Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers

doi:10.1007/s13659-023-00382-3

应用天然产物 ›› 2023, Vol. 13 ›› Issue (3): 19-19.DOI: 10.1007/s13659-023-00382-3

Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers

Inga Dammann¹, Claudia Keil², Iris Hardewig¹, Elżbieta Skrzydlewska³, Michał Biernacki³, Hajo Haase²

1. Sanity Group GmbH, Jägerstraße 28-31, 10117, Berlin, Germany;
2. Department of Food Chemistry and Toxicology, Technische Universität Berlin, Straße Des 17. Juni 135, 10623, Berlin, Germany;
3. Department of Analytical Chemistry, Medical University of Bialystok, A. Mickiewicza 2D, 15-222, Bialystok, Poland

收稿日期:2023-03-28 出版日期:2023-06-24 发布日期:2023-07-18
通讯作者: Inga Dammann,E-mail:inga.dammann@sanitygroup.com;Hajo Haase,E-mail:haase@tu-berlin.de
基金资助:
Hereby we acknowledge the contributions of BAFA Neu GmbH and Flavex Naturextrakte GmbH, which kindly donated the plant extracts used throughout this study. Research at the department of food chemistry and toxicology at TU Berlin has been supported by a donation from Sanity Group GmbH. We would also like to thank Dr. rer. nat. Cathrin Rohleder from Sanity Group GmbH for providing access to a licensed figure created with Biorende.com.

Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers

Inga Dammann¹, Claudia Keil², Iris Hardewig¹, Elżbieta Skrzydlewska³, Michał Biernacki³, Hajo Haase²

1. Sanity Group GmbH, Jägerstraße 28-31, 10117, Berlin, Germany;
2. Department of Food Chemistry and Toxicology, Technische Universität Berlin, Straße Des 17. Juni 135, 10623, Berlin, Germany;
3. Department of Analytical Chemistry, Medical University of Bialystok, A. Mickiewicza 2D, 15-222, Bialystok, Poland

Received:2023-03-28 Online:2023-06-24 Published:2023-07-18
Contact: Inga Dammann,E-mail:inga.dammann@sanitygroup.com;Hajo Haase,E-mail:haase@tu-berlin.de
Supported by:
Hereby we acknowledge the contributions of BAFA Neu GmbH and Flavex Naturextrakte GmbH, which kindly donated the plant extracts used throughout this study. Research at the department of food chemistry and toxicology at TU Berlin has been supported by a donation from Sanity Group GmbH. We would also like to thank Dr. rer. nat. Cathrin Rohleder from Sanity Group GmbH for providing access to a licensed figure created with Biorende.com.

摘要/Abstract

摘要： This study investigates the potential of cannabidiol (CBD), one major cannabinoid of the plant Cannabis sativa, alone and in combination with a terpene-enriched extract from Humulus lupulus (“Hops 1”), on the LPS-response of RAW 264.7 macrophages as an established in vitro model of inflammation. With the present study, we could support earlier findings of the anti-inflammatory potential of CBD, which showed a dose-dependent [0-5 μM] reduction in nitric oxide and tumor necrosis factor-alpha (TNF-α) released by LPS-stimulated RAW 264.7 macrophages. Moreover, we observed an additive anti-inflammatory effect after combined CBD [5 μM] and hops extract [40 μg/mL] treatment. The combination of CBD and Hops 1 showed effects in LPS-stimulated RAW 264.7 cells superior to the single substance treatments and akin to the control hydrocortisone. Furthermore, cellular CBD uptake increased dose-dependently in the presence of terpenes from Hops 1 extract. The anti-inflammatory effect of CBD and its cellular uptake positively correlated with terpene concentration, as indicated by comparison with a hemp extract containing both CBD and terpenes. These findings may contribute to the postulations for the so-called “entourage effect” between cannabinoids and terpenes and support the potential of CBD combined with phytomolecules from a non-cannabinoid source, such as hops, for the treatment of inflammatory diseases.

