Review the Analgesic Effect of Several Edible Mushrooms

Page 1 of 8

Review

The analgesic effect of several edible mushrooms

† †

Remedies H Wang , Y Liu , C Han*

Abstract substances that boost health and Introduction saccharopeptide and cordymin as Edible mushrooms, a valuable source β-glucan, agaricoglyceride A, poly- of bioactive compounds and nutrients, What is more, there are barely any increase longevity, which is attrib- have been consumed as part of the sidewell effects as other caused active by components.the toxicity uted to their far-ranging functions, diet in some countries for thousands of edible mushrooms in vitro and ascorbicfor example and so antinociceptive, on. Mushrooms anti- are of years. They are quite high in protein, quiteinflammatory, high in proteinimmunity, (19–35%) anti-tumour, and

applications.in vivo. However, further research mushrooms also contain relatively unsaturatedcarbohydrate fatty and fibreacids. and In lowaddition, in fat is required with clinical trials and largelow in amounts fat. Miles of et carbohydrateal. concluded thatand theycontent also withhave many low trans-isomerscomponents such of Introduction as triterpenes, phenolic compounds, Pain is a physiologically relevant and from 4% to 20%, respectively chitosan, eritadenine, sterols (such as sensation necessary to detect and/or fibre, ranging from 51% to 88% prevent injury; it is sometimes useful are considered momentous agents to us1,2. Typically, it is a direct response vitamins,(dry weight). namely In addition, thiamin, mushrooms ascorbic ergosterol), triterpenes, etc., which contain significant amounts of properties. Recently, edible mushrooms tissue damage, such as injury and 11,12. In addition to havefor some become hitherto increasingly unknown attractive healthy to an untoward event associated with theiracid, riboflavinnutritional andvalue, vitamin some D2,mush as as functional foods and medicines arise independently of any obvious roomswell as may minerals also have a medicinal to treat diseases including cancer, redisposinginflammation, cause, but severeor precipitate pain can - healing after injury for a relatively hypolipidemic effects have been to the presence of these active com long time. It can also occur as a con reportedvalue: anti-tumour,11–13. They form antiviral a huge, andbut ponents.diabetes, Paininflammation is an unpleasant and ache sensa due sequence of brain or nerve injury. - Pain signalling to the central nervous- 14,15. - largely untapped powerful source tion, which is a typical response to excitement and primary afferent littleof new fat pharmaceutical and are highly products suitable for an untoward event associated with system is initiated when harmful obeseThey are persons low-calorie16. Their foods consumption with very reporttissue damage, the positive such as analgesic injury and effect inflam of quently caused by activation of several severalmation. Theedible aims mushrooms of this review on are pain to typesnociceptive of ionotropic C and A fibreschannels are and fre and its relevant active constituents. etabotropic receptors3,4. In fact, tran countriesis widespread17–19. in China, Japan, Korea, Conclusion Taiwan, Italy and Spain, among other sensing ion channels participate in- the result of research on the antino including Pleurotus pulmonarius, generatingsient receptor nociceptive potential signals and acid- in ciceptionIn this review, effect of we edible intend mushrooms to discuss AgaricusIn our review, brasiliensis, the edible Agaricus mushrooms bisporus - var. hortensis, Agaricus macrosporus, stimuli4–6 Coriolus versicolor and Cordyceps channelsresponse toand various other specificproteins noxious impli supportingover the past mechanistic two decades, studies. empha We- sinensis have been investigated that cated in nociceptive. Activity of signalling some of thesepath selectedsising animal several studiestypical edible as well fungi as - kinase C7–9. Thus, pain is generated. - are to evaluate the analgesic effect of bioactivepossess antinociceptivecomponents andsuch anti-as ways can be upregulated by protein ediblewhich fungus,result in identify pain relief. some Our putative goals inflammatory effects owing to their and edible fruiting bodies of several bioactive compounds involved in the speciesEdible of mushrooms fungi, typically are theproduced fleshy above ground on soil or on its food * Corresponding author 10 effect and stimulate further work in Email: [email protected] source . They have been used as † These authors contributed equally to this study. Discussionthe field. School of Pharmacy, Shandong University of tional supplements for several centu The authors have referenced some of Traditional Chinese Medicine, Jinan 250355, ries.delicious For the foods Chinese, and someas healthy mushrooms nutri P. R. China are especially regarded as medical- protocols of these studies have been their own studies in this review. The

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

F : Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine

2013 Oct 01;1(3):22. none declared. interests: none declared. Conflict of interests: Competing the final manuscript. as well read and approved design, and preparation of the manuscript, the conception, to All authors contributed rules of disclosure. ethical Ethics (AME) for Medical the Association All authors abide by or citation purposes Page 2 of 8

