摘要Over the past few decades,complementary and alternative treatments have become increasingly popular worldwide.The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage.One such product is tea tree oil(TTO),a volatile essential oil primarily obtained from the native Australian plant,Melaleuca alternifolia,which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections.Its anti-inflammatory-linked immunomodulatory actions have also been reported.This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential.An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases,such as Web of Science,Google Scholar,PubMed,ScienceDirect,Scopus,and esteemed publishers such as Elsevier,Springer,Frontiers,and Taylor&Francis.Considering that the majority of pharmacological studies were conducted on crude oils only,the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement.In addition,the active constituents contributing to the activity of TTO have not been well justified,and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection.Therefore,this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.