Therapeutic potentials of n-hexane extracts of the three medicinal mushrooms regarding their anti-colon cancer, antioxidant, and hypocholesterolemic capabilities
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Abstract. Daba GM, Elkhateeb WA, El-Dien AN, Ahmed EF, El Hagrassi AM Fayad W, Wen TC. 2020. Therapeutic potentials of n-hexane extracts of the three medicinal mushrooms regarding their anti-colon cancer, antioxidant, and hypocholesterolemic capabilities. Biodiversitas 21: 2437-2445. Evaluating in vitro biological activities of the medicinal mushrooms Hericium erinaceus, Metacordyceps neogunnii, and Dictyophora indusiata n-hexane extracts revealed their capabilities as promising therapeutic sources. By assessing their DPPH radical scavenging activities, D. indusiata extract exhibited the highest antioxidant activity (87.8±1.2%) followed by H. erinaceus, then M. neogunnii 84.9±1.6%, and 77.3±1.3%, respectively. On the other hand, M. neogunnii extract exerted promising anti-colon cancer (68.6±3.6% cytotoxicity) against HCT116 human colon cancer cell lines at concentration 100 ?g/mL, whereas H. erinaceus and D. indusiata extracts exhibited weaker cytotoxic effects (18.3±1.7%, and 19.3±3.2%, respectively) using the same concentration. Investigating cholesterol reduction activities (CRA%) of the extracts revealed that activity depends on both extract concentration and incubation period. After 96 h of incubation at room temperature, all extracts exerted potent in vitro hypocholesterolemic activities (100±0% reduction in cholesterol concentration). Performing GC-Ms analyses on the extracts revealed presence of 22 compounds in D. indusiata extract, while 29 compounds were detected in M. neogunnii extract, and 33 in H. erinaceus extract. Most of compounds were esters of fatty acids. Results in this study encourage using these mushrooms as functional foods, and highlight the need for conducting further in vivo studies to support their use in pharmaceutical industry.
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References
8. References
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2. AM Y. 2017. Anticancer potential of Hericium erinaceus extracts against particular human cancer cell lines. Microbial Biosystems 2(1): 9-20.
3. Asghar SF, Choudahry MI. 2011. Gas chromatography-mass spectrometry (GC-MS) analysis of petroleum ether extract (oil) and bio-assays of crude extract of Iris germanica. International Journal of Genetics and Molecular Biology 3(7): 95-100.
4. Bashir R, Palombo E, Mahon P. 2017. Bioactive profile of Australian native Cordyceps gunnii 5th International Conference and Exhibition on Pharmacognosy, Phytochemistry & Natural Products, Melbourne, Australia.
5. Belakhdar G, Benjouad A, Abdennebi EH. 2015. Determination of some bioactive chemical constituents from Thesium humile Vahl. J Mater Environ Sci. 6(10): 2778-2783.
6. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. 2014. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiological reviews 94(2): 329-354.
7. Chang ST, Miles PG. 1989. Edible Mushrooms and their Cultivations. Boca Raton, FL: CRC Press Inc.
8. Charumathy M, Sudha G, Packialakshmi B. 2017 In vitro antioxidant activity analysis in Hericium erinaceus pers fruiting bodies International Journal of Pharmacy & Technology 9: 30118-30128.
9. Dommels YE, Haring MM, Keestra NG, Alink GM, van Bladeren PJ, van Ommen B. 2003. The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE 2 synthesis and cytotoxicity in human colorectal carcinoma cell lines. Carcinogenesis 24(3): 385-392.
10. Elkhateeb WA, Daba GM, Sheir D, El-Dein AN, Fayad W, Elmahdy EM, Shaheen MN, Thomas PW, Wen TC. 2019c. GC-MS analysis and in-vitro hypocholesterolemic, anti-rotavirus, anti-human colon carcinoma activities of the crude extract of a Japanese Ganoderma spp. Egyptian Pharmaceutical Journal 18: 102-110.
