Pharmacological and Pharmacokinetic Studies with Agaricoglycerides, Extracted from Grifola frondosa, in Animal Models of Pain and Inflammation

Abstract

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.

Antitumor, Anti-inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifola frondosa: A Review of Preclinical and Clinical Studies

“…The mechanism was a beneficial regulation of gut microbiota [79]. Moreover, a fermented GF extract had anti-inflammatory effect in an endotoxin-induced uveitis model in rats [80], and a GF extract reduced colon ulceration in an IBD rat model through an antioxidative and anti-inflammatory mechanism [81].…”

Mushrooms: A Potential Natural Source of Anti-Inflammatory Compounds for Medical Applications

“…They also exhibited significant anti-inflammatory activity. The agaricoglycerides isolated from Grifola frondosa (AGF) showed potent anti-inflammatory activity since they were able to reduce the level of many mediators, such as IL-1 β , NF- κ B, ICAM-1, COX-2, and iNOS in animal models [ 97 ]. This study showed that an oral dose of 500 mg/kg/day of the ethanolic extract of an agaricoglyceride mixture showed strong anti-inflammatory activity in a Wister rat animal model.…”

The analgesic effect of several edible mushrooms

“…Soluble β-d-glucan isolated from fruiting bodies of L. rufus produced potent inhibition of inflammatory pain caused by formalin when compared with the insoluble one 69 . Furthermore, a recent study stated that Grifola frondosa has important and antinociceptive effects in acetic acid-induced pain and formalininduced inflammatory pain at the dose level of 500 mg/kg in mice 70 . Therefore, G. frondosa may be used as an alternative medicine for inflammatory pain.…”

“…Pleurotus pulmonarius β-Glucans [25][26][27][28][29][30][31][32] Pleurotus florida Hydroethanolic extract [34] Pleurotus eous Methanol and aqueous extracts [35] Agaricus brasiliensis Fucogalactan (EPF-Ab) [37] Agaricus bisporus var. hortensis Fucogalactan (EPF-Ah) [37] Agaricus macrospores Agaricoglycerides [43][44][45][46][47][48] Coriolus versicolor Polysaccharopeptides [51][52][53][54][55][56][57] Cordyceps Cordymin [63][64][65] Termitomyces albuminosus Crude saponin extract Crude polysaccharide extract [66] Inonotus obliquus Methanol extract [67] Phellinus linteus EtOH extract [68] Lactarius rufus Soluble β-d-glucan [69] Grifola frondosa Agaricoglycerides [70]…”