Abstract
Background:
Pasteurella multocida is an opportunistic bacterium causes pneumonic pasteurellosis (PP). The common treatment against PP is using antibiotics in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs). This combination presents various complications, i.e., immune-depression. Hence, the alternative therapy to replace the effects of NSAIDs needs to be clarified. One of them is using fermented calabash (Crescentia cujete (L.)) (FCC).

Aim:
This study aimed to elucidate the efficacy of FCC in combination with enrofloxacin against artificially induced PP in rat models.

Methods:
The calabash was collected and fermented. Moreover, the product of FCC was standardised regarding its biochemical compounds using LC-MS/MS and HPLC. This study used 30 male Sprague Dawley rats, weight 251.52±2.65 grams, six months old. The rats were divided into six groups as follows: G1 (control); G2 (infected with Pasteurella multocida + untreated); G3 (infected + 20 mg/kg enrofloxacin); G4 (infected + 20 mg/kg enrofloxacin + 30 mg/kg ibuprofen); G5 (infected + 20 mg/kg enrofloxacin + 2.96 mg/kg FCC); and G6 (infected + 20 mg/kg enrofloxacin + 5.92 mg/kg FCC). The treatment was given once daily for seven days. On day eight, the rats were radiographed. The serum was collected and tested against C-reactive protein (CRP) and procalcitonin. The rats were euthanized and lung tissue was collected for histopathology and immunohistochemistry against CD4+, CD8+ and COX-2. The data was analyzed using SPSS.

Results:
This study indicated that FCC contains choline, phytonadione, alpha-tocopherol, and retinol. Moreover, using FCC as a combination therapy with enrofloxacin against PP in group G6 promotes a repair of radiology image compared to other treatments (p<0.05). Group G5 and G6 showed increase activity of BALT, immune expression of CD4+ and COX-2, and the level of CRP and procalcitonin within the lung tissue (p<0.05). Group G6 indicated the better effects in various parameters in this study. However, the FCC has not influenced the immune expression of CD8+ during PP (p>0.05).

Conclusion:
This study proved that FCC could be used in rat models as an alternative anti-inflammatory treatment in combination with enrofloxacin against PP. Further research is needed to explore other effects of FCC to support the current findings.

Key words: Anti-inflammatory, Fermented Crescentia cujete (L.), Lung, Pasteurella multocida, Pneumonia