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.
Tea Tree Oil/therapeutic use* ; Melaleuca ; Neuroprotection ; Drug Repositioning ; Neuroinflammatory Diseases ; Australia ; Oils, Volatile ; Anti-Inflammatory Agents/pharmacology*

The purpose of this study was to evaluate the relation between ocular discomfort and ocular Demodex infestation, and therapeutic effects of tea tree oil (TTO) in Demodex blepharitis patients. Three hundred and thirty-five patients with ocular discomfort were evaluated for ocular Demodex infestation and subjective symptoms with ocular surface discomfort index (OSDI) score. Among them, Demodex-infested patients were randomized to receive either eyelid scrubbing with TTO (TTO group,106 patients) or without TTO (Control group, 54 patients) for 1 month. Demodex were found in 84% of patients with ocular discomfort. The number of Demodex was significantly correlated with age (P = 0.04) and OSDI score (P = 0.024). After eyelid scrub treatment, Demodex count was reduced from 4.0 +/- 2.5 to 3.2 +/- 2.3 in the TTO group (P = 0.004) and from 4.3 +/- 2.7 to 4.2 +/- 2.5 in the control group (P = 0.27). Also, OSDI score was reduced from 34.5 +/- 10.7 to 24.1 +/- 11.9 in the TTO group (P = 0.001) and from 35.3 +/- 11.6 to 27.5 +/- 12.8 in the control group (P = 0.04). In conclusion, Demodex number showed a significant positive correlation with age and subjective ocular discomfort. The tea tree oil eyelid scrub treatment is effective for eliminating ocular Demodex and improving subjective ocular symptoms.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Animals ; Anti-Infective Agents, Local/pharmacology/therapeutic use ; Blepharitis/*drug therapy/pathology ; Eye Infections, Parasitic/*drug therapy/parasitology/pathology ; Eyelids/parasitology/pathology ; Female ; Humans ; Male ; Middle Aged ; Mite Infestations/*drug therapy/parasitology/pathology ; Mites/drug effects ; Phytotherapy ; Tea Tree Oil/pharmacology/*therapeutic use ; Young Adult

The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1beta, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1beta in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1beta and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.
Acari/drug effects/physiology ; Adolescent ; Adult ; Aged ; Animals ; Blepharitis/drug therapy/*immunology/parasitology ; Chemokine CCL4/analysis ; Female ; Granulocyte Colony-Stimulating Factor/analysis ; Humans ; Interleukin-12/analysis ; Interleukin-13/analysis ; Interleukin-17/analysis ; Interleukin-1beta/analysis ; Interleukin-5/analysis ; Interleukin-7/analysis ; Male ; Middle Aged ; Tea Tree Oil/therapeutic use ; Tears/metabolism