关键词: CBD, Terpenes, Cannabinoids, Entourage effect, Inflammation

Abstract: This study investigates the potential of cannabidiol (CBD), one major cannabinoid of the plant Cannabis sativa, alone and in combination with a terpene-enriched extract from Humulus lupulus (“Hops 1”), on the LPS-response of RAW 264.7 macrophages as an established in vitro model of inflammation. With the present study, we could support earlier findings of the anti-inflammatory potential of CBD, which showed a dose-dependent [0-5 μM] reduction in nitric oxide and tumor necrosis factor-alpha (TNF-α) released by LPS-stimulated RAW 264.7 macrophages. Moreover, we observed an additive anti-inflammatory effect after combined CBD [5 μM] and hops extract [40 μg/mL] treatment. The combination of CBD and Hops 1 showed effects in LPS-stimulated RAW 264.7 cells superior to the single substance treatments and akin to the control hydrocortisone. Furthermore, cellular CBD uptake increased dose-dependently in the presence of terpenes from Hops 1 extract. The anti-inflammatory effect of CBD and its cellular uptake positively correlated with terpene concentration, as indicated by comparison with a hemp extract containing both CBD and terpenes. These findings may contribute to the postulations for the so-called “entourage effect” between cannabinoids and terpenes and support the potential of CBD combined with phytomolecules from a non-cannabinoid source, such as hops, for the treatment of inflammatory diseases.

Key words: CBD, Terpenes, Cannabinoids, Entourage effect, Inflammation

Inga Dammann, Claudia Keil, Iris Hardewig, Elżbieta Skrzydlewska, Michał Biernacki, Hajo Haase. Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers[J]. 应用天然产物, 2023, 13(3): 19-19.

