Published online: 2018-10-11

Reviews

Pharmacological Properties of Geraniol – A Review

Authors
Yu Lei 1*, Peng Fu 2*, Xie Jun 1, Peng Cheng 1

Affiliations AB STR AC T
1 School of Pharmacy, Chengdu University of Traditional Geraniol is an acyclic isoprenoid monoterpene isolated from
Chinese Medicine, Chengdu, China the essential oils of aromatic plants including Cinnamomum
2 West China School of Pharmacy, Sichuan University, tenuipilum, Valeriana officinalis, and several other plants. The
Chengdu, China limited source of geraniol from plant isolation cannot fulfill

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
the great demand from the flavor and fragrance industries,
Key words which require maximizing geraniol production through bio-
geraniol, essential oil, pharmacology, monoterpene technology processes. The diverse activities of geraniol
suggested that geraniol could treat various diseases as a
received August 1, 2018 promising drug candidate. In order to evaluate the potential
revised September 6, 2018 of geraniol applied in a clinical trial, this review aims at provid-
accepted September 18, 2018 ing a comprehensive summary of the pharmacological effects
Bibliography of geraniol. The publications retrieved from PubMed,
DOI https://doi.org/10.1055/a-0750-6907 ScienceDirect, Springer, and Wiley databases were collected
Published online October 11, 2018 | Planta Med 2019; 85: and summarized for the last 6 years. Then, the potential appli-
48–55 © Georg Thieme Verlag KG Stuttgart · New York | cation of geraniol as a drug is discussed based on its pharma-
ISSN 0032‑0943 cological properties, including antitumor, anti-inflammatory,
antioxidative, and antimicrobial activities, and hepatoprotec-
Correspondence tive, cardioprotective, and neuroprotective effects. Hence,
Prof. Peng Cheng this review aims at providing evidence of the pharmacological
School of Pharmacy, Chengdu University of Traditional activities of geraniol in the context of further development as
Chinese Medicine a drug candidate in clinical application.
37 Shierqiao Road, Jinniu District, 611137 Chengdu, China
Phone: + 86 0 28 61 80 00 18, Fax: + 86 0 28 61 80 00 18
[email protected]

Finally, the highest production of GE was obtained in Saccharomy-

Introduction ces cerevisiae with GE synthase and arnesyl diphosphate synthase
GE (▶ Fig. 1), an acyclic isoprenoid monoterpene, can be ex- expression, reaching a yield of 1.68 g/L in 2017 [4].
tracted from the essential oils of several aromatic plants, such as Recently, GE was shown to possess various pharmacological
Cinnamomum tenuipilum Kosterm (Lauraceae), Valeriana officinalis properties, including antioxidant [5], anti-inflammatory [6], anti-
L. (Caprifoliaceae), Phyla scaberrima (Juss. ex Pers.) Moldenke microbial [7], and antitumor activities [8], through multiple sig-
(Verbenaceae), and Perilla frutescens var. hirtella (Nakai) Makino naling pathway regulation in diverse biological processes, sug-
(Lamiaceae) [1]. GE has been widely used in the flavor and fra- gesting that GE is a promising drug candidate. To provide novel
grance industries in the past decades. However, the limited pro- insights and support the clinical use of GE, we summarize the
duction of GE via plant extraction restrains market growth. Thus, pharmacological activities of GE based on PubMed, ScienceDirect,
several studies are aimed at identifying an effective method to Springer, and Wiley database searches. The scientific literature
biosynthesize GE. published in the years 2013 to 2018 was searched. However,
GE production maximization was achieved in Escherichia coli several papers published before 2013 were also included for in-
engineered to express GE synthase and with the YjgB mutation, sight in the introduction and explanation. We used GE either
resulting in an increase in geranyl diphosphate and prevention of alone or combined with antioxidant, anti-inflammatory, anti-
GE dehydrogenation, yielding 183 mg/L in 2014 [2]. GE pro- microbial, antitumor, hepatoprotective, cardioprotective, and
duction was further improved during both autotrophic and heter- neuroprotective as the key words for the literature searches. Ini-
otrophic growth in engineered Methanococcus maripaludis with
cloned GE synthase from sweet basil Ocimum basilicum and the
absence of puromycin, reaching 4.6 mg/g of dry weight [3]. * These two authors contributed equally to this work.

48 Lei Y et al. Pharmacological Properties of … Planta Med 2019; 85: 48–55

 A B B R E V I AT I O N S
4NQO 4-nitroquinoline-1-oxide
ACR acrylamide
AD atherogenic diet
ALT alkaline phosphatase ▶ Fig. 1 The chemical structure of geraniol using ChemBioDraw.
AST aspartate aminotransferase
CUMS chronic unpredictable mild stress
DMBA 7,12-dimethylbenz[a]anthracene
DSS dextran sulfate sodium
GE geraniol
GSH glutathione
GST glutathione S transferase