Review

approved by the relevant ethics com Pleurotus florida mittees related to the institution in P. pulmonarius had notable analgesic Pleurotus florida - Then, the results showed that mushroom, has been reported to pos sess antioxidant,, animmunostimulator, American oyster institutionwhich they guidelines. were performed. Animal cytokinesand anti-inflammatory29 effects due to - care was in accordance with the the inhibition of pro-inflammatory activities32,33 Analgesic effect of several edible . The structure of β-d-glucan anti-tumour and anti-inflammatoryP. florida mushrooms methylationwas characterised analysis using and a mono- controlled and evaluated using. The a analgesichot plate and method, anti- Oyster mushrooms Smithtwo-dimensional degradation NMR20,29 spectroscopy, inflammatory activity of was Pleurotus is a genus of gilled mush rooms . And the dates tail flick method, acetic acid-induced mushrooms. Species of Pleurotus are- showedO that it had a main chain of inwrithing, rats34 formalin-induced pain and , one of the most widely eaten (1 → 6)-linked α-d-galactopyranosyl hydroethanoliccarrageenan-induced extract inflammation (HEE) of rooms and are some of the most com tutedand 3- at -methyl-α-O d-galactopyranosyl P. florida. Animals treated orally with monlycommonly cultivated known edible as oyster mush mushrooms- units, both of which are partially substi- genus Pleurotus- In order-2 to by evaluateβ-d-mannopyranosyl the involve in a dose-dependent manner include edible and medicinal species, mentnon-reducing of transient ends receptor (Figure 1).potential demonstratedwere tested for P. nociceptive florida exerted response excel in the world. The (TRP) channels and protein kinase- with these methods. Then, results cialised in China20. The fungi are activity in rats on account of myocon- most of them being currently commer lent analgesic and anti-inflammatory BaggioC (PKC) onet antinociceptiveal.30 effect of a - rich in proteins, vitamins, carbo P.(1 pulmonarius→ 3), (1 → 6)-linked β-d-glucan (GL), peptidesstituents 34 like. Simultaneously, flavonoids, phenolics, the studiedhydrates, over minerals the past and 30 dietary years fibres.in the peritoneal administration isolated GLin mice. from antinociceptivepolysaccharides activity and polysaccharo of HEE of lightBasidiomycetes of their polysaccharide have been composi widely In this study, nociceptive to treat it withresponses, intra- P. florida is related to the activation tion and therapeutic application21,22. induced by intraplantar injections of of the opioid system. - capsaicin, cinnamaldehyde, menthol, Pleurotus pulmonarius Pleurotus eous and Pleurotus Pleurotus pulmonarius, ostreatus oyster mushroom, is a common edible acidified saline and phorbol myristate Pleurotus mushrooms are the second also known as acetate (PMA), were significantly inhib- most important mushrooms in terms to its several polysaccharides, besides temicited by GL.antinociceptive The results demonstrated properties highmushroom amount consumed of proteins, worldwide essential due inthat chemical GL displayed models pronounced of nociception sys- more, this species has been of interest amino acids and vitamins23,24 in mice as a result of the inhibition toof productionresearchers in becausethe world. its Further phyto of biological effects have been 30 chemical constituents are similar . A variety from P. pulmonarius could dramati to those of P. pulmonarius, P. florida,- callyof PKCε inhibit. In acute addition, and neuropathic GL isolated Pleurotus eous and Pleurotus ostreatus, tumoural,ascribed to immuno β-glucans,modulatory such as anti-and pain in mice through mechanisms- antinociceptiveinflammatory, properties antioxidant,25–28 . There anti- that involve the inhibition of iono cines. The ethyl acetate, methanol have been some literature research tropic glutamate receptors and the andwhich aqueous are popularly extracts of used P. eous in mush medi- P. pulmonarius have 31. - analgesic effects29–32. Smiderle et al.29 - showing that interleukin-1β pathway room were investigated to evaluate from the basidiomycete P. pulmonarius andisolated found β-glucan the glucan(GL) with had hot potent water

anti-inflammatory and antinociceptive activities in mice. Animals treated with β-glucan showed a reduction of of85 both± 5% the of writhes early (neurogenic induced by aceticpain) acid and the significant inhibition inand 43 the± 5% late and (inflammatory96 ± 4%, respectively. pain) Figure 1: Pleurotus pulmonarius. phases of formalin-induced licking Chemical structure of β-glucan isolated from Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

F : Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine

Review

the analgesic activity using acetic and A. macrosporus) in order to a central and peripheric level. These

