# (-)-Fenchone Ameliorates TNBS-Induced Colitis
## 1 Introduction  
Inflammatory bowel disease (IBD) is characterized by chronic and recurrent intestinal inflammation and tissue remodeling, which primarily affect the gastrointestinal tract [1, 2, 3], including two main forms called ulcerative colitis (UC) and Crohn's disease (CD) [2, 3]. IBDs are chronic diseases that affect the quality of life of individuals. More than two million Americans are estimated to be living with IBDs, and this population is expected toapproach four million by 2030 [4; 5]. Although the incidence is stabilizing in many Western countries, the number of cases remains high, as the estimated prevalence exceeds 0.3% of the population in North America and 0.7% in Europe [4; 6]. CD is characterized by irregular transmural inflammation that may involve the entire gastrointestinal tract. It is usually associated with complications such as strictures, abscesses, and fistulas [7]. UC, on the other hand, is a non-specific chronic inflammatory disease that affects the innermost lining of the large intestine colon and rectum (submu-cosal, mucosa) and is characterized by alternating active and remission periods [8]. The pathogenesis of UC is multifactorial, involving genetic abnormalities, altered dietary patterns, intestinal barrier dysfunction, microbiota dysbiosis, and abnormal host immune reactions [9]. The current pharmacotherapy includes the use of corticosteroids, immunosuppressive, 5-aminosalicylates, and biological therapies to reduce the inflammatory process through the immune system and sometimes surgical interventions (corticosteroids, mesalamine compounds, azathioprine, methotrexate, TNF-\(\alpha\), and IL-17A inhibition) [10; 11]. The main goal of UC treatment involves inducing and maintaining a long and stable remission, decreasing the incidence of relapses, and preventing further development [8]. However, current therapy fails to prevent relapse of the active phase of IBD; in addition, it is associated with several side effects that contribute to non-adherence to treatment [12; 13; 14]. In the search for new therapeutic alternatives, natural products have emerged; in the last two centuries, the pharmaceutical industry has used naturally occurring chemical compounds as active principles in and of themselves, as well as a basis for the development of new molecular architectures [15; 16]. Terpenes are the most abundant group of secondary metabolites obtained from plants and the main constituents of essential oils [17]. Monoterpenes are natural compounds derived from geranyl diphosphate (GPP) and constitute 90% of essential oils [18]. These compounds have several biological activities already evaluated in experimental models, such as anti-inflammatory [19], antibacterial [20], gastroprotective, and gastric healing [21]. (-)-Fenchone is a bicyclic monoterpene (1,3,3-trimethylbicyclo[2.2.1]heptane-2-one) formed by two isoprene units and an organic ketone function. It is present in the plant species _Foeniculum vulgare_ Mill, _Thuja occidentalis_ L. (tuja), and _Lavandula stoechus_ (lavender) [22; 23]. These plants have a therapeutic importance in the treatment of intestinal disorders. Pharmacological studies show that (-)-fenchone exhibits antimicrobial [24], anti-inflammatory [22], antioxidant [23], antiulcerogenic [25], antidiarrheal, and antifungal properties [26]. Previous studies have shown that (-)-fenchone has low acute toxicity LD50 Oral in rats (female) 2.000 mg/kg (OECD Test Guideline 423). Seeking to corroborate previous studies and expand toxicological information, [PERSON] et al. (2024) [25] evaluated the toxicity with the most effective dose of (-)-fenchone (150 mg/kg) in the acetic-acid-induced gastric ulcer rat model and oral treatment for 14 days. No changes in body mass were noted throughout the treatment. The weights of the organs were not detrimentally affected. In addition, evaluation of biochemical parameters indicated no detrimental effect on hepatic function (AST and ALT) or renal function (urea and creatinine).