Pharmacological and pharmacokinetic studies with agaricoglycerides, extracted from Grifola frondosa, in animal models of pain and inflammation.
The objective of the present study was to demonstrate the anti-inflammatory and antinociceptive properties of agaricoglycerides of the fermented mushroom of Grifola frondosa (AGF). The effects of AGF on interleukin-1β (IL-1β) levels, tumor necrosis factor-α (TNF-α) levels, nuclear factor kappa B (NF-κB) levels, intercellular adhesion molecule-1 (ICAM-1) levels, cyclooxygenase-2 (COX-2) levels, and inducible nitric oxide synthase (iNOS) levels were determined by ELISA. The antinociceptive effects of AGF were also analyzed in acetic acid-induced pain model and formalin-induced inflammatory pain model, respectively. At the same time, the pharmacokinetic assay of AGF was also made. AGF at the dose level of 500 mg/kg significantly inhibited LPS-induced upregulation of NF-κB activation and the production of IL-1β, TNF-α, iNOS, ICAM-1, and COX-2. Moreover, AGF at the dose level of 500 mg/kg suppressed the acetic acid-induced abdominal constrictions (p < 0.05) and the formalin-induced spontaneous nociceptive behaviors (p < 0.05) in rats. The total plasma concentrations of drug after oral administration of AGF at the dose level of 500 mg/kg led to an improvement in oral bioavailability. It accounts for the anti-inflammatory and antinociceptive activity of AGF. The present study demonstrated that AGF at the dose level of 500 mg/kg has important anti-inflammatory and antinociceptive effects in preclinical models of inflammation and in some models of pain and thus may be used as an alternative medicine for inflammatory pain.
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China.
Chuncho
C
Han
Bo
B
Cui
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000097:blood; D005557:Formaldehyde; D048691:Grifola / Q000737:chemistry*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005557:Formaldehyde; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2