Cuminaldeído como alternativa terapêutica para cistite intersticial induzida por ciclofosfamida: avaliação das propriedades analgésica e anti- inflamatória

Abstract

INTRODUCTION: Interstitial cystitis (IC), also known as painful bladder syndrome, is characterized by chronic pelvic pain and debilitating urinary symptoms, with limited response to conventional therapies. Cuminaldehyde, an organic compound found in cumin and cinnamon, has been studied for its anti-inflammatory and analgesic properties due to its ability to modulate the inflammatory response and reduce sensitization of nociceptive pathways. Preclinical studies suggest that cuminaldehyde can inhibit the production of pro-inflammatory cytokines and exert antioxidant effects, contributing to the protection of urothelial cells. In this context, molecular docking stands out as a key tool for investigating compounds with therapeutic potential, as it allows the prediction of interactions with molecular targets related to pain and inflammation, thereby optimizing the selection of candidates for experimental models. OBJECTIVES: To evaluate the analgesic and anti-inflammatory effects of cuminaldehyde in a rat model of cyclophosphamide-induced IC. METHODS: Molecular docking of cuminaldehyde was performed with target proteins associated with inflammatory pathways to assess affinity and molecular interactions. Experimentally, rats were divided into eight groups (n=5 each). SHAM group: healthy animals without cystitis induction and without treatment; Cystitis group: cystitis induced with cyclophosphamide and treated with 0.9% saline; Cuminaldehyde 2.5 mg/kg (7 days): cystitis induction and treatment with cuminaldehyde 2.5 mg/kg/day for 7 days; Cuminaldehyde 2.5 mg/kg (14 days): cystitis induction and treatment with cuminaldehyde 2.5 mg/kg/day for 14 days; Cuminaldehyde 5 mg/kg (7 days): cystitis induction and treatment with cuminaldehyde 5 mg/kg/day for 7 days; Cuminaldehyde 5 mg/kg (14 days): cystitis induction and treatment with cuminaldehyde 5 mg/kg/day for 14 days; Meloxicam 2.5 mg/kg group: cystitis induction and treatment with meloxicam 2.5 mg/kg/day. Pain was assessed using the Von Frey and Grimace scales; cytokines IL-1β and IL-10 were quantified by ELISA, along with histological evaluation and absolute mast cell counts. RESULTS: Cuminaldehyde showed good binding affinity to the evaluated proteins, particularly 3RZE (-6.9 kcal/mol) and 3ODU (-6.8 kcal/mol). The observed interactions reinforce its potential as a modulator of pain- and inflammation-related targets, highlighting it as a promising therapeutic candidate. In pain threshold assessment using the Von Frey test, a high response frequency was observed in induced groups at early stages. A statistically significant difference (p = 0.0006) was found between the group treated with 5 mg/kg cuminaldehyde for 7 days and the untreated group, indicating improved nociceptive threshold with treatment. No statistically significant differences were found in other behavioral data between groups throughout treatment. IL-1β levels were elevated in untreated induced animals, whereas treatment with cuminaldehyde significantly reduced these levels (p<0.05), suggesting inhibition of pro-inflammatory cytokines. An increase in IL-10 was also observed in treated animals, suggesting possible activation of endogenous anti-inflammatory mechanisms, promoting balance and modulating the immune response. A significant reduction in mast cell numbers was observed in animals treated with 5 mg/kg cuminaldehyde for 7 days compared to the untreated group (p = 0.014), with evident improvement in histological findings. CONCLUSION: Cuminaldehyde demonstrated analgesic, anti-inflammatory, and uroprotective effects in the interstitial cystitis model, with increased nociceptive threshold, reduced mast cells, and cytokine modulation (↓IL-1β; ↑IL-10). Molecular docking reinforces its therapeutic potential, positioning it as a promising alternative for managing pain and inflammation in this condition.