Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Dec 11

PMID 36497198

Authors

Marta Gerasymchuk

Gregory Ian Robinson

Alyssa Groves

Lucie Haselhorst

Sanjana Nandakumar

Cora Stahl

Olga Kovalchuk

Igor Kovalchuk

Affiliations

Soon will be listed here.

Abstract

In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation. Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin fibroblasts, the effects of pCBs on cellular viability, functional activity, metabolic function, and nuclear architecture were tested. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) within the range of 0.5 µM to 2.0 µM increased cell growth in a dose-dependent manner while significantly decreasing senescence as measured by beta-galactosidase activity. Utilizing a scratch assay, both THC and CBD (2.0 µM) significantly improved wound healing in both healthy and SIPS fibroblasts. THC and CBD altered nuclear architecture and mRNA levels of cell cycle regulators and genes involved in ECM production. Subsequently, we found ELN, Cyclin D1, PCNA, and BID protein levels altered by SIPS but ameliorated after pCBs exposure in human dermal fibroblasts. Lastly, we compared the efficacy of THC and CBD with common anti-aging nutrient signaling regulators in replicative senescent adult human dermal fibroblasts, CCD-1135Sk. Both THC and CBD were found to improve wound healing better than metformin, rapamycin, and triacetylresveratrol in replicative senescent CCD-1135Sk fibroblasts. Therefore, pCBs can be a valuable source of biologically active substances used in cosmetics, and more studies using clinical trials should be performed to confirm the efficacy of phytocannabinoids.

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References

MacCallum C, Russo E . Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018; 49:12-19. DOI: 10.1016/j.ejim.2018.01.004. View

Wisdom R, Johnson R, Moore C . c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. EMBO J. 1999; 18(1):188-97. PMC: 1171114. DOI: 10.1093/emboj/18.1.188. View

Tito A, Barbulova A, Zappelli C, Leone M, Ruvo M, Mercurio F . The Growth Differentiation Factor 11 is Involved in Skin Fibroblast Ageing and is Induced by a Preparation of Peptides and Sugars Derived from Plant Cell Cultures. Mol Biotechnol. 2019; 61(3):209-220. DOI: 10.1007/s12033-019-00154-w. View

Guarente L . Franklin H. Epstein Lecture: Sirtuins, aging, and medicine. N Engl J Med. 2011; 364(23):2235-44. DOI: 10.1056/NEJMra1100831. View

Gerasymchuk M, Cherkasova V, Kovalchuk O, Kovalchuk I . The Role of microRNAs in Organismal and Skin Aging. Int J Mol Sci. 2020; 21(15). PMC: 7432402. DOI: 10.3390/ijms21155281. View

Yessenkyzy A, Saliev T, Zhanaliyeva M, Masoud A, Umbayev B, Sergazy S . Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research. Nutrients. 2020; 12(5). PMC: 7285205. DOI: 10.3390/nu12051344. View

Kozela E, Juknat A, Kaushansky N, Rimmerman N, Ben-Nun A, Vogel Z . Cannabinoids decrease the th17 inflammatory autoimmune phenotype. J Neuroimmune Pharmacol. 2013; 8(5):1265-76. DOI: 10.1007/s11481-013-9493-1. View

Liu T, Zhang L, Joo D, Sun S . NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017; 2. PMC: 5661633. DOI: 10.1038/sigtrans.2017.23. View

Maida V, Shi R, Fazzari F, Zomparelli L . Promoting wound healing of uremic calciphylaxis leg ulcers using topical cannabis-based medicines. Dermatol Ther. 2020; 33(6):e14419. DOI: 10.1111/dth.14419. View

10.

Eberlein B, Eicke C, Reinhardt H, Ring J . Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). J Eur Acad Dermatol Venereol. 2008; 22(1):73-82. DOI: 10.1111/j.1468-3083.2007.02351.x. View

11.

Lang A, Grether-Beck S, Singh M, Kuck F, Jakob S, Kefalas A . MicroRNA-15b regulates mitochondrial ROS production and the senescence-associated secretory phenotype through sirtuin 4/SIRT4. Aging (Albany NY). 2016; 8(3):484-505. PMC: 4833141. DOI: 10.18632/aging.100905. View

12.

Saab R, Rodriguez-Galindo C, Matmati K, Rehg J, Baumer S, Khoury J . p18Ink4c and p53 Act as tumor suppressors in cyclin D1-driven primitive neuroectodermal tumor. Cancer Res. 2009; 69(2):440-8. PMC: 2629408. DOI: 10.1158/0008-5472.CAN-08-1892. View

13.

Szachowicz-Petelska B, Luczaj W, Wronski A, Jastrzab A, Dobrzynska I . The Differential Effect of Cannabidiol on the Composition and Physicochemical Properties of Keratinocyte and Fibroblast Membranes from Psoriatic Patients and Healthy People. Membranes (Basel). 2021; 11(2). PMC: 7913938. DOI: 10.3390/membranes11020111. View

14.

Lim M, Kirchhof M . Dermatology-Related Uses of Medical Cannabis Promoted by Dispensaries in Canada, Europe, and the United States. J Cutan Med Surg. 2018; 23(2):178-184. DOI: 10.1177/1203475418808761. View

15.

Zuardi A . History of cannabis as a medicine: a review. Braz J Psychiatry. 2006; 28(2):153-7. DOI: 10.1590/s1516-44462006000200015. View

16.

Liu C, Qi X, Alhabeil J, Lu H, Zhou Z . Activation of cannabinoid receptors promote periodontal cell adhesion and migration. J Clin Periodontol. 2019; 46(12):1264-1272. DOI: 10.1111/jcpe.13190. View

17.

Toutfaire M, Bauwens E, Debacq-Chainiaux F . The impact of cellular senescence in skin ageing: A notion of mosaic and therapeutic strategies. Biochem Pharmacol. 2017; 142:1-12. DOI: 10.1016/j.bcp.2017.04.011. View

18.

Turan V, Oktay K . BRCA-related ATM-mediated DNA double-strand break repair and ovarian aging. Hum Reprod Update. 2019; 26(1):43-57. PMC: 6935693. DOI: 10.1093/humupd/dmz043. View

19.

di Giacomo V, Recinella L, Chiavaroli A, Orlando G, Cataldi A, Rapino M . Metabolomic Profile and Antioxidant/Anti-Inflammatory Effects of Industrial Hemp Water Extract in Fibroblasts, Keratinocytes and Isolated Mouse Skin Specimens. Antioxidants (Basel). 2021; 10(1). PMC: 7823476. DOI: 10.3390/antiox10010044. View

20.

Lee S, Lee J, Lee H, Min K . Sirtuin signaling in cellular senescence and aging. BMB Rep. 2018; 52(1):24-34. PMC: 6386230. View