Gaultherin

Gaultherin is an orally active non-steroidal anti-inflammatory agent. Gaultherin selectively inhibits NF-κB, MAPK, COX-2 (IC₅₀ = 0.35 mg/mL), LOX (IC₅₀ = 0.56 mg/mL) and HYAL (IC₅₀ = 28.58 μg/mL) to exert anti-inflammatory, antipyretic and analgesic effects. Gaultherin exhibits modest direct antioxidant capacity, greater in cell-based models. Gaultherin does not affect COX-1 so that avoids the common gastrointestinal side effects of Aspirin (HY-14654)^[1][2]. In Vitro:Gaultherin acts only after it is transformed into methyl salicylate by intestinal bacteria and then the absorbed methyl salicylate is hydrolyzed rapidly by esterases in intestine, blood and liver to produce salicylate^[1].
. Gaultherin presents low antioxidant activity, ferric reducing activity, and scavenging potential towards O₂^•− with SC₅₀s of 265.69 μg/mL (DPPH), 0.64 mmol Fe^²⁺/g (FRAP), 451.76 μg/mL (O₂^•−), 488.52 μg/mL (•OH), 587.86 μg/mL (H₂O₂)^[2].
Gaultherin (25-75 μM) significantly inhibits the secretion of ROS in fMLP (HY-P0224)-stimulated human neutrophils and LPS (HY-D1056)-stimulated RAW264.7 murine macrophages^[2].
Gaultherin inhibits the release of pro-inflammatory cytokines including IL-8, IL-1β, TNF-α, MMP-9 and ELA-2 in LPS/fMLP + Cytochalasin B (HY-16928)-stimulated human neutrophils and NO, TNF-α, IL-1β and IL-6 in LPS-stimulated RAW264.7 murine macrophages^[2].
Gaultherin prevents phosphorylation and subsequent degradation of IκBα and blocks the translocation of NF-κB to the nucleus^[2].
Gaultherin inhibits directly or via upstream modulation of MAPK kinases, particularly MEK1/2, MKK3/6, and MKK4/7, and thus suppresses the phosphorylation/activation of MAPKs, including JNKs, p38, and ERKs^[2].
In Vivo:Gaultherin (400 mg/kg, p,o., single dose) inhibits the visceral pain induced by Acetic acid (HY-Y0319) in mice^[1].
Gaultherin (400 mg/kg, p,o., once daily for 3 days) significantly inhibits the ear swelling after the application of croton oil^[1].
Gaultherin (330 mg/kg, p,o., single dose) does not aggravate the stress-induced gastric damage and is significantly superior to Aspirin^[1].
Gaultherin (100-300 mg/kg, p,o., single dose) induces a reduction in rectal temperature in feverish mice^[2].