Holistic Terpenes & Healing Forests: The Science Behind The Entourage Effect

Are you as tired as I am of smug drug warriors who have all the research dollars locked up and then sneer that the Cannabis community can’t prove what we all know to be true because there isn’t any research? Well, now maybe there is – at least a little.

I’ll wait for others to voice their thoughts, but I’m thinking the research we’ll cover in this post means no more “You can’t prove it” bullshit about the Cannabis Entourage Effect from Pig Pharma & their federal shills.

The studies cited throughout this blog post reference terpenes and other phytochemicals found in the natural emissions and vapors of “Forest Bath” environments and prove their wide-ranging efficacy as inhaled and absorbed therapeutic & healing agents.

(Please see my previous post for a full discussion of “Forest Bathing” and Cannabis.)

The “Forest Bath” research also shows clearly that the healing potential of this class of phytochemicals is far from fully understood.

These same “Forest Bath” terpenes and other phytochemicals, exactly the same ones, are found in Cannabis emissions and vapors, in almost the same proportions, and they vary among Cannabis strains the same way that emissions from tree species vary among Healing Forests.

Hundreds of peer-reviewed scientific and medical research studies support the therapeutic validity of the ancient practice of Forest Bathing. Perhaps this same body of science, properly interpreted, would allow the Cannabis community to checkmate the anti-Cannabis propagandists and their scientific pretensions with some solid, relevant data. The planet is tight.

A Little Background

The totality of “Forest Bath” research provides precisely the range of scientific experimental evidence needed to validate ancient Cannabis wisdom and provide strong data-based support for the healing powers of the Cannabis “Entourage Effect”.

South Korean scientists and public health researchers have documented a wide range of positive health benefits from exposure to terpenes in the air of coniferous forests. They have established that variations among the emitted terpenes of different species of trees create highly diverse, differently beneficial micro-environments.

South Korean, Japanese & Taiwanese healing forests are all well mapped – this tall forested mountain valley for asthma; that craggy seaside forest for dermatitis. These healing forests have been well-known for hundreds of generations, and thousands of ancient shrines celebrate the spiritual qualities & health benefits of forested environments throughout Northeast Asia. Legends are filled with heroes suffering grievous battle wounds going alone into the forests and emerging weeks later miraculously healed.

Forest Bath research shows that the dominant terpenes in the air of the most highly-rated “healthy forests” are the same terpenes, primarily a-pinene, myrcene, linalool, and d-limonene, that dominate and differentiate the aromas, tastes and effects of various Cannabis strains.

Because inhaling both Forest terpenes and Cannabis terpenes involves inhaling virtually the same phytochemical mix, “Forest Bath” research pretty well refutes those smug anti-Cannabis arguments against the “Entourage Effect” that boil down to “You can’t prove it because there’s no research”.

Until now, we’ve been limited to a justifiably angry “Of course there isn’t any research you assholes – you’ll have anyone who tries to do the damn research arrested!” Which of course immediately provokes: “Well, that Cannabis certainly does make you people touchy,” followed by further self-satisfied smirks.  

Maybe Forest Bath research changes the balance of smirk-entitlement.

Forest Bath research provides a thoroughly validated database in support of the health benefits of inhaling the precise aerosolized natural terpenes involved in the Cannabis “Entourage Effect”, clearly establishing the link between inhaling a natural blend of specific aerosolized or vaporized terpenes and associated phytochemicals and obtaining cumulative, lasting, measurable health benefits..

Some of the research references that follow this introduction focus on studying the biological activity of a single terpene in a laboratory environment, such as a-pinene’s effect on cardiac cell inflammation in vitro, while others focus on measuring variables like blood pressure in people exposed to natural forest environments under experimental conditions. Taken as a whole they form a good platform for launching further Cannabis “Entourage Effect” research even in the presence of the Federal war on Citizens.

Note of caution in applying Forest Bath research to Cannabis:

When we’re looking at the science behind “Forest Bathing” to inform our understanding of inhaling/ingesting Cannabis terpenes, it’s important to differentiate between the terpene/phytochemical content of the smoke stream of combusted Cannabis and the terpene/phytochemical content of the vapors emitted under various conditions by the whole, non-combusted but “vaporized” Cannabis flower.

A combustion smoke stream contains both the byproducts of combustion itself, including particles of toxic soot, and vaporized organic compounds including THC and all the cannabinoids, terpenoids, flavonoids and other phytochemicals. These compounds are heated to the point of “boiling off” the plant materials ahead of advancing combustion, and those that are especially vulnerable to heat are partially degraded by that process.

On the other hand, dry distillation of Cannabis flowers, also called vaporizing, does not create combustion byproducts in the vapor stream – no toxic soot- because the heating process leading to the change of state from resin to vapor is non-destructive. Nothing burns. The terpene profile in a vapor stream is close to the natural profile of the terpenes in the whole flower before vaporizing occurs because even the most heat-sensitive Cannabis flower phytochemicals survive well-calibrated vaporizing, while far fewer survive even the gentlest combustion.

That difference may be medically significant. It seems likely that the “Forest Bath” science applies directly to an “Entourage Effect” from vaporized Cannabis flowers but somewhat less to combusted flowers.

In other words, inhaling Cannabis vapor is more like taking a pleasant walk through a forest, and inhaling Cannabis smoke is more like being in front of a nice campfire. Both excellent experiences; each very different.

So I’m suggesting that “Entourage Effect” discussions focus more on the health and sensual benefits of inhaling the natural emissions and vapors of Cannabis, as well as ingestion of the natural Cannabis flower by other means, and maybe focus a little less on inhaling Cannabis smoke which has the same toxic effects as inhaling any smoke regardless of benefits, and can’t be dismissed as a serious health hazard.

