REVIEW ON GERANIOL OIL

HERBAL DRUG TECHNOLOGY

Introduction: Herbal medicine are oldest remedies known to mankind.
Herbs have been used by all cultures throughout history but India has one of the oldest ,richest
and most diverse culture living traditional associated with the use of medicinal plants .In the
present scenario ,the demand for herbal products is growing exponentially throughout the world
and major pharmaceutical companies are currently conducting extensive research on plant
materials for their potential medicinal value .Herbal drug technology is used for converting
botanical materials into medicines , where standardization and quality control with proper
integration of modern scientific techniques and traditional knowledge is important . Herbal
formulation have reached widespread acceptability as therapeutic agents diabetes, arthritics.
Liver , diseases, cough and cold, and memory enhancement throughout the world. Herbs are
traditionally considered harmful and increasingly being consumed by a people without
prescription. The traditional medicine is increasingly solicited through the traditional
practitioners and herbalist in the treatment of infectious diseases .The house hold remedies
mostly consist of regular kitchen ingredients and area generally used as over the counter
medicines The major drawback of modern medicine is there side effects which may leads to
lived threatening of patients. Herbal medicine also have their list of side effects like any other
synthetic drug. Thus it is an essential to evaluate their clinical safety and efficiency .the role of
natural product, herbal medicines, traditional medicines is increasingly appreciated in recent
years for the prevention and cure of human elements. Natural product research is often based on
ethnobotanical information and many of drugs used today where implied in indigenous societies.
One of the aims of ethano pharmaceutical research is better understanding the pharmacological
effects of different medicinal plants traditionally used in health care. Plants have application in
the development of therapeutic agents and acts as a source of bioactive compounds for possible
used as drugs. Medicine is a substance that has nutritive, curative, or preventive properties, while
the term “herbal” refers to a botanical or plant-based preparation. Hence, the term “herbal
medicine” is used for plant based substances that consist of nutritive, curative, or preventive
properties. Herbal medicine is an interdisciplinary branch between herbal medicine and
Ayurveda as it covers all fields of herbal medicine related to botany, medicinal plant research,
Pharmacognosy, phytochemistry, phytotherapy, botanical medicines, Ayurveda, natural
chemistry, agriculture science, Unani medicine, biotechnology, and biochemistry. A person who
deals with herbs, especially medicinal herbs, is known as an herbalist. Herbal journals deal with
the use of plants in the treatment of diseases.With many people now using herbal medicine,
safety issues are also becoming an important concern. Indeed, certain HM have been implicated
in some important adverse events relating to cardio, neuro and nephro-toxicities as well cancers.
Toxicity due to HMs may occur and their seriousness may vary depending on the type of herb or
herbal material, preparation and user: varying from minor to severe and sometimes fatal.
Adulterations and concomitant use of herbal medicines with conventional medicines constitute
another area of attention, thus, the need for a strict regulation and enlightenment and control. In
contemporary times, HMs are prepared and used in different forms, which also affect their
activity outcomes. The dosage form of herbal medicines varies widely depending on such factors
as the type of disease to be treated, route of application, patient, culture and even philosophical
backgrounds. In homes and traditional medicine clinics, HMs are prepared often from fresh or
dried herbs which are commonly made into infusions, decoctions, poultices, powders to be
poured into open wounds or incorporated into native beverages, puddings, and so on.
Conventional commercial HMs products are commonly available as pills, capsules, tablets,
powders/granules, creams, ointments, and so on. The presentation of HMs in pharmaceutical
dosage forms is expected to enhance accurate dosing, esthetics as well as compliance by enticing
usage.

