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

Table 2

Examples of biological studies performed with anti-inflammatory compounds from mushrooms.

Bioactive compound/mushroom species	Assay model	Results/mechanism of action	References
Polysaccharides
Agaricus blazei	(i) Mouse bone marrow-derived mast cells (BMMCs) stimulated with PMA + A23187	(i) Inhibition of IL-6 production, downregulation of phosphorylation of Akt, inhibition of -hexosaminidase degranulation, inhibition of prostaglandin D(2), and leukotriene C(4) production.	[51]
	(i) Male Swiss mice (acetic acid induced inflammation)	(i) Dose-dependent anti-inflammatory response, inhibition of leukocyte migration (82%), IC50 of 1.19 (0.74–1.92) mg/kg, 3 mg/kg i.p. glucan injection reduced 85% of writhes	[60]
Pleurotus pulmonarius	(ii) Mice (3.5% dextran sulfate sodium, DSS in drinking water for 14 days, with 20 mg fruiting body or mycelia extract/mouse/day)	(ii) Fruiting body and mycelia extracts suppressed inflammatory reactions in vivo in DSS induced colonic inflammation by downregulating TNF-α secretion and inhibiting NF-B activation	[57, 58]
	(iii) Acetic acid induced colitis in rats (2% pleuran, or 0.44% hydrogel for 4 weeks)	(iii) Reduction in macroscopic damage score by 51 and 67% for pleuran diet and hydrogel, respectively; reduction in the activity of myeloperoxidase and neutrophil infiltration	[61]
	(iv) Murine macrophage RAW264.7 cells, female Balb/C mice	(iv) Suppression of LPS-induced dependent activation of TNF-, IL-6, and IL-12, inhibition of LPS-induced production of PGE2 and NO. Suppression of LPS-induced production of TNF- in mice and concanavalin A-stimulated proliferation and secretion of INF-, IL-2, and IL-6 in mouse splenocytes	[62]
Caripia montagnei	(i) Male Swiss mice treated with 10, 30, and 50 mg/kg with mushroom glucan	(i) 50 mg/kg glucan reduced inflammatory infiltrate produced by thioglycolate-induced peritonitis by 75.5%, reduced NO level, IL-1ra, IL-10, and IFN-	[63]
Lactarius rufus	(i) Swiss mice, formalin-induced nociception, 30 mg/kg i.p. of fruiting body extract (soluble, insoluble, and modified)	(i) Inhibition of neurogenic pain by 36, 47, and 58% for soluble, insoluble, and modified glucans, respectively	[64]
A. bisporus	(i) Male Swiss mice, formalin-induced licking	(i) Inhibition of neurogenic and inflammatory phases, antinociceptive effect with IC50 of 36.0 (25.8–50.3 mg/kg); (ii) Decreased iNOS and COX2	[65]
Lentinus edodes	(i) Male Swiss mice, acetic acid induced inflammation, 3–100 mg/kg i.p. fruiting body concentrate	(i) Inhibition of induced nociception with IC50 of 13.8 (7.8–23.5) mg/kg, 97% inhibition at 100 mg/kg; (ii) Inhibition of peritoneal capillary permeability and leukocyte infiltration (76% inhibition), IC50 13.9, 8.2–23.7, and 100% inhibition, IC50 6.5, 1.5–28.2 mg/kg, respectively	[66]
L. polychrous	(i) Carrageenan-induced paw edema in male Sprague-Dawley rats, murine macrophage RAW 264.7 cells	(i) Dose-dependent inhibition of NO, intracellular production; (ii) Decreased expression of iNOS, IL-1, IL-6, TNF-α, and COX-2	[67]
Termitomyces albuminosus	(i) Acetic acid induced writhing in male ICR mice, formalin test, xylene, and carrageenan induced ear edema	(i) Inhibition of ear swelling by 61.8, 79.0, and 81.6% for treatment with dry matter of the culture broth (1000 mg/kg), crude saponin extract (200 mg/kg), or crude polysaccharide extract (200 mg/kg), respectively	[68]
Phellinus linteus	(i) Croton oil induced ear edema and acetic acid induced writhing in male ICR mice	(i) Extract treatment with 1 mg/ear gave 45 and 41.5% inhibition in ear plug weight and thickness, respectively, oral administration of extract (100–400 mg/kg) inhibited writhing number (35.9–68.9%)	[69]