The following “Forest Bath” research literature citations, all from peer-reviewed scientific journals, are all curated in the US National Institutes of Health “PubMed” database. This provenance means that anti-Cannabis “scientists” cannot challenge the validity of the large body of “Forest Bath” research, nor its applicability to Cannabis and the “Entourage Effect”.

So, if you want to dig deeper into the science, here are the results of the “Forest Bathing” literature research brilliantly elucidated by the Korean Society of Toxicology team. I’ve added revised PubMed links to the original citations and edited a bit for clarity where I thought it was needed:

Therapeutic Potential Of Inhaled Conifer Forest Terpenes

Pinene

“ α-Pinene, found in oils of coniferous trees and rosemary, showed anti-inflammatory activity by decreasing the activity of mitogen-activated protein kinases (MAPKs), expression 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 macrophages (link to original research).”

“In ovalbumin-sensitized mouse model of allergic rhinitis, pretreatment with α-pinene decreased clinical symptoms and levels of immunoglobulin E and IL-4 (link to original research).”

“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 iNOS and matrix metalloproteinases (MMP)-1 and -13, suggesting its role as an anti-osteoarthritic agent (link to original research).”

“Strong anti-inflammatory activity was observed when α-pinene was used in combination with two active ingredients of frankincense, linalool and 1-octanol (link to original research).”

“The Anti-tumor effects of pinenes are well established on tumor lymphocytes as well as tumor cell lines (link to original research).”

“Matsuo et al. (link to original research) identified proapoptotic and anti-metastatic activities 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 (link to original research).”

“In addition, α-pinene triggers oxidative stress signaling pathways in A549 and HepG2 cells (link to original research).”

“Kusuhara et al. (link to original research) reported that mice kept in a setting enriched with α-pinene showed reduction in melanoma sizes, while in vitro treatment of melanoma cells with α-pinene had no inhibitory effect on cell proliferation, suggesting 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 (citation #1,citation #2).”

“α-pinene and 1, 8-cineole also exert neuroprotective effects by regulating gene expression. 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 dismutase, glutathione peroxidase, glutathione reductase, and HO-1 (link to original research).”

Myrcene

“Myrcene, the acyclic monoterpene, also exhibits significant 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 (citation #1,citation #2).”

“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 (link to original research).”

Linalool

“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 (link to original research).”

“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 (link to original research).”

“Similarly, linalool inhibited production of TNF-α, IL-1β, NO, and PGE₂ in LPS-stimulated microglia cells (link to original research).”

“Li et al. (link to original research) showed that the anti-inflammatory effect of linalool is involved in activation of Nrf2/heme oxygenase-1 (HO-1) signaling pathway.”

“Frankincense 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 (link to original research).”

Limonene

“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 (citation #1–citation #2).”

 “Another naturally occurring monoterpene d-limonene was reported to reduce allergic lung inflammation in mice probably via its antioxidant properties (link to original research).”

“It also reduced carrageenan-induced inflammation by reducing cell migration, cytokine production, and protein extravasation (link to original research).”

“Similar to α-pinene, d-limonene exerted an anti-osteoarthritic effect by inhibiting IL-1β-induced NO production in human chondrocytes (link to original research).”

“d-Limonene treatment reduced doxorubicin-induced production of two proinflammatory cytokines, TNF-α and prostaglandin E-2 (PGE₂) (link to original research).”

 “Lu et al. (link to original research) revealed that d-limonene could inhibit the proliferation of human gastric cancer cells by inducing apoptosis.”

“Later, it was demonstrated that apoptosis 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 (citation #1,citation #2).”

Cymene

“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) (link to original research).”

“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 (link to original research) and by reducing production of proinflammatory cytokines and infiltration of inflammatory cells (link to original research).”

“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 upregulated by p-cymene treatment. It also inhibited LPS-induced activation of ERK 1/2, p38, JNK, and IκBα (citation #1,citation #2).”

“p-Cymene has been reported to have cytotoxic effects on tumor cell lines (link to original research).”

“Recently, Li et al. (link to original research) evaluated beneficial effects of p-cymene on in vitro TPA-augmented invasiveness 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 candidate for the prevention of tumor invasion and metastasis.”

Terpinene

“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 (link to original research).”

“Terpinene-containing essential oil from Liquidambar formosana leaves reduced inflammatory response in LPS-stimulated mouse macrophages by reducing reactive oxygen species (ROS), JNK, ERK, p38 MAP kinase, and NF-κB (link to original research).”

“Another terpinene-containing essential oil from Citrus unshiu flower or fingered citron (C. medica L. var. sarcodactylis) reduced LPS-stimulated PGE₂ and NO production in RAW 264.7 cells. Furthermore, production of inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, was also reduced in macrophages (citation #1,citation #2).”

Boneol

“Borneol, a bicyclic monoterpene present in Artemisia, Blumea, and Kaempferia, has been used in traditional medicine. Borneol alleviated acute lung inflammation by reducing inflammatory infiltration, histopathological changes, and cytokine production in LPS-stimulated mice. It suppressed phosphorylation of NF-κB, IκBα, p38, JNK, and ERK (link to original research).”

“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_AR (Gamma-Aminobutyric Acid Type A Receptor)-mediated GABAergic transmission (link to original research).”

“Borneol inhibited migration of leukocytes into the peritoneal cavity in carrageenan-stimulated mice, suggesting its anti-inflammatory function (link to original research).”

“In addition, borneol inhibited TRPA1, a cation channel that is involved in inflammation and noxious-pain sensing, suggesting that its use as an anti-inflammatory agent for neuropathic-pain and trigeminal neuralgia (link to original research).”

“Previous studies showed that borneol has free radical scavenging activity (link to original research) and is a major component of essential oil of SuHeXiang Wan (link to original research) whose neuroprotective function has been reported in in vivo and in vitro models of Alzheimer’s disease (AD) (citation #1,citation #2).”

“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 (link to original research).”