ROSE :
 Health and disease are two important areas which have engaged attracted the attention of
mankind since time immemorial. The one and most important sources of medicines even since
the beginning of human civilization are the plant source. In spite of tremendous developments in
the th
field of allopathic during the 20 century, plants still remain one of the major sources of
drugs in modern as well as in traditional system of medicines through the world. Over 60% of all
pharmaceutical are plant based. In traditional medicine, there are many natural crude drugs
that have the potential activity to treat many disease and disorders one of them is Rosa
centifolia; Family: Rosaceae) popularly known as province rose, cabbage rose or Rose de mai
and commonly known as Gulab, Satapatri, Rosapoo, Troja .Generally the rose varieties are
cultivated for home and garden beautification and its rich perfumery fragrance in many parts
of the world. Traditionally the Plant pacifies vitiated VATA, PITTA, inflammation, burning
sensation, conjunctivitis, cough, skin disease, cardiac disability, fever, and general weakness
Various parts of rose such as fruits, flowers, leaves, and bark can be used in various product
development, including cosmetics, food, pharmaceuticals, and engineering. The medical benefits
of roses include the treatment of inflammation, diabetes, dysmenorrhea, depression, stress,
seizures, and aging .It is a naturally occurring plant material . It has various health benefits . It is
used in the cosmetic industries for various cosmetic products .
Chemical constituents:

• Geraniol
• Nerol
• Farnesol
• Citronellol
• Phenethyl Alcohol
• Eugenol
• Methyl Eugenol
• Rose oxide
• 1-nonadecene
• Heneicosane
• Geranyl acetate
• Citral
• Damascone
Health benefits of Rose Oil:
o It is an aphrodisiac.

o It is an astringent.

o It’s good for your skin.

o It is an emmenogogue.
o It is good for digestion.
o It protects the uterus.
o It stimulates circulation

EXTRACTION OF ROSE OIL : There are several methods of obtaining aromatic substances
from rose petals. Distillation is the most widely used and the most economical method of
extracting rose essential oils. In distillation, the rose flowers is heated in stills, either by placing
it in water which is brought to the boil or by passing steam through it. The heat and steam cause
the cell structure of the plant material to burst and break down, thus freeing the essential oils.
The essential oil molocules and steam are carried along a pipe and chanelled through a cooling
tank (condencer), where they return to the liquid form (extract) and are collected in a special tank
(Florentine). The emerging liquid is a mixture of oil and water, and since essential oils are not
water soluble they can be easily seperated from the water and and siphoned off. Essential oils
which are lighter than water will float on the surface in the florentine flask. The rose petals
collected from gardens and packed tightly in sacks are laid out on the floor of the factory in order
to allow slight decomposition, which aids in the development and improvement aromatic quality
of the essential oil. The rose petals are loaded into the stills. 3000 liter stills made copper and
steam jacketed are used for distillation. Coils inside the bottom of the still carry the steam which
heats the water in the still. Distillation is generally done in copper stills, which had a capacity of
500 kg flowers and 1500 liter warm water. The distillation in the stills is carried out for 1.5
hours. During the hydrodistillation of rose flowers, essential oils are liberated from the structures
where they are stored in the petals by diffusion. While distilling, the condenser temperature is
held at 35-45°C to prevent deposition of the waxes in the condenser, and at a specific gravity of
about 0.85 the oil constituents sit on the water surface Unfortunately, however, owing to the loss
of phenyl-ethyl alcohol, a large proportion of which remains dissolved in the distillation water,
the otto does not accurately represent the flower odour. The distillate is collected in 200 liter
florentine flasks of the copper stills. The oil that seperates out in the florentine flasks is called
decanted oil, first oil or direct oil. The bottom water and decanted oil in the florentine flasks are
then pumped into the stainless steel tanks to get the redistilled oil called water oil, second oil or
indirect oil. Later, the first and second rose oils are blended to get the final product sold in the
markets
Geraniol :

chemical structure :

Introduction :Geraniol (3, 7-dimethylocta-trans-2, 6-dien-1-ol) is a compound that is extracted

