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Terpenes from Forests and Human Health


Abstract and Figures

Forest bathing has beneficial effects on human health via showering of forest aerosols as well as physical relaxation. Terpenes that consist of multiple isoprene units are the largest class of organic compounds produced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-containing plant oil has been used to treat various diseases without knowing the exact functions or the mechanisms of action of the individual bioactive compounds. This review categorizes various terpenes easily obtained from forests according to their anti-inflammatory, anti-tumorigenic, or neuroprotective activities. Moreover, potential action mechanisms of the individual terpenes and their effects on such processes, which are described in various in vivo and in vitro systems, are discussed. In conclusion, the studies that show the biological effectiveness of terpenes support the benefits of forest bathing and propose a potential use of terpenes as chemotherapeutic agents for treating various human diseases.
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Toxicol. Res.
Vol. 33, No. 2, pp. 97-106 (2017)
plSSN: 1976-8257 eISSN: 2234-2753 Review Article
Open Access
Terpenes from Forests and Human Health
Kyoung Sang Cho
, Young-ran Lim
, Kyungho Lee
, Jaeseok Lee
, Jang Ho Lee
and Im-Soon Lee
Department of Biological Sciences, Konkuk University, Seoul, Korea
Research Center for Coupled Human and Natural Systems for Ecowelfare, Konkuk University, Seoul, Korea
(Received February 6, 2017; Revised February 14, 2017; Accepted February 16, 2017)
Forest bathing has beneficial effects on human health via showering of forest aerosols as well as physical
relaxation. Terpenes that consist of multiple isoprene units are the largest class of organic compounds pro-
duced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-con-
taining plant oil has been used to treat various diseases without knowing the exact functions or the
mechanisms of action of the individual bioactive compounds. This review categorizes various terpenes
easily obtained from forests according to their anti-inflammatory, anti-tumorigenic, or neuroprotective
activities. Moreover, potential action mechanisms of the individual terpenes and their effects on such pro-
cesses, which are described in various in vivo and in vitro systems, are discussed. In conclusion, the stud-
ies that show the biological effectiveness of terpenes support the benefits of forest bathing and propose a
potential use of terpenes as chemotherapeutic agents for treating various human diseases.
Key words: Cancer, Forest therapy, Health, Immune function, Neuronal health, Terpene
Exposure to natural environment is beneficial to human
health (1). Among environmental exposures, the effects of
forest have been emphasized in many studies (2). Recently,
it has been shown that a short trip to forest environments
has therapeutic effects in children with asthma and atopic
dermatitis (3). Based on these studies, healthcare programs to
use forest have been developed in several countries (2,4,5).
For example, in the United States, “forest recreation” became
recognized as the most valuable use of forest in the 1960s in
light of social welfare (4). In Germany, a complementary
and alternative medicine practice called “Kneipp therapy” is
frequently used (6). Kneipp therapy includes five preven-
tive and curative methods created by Sebastian Kneipp, a
German priest (5), in which exercise in a forest is one of the
five core methods (2). Japan is one of the countries where
the forest usage programs for human health are well devel-
oped. The Forest Agency of the Japanese government intro-
duced the term “Shinrin-yoku,” defined as “taking in the
forest atmosphere or forest bathing” in 1982, and instituted
the “Therapeutic effects of forests plan” in 2005 (2).
Many studies have shown meaningful physiological effects
of forest atmosphere on people (2,7,8). These effects are
believed to be achieved by inhaling the forest atmosphere,
which includes various phytochemicals mainly produced by
trees. The major components of the forest atmosphere are
terpenes, which are the largest class of naturally occurring
organic compounds (9) with more than 40,000 structures
reported so far (9,10). Their basic chemical structure con-
sists of an isoprene unit (C
) (11). Depending on the number
of isoprene units, terpenes are classified as mono-, sesqui-,
and di-terpenes (C10, C15, and C20, respectively) (Fig. 1A)
(12). Terpenes have enormous chemical structural diversity
that is generated by various terpenoid metabolic pathways
as well as the specialized cell types that participate in their
biosynthesis (13). The biosynthesis of terpenes uses two
common C5 building blocks, dimethylallyl pyrophosphate
(DMAPP) and isopentenyl pyrophosphate (IPP), derived
from acetyl coenzyme A (14). Head-to-tail condensation of
DMAPP and IPP generates the monoterpene precursor, ger-
Correspondence to: Im-Soon Lee, Department of Biological Sci-
ences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul
05029, Korea
The list of abbreviations: BCP, β-caryophyllene; GPP, geranyl pyro-
phosphate; DMAPP, dimethylallyl pyrophosphate; IPP, isopentenyl
pyrophosphate; MAPK, mitogen-activated protein kinase; NF-κB,
nuclear factor kappa B; IL, interleukin; TNF-α, tumor necrosis fac-
tor-α; NO, nitric oxide; LPS, lipopolysaccharide; MMP, matrix metal-
loproteinases; AD, Alzheimer’s disease; PD, Parkinson’s disease.
This is an Open-Access article distributed under the terms of the
Creative Commons Attribution Non-Commercial License (http:// which permits unrestricted
non-commercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.
98 K.S. Cho et al.
anyl pyrophosphate (GPP, C10) (Fig. 1B) (15). Furthermore,
sesquiterpenes and diterpenes are created by condensation
of additional IPP units to GPP (Fig. 1B) (15,16).
Terpenes are produced by various plants, particularly
conifers (13). Many of the terpenes are associated with not
only the defense mechanism of the plant against herbivores
and the environment (11,17) but also their developmental
physiology (9). Korean forests mainly consist of various
types of conifers, and many terpenes derived from them
have been detected, such as α-pinene, β-pinene, camphor,
camphene, sabinene, limonene, menthol, cymene, and
myrcene (18). Conifer oleoresins contain monoterpenes (e.g.,
pinene and camphor) and diterpenes (e.g., taxadiene and
phytane) as major components and sesquiterpenes (e.g.,
nerolidol and (E)-α-bisabolene) as minor components (17).
Given that the forest atmosphere is beneficial to human
health and that terpenes are the main components of forest
aerosols, we reviewed the effects of various terpenes from
Korean forests on human health, especially on immunity,
cancer, and neuronal health.
Studies in recent decades have demonstrated that ter-
penes exert anti-inflammatory effects by inhibiting various
proinflammatory pathways in ear edema, bronchitis, chronic
obstructive pulmonary disease, skin inflammation, and osteo-
arthritis (19-23).