“In addition, treatment with isoborneol, a monoterpenoid alcohol, significantly reduced 6-hydroxydopamine-induced ROS generation and cell death in human neuroblastoma SH-SY5Y cells, suggesting that isoborneol may be a potential therapeutic agent for treatment of neurodegenerative diseases associated with oxidative stress (link to original research).”

Caryophyllene

“α-Caryophyllene, known as humulene, is a naturally occurring monocyclic sesquiterpene. BCP, an isomer of α-caryophyllene, 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 inhibits lymph node metastasis of melanoma cells in high-fat diet-induced obese mice (citation #1,citation #2).”

“Sarvmeili et al. (link to original research) reported that Pinus eldarica essential oil, of which BCP was the major component, exerts cytotoxic effects on HeLa and MCF-7 cell lines.”

“β-caryophyllene (BCP) was reported 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 (link to original research).”

“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 (link to link to original research).”

“Prolonged administration of BCP reduced proinflammatory cytokines in pancreatic tissue of streptozotocin-induced diabetic rats (link to original research).”

“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 (link to original research).”

“BCP has antioxidant effects (link to original research), and functions as a regulator of several neuronal receptors and shows various pharmacological activities including neuroprotection (link to original research).”

“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 impairment and activation of inflammation through CB2 receptor activation and the PPARγ pathway (link to original research).”

RESEARCH BIBLIOGRAPHY: THE ROLE OF FOREST BATH TERPENES IN HUMAN HEALTH

No more “You can’t prove it” bullshit. The studies cited throughout this post reference terpenes and other phytochemicals found in natural emissions and vapors of “Forest Bath” environments. These same terpenes and other phytochemicals, exactly the same, are found in Cannabis emissions and vapors, in almost the same proportions, and vary between Cannabis strains the same way that emissions from tree species vary among Healing Forests. I hope that the connection between hundreds of peer-reviewed scientific and medical research studies that support the ancient practice of Forest Bathing and their direct applicability to the  Entourage Effect will allow the Cannabis community to finally checkmate the anti-Cannabis propagandists and their scientific pretensions.

REFERENCES: from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402865/

1. Frumkin H. Beyond toxicity: human health and the natural environment. Am J Prev Med. 2001;20:234–240. doi: 10.1016/S0749-3797(00)00317-2. PubMed    

2. Tsunetsugu Y, Park BJ, Miyazaki Y. Trends in research related to “Shinrin-yoku” (taking in the forest atmosphere or forest bathing) in Japan. Environ Health Prev Med. 2010;15:27–37. doi: 10.1007/s12199-009-0091-z. PMC free article  PubMed  

3. Seo SC, Park SJ, Park CW, Yoon WS, Choung JT, Yoo Y. Clinical and immunological effects of a forest trip in children with asthma and atopic dermatitis. Iran J Allergy Asthma Immunol. 2015;14:28–36. PubMed

4. Douglass RW. Forest recreation. 3rd edition. Pergamon Press; 1982.

5. Spievogel I, Spalek K. Medicinal plants uesed in pediatric prophylactic method of Sebastian Kneipp. Nat J. 2012;45:9–18.

6. Joos S, Rosemann T, Szecsenyi J, Hahn EG, Willich SN, Brinkhaus B. Use of complementary and alternative medicine in Germany: a survey of patients with inflammatory bowel disease. BMC Complement Altern Med. 2006;6:19. doi: 10.1186/1472-6882-6-19. PMC free article  PubMed  

7. Park BJ, Tsunetsugu Y, Kasetani T, Kagawa T, Miyazaki Y. The physiological effects of Shinrin-yoku (taking in the forest atmosphere or forest bathing): evidence from field experiments in 24 forests across Japan. Environ Health Prev Med. 2010;15:18–26. doi: 10.1007/s12199-009-0086-9. PMC free article  PubMed  

8. Song C, Ikei H, Miyazaki Y. Physiological effects of nature therapy: A review of the research in Japan. Int J Environ Res Public Health. 2016;13:E781. doi: 10.3390/ijerph13080781. PMC free article  PubMed  

9. Gershenzon J, Dudareva N. The function of terpene natural products in the natural world. Nat Chem Biol. 2007;3:408–414. doi: 10.1038/nchembio.2007.5. PubMed

10. Chappell J. The genetics and molecular genetics of terpene and sterol origami. Curr Opin Plant Biol. 2002;5:151–157. doi: 10.1016/S1369-5266(02)00241-8. PubMed

11. Mewalal R, Rai DK, Kainer D, Chen F, Külheim C, Peter GF, Tuskan GA. Plant-derived terpenes: A feedstock for specialty biofuels. Trends Biotechnol. 2016 S0167-7799(16)30128-7. PubMed

12. Kirby J, Keasling JD. Biosynthesis of plant isoprenoids: perspectives for microbial engineering. Annu Rev Plant Biol. 2009;60:335–355. doi: 10.1146/annurev.arplant.043008.091955. PubMed

13. Zulak KG, Bohlmann J. Terpenoid biosynthesis and specialized vascular cells of conifer defense. J Integr Plant Biol. 2010;52:86–97. doi: 10.1111/j.1744-7909.2010.00910.x. PubMed

14. Lange BM, Ahkami A. Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes: current status and future opportunities. Plant Biotechnol J. 2013;11:169–196. doi: 10.1111/pbi.12022. PubMed

15. Dubey VS, Bhalla R, Luthra R. An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants. J Biosci. 2003;28:637–646. doi: 10.1007/BF02703339. PubMed

16. Matsuba Y, Nguyen TT, Wiegert K, Falara V, Gonzales-Vigil E, Leong B, Schäfer P, Kudrna D, Wing RA, Bolger AM, Usadel B, Tissier A, Fernie AR, Barry CS, Pichersky E. Evolution of a complex locus for terpene biosynthesis in solanum. Plant Cell. 2013;25:2022–2036. doi: 10.1105/tpc.113.111013. PMC free article  PubMed  

17. Martin DM, Gershenzon J, Bohlmann J. Induction of volatile terpene biosynthesis and diurnal emission by methyl jasmonate in foliage of Norway spruce. Plant Physiol. 2003;132:1586–1599. doi: 10.1104/pp.103.021196. PMC free article  PubMed  

18. Lee DH, Kim MH, Park OH, Park KS, An SS, Seo HJ, Jin SH, Jeong WS, Kang YJ, An KW, Kim ES. A study on the distribution characteristics of terpene at the main trails of Mt. Mudeung. J Environ Health Sci. 2013;39:211–222. doi: 10.1080/10934529.2012.717818.

19. Rufino AT, Ribeiro M, Judas F, Salgueiro L, Lopes MC, Cavaleiro C, Mendes AF. Anti-inflammatory and chondroprotective activity of (+)-α-pinene: structural and enantiomeric selectivity. J Nat Prod. 2014;77:264–269. doi: 10.1021/np400828x. PubMed

20. Ma J, Xu H, Wu J, Qu C, Sun F, Xu S. Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF-κB activation. Int Immunopharmacol. 2015;29:708–713. doi: 10.1016/j.intimp.2015.09.005. PubMed

21. Rodrigues KA, Amorim LV, Dias CN, Moraes DFC, Carneiro SM, Carvalho FA. Syzygium cumini (L.) Skeels essential oil and its major constituent α-pinene exhibit anti-Leishmania activity through immunomodulation in vitro. J Ethnopharmacol. 2015;160:32–40. doi: 10.1016/j.jep.2014.11.024. PubMed

22. Li XJ, Yang YJ, Li YS, Zhang WK, Tang HB. α-Pinene, linalool and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2. J Ethnopharmacol. 2016;179:22–26. doi: 10.1016/j.jep.2015.12.039. PubMed

23. Yu PJ, Wan LM, Wan SH, Chen WY, Xie H, Meng DM, Zhang JJ, Xiao XL. Standardized myrtol attenuates lipopolysaccharide induced acute lung injury in mice. Pharm Biol. 2016;54:3211–3216. doi: 10.1080/13880209.2016.1216132. PubMed

24. Kim DS, Lee HJ, Jeon YD, Han YH, Kee JY, Kim HJ, Shin HJ, Kang J, Lee BS, Kim SH, Kim SJ, Park SH, Choi BM, Park SJ, Um JY, Hong SH. Alpha-pinene exhibits anti-inflammatory activity through the suppression of MAPKs and the NF-κB pathway in mouse peritoneal macrophages. Am J Chin Med. 2015;43:731–742. doi: 10.1142/S0192415X15500457. PubMed

25. Nam SY, Chung Ck, Seo JH, Rah SY, Kim HM, Jeong HJ. The therapeutic efficacy of α-pinene in an experimental mouse model of allergic rhinitis. Int Immunopharmacol. 2014;23:273–282. doi: 10.1016/j.intimp.2014.09.010. PubMed

26. Hansen JS, Nørgaard AW, Koponen IK, Sørli JB, Paidi MD, Hansen SW, Clausen PA, Nielsen GD, Wolkoff P, Larsen ST. Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice. J Immunotoxicol. 2016;13:793–803. doi: 10.1080/1547691X.2016.1195462. PubMed

27. Amorim JL, Simas DLR, Pinheiro MM, Moreno DS, Alviano CS, da Silva AJ, Fernandes PD. Antiinflammatory properties and chemical characterization of the essential oils of four citrus species. PLoS ONE. 2016;11:e0153643. doi: 10.1371/journal.pone.0153643. PMC free article  PubMed

28. Rufino AT, Ribeiro M, Sousa C, Judas F, Salgueiro L, Cavaleiro C, Mendes AF. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. Eur J Pharmacol. 2015;750:141–150. doi: 10.1016/j.ejphar.2015.01.018. PubMed

29. Rehman MU, Tahir M, Khan AQ, Khan R, Oday-O-Hamiza, Lateef A, Hassan SK, Rashid S, Ali N, Zeeshan M, Sultana S. D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX-2, iNOS and NFκB in kidneys of Wistar rats. Exp Biol Med (Maywood) 2014;239:465–476. doi: 10.1177/1535370213520112. PubMed

30. Games E, Guerreiro M, Santana FR, Pinheiro NM, de Oliveira EA, Lopes FD, Olivo CR, Tibério IF, Martins MA, Lago JH, Prado CM. Structurally related monoterpenes p-Cymene, carvacrol and thymol isolated from essential oil from leaves of lippia sidoides cham. (Verbenaceae) protect mice against elastase-induced emphysema. Molecules. 2016;21:E1390. doi: 10.3390/molecules21101390. PubMed

31. Chen L, Zhao L, Zhang C, Lan Z. Protective effect of p-cymene on lipopolysaccharide-induced acute lung injury in mice. Inflammation. 2014;37:358–364. doi: 10.1007/s10753-013-9747-3. PubMed

32. Xie G, Chen N, Soromou LW, Liu F, Xiong Y, Wu Q, Li H, Feng H, Liu G. p-Cymene protects mice against lipopolysaccharide-induced acute lung injury by inhibiting inflammatory cell activation. Molecules. 2012;17:8159–8173. doi: 10.3390/molecules17078159. PubMed    

33. Zhong W, Chi G, Jiang L, Soromou LW, Chen N, Huo M, Guo W, Deng X, Feng H. p-Cymene modulates in vitro and in vivo cytokine production by inhibiting MAPK and NF-κB activation. Inflammation. 2013;36:529–537. doi: 10.1007/s10753-012-9574-y. PubMed    

34. Huo M, Cui X, Xue J, Chi G, Gao R, Deng X, Guan S, Wei J, Soromou LW, Feng H, Wang D. Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model. J Surg Res. 2013;180:e47–e54. doi: 10.1016/j.jss.2012.10.050. PubMed    

35. Li Y, Lv O, Zhou F, Li Q, Wu Z, Zheng Y. Linalool inhibits LPS-induced inflammation in BV2 microglia cells by activating Nrf2. Neurochem Res. 2015;40:1520–1525. doi: 10.1007/s11064-015-1629-7. PubMed    

36. de Oliveira Ramalho TR, de Oliveira MT, de Araujo Lima AL, Bezerra-Santos CR, Piuvezam MR. Gamma-terpinene modulates acute inflammatory response in mice. Planta Med. 2015;81:1248–1254. doi: 10.1055/s-0035-1546169. PubMed    

37. Hua KF, Yang TJ, Chiu HW, Ho CL. Essential oil from leaves of Liquidambar formosana ameliorates inflammatory response in lipopolysaccharide-activated mouse macrophages. Nat Prod Commun. 2014;9:869–872. PubMed

38. Kim KN, Ko YJ, Yang HM, Ham YM, Roh SW, Jeon YJ, Ahn G, Kang MC, Yoon WJ, Kim D, Oda T. Anti-inflammatory effect of essential oil and its constituents from fingered citron (Citrus medica L. var. sarcodactylis) through blocking JNK, ERK and NF-κB signaling pathways in LPS-activated RAW 264.7 cells. Food Chem Toxicol. 2013;57:126–131. doi: 10.1016/j.fct.2013.03.017. PubMed    

39. Kim MJ, Yang KW, Kim SS, Park SM, Park KJ, Kim KS, Choi YH, Cho KK, Hyun CG. Chemical composition and anti-inflammation activity of essential oils from Citrus unshiu flower. Nat Prod Commun. 2014;9:727–730. PubMed

40. Zhong W, Cui Y, Yu Q, Xie X, Liu Y, Wei M, Ci X, Peng L. Modulation of LPS-stimulated pulmonary inflammation by borneol in murine acute lung injury model. Inflammation. 2014;37:1148–1157. doi: 10.1007/s10753-014-9839-8. PubMed    

41. Jiang J, Shen YY, Li J, Lin YH, Luo CX, Zhu DY. (+)-Borneol alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice. Eur J Pharmacol. 2015;757:53–58. doi: 10.1016/j.ejphar.2015.03.056. PubMed    

42. Almeida JR, Souza GR, Silva JC, Saraiva SR, Júnior RG, Quintans Jde S, Barreto Rde S, Bonjardim LR, Cavalcanti SC, Quintans LJ., Jr Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice. ScientificWorldJournal. 2013;2013:808460. doi: 10.1155/2013/808460. PMC free article  PubMed     

43. Sherkheli MA, Schreiner B, Haq R, Werner M, Hatt H. Borneol inhibits TRPA1, a proinflammatory and noxious pain-sensing cation channel. Pak J Pharm Sci. 2015;28:1357–1363. PubMed

44. Ojha S, Javed H, Azimullah S, Haque ME. β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation and salvages dopaminergic neurons in a rat model of Parkinson disease. Mol Cell Biochem. 2016;418:59–70. doi: 10.1007/s11010-016-2733-y. PubMed    

45. Varga ZV, Matyas C, Erdelyi K, Cinar R, Nieri D, Chicca A, Nemeth BT, Paloczi J, Lajtos T, Corey L, Hasko G, Gao B, Kunos G, Gertsch J, Pacher P. Beta-caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice. Br J Pharmacol. 2017 doi: 10.1111/bph.13722. PubMed    

46. Basha RH, Sankaranarayanan C. β-Caryophyllene, a natural sesquiterpene lactone attenuates hyperglycemia mediated oxidative and inflammatory stress in experimental diabetic rats. Chem Biol Interact. 2016;245:50–58. doi: 10.1016/j.cbi.2015.12.019. PubMed    

47. Cho HI, Hong JM, Choi JW, Choi HS, Kwak JH, Lee DU, Lee SK, Lee SM. β-Caryophyllene alleviates d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the TLR4 and RAGE signaling pathways. Eur J Pharmacol. 2015;764:613–621. doi: 10.1016/j.ejphar.2015.08.001. PubMed    

48. Kim MJ, Yang KW, Kim SS, Park SM, Park KJ, Kim KS, Choi YH, Cho KK, Lee NH, Hyun CG. Chemical composition and anti-inflammatory effects of essential oil from Hallabong flower. EXCLI J. 2013;12:933–942. PMC free article  PubMed

49. Chaiyana W, Anuchapreeda S, Leelapornpisid P, Phongpradist R, Viernstein H, Mueller M. Development of microemulsion delivery system of essential oil from Zingiber cassumunar Roxb. Rhizome for improvement of stability and anti-inflammatory activity. AAPS PharmSciTech. 2016:1–11. PubMed

50. Yang H, Zhao R, Chen H, Jia P, Bao L, Tang H. Bornyl acetate has an anti-inflammatory effect in human chondrocytes via induction of IL-11. IUBMB Life. 2014;66:854–859. doi: 10.1002/iub.1338. PubMed    

51. Sobral MV, Xavier AL, Lima TC, de Sousa DP. Antitumor activity of monoterpenes found in essential oils. Scientific World Journal. 2014;2014:953451. doi: 10.1155/2014/953451. PMC free article  PubMed     

52. Broitman SA, Wilkinson J, 4th, Cerda S, Branch SK. Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic “Metastases” in vitro. Adv Exp Med Biol. 1996;401:111–130. doi: 10.1007/978-1-4613-0399-2_9. PubMed    

53. Uedo N, Tatsuta M, Iishi H, Baba M, Sakai N, Yano H, Otani T. Inhibition by d-limonene of gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats. Cancer Lett. 1999;137:131–136. doi: 10.1016/S0304-3835(98)00340-1. PubMed    

54. Stratton S, Dorr R, Alberts D. The state-of-the-art in chemoprevention of skin cancer. Eur J Cancer. 2000;36:1292–1297. doi: 10.1016/S0959-8049(00)00108-8. PubMed    

55. Kaji I, Tatsuta M, Iishi H, Baba M, Inoue A, Kasugai H. Inhibition by D-limonene of experimental hepatocarcinogenesis in Sprague-Dawley rats does not involve p21ras plasma membrane association. Int J Cancer. 2001;93:441–444. doi: 10.1002/ijc.1353. PubMed    

56. Guyton KZ, Kensler TW. Prevention of liver cancer. Curr Oncol Rep. 2002;4:464–470. doi: 10.1007/s11912-002-0057-4. PubMed    

57. Lu XG, Zhan LB, Feng BA, Qu MY, Yu LH, Xie JH. Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene. World J Gastroenterol. 2004;10:2140–2144. doi: 10.3748/wjg.v10.i14.2140. PMC free article  PubMed     

58. Ji J, Zhang L, Wu YY, Zhu XY, Lv SQ, Sun XZ. Induction of apoptosis by d-limonene is mediated by a caspase-dependent mitochondrial death pathway in human leukemia cells. Leuk Lymphoma. 2006;47:2617–2624. doi: 10.1080/00268970600909205. PubMed    

59. Jia SS, Xi GP, Zhang M, Chen YB, Lei B, Dong XS, Yang YM. Induction of apoptosis by D-limonene is mediated by inactivation of Akt in LS174T human colon cancer cells. Oncol Rep. 2013;29:349–354. PubMed

60. Li Q. Effect of forest bathing trips on human immune function. Environ Health Prev Med. 2010;15:9–17. doi: 10.1007/s12199-008-0068-3. PMC free article  PubMed     

61. Bansal A, Moriarity DM, Takaku S, Setzer WN. Chemical composition and cytotoxic activity of the leaf essential oil of Ocotea tonduzii from Monteverde, Costa Rica. Nat Prod Commun. 2007;2:781–784.

62. Matsuo AL, Figueiredo CR, Arruda DC, Pereira FV, Scutti JA, Massaoka MH, Travassos LR, Sartorelli P, Lago JH. α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model. Biochem Biophys Res Commun. 2011;411:449–454. doi: 10.1016/j.bbrc.2011.06.176. PubMed    

63. Chen W, Liu Y, Li M, Mao J, Zhang L, Huang R, Jin X, Ye L. Anti-tumor effect of α-pinene on human hepatoma cell lines through inducing G2/M cell cycle arrest. J Pharmacol Sci. 2015;127:332–338. doi: 10.1016/j.jphs.2015.01.008. PubMed    

64. Jin KS, Bak MJ, Jun M, Lim HJ, Jo WK, Jeong WS. α-Pinene triggers oxidative stress and related signaling pathways in A549 and HepG2 cells. Food Sci Biotechnol. 2010;19:1325–1332. doi: 10.1007/s10068-010-0189-5.  

65. Kusuhara M, Urakami K, Masuda Y, Zangiacomi V, Ishii H, Tai S, Maruyama K, Yamaguchi K. Fragrant environment with α-pinene decreases tumor growth in mice. Biomed Res. 2012;33:57–61. doi: 10.2220/biomedres.33.57. PubMed    

66. Bakarnga-Via I, Hzounda JB, Fokou PVT, Tchokouaha LRY, Gary-Bobo M, Gallud A, Garcia M, Walbadet L, Secka Y, Dongmo PMJ, Boyom FF, Menut C. Composition and cytotoxic activity of essential oils from Xylopia aethiopica (Dunal) A. Rich, Xylopia parviflora (A. Rich) Benth. and Monodora myristica (Gaertn) growing in chad and cameroon. BMC Complement Altern Med. 2014;14:125. doi: 10.1186/1472-6882-14-125. PMC free article  PubMed     

67. Li YL, Yeung CM, Chiu L, Cen YZ, Ooi VE. Chemical composition and antiproliferative activity of essential oil from the leaves of a medicinal herb, Schefflera heptaphylla. Phytother Res. 2009;23:140–142. doi: 10.1002/ptr.2567. PubMed    

68. Meadows SM, Mulkerin D, Berlin J, Bailey H, Kolesar J, Warren D, Thomas JP. Phase II trial of perillyl alcohol in patients with metastatic colorectal cancer. Int J Gastrointest Cancer. 2002;32:125–128. doi: 10.1385/IJGC:32:2-3:125. PubMed    

69. Chen TC, Cho HY, Wang W, Wetzel SJ, Singh A, Nguyen J, Hofman FM, Schönthal AH. Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo. J Biomed Sci. 2015;22:71. doi: 10.1186/s12929-015-0175-6. PMC free article  PubMed     

70. Bardon S, Foussard V, Fournel S, Loubat A. Monoterpenes inhibit proliferation of human colon cancer cells by modulating cell cycle-related protein expression. Cancer Lett. 2002;181:187–194. doi: 10.1016/S0304-3835(02)00047-2. PubMed    

71. Yeruva L, Pierre KJ, Elegbede A, Wang RC, Carper SW. Perillyl alcohol and perillic acid induced cell cycle arrest and apoptosis in non small cell lung cancer cells. Cancer Lett. 2007;257:216–226. doi: 10.1016/j.canlet.2007.07.020. PubMed    

72. Ferraz RP, Bomfim DS, Carvalho NC, Soares MB, da Silva TB, Machado WJ, Prata APN, Costa EV, Moraes VRS, Nogueira PCL, Bezerra DP. Cytotoxic effect of leaf essential oil of Lippia gracilis Schauer (Verbenaceae) Phytomedicine. 2013;20:615–621. doi: 10.1016/j.phymed.2013.01.015. PubMed    

73. Li J, Liu C, Sato T. Novel antitumor invasive actions of p-Cymene by decreasing MMP-9/TIMP-1 expression ratio in human fibrosarcoma HT-1080 cells. Biol Pharm Bull. 2016;39:1247–1253. doi: 10.1248/bpb.b15-00827. PubMed    

74. Saleh M, Hashem F, Glombitza K. Cytotoxicity and in vitro effects on human cancer cell lines of volatiles of Apium graveolens var filicinum. Pharm Pharmacol Lett. 1998;8:97–99.