from the flowers of roses and many other plants (1,2). Geraniol is a natural component of the
plant’s essential oils which has a roselike odor and its taste is generally used as a flavoring in
the food industry (1) ). The U.S. Food and Drug Administration (FDA) approved it as a
generally safe component (3). Geraniol, as a clear to paleyellow oil, is poorly soluble in
aqueous solutions whereas has a high solubility in common organic solvents (4). Geraniol
presents several remarkable biochemical and pharmacological properties; it is an important
plant-based insect repellent (5), it has antimicrobial, antioxidant, anti-inflammatory (6), and
strong antibacterial activity (7), and is also an antifungal agent (8) . It shows anti-inflammatory
effects on monocytes cell line (9). Geraniol exhibits in vitro and in vivo antitumor effects on
murine leukemia, hematoma and melanoma cells (10, 11). Geraniol is a primary acyclic,
unsaturated terpene alcohol with the chemical formula C10H18O4. It has a distinctive rose-like
odor and the taste (at 10 ppm) is qualified as sweet floral rose-like, citrus with fruity and waxy
c (6). Geraniol is found in oily tissues of several plants as well as frequently co-exists with its
oxidation product like geranial and nerol (4). It is naturally found in many oils like Palmarosa,
geranium or rose oils (12). It is also a lead molecule in the development of anticancer drugs
(3,13,14). Researchers have proven that GE is a useful plant for repelling insects (5). Also,
several studies have specified the antimicrobial activity of this compound (8). In in vitro and in
vivo studies, GE has been shown to inhibit the growth of murine leukemia, hepatoma and
melanoma cells (15,16).

