Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Kits
2.2. Animals and Husbandry
2.3. Induction of EAE and Clinical Evaluation
2.4. Experimental Group and Study Design
2.4.1. Experiment One
2.4.2. Experiment Two
2.5. Histological Evaluation
2.6. Serum Preparation and Inspection of the Cytokines Profile
2.7. Separation of Lymphocyte from Spleen and Cell Culture
2.7.1. BrdU Cell Proliferation Assay
2.7.2. Examination of the Cytokines Profile
2.7.3. Evaluation of Intracellular Levels of Transcription Factors
2.8. Microglia Isolation
2.8.1. Cell Proliferation Assay
2.8.2. Evaluation of the Cytokine Levels
2.8.3. Evaluation of the Intracellular Levels of Arg-1 and iNOS
2.8.4. Evaluation of Urea and NO Levels
2.9. Statistical Analysis
3. Results
3.1. BCP Effect on Body Weight and the Clinical Score of EAE Mice
3.2. The BCP Effects on the Level of the Histopathological Score in EAE Mice
3.3. The BCP Effects on Serum Levels of Cytokines in EAE Mice
3.4. The Effects of BCP on Cell Proliferation and Cytokines Levels of Spleen Lymphocytes of EAE Mice with and without MOG Stimulation
3.5. The Effects of BCP on the Levels of Transcription Factors T-Bet (Th1), ROR-γt (Th17), Foxp3 (Treg), and GATA3 (Th2) of EAE Mice Lymphocytes with and without MOG Stimulation
3.6. The BCP Effects on Cell Proliferation, Cytokines Profile, and Markers of Microglia of EAE Mice with and without MOG Stimulation
3.7. The Relative Effects of BCP on the CNS Immunity and Systemic Immunity Levels in EAE Mice
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Score | Clinical Manifestations (Significant Comment) |
---|---|
0 | Without clinical symptoms |
1 | Partly limp tail (a tip of the tail droops, normal gait) |
2 | Paralyzed tail (tail droops, normal gait) |
3 | Uncoordinated movement, hind limb paresis (uncoordinated gait, hind limbs responding to pinching, tail limps) |
4 | One paralyzed hind limb (uncoordinated gait with dragging one hind limb, one hind limb not responding to pinch, tail limps) |
5 | Two paralyzed hind limbs (uncoordinated gait with both hind limbs dragging, two hind limbs not responding to pinch, tail limps) |
6 | Hind limbs paralyzed, weak forelimbs (uncoordinated gait with forelimbs struggling to pull body, tail limps, forelimbs reflex following pinching) |
7 | Hind limbs paralyzed, one paralyzed forelimb (no movement of the mouse, one forelimb responding to a toe pinch, tail limps) |
8 | Hind limbs paralyzed, both forelimbs paralyzed (no movement of the mouse, both forelimbs do not respond to a toe pinch, tail limps) |
9 | Moribund (worsened breathing, no movement) |
10 | Death |
Protocol | Groups | EAE | From Day 10 to 37 (Every Day) | |
---|---|---|---|---|
1 (n = 8/each group) | Sham | - | - | |
Control | ✓ | Vehicle | ||
BCP (2.5 mg/kg) | ✓ | BCP 2.5 mg/kg/day; p.o. | ||
BCP (5 mg/kg) | ✓ | BCP 5 mg/kg/day; p.o. | ||
DMF (60 mg/kg) | ✓ | DMF 30 mg/kg two times per day; p.o. | ||
2 (n = 8/each group) | 30 min later | |||
Sham | - | - | - | |
Control | ✓ | AM630 vehicle; i.p. | +BCP vehicle; p.o. | |
BCP (5 mg/kg) | ✓ | AM630 vehicle; i.p. | +BCP 5 mg/kg/day; p.o. | |
AM630 (1 mg/kg) + BCP (5 mg/kg) | ✓ | AM630 1 mg/kg/day; i.p. | +BCP 5 mg/kg/day; p.o. |
Groups | Incidence (Sick/Total) | MOD a | MMCS a | MCS at Peak EAE (Day 17) a | CDI a,b | Day Presents Significant Changes c |
---|---|---|---|---|---|---|
Sham | 0/16 (0%) | - | 0 ± 0 | 0 ± 0 | 0 | 0 |
Vehicle | 16/16 (100%) +++ | 6.72 ± 0.42 +++ | 7.75 ± 0.47 +++ | 7.75 ± 0.47 +++ | 29.20 ± 1.45 +++ | 9 d |
BCP 2.5 | 7/8 (87.5%) | 7.22 ± 0.25 | 4.00 ± 0.22 *** | 3.75 ± 0.18 *** | 15.68 ± 1.11 *** | 15 e |
BCP 5 | 9/16 (56.25%) ***, xxx | 6.82 ± 0.52 | 3.42 ± 0.18 ***, xxx | 2.75 ± 0.43 ***, xxx | 10.70 ± 0.83 ***, xxx | 15 e |
BCP 5 + AM630 | 8/8 (100%) ∆∆∆ | 7.11 ± 0.68 | 7.55 ± 0.48 ∆∆∆ | 7.35 ± 0.69 ∆∆∆ | 28.38 ± 2.12 ∆∆∆ | 9 d |
DMF 60 | 7/8 (87.5%) | 6.52 ± 0.55 | 4.62 ± 0.21 *** | 3.43 ± 0.31 *** | 15.81 ± 1.52 *** | 15 e |
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Askari, V.R.; Baradaran Rahimi, V.; Shafiee-Nick, R. Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial. Brain Sci. 2023, 13, 1092. https://doi.org/10.3390/brainsci13071092
Askari VR, Baradaran Rahimi V, Shafiee-Nick R. Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial. Brain Sciences. 2023; 13(7):1092. https://doi.org/10.3390/brainsci13071092
Chicago/Turabian StyleAskari, Vahid Reza, Vafa Baradaran Rahimi, and Reza Shafiee-Nick. 2023. "Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial" Brain Sciences 13, no. 7: 1092. https://doi.org/10.3390/brainsci13071092
APA StyleAskari, V. R., Baradaran Rahimi, V., & Shafiee-Nick, R. (2023). Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial. Brain Sciences, 13(7), 1092. https://doi.org/10.3390/brainsci13071092