Biomolecules & Therapeutics

  • 제32권5호
  • /
  • Pages.531-539
  • /
  • 2024
  • /
  • 1976-9148(pISSN)
  • /
  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
권호 표지
DOI QR코드

DOI QR Code

β-Lapachone Exerts Hypnotic Effects via Adenosine A1 Receptor in Mice

  • 투고 : 2024.06.24
  • 심사 : 2024.08.03
  • 발행 : 2024.09.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Sleep is one of the most essential physiological phenomena for maintaining health. Sleep disturbances, such as insomnia, are often accompanied by psychiatric or physical conditions such as impaired attention, anxiety, and stress. Medication used to treat insomnia have concerns about potential side effects with long-term use, so interest in the use of alternative medicine is increasing. In this study, we investigated the hypnotic effects of β-lapachone (β-Lap), a natural naphthoquinone compound, using pentobarbital-induced sleep test, immunohistochemistry, real-time PCR, and western blot in mice. Our results indicated that β-Lap exerts a significant hypnotic effect by showing a decrease in sleep onset latency and an increase in total sleep time in pentobarbital-induced sleep model. The results of c-Fos immunostaining showed that β-Lap decreased neuronal activity in the basal forebrain and lateral hypothalamus, which are wakefulness-promoting brain regions, while increasing in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly abolished by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor (A1R) antagonist. Western blot analysis showed that β-Lap increased extracellular signal-regulated kinase phosphorylation and nuclear factor-kappa B translocation from the cytoplasm to the nucleus; these effects were inhibited by DPCPX. Additionally, β-Lap increased the mRNA levels of A1R. Taken together, these results suggest that β-Lap exerts hypnotic effects, potentially through A1R.

키워드

과제정보

This research was supported by the GRRC program of Gyeonggi province (GRRCAjou2023-B01).

