Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts

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.

In Vitro Wound Healing Potential of a Fibroin Film Incorporating a Cannabidiol/2-Hydroxypropyl-β-cyclodextrin Complex

“…We found that the incorporation of the CBD/HP-β-CD complex into the fibroin film markedly enhanced the proliferation of the cells. These findings align with a previous study indicating CBD’s dose-dependent promotion of human dermal fibroblast growth [ 28 ] and prove our hypothesis on the synergistic interplay between fibroin and CBD. Regarding cell proliferation in relation to the cell cycle, these results are in concordance with our previous study in which fibroin exerted potential effects on cell division or G2/M phase [ 8 ], and they also align with the proliferation results obtained in this current study.…”

Exploring the neuroprotective activity of a lignanamides-rich extract in human neuroblastoma SH-SY5Y cells under dimethyl sulfoxide-induced stress

“…In the present study, we demonstrated that DMSO-induced oxidative stress is accompanied by the inhibition of SIRT3 and SOD2 and that LnHS prevented the downregulation of both enzymes induced by DMSO. Previously, a modulation of SIRT proteins had been highlighted but only by phytocannabinoids and never by the lignamide fraction ( Gerasymchuck et al, 2022 ; Wang et al, 2022 ). Similarly, the effects of hemp extracts on the modulation of IL-8 have been found for phytocannabinoids but not considering different extracts and cellular models such as lung epithelial cells, macrophages, and human keratinocytes ( Anil et al, 2021 ; Suryavanshi et al, 2022 ; Tortolani et al, 2023 ).…”

Cannabis Science and Therapeutics: An Overview for Clinicians

“…Topical cannabinoid preparations have therapeutic interest due to their anti-inflammatory, antioxidative, antiacne, anti-UVA/UVB damage, and antimicrobial properties in multiple studies. 110,111 When applied topically, cannabis preparations exert their effects by targeting the components of the ECS in the skin, including epidermal keratinocytes, cutaneous nerve fibers, dermal cells, melanocytes, eccrine sweat glands, and hair follicles. 112 By interacting with numerous receptors, including CB1, CB2, peroxisome proliferatoractivated nuclear receptors, and TRP channels, cannabinoids modulate vital processes to support the skin barrier, including anti-inflammatory, analgesic, and neuroprotective cellular effects.…”

“…Topical cannabinoid preparations have therapeutic interest due to their anti‐inflammatory, antioxidative, antiacne, anti‐UVA/UVB damage, and antimicrobial properties in multiple studies 110,111 . When applied topically, cannabis preparations exert their effects by targeting the components of the ECS in the skin, including epidermal keratinocytes, cutaneous nerve fibers, dermal cells, melanocytes, eccrine sweat glands, and hair follicles 112 .…”