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
HMGCR 3-hydroxy-3methylglutaryl coenzyme A
reductase
iNOS inducible nitric oxide synthase
LCAT lecithin cholesterol acyl transferase
LDL low-density lipoprotein
LPO lipid peroxidation
MAPK mitogen-activated protein kinase
MetS metabolic syndrome
MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ▶ Fig. 2 Criteria in this review for article searches and selection.
mRNA messenger ribonucleic acid
MS metabolic syndrome
NF-κB nuclear factor kappa-B
Nrf2 nuclear factor E2-related factor 2 cancer cell line colo-205 with an IC50 value of 20 µM. DAPI staining
PCNA proliferating cell nuclear antigen indicated that GE induces apoptosis, and a Western blot assay
PD Parkinsonʼs disease confirmed that GE upregulates Bax and downregulates Bcl-2. Bax
PH partial hepatectomy is a pro-apoptosis regulator and Bcl-2 is an anti-apoptosis regula-
PTEN phosphatase and tensin homolog deleted tor. Additionally, GE induces DNA damage and cell cycle arrest in
on chromosome ten colo-205 cells [10]. Endometrial carcinoma is a common cancer
ROS reactive oxygen species among women worldwide [11]. It is worthwhile to search for
SCI spinal cord injury novel drug candidates to treat endometrial carcinoma. Recent
STZ streptozotocin research showed that GE treatment and pretreatment could sup-
TNBS trinitro-benzene-sulfonic acid press endometrial carcinoma by inhibiting oncogenes and activat-
TPA 12-O-tetradecanoylphorbol 13-acetate ing tumor suppressor genes in a female Wistar rat model induced
VEGF vascular endothelial growth factor by N-methyl-N′-nitro-N-nitrosoguanidine at 150 mg/kg. The sup-
VLDL very-low-density lipoprotein pression effect of GE was more effective in the pretreatment
group. Real-time PCR results show that GE inhibits the transcrip-
tion of K‑ras, MAPK, PI3K, and β-catenin, and Western blot results
show that GE increases phosphatase and PTEN, progesterone re-
tially, 1569 research papers were selected from with the above ceptors, and E-cadherin protein expression. MAPKs includes JNK,
search strategy using a ScienceDirect database search. Only 944 p38, and ERKs [12]. K‑ras, MAPK, PI3K, and β-catenin are onco-
English written original articles about pharmacological effects genes, and PTEN, progesterone receptors, and E-cadherin are tu-
and production of GE were included, refined by the Wiley data- mor suppressive genes [13]. The endothelioma cell line eEND2
base. Articles also in the PubMed database or Springer database isolated from hemangiomas easily develops angiogenesis [14].
were collected in advance. Duplicate articles were excluded and A recent study exerted that GE showed an anti-angiogenesis ef-
articles with similar results were also excluded. Only 72 articles fect on the endothelioma cell line eEND2. GE inhibits the migra-
were finally included after reading the titles, abstracts, and whole tory activity of endothelial-like eEND2 cells, along with inhibition
papers (▶ Fig. 2). of PCNA expression. Furthermore, GE can block the transduction
of the VEGF/VEGFR-2 signal. VEGF promotes angiogenesis in can-
cer cells. The effect on angiogenesis was verified in vivo: GE ad-
Cytotoxic and Antitumor Activities ministration to BALB/c mice reduces the number of Ki67-positive
GE exerted cytotoxic and antitumor activities on various types of cells and CD31-positive microvessels through attenuating VEGFR-
cancers (▶ Table 1). Colon cancer ranks as the fourth leading 2 expression [15].
cause of cancer mortality worldwide [9]. A recent study demon- Primary liver cancer is the third leading cause of cancer death
strated that GE could significantly inhibit cell growth in the colon worldwide [16]. Pure compounds isolated from natural products

Lei Y et al. Pharmacological Properties of … Planta Med 2019; 85: 48–55 49

 Reviews

▶ Table 1 The cytotoxic and antitumor activities of GE.

Cancer type Suppressive effect Cellular processes Function study Reference

Colon cancer Anti-proliferation Apoptosis, DNA damage, and cell cycle arrest In vitro [10]
Endometrial carcinoma Anti-migration Antiangiogenesis In vitro and in vivo [15]
Liver cancer Anti-proliferation Apoptosis In vitro and in vivo [17–19]
Lung cancer Anti-proliferation Apoptosis In vitro [21]
Pancreatic cancer Anti-proliferation Apoptosis In vitro [26]
Prostate cancer Anti-proliferation Cell cycle arrest In vitro [28]
Skin cancer Anti-proliferation Apoptosis In vivo [30]

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
exerted a cytotoxic effect on liver cancer cells. In Hep-G2 hepatic Prostate cancer remains the first cause of mortality in the
cells, GE exerts an inhibitory effect by promoting apoptosis. Also, United States [27]. In prostate tumor cells, GE administration in-
GE inhibits HMGCR protein and mRNA expression, leading to a hibits growth and survival by downregulating the expression of
cholesterogenesis decrease [17]. Regarding an effect of GE on transcription factor E2F8. Via the inhibition of this pivotal cell
hepatic cell proliferation, GE significantly inhibits Hep-G2 prolifer- cycle control factor, the gene expression profile of genes involved
ation at a concentration as low as 5 µg/mL [18]. Also, GE shows an in the cell cycle was altered, and the E2F8 inhibition had a sup-
inhibitory effect on diethylnitrosamine-associated hepatocarcino- pressive effect on cell growth via inducing G2/M arrest [28].
genesis after a 12-week treatment, as shown by the reduction of Skin cancer incidences have been increasing in the last decades
AST and ALT levels in serum. Additionally, GE demonstrates a sup- [29]. Hence, it is worthy to identify a novel drug candidate to treat
pressive effect on both PCNA and GST-positive area ratios [19]. skin cancer. Recent reports show that GE significantly inhibits
Lung cancer ranks first as the cause of mortality among men DMBA/TPA-mediated skin tumorigenesis in Swiss albino mice. GE
and third among women worldwide [20]. Oral administration to suppresses the Ras/Raf/ERK1/2 signaling pathway and induces
nude mice of 25, 50, and 75 mmol/kg GE inhibits lung cancer cell apoptosis [30].
growth in vivo via an increase of cell apoptosis. This later study
shows that GE downregulates HMGCR levels and decreases mem-
brane-bound Ras protein amounts, leading to a decrease in cho- Anti-inflammatory and
lesterogenesis. Via the suppressive effect of GE on the mevalonate Antioxidant Activities
pathway, cell proliferation is inhibited, and apoptosis is promoted
in A549 tumors compared with normal cells where GE did not Inhibition of the inflammatory response and oxidative stress pre-
show any inhibitory effect on cell survival [21]. vents organs from damage, especially in the brain. The LPO and
Oral cancers account for 2–3 % of cancers worldwide, but their inflammatory reaction caused by TPA can be significantly de-
survival rate is poor [22]. Thus, it is urgent to search for a novel creased by GE. Further investigation demonstrated that GE pro-
drug candidate to treat oral cancer. In the 4NQO-induced cancer- motes the metabolism of inflammatory cells, increases GSH con-
ous mouse model, GE decreased the incidence of oral cancer as a tent, and stimulates antioxidant enzyme activities. Furthermore,
chemopreventive agent. Via the NF-κB pathway, GE reduces the GE exerts an inhibitory effect on the alteration of p38MAPK activ-
density of immature and mature mast cells and downregulates ity and alleviates the expression change of NF-κB and COX-2
the expression of downstream inflammatory mediators (e.g., caused by TPA [31]. Another study also exerted that GE could in-
TNF-α, IL-1β, COX-2, and iNOS) in this model [23]. Another study hibit inflammation through the inhibition of COX-2 [32]. GE has an
showed the suppressive effect of GE being effective at a concen- inhibitory effect on the pamidronate-induced inflammatory re-
tration of 200 mg/kg administered orally in the 4NQO-induced sponse by stimulating IL-10 production. Also, GE showed no toxin
mouse model, which results in the inhibition of the Nrf2 pathway effect on monocytes and did not impact the production of TNF-α
and drug metabolizing enzymes [24]. [33].
Pancreatic cancer ranks as the fourth leading cause of cancer A study tested biochemical parameters and hepatic oxidative
mortality in Western countries [25]. Accumulating evidence sug- stress after GE treatment on Wistar rats and concluded that GE
gests that natural products exerts a cytotoxic effect on pancreatic could work as an antioxidant during aromatherapy. GE administra-
cancer cells. In BXPC-3 human pancreatic carcinoma cells, GE tion was negatively correlated to the total cholesterol level but
significantly suppresses proliferation and induces apoptosis in a there was no difference in glycemia, triacylglycerol protein, and
dose- and time-dependent manner. Pretreatment with GE for urea levels. The GE-treated rats showed an increase of GSH perox-
24 h before gemcitabine treatment shows a maximal inhibition in idase and superoxide dismutase activity, leading to more peroxide
BXPC-3 cells. This study also reports that GE suppresses prolifera- accumulation in the liver. GE is able to upregulate the activity of
tion of prostate cancer cells by inducing ROS production and ALT by promoting oxidative stress but has no remarkable effect
downregulating phosphorylation of tyrosine kinase [26]. on AST activity [34]. GE was also shown to protect hamsters from
AD-induced abnormalities. AD-induced hamsters treated with

