Cannabidiol (CBD) Upregulates Vitamin D3 Receptors (VDRs) Expression That Modulates Cytokines (TNF-α, IL-6), Tissue Elasticity, Cellular Senescence, and Mitochondrial ATP Generation in Human and Rodent Cell Lines

Mahendra Kumar Trivedi,1 Alice Branton,1 Dahryn Trivedi,1 Sambhu Mondal,2 Snehasis Jana2 1Trivedi Global, Inc, Research & Development, Henderson, Nevada, USA; 2Trivedi Science Research Laboratory Pvt. Ltd, Research & Development, Thane (W), Maharashtra, IndiaCorrespondence: Snehasis Jana, Trivedi Science Research Laboratory Pvt. Ltd, Thane (W), Maharashtra, India, Tel +91-022-25811234, Email [email protected]: Cannabidiol (CBD) is a non-psychoactive cannabinoid derived from Cannabis sativa L. with very low toxicity for human and a wide variety of therapeutic uses as medicine. The study objective is to evaluate the impact of CBD on vitamin D3 receptor (VDR) protein expressions, tissue elasticity, anti-inflammatory, and anti-senescence activity in human and rodent cell lines.Methods: Cell viability was estimated by MTT assay. Relative quantification (RQ) of VDR protein expression was measured by RT-PCR. Tissue elasticity was measured by atomic force microscopy (AFM). Cellular senescence and ATP were performed using trypan blue exclusion test and colorimetric assay, respectively.Results: Cell viability assay data showed CBD was safe and nontoxic upto 7.5 μM. The VDR protein expression was significantly increased by 109.71% (p = 0.013), 236.96% (p ≤ 0.001), 170% (p ≤ 0.001), 100% (p = 0.019), 80% (p = 0.021), 427.27% (p ≤ 0.001), 366.67% (p ≤ 0.001), 56.31% (p = 0.016), and 63.84% (p ≤ 0.001) in MG-63, MDA-MB-231, SH-SY5Y, HEK-293, HT-29, EaHy-926, HepG2, A-549, and C2C12 cells, respectively compared to the normal control group. CBD treatment significantly reduced the levels of TNF-α (46.58%; p ≤ 0.049) and IL-6 (43.61%; p ≤ 0.001) at CBD-5 μM compared to the vehicle control group. Tissue elasticity was significantly (p ≤ 0.001) increased by 37.09% and 49.49% in CBD-2.5 and CBD-5 μM, respectively, compared to the vehicle control group. Significantly (p ≤ 0.001) reduced senescence cells by 39.22% in CBD-5 μM than the vehicle control group. The level of ATP was significantly (p ≤ 0.001) increased by 90.55, 117.06, and 153.54% in CBD-1, CBD-2.5, and CBD-5 μM, respectively, compared to the vehicle control group.Conclusion: Overall, data suggest that CBD considerably improved VDR protein expression, inflammation, cell growth, tissue elasticity, and enhanced mitochondrial bioenergetics in multiple cell lines. In this study, for the first time, we showed the evidence suggesting that the VDR plays a critical and multifaceted role in various types of human cells. Keywords: cannabidiol, inflammation, elasticity, VDR expression, senescence, ATP