参考文献

1 Psomadakis CE, Han G. New and emerging topical therapies for psoriasis and atopic dermatitis. J Clin Aesthet Dermatol. 2019;12:28-34.
2 Pantazi E, Valenza G, Hess M, Hamad B. The atopic dermatitis market. Nat Rev Drug Discov. 2018;17:237-8. https://doi.org/10.1038/nrd.2017.192.
3 Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol. 2001;33:289-94. https://doi.org/10.1097/00004836-200110000-00006.
4 Mounessa JS, Siegel JA, Dunnick CA, Dellavalle RP. The role of cannabinoids in dermatology. J Am Acad Dermatol. 2017;77:188-90. https://doi.org/10.1016/j.jaad.2017.02.056.
5 Modaresi F, Talachian K. The characteristics of clinical trials on cannabis and cannabinoids: a review of trials for therapeutic or drug development purposes. Pharmaceut Med. 2022;36:387-400. https://doi.org/10.1007/s40290-022-00447-7.
6 Wroński A, Jarocka-Karpowicz I, Stasiewicz A, Skrzydlewska E. Phytocannabinoids in the pharmacotherapy of psoriasis. Molecules. 2023;28:1192. https://doi.org/10.3390/molecules28031192.
7 Oláh A, Bíró T. Targeting cutaneous cannabinoid signaling in inflammation—a “High”-way to heal? EBioMedicine. 2017;16:3-5. https://doi.org/10.1016/j.ebiom.2017.01.003.
8 Sivesind TE, Maghfour J, Rietcheck H, Kamel K, Malik AS, Dellavalle RP. Cannabinoids for the treatment of dermatologic conditions. JID Innov. 2022;2:100095. https://doi.org/10.1016/j.xjidi.2022.100095.
9 Jarocka-Karpowicz I, Biernacki M, Wroński A, Gęgotek A, Skrzydlewska E. Cannabidiol effects on phospholipid metabolism in keratinocytes from patients with psoriasis vulgaris. Biomolecules. 2020. https://doi.org/10.3390/biom10030367.
10 Bergamaschi MM, Queiroz RHC, Zuardi AW, Crippa JAS. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011;6:237-49. https://doi.org/10.2174/157488611798280924.
11 Gharbi KA, Bonomo YA, Hallinan CM. Evidence from human studies for utilising cannabinoids for the treatment of substance-use disorders: a scoping review with a systematic approach. Int J Environ Res Public Health. 2023. https://doi.org/10.3390/ijerph20054087.
12 Martini S, Gemma A, Ferrari M, Cosentino M, Marino F. Effects of cannabidiol on innate immunity: experimental evidence and clinical relevance. Int J Mol Sci. 2023. https://doi.org/10.3390/ijms24043125.
13 Wang Y, Wang X, Yang Y, Quan Q, Huo T, Yang S, et al. Comparison of the in vitro anti-inflammatory effect of cannabidiol to dexamethasone. Clin Cosmet Investig Dermatol. 2022;15:1959-67. https://doi.org/10.2147/CCID.S378798.
14 Suryavanshi SV, Zaiachuk M, Pryimak N, Kovalchuk I, Kovalchuk O. Cannabinoids alleviate the LPS-induced cytokine storm via attenuating NLRP3 inflammasome signaling and TYK2-mediated STAT3 signaling pathways in vitro. Cells. 2022;11:1391. https://doi.org/10.3390/cells11091391.
15 Kozela E, Pietr M, Juknat A, Rimmerman N, Levy R, Vogel Z. Cannabinoids Δ9-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-κB and interferon-β/STAT proinflammatory pathways in BV-2 microglial cells. J Biol Chem. 2010;285:1616-26. https://doi.org/10.1074/jbc.M109.069294.
16 Fitzpatrick J-M, Minogue E, Curham L, Tyrrell H, Gavigan P, Hind W, et al. MyD88-dependent and -independent signalling via TLR3 and TLR4 are differentially modulated by Δ9-tetrahydrocannabinol and cannabidiol in human macrophages. J Neuroimmunol. 2020;343:577217. https://doi.org/10.1016/j.jneuroim.2020.577217.
17 Bíró T, Tóth BI, Haskó G, Paus R, Pacher P. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci. 2009;30:411-20. https://doi.org/10.1016/j.tips.2009.05.004.
18 Fernández-Ruiz J, Berrendero F, Hernández ML, Ramos JA. The endogenous cannabinoid system and brain development. Trends Neurosci. 2000;23:14-20. https://doi.org/10.1016/S0166-2236(99)01491-5.
19 Tóth KF, Ádám D, Bíró T, Oláh A. Cannabinoid signaling in the skin: therapeutic potential of the “c(ut)annabinoid” system. Molecules. 2019;24:1-56. https://doi.org/10.3390/molecules24050918.
