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

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-1ß, 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-1ß, 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.

Components study on gastroprotective effect and holistic mechanism of the herbal pair Alpinia officinarum - Cyperus rotundus based on spectrum-effect relationship and integrated transcriptome and metabolome analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal pair Alpinia officinarum-Cyperus rotundus (HPAC) has an extended history of use in the treatment of gastric ulcers, and its curative effect is definite. AIM OF THE STUDY: To explore the material basis and holistic mechanism of HPAC on ethanol-induced gastric ulcers. MATERIALS AND METHODS: Three chemometrics, GRA, OPLS, and BCA, were used to construct the spectrum-effect relationship between the HPLC fingerprints of HPAC extracts and the bioactivity indices (cell viability; the levels of TNF-α, IL-6, COX-2, and PGE2; and wound healing rate) against GES-1 cell damage to screen the bioactive ingredients. The bioactive components were isolated and validated in vitro. Simultaneously, the effects of HPAC with concentrated bioactive ingredients was tested on ethanol-induced gastric ulcers in vivo, and the mechanism was investigated using transcriptomics and metabolomics. The mechanism was further validated by Western blotting. Finally, the contents of the main components of HPAC were determined before and after compatibility. RESULTS: Twelve bioactive components were screened, and the structures of nine compounds were confirmed. An in vitro verification test showed that DPHA and galangin could protect GES-1 cells from injury, and that their content increased after compatibility. The CH2Cl2 fraction of HPAC (HP-CH2Cl2) can protect mice from ethanol-induced gastric mucosal injury by reducing hemorrhage and decreasing inflammatory cell infiltration. Western blot analysis indicated that this fraction may up-regulate TRPV1 protein and down-regulate PI3K and AKT proteins. CONCLUSIONS: DPHA and galangin may be the bioactive components against ethanol-induced GES-1 cell injury. HP-CH2Cl2 may exert gastroprotective effects by regulating PI3K, AKT and TRPV1 proteins.

Chemical Constituents and Anti-Gastric Ulcer Activity of Essential Oils of Alpinia officinarum (Zingiberaceae), Cyperus rotundus (Cyperaceae), and Their Herbal Pair.

The essential oil (EO) of the herbal pair (HP), Alpinia officinarum-Cyperus rotundus (HP G-X) has been conventionally used in traditional Chinese medicine (TCM) for 'warming the stomach' and relieving pain. However, its pharmacologically active compounds, as well as the mechanism of its anti-gastric ulcer properties remain unclear. In this study, the EOs obtained from HP G-X and its corresponding single herbs were analyzed using GC/MS. A total of 74, 56, and 85 compounds were detected in A. officinarum (GLJ), C. rotundus (XF), and HP G-X, accounting for 93.2 %, 89.5 %, and 92.0 % of the total content, respectively. GLJ mainly contains 1,8-cineol (22.0 %) and α-terpineol (11.8 %), whereas cyperenone (22.4 %) and cyperene (12.3 %) were the major constituents in XF. These four compounds were also detected in the HP G-X with relatively high composition as 11.8 %, 5.5 %, 11.8 %, and 10.6 %, respectively. Although no new compounds were detected in HP G-X, the relative concentration of some compounds increased, while others decreased or even disappeared. HP G-X showed the lowest toxicity (TC50 >800 µg/mL) against human gastric mucosal epithelial cells (GES-1) and had the best protective effect against ethanol-induced GES-1 cell damage compared to the individual herbs. In vitro studies demonstrated that HP G-X and the corresponding single herbs significantly reduced IL-6, TNF-α, and COX-2. In addition, in vivo investigations indicated that HP G-X can protect the gastric mucosa of mice from ethanol-induced damage by inhibiting the inflammatory reaction and providing analgesia. It can also inhibit the expression of NF-κBp65, COX-2, and TRPV1 protein, reduce the concentrations of IL-6 and TNF-α, and relieve heat-induced pain. This study further substantiated the traditional application of HP G-X against gastric ulcers through both in vivo and in vitro investigations.