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Article Publish Status: FREE
Abstract Title:

Anti-Inflammatory Activity in Colon Models Is Derived fromΔ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds inExtracts.

Abstract Source:

Cannabis Cannabinoid Res. 2017 ;2(1):167-182. Epub 2017 Jul 1. PMID: 29082314

Abstract Author(s):

Rameshprabu Nallathambi, Moran Mazuz, Aurel Ion, Gopinath Selvaraj, Smadar Weininger, Marcelo Fridlender, Ahmad Nasser, Oded Sagee, Puja Kumari, Diana Nemichenizer, Maayan Mendelovitz, Nave Firstein, Orly Hanin, Fred Konikoff, Yoram Kapulnik, Timna Naftali, Hinanit Koltai

Article Affiliation:

Rameshprabu Nallathambi

Abstract:

Inflammatory bowel diseases (IBDs) include Crohn's disease, and ulcerative colitis.preparations have beneficial effects for IBD patients. However,extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of wholeextracts has never been characterized in detail withandcolon models.The anti-inflammatory activity ofextracts was studied on three lines of epithelial cells and on colon tissue.flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR.The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions ofat a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 () and metalloproteinase-9 () gene expression in both cell culture and colon tissue.It is suggested that the anti-inflammatory activity of Cannabis extracts on colon epithelial cells derives from a fraction of the extract that contains THCA, and is mediated, at least partially, via GPR55 receptor. The cytotoxic activity of theextract was increased by combining all fractions at a certain combination of concentrations and was partially affected by CB2 receptor antagonist that increased cell proliferation. It is suggested that in a nonpsychoactive treatment for IBD, THCA should be used rather than CBD.

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