Table 4.

A summary of pharmacological and biological activities of nerolidol.

Bioactivity	Type of Nerolidol	Plant and Part of Plant Used (If Any)	Target Organism(s)	Screening Assay and Methods Used	Results	Possible Mechanisms of Action	Ref.
Antioxidant activity	cis-Nerolidol (Aldrich Chemical Co., Milwaukee, WI, USA)	-	-	DPPH and hydroxyl radical scavenging activity	(i) Exhibited DPPH radical scavenging activity	Mediates antioxidant activities via free radical scavenging activity	[73]
					(ii) Exhibited scavenging activity against hydroxyl radical with IC50 = 1.48 mM
	cis-Nerolidol (Sigma-Aldrich, St. Louis, MO, USA)	-	-	Thiobarbituric acid reactive substances (TBARS) assay	(i) Demonstrated 25.60% ± 0.98% malonaldehyde (MDA) reduction in hepatocytes at 1 mM under physiological conditions	Mediates antioxidant activity via lipid peroxidation inhibitory effect	[74]
					(ii) Demonstrated higher MDA reduction with value of 36.50% ± 4.47% at 1 mM in hepatocytes under oxidative stress induced by tert-BuOOH
	Mixture of cis- and trans-nerolidol (Sigma Chemical Company, St. Louis, MO, USA)	-	-	TBARS assay, nitrite assay, superoxide dismutase (SOD) activity and catalase activity	(i) At doses of 25, 50 and 75 mg/kg of nerolidol caused a significant decrease in lipid peroxidation by 59.97%, 74.79% and 91.31% respectively when compared to negative control	(i) Suggested to prevent oxidation of polyunsaturated fatty acids
					(ii) At doses of 25, 50 and 75 mg/kg of nerolidol caused a significant decrease in nitrite level by 71.1%, 66.6% and 63.35 % respectively when compared to negative control
					(iii) At doses of 25, 50 and 75 mg/kg of nerolidol increased superoxide dismutase activity by 31.1%, 34.8% and 66.1%, respectively when compared to negative control	(ii) Suggested to inactivate the enzyme nitric oxide synthase	[75]
					(iv) At doses of 25, 50 and 75 mg/kg of nerolidol increased catalase enzymatic activity by 109%, 148% and 177.7%, respectively when compared to negative control
Antibacterial activity	Mixture of cis- and trans-nerolidol (Sigma Chemical Company, St. Louis, MO, USA)	-	Staphylococcus aureus FDA 209P, 14 strains of methicillin-susceptible S. aureus (MSSA) and 20 strains of methicillin-resistant S. aureus (MRSA)	Broth-dilution with shaking method (BDS)	Exhibited dose-related inhibition against 34 clinical isolates of S. aureus. Inhibitory dose 50% (ID50) ranged from 5.0 to 22.0 μg/mL and from 2.6 to 10.6 μg/mL against MSSA and MRSA respectively.	Suggested the aliphatic chain of nerolidol mediates the antibacterial activity by damaging the bacterial cell membrane	[76]
	Mixture of cis- and trans-nerolidol (Sigma Chemical Company, (St. Louis, MO, USA)	-	Staphylococcus aureus FDA209P	Broth dilution with shaking (BDS) method and quantitation of the leakage of K+ ions using K+-selective electrode	Treatment of nerolidol caused a dose-dependent increase in amount of K+ ions leakage from bacterial cells.	Mediates the antibacterial activity via cell membrane-distrupting mechanism and hence resulting in the leakage of K+ ions from bacterial cells	[77]
	Mixture of cis- and trans-nerolidol (Sigma Chemical Company, St. Louis, MO, USA)	-	Staphylococcus aureus FDA209P	Broth dilution with shaking (BDS) method and quantitation of the leakage of K+ ions using K+-selective electrode	(i) Caused a dose-dependent increase in K+ ions leakage from bacterial cells		[78]
