2. Academic Validation
  3. Glycyrrhiza uralensis Fisch: A novel source of analgesic activity through NaV1.8 sodium channel modulation

Glycyrrhiza uralensis Fisch: A novel source of analgesic activity through NaV1.8 sodium channel modulation

  • Food Res Int. 2025 Dec;222(Pt 1):117620. doi: 10.1016/j.foodres.2025.117620.
Yalan Han 1,  Shutong Wu 2,  Hejiang Zhou 1,  Xiancui Lu 3,  Susu Cheng 2,  Jiaojiao Li 2,  Meiquan Li 4,  Yin Nian 5,  Ling-Yan Su 6
Affiliations

Affiliations

  • 1 College of Food Science and Technology, Yunnan Agricultural University, No. 452 Fengyuan Road, Kunming 650000, China; Yunnan International Joint Laboratory of China-Cambodia Signature Agro-Products Green Development, Yunnan Provincial Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650000, China.
  • 2 College of Food Science and Technology, Yunnan Agricultural University, No. 452 Fengyuan Road, Kunming 650000, China.
  • 3 College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150000, Heilongjiang, China.
  • 4 College of Agriculture and Life Sciences, Kunming University, Kunming 650000, China.
  • 5 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences Kunming, 650201, Yunnan, China. Electronic address: [email protected].
  • 6 College of Food Science and Technology, Yunnan Agricultural University, No. 452 Fengyuan Road, Kunming 650000, China; Yunnan International Joint Laboratory of China-Cambodia Signature Agro-Products Green Development, Yunnan Provincial Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650000, China. Electronic address: [email protected].
PMID: 41267240 DOI: 10.1016/j.foodres.2025.117620
Abstract

Glycyrrhiza uralensis Fisch. (G. uralensis) is a "medicine food homology" herbal medicine widely used in the pharmaceutical and food industries. G. uralensis has a variety of biological functions, including antioxidant, Antiviral, anti-inflammation and analgesic effects. However, the specific mechanism underlying the pain-relieving effects of G. uralensis remains to be explored. Here we investigated the analgesic properties of G. uralensis using rodent models of pain. The crude extracts of G. uralensis effectively alleviated acetic acid-induced inflammatory and paclitaxel-induced neuropathic pain. Further screening studies identified licoisoflavone A as the key bioactive compound of G. uralensis responsible for its analgesic activity, which inhibits the NaV1.8 Sodium Channel (IC50 = 7.53 μM). Combining electrophysiological experiments with molecular docking revealed that licoisoflavone A acts as a novel, highly potent pore blocker of the NaV1.8 channel by obstructing ion flow through the pore region. Moreover, in various murine pain models, licoisoflavone A showed a significant dose-dependent analgesic effect in reducing inflammatory and neuropathic pain, including those pain models induced by acetic acid, heat, complete Freund's Adjuvant, and paclitaxel. Cell cytotoxicity assays, open-field tests, and rotarod tests confirmed licoisoflavone A exhibits a favorable safety profile. Our study uncovers the underlying mechanism of G. uralensis analgesia and suggests that licoisoflavone A is a promising candidate for targeting NaV1.8 for pain therapy.

Keywords

Glycyrrhiza uralensis Fisch.; Licoisoflavone A; Na(V)1.8 sodium channel; Pain.

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