11. Elkhateeb WA, Daba GM, Thomas PW, Wen TC. 2019a. Medicinal mushrooms as a new source of natural therapeutic bioactive compounds. Egyptian Pharmaceutical Journal 18(2): 88-101.
12. Elkhateeb WA, Elnahas MO, Thomas PW, Daba GM. 2019b. To Heal or Not to Heal? Medicinal Mushrooms Wound Healing Capacities. ARC Journal of Pharmaceutical Sciences 5(4): 28-35.
13. Elkhateeb WA, Elnahas MO, Thomas PW, Daba GM. 2020. Trametes Versicolor and Dictyophora Indusiata, Champions of medicinal mushrooms. Open access Journal of pharmaceutical research 4(1): 1-7.
14. Golomb BA, Evans MA. 2008. Statin adverse effects. American Journal of Cardiovascular Drugs 8(6): 373-418.
15. Gong M, An J, Lu HZ, Wu CF, Li YJ, Cheng JQ, et al. 2004. Effects of denaturation and amino acid modification on fluorescence spectrum and hemagglutinating activity of Hericium erinaceum lectin. Acta Biochim Biophys Sin. 36(5): 343-50.
16. Han S, Ma C, Hu M, Wang Y, Ma F, Tao N, Qin Z. 2017. A polysaccharide from Dictyophora indusiata inhibits the immunosuppressive function of cancer?associated fibroblasts. Cell biochemistry and function 35(7): 414-419.
17. Horrobin DF, Ziboh VA. 1997. The importance of linoleic acid metabolites in cancer metastasis and in the synthesis and actions of 13-HODE. Adv. Exp. Med Biol. 433: 291-294.
18. Jeong SM, Choi S, Kim K, Kim SM, Lee G, Park SY, Kim YY, Son JS, Yun JM, Park SM. 2018. Effect of change in total cholesterol levels on cardiovascular disease among young adults. Journal of the American Heart Association 7(12): p.e008819.
19. Jiang S, Wang Y, Zhang X. 2016. Comparative studies on extracts from Hericium erinaceus by different polarity reagents to gain higher antioxidant activities. Experimental and therapeutic medicine 12(1): 513-517.
20. Katerji M, Filippova M, Duerksen-Hughes P. 2019. Approaches and Methods to Measure Oxidative Stress in Clinical Samples: Research Applications in the Cancer Field. Oxidative medicine and cellular longevity, 2019.
21. Kim SP, Nam SH, Friedman M. 2013. Hericium erinaceus (Lion’s Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-tansplanted mice. Journal of agricultural and food chemistry 61(20): 4898-4904.
22. Krishnamoorthy K, Subramaniam P. 2014. Phytochemical profiling of leaf, stem, and tuber parts of Solena amplexicaulis (Lam.) Gandhi using GC-MS. International scholarly research notices 1-13.
23. Kumar PP, Kumaravel S, Lalitha C. 2010. Screening of antioxidant activity, total phenolics and GC-MS study of Vitex negundo. African J Biochem Res. 4(7): 191-5.
24. Lee B, Kim J, Kang YM, Lim J, Kim Y, Lee M, Min-Ho J, Chang-Bum A, Jae-Young Je. 2010. Antioxidant activity and ?–aminobutyric acid (GABA) content in sea tangle fermented by Lactobacillus brevis BJ20 isolated from traditional fermented foods. Food Chem. 122: 271–276.
25. Lew SY, Yow YY, Lim LW, Wong KH. 2019. Antioxidant-mediated protective role of Hericium erinaceus (Bull.: Fr.) Pers. against oxidative damage in fibroblasts from Friedreich’s ataxia patient. Food Science and Technology 13: 1-9.
26. Li G, Yu K, Li F, Xu K, Li J, He S, Cao S, Tan G. 2014. Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers. Journal of ethnopharmacology 153(2): 521-530.