20 Sharkey KA, Wiley JW. The role of the endocannabinoid system in the brain-gut axis. Gastroenterology. 2016;151:252-66. https://doi.org/10.1053/j.gastro.2016.04.015.
21 Osafo N, Yeboah OK, Antwi AO. Endocannabinoid system and its modulation of brain, gut, joint and skin inflammation. Mol Biol Rep. 2021;48:3665-80. https://doi.org/10.1007/s11033-021-06366-1.
22 Booth JK, Bohlmann J. Terpenes in Cannabis sativa—from plant genome to humans. Plant Sci. 2019;284:67-72. https://doi.org/10.1016/j.plantsci.2019.03.022.
23 Silva Sofrás FM, Desimone MF. Entourage effect and analytical chemistry: chromatography as a tool in the analysis of the secondary metabolism of Cannabis sativa L. Curr Pharm Des. 2022. https://doi.org/10.2174/1381612829666221103093542.
24 Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, Vogel Z, et al. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol. 1998;353:23-31. https://doi.org/10.1016/s0014-2999(98)00392-6.
25 Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat Prod Rep. 1999;16:131-43. https://doi.org/10.1039/a703973e.
26 Rajan TS, Giacoppo S, Iori R, de Nicola GR, Grassi G, Pollastro F, et al. Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. Fitoterapia. 2016;112:104-15. https://doi.org/10.1016/j.fitote.2016.05.008.
27 Santiago M, Sachdev S, Arnold JC, McGregor IS, Connor M. Absence of entourage: terpenoids commonly found in Cannabis sativa do not modulate the functional activity of Δ 9 -THC at Human CB 1 and CB 2 receptors. Cannabis Cannabinoid Res. 2019;4:165-76. https://doi.org/10.1089/can.2019.0016.
28 Worth T. Cannabis’s chemical synergies. Nature. 2019;572:S12-3. https://doi.org/10.1038/d41586-019-02528-1.
29 Dawson DA. Debates and issues pertaining to the entourage effect. GSC Biol Pharm Sci. 2022;20:180-3. https://doi.org/10.30574/gscbps.2022.20.2.0327.
30 Namdar D, Voet H, Ajjampura V, Nadarajan S, Mayzlish-Gati E, Mazuz M, et al. Terpenoids and phytocannabinoids co-produced in Cannabis sativa strains show specific interaction for cell cytotoxic activity. Molecules. 2019;24:3031. https://doi.org/10.3390/molecules24173031.
31 Nuutinen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. Eur J Med Chem. 2018;157:198-228. https://doi.org/10.1016/j.ejmech.2018.07.076.
32 Hochman JS, Brill NQ. Marijuana intoxication: pharmacological and psychological factors. Dis Nerv Syst. 1971;32:676-9.
33 Gonçalves ECD, Baldasso GM, Bicca MA, Paes RS, Capasso R, Dutra RC. Terpenoids, cannabimimetic ligands, beyond the cannabis plant. Molecules. 2020. https://doi.org/10.3390/molecules25071567.
34 Kang G-J, Kang N-J, Han S-C, Koo D-H, Kang H-K, Yoo B-S, et al. The chloroform fraction of Carpinus tschonoskii leaves inhibits the production of inflammatory mediators in HaCaT keratinocytes and RAW264.7 macrophages. Toxicol Res. 2012;28:255-62. https://doi.org/10.5487/TR.2012.28.4.255.
35 Yoon W-J, Lee NH, Hyun C-G. Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E2, and Pro-inflammatory cytokines in RAW 264.7 macrophages. J Oleo Sci. 2010;59:415-21. https://doi.org/10.5650/jos.59.415.
36 Monga S, Fares B, Yashaev R, Melamed D, Kahana M, Fares F, et al. The effect of natural-based formulation (NBF) on the response of RAW264.7 macrophages to LPS as an in vitro model of inflammation. J Fungi (Basel). 2022. https://doi.org/10.3390/jof8030321.
37 Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014. https://doi.org/10.3389/fimmu.2014.00461.
38 Dong J, Li J, Cui L, Wang Y, Lin J, Qu Y, et al. Cortisol modulates inflammatory responses in LPS-stimulated RAW264.7 cells via the NF-κB and MAPK pathways. BMC Vet Res. 2018;14:30. https://doi.org/10.1186/s12917-018-1360-0.
39 Palsson-McDermott EM, O’Neill LAJ. Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. Immunology. 2004;113:153-62. https://doi.org/10.1111/j.1365-2567.2004.01976.x.
