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 publication@trivedisrl.comBackground: 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 ...