35. The perties of Agaricus. determines the function; it is the acid-induced writhing, hot-plate, tail elaborate the antinociceptive pro results showed that the structure P.immersion eous and tail-clip tests Agaricus rasiliensis and Agaricus dates showed that these extracts of bisporis var. hortensis gesic(1 → 6)-linkedproperty α-of dA-galactopyranosyl. brasiliensis and markedly produced raised the significant pain threshold reduc- Fucogalactans from A. brasiliensis A.main-chain bisporus var. that hortensis determines. Many the articles anal attion different in the numbertimes of ofobservation writhes and in A. bisporus var. hortensis have reported that a lot of other p < 0.05). basidiomycetes’ fruiting bodies or culti The extracts also caused a notable (EPF-Ab) and vated mycelium such as P. pulmonarius, comparison with the control ( Fucogalactans(EPF-Ah) have antinociceptiveplay a positive roleaction, in Lentinus edodes, Coprinus comatus- test. Thus, the results of this study which is related to their structures. and Hericium erinaceus, revealedinhibition that of painextracts in theof tail-clipP. eous possessed potent analgesic property activitiesantinociceptive, even after anti-inflammatory extraction37. nociception20,40–42. which have and could serve as a base for future Theand anti-sepsis.active ingredients Besides, arethey attained possess the main-chain, also can inhibit drugs35. by their aqueous extraction and a Agaricus macrosporus Agaricus macrosporus is another tial of P. ostreatus methylation analysis38 Similarly, the antinociceptive poten series of purification.37 According to effect by inhibiting neurolysin. The and formalin tests was36. The also reaction investigated times 3 g/mol) and GC–MS, had a activespecies ingredient which has ofobvious A. macrosporus analgesic in rats through the hot-plate, tail-flick Komuraa et al. concluded that EFP- Ab (Mw = 19.4 × 10 class of fungal secondary metabolites on hot-plate and tail-flick tests were (1 → 6)-linked α-d-Galp main-chain thatis agaricoglycerides, constitute esters which of chlorinated is a new insignificantly the formalin prolonged test. Theand painresearch was partially substituted 3 in g/mol) O-2 had by 43. significantly suppressedP. ostreatusin both phases had non-reducing end-units of α-l-Fucp. They are produced in cultures of the antinociception against neurogenic EPF-Ah (Mw = 31.1 × 10 4-hydroxy benzoic acid and glycerol results showed that a similar main-chain with O-2 substi- possibly by opioid mechanisms36. tution, but was partially methylated edible mushroom, which is different andIn continuoussummary, oyster inflammatory mushrooms pain at HO-3, as well as having 2.5% non- glyceridesfrom the two in species cultures described according above. to reducing end-units of β-d-Gal substi- There are seven structures of agarico tution (Figure 2). Analgesic activity the main active principle of the severalhave shown animal potent model antinociceptivestudies and no was determined using the hot-plate crudereports, extract and agaricoglycerideof A. macrosporus A is and anti-inflammatory properties in manymethod, other acetic acid-inducedclassic methods writhing,37,39. Thereformalin-induced are different pain modes in of rats action and nociceptiveside effects. mechanismsHowever, further in vivo, studies and (Figure 3). Neurolysin inhibitors are humanare needed intervention to investigate studies theof oyster anti likely to enhance the analgesic pro mushrooms alone or in combination among different experiments. Above inactivationperties of neurotensin of these and/or peptides dynor44,45. all, EFP-Ab and EFP-Ah prefer to cure phin A by inhibiting cleavage and inflammatory nociception and act at inwith humans. conventional chemotherapy are also demanded to establish efficacy Agaricus Agaricus is the most common eubac

The species number admitted by- taxonomiststerium among is the more whole than macrofungi. 200. It

Psalliota Kummer in the early days, includingis a large Agaricus family, bisporus, which is Agaricus named bitorquis, Agaricus blazei, Agaricus silvaticus, Agaricus macrospors and so on. We select three typical species Figure 2: (A. brasiliensis, A. bisporus var. hortensis tively from A. brasiliensis A. bisporus var. hortensis (B). Structure of the fucogalactans EPF-Ab and EPF-Ah, obtained respec- (A) and Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

F : Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine

Review

administration to ICR mice and found hot-plate test upon intraperitoneal to its attribute as an immunomodu that its analgesic activity would add - suppressedlatory and after anti-tumour receiving drug. an intra Pain peritonealresponse ininjection mice was of C. significantly versicolor - C. versicolor PSP possesses analgesic PSP. Then, it was demonstrated that patients as an immunomodulatory activity, which is beneficial54. In for addition cancer

analgesiaand anti-tumour produced drug by PSP is mediated to this, one study shows that the

inby IL-2,the mediobasal which is activated hypothalamus by PSP (MBH)and interacts55 with IL-2 receptors dom into different groups to test and the degree. Rats of analgesic were divided effect atof ranPSP-

fromwas evaluated baseline bypain the threshold.pain threshold The experiment(mA) or by theresults percentage demonstrated increase that the analgesia appeared only 1 h after PSP administration and began Figure 3: Chemical structures of metabolites isolated from Agaricus macrosporus. to decrease after another hour. The