40 Ferber SG, Namdar D, Hen-Shoval D, Eger G, Koltai H, Shoval G, et al. The “entourage effect”: terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Curr Neuropharmacol. 2020;18:87-96. https://doi.org/10.2174/1570159X17666190903103923.
41 LaVigne JE, Hecksel R, Keresztes A, Streicher JM. Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity. Sci Rep. 2021;11:8232. https://doi.org/10.1038/s41598-021-87740-8.
42 Danchine VD, Caldari C. Effects of cannabidiol on RAW 2647 macrophage viability and inflammatory markers. FASEB J. 2020;34:1-1. https://doi.org/10.1096/fasebj.2020.34.s1.04219.
43 Muthumalage T, Rahman I. Cannabidiol differentially regulates basal and LPS-induced inflammatory responses in macrophages, lung epithelial cells, and fibroblasts. Toxicol Appl Pharmacol. 2019;382:114713. https://doi.org/10.1016/j.taap.2019.114713.
44 Andre CM, Hausman J-F, Guerriero G. Cannabis sativa: the plant of the thousand and one molecules. Front Plant Sci. 2016;7:19. https://doi.org/10.3389/fpls.2016.00019.
45 Alvarez-Suarez JM, Carrillo-Perdomo E, Aller A, Giampieri F, Gasparrini M, González-Pérez L, et al. Anti-inflammatory effect of Capuli cherry against LPS-induced cytotoxic damage in RAW 264.7 macrophages. Food Chem Toxicol. 2017;102:46-52. https://doi.org/10.1016/j.fct.2017.01.024.
46 Raman SP, Keil C, Dieringer P, Hübner C, Bueno A, Gurikov P, et al. Alginate aerogels carrying calcium, zinc and silver cations for wound care: fabrication and metal detection. J Supercrit Fluids. 2019;153:104545. https://doi.org/10.1016/j.supflu.2019.104545.
47 Beutler B, Greenwald D, Hulmes JD, Chang M, Pan Y-CE, Mathison J, et al. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature. 1985;316:552-4. https://doi.org/10.1038/316552a0.
48 Baswan SM, Klosner AE, Glynn K, Rajgopal A, Malik K, Yim S, et al. Therapeutic potential of cannabidiol (CBD) for skin health and disorders. Clin Cosmet Investig Dermatol. 2020;13:927-42. https://doi.org/10.2147/CCID.S286411.
49 Sholler DJ, Schoene L, Spindle TR. Therapeutic efficacy of cannabidiol (CBD): a review of the evidence from clinical trials and human laboratory studies. Curr Addict Rep. 2020;7:405-12. https://doi.org/10.1007/s40429-020-00326-8.
50 Morel A, Lebard P, Dereux A, Azuar J, Questel F, Bellivier F, et al. Clinical trials of cannabidiol for substance use disorders: outcome measures, surrogate endpoints, and biomarkers. Front Psychiatry. 2021. https://doi.org/10.3389/fpsyt.2021.565617.
51 Couch DG, Cook H, Ortori C, Barrett D, Lund JN, O’Sullivan SE. Palmitoylethanolamide and cannabidiol prevent inflammation-induced hyperpermeability of the human gut in vitro and in vivo-a randomized, placebo-controlled double-blind controlled trial. Inflamm Bowel Dis. 2019;25:1006-18. https://doi.org/10.1093/ibd/izz017.
52 Lehmann C, Fisher NB, Tugwell B, Szczesniak A, Kelly M, Zhou J. Experimental cannabidiol treatment reduces early pancreatic inflammation in type 1 diabetes. Clin Hemorheol Microcirc. 2016;64:655-62. https://doi.org/10.3233/CH-168021.
53 Verrico CD, Wesson S, Konduri V, Hofferek CJ, Vazquez-Perez J, Blair E, et al. A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain. 2020;161:2191-202. https://doi.org/10.1097/j.pain.0000000000001896.
54 Scholfield CN, Waranuch N, Kongkaew C. Systematic review on transdermal/topical cannabidiol trials: a reconsidered way forward. Cannabis Cannabinoid Res. 2022. https://doi.org/10.1089/can.2021.0154.
55 Casiraghi A, Musazzi UM, Centin G, Franzè S, Minghetti P. Topical administration of cannabidiol: influence of vehicle-related aspects on skin permeation process. Pharmaceuticals. 2020;13:337. https://doi.org/10.3390/ph13110337.
56 Nahler G. Cannabidiol and contributions of major hemp phytocompounds to the “entourage effect” possible mechanisms. Altern Complement Integr Med. 2019;5:1-16. https://doi.org/10.24966/ACIM-7562/100066.
57 Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants (Basel). 2019. https://doi.org/10.3390/antiox9010021.