참고문헌

  1. Al-Awthan, Y. S., Rauf, A., Rashid, U., Bawazeer, S., Naz, S., Bahattab, O., Bawazeer, S., Muhammad, N., Waggas, D. S., Batiha, G. E., Shariati, M. A., Derkho, M. and Suleria, H. A. R. (2021) Sedative-hypnotic effect and in silico study of dinaphthodiospyrols isolated from Diospyros lotus Linn. Biomed. Pharmacother. 140, 111745.
  2. Alam, M. N., Kumar, S., Rai, S., Methippara, M., Szymusiak, R. and McGinty, D. (2009) Role of adenosine A(1) receptor in the perifornical-lateral hypothalamic area in sleep-wake regulation in rats. Brain Res. 1304, 96-104. https://doi.org/10.1016/j.brainres.2009.09.066
  3. Baranwal, N., Yu, P. K. and Siegel, N. S. (2023) Sleep physiology, pathophysiology, and sleep hygiene. Prog. Cardiovasc. Dis. 77, 59-69. https://doi.org/10.1016/j.pcad.2023.02.005
  4. Bawazeer, S. and Rauf, A. (2021) In vivo anti-inflammatory, analgesic, and sedative studies of the extract and naphthoquinone isolated from Diospyros kaki (persimmon). ACS Omega 6, 9852-9856. https://doi.org/10.1021/acsomega.1c00537
  5. Bermejo, M., Mangas-Sanjuan, V., Gonzalez-Alvarez, I. and Gonzalez-Alvarez, M. (2017) Enhancing oral absorption of β-lapachone: progress till date. Eur. J. Drug Metab. Pharmacokinet. 42, 1-10. https://doi.org/10.1007/s13318-016-0369-7
  6. Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E. and McCarley, R. W. (2012) Control of sleep and wakefulness. Physiol. Rev. 92, 1087-1187. https://doi.org/10.1152/physrev.00032.2011
  7. Chamberlin, N. L., Arrigoni, E., Chou, T. C., Scammell, T. E., Greene, R. W. and Saper, C. B. (2003) Effects of adenosine on gabaergic synaptic inputs to identified ventrolateral preoptic neurons. Neuroscience 119, 913-918. https://doi.org/10.1016/S0306-4522(03)00246-X
  8. Eban-Rothschild, A., Appelbaum, L. and de Lecea, L. (2018) Neuronal mechanisms for sleep/wake regulation and modulatory drive. Neuropsychopharmacology 43, 937-952. https://doi.org/10.1038/npp.2017.294
  9. Elmenhorst, D., Basheer, R., McCarley, R. W. and Bauer, A. (2009) Sleep deprivation increases A(1) adenosine receptor density in the rat brain. Brain Res. 1258, 53-58. https://doi.org/10.1016/j.brainres.2008.12.056
  10. Elmenhorst, D., Meyer, P. T., Winz, O. H., Matusch, A., Ermert, J., Coenen, H. H., Basheer, R., Haas, H. L., Zilles, K. and Bauer, A. (2007) Sleep deprivation increases A1 adenosine receptor binding in the human brain: a positron emission tomography study. J. Neurosci. 27, 2410-2415. https://doi.org/10.1523/JNEUROSCI.5066-06.2007
  11. Garrido-Suarez, B. B., Garrido-Valdes, M. and Garrido, G. (2022) Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals. Sleep Med. 98, 79-86. https://doi.org/10.1016/j.sleep.2022.06.011
  12. Gomes, C. L., de Albuquerque Wanderley Sales, V., Gomes de Melo, C., Ferreira da Silva, R. M., Vicente Nishimura, R. H., Rolim, L. A. and Rolim Neto, P. J. (2021) Beta-lapachone: natural occurrence, physicochemical properties, biological activities, toxicity and synthesis. Phytochemistry 186, 112713.
  13. Horner, R. L. and Peever, J. H. (2017) Brain circuitry controlling sleep and wakefulness. Continuum (Minneap. Minn.) 23, 955-972.
  14. Huang, L., Zhu, W., Li, N., Zhang, B., Dai, W., Li, S. and Xu, H. (2024) Functions and mechanisms of adenosine and its receptors in sleep regulation. Sleep Med. 115, 210-217. https://doi.org/10.1016/j.sleep.2024.02.012
  15. Imeri, L. and Opp, M. R. (2009) How (and why) the immune system makes us sleep. Nat. Rev. Neurosci. 10, 199-210. https://doi.org/10.1038/nrn2576
  16. Jamwal, S., Mittal, A., Kumar, P., Alhayani, D. M. and Al-Aboudi, A. (2019) Therapeutic potential of agonists and antagonists of A1, A2a, A2b and A3 adenosine receptors. Curr. Pharm. Des. 25, 2892-2905. https://doi.org/10.2174/1381612825666190716112319
  17. Lee, E. J., Ko, H. M., Jeong, Y. H., Park, E. M. and Kim, H. S. (2015) β-Lapachone suppresses neuroinflammation by modulating the expression of cytokines and matrix metalloproteinases in activated microglia. J. Neuroinflammation 12, 133.
  18. Lee, K. B., Latif, S. and Kang, Y. S. (2023) Differences in neurotransmitters level as biomarker on sleep effects in dementia patients with insomnia after essential oils treatment. Biomol. Ther. (Seoul) 31, 298-305. https://doi.org/10.4062/biomolther.2023.014
  19. Li, Y., Feng, M., Guo, T., Wang, Z. and Zhao, Y. (2023) Tailored beta-lapachone nanomedicines for cancer-specific therapy. Adv. Healthcare Mater. 12, 2300349.
  20. Liu, Y. J., Chen, J., Li, X., Zhou, X., Hu, Y. M., Chu, S. F., Peng, Y. and Chen, N. H. (2019) Research progress on adenosine in central nervous system diseases. CNS Neurosci. Ther. 25, 899-910. https://doi.org/10.1111/cns.13190
  21. Mikhail, C., Vaucher, A., Jimenez, S. and Tafti, M. (2017) ERK signaling pathway regulates sleep duration through activity-induced gene expression during wakefulness. Sci. Signal. 10, eaai9219.