27. Li Y, Zhang G, Ng TB, Wang H. 2010. A novel lectin with antiproliferative and HIV-1 reverse transcriptase inhibitory activities from dried fruiting bodies of the monkey head mushroom Hericium erinaceum. BioMed Research International 2010: 716515
28. Liang ZQ. 1985. Isolation and identification of the conidial stage of Cordyceps gunnii. Acta Mycologica Sinica 4 (3): 162–166.
29. Liao W, Lu Y, Fu J, Ning Z, Yang J, Ren J. 2015. Preparation and characterization of Dictyophora indusiata polysaccharide–zinc complex and its augmented antiproliferative activity on human cancer cells. Journal of agricultural and food chemistry 63(29): 6525-6534.
30. Liu Y, Zhang Y, Zhang X, Xu Q, Yang X, Xue C. 2017. Medium-chain fatty acids reduce serum cholesterol by regulating the metabolism of bile acid in C57BL/6J mice. Food & function 8(1): 291-298.
31. Mizuno T, Wasa T, Ito H, Suzuki C, Ukai N. 1992. Antitumor-active polysaccharides isolated from the fruiting body of Hericium erinaceum, an edible and medicinal mushroom called yamabushitake or houtou. Biosci Biotechnol Biochem 56(2): 347-8.
32. Mujeeb F, Bajpai P, Pathak N. 2014. Phytochemical evaluation, antimicrobial activity, and determination of bioactive components from leaves of Aegle marmelos. BioMed research international, 2014.
33. Narayanan A, Baskaran S, Amalaradjou M, Venkitanarayanan K. 2015. Anticarcinogenic properties of medium chain fatty acids on human colorectal, skin and breast cancer cells in vitro. International journal of molecular sciences 16(3): 5014-5027.
34. Oyetayo VO, Dong CH, Yao YJ. 2009. Antioxidant and antimicrobial properties of aqueous extract from Dictyophora indusiata. The Open Mycology Journal 3(1): 20-26.
35. Pan J, Zhang Q, Zhang Y, Ouyang Z, Zheng Q, Zheng R. 2005. Oxidative stress in heroin administered mice and natural antioxidants protection. Life Sci. 27, 77(2), 1: 83-93.
36. Peyrat?Maillard MN, Cuvelier ME, Berset C. 2003. Antioxidant activity of phenolic compounds in 2, 2??azobis (2?amidinopropane) dihydrochloride (AAPH)?induced oxidation: Synergistic and antagonistic effects. Journal of the American Oil Chemists' Society 80(10): p.1007.
37. Pinto ME, Araujo SG, Morais MI, Sá NP, Lima CM, Rosa CA, Siqueira EP, Johann S, Lima LA. 2017. Antifungal and antioxidant activity of fatty acid methyl esters from vegetable oils. Anais da Academia Brasileira de Ciências 89(3): 1671-1681.
38. Rahman MA, Abdullah N, Aminudin N. 2014. Inhibitory effect on in vitro LDL oxidation and HMG Co-A reductase activity of the liquid-liquid partitioned fractions of Hericium erinaceus (Bull.) Persoon (lion’s mane mushroom). BioMed research international 2014.
39. Sammar M, Abu Farich B, Rayan I, Falah M, Rayan A. 2019. Correlation between cytotoxicity in cancer cells and free radical scavenging activity: In vitro evaluation of 57 medicinal and edible plant extracts. Oncology Letters 18(6): 6563-6571.
40. She X, Yao T, Ding L, Gan Z, Tang M, Han Y. 2019. Identification and Analysis of Secondary Metabolites from CH3OH/H2O Extract of Metacordyceps neogunnii. In E3S Web of Conferences (Vol. 118, p. 01027). EDP Sciences.
41. Sullivan, R., Smith, J.E., Rowan, N.J. 2006. Medicinal mushrooms and cancer therapy: translating a traditional practice into Western medicine. Perspectives in biology and medicine 49(2): 159-170.
42. Thompson PD, Panza G, Zaleski A, Taylor B. 2016. Statin-associated side effects. Journal of the American College of Cardiology. 67: 2395-2410.
