Hinokitiol

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Hinokitiol (β-thujaplicin) is a natural monoterpenoid found in the wood of trees in the family Cupressaceae.[1]


History

Hinokitiol was first extracted from Taiwanese hinoki in 1936.[2]

Anti-microbial activity

Anti bacterial activity

Hinokitiol has a broad range of biological activities, many of which have been explored and characterised in literature. Recent research has shown that Hinokitiol has potential antimicrobial activity against many bacteria and fungi, including some antibiotic resistance bacteria e.g MRSA(Methicillin resistant Staphlococcus Aureus).[3] Specifically, Hinokitiol has been shown to be effective against Streptococcus pneumoniae, Streptococcus mutans and Staphylococcus Aureus, common human pathogens.[4] Additionally, Hinokitiol has been shown to possess inhibitory effects on Chlamydia trachomatis and may be clinically useful as a topical drug.[5]

Anti-viral activity

More recent studies have shown that Hinokitiol also demonstrates anti-viral action when used in combination with a zinc compound against a several human viruses including rhinovirus, coxsackievirus and mengovirus. It has been proposed that Hinokitiol inhibits viral replication by impairing viral polyprotein processing.[6]

Cancer Research

Hinokitiol is known to posses anti-inflammatory and anti-tumour activities which has been demonstrated in a number of in vitro cell studies and in vivo animal studies. Hinokitiol inhibits key inflammatory markers and pathways, such as TNF-a and NF-kB, and its potential for treatment of chronic inflammatory or autoimmune conditions is being explored. Hinokitiol was found to exert cytotoxicity on several prominent cancer cell lines by inducing autophagic processes.[7][8]

Zinc synergism

Zinc deficiency has been demonstrated in some cancer cells and returning optimum intra-cellular zinc levels can lead to suppression tumor growth. Hinokitiol is a documented Zinc Ionophore, however more research is required at this time to establish effective concentrations of delivery methods for Hinokitiol and Zinc.[9][10][11]

References

  1. Fallik, E.; Grinberg, Shoshana (1992-11-01). "Hinokitiol: a natural substance that controls postharvest diseases in eggplant and pepper fruits" (in en). Postharvest Biology and Technology 2 (2): 137–144. doi:10.1016/0925-5214(92)90016-I. ISSN 0925-5214. http://www.sciencedirect.com/science/article/pii/092552149290016I. 
  2. "Tetsuo Nozoe: chemistry and life". Chemical Record 12 (6): 599–607. December 2012. doi:10.1002/tcr.201200024. PMID 23242794. 
  3. Shih, Yin-Hua; Chang, Kuo-Wei; Hsia, Shih-Min; Yu, Cheng-Chia; Fuh, Lih-Jyh; Chi, Tzu-Yun; Shieh, Tzong-Ming (2013-06-12). "In vitro antimicrobial and anticancer potential of hinokitiol against oral pathogens and oral cancer cell lines" (in en). Microbiological Research 168 (5): 254–262. doi:10.1016/j.micres.2012.12.007. ISSN 0944-5013. http://www.sciencedirect.com/science/article/pii/S0944501312001462. 
  4. Domon, Hisanori; Hiyoshi, Takumi; Maekawa, Tomoki; Yonezawa, Daisuke; Tamura, Hikaru; Kawabata, Shigetada; Yanagihara, Katsunori; Kimura, Osamu et al. (2019). "Antibacterial activity of hinokitiol against both antibiotic-resistant and -susceptible pathogenic bacteria that predominate in the oral cavity and upper airways" (in en). Microbiology and Immunology 63 (6): 213–222. doi:10.1111/1348-0421.12688. ISSN 1348-0421. https://onlinelibrary.wiley.com/doi/abs/10.1111/1348-0421.12688. 
  5. Yamano, Hiroaki; Yamazaki, Tsutomu; Sato, Kozue; Shiga, Sadashi; Hagiwara, Toshikatsu; Ouchi, Kazunobu; Kishimoto, Toshio (2005-2006). "In Vitro Inhibitory Effects of Hinokitiol on Proliferation of Chlamydia trachomatis". Antimicrobial Agents and Chemotherapy 49 (6): 2519–2521. doi:10.1128/AAC.49.6.2519-2521.2005. ISSN 0066-4804. PMC 1140513. PMID 15917561. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140513/. 
  6. Krenn, B. M.; Gaudernak, E.; Holzer, B.; Lanke, K.; Van Kuppeveld, F. J. M.; Seipelt, J. (2009). "Antiviral Activity of the Zinc Ionophores Pyrithione and Hinokitiol against Picornavirus Infections". Journal of Virology 83 (1): 58–64. doi:10.1128/JVI.01543-08. ISSN 0022-538X. PMC 2612303. PMID 18922875. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612303/. 
  7. Lee, Tae Bok; Jun, Jin Hyun (2019-06-30). "Can Hinokitiol Kill Cancer Cells? Alternative Therapeutic Anticancer Agent via Autophagy and Apoptosis" (in en). Korean Journal of Clinical Laboratory Science 51 (2): 221–234. doi:10.15324/kjcls.2019.51.2.221. ISSN 1738-3544. http://www.kjcls.org/journal/view.html?doi=10.15324/kjcls.2019.51.2.221. 
  8. Jayakumar, Thanasekaran; Liu, Chao-Hong; Wu, Guan-Yi; Lee, Tzu-Yin; Manubolu, Manjunath; Hsieh, Cheng-Ying; Yang, Chih-Hao; Sheu, Joen-Rong (2018-03-22). "Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis". International Journal of Molecular Sciences 19 (4). doi:10.3390/ijms19040939. ISSN 1422-0067. PMC 5979393. PMID 29565268. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979393/. 
  9. Taccioli, C.; Chen, H.; Jiang, Y.; Liu, X. P.; Huang, K.; Smalley, K. J.; Farber, J. L.; Croce, C. M. et al. (2012). "Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature" (in en). Oncogene 31 (42): 4550–4558. doi:10.1038/onc.2011.592. ISSN 1476-5594. https://www.nature.com/articles/onc2011592. 
  10. Wang, Ying; Sun, Zhengyi; Li, Aipeng; Zhang, Yongsheng (2019-05-06). "Association between serum zinc levels and lung cancer: a meta-analysis of observational studies". World Journal of Surgical Oncology 17 (1): 78. doi:10.1186/s12957-019-1617-5. ISSN 1477-7819. PMC PMC6503426. PMID 31060563. https://doi.org/10.1186/s12957-019-1617-5. 
  11. Liu, Cong-Min; Liang, Di; Jin, Jing; Li, Dao-Juan; Zhang, Ya-Chen; Gao, Zhao-Yu; He, Yu-Tong (2017). "Research progress on the relationship between zinc deficiency, related microRNAs, and esophageal carcinoma" (in en). Thoracic Cancer 8 (6): 549–557. doi:10.1111/1759-7714.12493. ISSN 1759-7714. PMC PMC5668500. PMID 28892299. https://onlinelibrary.wiley.com/doi/abs/10.1111/1759-7714.12493.