BIOLOGICAL ACTIVITIES :
Insecticide & Repellent Effect
• Essential oils of a large number of
plants have the ability to be repellent against various Hematophagous arthropods (17,18). They
also presented repellent, and/or antifeedant effects and insecticidal action against insects (5).
Geraniol and eugenol are effective attractants and are able to trap Japanese beetles, Popillia
japonica Newman (19). It was shown that mixing doses of citronella, lemon (citrus lemon), rose
(Rosa damascene), lavender or basil . Essential oils with distilled water is very efficient in
preventing indoor insect pests (20). Hierro, Valero (21) have Investigated the activity of some
monoterpenoid compounds against Anisakis simplex. The results showed the Activity of GE,
citronellol, citral, carvacrol and cuminaldehyde at 125.5 µg mL-1 concentration. Geraniol and a
Number of compounds were found as fumigants against Musca domestica and T. castaneum.
Geraniol, carveol, Carvacrol, linalool, menthol, terpineol, thymol, verbenol and some other
compounds are ovicidal against M.domestica eggs (22). The acaricidal activities of GE from
Pelargonium graveolens oil on Tyrophagus Putrescentiae, and the storage food mite, and
comparing its activity with benzyl benzoate has been surveyed. The Results showed that GE
was more effective than benzyl benzoate with the 50% lethal dose value being 1.95 µg cm3 And
1.27 µg cm3, respectively (23). Mosquito bites lead to allergic responses and transfer several
diseases such as Malaria, yellow fever and dengue (24,25). It has been proved that GE is an
effective mosquito repellent (26). Geraniol-based products are available in several countries as
natural repellents. It was found that GE candles were More effective than linalool and citronella
candles in protecting a person from bites of mosquitoes and sand flies (27). A study comparing
three botanical natural repellents proved that the longest protection time of a person from Bites
of mosquitoes was attained when lemongrass extract was combined with 25% GE oil (28).
.
2) Anti-
microbial : Essential oils show a strong inhibitory effect on many bacteria and fungi. When the
essential oils are solved in the Phospholipids bilayer of the cell membranes, its antimicrobial
effect occurs (29). It was proved that some Monoterpene alcohols such as citronellol, geraniol,
Linalool and nerol, show more effective antibacterial properties Than antifungal properties
(30,31). Gaseous GE presents an antibacterial effect on respiratory tract pathogens, such As H.
Influenzae and S. Aureus. Friedman, Henika (32) compared essential oils (n=96) and oil
compounds (n=23) in Terms of bactericidal activity levels against C. Jejuni, E. coli, L.
monocytogenes and S. enterica from food and Clinical sources. Geraniol showed higher activity
against E. coli, L. Monocytogenes and S. enterica with a Bactericidal activity value (BA50) of
0.15, 0.28 and 0.15, respectively. Among 60 essential oils tested, GE was able To prevent human
and animal pathogens, S. typhimurium and E. coli (33). Citronellol, GE and nerol presented
Minimum inhibitory concentrations (MICs) from 64 to 128 µg ml-1 against Mycobacterium
tuberculosis (34). The GE obtained from M/s S H Kelkar, Mumbai was found to show stronger
bacterial sensitivity to E. faecalis, M. Smegmatis, P. aeruginosa, S. aureus and S. epidermidis
over the sample obtained from another source. The GE Exhibited 312.5 µg mL-1 MIC against E.
coli, M. smegmatis, P. aeruginosa, S. typhi and Y. enterocolitica. However, 100 µg mL-1 strong
activity from GE was found against S. mutans (35). Geraniol in an essential oil extracted from
Palmarosa leads to the antifungal action against S. cerevisiae (36). Geraniol showed a strong
antifungal effect on C Palmarosa exhibits inhibitory activity against Cryptococcus neoformans, a
fungus causing infection during The last stages of AIDS (37). Geraniol displayed 312.5 µg mL-1
MIC against Aspergillus flavus whereas MIC of 625 µg mL-1 was obtained against
Trichophyton rubrum and Microsporum gypseum (35). It has shown the main antifungal
activities against Colletotrichum camelliae (MIC value 440 µg mL-1) (38). Geraniol (25 µg mL-
1), in combination with vaginal washing, mainly inhibited the growth of viable C. albicans cells
and improved vaginal inflammation
.
3) Anti-oxidant effects : Free radicals cause molecular alteration related to
Alzheimer’s disease, aging, asthma, arteriosclerosis, cancer, and Diabetes by oxidation of
biomolecules (39). Experimental studies described several pharmacological activities of GE
Including anticancer and antioxidant activities (40). Mahmoud A. Saleh et al. evaluated the
antioxidant activity of Various essential oils and showed that the essential oils of the Rosaceae
family were among the most effective Compounds (41). The radical scavenging activity of P.
graveolens essential oils was investigated using the 1,1Diphenyl-2-pycrylhydrazyl (DPPH)
method. The antioxidant activity values were obtained between 63.70 mg mL-1 For leaves to
64.88 mg mL-1 for stems (42). Recent studies showed that GE oil had antiradical activity (IC50
= 14.49 Mg mL-1) mainly stronger than acetone extract of the plant (IC50 = 66.45 mg mL-1)
(43). In a study on evaluating The antioxidant activity of Thymus daenensis (TD) containing
66.8% GE, 13.9% geranyl acetate, and 9.6% β-Caryophyllene, DPPH radical scavenging
represented that TD essential oil extract had higher IC50 values than the Antioxidant standards.
Moreover, TD extract exhibited lower IC50 value (194.24 ± 0.021 µg mL-1) than TD essential
Oil (44). In another study, the antioxidant activity of GE, geranyl acetate, gingerol and eugenol
were evaluated. Lower IC50 value inferred higher antioxidant activity. Among these essential
oils, GE, geranyl acetate, gingerol and Eugenol exhibited 24.6, 4.2, 68.4 and 0.9 µg mL1 IC50
values, respectively (45). The essential oils extracted from Old leaves and flowers demonstrated
the highest scavenging activity, which may be attributed to the presence of GE, Nerol and some
other terpenes in the Neroli oil (47,47). The radical scavenging activity of 34 kinds of citrus
Essential oils and their volatile components was investigated by researchers (48). They used the
DPPH method and Compared the activity of essential oils with trolox as a standard antioxidant.
Geraniol exhibited significant Scavenging activity against the DPPH radical (87.7%, 235.9 mg of
trolox equiv ml-1). Antioxidant and anticancer Effects of geranium oil are related to citronellol
and trans-geraniol, the main components of it. Geraniol has a Significant inhibitory potential to
the growth of tumor cells of pancreas, as well (43). Antioxidant effect of GE in Different in vitro
models indicates the potential benefit of GE against oxidative stress (OS), a progressive
Pathological feature of neurodegenerative disorders (49).
.
4) Anticancer Activities
The effects of geraniol on various types of cancer :
Geraniol has been found to be effective against a broad range of cancers, including breast, lung,
colon, prostate, pancreatic, skin, liver, kidney and oral cancers . However, it is emphasized that
this can be research or publication bias: for example, it is still not reported whether geraniol
affects avoidance of immune destruction or activating invasion and metastasis.
.

