Metabolomic and transcriptomic analyses of the anti-rheumatoid arthritis potential of xylopic acid in a bioinspired lipoprotein nanoformulation.

Xylopic acid (XA), a diterpene kaurene and the major active ingredient of the African spice Xylopia aethiopica (Annonaceae), is reported to possess anti-inflammatory and analgesic properties. Here, we investigated the therapeutic potential of XA for rheumatoid arthritis (RA), a debilitating autoimmune inflammatory disease characterized by joint damage, in the complete Freund's adjuvant (CFA)-induced arthritis model in rats. We synthesized bioinspired reconstituted high-density lipoprotein (rHDL) nanoparticles loaded with purified XA crystals (rHDL/XA) that passively accumulate in inflamed joints of CFA-induced arthritic rats. Treatment with rHDL/XA minimized mononuclear cell infiltration of CFA-induced arthritic sites and ameliorated disease burden. Metabolomic and transcriptomic analyses revealed that the major molecular pathways perturbed following CFA-induced arthritis correlated with amino acid and lipid metabolism, which were restored to normal states by rHDL/XA treatment. This work demonstrates the anti-RA potential of XA in a nanoformulation and uncovers its underlying therapeutic mechanisms at the transcript and metabolite levels.

GC-MS-based metabolomics, antibacterial and anti-inflammatory investigations to characterize the quality of essential oil obtained from dried Xylopia aethiopica fruits from Ghana and Nigeria.

OBJECTIVES: This study sought to determine the quality of essential oil from Xylopia aethiopica fruits of different geographical origins using GC-MS-based metabolomics, bacterial quorum sensing and anti-inflammation assessment. METHODS: Essential oil was obtained from eight batches of X. aethiopica fruits from Ghana and Nigeria by hydrodistillation, characterized using gas chromatography-mass spectrometry and differences therein found using metabolomics. The respective antibacterial activity of the oils was tested against four bacterial strains: two Gram-positive strains, Staphylococcus aureus (ATCC 25923) and Bacillus licheniformis (ATCC12759), and two Gram-negative strains, Escherichia coli (ATCC25922) and Klebsiella pneumoniae (ATCC 13883). Anti-inflammation was tested using RAW 264.7 macrophage cells. KEY FINDINGS: The outcome of the study revealed that the oil of the Ghana-sourced samples exhibited superior antibacterial, cytotoxic and anti-inflammatory effects than those from Nigeria. This could be attributed to the higher levels of the bioactive compounds present in those samples. This distinction between the samples from the two countries was clearly established using the metabolomics approach, and 14 differential metabolites were found to be potential chemical markers. CONCLUSIONS: The study lends credence to the traditional uses of the essential oil of X. aethiopica as an antimicrobial and anti-inflammatory agent.

Xylopia aethiopica Seeds from Two Countries in West Africa Exhibit Differences in Their Proteomes, Mineral Content and Bioactive Phytochemical Composition.

Aside from its multiple medicinal uses, the fruit of Xylopia aethiopica is widely used in Africa as food. Herein, we characterize the protein profiles, mineral content and bioactive phytochemical composition of the seeds of this plant sourced in Ghana and Nigeria. Using label-free proteomics, a total of 677 proteins were identified, with 260 found in the Ghana-sourced samples while 608 proteins were detected in the samples from Nigeria. However, 114 proteins were common between the samples from the two countries, among which 48 were significantly changed. Bioinformatics and functional analyses revealed that the differential levels of the proteins were mainly linked to pathways involved amino acids metabolism and biosynthesis. The significantly changed proteins related mainly to catalytic activity and carbon metabolism. The samples from Nigeria also exhibited superior qualities in terms of their antioxidant effects, and total phenolic and flavonoid content. Finally, only the content of Na varied to a statistically significant level. This study lends support to its culinary use and hints towards the impact of location of cultivation on the quality of the seeds. There is however need for further mechanistic investigations to unravel the underlying reasons for the observed differences.