## 2 Biological Activities of Monoterpenes
### Acyclic Monoterpenes
Citronellal (**1a**, Figure 3), a prominent constituent of essential oils, has been reported to display anticancer and antioxidant properties [23]. In addition, citronellal was identified as a promising agent against triple negative breast cancer cell lines. [PERSON] showed that a crude extracts of _Citrus lustris_ DC, citronellol, and citronellal significantly reduced cell proliferation and migration by inducing cell cycle arrest in the MDA-MB-231 cell line [23]. The IC\({}_{50}\) values of the aforementioned extracts were in the millimolar range while those of compounds citronellol and citronellal were 1.16 and 1.41 nM respectively. However, the cytotoxicity of these compounds on normal tissue is of concern as the IC\({}_{50}\) values of citronellol and citronellal were shown to be 1.96 and 1.81 nM respectively when tested against human monocyte derived macrophages. Independent antiproliferative studies of citronellal using Sulforhodamine B (SRB), MTT, and NRU (neutral red uptake) antiproliferative assays indicate its potential against a triple-negative breast cancer cell model (MDA-MB-231) [24]. The study also conducted in vitro experiments to evaluate citronellal's activity against LOX-5 (arachidonate 5-lipoxygenase), finding the IC\({}_{50}\) value to be in the low micromolar range [24]. Furthermore, the compounds efficacy was evaluated using the Ehrlich Ascites Carcinoma (EAC) model where it was found to inhibit tumor cell growth by 46% at 75 mg/kg, well below the lethal dose of 1000 mg/kg [25]. The anti-inflammatory and redox-protective effects of citronellal, indicated by in vitro and in vivo methods were also reported using leukocyte injected mouse models and carrageenan rat models [25]. The redox protective effects were demonstrated by reduced hepatic lipoperoxidation, as well as oxidation of certain protein. citronellal administration via intraperitoneal route was able to inhibit the carrageenan and arachidonic acid- induced rat hind paw edema models (popular methods for evaluation of anti-inflammatory activity of lipoxygenase inhibitors) [25]. citronellol (**1b**, Figure 3) has demonstrated notable anticancer properties as well as citronellol-containing essential oils have been reported to display anticancer potential in cell models [21; 26]. Geranic acid (**2e**, Figure 3) isolated from _Thymus \(\times\)citridorus_ was recently identified as an anti-inflammatory agent [27]. It is worth noting that in some instances of treatment the required concentrations to elicit a favorable biochemical response proved cytotoxic. While the findings of this study are promising, further work is required prior to the use of the relevant compounds as potential therapeutic agents. Geraniol (**2b**, Figure 3) has been identified as a main bioactive component in essential oils and validated as a pure compound. Geraniol is a major component of Palmarosa, lemon grass, and rose essential oils which have been documented for their beneficial attributes. Geraniol has been shown to protect against cyclophosphamide-induced hepatotoxicity in rat models by modulating expression levels of NFK-\(\beta\), PPAR\(\gamma\), inducible nitric oxide synthase, and cyclo-oxygenase 2 [28]. Cyclophosphamide is a chemotherapeutic agent with liabilities due to its hepatotoxicity so identification of compounds that can prevent this unfavorable effect are highly desirable. Dosing of rats was done at a concentration of 25 mg/kg once daily one hour after their respective treatments of corn oil (vehicle), or geraniol (100 and 200 mg/kg). The groups treated with geraniol showed lowered expression levels of IL-1\(\beta\), TNF-\(\alpha\), MDA and other hepatotoxicity markers. The only enzymes shown to be upregulated when treated with geraniol were GSH, and PPAR\(\gamma\). The data shows the promising ability of geraniol to curb some negative side effects caused by the treatment of patients with this effective and well-documented cancer drug.