Chinese licorice (Gan Cao): proven anti-inflammatory properties

Chinese licorice, known in traditional Chinese medicine as Gan Cao and botanically corresponding to Glycyrrhiza uralensis Fisch. (Fabaceae family), is a perennial plant whose roots and rhizomes have been used for over two millennia for their therapeutic properties. In traditional Chinese medicine, Gan Cao is classified among the plants that tonify Qi, harmonize formulas, alleviate spasms, and reduce inflammation. Modern pharmacological research has confirmed these empirical uses by demonstrating significant anti-inflammatory effects, mediated by several classes of bioactive compounds and well-characterized molecular mechanisms. Bioactive Compounds Responsible for Anti-Inflammatory Effects

The main constituents responsible for these properties are glycyrrhizin (or glycyrrhizic acid), a major triterpene saponin representing 2 to 15% of the drug’s dry weight, as well as its active metabolites (18β-glycyrrhetinic acid). The plant also contains a rich diversity of flavonoids, including liquiritigenin, isoliquiritigenin, glabridin, and licochalcone. Polysaccharides of varying molecular weights complement this phytochemical profile and contribute to immunomodulatory activities.

Anti-inflammatory Mechanisms of Action

The anti-inflammatory effects of Glycyrrhiza uralensis are exerted via several key signaling pathways. Glycyrrhizin and its derivatives inhibit phospholipase A2, reducing the release of arachidonic acid and, consequently, the synthesis of prostaglandins and leukotrienes. They also suppress the activation of the transcription factor NF-κB, decreasing the expression of pro-inflammatory cytokines such as TNF-α and IL-6, as well as mediators like nitric oxide (NO) and prostaglandin E2 (PGE2). Studies in cell models (RAW264.7 macrophages stimulated by lipopolysaccharide) have demonstrated a dose-dependent inhibition of these inflammatory markers. Furthermore, Gan Cao extracts modulate the NOD2/RIP2/NF-κB pathway, involved in intestinal inflammatory responses, and inhibit the MAPK/ERK pathway in models of inflammatory pain. Flavonoids, particularly licochalcone, block the expression of matrix metalloproteinases (MMP-1, MMP-3, MMP-13) and cell adhesion molecules in chondrocytes stimulated by IL-1β. Polysaccharides, for their part, stimulate IL-7 expression and promote lymphocyte proliferation, enhancing the overall immunomodulatory effect.

Evidence from preclinical studies

In a rat model of trinitrobenzenesulfonic acid (TNBS)-induced ulcerative colitis, administration of an aqueous extract of

G. uralensis significantly reduced macroscopic and histological lesions as well as inflammatory markers, via regulation of the NOD2/RIP2/NF-κB pathway.

A study in a mouse model of acetic acid-induced acute inflammatory pain showed that a low-dose isolated protein from Gan Cao inhibited nociceptive responses by more than 70%, by modulating cytokines and suppressing prostaglandin synthesis through inhibition of the MAPK/ERK pathway.

Studies on low molecular weight polysaccharides have revealed antiproliferative activity against colon cancer cell lines while simultaneously stimulating healthy intestinal epithelial cells, with significant upregulation of IL-7.

Precautions for use

Although beneficial, glycyrrhizin can induce pseudo-aldosteronism (hypertension, hypokalemia, sodium and water retention) at high or prolonged doses (> 50 mg/day). Drug interactions are possible with corticosteroids and diuretics. Deglycyrrhizinated preparations retain some of the anti-inflammatory effects while minimizing these risks.