					(ii) Exhibited minimum inhibitory concentration at 40 μg/mL
	trans-Nerolidol	Momordica charantia L., seed	Staphylococcus aureus ATCC 6538	Broth microdilution method (MIC)	(i) Exhibited anti-microbial activity with MIC ranged from 125–500 μg/mL.	-	[7]
	Nerolidol (n.s.)	Camellia sinensis (L.) Kuntze, leaves	Staphylococcus aureus and Streptococcus mutans	Broth dilution method	Exhibited antibacterial activity against S. aureus and S. mutans with MIC measured at 200 and 25 μg/mL respectively	-	[79]
	Nerolidol (n.s.)	Ginkgo biloba L., leaves	Salmonella enterica, Staphylococcus aureus and Aspergillus niger	Disc-diffusion and broth dilution methods	(i) Exhibited antibacterial activity against S. enterica, S. aureus and A. niger with MIC, MBC and MFC values measured ranging from 3.9–15.6 μg/mL, 31.3–62.5 μg/mL and 62.5 μg/mL respectively.	-	[31]
	cis-Nerolidol and the racemic mixture of cis- and trans-nerolidol (Aldrich Chemical Co., Milwaukee, WI, USA)	-	Escherichia coli and Staphylococcus aureus	Agar-disc diffusion assay	Nerolidol (cis-nerolidol and the racemic mixture of cis- and trans-isomers) potentiated the action of antibiotics:	-	[80]
					(i) amoxicillin/clavulanic acid against S. aureus and
					(ii) amoxicilline/clavulanic acid, ceftadizine and imipenem against E. coli
	Nerolidol (n.s.) (Sigma, St. Louis, MO, USA)		Escherichia coli ATCC 25922 and Staphylococcus aureus	Disc-diffusion assay	(i) Nerolidol concentrations ranged from 0.5 to 2 mM enhanced the susceptibility of S. aureus to ciprofloxacin, clindamycin, erythromycin, gentamicin, tetracycline, and vancomycin	-	[81]
					(ii) Nerolidol (1 mM) enhanced the susceptibility of E. coli to polymyxin B
	Racemic mixture of cis- and trans-nerolidol (1:1) (Aldrich, Madrid, Spain)	-	Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923	Antibiotic disc assay	Nerolidol (20 mM) potentiated the susceptibility of E. coli and S. aureus towards ciprofloxacin, erythromycin, gentamicin and vancomycin	-	[82]
Anti-biofilm activity	Mixture of cis- and trans-nerolidol	Black pepper, cananga, and myrrh EOs (Berjé (Bloomfield, NJ, USA), Jin Aromatics (Anyang, Gyeonggi Province, Korea) and Sigma-Aldrich (St. Louis, USA))	Staphylococcus aureus	Crystal violet biofilm assay	Cis-nerolidol at 0.01% (v/v) inhibited S. aureus biofilm formation by > 80 %; trans-nerolidol at similar concentration exerted 45% inhibition	-	[45]
	trans-Nerolidol	Piper claussenianum (Miq.) C. DC., leaves	Candida albicans	MTT assay	Concentrations of 0.06%–1.0% inhibited biofilm formation by 30% and 50% after 24 and 48 h incubation respectively	-	[32]
	cis,trans-Nerolidol and cis-nerolidol (Sigma Aldrich)	-	Candida albicans	MTT assay	1.0% of cis,trans-nerolidol exerted 76.1% reduction in the viability of pre-formed biofilm while only 67.0% reduction observed from 1.0% cis-nerolidol	-	[32]
Anti-fungal activity	Nerolidol (n.s.)	Chamaecyparis obtusa (Siebold & Zucc.) Endl. (Japanese cypress)	Microsporum gypseum	Broth microdilution method Skin lesion scoring in guinea pig model	(i) Exhibited MIC concentrations of 0.5%–2% against M. gypseum	-	[83]
					(ii) Nerolidol-treated group exhibited a significant improvement (p < 0.05) in lesion as compared to eugenol and econazole (positive control) treated groups