TYPES :

▪ Breast cancer
▪ Lung cancer

▪ Colon cancer

▪ Prostate cancer

▪ Pancreatic cancer

▪ Skin cancer

▪ Liver cancer

4.1) Breast cancer

Geraniol suppressed the growth of MCF-7 breast cancer cells via the induction of cell cycle
arrest in the G1 phase(54).The protein levels of cyclin D1, cyclin- dependent kinase 4 ,cyclin E,
and cyclin A were reduced in geraniol-treated MCF-7 cells, whereas those of p27Kip1 were
elevated by geraniol(54) .In contrast, geraniol did not affect the growth of MCF-10F normal
breast epithelial cells (54), which indicates that its activity is tumor-specific. Although geraniol
inhibited 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, geraniol-
induced cell cycle arrest was not rescued by supplementation with mevalonate, which is a
reaction product of HMG-CoA reductase (54). These results indicate that the anti-proliferative
effect of geraniol on MCF-7 cells is not related to a reduction in HMG-CoA reductase activity
or the limitation of cellular mevalonate levels, but rather, that it is linked to other molecular
mechanisms.
4.2) Lung cancer
Experiments in xenograft models revealed that geraniol reduced tumor weight and volume in
mice bearing tumors that formed from A549 cells(55) which showed an increased TUNEL-
positive tumor cell population and elevated caspase-3 activity. Geraniol also inhibited
cholesterol synthesis in A549 cells and reduced the serum levels of cholesterol in mice with
A549 cell xenografts through the suppression of HMG-CoA reductase activity(55) In addition,
geraniol reduced the expression levels of membrane-bound Ras in A549 cellbearing mice
without corresponding changes in the total protein levels of Ras (55).This was probably due to
the actions of geraniol that are related to the inhibition of mevalonate pathways and the
resultant reduction in Ras prenylation (56)),However, it is unclear whether mevalonate
supplementation can rescue geraniol-induced phenotypes.

4.3) Colon cancer

Geraniol exerted anti-proliferative activity against Caco-2 colorectal adenocarcinoma cells
through the induction of S phase cell cycle arrest . In addition, geraniol elicited apoptosis in
mouse xenograft models using CT26 colon carcinoma cells . Geraniol affected polyamine
metabolism in Caco-2 cells through the reduction of ornithine decarboxylase (ODC) activity .
This is clinically relevant because polyamine metabolism is a promising target of
chemotherapeutic and chemopreventive drug development strategies (56). Geraniol also
induced the depolarization of the plasma membrane potential with a decrease in membrane
resistance in Caco-2 cells , which led to the reduction in the activities of protein kinase C
(PKC) and extracellular signal- regulated protein kinases (ERK) . Under the experimental
conditions, mevalonate supplementation did not reverse geraniol-mediated inhibition of cell
growth , which indicates that HMG-CoA reductase is not linked to the antitumor actions of
geraniol. Geraniol sensitized cultured Caco-2 cells and SW620 colorectal adenocarcinoma
cells to 5-FU and also sensitized mice with xenografts of TC118 colon cancer cells to 5-FU .
In addition, geraniol elevated the uptake rate of 5FU in colon cancer cells . Geraniol
effectively decreased the expression levels of thymidine kinase and thymidylate synthase ,
which are important targets for the development of anticancer drugs and chemosensitizing
agents . These results suggest that geraniol might serve as a chemosensitizer.
Geraniol was found to elicit chemopreventive activities . It decreased the total number of
aberrant crypt foci in the colons of Wistar rats that were treated with dimethylhydrazine . Under
this condition, geraniol reduced DNA damage in the colonic mucosa. In addition, apoptosis in
the distal colon was significantly higher in the geraniol-treated group compared with the
control group. Moreover, the expression levels of Bcl-2 were significantly decreased in the
geraniol-treated group

