Phytochemical profiling of Ananas comosus fruit via UPLC-MS and its anti-inflammatory and anti-arthritic activities: In Silico, In Vitro and In Vivo Approach

Ananas comosus [L.] is one of the most appreciated sources of metabolites for nutraceuticals and therapeutics. Traditional use of A. comosus fruit as anti-inflammatory and anti-arthritic agents warrants scientific validation. A. comosus fruit is well-known for its polyphenolic content and antioxidant activity that pose it good candidate in alleviating arthritis. This study aims to investigate the potential of A. comosus fruit as anti-arthritic and anti-inflammatory agent using different approaches in an attempt to reveal the underlying mechanism of action in accordance to its phytoconstituents. Results revealed that total ethanol extract of A. comosus (TEA) has potent in vitro antioxidant, anti-inflammatory and anti-arthritic activities. Also, TEA (500 and 1000 mg/kg) manifested promising in vivo anti-arthritic activity by alleviating paw edema to only 20.2 and 16.4% increase, respectively. High dose of TEA showed significant reduction in inflammatory biomarkers reverting IL- 6 to near normal value (46.93 pg/mL). TEA reversed the induced histopathological damage caused by the adjuvant and inhibit inducible nitric oxide synthase expression. UPLC/QTOF-MS-MS was carried out for metabolite profiling with a total of 53 metabolites identified including hydroxycinnamic acids (HCA), their depsides, glycerides and glycosides derivatives together with hydroxybenzoic acid glycosides, and amino acids. In silico studies displayed inhibitory potential against TNF-alpha for most of studied HCA derivatives especially dicinnamoyl glycerides and methoxylated HCA. This study is considered the first pharmacological validation of pineapple fruit traditional use. These observed results are attributed to TEA metabolite profile that exhibited favorable pharmacokinetics and drug likeness properties, suggesting their potential as lead drugs.