50 Lei Y et al. Pharmacological Properties of … Planta Med 2019; 85: 48–55

100 mg/kg GE showed that the underlying mechanism consists of drial function, broke the iron homeostasis, and mitigated genetic
alleviating the change in the lipid profile and endothelial function toxicity [42]. Another study showed that the minimum inhibitory
marker, promoting antioxidant enzyme activities and abating al- concentration of GE is 16 µg/mL against C. albicans and the anti-
terations in the LPO markers and Nrf2 expression. Histologically, mycotic effect of GE is concentration dependent. The morpholog-
GE negatively affected oxidative stress by increasing the activity ical interference test demonstrates that GE shows a suppressive
of Nrf2 [35]. In the meantime, GE could exert anti-inflammatory effect on pseudohyphae and chlamydoconidia formation [43].
and antioxidant effects. Trichophyton rubrum is one of the most common fungi found in
Ulcerative colitis severely impairs the quality of life of patients, chronic dermatophytosis cases [44]. GE could treat T. rubrum in-
and no definitive standard of care has been proven effective, to fections of the skin via its antifungal activity. A high concentration
date, for this indication. GE administration decreases the intesti- of GE could suppress mycelial and fungal growth, and also inhibit
nal damage caused by DSS, as reflected in disease activity index conidia germination. GE treated the T. rubrum infection mostly
scores such as colon length and stool consistency. Pretreatment through leakage of the intracellular material and inhibition of er-
with GE showed an inhibitory effect on the amount of proinflam- gosterol biosynthesis to destroy the cell wall and cell membrane

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
matory cytokines and the activity of myeloperoxidase in colon tis- [45].
sue. GE downregulated the expression of downstream target
proinflammatory enzymes but upregulated antioxidant mole-
cules: GSH and superoxide dismutase activity were suppressed
Hepatoprotective Effects
and LPO and nitrites increases were prevented [36]. GE could alleviate non-alcoholic steatohepatitis in a methionine-
GE oral administration was deemed to protect liver tissue from choline-deficient diet-induced rat model through 200 mg/kg GE
cancer by abating oxidative stress, inflammation, hyperprolifera- oral supplement. In this model, GE administration showed an in-
tion, and apoptotic tissue damage induced by 2-acetylamino- hibitory effect on histological scores, fibrosis, and apoptosis in
fluorene. Additionally, GE administration restored the damaged the liver. On the molecular level, GE inhibits the activities of ala-
structure of the liver tissue. Regarding molecular mechanisms, nine aminotransferase and aspartate aminotransferase in serum.
GE decreased tissue LPO but increased enzymatic activities of GE protects the hepatic mitochondrial function through suppres-
catalase, GSH peroxidase, GSH reductase, and superoxide dismu- sion of hepatic mitochondrial ROS, mitochondrial electron trans-
tase. GE inhibited the expression of caspase-3, caspase-9, COX-2, port chain enzyme activity, and mitochondrial DNA content. Fur-
NF-κB, PCNA, iNOS, and VEGF, and disintegration of DNA was re- ther, GE administration attenuates malondialdehyde and 3-nitro-
markably reduced [37]. GE could also decrease MetS-induced in- tyrosine formation, and inhibits the expression of iNOS and cyto-
flammation and free radical injury by suppressing visceral adipos- chrome P450 2E1 in the liver. Moreover, GE shows an inhibitory
ity and decreasing fasting blood glucose and the glycemic excur- effect on inflammation in the liver with the inhibition of TNF-α
sion [38]. and IL-6 expression and myeloperoxidase activity [46]. According
Another study showed that GE could prevent the ecological to hematoxylin and eosin staining and PCR results, GE exhibits a
disturbances associated with colitis and reduce the inflammatory hepatoprotective effect in rats after a 70 % PH, as intraperitoneal
systemic profile in a colitis mouse model induced by DSS, suggest- administration of GE promoted liver tissue regeneration via im-
ing that the clinical symptoms of colitis could be improved by GE. proving the expression levels of TNF-α and IL-6. Also, GE remark-
Further, the study showed that GE attenuated COX-2 expression ably suppressed the ALT level in serum, which regulates the func-
in the gut wall [39]. The SCI rat model was used to study the tion recovery of liver cells [47]. GE is a natural compound remark-
mechanism of anti-inflammatory and antioxidant effects of GE ably stimulating liver regeneration as shown in the rat model with
and showed that GE negatively affected spinal cord water content a PH that was injected with GE 100 mg/kg. Regarding the mecha-
and increased Beattie and Bresnahan scores when rats were treat- nism, GE increases the expression of NF-κB, TNF-α, and IL-6 mRNA
ed for 4 weeks with 250 mg/kg/d GE. Further, the inhibitory effect and protein levels, and inhibits HSP27 and HSP60 protein levels
of GE on inflammation and oxidative stress was mediated by at- [48]. GE could partly restore the oxidative hepatic damage
tenuating the NF‑κB and p38 MAPK pathways [40]. through the administration of a 50 mg/kg GE intraperitoneal in-
jection in a H2O2-induced oxidative stress rat model. The mecha-
nism entails the regulation by GE of malondialdehyde and GSH
Antimicrobial Activity variations caused by H2O2 and a suppressive effect on hepatic
Candida albicans is a human fungal pathogen leading to immuno- catalase activities [49].
compromized patients and a high rate of mortality [41]. A recent
study showed that treatment with GE weakened the activities of
albicans and non-albicans species of Candida. Oral administration
Cardioprotective Effects
of GE showed an inhibitory effect on the biofilm formation of GE could alleviate hyperlipidemia and reduce the incidence of
pathogenic fungi and hyphal morphogenesis. GE destroyed the coronary heart disease in an AD feeding mouse model. GE reduces
cell wall function by downregulating the activity of plasma mem- blood fat via the downregulation of HMGCR and the inhibition of
brane ATPase and reducing ergosterol levels. GE suppressed fun- lipogenesis. GE suppresses LCAT, decreasing cholesterol esters
gal expansion by promoting the sensitivity of a calcineurin signal- levels. At the same time, treatment with GE increases the activity
ing mutant while enhancing drug resistance to the calcineurin of C-reactive protein [50]. GE protects the cardiovascular system
overexpressing strain. Additionally, GE destroyed the mitochon- from body injury caused by high blood lipids. In particular, GE