1: Agaricoglyceride A; 2: Agaricoglyceride B; 1a/b: Monoacetyl-agaricoglycerides produced analgesia might be mediated phenomenon suggested that PSP- A (isolated as inseparable mixture); 3: Agaricoglyceride C; 4: Agaricoglyceride D; by some intermediary substances 55 5: DCMB; 6: 3,5-Dichloro-4-anisic acid; 7: Agaricic ester. activated by PSP . active medicinal components are C. versicolor as a strong activities against neurolysin. The agaricoglyceride A just shows to Ontreat the cancer whole, and enhance the ction of agaricoglycerides and related extracellularbiological response and intracellular modifiers calledpoly medicinal mushroom is widely used Many studies suggested that the produ saccharopeptidesprotein-bound polysaccharides. of C. versicolor Both the main bioactive components pos in the genus Agaricus46–48 and other are physiologically active as bio- immune system. Its PSK and PSP are generametabolites and families, in culture such is widespreadas Triticum, - Psathyrella, Hypholoma49,50 and - Evensessing so, the anti-tumour, clinical applications antimicrobial, need Stropharia, are able to synthesise peptidelogical response preparations modifiers. of C. versicolor The best furtherhepato-protective study. and analgesic effects. these aromatic triglycerides. known commercial polysaccharo- The genus Agaricus generally has Cordyceps an analgesic effect in spite of the are polysaccharopeptide Krestin kinds of effective ingredients and the been(PSK) andinvestigated polysaccharopeptide for possessing (PSP). Cordyceps is a special genus of ento different modes of action. What is more, PSP and PSK have mogenousAmong the fungi whole that macrofungi forms a fruiting family, body mainly on pupae or larvae58-. Coriolus versicolor potentiationanticancer, 51–55 anti-inflammatory. and The most typical species is Cordyceps Coriolus versicolor, also referred to as antinociceptiveThe PSP from activities the andmushroom immuno sinensis (CS, caterpillar fungus). It C. versicolor has immunomodulatory actthe to turkey-tail stimulate mushroom,the immune contains system. has been used as a drug for cancer is named Dong-Chong-Xia-Cao in Corioluslarge quantities can dramatically of β-glucans regenerate that patientsand anti-tumour56,57 activities,54 studied which the manyChinese, pharmacological which translates actions as winter such and rejuvenate the body. Its most analgesic activity of PSP in the asworm modulation and summer of immune grass. response, CS has . Ng et al. Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

F : Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine

Review

Table 1 Bioactive components/extracts from edible mushrooms with analgesic tion of cell apoptosis, antinociception effect andinhibition so on59–62 of . The tumour effective growth, constituent induc- of antinociception in CS is cordymin, a Edible mushrooms Bioactive components/extracts References of analgesic effect fruiting bodies. Some studies have peptide purified from its culture and Pleurotus pulmonarius β-Glucans [25–32] Pleurotus florida Hydroethanolic extract [34] shown that cordymin inhibits the acetic acid-induced abdominal con- Pleurotus eous Methanol and aqueous extracts [35] hadstriction a peripheralin mice in a dose-dependentantinociceptive Agaricus brasiliensis Fucogalactan (EPF-Ab) [37] effect.manner, In which addition shows to that the cordymin results Agaricus bisporus var. hortensis Fucogalactan (EPF-Ah) [37] for the assessment of the central Agaricus macrospores Agaricoglycerides [43–48] antinociceptiveof the hot-plate testeffect, which cordymin is used Coriolus versicolor Polysaccharopeptides [51–57] time to thermal stimuli63,64. In brief, Cordyceps Cordymin [63–65] significantly inhibited the reaction cordymin has antinociceptive effect Termitomyces albuminosus Crude saponin extract [66] in both peripheral and central Crude polysaccharide extract Inonotus obliquus Methanol extract [67] aspects. Cordymin-1, cordymin-2 Phellinus linteus EtOH extract [68] neurolysinand cordymin-4 has been inhibited reported neurolysin to have analgesicin a dose-dependent properties in animal manner models and65. Lactarius rufus Soluble β-d-glucan [69] Grifola frondosa Agaricoglycerides [70] andAs a CSresult, is an cordymin effective isanalgesic. a potent anti- inflammatory and analgesic medicine Others acid in mice. The results indicated medicines to treat diseases including that PLE had potent antinocicep diabetes and cancer, and to stimulate above but also many others have the immune system. Pain is intuitive theNot onlyeffect the of four analgesia. genuses Lu described et al.66 68-. for feelings of these diseases such as concluded that the dry matter of Moreover,tive effect, Rutheswhich mightet al.69 be studied mediated and Termitomyces foundby its that anti-inflammatory Lactarius rufus actionhad the albuminosus in submerged culture, cancer, inflammation and injuries. itsculture crude broth saponin (DMCB) extract of (CSE) and tive potential of their polysaccharides ofAs applications. a result, the The analgesic active compo effects crude polysaccharide extract (CPE) evaluatedanti-inflammatory using the and formalin antinocicep model.- of edible fungi have a wide range analgesic effects are very clear. In our- 61.8%, 79.0% and 81.6%, respec fruiting bodies of L. rufus produced nents in many mushrooms with tively.inhibited Then the the mouse dates ear illustrated swelling that by Soluble β-d-glucan isolated from P. pulmonarius, A. brasiliensis, A. T. albuminosus possessed the anal- bisporusreview, ediblevar. hortensis, mushrooms A. macrosporus, including potent inhibition of inflammatory69. C. versicolor and CS have been investi - Furthermore,pain caused a byrecent formalin study stated when gated that possessed antinociceptive activegesic activity constituents owing 66to saponins and thatcompared Grifola with frondosa the insoluble has important one - designedpolysaccharides, by Park whichet al., demonstrated are its major and antinociceptive effects in acetic to their bioactive components such that the methanol . extract One study,from and anti-inflammatory effects owing Inonotus obliquus had analgesic polysaccharopeptide and cordymin levelacid-induced of 500 mg/kg pain in mice and70 . Therefore, formalin- as β-glucan, agaricoglyceride A, G.induced frondosa inflammatory may be used pain as anat thealterna dose (Table 1). What is more, there are activity due to the inhibition of iNOS67. barelyas well any as otherside activeeffects components caused by and COX-2 expression via68 foundthe down- that - toxicity of edible mushrooms in regulation of NF-κB bindingPhellinus activity linteus Conclusiontive medicine for inflammatory pain. In addition, Kim et al. the EtOH extract of used in some cultures as traditional trialsvitro and applications. in vivo. However, further (PLE) could significantly reduce the Edible mushrooms have been widely research is required with clinical numbers Licenseeof writhing OAinduced Publishing by acetic London 2013. Creative Commons Attribution License (CC-BY)

F : Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine

Review

Abbreviations list activity. Trends Food Sci Technol. 2007; CPE, crude polysaccharide extract; cultivation, nutritional value, medicinal 18:4–19. 10. Chang ST, Miles PG. Mushrooms: CS, Cordyceps sinensis; CSE, crude effect, and environmental impact. Boca Raton, Florida: CRC Press; 1989.pp.4–6. charide23. Wasonga extracts CG, delay Okoth progression SA, Mukuria of JC, Omwandho CO. Mushroom polysac saponin extract; DMCB, dry matter biology. Concise basics and current carcinogenesis in mice. ethanolic extract; MBH, mediobasal 11. Miles P, Chang S-T. Mushroom 2008;7(2):147–52. of culture broth; HEE, hydro J Exp Ther Oncol. developments. Singapore, New Jersey, hypothalamus; PKC, protein kinase C; valueLondon, of Hong specialty Kong: Worldmushrooms. Scientific; J 1997.Food ratake24. Yatsuzuka (Pleurotus R, Nakanopulmonarius Y, Jiang S, Ueda PSP,PMA, phorbolpolysaccharopeptide; myristate acetate;TRP, Protect.12. Breene 1990;53:883. WM. Nutritional and medicinal Y, Kishi Y, Suzuki Y, et al. Effect of Usuhi- transientPSK, polysaccharopeptide receptor potential. Krestin; ) on sneez- ing and nasal rubbing in BALB/c mice. Biol 13. Johl PP, Sodhi HS, Dhanda S, Kapoor Pharm Bull. 2007 Aug;30(8):1557–60. Acknowledgement J Plant Sci Res. 1995–6;11–12:73. S. Mushrooms as medicine—a review. tumor25. Mizuno activity T, Hagiwaraand some T, propertiesNakamura of T, of different strains of Pleurotus species Ito H, Shimura K, Sumiya T, et al. Anti- Foundation of Ji’nan Science and 14. Obodai M, Vowotor KA. Performance This work was supported by the “Himematsutake,” from the fruiting body ofwater-soluble Agaricus blazei polysaccharides Murill from (201302055). under Ghanian conditions. J Food Technol 1990;54:2889–96. Technology Development Program Afr. 2002;1:98–100. . Agric Biol Chem. References activity15. Tong of HB,a novel Xia polysaccharide FG, Feng K. Structural isolated fromcharacterization the fruiting and bodies in vitro of antitumorPleurotus 26. Toklu HZ, Sener G, Jahovic N, Uslu B, ostreatus. Bioresour Technol. 2009 Feb; damageArbak S, in Yegen rats. Int BÇ. Immunopharmacol. β-Glucan protects Sep;413(6852):203–10.1. Julius D, Basbaum AI. Molecular 100(4):1682–6. 2006against Feb;6(2):156–69. burn-induced oxidative organ mechanisms of nociception. Nature. 2001 SM. Protein kinase C in pain: involve ment2. Velazquez of multiple KT, Mohammad isoforms. H,Pharmacol Sweitzer 16. Garcha HS, Khann PK, Soni GL. 27. Dore CMPG, Azevedo TCG, Souza Res. 2007 Jun;55(6):578–89. - MushroomNutritional biology importance and mushroom of mushroom. prod MCR, Rego LA, Dantas JCM, Silva FRF, In: Chang ST, Buswell JA, Chin S, editors. extractet al. from Anti-inflammatory, Geastrum saccatum antioxidant mush Press; 1993.pp.227–35. - room.and cytotoxic Int Immunopharmacol. actions of β-glucan-rich 2007 3. Scholz J, Woolf CJ. Can we conquer ucts. Hong Kong: The Chinese University Sep;7(9):1160–9. - channels.pain? Nat Neurosci.Handb Exp 2002 Pharmacol. Nov;5:1062–7. 