43. Thongbai B, Rapior S, Hyde KD, Wittstein K, Stadler M. 2015. Hericium erinaceus, an amazing medicinal mushroom. Mycological Progress 14(10): p.91.
44. Viswanathan SG. 2014. GC-MS Analysis of Phytocomponents in Spermacoce articularis L. f. leaf. Research in Pharmacy 4(4): 01-07.
45. Wang XY, Yin JY, Nie SP, Xie, M.Y. 2018. Isolation, purification and physicochemical properties of polysaccharide from fruiting body of Hericium erinaceus and its effect on colonic health of mice. International journal of biological macromolecules 107: 1310-1319.
46. Wei LS, Wee W, Siong JY, Syamsumir DF. 2011. Characterization of anticancer, antimicrobial, antioxidant properties and chemical compositions of Peperomia pellucida leaf extract. Acta Medica Iranica 670-674.
47. Wen TC, Xiao YP, Han YF, Huang SK, Zha LS, Hyde KD, Kang JC. 2017. Multigene phylogeny and morphology reveal that the Chinese medicinal mushroom Metacordyceps neogunnii sp. nov. Phytotaxa 302(1): 27-39.
48. World health organization cardiovascular-diseases-(cvds) fact sheet, 17 May 2017. http://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
49. World health organization fact sheet, 12 September 2018. https://www.who.int/news-room/fact-sheets/detail/cancer.
50. Xiao Z, Storms R, Tsang A. 2006. A quantitative starch–iodine method for measuring alphaamylase and glucoamylase activities. Analytical biochemistry 351(1): 146-148.
51. Yang CH, Kao YH, Huang KS, Wang CY, Lin LW. 2012. Cordyceps militaris and mycelial fermentation induced apoptosis and autophagy of human glioblastoma cells. Cell death & disease 3: e431.
52. Yeong LH, Nancy KG, Micheal WP. 1989. Newly recognized nticarcinogenic fatty acids: identification and quantification in natural and processed cheeses: J. Agric. Food Chem. 37: 75-81.
53. Yim MH, Shin JW, Son JY, Oh SM, Han SH, Cho JH, et al. 2007. Soluble components of Hericium erinaceum induce NK cell activation via production of interleukin-12 in mice splenocytes. Acta Pharmacol Sin. 28(6): 901-907.
54. Zhang J, Shi R, Li H, Xiang Y, Xiao L, Hu M, Ma F, Ma CW, Huang Z. 2016. Antioxidant and neuroprotective effects of Dictyophora indusiata polysaccharide in Caenorhabditis elegans. Journal of ethnopharmacology 192: 413-422.
55. Zhang Z, Lv G, Pan H, Pandey A, He W, Fan L. 2012. Antioxidant and hepatoprotective potential of endo-polysaccharides from Hericium erinaceus grown on tofu whey. Int J Biol Macromol. 51(5): 1140-1146.
1. Adams RP. 1995. Identification of Essential Oil Components By Gas Chromatography/ Mass Spectroscopy, Allured Publishing Corporation, Carol Stream ash samples. Journal of Chromatography A 985: 137-145.
2. AM Y. 2017. Anticancer potential of Hericium erinaceus extracts against particular human cancer cell lines. Microbial Biosystems 2(1): 9-20.
3. Asghar SF, Choudahry MI. 2011. Gas chromatography-mass spectrometry (GC-MS) analysis of petroleum ether extract (oil) and bio-assays of crude extract of Iris germanica. International Journal of Genetics and Molecular Biology 3(7): 95-100.
4. Bashir R, Palombo E, Mahon P. 2017. Bioactive profile of Australian native Cordyceps gunnii 5th International Conference and Exhibition on Pharmacognosy, Phytochemistry & Natural Products, Melbourne, Australia.
5. Belakhdar G, Benjouad A, Abdennebi EH. 2015. Determination of some bioactive chemical constituents from Thesium humile Vahl. J Mater Environ Sci. 6(10): 2778-2783.
6. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. 2014. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiological reviews 94(2): 329-354.