Lei Y et al. Pharmacological Properties of … Planta Med 2019; 85: 48–55 51

 Reviews

treatment reduces total cholesterol and total triglyceride pro- damaged area and decreased the activity of caspase-3. Further,
duction in the plasma, and inhibits the biosynthesis of hepatic the study demonstrated that GE treatment in SCI rats decreased
fatty acids, total lipids, and non-saponifiable lipids. GE increases malondialdehyde and 3-nitrotyrosine levels, promoted the pro-
the uptake of serum LDL by increasing LDL mRNA and VLDL recep- tein expression of nuclear factor erythroid 2-related factor 2 and
tor mRNA. Finally, GE suppresses triglyceride synthesis with a de- heme oxygenase 1, and decreased the expression of iNOS. In sum-
crease of fatty acid synthesis [51]. Over the years, attention has mary, GE exerts a positive effect on SCI recovery and alleviates
shifted toward GE as a candidate for the treatment of endothelial neuropathic pain. Hence, GE represents a candidate drug for SCI
cell function disorder resulting from a high-fat diet. In addition, treatment [59].
GE downregulates serum thiobarbituric acid reactive substances
and aortic ROS production. A GE supplement could protect high-
fat diet-induced vascular endothelial dysfunction by inhibiting
Antidiabetic Effects
NOX-2 expression in the aorta [52]. GE inhibits ROS levels and re- Diabetes is a metabolic disorder presenting with high blood sugar
duces the injury during myocardial ischemia-reperfusion, and levels and potentially leading to various complications. In an STZ-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
promotes the function and viability of myocardial cells. GE admin- induced diabetic rat model, GE could be used to treat diabetes, as
istration in neonatal rat ventricular cardiomyocytes decreased the GE administration for 45 days decreased plasma glucose and
endogenous production of ROS and exerted a positive modulation hemoglobin HbA1C and could restore the insulin response. The
of pAMPK levels while attenuating pERK1/2 levels (pAMPK and activities of many enzymes involved in glucose production and
pERK1/2 are key factors regulating cell survival). Hence, GE utilization were restored, leading to an amelioration in carbohy-
showed a protective effect on myocardial cells [53]. GE exerted a drate metabolism and the restoration of glucose homeostasis
cardioprotective effect against cardiac dysfunction induced by [60]. Another study in an STZ-induced diabetic rat model showed
diabetes by inhibiting oxidative stress and increasing the marker that GE treatment has a protective effect on diabetic neuropathy
of oxidative stress 8-isoprostane [54]. and improved the sensory and motor functions by decreasing
enzyme activities (i.e., complexes I–III, succinate dehydrogenase,
and citrate synthase) in the sciatic nerve cytosol and selected re-
Neuroprotective Effects gions of the brain. GE could alleviate cytosolic calcium levels and
In the Drosophila model of ACR-induced nerve injury, GE shows a acetylcholinesterase activity. Meanwhile, GE could inhibit the pro-
neuroprotective effect, as mortality caused by ACR is decreased tein of carbonyls and nitrites [61]. GE attenuates another diabetic
significantly. GE supplementation can attenuate ACR-induced induced complication, i.e., diabetes-induced cardiac functional
oxidative stress, mitochondrial dysfunction, and neurotoxicity. disorder, by inhibiting oxidative stress and decreasing hyperglyce-
The mechanism involves the recovery of GSH and total thiol levels mia. The treatment with GE could increase the cardiac systolic
with an increase of detoxifying enzymes activities. In addition, co- function and recover the diastolic function injured by hyperglyce-
administration of GE with curcumin showed a negative effect on mia. In addition, GE inhibited dramatic oxidative stress by pre-
cholinergic function with a decrease of acetylcholinesterase activ- venting 8-isoprostane increases [62]. GE could attenuate the
ity [55]. PD refers to a long-term degenerative disorder of the vascular responsiveness damage of mice with diabetes or MS.
central nervous system affecting the motor system. GE pretreat- Namely, GE administration improved the excessive vasoconstric-
ment had a protective effect on the nervous system damage tion induced by diabetes or MS exposed to methylglyoxal in a
caused by PD in a MPTP-induced PD mouse model. GE oral admin- dose-dependent manner. The study further demonstrated that
istration ameliorated the neuromuscular disorder via the increase preincubation with GE ameliorates vasoconstriction. In addition,
of tyrosine hydroxylase immunoreactive expression and the GE had a suppressive effect on vasoconstriction induced by volt-
decrease of α-synuclein expression [56]. GE could reduce the age-dependent and receptor-mediated calcium channels. GE re-
motor behavior and neurotrophic factors inadequacy in an MPTP- duces the reaction of the damaged vessels by blocking these
induced PD mouse model [57]. Another study demonstrated that types of calcium channels [63].
GE administration in the MPTP-induced PD mouse model regulat-
ed the Bcl-2/Bax ratio and inhibited the expression of cytochrome
c and caspase-9, resulting in alleviating the neurodegeneration
Other Effects
and disordered movements. Cytochrome c binds to cardiolipin to GE shows an antiarrhythmic effect on ouabain-induced arrhyth-
release it out of the mitochondria and initiate apoptosis. Caspase- mias in mammalian models. GE alleviates ouabain-induced ar-
9 is an enzyme initiating the apoptotic pathway [41]. GE adminis- rhythmias through the downregulation of the contractile force of
tration exerts an inhibitory effect on the PD clinical symptoms of the heart. GE administration blocks the transient outward potassi-
transgenic PD model Drosophila. GE regulates oxidative stress um (K+) current (59.7 %), the non-inactivation K+ current (39.2 %),
through a decrease of GSH content and an increase of protein car- and the inward rectifier K+ current (33.7 %), leading to an action
bonyl content, LPO, and GST activity. GE significantly inhibits α- potential duration, which increased by 50 %. GE also decreased left
synuclein expression, leading to the attenuation of the PD clinical ventricular pressure (83 %) and the heart rate (16.5 %). GE also
symptoms in flies [58]. In rats with SCI, GE could attenuate the prolonged the onset of ouabain-induced arrhythmias by 128 %
neuropathic pain and functional impairment through GE adminis- and decreased the resting tension by 30 % [64].
tration. Moreover, GE had a positive effect on NeuN-positive cells, GE shows excellent anti-ulcerogenic activity on gastric and
but inhibited the expression of glial fibrillary acidic protein in the duodenal mucosa. After GE oral administration to rats, a dose of

