A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome
Abstract Background Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolute...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Journal of Cannabis Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s42238-021-00101-0 |
| _version_ | 1830409078624485376 |
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| author | Hesam Khodadadi Évila Lopes Salles Eunice Shin Abbas Jarrahi Vincenzo Costigliola Pritesh Kumar Jack C. Yu John C. Morgan David C. Hess Kumar Vaibhav Krishnan M. Dhandapani Babak Baban |
| author_facet | Hesam Khodadadi Évila Lopes Salles Eunice Shin Abbas Jarrahi Vincenzo Costigliola Pritesh Kumar Jack C. Yu John C. Morgan David C. Hess Kumar Vaibhav Krishnan M. Dhandapani Babak Baban |
| author_sort | Hesam Khodadadi |
| collection | DOAJ |
| description | Abstract Background Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS. Methods We used, for the first time, an inhalant CBC treatment as a potential therapeutic target in a murine model of ARDS-like symptoms. ARDS was induced by intranasal administration of Poly(I:C), a synthetic mismatched double-stranded RNA, into the C57BL/6 mice (6–10 male mice/group, including sham, placebo, and CBC treated), three once-daily doses followed by a daily dose of inhalant CBC or placebo for the period of 8 days starting the first dose 2 h after the second Poly(I:C) treatment. We employed histologic, immunohistochemistry, and flow cytometry methods to assess the findings. Statistical analysis was performed by using one way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test to determine the differences among the means of all experimental groups and to establish significance (p < 0.05) among all groups. Results Our data showed that CBC was able to reverse the hypoxia (increasing blood O2 saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance. Conclusion Our findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research. |
| first_indexed | 2024-12-20T19:03:29Z |
| format | Article |
| id | doaj.art-50e06b2e0d2a438ca9981ccdcfb309b7 |
| institution | Directory Open Access Journal |
| issn | 2522-5782 |
| language | English |
| last_indexed | 2024-12-20T19:03:29Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cannabis Research |
| spelling | doaj.art-50e06b2e0d2a438ca9981ccdcfb309b72022-12-21T19:29:20ZengBMCJournal of Cannabis Research2522-57822021-10-01311710.1186/s42238-021-00101-0A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndromeHesam Khodadadi0Évila Lopes Salles1Eunice Shin2Abbas Jarrahi3Vincenzo Costigliola4Pritesh Kumar5Jack C. Yu6John C. Morgan7David C. Hess8Kumar Vaibhav9Krishnan M. Dhandapani10Babak Baban11Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta UniversityDepartment of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta UniversityMedical College of Georgia, Augusta UniversityDepartment of Neurosurgery, Medical College of Georgia, Augusta UniversityEuropean Medical Association (EMA)Cannabinoid Research Program, Canadore CollegeDepartment of Surgery, Medical College of Georgia, Augusta UniversityParkinson’s Foundation Center of Excellence, Movement Disorders, Program, Department of Neurology, Medical College of Georgia, Augusta UniversityDepartment of Neurology, Medical College of Georgia, Augusta UniversityDepartment of Neurosurgery, Medical College of Georgia, Augusta UniversityDepartment of Neurosurgery, Medical College of Georgia, Augusta UniversityDepartment of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta UniversityAbstract Background Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS. Methods We used, for the first time, an inhalant CBC treatment as a potential therapeutic target in a murine model of ARDS-like symptoms. ARDS was induced by intranasal administration of Poly(I:C), a synthetic mismatched double-stranded RNA, into the C57BL/6 mice (6–10 male mice/group, including sham, placebo, and CBC treated), three once-daily doses followed by a daily dose of inhalant CBC or placebo for the period of 8 days starting the first dose 2 h after the second Poly(I:C) treatment. We employed histologic, immunohistochemistry, and flow cytometry methods to assess the findings. Statistical analysis was performed by using one way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test to determine the differences among the means of all experimental groups and to establish significance (p < 0.05) among all groups. Results Our data showed that CBC was able to reverse the hypoxia (increasing blood O2 saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance. Conclusion Our findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research.https://doi.org/10.1186/s42238-021-00101-0CannabichromeneCBCARDSTRPA1TRPV1COVID-19 |
| spellingShingle | Hesam Khodadadi Évila Lopes Salles Eunice Shin Abbas Jarrahi Vincenzo Costigliola Pritesh Kumar Jack C. Yu John C. Morgan David C. Hess Kumar Vaibhav Krishnan M. Dhandapani Babak Baban A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome Journal of Cannabis Research Cannabichromene CBC ARDS TRPA1 TRPV1 COVID-19 |
| title | A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome |
| title_full | A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome |
| title_fullStr | A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome |
| title_full_unstemmed | A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome |
| title_short | A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome |
| title_sort | potential role for cannabichromene in modulating trp channels during acute respiratory distress syndrome |
| topic | Cannabichromene CBC ARDS TRPA1 TRPV1 COVID-19 |
| url | https://doi.org/10.1186/s42238-021-00101-0 |
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