7. Chang ST, Miles PG. 1989. Edible Mushrooms and their Cultivations. Boca Raton, FL: CRC Press Inc.
8. Charumathy M, Sudha G, Packialakshmi B. 2017 In vitro antioxidant activity analysis in Hericium erinaceus pers fruiting bodies International Journal of Pharmacy & Technology 9: 30118-30128.
9. Dommels YE, Haring MM, Keestra NG, Alink GM, van Bladeren PJ, van Ommen B. 2003. The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE 2 synthesis and cytotoxicity in human colorectal carcinoma cell lines. Carcinogenesis 24(3): 385-392.
10. Elkhateeb WA, Daba GM, Sheir D, El-Dein AN, Fayad W, Elmahdy EM, Shaheen MN, Thomas PW, Wen TC. 2019c. GC-MS analysis and in-vitro hypocholesterolemic, anti-rotavirus, anti-human colon carcinoma activities of the crude extract of a Japanese Ganoderma spp. Egyptian Pharmaceutical Journal 18: 102-110.
11. Elkhateeb WA, Daba GM, Thomas PW, Wen TC. 2019a. Medicinal mushrooms as a new source of natural therapeutic bioactive compounds. Egyptian Pharmaceutical Journal 18(2): 88-101.
12. Elkhateeb WA, Elnahas MO, Thomas PW, Daba GM. 2019b. To Heal or Not to Heal? Medicinal Mushrooms Wound Healing Capacities. ARC Journal of Pharmaceutical Sciences 5(4): 28-35.
13. Elkhateeb WA, Elnahas MO, Thomas PW, Daba GM. 2020. Trametes Versicolor and Dictyophora Indusiata, Champions of medicinal mushrooms. Open access Journal of pharmaceutical research 4(1): 1-7.
14. Golomb BA, Evans MA. 2008. Statin adverse effects. American Journal of Cardiovascular Drugs 8(6): 373-418.
15. Gong M, An J, Lu HZ, Wu CF, Li YJ, Cheng JQ, et al. 2004. Effects of denaturation and amino acid modification on fluorescence spectrum and hemagglutinating activity of Hericium erinaceum lectin. Acta Biochim Biophys Sin. 36(5): 343-50.
16. Han S, Ma C, Hu M, Wang Y, Ma F, Tao N, Qin Z. 2017. A polysaccharide from Dictyophora indusiata inhibits the immunosuppressive function of cancer?associated fibroblasts. Cell biochemistry and function 35(7): 414-419.
17. Horrobin DF, Ziboh VA. 1997. The importance of linoleic acid metabolites in cancer metastasis and in the synthesis and actions of 13-HODE. Adv. Exp. Med Biol. 433: 291-294.
18. Jeong SM, Choi S, Kim K, Kim SM, Lee G, Park SY, Kim YY, Son JS, Yun JM, Park SM. 2018. Effect of change in total cholesterol levels on cardiovascular disease among young adults. Journal of the American Heart Association 7(12): p.e008819.
19. Jiang S, Wang Y, Zhang X. 2016. Comparative studies on extracts from Hericium erinaceus by different polarity reagents to gain higher antioxidant activities. Experimental and therapeutic medicine 12(1): 513-517.
20. Katerji M, Filippova M, Duerksen-Hughes P. 2019. Approaches and Methods to Measure Oxidative Stress in Clinical Samples: Research Applications in the Cancer Field. Oxidative medicine and cellular longevity, 2019.
21. Kim SP, Nam SH, Friedman M. 2013. Hericium erinaceus (Lion’s Mane) mushroom extracts inhibit metastasis of cancer cells to the lung in CT-26 colon cancer-tansplanted mice. Journal of agricultural and food chemistry 61(20): 4898-4904.
22. Krishnamoorthy K, Subramaniam P. 2014. Phytochemical profiling of leaf, stem, and tuber parts of Solena amplexicaulis (Lam.) Gandhi using GC-MS. International scholarly research notices 1-13.