52 Lei Y et al. Pharmacological Properties of … Planta Med 2019; 85: 48–55

7.50 mg/kg GE induces an increase of GSH content and a decrease citability. Particularly, the behavioral test showed that GE treat-
of myeloperoxidase levels. Moreover, GE reduces the ischemia/re- ment reduced the number of writhes induced by acetic acid. In
perfusion-induced duodenal ulcerative injury by 71 % and cyste- addition, GE administration reduced mice paw licking time
amine-induced duodenal ulcers by 68 %. GE protects the gastric through the regulation of glutamatergic neurotransmission. GE
and duodenal mucosa by enhancing the activities of protective treatment could relieve pain by suppressing neurotransmitters
factors, including endogenous prostaglandins and the nitric oxide and mediators of inflammation production [71]. Also, GE showed
pathway. The protection mechanism also involves the increase of gastroprotective and gastric healing effects on acute ethanol-
mucus secretion with antioxidant properties. GE increases the re- induced ulcers and chronic acetic acid-induced ulcers [72].
lease of calcitonin gene-related peptide [65]. GE has a protective
effect on TNBS-induced colitis injury. Specifically, TNBS-induced
colitis rats treated with GE for 11 days showed an improvement
Conclusion
of clinical symptoms (e.g., weight loss, colon edema, ulcerative Recently, pure compounds from natural products are gaining ac-
area, and colon/spleen mass indices). GE and/or sulfasalazine ceptance as potentially promising complementary and alternative

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
could prevent the levels of nitric oxide and lipid peroxide from ris- medicines for the treatment of various diseases. Generally, single
ing, and restored antioxidant activity in the colitis rat model. On compounds could target DNA, mRNA, protein, and even micro-
the molecular level, GE inhibits apoptosis and inflammatory cell RNA. Accumulating evidence in last the decades has indicated
infiltration by reducing the levels of caspase-3, intercellular adhe- that GE is a pure botanical compound without adverse effects,
sion molecule-1, and myeloperoxidase. Intercellular adhesion exerting diverse activities by mainly regulating protein expres-
molecule-1 is a transmembrane protein, and could stabilize cell- sion, suggesting that GE could become a novel drug candidate to
cell interactions and facilitate leukocyte endothelial transmigra- treat various diseases. The cytotoxic effect of GE on cancer cells
tion. Myeloperoxidase oxidation reduces inhibition of apoptosis indicates that GE could treat cancer and reduce the mortality of
and inflammation. Conversely, the anti-inflammatory effect of cancer patients. The anti-inflammatory and oxidative effects of
GE was related to the downregulation of the colon contents of GE indicates that GE could protect organ damage and treat ulcer-
prostaglandin E2 and IL-1β [66]. ative colitis. The antifungal activity of GE indicates that GE could
GE oral administration for 3 weeks showed an antidepressant- protect patients from fungal infection. The antidiabetic effect of
like effect on CUMS in rat models and greatly shortened the GE indicates that GE could treat diabetes. The antinociceptive ac-
immobile time in tail suspension tests. More specially, GE de- tivity of GE indicates that GE could be used as an analgesic in clin-
creased CUMS-induced proinflammatory IL-1β levels, resulting in ical trials. However, anticancer effects of GE should be clarified in
the amelioration of the depressive behavior. GE treatment vivo in more animal models, and later in human patients, to con-
showed a suppressive effect on NF-κB pathway activation. Fur- firm the inhibitory effect of GE on malignancy. Also, it is worth-
thermore, GE adjusted nucleotide binding and the expression of while to explore the molecular basis underlying pharmacological
oligomerization domain-like receptor family pyrin domain-con- actions (e.g., antimicrobial and antiarrhythmic activities). The lack
taining 3 inflammasomes [67]. Treatment with GE (100 mg/kg b. of information about definitive targets of GE would be a reason
w) attenuates atherosclerosis-induced tissue fibrosis by hindering against the application of GE in clinical trials.
tissue remodeling via the suppression of transcription factor NF-
κB. The weak expression of NF-κB alleviates oxidative stress and in- Acknowledgements
flammatory response, showing a protective effect on tissue fibers
[68]. This work was supported by the National Natural Science Foundation of
GE could treat Trichomonas vaginalis by killing the parasite. GE China NO. 81630101.
destroyed the nuclear membrane and nuclei, leading to chroma-
tin accumulation and a large number of vacuoles appearing in the Conflict of Interest
cytoplasm. Also, ribosomes were reduced, organelles were disin-
tegrated, and the cell membrane was even damaged. Interesting- The authors declare no conflict of interest.

ly, GE did not show an inhibitory effect in a time-dependent man-

ner [69].
References
GE administration at a dose of 100 or 200 mg/kg alleviated al-
[1] van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R. The
lergic asthma in an ovalbumin-sensitized rat model. The study
Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med
showed that GE had an inhibitory effect on eotaxin levels in bron- Chem 2004; 11: 607–628
choalveolar lavage fluid and infiltration of eosinophils. Namely, GE
[2] Zhou J, Wang C, Yoon SH, Jang HJ, Choi ES, Kim SW. Engineering Esche-
intervention decreased TH2 cytokines but stimulated TH1 cyto- richia coli for selective geraniol production with minimized endogenous
kine interferon in bronchoalveolar lavage fluid. Moreover, GE dehydrogenation. J Biotechnol 2014; 169: 42–50
promoted the expression of Nrf2 protein and intensified Nrf2- [3] Lyu Z, Jain R, Smith P, Fetchko T, Yan Y, Whitman WB. Engineering the
directed antioxidant pathways (e.g., glutamate-cysteine ligase, autotroph Methanococcus maripaludis for geraniol production. ACS Synth
superoxide dismutase, and GST). GE also increased the production Biol 2016; 5: 577–581

of GSH [70]. In experimental mice models, GE showed an antino- [4] Jiang GZ, Yao MD, Wang Y, Zhou L, Song TQ, Liu H, Xiao WH, Yuan YJ.
Manipulation of GES and ERG20 for geraniol overproduction in Saccharo-
ciceptive activity following pain caused by inflammation. The anti-
myces cerevisiae. Metab Eng 2017; 41: 57–66
nociceptive activity was due to a decrease in peripheral nerve ex-