Pholiota nameko	(i) Xylene induced ear edema, adult Swiss mice and Sprague-Dawley rats, formaldehyde, egg albumin, and carrageenan induced paw edema in rats and mice	(i) Extract (5 mg/ear) inhibited ear edema, suppression of egg albumin, carrageenan and formaldehyde-induced paw edema at 100–400 mg/kg i.p., 10.96–43.75% inhibition of granuloma tissue growth, no production of gastric lesions in rats	[71]
Flammulina velutipes	(i) Male Wistar rats, fed 100–300 mg/kg mushroom for 30 days	(i) Decreased levels of CD4^+ CD8^+, MPO, and ICAM-1, with increased level in IL-10 in serum	[72]
Terpenoids
Cyathus africanus	(i) Mouse monocyte-macrophage RAW 264.7 cells, NO assay	(i) Cyathins D-H 3 and 5, neosarcodonin, and 11-O-acetylcyatha-triol inhibited NO production with an IC50 value of 2.75, 1.47, 12.0, and 10.73 M, respectively	[76]
C. hookeri	(i) Mouse monocyte-macrophage RAW 264.7 cells, NO assay	(i) Inhibition of NO production with an IC50 of 15.5, 52.3, and 16.8 M, respectively.	[77]
Ganoderma lucidum	(i) LPS-stimulated murine macrophage RAW 264.7 cells, NO assay	(i) Inhibition of TNF-, IL-6, NO, and PGE2, downregulation of iNOS and COX-2, inhibition of NF-B, decreased NF-B-DNA binding activity, and suppression of p65 phosphorylation	[78]
	(ii) Acetic acid induced ear edema in female ICR and SENCAR mice	(ii) Significant inhibition of inflammation (1 g/ear) in mice with IC50 values between 0.07 and 0.39 mg/ear, with inhibition ratio ranging from 58 to 97%	[81]
		(i) Reduced nitrate levels by an average of 50%, dose-dependent inhibition of IL-1, IL-6, and TNF	[82]
Inonotus obliquus	(i) Murine macrophage RAW 164.7 cells	(ii) Trametenolic acid, ergosterol peroxide, 3-hydroxy-8,24-dien-21-al, ergosterol and inotodiol inhibited NO production, and NF-B luciferase activity, with an inhibition percentage of 50.04, 36.88, 20.36, 6.00, and 3.13%, respectively	[84]
		(iii) Methanolic extract inhibited production of NO, prostaglandin E2, and TNF-, inhibition of mRNA expression of iNOS and COX-2	[83]
Peptides
Cordyceps sinensis	(i) Acetic acid induced inflammation in mice	(i) Decreased level of TNF-, IL-1, dose-dependent inhibition of abdominal constrictions	[86]
Phenolics
Lactarius deliciosus	(i) LPS-stimulated RAW 364.7 macrophage cells, nitrite, and cytokine assays	(i) 0.5 mg/mL mushroom extract inhibited NO production and expression of iNOS, IL-1, and IL6 mRNAs	[91]
Daldinia childiae	(i) LPS-stimulated RAW 264.7 macrophage cells	(i) Daldinals suppressed NO production with IC50 values ranging between 4.6 and 15.2 M and inhibited iNOS mRNA synthesis	[72]
Albatrellus caeruleoporus	(i) LPS-stimulated mouse macrophage RAW 264.7 cells	(i) Grifolins inhibited NO production with IC50 values ranging between 22.9 and 29 M	[94]
Syringaldehyde and syringic acid
Elaphomyces granulates	(i) Mouse macrophage RAW 264.7 cells	(i) Crude ethanolic extract (50 g/mL) inhibited COX-2 activity by 68%, purified syringaldehyde, and syringic acid inhibited COX-2 activity in a dose-dependent manner, with an IC50 of 3.5 and 0.4 g/mL, respectively	[96]
Agaricoglycerides
Grifola frondosa	(i) Acetic acid- and formalin-induced inflammation in Wister rats, treatment with orally fed extracts (100–500 mg/kg/day)	(i) 500 mg/kg/day inhibited induced upregulation of NF-B and the production of IL-1, TNF-, ICAM-1, COX-2, and iNOS, suppressed acetic acid induced abdominal constrictions and formalin-induced spontaneous nociceptive behavior	[97]