23. Kumar PP, Kumaravel S, Lalitha C. 2010. Screening of antioxidant activity, total phenolics and GC-MS study of Vitex negundo. African J Biochem Res. 4(7): 191-5.
24. Lee B, Kim J, Kang YM, Lim J, Kim Y, Lee M, Min-Ho J, Chang-Bum A, Jae-Young Je. 2010. Antioxidant activity and ?–aminobutyric acid (GABA) content in sea tangle fermented by Lactobacillus brevis BJ20 isolated from traditional fermented foods. Food Chem. 122: 271–276.
25. Lew SY, Yow YY, Lim LW, Wong KH. 2019. Antioxidant-mediated protective role of Hericium erinaceus (Bull.: Fr.) Pers. against oxidative damage in fibroblasts from Friedreich’s ataxia patient. Food Science and Technology 13: 1-9.
26. Li G, Yu K, Li F, Xu K, Li J, He S, Cao S, Tan G. 2014. Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers. Journal of ethnopharmacology 153(2): 521-530.
27. Li Y, Zhang G, Ng TB, Wang H. 2010. A novel lectin with antiproliferative and HIV-1 reverse transcriptase inhibitory activities from dried fruiting bodies of the monkey head mushroom Hericium erinaceum. BioMed Research International 2010: 716515
28. Liang ZQ. 1985. Isolation and identification of the conidial stage of Cordyceps gunnii. Acta Mycologica Sinica 4 (3): 162–166.
29. Liao W, Lu Y, Fu J, Ning Z, Yang J, Ren J. 2015. Preparation and characterization of Dictyophora indusiata polysaccharide–zinc complex and its augmented antiproliferative activity on human cancer cells. Journal of agricultural and food chemistry 63(29): 6525-6534.
30. Liu Y, Zhang Y, Zhang X, Xu Q, Yang X, Xue C. 2017. Medium-chain fatty acids reduce serum cholesterol by regulating the metabolism of bile acid in C57BL/6J mice. Food & function 8(1): 291-298.
31. Mizuno T, Wasa T, Ito H, Suzuki C, Ukai N. 1992. Antitumor-active polysaccharides isolated from the fruiting body of Hericium erinaceum, an edible and medicinal mushroom called yamabushitake or houtou. Biosci Biotechnol Biochem 56(2): 347-8.
32. Mujeeb F, Bajpai P, Pathak N. 2014. Phytochemical evaluation, antimicrobial activity, and determination of bioactive components from leaves of Aegle marmelos. BioMed research international, 2014.
33. Narayanan A, Baskaran S, Amalaradjou M, Venkitanarayanan K. 2015. Anticarcinogenic properties of medium chain fatty acids on human colorectal, skin and breast cancer cells in vitro. International journal of molecular sciences 16(3): 5014-5027.
34. Oyetayo VO, Dong CH, Yao YJ. 2009. Antioxidant and antimicrobial properties of aqueous extract from Dictyophora indusiata. The Open Mycology Journal 3(1): 20-26.
35. Pan J, Zhang Q, Zhang Y, Ouyang Z, Zheng Q, Zheng R. 2005. Oxidative stress in heroin administered mice and natural antioxidants protection. Life Sci. 27, 77(2), 1: 83-93.
36. Peyrat?Maillard MN, Cuvelier ME, Berset C. 2003. Antioxidant activity of phenolic compounds in 2, 2??azobis (2?amidinopropane) dihydrochloride (AAPH)?induced oxidation: Synergistic and antagonistic effects. Journal of the American Oil Chemists' Society 80(10): p.1007.
37. Pinto ME, Araujo SG, Morais MI, Sá NP, Lima CM, Rosa CA, Siqueira EP, Johann S, Lima LA. 2017. Antifungal and antioxidant activity of fatty acid methyl esters from vegetable oils. Anais da Academia Brasileira de Ciências 89(3): 1671-1681.