2007; 179:489–505.4. Tominaga M. Nociception and TRP 17. Chang ST. The development of the 2005;12:3–19.mushroom industry in China, with a note 28. Zhang M, Cui SW, Cheung PCK, Wang Q. on possibilities for Africa. Acta Ed Fung. process,Antitumor structural polysaccharides characteristics from mush and- 5. Caterina MJ, Julius D. Sense and antitumorrooms: a reviewactivity. onTrends their Food isolation Sci specificity: a molecular identity for 18. Moreno-Rojas R, Díaz-Valverde MA, Technol. 2007;18:4–19. nociceptors. Curr Opin Neurobiol. 1999 ponderosa).Arroyo BM, Food González Chem. 2004;85:325–30. TJ, Capote CJB. Oct;9(5):525–30. Mineral content of gurumelo (Amanita ER, Baggio CH, Freitas CS, Marcon R, 61:835–56.6. McCleskey EW, Gold MS. Ion channels 29. Smiderle FR, Olsen LM, Carbonero of nociception. Annu Rev Physiol. 1999; 19. Manzi P, Gambelli L, Marconi S, properties in a rodent model of a tiveVivanti study. V, PizzoferratoFood Chem. 1999;65:477–82.L. Nutrients in edi- et al. Anti-inflammatory and analgesic 7. Baron A, Deval E, Salinas M, Lingueglia ble mushrooms: an inter-species compara from Pleurotus pulmonarius. Eur J E, Voilley N, Lazdunski M. Protein kinase ER, Marcon R, Baggio CH, Freitas CS, et al. (1→3),(1→6)-linked β-glucan isolated C stimulates the acid-sensing ion channel 20. Smiderle FR, Olsen LM, Carbonero 277(52):50463–8.ASIC2a via the PDZ domain-containing Pleurotus pulmonarius: structure and Pharmacol. 2008 Nov;597(1–3):86–91. protein PICK1. J Biol Chem. 2002 Dec; antinociceptiveA 3-O-methylated effect. mannogalactan Phytochemistry. from 30. Baggio CH, Freitas CS, Marcon R, Calixto JB. Mechanisms involved in the Pleurotusde Paula Wernera pulmonarius MF, Rae is GA,possibly Smiderle related FR, nociception8. Ferreira J, produced Triches KM,by Medeirosperipheral R, toet al.protein Antinociception kinase C inhibition. of β-d-glucan Int Jfrom Biol protein kinase c activation in mice. Pain. role2008 ofNov;69(15):2731–6. polysaccharides derived from 2005 Sep;117(1–2):171–81. medicinal21. Smith mushrooms JE, Sullivan in R, cancer Rowan treatment N. The Macromol. 2012 Apr;50(3):872–7. Int J Med Mushrooms. 2003;5:217–23. 31. Baggio CH, Freitas CS, Martins DF, of9. Premkumar transient receptor LS, Raisinghani potential melastatin M, Pingle programs: current perspectives (review). Mazzardo L, Smiderle FR, Sassaki GL, SC, Long C, Pimentel F. Down-regulation Pleurotuset al. Antinociceptive pulmonarius in effects models of of (1/3), acute 22. Zhang M, Cui SW, Cheung PCK, Wang Q. and(1/6)-linked neuropathic β-glucan pain in mice: isolated evidence from 11322–9.8 by protein kinase C-mediated dephos- structuralAntitumor characteristics polysaccharides and from antitumor mush- for a role for glutamatergic receptors phorylation. J Neurosci. 2005 Dec;25(49): rooms: a review on their isolation process,

