Effect of encapsulated spice oleoresins on chronic unpredictable mild stress-induced depression and gut microbiome modulation in mice model

Depression affects millions globally, prompting the search for novel treatments. Natural compounds like spice oleoresins show promise due to their bioactive constituents. This study explores the use of Hydroxypropyl-beta-cyclodextrin (HPBCD) for nano-encapsulation to enhance the efficacy of pepper, turmeric, and chilli oleoresins in alleviating depression in a mice model. Chronic unpredictable mild stress (CUMS) was induced for 28 days, followed by administering nano-encapsulated oleoresins (25 mg/kg). Behavioural analyses revealed improved activity, while neurochemical studies showed increased serotonin and dopamine levels with reduced monoamine oxidase (MAO) activity. Western blot highlighted changes in BDNF, supported by histopathological evidence of neuroprotection. Biochemical assays indicated reduced oxidative stress, acetylcholinesterase activity, and enhanced catalase and superoxide dismutase levels. 16S rRNA sequencing revealed improved gut microbiota, with increased beneficial bacteria. Notably, nano-encapsulated chilli oleoresin exhibited the highest efficacy. These findings support the multi-targeted potential of nano-encapsulated spice oleoresins as complementary treatments for depression, addressing neurobiological and gut-related factors.