Hinokithiol (β-thujaplicine, 2-hydroxy-4-isopropyl-2,4,6 cycloheptatrien-1-one) is a biologically active substance from the group of tropolone compounds with the general formula C10H12O2 [1] and molecular weight 164,2 g/mol. It occurs naturally in the bark and roots of trees from the Cypress family (Cuperssaceae), incl. the giant thuja (Thuja plicata), the thuja Japanese thuja (Thujopsis dolabrata) and the Taiwanese cypress (Chamaecyparis taiwanesis). It has the form of a light yellow or white powder with a melting point of 50-52°C and a characteristic odor. It’s soluble in ethanol and dimethylsulfoxide (DMSO) [2]. In vitro studies with hinokithiol confirmed its antimicrobial and antiradical activity. This compound has the ability to complex zinc and copper ions, which are the basic factors in the biological activity of tyrosinase. By blocking the activity of tyrosinase, it reduces the synthesis of melanin responsible for the formation of discoloration [3]. It also has the ability to activate capsase-3, thus inducing the apoptosis process of cancer cells. It exhibits anti-inflammatory activity, which is related to the ability to modify the activity of lipoxygenase and carboxypeptidase A and the ability to inhibit the production of tumor necrosis factor alpha (TNF-α), the transcription factor κβ (NF-κB) and the transcription factor HIF-1 [4]. Additionally, in vivo, hinokitiol reduces the occurrence of photodamage to the skin caused by UVB radiation, which is related to the anti-radical activity of β-thujaplicin [5]. In modern cosmetology, hinokitiol is used in preparations for the care of oily and sensitive skin, as well as in anti-discoloration cosmetics, toothpastes and preparations for hair care [6].

Hinokitiol was discovered in 1936 by Dr. Tetsuo Nozoe from the essential oil component of Taiwan Hinoki. At the time, the discovery of this compound with a heptagonal molecular structure, which was said not to exist in nature at that time, was globally recognized as a great achievement in the history of chemistry.

Anti-inflammatory effect of hinokitiol

It has also been proved that hinokithiol has strong anti-inflammatory properties related to the ability of β-thujaplicine to chelate multivalent metal ions present in the active center of pro-inflammatory metallo-dependent enzymes, as well as the ability to inhibit pro-inflammatory cytokines [7]. In vivo studies carried out on rats, it was observed that hinokithiol reduces the expression of metalloproteinases types 1, 3, 13 and beta-catenine in IL-1β stimulated chondrocytes, thus reducing the risk of osteoarthritis [2, 7].

Antimicrobial properties of hinokithiol

In vitro studies of hinokithiol have demonstrated the antibacterial, antifungal, antiviral, and insecticidal activity of this. The mechanism of this action may be related to the ability to inhibit the activity of proteolytic enzymes, disturbance of the nucleic acid synthesis process, as well as an increase in the permeability of the cell wall to exogenous substances [8]. For this reason, some products, such as oral care cosmetics, preparations for hair and body contain β-thujaplycin, which exhibits antimicrobial activity against the pathogenic microorganisms of the skin, hair, and teeth. Bacterial and fungistatic activity of hinokithiol depends on the concentration of this compound, and a specific paradox of β-thujaplicin action is observed in relation to pathogenic microorganisms of the species Staphyloccocus aureus, Aggregatibacter actinomycetemcomitans and Streptococcus mutans occurring in the oral cavity. This compound at a low concentration inhibits the growth of microorganisms, while at a higher concentration it promotes the growth of these microorganisms, and at an even higher concentration, complete inhibition of growth is observed. As demonstrated by the simultaneous use of β-thujaplicin and zinc ions, the phenomenon of the so-called the paradox of the zone of inhibition of the growth of Staphyloccocus aureus microorganisms is limited and at the same time an improvement in the antimicrobial activity of hinokithiol is observed [9]. In recent studies [8] it has been proved that hinokitiol can reduce the growth of pathogenic microorganisms of the oral cavity, such as Staphyloccocus aureus, Aggregatibacter actinomycetemcomitans, Streptococcus mutans and Candida albicans.

Effects of hinokitiol on hair

In vivo studies in mice showed the effect of hinokithiol on stimulating of hair growth. In the experiment, mice were divided into four groups and treated with the hinokitiol present in the shampoo and 3% minoxidil solution, which stimulates the hair follicles. However, the skin of mice from the control group was treated with phosphate buffer. During experiment a hair growth has already been observed on day 12 in mice whose skin had been treated with hinokithiol, while in control group hair growth began only on day 14. Hair growth in the treatment group with hinokitiol was similar to the hair growth of the group with 3% Minoxidil. Moreover, it was observed that the density of The hair of the mice on the 16th day of the experiment after the use of hinokithiol was 1.5-2 times higher than in the control group In addition, the obtained effect was similar to that of minoxidil [10].

