PD25-11 ANTI-INFLAMMATORY EFFECT OF BETULINIC ACID IS DEPENDENT ON METABOLIC REPROGRAMMING OF IMMUNE CELLS

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (PD25)1 May 2024PD25-11 ANTI-INFLAMMATORY EFFECT OF BETULINIC ACID IS DEPENDENT ON METABOLIC REPROGRAMMING OF IMMUNE CELLS Anirban Ganguly, Stephanie Daugherty, Keara Healy, Jonathan Beckel, and Pradeep Tyagi Anirban GangulyAnirban Ganguly , Stephanie DaughertyStephanie Daugherty , Keara HealyKeara Healy , Jonathan BeckelJonathan Beckel , and Pradeep TyagiPradeep Tyagi View All Author Informationhttps://doi.org/10.1097/01.JU.0001008584.88541.ff.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The bark of white Willow and white Birch (Betula alba) have been used as pain killers in many cultures for centuries before the identification of their pharmacologically active ingredients, salicylic acid (SA) and Betulinic acid (BA), respectively. With a phenolic backbone, SA (138.12 Daltons) is the prototype of nonsteroidal anti-inflammatory drugs (NSAIDs) and although BA shares the steroid backbone of glucocorticoids, BA (456.7 Daltons) is not an analog of Dexamethasone. Thus, BA may avoid the hallmark toxicity of NSAIDs and steroidal anti-inflammatory drugs (SAIDs) in the clinical trial, NCT00346502. Since antiproliferative effect of SA on lymphocytes is predictive of its anti-inflammatory effect, we assessed the proliferation of human T lymphocyte, Jurkat cell line at low and high glucose to tease out if the antiproliferative effect of BA and SA is dependent on metabolic reprogramming. METHODS: Cytotoxicity of BA relative to SA was assessed on human Jurkat cells cultured on RPMI media with 10% FBS and benign human urothelial cells TRT-HU1(Keratinocyte Serum Free media) with 5% (normal) and 10% glucose (high). Cell lines were exposed to BA and SA for 18h prior to MTT assay for IC50 determination. RESULTS: While superior anti-inflammatory efficacy of SA is evinced by a three-fold lower IC50 than BA, the irritant action on bladder is validated by just 14-fold higher IC50 of SA as opposed to a 19-fold higher IC50 of BA on benign TRT-HU1 cells relative to their respective IC50 on Jurkat cells. The rightward shift in the dose response curve of BA (black to green) and SA (blue to orange) implies that high glucose induces a faster proliferation of immune cells that offsets the anti-proliferative effect of BA and SA. CONCLUSIONS: Although a weaker anti-inflammatory drug than classical NSAIDs or SAIDs, the unique mechanism of action of BA may not provoke mucosal ulceration in stomach and bladder of interstitial cystitis/bladder pain syndrome (IC/BPS) patients. High glucose averts the Jurkat cell proliferation evoked nutrient scarcity at the default state of normal glucose that triggers metabolic reprogramming and allow poisoning of mitochondria by BA. Since caloric restriction boosts immunity, the stunted antiproliferative effect of BA and SA implies that high glucose induces proliferation of immature immune cells and faster proliferation impedes maturation. Download PPT Source of Funding: CA263243 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e541 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Anirban Ganguly More articles by this author Stephanie Daugherty More articles by this author Keara Healy More articles by this author Jonathan Beckel More articles by this author Pradeep Tyagi More articles by this author Expand All Advertisement PDF downloadLoading ...