Characterization and Isolation of Ginger Phenols from Zingiber officinale Rhizomes through in Silico-Based Reverse Annotation and Molecular Networking

Ginger
is a rich source of ginger phenols with an anti-inflammatory
property. Antineuroinflammatory pathways represent a promising therapeutic
strategy for neurodegenerative diseases. Ginger was selected as our
research object to discover bioactive constituents responsible for
the antineuroinflammatory effect. An in silico-based reverse annotation
strategy, in conjunction with molecular networking, was employed for
the large-scale annotation of ginger phenols from ginger. A total
of 174 ginger phenols and 235 ginger phenol dimers were annotated.
Five new ginger phenols (1–5) and 18 known ginger
phenols (6–23) were isolated following this proposed
strategy, among which compound 1 was a new natural product
and compounds 2–3 were novel ginger phenol dimers.
Their structures were elucidated using extensive spectroscopic data
and semisynthesis methods. Compounds 2, 8, 12, 18, and 19 exhibited
a capacity to inhibit nitric oxide (NO) production and demonstrated
antineuroinflammatory activity in lipopolysaccharide (LPS)-induced
BV2 cells at the concentrations of 10, 20, and 40 μM. Enzyme-linked
immunosorbent assay (ELISA) showed that compounds 2, 18, and 19 could significantly reduce the expression
levels of cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β).
In addition, compounds 2 and 18 displayed
a certain inhibitory effect on the expressions of interleukin-10 (IL-10)
and interleukin-6 (IL-6). The Western blot analysis revealed that
compounds 18 and 19 effectively attenuated
the expression of IL-1β, while only compound 2 inhibited
the expression of phosphorylated nuclear factor kappa B (p-NF-κB)
in BV2 cells. This study demonstrates the great potential and prospect
of the proposed strategy in the utilization of ginger resources. Additionally,
it reveals that ginger contains diverse ginger phenols with antineuroinflammation
activity.