Väitös (farmakologia, lääkekehitys ja lääkehoito): MSc Ali Benkherouf
Aika
12.1.2024 klo 12.00 - 16.00
MSc Ali Benkherouf esittää väitöskirjansa ”Nature’s brewery to bedtime: The Role of hops in GABA(A) receptor modulation and sleep promotion” julkisesti tarkastettavaksi Turun yliopistossa perjantaina 12.01.2024 klo 12.00 (Turun yliopisto, Medisiina C, Osmo Järvi -sali, Turku).
Yleisön on mahdollista osallistua väitökseen myös etäyhteyden kautta: https://echo360.org.uk/section/4568cb85-265c-4f9c-8fa3-dbb43385e822/public
Vastaväittäjänä toimii professori Esa Korpi (Helsingin yliopisto) ja kustoksena professori Ullamari Pesonen (Turun yliopisto). Tilaisuus on englanninkielinen. Väitöksen alana on farmakologia, lääkekehitys ja lääkehoito.
Väitöskirja yliopiston julkaisuarkistossa: https://www.utupub.fi/handle/10024/176245
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Tiivistelmä väitöstutkimuksesta:
In the face of modern life's relentless pace, sleep remains a vital pillar of well-being. However, many individuals struggle with sleep disturbances, particularly insomnia. Conventional hypnotics, such as benzodiazepines, often provide relief but carry potential risks of dependence and cognitive impairment. Nature offers a wealth of resources to help restore balance and facilitate restful sleep. Among these natural allies are hops, the female flowers of the Humulus lupulus plant. Renowned for their characteristic aroma and bitterness in beer, hops have long been used in traditional herbal remedies as a relaxant and sleep aid.
Despite their long-standing use, the active compounds and mechanisms underlying hops sleep-promoting effects have remained elusive. GABA(A) receptors, distributed throughout the nervous system, play a central role in regulating sleep patterns. Upon binding to GABA, the primary inhibitory neurotransmitter, GABA(A) receptors open their ion channels, allowing chloride ions to flow into the cell, thereby reducing neuronal excitation and initiating sleep. Comprehending hops pharmacological properties necessitates unraveling its interactions with these crucial receptors.
My research reveals that hops contain several compounds that can influence GABA(A) receptor activity. Of particular importance is humulone, a bitter acid that acts as a positive allosteric modulator of GABA(A) receptors. This means that humulone enhances the ability of GABA to open the receptor chloride channels, leading to a decrease in neuronal firing. Additionally, I identified several hop prenylflavonoids, including isoxanthohumol and 6-prenylnaringenin, that additively amplify humulones effects on GABA(A) receptors, suggesting that hops sleep-promoting effects arise from a complex interplay of these phytochemicals. Notably, the identified hop compounds interact with specific sites on the receptor proteins, excreting their action independently of the benzodiazepine binding site.
To further evaluate the sleep-enhancing properties of hops, I conducted behavioral experiments in mice. My findings showed that humulone significantly shortens drug-induced sleep onset and prolongs sleep duration. My research also explored the potential interactions of hops with alcohol, a depressant that also influences GABA(A) receptor activity. Interestingly, humulone and alcohol exhibit synergistic effects, suggesting that hops may boost the intoxicating effects of alcohol in beer. This finding emphasizes the importance of moderate consumption and responsible use of hops-containing beverages.
In conclusion, this research provides a novel understanding of the mechanisms by which hop constituents modulate GABA(A) receptors and promote sleep. These findings highlight the potential of hops as a natural sleep aid with distinct advantages over conventional medications. Further research could pave the way for the development of more targeted and effective insomnia therapies.
Yleisön on mahdollista osallistua väitökseen myös etäyhteyden kautta: https://echo360.org.uk/section/4568cb85-265c-4f9c-8fa3-dbb43385e822/public
Vastaväittäjänä toimii professori Esa Korpi (Helsingin yliopisto) ja kustoksena professori Ullamari Pesonen (Turun yliopisto). Tilaisuus on englanninkielinen. Väitöksen alana on farmakologia, lääkekehitys ja lääkehoito.
Väitöskirja yliopiston julkaisuarkistossa: https://www.utupub.fi/handle/10024/176245
***
Tiivistelmä väitöstutkimuksesta:
In the face of modern life's relentless pace, sleep remains a vital pillar of well-being. However, many individuals struggle with sleep disturbances, particularly insomnia. Conventional hypnotics, such as benzodiazepines, often provide relief but carry potential risks of dependence and cognitive impairment. Nature offers a wealth of resources to help restore balance and facilitate restful sleep. Among these natural allies are hops, the female flowers of the Humulus lupulus plant. Renowned for their characteristic aroma and bitterness in beer, hops have long been used in traditional herbal remedies as a relaxant and sleep aid.
Despite their long-standing use, the active compounds and mechanisms underlying hops sleep-promoting effects have remained elusive. GABA(A) receptors, distributed throughout the nervous system, play a central role in regulating sleep patterns. Upon binding to GABA, the primary inhibitory neurotransmitter, GABA(A) receptors open their ion channels, allowing chloride ions to flow into the cell, thereby reducing neuronal excitation and initiating sleep. Comprehending hops pharmacological properties necessitates unraveling its interactions with these crucial receptors.
My research reveals that hops contain several compounds that can influence GABA(A) receptor activity. Of particular importance is humulone, a bitter acid that acts as a positive allosteric modulator of GABA(A) receptors. This means that humulone enhances the ability of GABA to open the receptor chloride channels, leading to a decrease in neuronal firing. Additionally, I identified several hop prenylflavonoids, including isoxanthohumol and 6-prenylnaringenin, that additively amplify humulones effects on GABA(A) receptors, suggesting that hops sleep-promoting effects arise from a complex interplay of these phytochemicals. Notably, the identified hop compounds interact with specific sites on the receptor proteins, excreting their action independently of the benzodiazepine binding site.
To further evaluate the sleep-enhancing properties of hops, I conducted behavioral experiments in mice. My findings showed that humulone significantly shortens drug-induced sleep onset and prolongs sleep duration. My research also explored the potential interactions of hops with alcohol, a depressant that also influences GABA(A) receptor activity. Interestingly, humulone and alcohol exhibit synergistic effects, suggesting that hops may boost the intoxicating effects of alcohol in beer. This finding emphasizes the importance of moderate consumption and responsible use of hops-containing beverages.
In conclusion, this research provides a novel understanding of the mechanisms by which hop constituents modulate GABA(A) receptors and promote sleep. These findings highlight the potential of hops as a natural sleep aid with distinct advantages over conventional medications. Further research could pave the way for the development of more targeted and effective insomnia therapies.
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