Differential Impacts of Gingerols- and Shogaols-Enriched Ginger Root Extracts on Fecal Metabolites in Rats with Neuropathic Pain

Abstract

Abstract Objectives Emerging evidence suggests that gut microbiota-derived mediators play key roles in the development of chronic pain, particularly, neuropathic pain (NP), by serving as critical modulators. We evaluated the effects of two ginger root extracts, gingerols and shogaols respectively, on gut microbiota-derived metabolites in the feces of animals with NP. Methods Sixteen male rats were randomly divided into 4 groups: sham group, SNL group, SNL+gingerols-enriched ginger (GEG) extract group, and SNL+shogoals-enriched ginger (SEG) extract group. At 30 days, fecal samples were processed or LC-MS/MS analysis. Principle Component Analysis was performed to assess the different profiling of the metabolites detected and quantified among 4 groups. Data were analyzed using compound discover software (3.1) to identify and quantify metabolites. t-test was performed to determine the number of statistically different metabolites in SNL group compared to the other groups. Results Among all identified pathways, three amino acid- associated pathways (namely, branched chain amino acid biosynthesis (BCAAB), anaerobic aromatic compound degradation (AACD), and aromatic amino acid biosynthesis (AAAB)) were significantly affected in the paired comparisons. The SNL group tended to have higher concentration of phenylacetadehyde (AACD pathway) than that in the sham group (P = 0.09). In BCAAB pathway, relative to the SNL group, (i) GEG group had an increase in L-glutamate, 4-methyl-2-oxopentanoate, and (S)-3-methyl-2-oxopentanoate, and a decrease in (S)-2-acetolactate, and (ii) SEG group showed increased L-valine and decreased 2-oxoglutarate levels. In AACD pathway, compared to the SNL group, R-2-benzylsuccinate, phenylacetate, phenlacetadehyde, and L-glutamate levels were increased in the GEG group, while only phenlacetate level was increased in the SEG group. In AAAB pathway, compared to the SNL group, increased L-glutamate and decreased D-erythrose 4-phospahte level was seen in the GEG group; whereas the SEG group tended to have lower fecal L-glutamine level. Conclusions Based on the results of fecal metabolite analyses, gingerols and shogaols supplementation had significant but differential impacts on the amino acid-associated pathways. Funding Sources Texas Tech University Health Sciences Center.