MS/MS-based molecular networking for mapping the chemical diversity of the pulp and peel extracts from Citrus japonica Thunb.; in vivo evaluation of their anti-inflammatory and anti-ulcer potential

Abstract

Although inflammation is a beneficial response to harmful triggers, the associated diseases develop the potential for death-threatening conditions. Citrus species are valuable sources of chemical compounds with diverse structural properties that could alleviate damaging inflammation and reduce serious side effects of synthetic drugs. Kumquats are the smallest trees among the citrus family widely distributed in Asia, Europe, and North America, with little cultivation in Africa. The current study aims to conduct comprehensive chemical, anti-inflammatory and anti-ulcer studies of Citrus japonica, thus focusing attention on extensive cultivation of these species in Africa to enhance their beneficial uses. A comparative chemical profiling of peel and pulp extracts was performed via HPLC-MS/MS analysis, 164 metabolites were annotated aided by the spectral similarity networks. Around 148 of which were visualized as a species-first documentation. Phenolics were the predominant classes including methoxylated flavonoids, O/C-glycosylated flavones, and flavanones with the less common O- or C-O-triglycosyl methoxylated flavones among the genus Citrus. Moreover, the anti-inflammatory study demonstrated the significant activity of the pulp and peel extracts (200 and 400 mg/kg, p.o.) via reducing paw swelling induced by carrageenan at all-time points and decreasing the formation of TNF-α and IL-1β. Moreover, in ethanol-induced gastric ulcer rat model, the high doses of both extracts significantly improved ulcer indexes and suppressed gastric inflammation by inhibiting myeloperoxidase activity and possessed an antioxidant effect via increasing reduced glutathione, decreasing malondialdehyde, and nitric oxide. Additionally, histopathological investigations confirmed the anti-inflammatory and anti-ulcer effects. Considering the two fruit tissues, peels markedly improved inflammatory and gastroprotective properties associated with the high diversity of their flavonoid structures.