Lei Y et al. Pharmacological Properties of … Planta Med 2019; 85: 48–55 53

 Reviews

[5] Shoff SM, Grummer M, Yatvin MB, Elson CE. Concentration-dependent carcinogenesis through downregulating the activation of NF-kappaB in
increase of murine P388 and B16 population doubling time by the acy- rats. Mol Cell Biochem 2017; 434: 7–15
clic monoterpene geraniol. Cancer Res 1991; 51: 37–42 [24] Madankumar A, Jayakumar S, Gokuladhas K, Rajan B, Raghunandhaku-
[6] de Cássia da Silveira e Sá R, Andrade LN, de Sousa DP. A review on anti- mar S, Asokkumar S, Devaki T. Geraniol modulates tongue and hepatic
inflammatory activity of monoterpenes. Molecules 2013; 18: 1227– phase I and phase II conjugation activities and may contribute directly to
1254 the chemopreventive activity against experimental oral carcinogenesis.
[7] Solorzano-Santos F, Miranda-Novales MG. Essential oils from aromatic Eur J Pharmacol 2013; 705: 148–155
herbs as antimicrobial agents. Curr Opin Biotechnol 2012; 23: 136–141 [25] Del Chiaro M, Segersvard R, Lohr M, Verbeke C. Early detection and pre-
[8] Carnesecchi S, Bras-Goncalves R, Bradaia A, Zeisel M, Gosse F, Poupon vention of pancreatic cancer: is it really possible today? World J Gastro-
MF, Raul F. Geraniol, a component of plant essential oils, modulates enterol 2014; 20: 12118–12131
DNA synthesis and potentiates 5-fluorouracil efficacy on human colon [26] Jin X, Sun J, Miao X, Liu G, Zhong D. Inhibitory effect of geraniol in com-
tumor xenografts. Cancer Lett 2004; 215: 53–59 bination with gemcitabine on proliferation of BXPC‑3 human pancreatic
[9] Klobučar M, Grbčić P, Pavelić SK, Jonjić N, Visentin S, Sedić M. Acid cancer cells. J Int Med Res 2013; 41: 993–1001
ceramidase inhibition sensitizes human colon cancer cells to oxaliplatin [27] Mirzaei M, Mirzadeh M, Mirzaei M. Mortality rate and years of life lost
through downregulation of transglutaminase 2 and beta1 integrin/FAK- due to prostate cancer in Yazd province, Iran: A 10-year study. Sultan

