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Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper\u2010production of pro\u2010inflammatory mediators such as interleukin (IL)\u20101\u03b2, IL\u20106, tumor\u2010necrosis factor (TNF)\u2010\u03b1, and high\u2010mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro\u2010inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well\u2010known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti\u2010inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life\u2010threatening complications, such as multi\u2010organ failure.<\/jats:p>","DOI":"10.1002\/biof.1694","type":"journal-article","created":{"date-parts":[[2020,11,21]],"date-time":"2020-11-21T08:38:01Z","timestamp":1605947881000},"page":"19-40","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3236-1970","authenticated-orcid":false,"given":"Babak","family":"Alikiaii","sequence":"first","affiliation":[{"name":"Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences  Isfahan 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