58 Tanikawa T, Kitamura M, Hayashi Y, Tomida N, Uwaya A, Isami F, et al. Anti-inflammatory effect of a combination of cannabidiol and Morinda citrifolia extract on lipopolysaccharide-stimulated RAW264 macrophages. In Vivo. 2023;37:591-5. https://doi.org/10.21873/invivo.13117.
59 Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1:1333-49. https://doi.org/10.4155/fmc.09.93.
60 Nichols JM, Kaplan BLF. Immune responses regulated by cannabidiol. Cannabis Cannabinoid Res. 2020;5:12-31. https://doi.org/10.1089/can.2018.0073.
61 Brieger A, Rink L, Haase H. Differential regulation of TLR-dependent MyD88 and TRIF signaling pathways by free zinc ions. J Immunol. 2013;191:1808-17. https://doi.org/10.4049/jimmunol.1301261.
62 Han KH, Lim S, Ryu J, Lee C-W, Kim Y, Kang J-H, et al. CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages. Cardiovasc Res. 2009;84:378-86. https://doi.org/10.1093/cvr/cvp240.
63 McCoy KL. Interaction between cannabinoid system and toll-like receptors controls inflammation. Mediators Inflamm. 2016;2016:5831315. https://doi.org/10.1155/2016/5831315.
64 Silva RL, Silveira GT, Wanderlei CW, Cecilio NT, Maganin AGM, Franchin M, et al. DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A2A receptor. Toxicol Appl Pharmacol. 2019;368:63-71. https://doi.org/10.1016/j.taap.2019.02.011.
65 Millar SA, Stone NL, Yates AS, O’Sullivan SE. A systematic review on the pharmacokinetics of cannabidiol in humans. Front Pharmacol. 2018. https://doi.org/10.3389/fphar.2018.01365.
66 Millar SA, Stone NL, Bellman ZD, Yates AS, England TJ, O’Sullivan SE. A systematic review of cannabidiol dosing in clinical populations. Br J Clin Pharmacol. 2019;85:1888-900. https://doi.org/10.1111/bcp.14038.
67 Chen X, Su J, Wang R, Hao R, Fu C, Chen J, et al. Structural optimization of cannabidiol as multifunctional cosmetic raw materials. Antioxidants. 2023;12:314. https://doi.org/10.3390/antiox12020314.
68 Petrosino S, Verde R, Vaia M, Allarà M, Iuvone T, Di Marzo V. Anti-inflammatory properties of cannabidiol, a nonpsychotropic cannabinoid, in experimental allergic contact dermatitis. J Pharmacol Exp Ther. 2018;365:652-63. https://doi.org/10.1124/jpet.117.244368.
69 Nahler G. Pure cannabidiol versus cannabidiol-containing extracts: distinctly different multi-target modulators. Alternative Complement Integr Med. 2018;4:1-11. https://doi.org/10.24966/ACIM-7562/100048.
70 Koltai H, Namdar D. Cannabis phytomolecule “entourage”: from domestication to medical use. Trends Plant Sci. 2020;25:976-84. https://doi.org/10.1016/j.tplants.2020.04.007.
71 Adriana Estrella G-R, María Eva G-T, Alberto H-L, María Guadalupe V-D, Azucena C-V, Sandra O-S, et al. Limonene from Agastache mexicana essential oil produces antinociceptive effects, gastrointestinal protection and improves experimental ulcerative colitis. J Ethnopharmacol. 2021;280:114462. https://doi.org/10.1016/j.jep.2021.114462.
72 Tambe Y, Tsujiuchi H, Honda G, Ikeshiro Y, Tanaka S. Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, β-caryophyllene. Planta Med. 1996;62:469-70. https://doi.org/10.1055/s-2006-957942.
73 Refaat B, El-Boshy M. Protective antioxidative and anti-inflammatory actions of β-caryophyllene against sulfasalazine-induced nephrotoxicity in rat. Exp Biol Med (Maywood). 2022;247:691-9. https://doi.org/10.1177/15353702211073804.
74 Rufino AT, Ribeiro M, Sousa C, Judas F, Salgueiro L, Cavaleiro C, et al. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. Eur J Pharmacol. 2015;750:141-50. https://doi.org/10.1016/j.ejphar.2015.01.018.
75 Yang L, Liao M. Influence of myrcene on inflammation, matrix accumulation in the kidney tissues of streptozotocin-induced diabetic rat. Saudi J Biol Sci. 2021;28:5555-60. https://doi.org/10.1016/j.sjbs.2020.11.090.
76 Gallily R, Yekhtin Z, Hanuš LO. The anti-inflammatory properties of terpenoids from cannabis. Cannabis Cannabinoid Res. 2018;3:282-90. https://doi.org/10.1089/can.2018.0014.