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

F : Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine

Review

fruiting bodies of the fungus, Hericium 11(10):965–71. and cytokine pathways. J Pain. 2010 Oct; 341(5):645–9. polysaccharide, PSK (review). Anticancer erinaceus. Carbohydr Res. 2006 Apr; Res. 1991 Mar–Apr;11(2):993–1000. 32. Roy SK, Das D, Mondal S, Maiti D, polysaccharides53. Li XY, Wang JF,peptides Zhu PP, isolated Liu L, Ge from JB, Bhunia B, Maiti TK, et al. Structural studies analgesic43. Stadler triglycerides M, Hellwig V, Mayer-Bartschmidfrom cultures of CoriolusYang SX. versicolor Immune enhancement of a anof anedible immunoenhancing mushroom, Pleurotus water-soluble florida, AgaricusA, Denzer macrospores D, Wiese B, Burkhardtand other N.basidio Novel glucan isolated from hot water extract of mycetes as selective inhibitors of neuroly . Acta Pharmacol Sinica. - peptide1990 Nov;11(6):542–5. from the mushroom Coriolus cultivar Assam Florida. Carbohydr Res. - versicolor54. Ngand possesses TB, Chan WY.analgesic Polysaccharo activity- Methanol2009 Dec;344(18):2596–601. extract of the oyster mushroom, sin. J Antibiot. 2005 Dec;58(12):775–86. but does not produce adverse effects on Pleurotus33. Jose N, florida Ajith TA, Janardhanan KK. 44. Vincent B, Dive V, Yiotakis A, Smadja female reproductive or embryonic devel and platelet aggregation. Phytother Res. inhibitorsC, Maldonado of endopeptidase R, Vincent JP, 3.et 4. al. 24. Phos 15- opment in mice gen. Pharmacology. 1997; 2004 Jan;18(1):43–6., inhibits inflammation andphorus-containing 3. 4. 24.16: effect peptides on neurotensin as mixed 29(2):269–73. - degradation in vitro and in vivo. Brit J Pharmacol. 1995 Jul;115(6):1053–63. 34. Ganeshpurkar A, Rai G. Experimental 55. Shan G, Hui-Qin Z, Wei-Ping Y, mushroomevaluation Pleurotus of analgesic florida and. Indian anti- J producedQi-Zhang by Y, Codolus Yi Z, Zhen-Lun versicolor G,polysac et al. Pharmacol.inflammatory 2013 potentialJan–Feb;45(1):66–70. of Oyster 45. Jirácek J, Yiotakis A, Vincent B, Checler F, Involvement of interleukin-2 in analgesia peptidaseDive V. Development neurolysin ofusing the a first schematic potent Sinica. 1998 Jan;19(1):67–70. - approachand selective based inhibitor on combinatorial of the zinc chemendo- charide peptides. Acta Pharmacologica gesic35. Suseem activity SR,of ethyl Saral acetate, MA, Reddy methanol NP, istry of phosphinic peptides. J Biol Chem. tests of PSP in the treatment of lung andGregory aqueous M. extracts Evaluation of Pleurotus of the analeous - 56. Liao ML, Zhao JM. Stage 11 clinical