	trans-Nerolidol	Piper claussenianum (Miq.) C. DC., Piperaceae, leaves	Candida albicans	Broth microdilution and trypan blue exclusion method	(i) Exhibited anti-fungal activity with MIC values ranging from 0.24% to 1.26%.	-	[32]
					(ii) Exhibited inhibitory effect on yeast-to-hyphae transition by 81%
	Nerolidol (n.s.) (Sigma-Aldrich, Yongin, Korea)	-	Trichophyton mentagrophytes	Agar dilution method	Inhibited the hyphal growth of T. mentagrophytes at the concentration of 0.4 mg/mL.	-	[16]
	Nerolidol (n.s.)	Camellia sinensis (L.) Kuntze, leaves		Broth dilution method	Inhibited the growth of T. mentagrophytes at 12.5 μg/mL	-	[79]
	trans-Nerolidol	Lantana radula Sw., leaves	Corynespora cassiicola	Poison food (PF) technique	(i) L. radula EO at the concentration of 1000 mg/L and 3000 mg/L inhibited the growth of C. cassiicola by 17.2% and 40.6% respectively	-	[33]
					(ii) L. radula EO at the concentration of 5000 mg/L and 10,000 mg/L completely inhibited the growth of C. cassiicola
	trans-Nerolidol	Piper chaba Hunter, leaves	Fusarium oxysporum, Phytophthora capsici, Colletotrichum capsici, Fusarium solani and Rhizoctonia solani	Spore germination assay and agar dilution method	Caused 55.1%–70.3% growth inhibition at concentration ranging from 125 to 500 µg/mL.	-	[34]
	trans-Nerolidol	Warionia saharae ex Benth. & Coss., aerial part	Alternaria sp., Penicillium expansum and Rhizopus stolonifer	Poisoned food (PF) technique and volatile activity (VA) assay	Inhibited the fungal spore production of Alternaria sp., P. expansum and R. stolonifera at 1, 2 and 2 µL/mL air respectively	-	[26]
	Nerolidol	Allium sativum L., bulb	Sclerotium cepivorum	Disc diffusion method; scanning electron microscopy	(i) Nerolidol ranged from 2.0 to 5.0 µg/disc displayed fungistatic property by inhibiting mycelial growth by ~85%	-	[84]
					(ii) Nerolidol ranged from 2.0 to 5.0 µg/disc inhibited the production of sclerotial by ~84%
					(ii) Nerolidol at 4.0 µg/disc caused morphological alterations such as shorter branching, hyphal shrinkage and partial distortion
Anti-trypanosomal activity	trans-Nerolidol	Strychnos spinosa Lam., leaves	Trypanosoma brucei	Alamar Blue™ assay.	Exhibited anti-trypanosomal activity with IC50 measured at 1.7 µg/mL (7.6 µM)	-	[35]
	cis-Nerolidol	Leonotis ocymifolia (Burm.f.) Iwarsson, aerial part		Trypanocidal and cytotoxic assays	Exhibited anti-trypanosomal activity with IC50 measured at 15.78 µg/mL	-	[27]
	Mixture of ±40% cis-nerolidol and ±55% of trans-nerolidol (Merck, Darmstadt, Germany)	-	Trypanosoma evansi	Collection of blood samples from T. evansi-infected mice for observation using light and electron microscopes	(i) Adverse morphological changes observed in nerolidol-treated group. The parasites lost their undulating membrane after 23 day post-treatment.	-	[85]
					(ii) Total disfigurement observed after 27 day post-treatment
Anti-leishmanial activity	A mixture of cis- and trans-nerolidol	-	Leishmania (L.) amazonensis, L. braziliensis, and L. chagasi	MTT assay and metabolic labeling with [2-14C] mevalonic acid, [1-14C] acetic acid, [1(n)-3H] farnesyl pyrophosphate and l-[35S]methionine	(i) Inhibited the growth of L. amazonensis, L. braziliensis and L. chagasi promastigotes, and L. amazonensis amastigotes with IC50 of 85, 74, 75, and 67 µM respectively	Inhibition of the isoprenoid biosynthesis pathway	[86]
					(ii) Nerolidol at 100 µM reduced the percentage of intracellular parasitism of L. amazonensis by 95% from the pre-infected macrophages culture
	trans-Nerolidol	Baccharis dracunculifolia DC., leaves	Leishmania donovani	Parasite lactate dehydrogenase (pLDH) assay, antileishmanial assay, schistosomicidal assay and cytotoxicity assay using the mammalian cells Vero.	Exhibited anti-leishmanial activity against promastigotes of L. donovani with IC50 and IC90 values of 42 and 85 µg/mL respectively.	-	[8]
	Nerolidol	Piper claussenianum (Miq.) C. DC., Piperaceae, leaves	Leishmania amazonensis	Protozoal arginase activity, nitrite determination and cytotoxicity assay using L929 fibroblast cells (mouse) and Raw cells (mouse macrophages)	(i) Nerolidol inhibited the arginase activity by 62.17% in the promastigotes of Leishmania amazonensis	Interferes with parasite-host cell interaction	[9]
					(ii) Nerolidol caused an increase in NO production (20.5%)
	Nerolidol (n.s.) (Acros Organics, Geel, Belgium)	-	Promastigotes of Leishmania amazonensis	Anti-proliferative activity assay and electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid	Nerolidol modulated the molecular dynamics of the lipid component in the Leishmania plasma membrane	Insertion of nerolidol into the lipid bilayer increased the fluidity of membranes, thus causing leakage of cytoplasmic content and eventually the death of Leishmania cells	[87]
Anti-schistosomal activity	Nerolidol (n.s.)	Baccharis dracunculifolia DC. (Asteraceae), leaves	Schistosoma mansoni	Schistosomicidal assay	100% mortality of S. mansoni adult worms after 24 h incubation with 10 to 100 mg/mL of EO containing nerolidol as the main constituent	-	[8]
	Racemic mixture of cis- and trans-nerolidol (1:1) (Sigma-Aldrich, St. Louis, MO, USA)	-		In vitro anti-schistosomal assay and microscopy studies	Exhibited anti-schistosomal activity by reducing worm motor activity and caused 100% mortality of male and female schistosomes at concentration of 31.2 and 62.5 µM respectively	(i) Induced severe tegumental damage in adult schistosomes.	[88]
						(ii) Caused alterations on the tubercles of male parasites
Anti-malarial activity	Nerolidol (n.s.)	Virola surinamensis (Rol. ex Rottb.) Warb., leaves	Plasmodium falciparum	In vitro anti-plasmodial assay	Treatment with 100 µg/mL of nerolidol caused 100% inhibition in the development of young trophozoite to the schizont stage after 48 h	-	[29]
	trans-Nerolidol	Piper claussenianum (Miq.) C. DC., leaves			Exerted anti-malarial activity with IC50 of 11.1 μg/mL	-	[89]
	Nerolidol (n.s.) (Sigma, St. Louis, MO, USA)	-		Immunoprecipitation assays and metabolic labeling	Exhibited inhibitory activity on the biosynthesis of the isoprenic side chain of the benzoquinone ring in ubiquinones during the schizont stage	Interferes with the elongation of isoprenic chains via inhibition of isoprenyl diphosphate synthases	[90]
	Nerolidol (n.s.) (Sigma, St. Louis, MO, USA)	-			Nerolidol at 50 nM inhibited the synthesis of the isoprenic chain attached to coenzyme Q at all intraerythrocytic stages	-	[91]
	Nerolidol (n.s.)	-		Isobolographic analysis	Nerolidol mediated supra-additive (the sum of the fractions of IC50 of < 1) interaction with fosmidomycin and squalestatin with average IC50 values of 0.57 and 0.62 µM, respectively in the inhibition of plasmodial isoprenoid pathway	-	[92]
Other anti-parasite activities	Mixture of cis- and trans-nerolidol (Sigma-Aldrich, St. Louis, MO, USA)	-	Four Babesia species (B. bovis, B. bigemina, B. ovata, and B. caballi)	In vitro growth inhibition assay	Inhibited in vitro growth of B. bovis, B. bigemina, B. ovata, and B. caballi with IC50 values of 21 ± 1, 29.6 ± 3, 26.9 ± 2, and 23.1 ± 1 µM respectively	Inhibits the isoprenoid biosynthesis pathway in a similar mechanism with that of P. falciparum	[93]
	Mixture of cis- and trans-nerolidol (Sigma Chemical Company, St. Louis, MO, USA)	-	Caenorhabditis elegans	Mortality assay against Caenorhabditis elegans	Caused 74.0% mortality of C. elegans at 50 µg/mL	-	[94]
	Nerolidol (n.s.)	-	L3 larvae of Anisakis	In vitro and in vivo larvicidal activity	(i) Nerolidol at both 31.5 and 62.5 µg/mL resulted in 100% mortality of L3 larvae of Anisakis type I after 4 h.	-	[95]
					(ii) Only 20% of nerolidol-treated rats were affected by gastric wall lesions caused by Anisakis larvae in comparison to 86% of the control rats
Insecticidal activity	trans-Nerolidol	Siam-wood (Fokienia hodginsii (Dunn) A.Henry & H H.Thomas), wood	Mosquito and house flies	House fly toxicity test	Exhibited insecticidal activity with LD50 measured at 0.17 µmol/fly	-	[51]
	Combination of nerolidol (n.s.) and linalool	Capparis tomentosa, leaves	Maize weevil (Sitophilus zeamais)	Repellency assay using a glass Y-tube Olfactometer	Exhibited mean repellency value of 58.23% ± 2.95% against S. zeamais at 2 µL	-	[30]
	Nerolidol (n.s.) (Moellhausen SpA,Vimercate, Milano, Italy)	Melaleuca alternifolia (Maiden & Betche) Cheel (tea tree oil)	Pediculus capitis (head lice) and its eggs	Pediculicidal and ovicidal activities	Nerolidol in combination with tea tree oil with ratio of 1:2 (tea tree oil 0.5% plus nerolidol 1%), exerted a total killing effect of lice within 30 min and abortive effect of louse eggs after 5 days.	-	[96]
	Nerolidol (n.s.)	Magnolia denudata Desr., seeds	Culex pipiens pallens, Aedes aegypti, Aedes albopictus and Anopheles sinensis	Direct-contact mortality bioassay	Exerted larvacidal activity against Culex pipiens pallens, Aedes aegypti, Aedes albopictus and Anopheles sinensis with LD50 value of 9.84, 13.85, 16.34 and 20.84 mg/L respectively	-	[47]
	trans-Nerolidol	Melaleuca quinquenervia (Cav.) S.T.Blake, leaves	Aedes aegypti	Larvicidal activity test	Exerted larvicidal activity with ≥ 95% and > 80% mortality of A. aegypti at 0.1 mg/mL and 0.05mg/mL respectively	-	[36]
		Piper aduncum L., leaves	Tetranychus urticae Koch	Fumigant, contact, repellency and two-choice assay	Exerted acaricidal activity with repellency value of 83.2% ± 0.59 % at 9.8 µg/mL	-	[37]
	Nerolidol (n.s.)	Baccharis dracunculifolia DC., leaves	Rhipicephalus microplus	Larval packet test (LPT) and engorged female immersion test	(i) Exerted acaricidal activity when concentration more than 5mg/mL and 100% mortality of larvae at 15 mg/mL	-	[97]
					(ii) Reduced the quality of the egg and larval hatching rate with increasing concentration from 20 to 50 mg/mL
Antiulcer activity	Nerolidol (n.s.)	Baccharis dracunculifolia DC., leaves	-	In vivo antiulcer activity in male Wistar rat ulcer models induced with ethanol, indomethacin and stress	Nerolidol displayed gastroprotective activity by inhibiting the formation of ulcers induced by all physical and chemical agents in dose-dependent manner (50, 250, 500 mg/kg)	-	[98]
Skin penetration enhancer activity	Nerolidol (n.s.) (Aldrich, Gillingham, UK)	-	-	In vitro diffusion studies and stratum corneum-water partitioning studies	Increased diffusion rate by over 20-fold for transdermal delivery of drugs such as 5-fluorouracil	Nerolidol exhibits a chemical structure that allows it to align within the lipid lamellae of the stratum corneum in order to disrupt the organization of stratum corneum	[99]
	Nerolidol (n.s.) (Alfa Aesar Ltd., Haverhill, MA, USA)	-	-	Solubility studies, ex vivo permeation studies and histopathological studies	The enhancement effect is increased with the increasing lipophilicity; the rank of order (nerolidol > farnesol > limonene > linalool > geraniol > carvone > fenchone > menthol) in facilitating transdermal delivery of alfuzosin hydrochloride		[100]
	Nerolidol (n.s.) (Merck-Schuchardt, Hohenbrunn, Germany)	-	-	In vitro permeation studies	Exhibited the highest permeation enhancing ability with a 3.2-fold increase in permeation of selegiline hydrochloride across the rat skin, followed by the effect of carvone (2.8-fold increase) and anethole (2.6-fold increase)	-	[101]
	Nerolidol (n.s.) (Aldrich Chemical Co. Milwaukee, WI, USA)	-	-	In vitro skin permeability studies	Most effective terpene enhancer for percutaneous permeation of four different drug models (nicardipine hydrochloride, hydrocortisone, carbamazepine, and tamoxifen) when compared to fenchone, thymol and limonene	-	[102]
Anti-nociceptive and anti-inflammatory activities	trans-Nerolidol	Peperomia serpens (Sw.) Loudon, leaves	-	(i) Chemical (acetic acid and formalin) and thermal (hot plate) models of nociception	trans-Nerolidol could be responsible for the anti-inflammatory and anti-nociceptive effects displayed by essential oils of both Peperomia serpens (Sw.) Loudon and Piper aleyreanum C. DC	-	[38]
				(ii) Carrageenan- and dextran-induced paw edema tests in rats croton oil-induced ear edema
				(iii) Cell migration, rolling and adhesion activities
	trans-Nerolidol	Piper aleyreanum C. DC, aerial parts	-	(i) Nociception induced by formalin		-	[10]
				(ii) Evaluation of locomotor activity
				(iii) Induction of acute gastric lesions
	Nerolidol (n.s.) (Sigma, St. Louis, MO, USA)	-	-	(i) Rotarod, acetic acid-induced writhing, formalin and hot-plate tests (ii) Involvement of ATP-sensitive opioid and GABAergic K+ channels (iii)Carrageenan-induced paw edema (iv) Analysis of leukocytes, tumor necrosis factor (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 in peritoneal lavage	(i) For acetic acid-induced writhing test, at the doses of 200, 300 and 400 mg/kg, nerolidol reduced the frequency of acetic acid-induced writhing at all three doses tested compared to the mice in the control group (55% ± 1.1%, 53% ± 4.5%, and 41% ± 2.4%, respectively) (ii) For formalin test, at the doses of 200, 300 and 400 mg/kg, nerolidol significantly inhibited licking time by 20% ± 3.3%, 33% ± 5.9% and 37% ± 4.8%, respectively when compared to the control mice. (iii) For hot-plate test, no increase in the reaction time to painful stimulation in the mice treated with nerolidol when compared to the control mice. (iv) Reduced leukocytes level by 51% ± 0.7%, 37% ± 0.5% and 57% ± 0.4% at doses of 200, 300 and 400 mg/kg respectively (v) Reduced the level of tumor necrosis factor (TNF-α) at doses of 300 (59.3% ± 30.2%) and 400 (62.2% ± 13.7%) in peritoneal lavage. (vi) IL-1β production was inhibited after treatment with nerolidol (1, 10, 50 and 100 µM) whereas IL-6 level was unchanged	(i) Anti-nociceptive activtity of nerolidol was indicated to be mediated by GABAA receptors, as the use of bicuculline, a GABAA antagonist inhibited the effect of nerolidol in reducing the paw licking times (ii) Anti-inflammatory activity of nerolidol was suggested to be mediated by inhibiting the production or the activity of pro-inflammatory cytokines such as TNF-α analgesic and IL-1β	[103]
Anti-cancer or anti-tumor activity	Nerolidol (a combination of cis-nerolidol 40.7%, trans-nerolidol 58.3%, cis-dihydronerolidol 0.4% and trans-dihydro-nerolidol) (Kurt Kitzing Co. Wallerstein, Germany)	-	-	Cytotoxicity assay on HeLa cell lines using CytoTox-96®-assay	Exhibited anticancer effect against HeLa cells with CC50 value at 1.5 ± 0.7 µM	-	[104]
	cis-Nerolidol (Charabot S.A. Grasse, France)	-	-	Cytotoxicity and cytoproliferative activity on HeLa cell lines using Cytotoxicity Detection Kit (LDH) and the Cell Proliferation Reagent WST-1, respectively	Exhibited cytotoxic effect (16.5 ± 6.7 μM) against HeLa cells	-	[105]
	Nerolidol (n.s.)	Camellia sinensis (L.) Kuntze, leaves	-	MTT assay	Exhibited cytotoxic effect with IC50 value of 2.96 and 3.02 µg/mL against BT-20 breast carcinoma and HeLa cells respectively	-	[106]
	trans-Nerolidol	Zornia brasiliensis Vogel, leaves	-	In vitro cytotoxic activity assay using Alamar blue assay, and in vivo antitumor activity assay	(i) trans-Nerolidol induced cytotoxic effect on B16-F10, HepG2, HL-60 and K562 cells with IC50 value of >25, >25, 21.99 and 17.58 µg/mL respectively	-	[39]
					(ii) The EO at dose of 100 mg/kg containing trans-nerolidol as major constituent reduced the weight of tumor in mice injected with B16-F10 melanoma by 38.61%
		Myrica rubra (Lour.) Siebold & Zucc., leaves	-	Neutral red uptake (NRU) test, MTT assay and 2′,7′-dichlorodihydrofluorescein-diacetate (H2DCF-DA) oxidation	Potentiated the action of doxorubicin, an anticancer drug in the modulation of CaCo-2 cancer cells	-	[40]
	Nerolidol (n.s.) (Sigma Aldrich Chemical Company)	-	-	In vivo anti-cancer study	(i) Reduction of incidence of intestinal neoplasia from 82% to 33% in rats fed with nerolidol	Modulation of nerolidol on protein prenylation which responsible for the formation of cancer	[107]
					(ii) Reduction of number of tumors/rat from 1.5 to 0.7 in rats fed with nerolidol
	Combination of farnesol and nerolidol (n.s.)	-	-	In vitro anti-cancer study	The combination suppressed the proliferation of human HL-60 acute promyelocytic leukemia (HL-60) cells by 20%. Meanwhile, farnesol isomers (2.5 µmol/L) and nerolidol (5 µmol/L) individually suppressed the proliferation of HL-60 cells by 4 and 9%, respectively	Nerolidol induced cell cycle arrest at the G0-G1/S interphase in HL-60 cells and eventually lead to apoptotic cell death	[108]
	trans-Nerolidol	Myrica rubra (Lour.) Siebold & Zucc., leaves	-	Cell adhesion and apoptosis luminescent assays	(i) Reduced adhesion of HT29 to collagen.	Nerolidol induced apoptosis in cancer cells	[109]
					(ii) Suppressed cell adhesion of HT29 cells in the presence TNFα cytokines
					(iii) Decreasing the phosphorylation of NF-κB and increased the activity of caspases

Key: n.s. = not specified.