Other effects of hinokitiol

Hinokitiol strongly inhibits the proliferation of a wide range of tumor cell lines. Research studies showed that hinokitiol suppresses androgen / AR-mediated cell growth and androgen-stimulated DNA synthesis and significantly suppresses AR mRNA and protein expression in a dose- and time-dependent manner [11]. In addition, hinokitiol blocks the binding of the synthetic androgen [(3) H] R1881 to AR in LNCaP cells [12]. These results suggest that hinokitiol is potentially effective against prostate cancer in vitro. It was found that hinokitiol suppresses factors that promote follicular apoptosis, such as TNF-alpha, and could be used to stimulate hair growth. Hinokitiol also increases the transcription of vascular endothelial growth factor, giving it the potential in the treatment of ischemic diseases. Hinokitiol further inhibits platelet activation and thrombus formation and offers the possibility of its use in thromboembolic stroke.

Summary

Hinokitiol (β-thujaplycin) is a plant material found mainly in the bark and roots of trees of the Cypress family (Cuperssaceae). Its wide spectrum of properties (antimicrobial, anti-inflammatory, anti-aging, anti-radical, and antioxidant) makes it increasingly used in cosmetology. In addition, as shown in in vitro studies, it can inhibit the melanogenesis process, while in vivo its effect on hair growth was observed. The scientifically proven biological activity of hinokitiol suggests that it will be increasingly used in pharmacy and cosmetology.

References

1. Jayakumar, T., Hsu, W. H., Yen, T. L., Luo, J. Y., Kuo, Y. C., Fong, T. H., & Sheu, J. R. (2013). Hinokitiol, a natural tropolone derivative, offers neuroprotection from thromboembolic stroke in vivo. Evidence-based complementary and alternative medicine, 2013.
2. Shih, Y. H., Lin, D. J., Chang, K. W., Hsia, S. M., Ko, S. Y., Lee, S. Y., ... & Shieh, T. M. (2014). Evaluation physical characteristics and comparison antimicrobial and anti-inflammation potentials of dental root canal sealers containing hinokitiol in vitro. PloS one, 9(6), e94941.
3. Liu, S., & Yamauchi, H. (2006). Hinokitiol, a metal chelator derived from natural plants, suppresses cell growth and disrupts androgen receptor signaling in prostate carcinoma cell lines. Biochemical and biophysical research communications, 351(1), 26-32.
4. Lin, K. H., Kuo, J. R., Lu, W. J., Chung, C. L., Chou, D. S., Huang, S. Y., ... & Sheu, J. R. (2013). Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo. Biochemical Pharmacology, 85(10), 1478-1485.
5. Huang, C. H., Lu, S. H., Chang, C. C., Thomas, P. A., Jayakumar, T., & Sheu, J. R. (2015). Hinokitiol, a tropolone derivative, inhibits mouse melanoma (B16-F10) cell migration and in vivo tumor formation. European journal of pharmacology, 746, 148-157.
6. Higashi, Y., Sakata, M., & Fujii, Y. (2009). High-performance liquid chromatography with dual-wavelength ultraviolet detection for measurement of hinokitiol in personal care products. Journal of cosmetic science, 60(5), 519-525.
7. Lin, K. H., Kuo, J. R., Lu, W. J., Chung, C. L., Chou, D. S., Huang, S. Y., ... & Sheu, J. R. (2013). Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo. Biochemical Pharmacology, 85(10), 1478-1485.
8. Shih YH, Chang KW, Hsia SM, Yu CC, Fuh LJ, Chi TY, Shieh TM.In vitro antimicrobial and anticancer potential of hinokitiol against oral pathogens and oral cancer cell lines. Microbiol Res 2013
9. Arima, Y., Nakai, Y., Hayakawa, R., & Nishino, T. (2003). Antibacterial effect of β-thujaplicin on staphylococci isolated from atopic dermatitis: relationship between changes in the number of viable bacterial cells and clinical improvement in an eczematous lesion of atopic dermatitis. Journal of antimicrobial Chemotherapy, 51(1), 113-122.
10. Hwang, S. L., & Kim, J. C. (2008). In vivo hair growth promotion effects of cosmetic preparations containing hinokitiol-loaded poly (ε-caprolacton) nanocapsules. Journal of microencapsulation, 25(5), 351-356.
11. Lee, J. H., Jeong, J. K., & Park, S. Y. (2018). AMPK activation mediated by hinokitiol inhibits adipogenic differentiation of mesenchymal stem cells through autophagy flux. International Journal of Endocrinology, 2018.
12. Tu, D. G., Yu, Y., Lee, C. H., Kuo, Y. L., Lu, Y. C., Tu, C. W., & Chang, W. W. (2016). Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome mediated degradation of epidermal growth factor receptor. Oncology letters, 11(4), 2934-2940.

0.00 (0 votes)