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
mediated signalling. Biochem Biophys Res Commun 2018; 503: 843– Qaboos Univ Med J 2017; 17: e424–e429
848 [28] Lee S, Park YR, Kim SH, Park EJ, Kang MJ, So I, Chun JN, Jeon JH. Geraniol
[10] Qi F, Yan Q, Zheng Z, Liu J, Chen Y, Zhang G. Geraniol and geranyl ace- suppresses prostate cancer growth through down-regulation of E2F8.
tate induce potent anticancer effects in colon cancer Colo-205 cells by Cancer Med 2016; 5: 2899–2908
inducing apoptosis, DNA damage and cell cycle arrest. J BUON 2018; [29] Donaldson MR, Coldiron BM. No end in sight: the skin cancer epidemic
23: 346–352 continues. Semin Cutan Med Surg 2011; 30: 3–5
[11] Dong G, Golden SS. How a cyanobacterium tells time. Curr Opin Micro- [30] Chaudhary SC, Siddiqui MS, Athar M, Alam MS. Geraniol inhibits murine
biol 2008; 11: 541–546 skin tumorigenesis by modulating COX‑2 expression, Ras-ERK1/2 signal-
[12] Zhang Z, Zhao S, Li X, Zhuo X, Zhang W, Nie Q, Wang S, Yan L, Sun Y. ing pathway and apoptosis. J Appl Toxicol 2013; 33: 828–837
Amentoflavone inhibits osteoclastogenesis and wear debris-induced [31] Khan AQ, Khan R, Qamar W, Lateef A, Rehman MU, Tahir M, Ali F, Hamiza
osteolysis via suppressing NF-κB and MAPKs signaling pathways. Planta OO, Hasan SK, Sultana S. Geraniol attenuates 12-O-tetradecanoylphor-
Med 2018; 84: 759–767 bol-13-acetate (TPA)-induced oxidative stress and inflammation in
[13] Shanmugapriya S, Subramanian P, Kanimozhi S. Geraniol inhibits endo- mouse skin: possible role of p38 MAP Kinase and NF-kappaB. Exp Mol
metrial carcinoma via downregulating oncogenes and upregulating Pathol 2013; 94: 419–429
tumour suppressor genes. Indian J Clin Biochem 2017; 32: 214–219 [32] Su YW, Chao SH, Lee MH, Ou TY, Tsai YC. Inhibitory effects of citronellol
[14] Williams RL, Risau W, Zerwes HG, Drexler H, Aguzzi A, Wagner EF. Endo- and geraniol on nitric oxide and prostaglandin E2 production in macro-
thelioma cells expressing the polyoma middle T oncogene induce phages. Planta Med 2010; 76: 1666–1671
hemangiomas by host cell recruitment. Cell 1989; 57: 1053–1063 [33] Murbach Teles Andrade BF, Conti BJ, Santiago KB, Fernandes Júnior A,
[15] Wittig C, Scheuer C, Parakenings J, Menger MD, Laschke MW. Geraniol Sforcin JM. Cymbopogon martinii essential oil and geraniol at noncyto-
suppresses angiogenesis by downregulating vascular endothelial growth toxic concentrations exerted immunomodulatory/anti-inflammatory
factor (VEGF)/VEGFR‑2 signaling. PLoS One 2015; 10: e0131946 effects in human monocytes. J Pharm Pharmacol 2014; 66: 1491–1496
[16] Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin [34] Andrade BF, Braga CP, Dos Santos KC, Barbosa LN, Rall VL, Sforcin JM,
DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sour- Fernandes AA, Fernandes Júnior A. Effect of inhaling Cymbopogon marti-
ces, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; nii essential oil and geraniol on serum biochemistry parameters and oxi-
136: E359–E386 dative stress in rats. Biochem Res Int 2014; 2014: 493183
[17] Crespo R, Montero Villegas S, Abba MC, de Bravo MG, Polo MP. Tran- [35] Jayachandran M, Chandrasekaran B, Namasivayam N. Geraniol attenu-
scriptional and posttranscriptional inhibition of HMGCR and PC biosyn- ates oxidative stress by Nrf2 activation in diet-induced experimental
thesis by geraniol in 2 Hep-G2 cell proliferation linked pathways. Bio- atherosclerosis. J Basic Clin Physiol Pharmacol 2015; 26: 335–346
chem Cell Biol 2013; 91: 131–139 [36] Medicherla K, Sahu BD, Kuncha M, Kumar JM, Sudhakar G, Sistla R. Oral
[18] Queiroz TB, Santos GF, Ventura SC, Hiruma-Lima CA, Gaivao IOM, administration of geraniol ameliorates acute experimental murine colitis
Maistro EL. Cytotoxic and genotoxic potential of geraniol in peripheral by inhibiting pro-inflammatory cytokines and NF-kappaB signaling. Food
blood mononuclear cells and human hepatoma cell line (HepG2). Genet Funct 2015; 6: 2984–2995
Mol Res 2017; 16. doi:10.4238/gmr16039777 [37] Hasan SK, Sultana S. Geraniol attenuates 2-acetylaminofluorene induced
[19] Sawada S, Okano J, Imamoto R, Yasunaka Y, Abe R, Koda M, Murawaki Y, oxidative stress, inflammation and apoptosis in the liver of wistar rats.
Isomoto H. Preventive effect of geraniol on diethylnitrosamine-induced Toxicol Mech Methods 2015; 25: 559–573
hepatocarcinogenesis in rats. Yonago Acta Med 2016; 59: 37–43 [38] Ibrahim SM, El-Denshary ES, Abdallah DM. Geraniol, alone and in combi-
[20] Shtivelman E, Hensing T, Simon GR, Dennis PA, Otterson GA, Bueno R, nation with pioglitazone, ameliorates fructose-induced metabolic syn-
Salgia R. Molecular pathways and therapeutic targets in lung cancer. drome in rats via the modulation of both inflammatory and oxidative
Oncotarget 2014; 5: 1392–1433 stress status. PLoS One 2015; 10: e0117516
[21] Galle M, Crespo R, Kladniew BR, Villegas SM, Polo M, de Bravo MG. [39] De Fazio L, Spisni E, Cavazza E, Strillacci A, Candela M, Centanni M, Ricci
Suppression by geraniol of the growth of A549 human lung adenocarci- C, Rizzello F, Campieri M, Valerii MC. Dietary geraniol by oral or enema
noma cells and inhibition of the mevalonate pathway in culture and in administration strongly reduces dysbiosis and systemic inflammation in
vivo: potential use in cancer chemotherapy. Nutr Cancer 2014; 66: dextran sulfate sodium-treated mice. Front Pharmacol 2016; 7: 38
888–895 [40] Wang J, Su B, Zhu H, Chen C, Zhao G. Protective effect of geraniol inhib-
[22] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA its inflammatory response, oxidative stress and apoptosis in traumatic
Cancer J Clin 2005; 55: 74–108 injury of the spinal cord through modulation of NF-kappaB and p38
[23] Madankumar A, Tamilarasi S, Premkumar T, Gopikrishnan M, MAPK. Exp Ther Med 2016; 12: 3607–3613
Nagabhishek N, Devaki T. Geraniol attenuates 4NQO-induced tongue

54 Lei Y et al. Pharmacological Properties of … Planta Med 2019; 85: 48–55

[41] Rekha KR, Selvakumar GP. Gene expression regulation of Bcl2, Bax and [57] Rekha KR, Selvakumar GP, Sethupathy S, Santha K, Sivakamasundari RI.
cytochrome-C by geraniol on chronic MPTP/probenecid induced Geraniol ameliorates the motor behavior and neurotrophic factors
C57BL/6 mice model of Parkinsonʼs disease. Chem Biol Interact 2014; inadequacy in MPTP-induced mice model of Parkinsonʼs disease. J Mol
217: 57–66 Neurosci 2013; 51: 851–862
[42] Singh S, Fatima Z, Hameed S. Insights into the mode of action of antican- [58] Siddique YH, Naz F, Jyoti S, Ali F, Fatima A, Rahul, Khanam S. Protective
didal herbal monoterpenoid geraniol reveal disruption of multiple MDR effect of Geraniol on the transgenic Drosophila model of Parkinsonʼs dis-
mechanisms and virulence attributes in Candida albicans. Arch Microbiol ease. Environ Toxicol Pharmacol 2016; 43: 225–231
2016; 198: 459–472 [59] Lv Y, Zhang L, Li N, Mai N, Zhang Y, Pan S. Geraniol promotes functional
[43] Leite MC, de Brito Bezerra AP, de Sousa JP, de Oliveira Lima E. Investigat- recovery and attenuates neuropathic pain in rats with spinal cord injury.
ing the antifungal activity and mechanism(s) of geraniol against Candida Can J Physiol Pharmacol 2017; 95: 1389–1395
albicans strains. Med Mycol 2015; 53: 275–284 [60] Babukumar S, Vinothkumar V, Sankaranarayanan C, Srinivasan S. Gera-
[44] da Silva BC, Paula CR, Auler ME, Ruiz Lda S, Dos Santos JI, Yoshioka MC, niol, a natural monoterpene, ameliorates hyperglycemia by attenuating
Fabris A, Castro LG, Duarte AJ, Gambale W. Dermatophytosis and immu- the key enzymes of carbohydrate metabolism in streptozotocin-induced
novirological status of HIV-infected and AIDS patients from Sao Paulo diabetic rats. Pharm Biol 2017; 55: 1442–1449
city, Brazil. Mycoses 2014; 57: 371–376 [61] Prasad SN, Muralidhara. Protective effects of geraniol (a monoterpene)

