Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity

• DOI: 10.1111/bph.14019
• Publication Date: 2017-08-30T03:06:41Z
• Authors: Xavier Nadal; Carmen del Río; Salvatore Casano; Belén Palomares; Carlos Ferreiro‐Vera; Carmen Navarrete; Carolina Sánchez‐...; Irene Cantarero; Maria Luz Bellido; Stefan Meyer; Gaetano Morello; Giovanni Appendino; Eduardo Muñoz
• Keywords: Male; 0301 basic medicine; Ratones endogámicos C57BL; Huntingtin protein; Disease models, animal; Nitrocompuestos; Neuroprotective agents; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Fármacos neuroprotectores; Dronabinol; Mice, inbred C57BL; Mitocondrias; Cannabis; Huntingtin Protein; Proteína huntingtina; Huntington disease; Nitro Compounds; 3. Good health; Mitochondria; Mice, Inbred C57BL; PPAR gamma; Disease Models, Animal; Cell line, tumor; Enfermedad de Huntington; Huntington Disease; Neuroprotective Agents; Nitro compounds; Propionatos; Propionates

Background and Purpose Phytocannabinoids are produced in Cannabis sativa L. acidic form decarboxylated upon heating, processing storage. While the biological effects of cannabinoids such as Δ 9 ‐tetrahydrocannabinol have been extensively investigated, bioactivity ‐tetahydrocannabinol acid (Δ ‐THCA) is largely unknown, despite its occurrence different preparations. Here we assessed possible neuroprotective actions ‐THCA through modulation PPARγ pathways. Experimental Approach The six phytocannabinoids on binding transcriptional activity were investigated. effect mitochondrial biogenesis coactivator 1‐α expression was investigated Neuro‐2a (N2a) cells. analysed ST Hdh Q111/Q111 cells expressing a mutated huntingtin protein N2a infected with an adenovirus carrying human containing 94 polyQ repeats (mHtt‐q94). vivo mice intoxicated toxin 3‐nitropropionic (3‐NPA). Key Results Cannabinoid acids bind activate higher potency than their products. increased mass neuroblastoma prevented cytotoxicity induced by serum deprivation mutHtt‐q94 ‐THCA, PPARγ‐dependent pathway, treated 3‐NPA, improving motor deficits preventing striatal degeneration. In addition, attenuated microgliosis, astrogliosis up‐regulation proinflammatory markers 3‐NPA. Conclusions Implications shows potent activity, which worth considering for treatment Huntington's disease possibly other neurodegenerative neuroinflammatory diseases.