38. Rahman MA, Abdullah N, Aminudin N. 2014. Inhibitory effect on in vitro LDL oxidation and HMG Co-A reductase activity of the liquid-liquid partitioned fractions of Hericium erinaceus (Bull.) Persoon (lion’s mane mushroom). BioMed research international 2014.
39. Sammar M, Abu Farich B, Rayan I, Falah M, Rayan A. 2019. Correlation between cytotoxicity in cancer cells and free radical scavenging activity: In vitro evaluation of 57 medicinal and edible plant extracts. Oncology Letters 18(6): 6563-6571.
40. She X, Yao T, Ding L, Gan Z, Tang M, Han Y. 2019. Identification and Analysis of Secondary Metabolites from CH3OH/H2O Extract of Metacordyceps neogunnii. In E3S Web of Conferences (Vol. 118, p. 01027). EDP Sciences.
41. Sullivan, R., Smith, J.E., Rowan, N.J. 2006. Medicinal mushrooms and cancer therapy: translating a traditional practice into Western medicine. Perspectives in biology and medicine 49(2): 159-170.
42. Thompson PD, Panza G, Zaleski A, Taylor B. 2016. Statin-associated side effects. Journal of the American College of Cardiology. 67: 2395-2410.
43. Thongbai B, Rapior S, Hyde KD, Wittstein K, Stadler M. 2015. Hericium erinaceus, an amazing medicinal mushroom. Mycological Progress 14(10): p.91.
44. Viswanathan SG. 2014. GC-MS Analysis of Phytocomponents in Spermacoce articularis L. f. leaf. Research in Pharmacy 4(4): 01-07.
45. Wang XY, Yin JY, Nie SP, Xie, M.Y. 2018. Isolation, purification and physicochemical properties of polysaccharide from fruiting body of Hericium erinaceus and its effect on colonic health of mice. International journal of biological macromolecules 107: 1310-1319.
46. Wei LS, Wee W, Siong JY, Syamsumir DF. 2011. Characterization of anticancer, antimicrobial, antioxidant properties and chemical compositions of Peperomia pellucida leaf extract. Acta Medica Iranica 670-674.
47. Wen TC, Xiao YP, Han YF, Huang SK, Zha LS, Hyde KD, Kang JC. 2017. Multigene phylogeny and morphology reveal that the Chinese medicinal mushroom Metacordyceps neogunnii sp. nov. Phytotaxa 302(1): 27-39.
48. World health organization cardiovascular-diseases-(cvds) fact sheet, 17 May 2017. http://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
49. World health organization fact sheet, 12 September 2018. https://www.who.int/news-room/fact-sheets/detail/cancer.
50. Xiao Z, Storms R, Tsang A. 2006. A quantitative starch–iodine method for measuring alphaamylase and glucoamylase activities. Analytical biochemistry 351(1): 146-148.
51. Yang CH, Kao YH, Huang KS, Wang CY, Lin LW. 2012. Cordyceps militaris and mycelial fermentation induced apoptosis and autophagy of human glioblastoma cells. Cell death & disease 3: e431.
52. Yeong LH, Nancy KG, Micheal WP. 1989. Newly recognized nticarcinogenic fatty acids: identification and quantification in natural and processed cheeses: J. Agric. Food Chem. 37: 75-81.
53. Yim MH, Shin JW, Son JY, Oh SM, Han SH, Cho JH, et al. 2007. Soluble components of Hericium erinaceum induce NK cell activation via production of interleukin-12 in mice splenocytes. Acta Pharmacol Sin. 28(6): 901-907.
54. Zhang J, Shi R, Li H, Xiang Y, Xiao L, Hu M, Ma F, Ma CW, Huang Z. 2016. Antioxidant and neuroprotective effects of Dictyophora indusiata polysaccharide in Caenorhabditis elegans. Journal of ethnopharmacology 192: 413-422.
55. Zhang Z, Lv G, Pan H, Pandey A, He W, Fan L. 2012. Antioxidant and hepatoprotective potential of endo-polysaccharides from Hericium erinaceus grown on tofu whey. Int J Biol Macromol. 51(5): 1140-1146.
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