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
[45] Pereira Fde O, Mendes JM, Lima IO, Mota KS, Oliveira WA, Lima Ede O. in a diabetic neuropathy rat model: attenuation of behavioral impair-
Antifungal activity of geraniol and citronellol, two monoterpenes alco- ments and biochemical perturbations. J Neurosci Res 2014; 92: 1205–
hols, against Trichophyton rubrum involves inhibition of ergosterol bio- 1216
synthesis. Pharm Biol 2015; 53: 228–234 [62] El-Bassossy HM, Ghaleb H, Elberry AA, Balamash KS, Ghareib SA, Azhar
[46] Chen J, Fan X, Zhou L, Gao X. Treatment with geraniol ameliorates A, Banjar Z. Geraniol alleviates diabetic cardiac complications: Effect on
methionine-choline-deficient diet-induced non-alcoholic steatohepatitis cardiac ischemia and oxidative stress. Biomed Pharmacother 2017; 88:
in rats. J Gastroenterol Hepatol 2016; 31: 1357–1365 1025–1030
[47] Canbek M, Uyanoglu M, Canbek S, Ceyhan E, Ozen A, Durmus B, [63] El-Bassossy HM, Elberry AA, Ghareib SA. Geraniol improves the impaired
Turgak O. The effect of geraniol on liver regeneration after hepatectomy vascular reactivity in diabetes and metabolic syndrome through calcium
in rats. In Vivo 2017; 31: 209–213 channel blocking effect. J Diabetes Complications 2016; 30: 1008–1016
[48] Ceyhan E, Canbek M. Determining the effects of geraniol on liver regen- [64] de Menezes-Filho JE, Gondim AN, Cruz JS, de Souza AA, Santos JN,
eration via the nuclear factor kB pathway after partial hepatectomy. Conde-Garcia EA, de Sousa DP, Santos MS, de Oliveira ED, de Vasconce-
Altern Ther Health Med 2017; 23: 38–45 los CM. Geraniol blocks calcium and potassium channels in the mamma-
[49] Ozkaya A, Sahin Z, Gorgulu AO, Yuce A, Celik S. Geraniol attenuates lian myocardium: useful effects to treat arrhythmias. Basic Clin Pharma-
hydrogen peroxide-induced liver fatty acid alterations in male rats. col Toxicol 2014; 115: 534–544
J Intercult Ethnopharmacol 2017; 6: 29–35 [65] de Carvalho KI, Bonamin F, Dos Santos RC, Perico LL, Beserra FP, de Sousa
[50] Jayachandran M, Chandrasekaran B, Namasivayam N. Effect of geraniol, DP, Filho JM, da Rocha LR, Hiruma-Lima CA. Geraniol-a flavoring agent
a plant derived monoterpene on lipids and lipid metabolizing enzymes in with multifunctional effects in protecting the gastric and duodenal
experimental hyperlipidemic hamsters. Mol Cell Biochem 2015; 398: mucosa. Naunyn Schmiedebergs Arch Pharmacol 2014; 387: 355–365
39–53 [66] Soubh AA, Abdallah DM, El-Abhar HS. Geraniol ameliorates TNBS-
[51] Galle M, Kladniew BR, Castro MA, Villegas SM, Lacunza E, Polo M, de induced colitis: Involvement of Wnt/beta-catenin, p38 MAPK, NFkappaB,
Bravo MG, Crespo R. Modulation by geraniol of gene expression involved and PPARgamma signaling pathways. Life Sci 2015; 136: 142–150
in lipid metabolism leading to a reduction of serum-cholesterol and [67] Deng XY, Xue JS, Li HY, Ma ZQ, Fu Q, Qu R, Ma SP. Geraniol produces
triglyceride levels. Phytomedicine 2015; 22: 696–704 antidepressant-like effects in a chronic unpredictable mild stress mice
[52] Wang X, Zhao S, Su M, Sun L, Zhang S, Wang D, Liu Z, Yuan Y, Liu Y, Li Y. model. Physiol Behav 2015; 152: 264–271
Geraniol improves endothelial function by inhibiting NOX‑2 derived oxi- [68] Jayachandran M, Chandrasekaran B, Namasivayam N. Geraniol attenu-
dative stress in high fat diet fed mice. Biochem Biophys Res Commun ates fibrosis and exerts anti-inflammatory effects on diet induced
2016; 474: 182–187 atherogenesis by NF-kappaB signaling pathway. Eur J Pharmacol 2015;
[53] Crespo R, Wei K, Rodenak-Kladniew B, Mercola M, Ruiz-Lozano P, 762: 102–111
Hurtado C. Effect of geraniol on rat cardiomyocytes and its potential [69] Dai M, Peng C, Peng F, Xie C, Wang P, Sun F. Anti-Trichomonas vaginalis
use as a cardioprotective natural compound. Life Sci 2017; 172: 8–12 properties of the oil of Amomum tsao-ko and its major component,
[54] El-Bassossy HM, Ghaleb H, Elberry AA, Balamash KS, Ghareib SA, Azhar geraniol. Pharm Biol 2016; 54: 445–450
A, Banjar Z. Geraniol alleviates diabetic cardiac complications: effect on [70] Xue Z, Zhang XG, Wu J, Xu WC, Li LQ, Liu F, Yu JE. Effect of treatment
cardiac ischemia and oxidative stress. Biomed Pharmacother 2017; 88: with geraniol on ovalbumin-induced allergic asthma in mice. Ann Allergy
1025–1030 Asthma Immunol 2016; 116: 506–513
[55] Prasad SN, Muralidhara. Neuroprotective effect of geraniol and curcu- [71] La Rocca V, da Fonsêca DV, Silva-Alves KS, Ferreira-da-Silva FW, de Sousa
min in an acrylamide model of neurotoxicity in Drosophila melanogaster: DP, Santos PL, Quintans-Júnior LJ, Leal-Cardoso JH, de Almeida RN.
relevance to neuropathy. J Insect Physiol 2014; 60: 7–16 Geraniol induces antinociceptive effect in mice evaluated in behavioural
[56] Rekha KR, Selvakumar GP, Santha K, Inmozhi Sivakamasundari R. Gera- and electrophysiological models. Basic Clin Pharmacol Toxicol 2017;
niol attenuates alpha-synuclein expression and neuromuscular impair- 120: 22–29
ment through increase dopamine content in MPTP intoxicated mice by [72] Venzon L, Mariano LNB, Somensi LB, Boeing T, de Souza P, Wagner TM,
dose dependent manner. Biochem Biophys Res Commun 2013; 440: Andrade SF, Nesello LAN, da Silva LM. Essential oil of Cymbopogon citra-
664–670 tus (lemongrass) and geraniol, but not citral, promote gastric healing
activity in mice. Biomed Pharmacother 2018; 98: 118–124

Lei Y et al. Pharmacological Properties of … Planta Med 2019; 85: 48–55 55