77 Farag MA, Wessjohann LA. Cytotoxic effect of commercial Humulus lupulus L. (hop) preparations—in comparison to its metabolomic fingerprint. J Adv Res. 2013;4:417-21. https://doi.org/10.1016/j.jare.2012.07.006.
78 Gertsch J, Leonti M, Raduner S, Racz I, Chen J-Z, Xie X-Q, et al. Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci. 2008;105:9099-104. https://doi.org/10.1073/pnas.0803601105.
79 Wu C, Jia Y, Lee JH, Jun H, Lee H-S, Hwang K-Y, et al. trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-α. Bioorg Med Chem Lett. 2014;24:3168-74. https://doi.org/10.1016/j.bmcl.2014.04.112.
80 Bento AF, Marcon R, Dutra RC, Claudino RF, Cola M, Pereira Leite DF, et al. β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. Am J Pathol. 2011;178:1153-66. https://doi.org/10.1016/j.ajpath.2010.11.052.
81 Souza MC, Siani AC, Ramos MFS, Menezes-de-Lima OJ, Henriques MGMO. Evaluation of anti-inflammatory activity of essential oils from two Asteraceae species. Pharmazie. 2003;58:582-6.
82 Finlay DB, Sircombe KJ, Nimick M, Jones C, Glass M. Terpenoids from cannabis do not mediate an entourage effect by acting at cannabinoid receptors. Front Pharmacol. 2020;11:359. https://doi.org/10.3389/fphar.2020.00359.
83 Fernandes ES, Passos GF, Medeiros R, da Cunha FM, Ferreira J, Campos MM, et al. Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur J Pharmacol. 2007;569:228-36. https://doi.org/10.1016/j.ejphar.2007.04.059.
84 Lewis M, Russo E, Smith K. Pharmacological Foundations of Cannabis Chemovars. Planta Med. 2018. https://doi.org/10.1055/s-0043-122240.
85 Cal K, Kupiec K, Sznitowska M. Effect of physicochemical properties of cyclic terpenes on their ex vivo skin absorption and elimination kinetics. J Dermatol Sci. 2006;41:137-42. https://doi.org/10.1016/j.jdermsci.2005.09.003.
86 Williams AC, Barry BW. Terpenes and the lipid-protein-partitioning theory of skin penetration enhancement. Pharm Res. 1991;8:17-24. https://doi.org/10.1023/a:1015813803205.
87 Atalay S, Dobrzyńska I, Gęgotek A, Skrzydlewska E. Cannabidiol protects keratinocyte cell membranes following exposure to UVB and hydrogen peroxide. Redox Biol. 2020;36:101613. https://doi.org/10.1016/j.redox.2020.101613.
88 International A. AOAC Guidelines for Single Laboratory Validation of Chemical Methods for Dietary Supplements and Botanicals. Association of Official Analytical Chemists; 2002.
89 Raschke WC, Baird S, Ralph P, Nakoinz I. Functional macrophage cell lines transformed by abelson leukemia virus. Cell. 1978;15:261-7. https://doi.org/10.1016/0092-8674(78)90101-0.
90 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55-63. https://doi.org/10.1016/0022-1759(83)90303-4.
91 Griess P. Bemerkungen zu der Abhandlung der HH. Weselsky und Benedikt ?Ueber einige Azoverbindungen”. Ber Dtsch Chem Ges. 1879;12:426-8. https://doi.org/10.1002/cber.187901201117.
92 Keil C, Hübner C, Richter C, Lier S, Barthel L, Meyer V, et al. Ca-Zn-Ag alginate aerogels for wound healing applications: swelling behavior in simulated human body fluids and effect on macrophages. Polymers (Basel). 2020. https://doi.org/10.3390/polym12112741.
93 BD Biosciences: Mouse TNF (Mono/Mono) ELISA Set, Last accessed: 15 May 2023 https://www.bdbiosciences.com/en-us/products/reagents/immunoassay-reagents/elisa/elisa-kits/mouse-tnf-mono-mono-elisa-set.555268.
94 Luque-Córdoba D, Calderón-Santiago M, Luque de Castro MD, Priego-Capote F. Study of sample preparation for determination of endocannabinoids and analogous compounds in human serum by LC-MS/MS in MRM mode. Talanta. 2018;185:602-10. https://doi.org/10.1016/j.talanta.2018.04.033.
95 Kaminski NE. Immune regulation by cannabinoid compounds through the inhibition of the cyclic AMP signaling cascade and altered gene expression. Biochem Pharmacol. 1996;52:1133-40. https://doi.org/10.1016/0006-2952(96)00480-7.