4.4) Prostate cancer Geraniol inhibited tumor cell growth via the induction of apoptosis in
cultured and grafted PC-3 prostate cancer cells , due to the depolarization of mitochondrial
membrane potential, the activation of caspase-3, the reduction in the expression levels of Bcl-2
and Bcl-w, and the increased expression levels of Bax and BNIP3 . Geraniol also potently
induced autophagy, which is crucial for the effective stimulation of cell death . The combined
inhibition of apoptosis and autophagy restored cell growth in geraniol-treated PC-3 cells. In
addition, cell cycle arrest at G1 phase, and a slight arrest at G2 phase, were observed in geraniol-
treated PC-3 cells , which was confirmed by the decreased expression levels of cyclins A, B, D
and E and CDK1 and CDK4, as well as by the elevated levels of p21Cip1 and p27Kip1. At the
molecular level, geraniol has been found to inhibit AKT-mTOR signaling without affecting
mitogen-activated protein kinase (MAPK) activity (30). For example, the PP2A inhibitor okadaic
acid, but not the PP1 inhibitor tautomycin, reversed geraniol-mediated inhibition of AKT.
Concomitantly, geraniol activated AMP-activated protein kinase (AMPK). The combined
treatment with the AKT inhibitor perifosine and the AMPK activator AICAR synergistically
inhibited tumor cell growth . However, under the condition, geraniol did not affect the activity of
transient receptor potential melastatin type 8 (TRPM8) channel or calcium mobilization . In
addition, mevalonate supplementation did not reverse the geraniol-mediated inhibition of cell
growth. Geraniol increased the therapeutic response of PC-3 cells to chemotherapy agents, such
as docetaxel, doxorubicin, paclitaxel, etoposide, 5-FU and cisplatin. Particularly, the combination
of the sub-optimal doses of geraniol and docetaxel noticeably suppressed the growth of prostate
cancer cells in culture and those in mouse xenografts; the percentage of active caspase-3-positive
cells was markedly increased in tumor tissues that were treated with geraniol and docetaxel
compared with the treatment of cells with either drug alone.

4.5) Pancreatic cancer Geraniol inhibited the proliferation of MIA PaCa-2 pancreatic
carcinoma cells and BxPC-3 pancreatic adenocarcinoma cells and reduced tumor volume in
hamsters injected with PC-1 pancreatic ductal adenocarcinoma cells . In addition, geraniol
induced G1 phase cell cycle arrest in MIA PaCa-2 cells and elevated the expression levels of
p21Cip1 and p27Kip1 but reduced those of cyclin A, cyclin B1 and CDK2. siRNAs against
p21Cip1 and p27Kip1 subsequently alleviated geraniol-induced cell cycle arrest . Finally, the
protein levels of cyclin D1 were reduced by geraniol in MIA PaCa-2 cells, but not in BxPC-
3 cells.When the tumor cells were incubated with geraniol before they were treated with
gemcitabine, which is one of the first-line treatments for advanced pancreatic cancer,
proliferation of BxPC-3 cells was significantly inhibited compared with when the cells were
treated with either drug alone . In addition, geraniol markedly enhanced the apoptosis-inducing
effect of gemcitabine on BxPC-3 cells

4.6) Skin cancer

Geraniol inhibited skin edema and epidermal hyperplasia in mice that were stimulated with 12-
O-tetradecanolyphorbal-13-acetate (TPA)/7, 12-dimethyl- benzanthracene (DMBA) . The
chemopreventive effects of geraniol on skin tumorigenesis are ascribed to the activation of
apoptotic pathways and the attenuation of Ras-mediated cell proliferation pathways. Particularly,
geraniol reduced the levels of membrane-bound Ras in DMBA/TPA-stimulated mice and also
decreased Raf expression
and ERK activity. However, it is unclear whether geraniol inhibits HMG-CoA reductase activity
in this setting and whether mevalonate rescues the geraniol-induced phenotypic changes. In
addition, geraniol suppressed the TPA-induced increase in cutaneous ODC activity andthe
thymidine incorporation rate in mouse skin . Geraniol suppressed skin inflammation through the
inhibition of cyclooxygenase (COX)-2 induction in DMBA/TPA-treated mice . Geraniol also
inhibited the altered expression of nuclear factor (NF)-κB; the production of cutaneous
proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and
pp38; and the formation of superoxide dismutase (SOD) and nitric oxide (NO) (52). In addition,
geraniol exerted antioxidant activity to reduce TPA-induced malondialdehyde (MDA) production
through modulation of the following: glutathione (GSH), glutathione reductase (GR), glutathione
peroxidase (GPX), glutathione-S-transferase (GST), catalase (CAT), lipid peroxidation, glucose
6-phosphate dehydrogenase (G6PD) and quinone reductase

4.7) Liver cancer :

In one study, geraniol exerted anti-proliferative activity in HepG2 hepatocarcinoma cells and G1
phase cell cycle arrest and apoptosis were observed in geraniol-treated cells . In addition,
geraniol suppressed tumor growth in mice that received transplanted Morris 7777 hepatoma cells
. Geraniol inhibited HMG-CoA reductase activity in HepG2 cells and 2-
acetylaminofluorenetreated Wistar rat and reduced the level of RhoA in hepatic membranes .
Although geraniol affected various lipid metabolic pathways, including HMG-CoA reductase or
Δ5-desaturase , it is uncertain whether its effects are linked to tumor suppression. Geraniol
exhibited chemopreventive activity against hepatocarcinogenesis in rats that were stimulated
with diethylnitrosamine and 2-acetylaminofluorene. It also inhibited cell proliferation and DNA
damage in preneoplastic lesions (PNLs) and caused an elevation in apoptosis in PNLs

4.8) Kidney cancer

Geraniol demonstrated chemopreventive activity in Wistar rats treated with ferric

nitrilotriacetate (Fe-NTA) in that it effectively reduced renal oxidative stress and tumor
incidence via the modulation of multiple molecular targets that are involved in proliferation,
apoptosis, or inflammation. Geraniol restored the activities of GSH-dependent antioxidant
enzymes, such as glutathione S- transferase, glutathione peroxidase, and catalase in Fe-NTA-
injected rats, which suppressed Fe-NTA-induced renal toxicity (50). In the rats that were
treated with Fe-NTA and N-nitrosodiethylamine, geraniol downregulated kidney injury
molecule-1 , NF-κB, proliferating cell nuclear antigen , and p53 and upregulated caspase-3, -8
and -9.

4.9) Oral squamous cell carcinoma

Geraniol prevented DMBA-induced buccal pouch carcinogenesis in the hamster . Its anti-
inflammatory, anti-angiogenic, anti-proliferative, and apoptosis- inducing properties contributed
to the suppression of histological changes, such as keratosis, dysplasia and hyperplasia, in the
buccal pouch of DMBA- treated hamsters. Geraniol also exerted its chemopreventive potential
against 4nitroquinoline-1-oxide (4NQO)-induced oral carcinogenesis in Wistar rats . Geraniol
reduced the plasma concentrations of lipid peroxidation by-products in DMBA-stimulated
hamsters . Geraniol also restored the DMBA-induced disturbance in the status of antioxidants in
terms of glutathione peroxidase, reduced glutathione, vitamin E, superoxide dismutase, and
catalase in the plasma and in the buccal mucosa . In addition, the chemopreventive potential of
geraniol relies on modulatory effects on phase I (cytochrome P450 and cytochrome b5) and II
(glutathione-S-transferase, glutathione reductase and DTdiaphorase) detoxification enzymes to
excrete carcinogenic metabolites during DMBA-induced buccal pouch carcinogenesis in the
hamster . Similar effects of geraniol were observed in 4NQO-stimulated models of oral
squamous cell carcinoma Geraniol reduced the expression levels of Bcl-2, PCNA, mutant p53,
VEGF, c-fos, COX-2, NF-κB, and cyclin D1, whereas it elevated Bax, caspase-3 and -9 activity
in DMBA-treated hamsters . In addition, geraniol increased the nuclear levels of nuclear factor
erythroid 2-related factor 2 , a redox-sensitive transcription factor, in 4NQO-stimulated rats.

5) Anti-inflammatory activities

Inflammation is a normal protective response provoked by tissue injury or infections, and

functions to conflict invaders in the body (50). There is some evidence that essential oils have
anti-inflammatory
activity (51). For instance, citral, Geraniol, citronellol and carvone can prevent the formation of
proinflammatory cytokines such as TNF-α
(52). It is proven that Geraniol and some essential oils inhibit the formation of leukotriene, as a
mediator of inflammation. Hence, they are beneficial in the treatment of various inflammatory
diseases, including asthma, chronic bronchitis and allergic rhinitis among others (53). The
studies that performed the antiallergic effects (allergic rhinitis or pollinosis) of flavored and non-
flavored chewing gums displayed that gums fortified with peppermint oils such as geraniol,
1menthol, citronellol and 1, 8 –cineole were more efficient in decreasing rhinitis symptoms in
comparison with non flavoured gums and normal pappermint flavoured gums.
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