  22. Morairty, S., Rainnie, D., McCarley, R. and Greene, R. (2004) Disinhibition of ventrolateral preoptic area sleep-active neurons by adenosine: a new mechanism for sleep promotion. Neuroscience 123, 451-457. https://doi.org/10.1016/j.neuroscience.2003.08.066
  23. Oh, J., Petersen, C., Walsh, C. M., Bittencourt, J. C., Neylan, T. C. and Grinberg, L. T. (2019) The role of co-neurotransmitters in sleep and wake regulation. Mol. Psychiatry 24, 1284-1295. https://doi.org/10.1038/s41380-018-0291-2
  24. Park, J. S., Leem, Y. H., Park, J. E., Kim, D. Y. and Kim, H. S. (2019) Neuroprotective effect of β-Lapachone in MPTP-induced Parkinson's disease mouse model: involvement of astroglial p-AMPK/Nrf2/HO-1 signaling pathways. Biomol. Ther. (Seoul) 27, 178-184. https://doi.org/10.4062/biomolther.2018.234
  25. Rauf, A., Abu-Izneid, T., Alhumaydhi, F. A., Muhammad, N., Aljohani, A. S. M., Naz, S., Bawazeer, S., Wadood, A. and Mubarak, M. S. (2020) In vivo analgesic, anti-inflammatory, and sedative activity and a molecular docking study of dinaphthodiospyrol G isolated from Diospyros lotus. BMC Complement. Med. Ther. 20, 237.
  26. Sachdeva, S. and Gupta, M. (2013) Adenosine and its receptors as therapeutic targets: an overview. Saudi Pharm. J. 21, 245-253. https://doi.org/10.1016/j.jsps.2012.05.011
  27. Saddichha, S. (2010) Diagnosis and treatment of chronic insomnia. Ann. Indian Acad. Neurol. 13, 94-102. https://doi.org/10.4103/0972-2327.64628
  28. Saper, C. B. and Fuller, P. M. (2017) Wake-sleep circuitry: an overview. Curr. Opin. Neurobiol. 44, 186-192. https://doi.org/10.1016/j.conb.2017.03.021
  29. Scammell, T. E., Arrigoni, E. and Lipton, J. O. (2017) Neural circuitry of wakefulness and sleep. Neuron 93, 747-765. https://doi.org/10.1016/j.neuron.2017.01.014
  30. Sheth, S., Brito, R., Mukherjea, D., Rybak, L. P. and Ramkumar, V. (2014) Adenosine receptors: expression, function and regulation. Int. J. Mol. Sci. 15, 2024-2052. https://doi.org/10.3390/ijms15022024
  31. Silvers, M. A., Deja, S., Singh, N., Egnatchik, R. A., Sudderth, J., Luo, X., Beg, M. S., Burgess, S. C., DeBerardinis, R. J., Boothman, D. A. and Merritt, M. E. (2017) The NQO1 bioactivatable drug, β-lapachone, alters the redox state of NQO1+ pancreatic cancer cells, causing perturbation in central carbon metabolism. J. Biol. Chem. 292, 18203-18216. https://doi.org/10.1074/jbc.M117.813923
  32. Spanoghe, J., Larsen, L. E., Craey, E., Manzella, S., Van Dycke, A., Boon, P. and Raedt, R. (2020) The signaling pathways involved in the anticonvulsive effects of the adenosine A(1) receptor. Int. J. Mol. Sci. 22, 320.
  33. Strecker, R. E., Morairty, S., Thakkar, M. M., Porkka-Heiskanen, T., Basheer, R., Dauphin, L. J., Rainnie, D. G., Portas, C. M., Greene, R. W. and McCarley, R. W. (2000) Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state. Behav. Brain Res. 115, 183-204. https://doi.org/10.1016/S0166-4328(00)00258-8
  34. Thakkar, M. M., Delgiacco, R. A., Strecker, R. E. and McCarley, R. W. (2003) Adenosinergic inhibition of basal forebrain wakefulness-active neurons: a simultaneous unit recording and microdialysis study in freely behaving cats. Neuroscience 122, 1107-1113. https://doi.org/10.1016/j.neuroscience.2003.08.006
  35. Thakkar, M. M., Engemann, S. C., Walsh, K. M. and Sahota, P. K. (2008) Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness. Neuroscience 153, 875-880. https://doi.org/10.1016/j.neuroscience.2008.01.017
  36. Thakkar, M. M., Winston, S. and McCarley, R. W. (2002) Orexin neurons of the hypothalamus express adenosine A1 receptors. Brain Res. 944, 190-194. https://doi.org/10.1016/S0006-8993(02)02873-1
  37. Trinh, N. H. P. (2021) Coincident Modulation of Adenosine Receptor and Metabotropic Glutamate Receptor 5. Monash University.
  38. Trinh, P. N. H., Baltos, J. A., Hellyer, S. D., May, L. T. and Gregory, K. J. (2022) Adenosine receptor signalling in Alzheimer's disease. Purinergic Signal. 18, 359-381. https://doi.org/10.1007/s11302-022-09883-1
  39. Um, S., Jeong, H., An, J. S., Jo, S. J., Kim, Y. R., Oh, D. C. and Moon, K. (2023) Chromatographic determination of the absolute configuration in sanjoinine A that increases nitric oxide production. Biomol. Ther. (Seoul) 31, 566-572. https://doi.org/10.4062/biomolther.2023.028
  40. Van Dort, C. J., Baghdoyan, H. A. and Lydic, R. (2009) Adenosine A(1) and A(2A) receptors in mouse prefrontal cortex modulate acetylcholine release and behavioral arousal. J. Neurosci. 29, 871-881. https://doi.org/10.1523/JNEUROSCI.4111-08.2009
  41. Wang, Y. Q., Zhang, M. Q., Li, R., Qu, W. M. and Huang, Z. L. (2018) The mutual interaction between sleep and epilepsy on the neurobiological basis and therapy. Curr. Neuropharmacol. 16, 5-16.
  42. Winkelman, J. W. (2015) Insomnia disorder. N. Engl. J. Med. 373, 1437-1444. https://doi.org/10.1056/NEJMcp1412740