α-Pinene, found in oils of coniferous trees and rosemary,
showed anti-inflammatory activity by decreasing the activ-
ity of mitogen-activated protein kinases (MAPKs), expres-
sion of nuclear factor kappa B (NF-κB), and production of
interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and
nitric oxide (NO) in lipopolysaccharide (LPS)-induced mac-
rophages (24). In ovalbumin-sensitized mouse model of
allergic rhinitis, pretreatment with α-pinene decreased clini-
cal symptoms and levels of immunoglobulin E and IL-4
(25). In human chondrocytes, α-pinene inhibited IL-1β-
induced inflammation pathway by suppressing NF-κB, c-
Jun N-terminal kinase (JNK) activation, and expression of
Fig. 1. Structures of various terpenes (A) and terpene biosynthesis pathway for pinenes (B). (A) Depending on the carbon number,
terpenes are classified as mono-, sesqui-, and di-terpenes. (B) Using DMAPP and IPP as building blocks, monoterpenes are produced
from GPP. Especially, α-pinene and β-pinene are generated via cyclisation of linaloyl pyrophosphate and the loss of a proton from the
carbocation equivalent.
Terpenes and Human Health 99
iNOS and matrix metalloproteinases (MMP)-1 and -13,
suggesting its role as an anti-osteoarthritic agent (19). Strong
anti-inflammatory activity was observed when α-pinene
was used in combination with two active ingredients of
frankincense, linalool and 1-octanol (22).
Another naturally occurring monoterpene d-limonene was
reported to reduce allergic lung inflammation in mice prob-
ably via its antioxidant properties (26). It also reduced car-
rageenan-induced inflammation by reducing cell migration,
cytokine production, and protein extravasation (27). Simi-
lar to α-pinene, d-limonene exerted an anti-osteoarthritic
effect by inhibiting IL-1β-induced NO production in human
chondrocytes (28). d-Limonene treatment reduced doxoru-
bicin-induced production of two proinflammatory cytokines,
TNF-α and prostaglandin E-2 (PGE
) (29).
Monoterpene p-cymene treatment reduced elastase-induced
lung emphysema and inflammation in mice. It reduced the
alveolar enlargement, number of macrophages, and levels
of proinflammatory cytokines such as IL-1β, IL-6, IL-8,
and IL-17 in bronchoalveolar lavage fluid (BALF) (30).
Similarly, p-cymene showed a protective effect in a mouse
model of LPS-induced acute lung injury by reducing the
number of inflammatory cells in the BALF and expression
of NF-κB in the lungs (31) and by reducing production of
proinflammatory cytokines and infiltration of inflammatory
cells (32). Mechanistically, p-cymene blocks NF-κB and
MAPK signaling pathways. It has been reported that p-
cymene reduces production of TNF-α, IL-6, and IL-β in
LPS-treated RAW 264.7 macrophages. In C57BL/6 mice,
TNF-α and IL-1β were downregulated and IL-10 was upreg-
ulated by p-cymene treatment. It also inhibited LPS-induced
activation of ERK 1/2, p38, JNK, and IκBα (32,33).
Treatment with linalool, a natural compound found in
essential oils of aromatic plants, inhibited cigarette smoke-
induced acute lung inflammation by inhibiting infiltration
of inflammatory cells and production of TNF-α, IL-6, IL-
1β, IL-8, and monocyte chemoattractant protein - 1 (MCP-
1), as well as NF-κB activation (20). In another lung injury
model, linalool attenuated lung histopathologic changes in
LPS-induced mice. In in vitro experiments, linalool reduced
production of TNF-α and IL-6 and blocked phosphorylation
of IκBα protein, p38, and JNK in LPS-stimulated RAW
264.7 macrophages (34). Similarly, linalool inhibited pro-
duction of TNF-α, IL-1β, NO, and PGE
in LPS-stimulated
microglia cells (35). Li et al. (35) showed that the anti-
inflammatory effect of linalool is involved in activation of
Nrf2/heme oxygenase-1 (HO-1) signaling pathway. Frank-
incense oil extract, which contains linalool, exhibited anti-
inflammatory and analgesic effects in a xylene-induced ear
edema model and a formalin-inflamed hind paw model by
inhibiting COX-2 (22).
The monoterpene γ-terpinene, present in the essential oil
of many plants including Eucalyptus, reduced the acute
inflammatory response. It reduced carrageenan-induced paw
edema, migration of neutrophil into lung tissue, and IL-1β
and TNF-α production and inhibited fluid extravasation
(36). Terpinene-containing essential oil from Liquidambar
formosana leaves reduced inflammatory response in LPS-
stimulated mouse macrophages by reducing reactive oxy-
gen species (ROS), JNK, ERK, p38 MAP kinase, and NF-
κB (37). Another terpinene-containing essential oil from
Citrus unshiu flower or fingered citron (C. medica L. var.
sarcodactylis) reduced LPS-stimulated PGE
and NO pro-
duction in RAW 264.7 cells. Furthermore, production of
inflammatory cytokines, such as IL-1β, TNF-α, and IL-6,
was also reduced in macrophages (38,39).
Borneol, a bicyclic monoterpene present in Artemisia,
Blumea, and Kaempferia, has been used in traditional medi-
cine. Borneol alleviated acute lung inflammation by reduc-
ing inflammatory infiltration, histopathological changes, and
cytokine production in LPS-stimulated mice. It suppressed
phosphorylation of NF-κB, IκBα, p38, JNK, and ERK (40).
Oral administration and intrathecal injection of borneol
showed antihyperalgesic effects on inflammatory pain in
complete Freund’s adjuvant-induced hypersensitive animal
models by enhancing GABA
R (Gamma-Aminobutyric Acid
Type A Receptor)-mediated GABAergic transmission (41).
Borneol inhibited migration of leukocytes into the perito-
neal cavity in carrageenan-stimulated mice, suggesting its
anti-inflammatory function (42). In addition, borneol inhib-
ited TRPA1, a cation channel that is involved in inflamma-
tion and noxious-pain sensing, suggesting that its use as an
anti-inflammatory agent for neuropathic-pain and trigemi-
nal neuralgia (43).
A natural sesquiterpene β-caryophyllene (BCP) was re-
ported to protect against neuroinflammation in a rat model
of Parkinson’s disease (PD) by attenuating production of
proinflammatory cytokines and inflammatory mediators such
as COX-2 and iNOS (44). Chronic treatment with BCP
attenuated alcohol-induced liver injury and inflammation by
reducing the proinflammatory phenotypic switch of hepatic
macrophages and neutrophil infiltration. The beneficial
effects of BCP on liver injury are mediated by cannabinoid
2 (CB2) receptor activation (45). Prolonged administration
of BCP reduced proinflammatory cytokines in pancreatic
tissue of streptozotocin-induced diabetic rats (46). BCP
reduced expression of Toll-like receptor 4 and macrophage
inflammatory protein-2, and phosphorylation of ERK, p38,
JNK, and NF-κB in D-galactosamine and LPS-induced
liver injury mouse model (47).
Besides the aforementioned terpenes, anti-inflammatory
effects have been reported with sabinene itself or sabinene-
containing oil (48,49), bornyl acetate (50) and myrcene (28).
Tumorigenesis is a multifaceted process, the progression
of which is associated with several hallmarks, including
100 K.S. Cho et al.
uncontrolled cell growth, dysregulation of apoptosis, activa-
tion of invasion, induction of angiogenesis, and metastasis.
Terpenes have been shown to exert anti-tumorigenic effects
against such processes in a number of in vivo and in vitro
systems, thus suggesting their potential uses as chemothera-
peutic agents for treating tumors.
A number of monoterpenes have been reported to exert
chemopreventive effects against tumors (51). Of these, the
anti-tumorigenic activity of d-limonene is well-established.
Numerous studies have demonstrated the protective effects
of d-limonene against chemical-induced tumors in various
tissue types such as breast, intestine, pancreas, liver, and
colon (52-57). Lu et al. (57) revealed that d-limonene could
inhibit the proliferation of human gastric cancer cells by
inducing apoptosis. Later, it was demonstrated that apopto-
sis of tumor cells by d-limonene could be mediated by the
mitochondrial death pathway via activated caspases and
PARP cleavage as well as by the suppression of the PI3K/
Akt pathway (58,59). In addition, positive effects on NK
(Natural Killer) activities were demonstrated not only in the
in vitro treatment of tumor cell lines with monoterpenes
released from trees, such as d-limonene and α-pinene, but
also in forest bathing trips by increasing intracellular levels
of anti-tumor proteins such as perforin, granulysin, and
granzymes A/B (60).
Anti-tumor effects of pinenes are well established on
tumor lymphocytes as well as tumor cell lines (61). Matsuo
et al. (62) identified proapoptotic and anti-metastatic activi-
ties of α-pinene in a melanoma model. Later, it was revealed
in human hepatoma Bel-7402 cells that the proapoptotic
effect of α-pinene is associated with induction of G2/M cell
cycle arrest (63). In addition, α-pinene triggers oxidative
stress signaling pathways in A549 and HepG2 cells (64).
However, Kusuhara et al. (65) reported that mice kept in a
setting enriched with α-pinene showed reduction in mela-
noma sizes, while in vitro treatment of melanoma cells with
α-pinene had no inhibitory effect on cell proliferation, sug-
gesting that the in vivo result may not be due to a direct
effect of α-pinene. Investigation of β-pinene also revealed
its cytotoxic activity against cancer and normal cell lines
with a more pronounced effect on neoplastic cells in the
majority of cases, showing acceptable chemotherapeutic
potency (66,67).
Perillyl alcohol is a naturally occurring monoterpene, and
a metabolite of limonene. Despite preclinical evidence of
anticancer activity, perillyl alcohol appeared to have no clini-
cal antitumor activity upon oral administration to patients
with advanced colorectal carcinoma (68). However, currently,
it is under preclinical development as a potential clinical
treatment for patients with brain tumor (69). Perillic acid is
a major metabolite of perillyl alcohol. Upon examining the
effects of perillic acid on lung metastasis induced by mela-
noma cells in mice, it was observed that administration of
perillic acid remarkably reduced the metastatic tumor nod-
ule formation by exerting an inhibitory effect on cell growth
by G1 arrest (70,71).
p-Cymene has been reported to have cytotoxic effects on
tumor cell lines (72). Recently, Li et al. (73) evaluated ben-
eficial effects of p-cymene on in vitro TPA-augmented inva-
siveness of HT-1080 cells, and found that it inhibits MMP-9
expression, but enhances TIMP-1 production along with the
suppression of ERK1/2 and p38 MAPK signal pathways in
tumor cells, suggesting that p-cymene is an effective candi-
date for the prevention of tumor invasion and metastasis.
Myrcene, the acyclic monoterpene, also exhibits signifi-
cant antiproliferative and cytotoxic effects in various tumor
cell lines such as MCF-7 (breast carcinoma), HeLa (human
cervical carcinoma), A549 (human lung carcinoma), HT-29
(human colon adenocarcinoma), P388 (leukemia), and Vero
(monkey kidney) as well as mouse macrophages (74,75).
Essential oil from Vepris macrophylla demonstrated a strong
cytotoxic effect, suggesting that the effect may be attributed
to the presence of specific components, among which is
myrcene (76).
Terpenes with more complex structures than monoterpenes,
including sesquiterpenoids derived from sesquiterpenes by
biochemical modifications, have demonstrated anticancer
ability as well. The anticancer effect of various sesquiter-
penoids is mediated via inhibition of inflammatory responses,
prevention of metastasis, and induction of apoptosis (77).
α-Caryophyllene, known as humulene, is a naturally occur-
ring monocyclic sesquiterpene. BCP, an isomer of α-caryo-
phyllene, has been identified as an active component of an
essential oil mixture that not only prevents solid tumor
growth and proliferation of cancer cell lines but also inhib-
its lymph node metastasis of melanoma cells in high-fat
diet-induced obese mice (78,79). Sarvmeili et al. (80) re-
ported that Pinus eldarica essential oil, of which BCP was
the major component, exerts cytotoxic effects on HeLa and
MCF-7 cell lines.
As described above, numerous in vitro and in vivo experi-
mental results have demonstrated that the toxicity of ter-
pene affects mainly cancer cells without harming healthy
ones, confirming their efficiency in chemotherapeutic treat-
ment of cancer. Thus, it is noteworthy that the use of ter-
pene and its derivatives can be considered to potentiate the
action of existing conventional therapies (81,82).
Numerous studies have shown that essential oils derived
from various plants have neuroprotective effects against neu-
rodegenerative conditions in vivo and in vitro (83-90). There-
fore, as a main component of plant essential oils, terpenes
may be beneficial to human neuronal health. However, only
few studies have focused on the beneficial effects of ter-
pene components of plant essential oils on neuronal health.
So far, several terpenes, produced by a variety of plants,
Terpenes and Human Health 101
Tab le 1. Studies reporting the effects of terpenes on human health
Class Terpene Structure Effect Related literature
Mono- 1,8-Cineole Antioxidation
1-Octanol Anti-inflammation (73)
Borneol Anti-inflammation
Bornyl acetate Anti-inflammation (50)
Cymene Anti-inflammation
Limonene Anti-inflammation
Linalool Anti-inflammation (20,22,34,35)
Myrcene Anti-inflammation
Perillyl alcohol Anti-cancer (68-71)
Pinene Anti-inflammation
Sabinene Anti-inflammation (48,49)
Terpinene Anti-inflammation (36-39)
Sesqui- Caryophyllene Anti-inflammation
102 K.S. Cho et al.
have been associated with neuronal health. Among those,
borneol is a bicyclic monoterpene present in several medici-
nal plants (91-94). Previous studies showed that borneol has
free radical scavenging activity (95) and is a major compo-
nent of essential oil of SuHeXiang Wan (92) whose neuro-
protective function has been reported in in vivo and in vitro
models of Alzheimer’s disease (AD) (96-99). Moreover, a
recent study showed that borneol exerts a neuroprotective
effect against β-amyloid (Aβ) cytotoxicity via upregulation
of nuclear translocation of Nrf2 and expression of Bcl-2
(100). In addition, treatment with isoborneol, a monoter-
penoid alcohol, significantly reduced 6-hydroxydopamine-
induced ROS generation and cell death in human neuroblas-
toma SH-SY5Y cells, suggesting that isoborneol may be a
potential therapeutic agent for treatment of neurodegenera-
tive diseases associated with oxidative stress (101). Salvi-
anic borneol ester, a new compound synthesized from salvianic
acid A and borneol, also exerts anti-amyloid and neuropro-
tective effects in both SH-SY5Y cells and motor neuron
hybridoma VSC 4.1 cells (102).
BCP also has neuroprotective functions. It has been
reported that BCP has antioxidant effects (103), and func-
tions as a regulator of several neuronal receptors and shows
various pharmacological activities including neuroprotec-
tion (104). Neuroprotective effects of BCP have been reported
in both AD and PD animal models. Oral treatment with BCP
prevented AD-like phenotype such as cognitive impair-
ment and activation of inflammation through CB2 receptor
activation and the PPARγ pathway (105). As described above,
BCP administration also exerts neuroprotective effects in
rotenone-challenged rat model of PD by reducing neuro-
inflammation (44).
Other monoterpenes such as α-pinene and 1, 8-cineole
also exert neuroprotective effects by regulating gene expres-
sion. They protected PC12 cells against oxidative stress-
induced apoptosis through ROS scavenging and induction
of nuclear Nrf2 factor followed by enhanced expression of
antioxidant enzymes including catalase, superoxide dis-
mutase, glutathione peroxidase, glutathione reductase, and
HO-1 (106). Similarly, p-cymene has cholinergic effects
through regulation of expression of several genes in Caenor-
habditis elegans (107). Given that terpenes are major com-
ponents of essential oils of various medicinal plants with
neuroprotective functions, studies to find the beneficial roles
of terpenes in neurodegenerative diseases will provide a
promising way to develop therapeutics.
Essential oils obtained from plants have been used in
diverse traditional medicines because of their broad benefi-
cial effects on human health (108). To date, many terpenes
from essential oils as well as forest bathing have been
reported to exhibit strong biological activities. This review
categorized the terpenes that have presented important results
in cell and animal systems according to their anti-inflamma-
tory, anti-tumorigenic, or neuroprotective activities (Table
1). Although data elucidating the possible action mecha-
nisms of these compounds are increasing, numerous stud-
ies still present only preliminary screening results. Thus, to
investigate the future chemotherapeutic uses of terpenes, it
is necessary to explore further the detailed action mecha-
nisms including signaling pathways that are associated with
their biological functions. In addition, understanding of the
relationship between the diverse chemical structures of ter-
penes and the in vivo physiological roles of these compounds
may provide critical insights for the future development of
therapeutics with enhanced selectivity and specificity.
So far, many studies have extensively reported the phar-
maceutical activities of monoterpenes among the terpenes.
Monoterpenes, formed from the coupling of two isoprene
units (C10), are the major molecules consisting 90% of the
essential oils (109). However, in recent years, small sub-
groups of other terpenes and terpenoids that exhibit diverse
biological activities have been isolated or synthesized, pro-
viding a source of novel chemotherapeutic molecules. The
use of various terpenes in clinical trials is currently limited
due to insufficient data from human studies. However, their
use as potent chemotherapeutic compounds alone, as well
as in combination with previously proven chemotherapeu-
tic drugs, to increase effectiveness and decrease doses is
expected to increase as data on their safety and efficacy in
in vivo and in vitro systems are accumulated.
The authors declare that they have no competing inter-
This research was supported by the National Research
Foundation of Korea (NRF) funded by the Ministry of Sci-
ence, ICT and Future Planning (NRF-2016M3C1B6928005).
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... It is claimed that biogenic volatile organic compounds (BVOCs) in the forest air are one of the main forest attributes contributing to human health improvement [12]. Air BVOCs include, among others, the atmospheric trace gas compounds named terpenes, which have been demonstrated to have different biological activities that could contribute to human health. ...
... For this research, the composition of terpenes in the needles of two common coniferous species, fir (Abies alba) and spruce (Picea abies) growing in NP Tara was investigated in order to define their potential to positively impact human health. Further, the composition of terpenes, with the focus on monoterpenes and sesquiterpenes, was further investigated since there is a general opinion that these trees' compounds are one of the main factors that contribute to the improvement of human health [12]. ...
... Some of the major benefits that have been extrapolated in previous research are embodied in the fact that these compounds have the potential to be used in therapeutic and medicinal purposes as an anti-inflammatory, antibacterial, analgesics, and many other curative, therapeutic, or preventive agents, as discussed in the previous section [74,75]. A deep inhalation of the forest atmosphere during a 2-h forest bathing walk may, therefore, be sufficient for the lungs to be filled with a variety of terpenes that have the power to address different aspects of human health [12]. ...
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Numerous medical studies have shown the positive effects of forests on different aspects of human health. This study deals with the content of major terpenes in dominant coniferous species in Tara National Park, Serbia, in order to explore the potential for the development of a novel health tourism programme based on forest therapy. Main terpenes were analysed using a headspace-sampling technique coupled with gas-chromatography-mass spectrometry (Head-space-GC/MS). Needles of fir and spruce growing in the vicinity of hiking trails were investigated for possibilities to perform such therapy. Major detected terpenes were α-cadinol and spathulenol previously described as antiviral, antitumor, antimicrobial and immunomodulatory agents. The results of the study were favourable and worked well with the existing walking infrastructure in the observed area of the Tara Mountain, as they act as invaluable resources for designing the structured forest bathing walks. The study not only adds to the knowledge in the environmental and public health realm but also to tourism and sustainability studies.
... Source: (a): [39]; (b) [91] (c) [92]. (M) monoterpenes, (S) sesquiterpenes). ...
... As previously stated, monoterpenes and sesquiterpenes constitute the resources (terpenoids) having the greatest potential for functional purposes [39,81,87,91,92]. Table 2 lists the breadth of the BVOCs potentially released by the major European forest tree species. ...
... By adopting this approach, FT-ES can be described as the set of information allowing general medicine practitioners (GMPs) to interact with information provided for preventive, integrative, and rehabilitative medical purposes. Table 3 reports the heterogeneity of effects of terpenes on human health [39]. The HD3 dynamic-relational model focuses on the ability of the single tree species to produce BVOCs performing very specific (antioxidative, anti-inflammatory, neuroprotective, and immunostimulative) functions. ...
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Background: Several studies have suggested the possibility of obtaining specific respiratory benefits by experiencing forests and other natural resources. Despite this, forests have never been considered according to such potential. This study aims to compare municipalities by considering the absence/presence of tree species generating ‘above threshold’ potential respiratory benefits. Methods: The autonomous Region of Friuli Venezia Giulia in Italy has been assumed as a research area. The natural resource based view (NRBV), postulating the strategic role played by natural resources in achieving both above-average (thus ‘valuable’) and ‘concentrated’ (thus ‘rare’ among competitors) performance, has been adopted. The literature reviews dealing with potential respiratory benefits of biogenic organic compounds (BVOCs) emitted by trees, published within the ‘forest therapy’ research field, have been adopted. Three analysis models rating tree species by their potential respiratory benefits in ‘holistic-general’ (P1), ‘particular’ (P2), and ‘dynamic” terms (P3) have been outlined. The resulting overall potentials of tree species have been assessed by adopting the well-rooted Hollerith distance (HD) model. Tree species have been rated “1” when they satisfy one or more of 58 potential respiratory benefits. Municipalities have been ranked by considering the surface area covered by forest types whose dominant tree species achieve above-average potential respiratory benefits. QGIS software has been adopted to geographically reference the results obtained. Results: (P1) Valuable municipalities include those covered by both coniferous and deciduous forests; (P2–3) Municipalities achieving the highest potential respiratory benefits, in both particular and dynamic terms, have been mapped. Discussion: Forest-based initiatives that are running in the preselected municipalities can be both further improved and diversified in a targeted way. Conclusions: Despite some limitations mostly embedded in the concept of ‘model’, this study allows scholars to reduce uncertainties when locating municipalities in which to conduct local-scale experiments.
... Therefore, forest tourism offers a wide range of benefits including recreation, health, medical treatment, culture, and education [65][66][67][68][69]. Furthermore, the pursuit of wellness is a major motive of forest tourists [3,70]. With pure air, high-quality surface water, dense anions, a high concentration of terpenes, and a pleasant climate, forests enable tourists to enjoy physical and mental health benefits [71,72]. In addition, the quality and value of products and services are considered perceived-value benefits [73,74]. ...
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Establishing a relationship model between environmental protection and resource utilization attitude and consumption intention is the key to promoting the sustainable development of forest tourism. From the standpoint of the Stimulus–Organism–Response (SOR) framework, the purpose of this study is to explore the complex causal relationships between perceived benefits, attitudes toward environmental protection, resource utilization attitudes, and consumption intentions in the context of forest tourism. The research data have been collected using a questionnaire survey of 436 tourists at Siming Mountain in the suburbs of Ningbo city, China. Furthermore, it is analyzed by structural equation modeling. The results indicate a positive correlation between the perceived benefits and tourists’ consumption intention that is mediated by the tourists’ attitude toward resource utilization. Although the independent mediating effect of environmental protection attitude is not supported in this study, both attitudes have played a chain-mediating role between perceived benefit and consumption intention. This study contributes to the existing knowledge by measuring the impact of perceived benefits and environmental attitudes of forest tourists on consumption intentions.
... Indeed, empirical evidence suggests that exposition to natural environments improves per se well-being, reduces stress and depressive mood (Antonelli et (2020). Some authors suggest that the inhalation of terpenes, as main volatile oils contained in forest aerosols, is the mechanism that mediates the relationship between exposition to forests and health improvements (Cho et al. 2017). It is also argued that the speci c biome of the forest to which people are exposed is also a factor to understand how exposure to forests have such a restorative and healing effect for humans' health (Bach et al. 2020a(Bach et al. , 2020b. ...
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Forest Bathing (FB) is a nature-therapeutic modality that has evidenced positive effects on individuals' mental health and it is also considered a sustainable touristic activity. However, its benefits have mainly been studied in Asian biomes and more cross-cultural research is needed to evaluate if its benefits are also generalizable to other forests and biomes of the world, such as the Mediterranean. Accordingly, 86 healthy adults of the general population were assessed before and after a FB near Barcelona (Spain) during the COVID-19 pandemic. A control hiking-group of participants was also analysed to contrast the FB effects on anxiety, affect, mood states and mindfulness. Results have shown that the guided practice of FB in Mediterranean-Catalan forests enhances significanlty mindfulness states and positive affect and reduces anxiety and negative affect, with effect sizes being large to very large. Hiking also induced significant changes in all variables tested, but FB showed higher effect sizes. An exploratory analysis also revealed a different profile of the FB participants compared to the hiking practitioners, being highly educated women living in urban areas and with lower basal levels of psychological wellbeing. Accordingly, it is concluded that Mediterranean FB, and also hiking to a lesser degree, might be cost-effective strategies to promote and restore psychological well-being after the Covid-19 pandemic and to promote sustainable tourism in Mediterranean biomes of the European forested and protected areas.
... The key to shinrin-yoku is connecting with the atmosphere of the forest, taking in forest aerosols, volatile organic compounds known phytoncides [4]. Phytoncides are inhaled airborne particles that trees naturally emit during different stages of development [5][6][7][8][9]. ...
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Shinrin-yoku, forest bathing, may provide relief from chronic and breakthrough pain in patients with axial spondyloarthritis and improve immune function through increasing NK cell numbers and activity and their downstream effectors, perforin and granulysin, after chemo- or radiation therapy in breast and prostate cancer patients. The aim of this paper is to describe the study protocol for a simulated forest immersion therapy using virtual reality and atomized phytoncides, volatile organic compounds found in forested areas designed to effect positive change for these two patient populations. The setting, including the room set up and samples with inclusion/exclusion specific to this type of intervention, is outlined. Measures and calibration procedures pertinent to determining the feasibility of simulated forest immersion therapy are presented and include: ambient and surface room temperatures and relative humidity in real time, ambient ultrafine particulate matter, ambient droplet measurement that coincides with volatile organic compounds, specific phytoncides, and virtual reality and atomization of phytoncide set up. Particular lessons learned while training and setting up the equipment are presented. Simulated forest immersion therapy is possible with attention to detail during this early phase when development of methods, equipment testing, and feasibility in deploying the intervention become operational. The expected outcome of the development of the methods for this study is the creation of a standardized approach to simulating forest therapy in a controlled laboratory space.
... • Das gedämpfte Licht im Wald sowie das ständig wechselnde Spiel von Licht und Schatten lässt visuelle Eindrücke permanent variieren und unterstützt eine Form von ungerichteter Aufmerksamkeit, welche zur Entspannung beiträgt (Kaplan & Kaplan, 1989). • Natürliche Gerüche machen sich besonders bei Nadelhölzern nach Regenereignissen oder bei Trockenheit durch volatile Terpene positiv in der olfaktorischen Wahrnehmung bemerkbar (Cho et al., 2017 . Daneben lassen sich weitere positive gesundheitliche Aspekte von Waldbesuchen beschreiben. ...
Auch im Ökosystem Wald ist ein erheblicher Artenschwund festzustellen. Neben der Ausweitung von Schutzgebieten bzw. der weiteren Nutzungseinstellung, um diesem entgegenzuwirken, besteht eine Alternative auch darin, in weiter wirtschaftlich genutzten Wäldern mehr natürliche Strukturen als bisher zuzulassen. Dazu zählen etwa das Belassen bzw. die Anreicherung von Totholz. Dieser Beitrag thematisiert, wie sich diese Veränderungen auf die Erholungsleistung auswirken, eine der wichtigsten kulturellen Ökosystemleistungen (ÖSL) von Wäldern. Zur Operationalisierung der Erholungswirkung von Wäldern wurde ein Choice Experiment eingesetzt, das auf einer Befragung einer repräsentativen Bevölkerungsstichprobe in Bayern basiert. Die Ergebnisse zeigen, dass die Totholz-Menge keine Auswirkungen auf die Erholungspräferenzen der Bevölkerung hat. Allerdings hat die Totholzqualität durchaus einen Einfluss, wobei die an natürliche Strukturen erinnernden Zustände präferiert werden. Da die Befragten gleichzeitig stärkeren Artenschutz in Wäldern bevorzugen, besteht kein Widerspruch zwischen den ÖSL Habitatleistung und Erholung, was für die weitere Umsetzung von integrativen Waldnaturschutzkonzepten in der Forstpraxis spricht.
... • Das gedämpfte Licht im Wald sowie das ständig wechselnde Spiel von Licht und Schatten lässt visuelle Eindrücke permanent variieren und unterstützt eine Form von ungerichteter Aufmerksamkeit, welche zur Entspannung beiträgt (Kaplan & Kaplan, 1989). • Natürliche Gerüche machen sich besonders bei Nadelhölzern nach Regenereignissen oder bei Trockenheit durch volatile Terpene positiv in der olfaktorischen Wahrnehmung bemerkbar (Cho et al., 2017). Ob sich darüber hinaus positive gesundheitliche Effekte ableiten lassen, ist jedoch noch offen. ...
Global sind Wälder seit Jahrzehnten sowohl durch den anthropogen verstärkten Klimawandel als auch durch den damit teilweise einhergehenden Biodiversi-tätsverlust von massiven Änderungen betroffen. Dass Menschen dabei immer stärker in bislang kaum berührte Ökosysteme eingreifen, eröffnet neue Über-tragungswege für Zoonosen, die ihren Niederschlag in Pandemien finden können. Zusätzlich bieten, auf einer globalen Skala, Wälder den Wohn-und Lebensraum indigener und auch isolierter Völker und sind auch vor diesem Hintergrund zu schützen. Denn Wälder stellen zahlreiche Ökosystemleistun-gen für das Überleben, das Wohlbefinden und die Erhaltung und Stärkung von Gesundheit von Menschen zur Verfügung. Wälder bieten Erholungsräume, die sämtliche Sinne positiv ansprechen können, welche daher als eine Ressource angesehen werden können, die sowohl auf körperliche, mentale und soziale Aspekte von Gesundheit wirkt.
... Terpenoids or isoprenoids are high in plants where many can be considered secondary metabolites and have fundamental roles in the metabolism of all organisms [23]. Terpenoid secondary metabolism in plants began with the recruitment of genes from primary metabolism [24] and accelerated due to the proliferation of cytochrome P450 and terpene synthase gene families in the genomes of plants [25]. ...
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Natural products are substances that are confined from living organisms, they are in the form of primary or secondary metabolites. Secondary metabolites are compounds with varied chemical structures, produced by some plants and strains of microbial species. Unlike primary metabolites (nucleotides, amino acids, carbohydrates , and lipids) that are essential for growth, secondary metabolites are not. Secondary metabolites are produced or synthesized during the stationary stage. In this chapter, we will discuss secondary metabolites from natural products synthesized mainly by plants, fungi, and bacteria. Plants synthesize a large diversity of secondary metabolites; plant secondary metabolites are split into four groups namely alkaloids, phenolic compounds, terpenoids, and glucosinolates. Several classes of fungal and bacterial secondary metabolites, their sources, and pharmacological uses associated with the secondary metabolites are also discussed. Therefore, several classes of secondary metabolites are responsible for the biological and pharmacological activities of plants and herbal medicines.
... Depending on the number of linked isoprene units, the resulting terpenes are classified into hemi-, mono-, sesqui-, di-, sester-, tri-, sesquar-, tetra-, and polyterpenes. For many decades, it has been suggested that terpenes and terpenoids are potential chemopreventive and therapeutic agents for various diseases (209). ...
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Percutaneous coronary intervention (PCI) is one of the most effective reperfusion strategies for acute myocardial infarction (AMI) despite myocardial ischemia/reperfusion (I/R) injury, causing one of the causes of most cardiomyocyte injuries and deaths. The pathological processes of myocardial I/R injury include apoptosis, autophagy, and irreversible cell death caused by calcium overload, oxidative stress, and inflammation. Eventually, myocardial I/R injury causes a spike of further cardiomyocyte injury that contributes to final infarct size (IS) and bound with hospitalization of heart failure as well as all-cause mortality within the following 12 months. Therefore, the addition of adjuvant intervention to improve myocardial salvage and cardiac function calls for further investigation. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in Chinese herbal medicine. Great effort has been put into phytochemicals because they are often in line with the expectations to improve myocardial I/R injury without compromising the clinical efficacy or to even produce synergy. We summarized the previous efforts, briefly outlined the mechanism of myocardial I/R injury, and focused on exploring the cardioprotective effects and potential mechanisms of all phytochemical types that have been investigated under myocardial I/R injury. Phytochemicals deserve to be utilized as promising therapeutic candidates for further development and research on combating myocardial I/R injury. Nevertheless, more studies are needed to provide a better understanding of the mechanism of myocardial I/R injury treatment using phytochemicals and possible side effects associated with this approach.
Since the 19th century, Italy’s mountain regions have suffered from depopulation and land abandonment. How can we counter this phenomenon? Here, we present three cases of innovative and participatory approaches implemented in the Eastern Alps of Friuli Venezia Giulia. Forest therapy is a new approach to medical therapy based on the beneficial effects on the human health of frequenting forests. It also has the potential to provide space for local economic initiatives, e.g., hospitality services. Land consolidation associations were created in France to collectively restore the productivity of fragmented and abandoned farmland. They can evolve into long-term planning for the conservation of landed wealth and the valorization of territories. Finally, Mountaineering villages have the potential to develop a more sustainable form of tourism by fostering a sense of responsibility for the natural and cultural heritage of the European Alps, in accordance with the Alpine Convention. These initiatives share the involvement of local actors in the definition of local development strategies, the capability of enhancing endogenous resources and increasing the environmental value of places, the importance of offering qualified and organized services, and the ability to support the local socioeconomic system. The adoption of innovative and participatory approaches such as these has the potential to revert depopulation and economic depression trends in mountain areas.
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Several attempts have so far been made in the search of new anticancer agents of plant origin. Some studies have reported that different species of Pine genus possess cytotoxic activities against various cancer cell lines. In the present study, we evaluated the cytotoxic effects of Pinus eldarica bark and leaf extracts or leaf essential oil on HeLa and MCF-7 tumor cell lines. Hydroalcoholic and phenolic extracts and the essential oil of plant were prepared. Total phenolic contents of the extracts were measured using Folin-Ciocalteu reagent. Essential oil components were determined by gas chromatography-mass spectroscopy (GC-MS). Cytotoxic activity of the extracts and essential oil against HeLa and MCF-7 tumor cell lines were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The polyphenolic content of hydroalcoholic and phenolic extracts of the bark and hydroalcoholic extract of the leaf were 48.31%, 47.2%, and 8.47%, respectively. According to the GC-MS analysis, the major components of the leaf oil of P. eldarica were: β -caryophyllene (14.8%), germacrene D (12.9%), α–terpinenyl acetate (8.15%), α –pinene (5.7%), and –α humulene (5.9%). Bark extracts and leaf essential oil of P. eldarica significantly reduced the viability of both HeLa and MCF-7 cells in a concentration dependent manner. However, leaf extract showed less inhibitory effects against both cell lines. The essential oil of P. eldarica was more cytotoxic than its hydroalcoholic and phenolic extracts. The terpenes and phenolic compounds were probably responsible for cytotoxicity of P. eldarica. Therefore, P. eldarica might have a good potential for active anticancer agents.
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Cholinergic dysfunction is manifested in a plethora of neurodegenerative and psychiatric disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. The extent of cholinergic affliction is maximum in Alzheimer’s disease which is a progressive neurodegenerative disorder involving death of cholinergic neurons. To this date, the therapeutic management of cholinergic dysfunction is limited to provide symptomatic relief through the use of acetylcholinesterase (Ache) inhibitors only. The present study elaborates the potential of thyme oil and its individual components in curtailing cholinergic deficits. We found that thyme oil augments neurotransmission by modulating synaptic acetylcholine (Ach) levels and nicotinic acetylcholine receptor activity, being orchestrated through upregulation of genes cho-1, unc-17 and unc-50. Studies on individual components revealed para-cymene (1-methyl-4-propan-2-ylbenzene) as the active component of thyme oil, contributing its effects through upregulation of cho-1, cha-1, unc-17 and unc-50, while downregulating ace-1 and ace-2. Interestingly, thymol and gamma-terpinene which although were devoid of any activity individually, exhibited significantly enhanced synaptic Ach levels and nicotinic acetylcholine receptor (nAchR) responsiveness, when administered in combination. Our findings advocate thyme oil and its constituents as potential candidates for amelioration of cholinergic dysfunction. The study is speculated to make a way for a new line of “phytomolecules-based drugs” from the diverse pool of natural compounds.
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Humans have evolved into what they are today after the passage of 6-7 million years. If we define the beginning of urbanization as the rise of the industrial revolution, less than 0.01% of our species’ history has been spent in modern surroundings. Humans have spent over 99.99% of their time living in the natural environment. The gap between the natural setting, for which our physiological functions are adapted, and the highly urbanized and artificial setting that we inhabit is a contributing cause of the “stress state” in modern people. In recent years, scientific evidence supporting the physiological effects of relaxation caused by natural stimuli has accumulated. This review aimed to objectively demonstrate the physiological effects of nature therapy. We have reviewed research in Japan related to the following: (1) the physiological effects of nature therapy, including those of forests, urban green space, plants, and wooden material and (2) the analyses of individual differences that arise therein. The search was conducted in the PubMed database using various keywords. We applied our inclusion/exclusion criteria and reviewed 52 articles. Scientific data assessing physiological indicators, such as brain activity, autonomic nervous activity, endocrine activity, and immune activity, are accumulating from field and laboratory experiments. We believe that nature therapy will play an increasingly important role in preventive medicine in the future.
Background and aims: Beta-caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo reported to involve activation of cannabinoid 2 receptors (CB2) that are predominantly expressed in immune cells. Herein, we evaluated the translational potential of BCP using a well-established model of chronic and binge alcohol-induced liver injury. Methods: In this study we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses. Serum and hepatic BCP levels were also determined by GC/MS. Results: Chronic treatment with BCP attenuated the chronic and binge alcohol-induced liver injury and inflammation by attenuating the pro-inflammatory phenotypic `M1` switch of Kupffer cells and by decreasing the expression of vascular adhesion molecules ICAM-1, E-Selectin and P-Selectin, as well as the neutrophil infiltration. It also beneficially influenced hepatic metabolic dysregulation (steatosis, protein hyperacetylation, and PPAR-ɑ signaling). The above mentioned protective effects of BCP against alcohol-induced liver injury were attenuated in CB2 knockout mice, indicating that the beneficial effects of this natural product in liver injury involve CB2 receptor activation. Following acute or chronic administration BCP was detectable both in the serum and liver tissue homogenates but not in the brain. Conclusions: Given the safety of BCP in humans this food additive has a high translational potential in treating or preventing hepatic injury associated with oxidative stress, inflammation and steatosis.
Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Methods: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. Results: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1β, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide (p < 0.05). Conclusion: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.
Alzheimer's disease (AD), the most common neurodegenerative disease, has a complex and widespread pathology that is characterized by the accumulation of amyloid [Formula: see text]-peptide (A[Formula: see text]) in the brain and various cellular abnormalities, including increased oxidative damage, an amplified inflammatory response, and altered mitogen-activated protein kinase signaling. Based on the complex etiology of AD, traditional medicinal plants with multiple effective components are alternative treatments for patients with AD. In the present study, we investigated the neuroprotective effects of an ethanol extract of Coriandrum sativum (C. sativum) leaves on A[Formula: see text] cytotoxicity and examined the molecular mechanisms underlying the beneficial effects. Although recent studies have shown the benefits of the inhalation of C. sativum oil in an animal model of AD, the detailed molecular mechanisms by which C. sativum exerts its neuroprotective effects are unclear. Here, we found that treatment with C. sativum extract increased the survival of both A[Formula: see text]-treated mammalian cells and [Formula: see text]42-expressing flies. Moreover, C. sativum extract intake suppressed [Formula: see text]-induced cell death in the larval imaginal disc and brain without affecting A[Formula: see text]42 expression and accumulation. Interestingly, the increases in reactive oxygen species levels and glial cell number in AD model flies were reduced by C. sativum extract intake. Additionally, C. sativum extract inhibited the epidermal growth factor receptor- and A[Formula: see text]-induced phosphorylation of extracellular signal-regulated kinase (ERK). The constitutively active form of ERK abolished the protective function of C. sativum extract against the [Formula: see text]-induced eye defect phenotype in Drosophila. Taken together, these results suggest that C. sativum leaves have antioxidant, anti-inflammatory, and ERK signaling inhibitory properties that are beneficial for patients with AD.
Research toward renewable and sustainable energy has identified specific terpenes capable of supplementing or replacing current petroleum-derived fuels. Despite being naturally produced and stored by many plants, there are few examples of commercial recovery of terpenes from plants because of low yields. Plant terpene biosynthesis is regulated at multiple levels, leading to wide variability in terpene content and chemistry. Advances in the plant molecular toolkit, including annotated genomes, high-throughput omics profiling, and genome editing, have begun to elucidate plant terpene metabolism, and such information is useful for bioengineering metabolic pathways for specific terpenes. We review here the status of terpenes as a specialty biofuel and discuss the potential of plants as a viable agronomic solution for future terpene-derived biofuels.
Context: Standardized myrtol, an essential oil containing primarily cineole, limonene and α-pinene, has been used for treating nasosinusitis, bronchitis and chronic obstructive pulmonary disease (COPD). Objective: To investigate the effects of standardized myrtol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). Materials and methods: Male BALB/c mice were treated with standardized myrtol for 1.5 h prior to exposure of atomized LPS. Six hours after LPS challenge, lung injury was determined by the neutrophil recruitment, cytokine levels and total protein concentration in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissue. Additionally, pathological changes and NF-κB activation in the lung were examined by haematoxylin and eosin staining and western blot, respectively. Results: In LPS-challenged mice, standardized myrtol at a dose of 1200 mg/kg significantly inhibited the neutrophile counts (from 820.97 ± 142.44 to 280.42 ± 65.45, 10(3)/mL), protein concentration (from 0.331 ± 0.02 to 0.183 ± 0.01, mg/mL) and inflammatory cytokines level (TNF-α: from 6072.70 ± 748.40 to 2317.70 ± 500.14, ng/mL; IL-6: from 1184.85 ± 143.58 to 509.57 ± 133.03, ng/mL) in BALF. Standardized myrtol also attenuated LPS-induced MPO activity (from 0.82 ± 0.04 to 0.48 ± 0.06, U/g) and pathological changes (lung injury score: from 11.67 ± 0.33 to 7.83 ± 0.79) in the lung. Further study demonstrated that standardized myrtol prevented LPS-induced NF-κB activation in lung tissues. Discussion and conclusion: Together, these data suggest that standardized myrtol has the potential to protect against LPS-induced airway inflammation in a model of ALI.
The present study aims to investigate the major constituents of the essential oil from Zingiber cassumunar rhizome (EO) and to develop microemulsions with enhanced chemical stability and anti-inflammatory activity of EO. The major constituents of EO were terpinen-4-ol (40.5 ± 6.6%) and sabinene (17.4 ± 1.4%) as determined by gas chromatography–mass spectrometry. These compounds were responsible for the anti-inflammatory activities of EO. Sabinene and terpinen-4-ol significantly reduced nuclear factor-kappa B (NF-kB) expression by 47 ± 5 and 78 ± 8%, respectively (p < 0.001) and significantly reduced the interleukin-6 (IL-6) secretion levels to 64 ± 4% (p < 0.05) and 50 ± 1% (p < 0.001), respectively. EO microemulsions, developed using the system of EO/Tween 20 and propylene glycol (2:1)/water, showed the internal droplet size in the range of 211.5 ± 63.3 to 366.7 ± 77.8 nm. Both EO and EO microemulsions were shown to be safe for human use since there was no apparent toxic effect on human peripheral blood mononuclear cells. Interestingly, EO microemulsion could significantly protect sabinene from the evaporation after heating–cooling stability test, which leads to a good stability and high efficacy. Moreover, EO microemulsions significantly enhanced the anti-inflammatory effect comparing to the native EO. Therefore, microemulsions were attractive delivery system for natural anti-inflammatory compounds since they could enhance both efficacy and stability of EO.