Analgesic and anti-inflammatory effects of Glycyrrhiza protein in an acute inflammatory pain model: Insights from metabolomic and transcriptomic profiling.

Ethnopharmacological Relevance: Licorice has been used as an herbal remedy in alternative medicinal systems, such as Ayurveda and traditional Chinese medicine (TCM), for millennia. According to traditional Chinese medicine theory, Glycyrrhiza protein (GP) relieves pain. Some studies have found that GP can be used as a drug delivery carrier, indirectly or directly promoting anti-inflammatory and analgesic effects. However, research on its direct anti-inflammatory and analgesic effects and mechanisms remains unclear.

Aim Of The Study: This study aimed to evaluate the analgesic effect of Glycyrrhiza protein (GP) using the acetic acid-induced writhing test and explore its mechanism through metabolome and transcriptome analyses to provide theoretical support for developing new analgesic drugs.

Methods: An acetic acid-induced writhing model was used to assess GP's analgesic efficacy. Writhing inhibition rate and inflammatory cytokine levels (ELISA) in serum/peritoneal lavage fluid were measured. Mechanistic insights were obtained through serum metabolomics, spinal cord transcriptomics, RT-qPCR, and glial activation analysis.

Results: GP administration (0.6 mg/10 g) significantly attenuated acetic acid-induced nociceptive responses, demonstrating a 73.43 % writhing inhibition rate (P < 0.05). Treatment with GP effectively modulated inflammatory cytokine levels, suppressed prostaglandin synthesis (P < 0.05), and downregulated MAPK/ERK pathway gene expression (P < 0.05). Furthermore, GP significantly inhibited glial cell activation (P < 0.05), collectively contributing to its anti-inflammatory and analgesic effects.

Conclusion: GP demonstrates considerable potential as an analgesic agent, with its pharmacological mechanism primarily involving the suppression of PGs, the MAPK/ERK signaling pathway, and spinal glial cell activation.