Feb;4(2):117–20. 1996 Aug;271(32):19608–11. siumcancer. on In: PSP. Yang Shanghai, QY, Kwok China: CY, editors.Fudan mushroom. Asian Pac J Trop Med. 2011 46. Hirotani M, Sai K, Nagai R, Hirotani S, UniversityProceedings Press; of 1993.pp.243–56. international sympo theTakayanagi cultured H,mycelia Yoshikawa of the T. fungus Blazeispirane Agaricus Pleurotus36. Vasudewa ostreatus NS, Abeytunga, an edible mushroomDT, Ratna- blazeiand protoblazeispirane derivatives from research of the effect of PSP on the insooriya rats. Pharm WD. Antinociceptive Biol. 2007;45:533–40. activity of 589–95. immunological57. Shi JH, Chen function T, Lian of stomach ZR. Clinical cancer . Phytochemistry. 2002 Nov;61(5): patients during operation and chemo therapy. In: Change ST, editor. Proceedings Structure37. Komuraa of AgaricusDL, Carbonerob spp. fucogalactans ER, Grachera 47. Hirotani M, Sai K, Hirotani S, Yoshikawa of international symposium on PSP.- AHP, Baggio CH, Freitas CS, Marcon R, et al. T. Blazeispirols B, C, E and F, des-A- Shanghai, China: Fudan University Press; ciceptive properties. Bioresour Technol. Phytochemistry.ergostane-type compounds2002 Mar;59(5):571–7. from the cul- 1993.pp.232–40. and their anti-inflammatory and antino- tured mycelia of the fungus Agaricus blazei. matory and related pharmacological method2010 Aug;101(15):6192–9. for the permethylation of carbohy 48. Zapf S, Anke T, Dasenbrock H, activities58. So-Young of cultured W, Eun-Hee mycelia P. Anti-inflamand fruiting- drates.38. Ciucanu Carbohydr I, Kerek Res. F. 1984;131:209–17.A simple and rapid Steglich W. Antifungal metabolites from bodies of Cordyceps militaris. Seoul, - ascomycetesAgaricus sp. 89139. and Bioengeneering.basidiomycetes 1:92. for Paiva SM, Carbonero ER, Córdova 49. Hautzel R, Anke H. Screening of Sookmyung Women’s University. MM,39. Ruthes Baggio AC, CH, Rattmann et al. Agaricus YD, Malquevicz- bisporus introduction of the gibberrellic acid South Korea: College of Pharmacy, inducedplant growth de novo regulating synthesis of substances: hydrolytic SC, Lim CY, Shiao MS. Regulation of and pharmacological approaches. Carbo 59. Kuo YC, Tsai WJ, Wang JY, Chang hydrfucogalactan: Polym. 2013 structural Jan;92(1):184–91. characterization tion by the immunomodulatory agents - 1990;45C:1093–8.enzymes in embryoless seeds of Triticum frombronchoalveolar Cordyceps sinensis lavage . fluids Life Sci. cell 2001 func- et al. Lentinus edodes heterogalactan: aestivum as test system. Z Naturforsch. Jan;68(9):1067–82. 40. Carbonero ER, Gracher AHP, Komura, from50. Swarts Hypholoma HJ, Verhagen elongatum FJM,. Phytochem Field JA, antinociceptive and anti-inflammatory effe istry.Wijnberg 1998;49:203–6. JBPA. Trichlorinated phenols tumor60. Kuo cells YC, Linin CordycepsCY, Tsai WJ, sinensis Wu CL, otherChen cts. Food Chem. 2008 Dec;111(3):531–7. - thanCF, Shiao cordycepin MS. Growth and inhibitorspolysaccharides. against tral41. Fan fucogalactan J, Zhang J,from Tang the Q, myceliumLiu Y, Zhang of Studies of constituents of higher fungi of Cancer Invest. 1994;12(6):611–5. CoprinusA, Pan Y. Structuralcomatus. Carbohydr elucidation Res. of a 2006 neu- 51. Cho HJ, Shim MJ, Choi EC, Kim BK. Jul;341(9):1130–4. tumor constituents of Coriolus versicolor. Korea LVII. Comparison of various anti- from61. Bok the JW, mycelia Lermer of L, ChiltonCordyceps J, Klingeman sinensis. Yang Y, Liu Y, et al. Structural elucida HG, Towers GH. Antitumor sterols tion42. Zhang of a novel A, fucogalactan Zhang J, Tang that Q, contains Jia W, TanumaKor J Mycol. SI. 1988;16:162–74.Induction of immunopo - 52. Sakagami H, Aoki T, Simpson A, Phytochemistry. 1999 Aug;51(7):891–8.Cordyceps sinensis - 62. Yang LY, Huang WJ, Hsieh HG, Lin CY. 3-O-methyl rhamnose isolated from the tentiation activity by a protein-bound H1-A extracted from

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

F : Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine

Review

suppresses the proliferation of human additional neurotensin receptor subtypes: mesangial cells and promotes apoptosis, neurotensin analogues that distinguish probably by inhibiting the tyrosine phos related68. Kim pharmacological SH, Song YS, Kim activities SK, Kim BC,of thermia and antinociception. Brain Res. Lim CJ, Park EH. Anti-inflammatory and Med. 2003 Jan;141(1):74–83. - 1998between May;792(2):246–52. neurotensin-mediated hypo- Phellinus linteus. J Ethnopharmacol. phorylation of Bcl-2 and Bcl-XL. J Lab Clin 2004the n-BuOH Jul;93(1):141–6. subfraction of mushroom Schneider C. The abdominal constriction response63. Collier and HO, its Dinneensuppression JC, Johnsonby analgesic CA, 66. Lu YY, Ao ZH, Lu ZM, Xu HY, Zhang drugs in the mouse. Br J Pharmacol cultureXM, Dou broth WF, of et Termitomyces al. Analgesic albuminosus and anti- et69. Ruthes al. Lactarius AC, Carbonerorufus ER, Córdova Chemother. 1968;32:295–310. andinflammatory its extracts. effects J Ethnopharmacol. of the dry matter 2008 of glucans:MM, Baggio structure, CH, Santos antinociceptive ARS, Sassaki andGL, (1→3),(1→6)-β-d-

64. Qian GM, Pan GF, Guo JY. Anti- Dec;120(3):432–6. anti-inflammatory effects. Carbohydr medicinalinflammatory mushroom and antinociceptive Cordyceps sinensis effects. 67. Park YM, Won JH, Kim YH, Choi JW, Polym. 2013 Apr;94(1):129–36. of cordymin, a peptide purified from the ofPark the HJ, methanol Lee KT. extract In vivo of andInonotus in vitro obliquus anti-. cerides,70. Han extracted C, Cui B. from Pharmacological Grifola frondosa and, in inflammatory and anti-nociceptive effects pharmacokinetic studies with agaricogly SouderNat Prod T, Res. Richelson 2012;26(24):2358–62. E. Evidence for 120–8. 65. Tyler BM, Cusack B, Douglas CL, J Ethnopharmacol. 2005 Oct;101(1–3): animal models of pain and inflammation. Inflammation. 2012 Aug;35(4):1269–75.

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

F : Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine