Terpinolene

Phytomedicine, 2005, 12(6-7):416-423.

The monoterpene terpinolene from the oil of Pinus mugo L. in concert with α-tocopherol and β-carotene effectively prevents oxidation of LDL.[Reference: WebLink]

Antioxidants from several nutrients, e.g. vitamin E, β-carotene, or flavonoids, inhibit the oxidative modification of low-density lipoproteins. This protective effect could possibly retard atherogenesis and in consequence avoid coronary heart diseases. Some studies have shown a positive effect of those antioxidants on cardiovascular disease. Another class of naturally occurring antioxidants are terpenoids, which are found in essential oils. The essential oil of Pinus mugo and the contained monoterpene Terpinolene effectively prevent low-density lipoprotein (LDL)-oxidation.
METHODS AND RESULTS:
In order to test the mechanism by which Terpinolene protects LDL from oxidation, LDL from human blood plasma enriched in Terpinolene was isolated. In this preparation not only the lipid part of LDL is protected against copper-induced oxidation — as proven by following the formation of conjugated dienes, but also the oxidation of the protein part is inhibited, since loss of tryptophan fluorescence is strongly delayed. This inhibition is due to a retarded oxidation of intrinsic carotenoids of LDL, and not, as in the case of some flavonoids, attributable to a protection of intrinsic α-tocopherol.
CONCLUSIONS:
These results are in agreement with our previous results, which showed the same effects for a monoterpene from lemon oil, i.e. -terpinene.

Cytotechnology,2015,67:409–418.

Genotoxic and oxidative damage potentials in human lymphocytes after exposure to terpinolene in vitro.[Reference: WebLink]

Terpinolene (TPO) is a monocyclic monoterpene found in the essential oils of various fir and pine species. Recent reports indicated that several monoterpenes could exhibit antioxidant effects in both human and animal experimental models. However, so far, the nature and/or biological roles of TPO have not been elucidated in human models yet.
METHODS AND RESULTS:
The aim of this study was to investigate the genetic, oxidative and cytotoxic effects of TPO in cultured human blood cells (n = 5) for the first time. Human blood cells were treated with TPO (0–200 mg/L) for 24 and 48 h, and then cytotoxicity was detected by lactate dehydrogenase (LDH) release and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, while DNA damage was also analyzed by micronucleus assay, sister chromatid exchanges assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, biochemical parameters [total antioxidant capacity (TAC) and total oxidative stress (TOS)] were examined to determine oxidative effects. The results of LDH and MTT assays showed that TPO (at concentrations greater than 100 mg/L) decreased cell viability. In our in vitro test systems, it was observed that TPO had no genotoxicity on human lymphocytes. Again, TPO (at 10, 25, 50 and 75 mg/L) treatment caused statistically important (p < 0.05) increases of TAC levels in human lymphocytes without changing TOS levels.
CONCLUSIONS:
In conclusion, TPO can be a new resource of therapeutics as recognized in this study with its non-genotoxic and antioxidant features.

Oncology Letters, 18 Nov 2011, 3(2):321-324.

Terpinolene, a component of herbal sage, downregulates AKT1 expression in K562 cells.[Reference: WebLink]

Protein kinase AKT mediates cell proliferation and survival signals, and also contributes to cancer progression. Increased expression and/or activation of AKT is involved in a variety of human cancers.
METHODS AND RESULTS:
In cells treated with sage or rosemary extract, mRNA and protein expression levels of AKT1 were reduced compared with those of the control cells 48 h after the herbal treatments.
CONCLUSIONS:
We found that Terpinolene, a common component of sage and rosemary, markedly reduced the protein expression of AKT1 in K562 cells and inhibited cell proliferation.

Arh Hig Rada Toksikol, 2013, 64(3):415-424.

Anticancer and antioxidant properties of terpinolene in rat brain cells.[Reference: WebLink]

Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored.
METHODS AND RESULTS:
In this in vitro study we investigated TPO's antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L(-1), 25 mg L(-1), 50 mg L(-1), 100 mg L(-1), 200 mg L(-1), and 400 mg L(-1)) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L(-1) and in N2a neuroblastoma cells starting with 50 mg L(-1). TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L(-1), 25 mg L(-1), and 50 mg L(-1) increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L(-1) it increased TOS in both cell types.
CONCLUSIONS:
Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

Phytochemistry, 2003, 62(5):683-689.

Monoterpenoid accumulation in 1,8-cineole, terpinolene and terpinen-4-ol chemotypes of Melaleuca alternifolia seedlings.[Reference: WebLink]

Individual leaves of the three most common chemotypes of Melaleuca alternifolia were examined both quantitatively and qualitatively for volatile constituents from the emergence of the first true leaves, through to 6-week-old tenth leaf set material.
METHODS AND RESULTS:
The 1,8-cineole and Terpinolene chemotypes were investigated and compared with the recently reported commercial terpinen-4-ol chemotype. The 1,8-cineole chemotype was found to accumulate 1,8-cineole and associated p-menthanes limonene, terpinen-4-ol and α-terpineol gradually with increasing leaf set number. As with the terpinen-4-ol variety, higher than expected concentrations of the pinenes and Terpinolene were found only in the early leaf sets.
CONCLUSIONS:
The Terpinolene variety showed two stages of Terpinolene accumulation, the first at leaf sets 2–3 similar to the unexpected biosynthesis of Terpinolene in the terpinen-4-ol chemotype and the second at leaf sets 8–9 which is characteristic of the Terpinolene variety.