Protective and Therapeutic Effects of Orlistat in Combination with Elettaria cardamomum “Cardamom” Extract on Learning, Memory, Anxiety, and Neuroinflammation in Obese Mice

<i>Introduction and Objective</i>: Obesity has increased worldwide, and existing anti-obesity medications have treatment limitations that diminish their overall benefits. This study aimed to investigate the effects of orlistat in combination with <i>Elettaria cardamomum</i> "Cardamom" (CAR) extract on working memory, recognition memory, anxiety, and inflammation within hippocampal tissue. <i>Methods</i>: Mice were categorized into two groups: a control group (CD) and a cafeteria diet (CAF) group induced with obesity (CAF) for 10 weeks. The groups were then subdivided into a CAF group treated with orlistat (CAF-ORL), a CAF group treated with orlistat and <i>Elettaria cardamomum</i> (CAF-ORL-CARD), and a group that continued on the CAF. The CAF-ORL group received orlistat at a dosage of 10 mg/kg/day for four weeks, while the CAF-ORL-CARD group received 10 mg/kg/day of orlistat and 500 mg/kg of CAR extract via oral gavage. In the 14th week, various assessments were conducted, including the novel object recognition (NOR) test, Y maze test, marble-burying test (MBT), open-field test, and TNF-α levels in the hippocampus. <i>Result</i>: TNF-α levels in the hippocampal tissue of the CAF group were elevated compared to the CD group (<i>p</i> < 0.01), whereas the CAF-ORL group exhibited reduced TNF-α levels compared to the CAF group (<i>p</i> < 0.01). Moreover, TNF-α levels in the CAF-ORL-CARD group were significantly lower than in the CAF-ORL group (<i>p</i> < 0.01). The recognition index was notably higher in the CAF-ORL group compared to the CAF group (<i>p</i> < 0.01) and higher in the CAF-ORL-CARD group compared to the CAF-ORL group (<i>p</i> < 0.01). However, there were no changes in the open-field test and Y maze test (<i>p</i> > 0.05). <i>Conclusions</i>: Orlistat combined with CAR has positive effects on neuroinflammation and memory, suggesting that this combination may offer potential therapeutic benefits for cognitive impairments and hippocampal dysfunction associated with obesity.