Korean J Pain.  2024 Apr;37(2):151-163. 10.3344/kjp.23363.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation

• Lin K
• Fu D
• Wang Z
• Zhang X
• Zhu C

• KMID: 2554955
• DOI: http://doi.org/10.3344/kjp.23363

Abstract

Background
Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear.
Methods
Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalininduced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX- 2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR.
Results
Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenantriggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF- κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA.
Conclusions
Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

Keyword

Analgesics; Anti-Inflammatory Agents; Capsaicin; Galangin; Molecular Docking Simulation; Neuro peptides; Pain

Figure

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  Fig. 1 Potential analgesic and anti-inflammatory effects of galangin. TRPV1: transient receptor potential vanilloid 1, CGRP: calcitonin gene-related peptide, SP: substance P, COX-2: cyclooxygenase-2, PGE2: prostaglandin E2, IL: interleukin, TNF-α: tumor necrosis factor-α.

• 

  Fig. 2 Effect of galangin on hot plate experiment. (A) During different time intervals within 210 minutes, the effects of galangin and celecoxib on the latency period of the hot plate in mice. (B) Average percentage of maximum effect of the drug (%MPE). Data were expressed as means ± standard error of the mean (n = 6).

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  Fig. 3 Effect of galangin on acetic acid induction test. (A) Effect of galangin on twisting times of mice. (B) Effect of drugs on torsion inhibition rate. (C) Effects of drugs on vascular permeability. Compared with control group, *P < 0.05 and **P < 0.01 (n = 6). OD: optical density, i.g.: intragastrical administration.

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  Fig. 4 The experimental effect of galangin on formalin pain and carrageenan foot swelling. (A) The effect of drugs on first-phase pain caused by formalin. (B) The effect of drugs on the pain caused by formalin in the second phase. (C) The effect of drugs on the inhibition rate of carrageenan induced foot swelling in mice. Compared to the control group, **P < 0.01; ##P < 0.01, (n = 6). i.g.: intragastrical administration.

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  Fig. 5 The effect of galangin on the licking time induced by capsaicin in mice. Compared to the control group, **P < 0.01 and ##P < 0.01, (n = 6). i.g.: intragastrical administration, i.v.: intravenous injection.

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  Fig. 6 Galangin inhibits the release of capsaicin-induced related factors. (A–E) The levels of inflammatory factors IL-1β, IL-6, TNF-α, PGE2, and the active concentration of COX-2 in serum. (F) Effect of galangin on CGRP and SP levels in serum. ##P < 0.01 compared with control group; **P < 0.01 compared with model group, (n = 6). IL: interleukin, TNF-α: tumor necrosis factor-α, PGE2: prostaglandin E2, COX-2: cyclooxygenase-2, CGRP: calcitonin gene-related peptide, SP: substance P, i.g.: intragastrical administration, i.v.: intravenous injection.

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  Fig. 7 Molecular docking and PPI network recognition of key genes; Western blot and qPCR validation experiments. (A) Galangin inhibited mRNA expression induced by capsaicin. (B) Molecular docking of galangin with TRPV1, NF-κB, COX-2 and TNF-α. (C, D) Galangin inhibited the expression of TRPV1 protein in dorsal root ganglion induced by capsaicin. (E) PPI network recognition of key genes. #P < 0.05 and ##P < 0.01 compared with the normal group; *P < 0.05 and **P < 0.01 compared with the model group. Values are expressed as means ± standard deviation (n = 3). PPI: protein-protein interaction network, TRPV1: transient receptor potential vanilloid 1, NF-κB: nuclear factor kappa B, COX-2: cyclooxygenase-2, TNF-α: tumor necrosis factor-α, CGRP: calcitonin gene-related peptide, SP: substance P, PGE2: prostaglandin E2, i.g.: intragastrical administration, i.v.: intravenous injection.

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