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Among experimental paradigms, lipopolysaccharide (LPS) provides a stimulus for probing inflammatory signalling and for evaluation of phytochemicals. However, heterogeneity in LPS provenance, chemotype, purification grade, dose, route, exposure duration and endpoint timing compromises cross-study comparability, mechanistic attribution and translational interpretation. This review synthesises evidence from in vitro and in vivo LPS-induced neuroinflammation models used for phytochemical screening and proposes a kinetics- and mechanism-informed framework for experimental design. In vitro, murine microglial systems predominate, particularly BV-2, N9 and primary microglia, with complementary use of astroglia, neuronal and human myeloid or microglia-like platforms. LPS concentrations range from 100 ng\/mL to 1\u00a0\u00b5g\/mL, with signalling activation occurring within minutes to hours and inflammatory phenotypes typically assessed at 24\u201348\u00a0h. Frequently used pharmacodynamic readouts include tumour necrosis factor-\u03b1, interleukin-1\u03b2, interleukin-6, inducible nitric oxide synthase\/nitric oxide, cyclooxygenase-2\/prostaglandin E2, reactive oxygen species, glial activation markers and viability indices, combined with mechanistic interrogation of NF-\u03baB, MAPK, PI3K\u2013Akt, Nrf2\u2013HO-1 and NLRP3-associated pathways. In vivo, repeated intraperitoneal LPS administration predominates in rodent models, whereas intracerebroventricular and zebrafish models provide complementary spatial and kinetic insights. Overall, LPS challenge should be interpreted as a controlled inflammatory trigger rather than a disease-equivalent surrogate. Rigorous LPS reporting, closer alignment of endpoints with inflammatory kinetics, and multi-endpoint validation across models should strengthen mechanistic inference and support translational evaluation of phytochemical leads.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>Kinetics and mechanism informed framework for phytochemical screening in LPS-induced neuroinflammation. Created in BioRender. Zhou, P. (2026) https:\/\/BioRender.com\/8jznpa5.<\/jats:p>","DOI":"10.1007\/s11033-026-12817-4","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:38:23Z","timestamp":1791434303000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kinetics and mechanisms in lipopolysaccharide-induced neuroinflammation: a framework for phytochemicals screening"],"prefix":"10.1007","volume":"53","author":[{"given":"Muhammad Mazhar","family":"Munir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"1","key":"12817_CR1","doi-asserted-by":"publisher","first-page":"5790","DOI":"10.1038\/s41598-019-42286-8","volume":"9","author":"J Zhao","year":"2019","unstructured":"Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J, Lu D, Wei W, Wang Y, Li H, Fu Y, Zhu L (2019) Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. 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