810999160628105549"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x13666150205143555"},{"key":"e_1_2_9_26_2","first-page":"11479","article-title":"Metformin regulates of Th17\/treg cell balance and reduces hyperplastic synovium via activating AMPK and inhibiting mTOR in a collagen-induced arthritis rat model","volume":"10","author":"Yang M.","year":"2017","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12265"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.32604\/biocell.2022.020865"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.14740\/jocmr2922e"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.05.043"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02744-7"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8546-3-10"},{"key":"e_1_2_9_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2470-8"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5116"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2012.03.004"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.1139\/y09-136"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf071868c"},{"key":"e_1_2_9_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.01.022"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2399"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2968"},{"key":"e_1_2_9_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105439"},{"key":"e_1_2_9_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0049-3848(02)00133-0"},{"key":"e_1_2_9_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-8741(98)00162-7"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-005-9003-4"},{"key":"e_1_2_9_45_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90599.2008"},{"key":"e_1_2_9_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-019-00638-w"},{"key":"e_1_2_9_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(90)90131-2"},{"key":"e_1_2_9_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(79)90289-7"},{"key":"e_1_2_9_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0076-6879(84)05016-3"},{"key":"e_1_2_9_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(61)90145-9"},{"key":"e_1_2_9_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-016-0376-5"},{"key":"e_1_2_9_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(92)90012-u"},{"key":"e_1_2_9_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020719"},{"key":"e_1_2_9_54_2","doi-asserted-by":"publisher","DOI":"10.1006\/brbi.1996.0019"},{"key":"e_1_2_9_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-200"},{"key":"e_1_2_9_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-017-0409-1"},{"key":"e_1_2_9_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2013.06.004"},{"key":"e_1_2_9_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri910"},{"key":"e_1_2_9_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6160"},{"key":"e_1_2_9_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24062"},{"key":"e_1_2_9_61_2","doi-asserted-by":"publisher","DOI":"10.1159\/000444187"},{"key":"e_1_2_9_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0889-1591(02)00077-6"},{"key":"e_1_2_9_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2008.11.041"},{"key":"e_1_2_9_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2019.577049"},{"key":"e_1_2_9_65_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1117638"},{"key":"e_1_2_9_66_2","doi-asserted-by":"publisher","DOI":"10.3233\/jad-2004-6206"},{"key":"e_1_2_9_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2017.09.050"},{"key":"e_1_2_9_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0964-9"},{"key":"e_1_2_9_69_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175481"},{"key":"e_1_2_9_70_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.8674"},{"key":"e_1_2_9_71_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-018-0349-5"},{"key":"e_1_2_9_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.08.003"},{"key":"e_1_2_9_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.12.143"},{"key":"e_1_2_9_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2007.03.005"},{"key":"e_1_2_9_75_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology9110359"},{"key":"e_1_2_9_76_2","doi-asserted-by":"publisher","DOI":"10.1097\/wnr.0000000000001401"},{"key":"e_1_2_9_77_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-021-00678-5"},{"key":"e_1_2_9_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110808"},{"key":"e_1_2_9_79_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-022-00992-9"},{"key":"e_1_2_9_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113475"},{"key":"e_1_2_9_81_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m115.662114"},{"key":"e_1_2_9_82_2","doi-asserted-by":"publisher","DOI":"10.3109\/13880209.2013.840851"},{"key":"e_1_2_9_83_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26164733"},{"key":"e_1_2_9_84_2","first-page":"1474","article-title":"Effects of berberine on serum levels of inflammatory factors and inflammatory signaling pathway in obese mice induced by high fat diet","volume":"35","author":"Shang W.","year":"2010","journal-title":"Zhongguo Zhongyao Zazhi"},{"key":"e_1_2_9_85_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-7-78"},{"key":"e_1_2_9_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2010.02.005"},{"key":"e_1_2_9_87_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42286-8"},{"key":"e_1_2_9_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2005.05.003"},{"key":"e_1_2_9_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(96)00233-x"},{"key":"e_1_2_9_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.10.014"},{"key":"e_1_2_9_91_2","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-020-00095-1"},{"key":"e_1_2_9_92_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-017-0147-5"},{"key":"e_1_2_9_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.03.001"},{"key":"e_1_2_9_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.04.041"},{"key":"e_1_2_9_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.10.043"},{"key":"e_1_2_9_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2020.129073"}],"container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2024\/8599268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T11:05:40Z","timestamp":1726916740000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2024\/8599268"}},"subtitle":[],"editor":[{"given":"Mozaniel","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":96,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1155\/2024\/8599268"],"URL":"https:\/\/doi.org\/10.1155\/2024\/8599268","archive":["Portico"],"relation":{},"ISSN":["2633-4682","2633-4690"],"issn-type":[{"value":"2633-4682","type":"print"},{"value":"2633-4690","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2024-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"8599268"}}