[1]	Rui Ma, Xu-Yao Feng, Jiang-Jiang Tang, Wei Ha, Yan-Ping Shi. 5α-Epoxyalantolactone from Inula macrophylla attenuates cognitive deficits in scopolamine-induced Alzheimer’s disease mice model[J]. 应用天然产物, 2024, 14(5): 39-39.
[2]	Zhe-Wei Yu, Bang-Ping Cai, Su-Zhi Xie, Yi Zhang, Wen-Hui Wang, Shun-Zhi Liu, Yan-Lin Bin, Qi Chen, Mei-Juan Fang, Rong Qi, Ming-Yu Li, Ying-Kun Qiu. Compounds from Agathis dammara exert hypoglycaemic activity by enhancing glucose uptake: lignans, terpenes and others[J]. 应用天然产物, 2024, 14(3): 23-23.
[3]	Tian Lan, Wen Wang, De-Lian Huang, Xi-Xi Zeng, Xiao-Xiao Wang, Jian Wang, Yu-Hua Tong, Zhu-Jun Mao, Si-Wei Wang. Essential oil extracted from Quzhou Aurantii Fructus prevents acute liver failure through inhibiting lipopolysaccharide-mediated inflammatory response[J]. 应用天然产物, 2023, 13(5): 36-36.
[4]	Qing Tao, Jinhua Zhang, Qiao liang, Shiyu Song, Shuxia Wang, Xiaoming Yao, Qian Gao, Lei Wang. Puerarin alleviates sleep disorders in aged mice related to repairing intestinal mucosal barrier[J]. 应用天然产物, 2023, 13(4): 29-29.
[5]	Suhad A. A. Al-Salihi, Fabrizio Alberti. Naturally Occurring Terpenes: A Promising Class of Organic Molecules to Address Influenza Pandemics[J]. 应用天然产物, 2021, 11(4): 405-419.
[6]	Yi-Jie Zhai, Jian-Nan Li, Yu-Qi Gao, Lin-Lin Gao, Da-Cheng Wang, Wen-Bo Han, Jin-Ming Gao. Structurally Diverse Sesquiterpenoids with Anti-neuroinflammatory Activity from the Endolichenic Fungus Cryptomarasmius aucubae[J]. 应用天然产物, 2021, 11(3): 325-332.
[7]	I. Poulopoulou, I. Hadjigeorgiou. Evaluation of Terpenes' Degradation Rates by Rumen Fluid of Adapted and Non-adapted Animals[J]. 应用天然产物, 2021, 11(3): 307-314.
[8]	Xin-Yu Jia, Yong-Mei Wu, Jing-Ya Li, Chun Lei, Ai-Jun Hou. Alkaloid Constituents of Ficus hispida and Their Antiinflammatory Activity[J]. 应用天然产物, 2020, 10(1): 45-49.
[9]	Jia-Huan Shang, Guo-Wei Xu, Hong-Tao Zhu, Dong Wang, Chong-Ren Yang, Ying-Jun Zhang. Anti-inflammatory and Cytotoxic Triterpenes from the Rot Roots of Panax notoginseng[J]. 应用天然产物, 2019, 9(4): 287-295.
[10]	Kennedy D. Nyongbela, Fidele Ntie-Kang, Thomas R. Hoye, Simon M. N. Efange. Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment[J]. 应用天然产物, 2017, 7(3): 235-247.
[11]	Joseph Sakah Kaunda, Ying-Jun Zhang. The Genus Carissa: An Ethnopharmacological, Phytochemical and Pharmacological Review[J]. 应用天然产物, 2017, 7(2): 181-199.
[12]	Rong-Hua Yin, Zhen-Zhu Zhao, Xu Ji, Ze-Jun Dong, Zheng-Hui Li, Tao Feng, Ji-Kai Liu. Steroids and Sesquiterpenes From Cultures of the Fungus Phellinus igniarius[J]. 应用天然产物, 2015, 5(1): 17-22.
[13]	Can-Bin Ouyang, Xiao-Man Liu, Qi Liu, Jie Bai, Hou-Yong Li, Yuan Li, Qiu-Xia Wang, Dong-Dong Yan, Lian-Gang Mao, Aocheng Cao, Mei-Xia Guo. Toxicity Assessment of Cadinene Sesquiterpenes from Eupatorium adenophorum in Mice[J]. 应用天然产物, 2015, 5(1): 29-36.
[14]	Zi-Ming Chen, Qiong-Ying Fan, Xia Yin, Xiao-Yan Yang, Zheng-Hui Li, Tao Feng, Ji-Kai Liu. Three New Humulane Sesquiterpenes from Cultures of the Fungus Antrodiella albocinnamomea[J]. 应用天然产物, 2014, 4(4): 207-211.
[15]	Xia Yin, Tao Feng, Zheng-Hui Li, Ying Leng, Ji-Kai Liu. Five New Guanacastane-Type Diterpenes from Cultures of the Fungus Psathyrella candolleana[J]. 应用天然产物, 2014, 4(3): 149-155.

Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers

Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价