75. Silva SLD, Figueiredo PM, Yano T. Cytotoxic evaluation of essential oil from Zanthoxylum rhoifolium Lam. leaves. Acta Amaz. 2007;37:281–286. doi: 10.1590/S0044-59672007000200015.  

76. Maggi F, Fortuné Randriana R, Rasoanaivo P, Nicoletti M, Quassinti L, Bramucci M, Lupidi G, Petrelli D, Vitali LA, Papa F, Vittori S. Chemical composition and in vitro biological activities of the essential oil of Vepris macrophylla (Baker) I. Verd. endemic to Madagascar. Chem Biodivers. 2013;10:356–366. doi: 10.1002/cbdv.201200253. PubMed    

77. Kuo YH, Kuo YJ, Yu AS, Wu MD, Ong CW, Kuo LMY, Huang JT, Chen CF, Li SY. Two novel sesquiterpene lactones, cytotoxic vernolide-A and-B, from Vernonia cinerea. Chem Pharm Bull. 2003;51:425–426. doi: 10.1248/cpb.51.425. PubMed    

78. Dahham SS, Tabana YM, Iqbal MA, Ahamed MB, Ezzat MO, Majid AS, Majid AM. The anticancer, antioxidant and antimicrobial properties of the sesquiterpene β-caryophyllene from the essential oil of Aquilaria crassna. Molecules. 2015;20:11808–11829. doi: 10.3390/molecules200711808. PubMed    

79. Jung JI, Kim EJ, Kwon GT, Jung YJ, Park T, Kim Y, Yu R, Choi MS, Chun HS, Kwon SH, Her S, Lee KW, Park JH. β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice. Carcinogenesis. 2015;36:1028–1039. doi: 10.1093/carcin/bgv076. PubMed    

80. Sarvmeili N, Jafarian-Dehkordi A, Zolfaghari B. Cytotoxic effects of Pinus eldarica essential oil and extracts on HeLa and MCF-7 cell lines. Res Pharm Sci. 2016;11:476–483. doi: 10.4103/1735-5362.194887. PMC free article  PubMed     

81. Legault J, Pichette A. Potentiating effect of β-caryophyllene on anticancer activity of α-humulene, isocaryophyllene and paclitaxel. J Pharm Pharmacol. 2007;59:1643–1647. doi: 10.1211/jpp.59.12.0005. PubMed    

82. Lesgards JF, Baldovini N, Vidal N, Pietri S. Anticancer activities of essential oils constituents and synergy with conventional therapies: a review. Phytother Res. 2014;28:1423–1446. doi: 10.1002/ptr.5165. PubMed    

83. Savelev SU, Okello EJ, Perry EK. Butyryl-and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Phytother Res. 2004;18:315–324. doi: 10.1002/ptr.1451. PubMed    

84. Liu ZB, Niu WM, Yang XH, Yuan W, Wang WG. Study on perfume stimulating olfaction with volatile oil of Acorus gramineus for treatment of the Alzheimer’s disease rat. J Tradit Chin Med. 2010;30:283–287. doi: 10.1016/S0254-6272(10)60057-X. PubMed    

85. Majlessi N, Choopani S, Kamalinejad M, Azizi Z. Amelioration of amyloid β-induced cognitive deficits by Zataria multiflora Boiss. essential oil in a rat model of Alzheimer’s disease. CNS Neurosci Ther. 2012;18:295–301. doi: 10.1111/j.1755-5949.2011.00237.x. PubMed    

86. Cioanca O, Hritcu L, Mihasan M, Trifan A, Hancianu M. Inhalation of coriander volatile oil increased anxiolytic-antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1–42) rat model of Alzheimer’s disease. Physiol Behav. 2014;131:68–74. doi: 10.1016/j.physbeh.2014.04.021. PubMed    

87. Oboh G, Olasehinde TA, Ademosun AO. Essential oil from lemon peels inhibit key enzymes linked to neurodegenerative conditions and pro-oxidant induced lipid peroxidation. J Oleo Sci. 2014;63:373–381. doi: 10.5650/jos.ess13166. PubMed    

88. Abuhamdah S, Abuhamdah R, Howes MJ, Al-Olimat S, Ennaceur A, Chazot PL. Pharmacological and neuroprotective profile of an essential oil derived from leaves of Aloysia citrodora Palau. J Pharm Pharmacol. 2015;67:1306–1315. doi: 10.1111/jphp.12424. PubMed    

89. Ayaz M, Junaid M, Ullah F, Sadiq A, Khan MA, Ahmad W, Shah MR, Imran M, Ahmad S. Comparative chemical profiling, cholinesterase inhibitions and anti-radicals properties of essential oils from Polygonum hydropiper L: A Preliminary anti-Alzheimer’s study. Lipids Health Dis. 2015;14:141. doi: 10.1186/s12944-015-0145-8. PMC free article  PubMed     

90. Klein-Júnior LC, dos Santos Passos C, Tasso de Souza TJ, Gobbi de Bitencourt F, Salton J, de Loreto Bordignon SA, Henriques AT. The monoamine oxidase inhibitory activity of essential oils obtained from Eryngium species and their chemical composition. Pharm Biol. 2016;54:1071–1076. doi: 10.3109/13880209.2015.1102949. PubMed    

91. Mühlbauer R, Lozano A, Palacio S, Reinli A, Felix R. Common herbs, essential oils and monoterpenes potently modulate bone metabolism. Bone. 2003;32:372–380. doi: 10.1016/S8756-3282(03)00027-9. PubMed    

92. Koo BS, Lee SI, Ha JH, Lee DU. Inhibitory effects of the essential oil from SuHeXiang Wan on the central nervous system after inhalation. Biol Pharm Bull. 2004;27:515–519. doi: 10.1248/bpb.27.515. PubMed    

93. Lima B, López S, Luna L, Agüero MB, Aragón L, Tapia A, Zacchino S, López ML, Zygadlo J, Feresin GE. Essential oils of medicinal plants from the central andes of Argentina: chemical composition, and antifungal, antibacterial, and insect-repellent activities. Chem Biodivers. 2011;8:924–936. doi: 10.1002/cbdv.201000230. PubMed    

94. El-Seedi HR, Khalil NS, Azeem M, Taher EA, Göransson U, Pålsson K, Borg-Karlson AK. Chemical composition and repellency of essential oils from four medicinal plants against Ixodes ricinus nymphs (Acari: Ixodidae) J Med Entomol. 2012;49:1067–1075. doi: 10.1603/ME11250. PubMed    

95. Mkaddem M, Bouajila J, Ennajar M, Lebrihi A, Mathieu F, Romdhane M. Chemical composition and antimicrobial and antioxidant activities of Mentha (longifolia L. and viridis) essential oils. J Food Sci. 2009;74:M358–M363. doi: 10.1111/j.1750-3841.2009.01272.x. PubMed    

96. Hong YK, Park SH, Lee S, Hwang S, Lee MJ, Kim D, Lee JH, Han SY, Kim ST, Kim YK, Jeon S, Koo BS, Cho KS. Neuroprotective effect of SuHeXiang Wan in Drosophila models of Alzheimer’s disease. J Ethnopharmacol. 2011;134:1028–1032. doi: 10.1016/j.jep.2011.02.012. PubMed    

97. Park SH, Lee S, Hong YK, Hwang S, Lee JH, Bang SM, Kim YK, Koo BS, Lee IS, Cho KS. Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer’s disease. Biol Pharm Bull. 2013;36:390–398. doi: 10.1248/bpb.b12-00792. PubMed    

98. Liu QF, Jeong H, Lee JH, Hong YK, Oh Y, Kim YM, Suh YS, Bang S, Yun HS, Lee K, Cho SM, Lee SB, Jeon S, Chin YW, Koo BS, Cho KS. Coriandrum sativum suppresses Aβ42-induced ROS increases, glial cell proliferation and ERK activation. Am J Chin Med. 2016;44:1325–1347. doi: 10.1142/S0192415X16500749. PubMed    

99. Liu QF, Lee JH, Kim YM, Lee S, Hong YK, Hwang S, Oh Y, Lee K, Yun HS, Lee IS, Jeon S, Chin YW, Koo BS, Cho KS. In vivo screening of traditional medicinal plants for neuroprotective activity against Aβ42 cytotoxicity by using Drosophila models of Alzheimer’s disease. Biol Pharm Bull. 2015;38:1891–1901. doi: 10.1248/bpb.b15-00459. PubMed    

100. Hur J, Pak SC, Koo BS, Jeon S. Borneol alleviates oxidative stress via upregulation of Nrf2 and Bcl-2 in SH-SY5Y cells. Pharm Biol. 2013;51:30–35. doi: 10.3109/13880209.2012.700718. PubMed    

101. Tian LL, Zhou Z, Zhang Q, Sun YN, Li CR, Cheng C, Zhong ZY, Wang SQ. Protective effect of (±) isoborneol against 6-OHDA-induced apoptosis in SHSY5Y cells. Cell Physiol Biochem. 2007;20:1019–1032. doi: 10.1159/000110682. PubMed    

102. Han M, Liu Y, Zhang B, Qiao J, Lu W, Zhu Y, Wang Y, Zhao C. Salvianic borneol ester reduces β-amyloid oligomers and prevents cytotoxicity. Pharm Biol. 2011;49:1008–1013. doi: 10.3109/13880209.2011.559585. PubMed    

103. Calleja MA, Vieites JM, Montero-Meterdez T, Torres MI, Faus MJ, Gil A, Suárez A. The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Br J Nutr. 2013;109:394–401. doi: 10.1017/S0007114512001298. PubMed    

104. Sharma C, Al Kaabi JM, Nurulain SM, Goyal SN, Kamal MA, Ojha S. Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Curr Pharm Des. 2016;22:3237–3264. doi: 10.2174/1381612822666160311115226. PubMed    

105. Cheng Y, Dong Z, Liu S. β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 mice through CB2 receptor activation and the PPARγ pathway. Pharmacology. 2014;94:1–12. doi: 10.1159/000362689. PubMed    

106. Porres-Martínez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP. In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z Naturforsch, C, J Biosci. 2016;71:191–199. PubMed

107. Sammi SR, Trivedi S, Rath SK, Nagar A, Tandon S, Kalra A, Pandey R. 1-Methyl-4-propan-2-ylbenzene from Thymus vulgaris Attenuates Cholinergic Dysfunction. Mol Neurobiol. 2016 doi: 10.1007/s12035-016-0083-0. PubMed   

108. Lee Y. Cytotoxicity evaluation of essential oil and its component from zingiber officinale roscoe. Toxicol Res. 2016;32:225–230. doi: 10.5487/TR.2016.32.3.225. PMC free article  PubMed     

109. Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological effects of essential oils-a review. Food Chem Toxicol. 2008;46:446–475. doi: 10.1016/j.fct.2007.09.106. PubMed