In Vitro and In Vivo Anti-Inflammatory Effects of Cannabidiol Isolated from Novel Hemp ( L.) Cultivar Pink Pepper

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Sep 28

PMID 37764215

Authors

Jong-Hui Kim

Min Hong

Joon-Hee Han

Byeong Ryeol Ryu

Young Seok Lim

Jung Dae Lim

Chang Hyeug Kim

Soo-Ung Lee

Tae-Hyung Kwon

Affiliations

Soon will be listed here.

Abstract

L. contains more than 80 cannabinoids, among which cannabidiol (CBD) is the main neuroactive component. We aimed to investigate the anti-inflammatory efficacy of CBD in vitro and in vivo isolated from "Pink pepper", a novel hemp cultivar, by repeating the method of selecting and cultivating individuals with the highest CBD content. We investigated the effects of CBD on inflammatory markers elevated by lipopolysaccharide (LPS) treatment in RAW 264.7 mouse macrophage cells through Western blot and RT-PCR. In addition, we confirmed these effects through the ELISA of inflamed paw tissue of a λ-carrageenan-induced mouse edema model that received an oral administration of CBD. CBD inhibited the LPS-induced phosphorylation of NF-κB and MAPK in RAW 264.7 and exhibited anti-inflammatory effects by participating in these pathways. In our in vivo study, we confirmed that CBD also inhibited the inflammatory mediators of proteins extracted from edematous mouse paw tissue. These results show that CBD isolated from "Pink pepper" exhibits potent anti-inflammatory effects. These anti-inflammatory effects of CBD have pharmacological and physiological significance, highlighting the industrial value of this novel cultivar.

Citing Articles

∆-Tetrahydrocannabinol Increases Growth Factor Release by Cultured Adipose Stem Cells and Adipose Tissue in vivo.

Ruhl T, Benic S, Plum M, Kim B, Beier J, Schaefer B Tissue Eng Regen Med. 2025; 22(2):225-235.

PMID: 39825991 PMC: 11794773. DOI: 10.1007/s13770-024-00692-8.

Renal Outcomes and Other Adverse Effects of Cannabinoid Supplementation.

Mlynarska E, Kustosik N, Mejza M, Lyson Z, Delebis D, Orlinski J Nutrients. 2025; 17(1.

PMID: 39796493 PMC: 11722839. DOI: 10.3390/nu17010059.

References

Greenhough A, Smartt H, Moore A, Roberts H, Williams A, Paraskeva C . The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis. 2009; 30(3):377-86. DOI: 10.1093/carcin/bgp014. View

Byun E, Sung N, Byun E, Song D, Kim J, Park J . The procyanidin trimer C1 inhibits LPS-induced MAPK and NF-κB signaling through TLR4 in macrophages. Int Immunopharmacol. 2012; 15(2):450-6. DOI: 10.1016/j.intimp.2012.11.021. View

Morris C . Carrageenan-induced paw edema in the rat and mouse. Methods Mol Biol. 2003; 225:115-21. DOI: 10.1385/1-59259-374-7:115. View

Das L, Liu E, Saeed A, Williams D, Hu H, Li C . Industrial hemp as a potential bioenergy crop in comparison with kenaf, switchgrass and biomass sorghum. Bioresour Technol. 2017; 244(Pt 1):641-649. DOI: 10.1016/j.biortech.2017.08.008. View

Sun P, Zhou K, Wang S, Li P, Chen S, Lin G . Involvement of MAPK/NF-κB signaling in the activation of the cholinergic anti-inflammatory pathway in experimental colitis by chronic vagus nerve stimulation. PLoS One. 2013; 8(8):e69424. PMC: 3732220. DOI: 10.1371/journal.pone.0069424. View

Whiting P, Wolff R, Deshpande S, Di Nisio M, Duffy S, Hernandez A . Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015; 313(24):2456-73. DOI: 10.1001/jama.2015.6358. View

Blaskovich M, Kavanagh A, Elliott A, Zhang B, Ramu S, Amado M . The antimicrobial potential of cannabidiol. Commun Biol. 2021; 4(1):7. PMC: 7815910. DOI: 10.1038/s42003-020-01530-y. View

Lechner M, Lirk P, Rieder J . Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin. Semin Cancer Biol. 2005; 15(4):277-89. DOI: 10.1016/j.semcancer.2005.04.004. View

Al-Khayri J, Sahana G, Nagella P, Joseph B, Alessa F, Al-Mssallem M . Flavonoids as Potential Anti-Inflammatory Molecules: A Review. Molecules. 2022; 27(9). PMC: 9100260. DOI: 10.3390/molecules27092901. View

10.

Turu G, Hunyady L . Signal transduction of the CB1 cannabinoid receptor. J Mol Endocrinol. 2009; 44(2):75-85. DOI: 10.1677/JME-08-0190. View

11.

Hagenbach U, Luz S, Ghafoor N, Berger J, Grotenhermen F, Brenneisen R . The treatment of spasticity with Delta9-tetrahydrocannabinol in persons with spinal cord injury. Spinal Cord. 2006; 45(8):551-62. DOI: 10.1038/sj.sc.3101982. View

12.

Iftikhar A, Zafar U, Ahmed W, Shabbir M, Sameen A, Sahar A . Applications of L. in Food and Its Therapeutic Potential: From a Prohibited Drug to a Nutritional Supplement. Molecules. 2021; 26(24). PMC: 8708517. DOI: 10.3390/molecules26247699. View

13.

Zarghi A, Arfaei S . Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships. Iran J Pharm Res. 2013; 10(4):655-83. PMC: 3813081. View

14.

Khan M, Sobocinska A, Czarnecka A, Krol M, Botta B, Szczylik C . The Therapeutic Aspects of the Endocannabinoid System (ECS) for Cancer and their Development: From Nature to Laboratory. Curr Pharm Des. 2015; 22(12):1756-66. PMC: 5412000. DOI: 10.2174/1381612822666151211094901. View

15.

Verrico C, Wesson S, Konduri V, Hofferek C, Vazquez-Perez J, Blair E . A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain. 2020; 161(9):2191-2202. PMC: 7584779. DOI: 10.1097/j.pain.0000000000001896. View

16.

Porter B, St Marie B, Milavetz G, Herr K . Cannabidiol (CBD) Use by Older Adults for Acute and Chronic Pain. J Gerontol Nurs. 2021; 47(7):6-15. PMC: 8344100. DOI: 10.3928/00989134-20210610-02. View

17.

Bergamaschi M, Queiroz R, Chagas M, de Oliveira D, De Martinis B, Kapczinski F . Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 2011; 36(6):1219-26. PMC: 3079847. DOI: 10.1038/npp.2011.6. View

18.

Wen Y, Wang Z, Zhang R, Zhu Y, Lin G, Li R . The antinociceptive activity and mechanism of action of cannabigerol. Biomed Pharmacother. 2023; 158:114163. DOI: 10.1016/j.biopha.2022.114163. View

19.

Tanaka T, Narazaki M, Kishimoto T . Interleukin (IL-6) Immunotherapy. Cold Spring Harb Perspect Biol. 2017; 10(8). PMC: 6071487. DOI: 10.1101/cshperspect.a028456. View

20.

Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J . Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018; 9(6):7204-7218. PMC: 5805548. DOI: 10.18632/oncotarget.23208. View