Comparative Analysis of Bioactive Ingredients and Medicinal Functions of Natural and Cultivated Ophiocordyceps sinensis (Berk.)

Abstract

The Chinese caterpillar fungus Ophiocordyceps sinensis (Berk.) is a valuable traditional medicine, also known throughout Asia by its Tibetan name (Yartsa Gunbu), meaning “summer grass, winter worm”. The mature fungus O. sinensis contains abundant active biological components, including polysaccharides, alkaloids, amino acids, inorganic elements, and others. Studies have previously confirmed that O. sinensis possesses multiple pharmacological activities. Therefore, it holds high value in the commercial market and is in increasing demand. However, the unique formation process and harsh growth environment contribute to the preciousness and scarcity of the species. To meet market demand, multiple mycelium types have been isolated from natural O. sinensis and cultivated artificially using fermentation technology. Currently, both natural and cultivated O. sinensis products are available as healthy Chinese herbal medicines on the market. However, there is a lack of comparative reviews on the two types of O. sinensis in terms of their compositions and medicinal functions. This mini-review will focus on the bioactive ingredients and medicinal functions of both natural and cultivated O. sinensis, intending to elucidate their medical values as traditional Chinese medicines for human use.

Keywords

Ophiocordyceps sinensis / Natural O. sinensis / Cultivated O. sinensis / Bioactive ingredients / Pharmacological effects / Compositional analysis

Acknowledgments

We thank the anonymous reviewers for their constructive com-ments, which greatly improved the quality of the manuscript.

Funding

No funding was received for the study.

Conflict of interest

LW has been an editorial board member of Future Integrative Medicine since October 2021. The authors declare that the research was conducted in the absence of any commercial or financial rela-tionships that could be construed as a potential conflict of interest.

Author contributions

Topic conception, logical framework, student supervision, project administration (LW), discussions (YRT), investigation, image vis-ualization (ZWM), writing of the original draft, and performing the literature review (ZWM, QHL, YXH, JC, JWT). All the authors approved the final version and publication of the manuscript.

References

[1] Lo HC, Hsieh C, Lin FY, Hsu TH. A Systematic Review of the Mysterious Caterpillar Fungus Ophiocordyceps sinensis in Dong-ChongXiaCao ( Dōng Chóng Xià Căo) and Related Bioactive Ingredients. J Tradit Comple-ment Med 2013; 3(1):16-32. doi:10.4103/2225-4110.106538,PMID:24716152.

[2] Yan Y, Li Y, Wang WJ, He JS, Yang RH, Wu HJ, et al. Range shifts in response to climate change of Ophiocordyceps sinensis, a fungus endemic to the Tibetan Plateau. Biol Conserv 2017; 206:143-150. doi:10.1016/j.biocon.2016.12.023.

[3] Das G, Shin HS, Leyva-Gómez G, Prado-Audelo MLD, Cortes H, Sin-gh YD, et al. Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials. Front Pharmacol 2020;11:602364. doi:10.3389/fphar.2020.602364,PMID:33628175.

[4] Xu C, Wu F, Zou Z, Mao L, Lin S. Discovery of the chemical constit-uents, structural characteristics, and pharmacological functions of Chinese caterpillar fungus. Open Chem 2023; 21(1):20220337. doi:10.1515/chem-2022-0337.

[5] Shrestha B, Zhang W, Zhang Y, Liu X. The medicinal fungus Cordyceps militaris: research and development. Mycol Prog 2012; 11(3):599-614. doi:10.1007/s11557-012-0825-y.

[6] Olatunji OJ, Tang J, Tola A, Auberon F, Oluwaniyi O, Ouyang Z. The genus Cordyceps: An extensive review of its traditional uses, phy-tochemistry and pharmacology. Fitoterapia 2018; 129:293-316. doi:10.1016/j.fitote.2018.05.010,PMID:29775778.

[7] Wei Y, Zhang L, Wang J, Wang W, Niyati N, Guo Y, et al. Chinese caterpillar fungus (Ophiocordyceps sinensis) in China: Current dis-tribution, trading, and futures under climate change and overex-ploitation. Sci Total Environ 2021; 755(Pt 1):142548. doi:10.1016/j.scitotenv.2020.142548, PMID:33035977.

[8] Das SK, Masuda M, Sakurai A, Sakakibara M. Medicinal uses of the mushroom Cordyceps militaris: current state and prospects. Fitotera-pia 2010; 81(8):961-968. doi:10.1016/j.fitote.2010.07.010,PMID:20650308.

[9] Zhang Y, Liu SJ. Cordyceps as potential therapeutic agents for ath-erosclerosis. J Integr Med 2024; 22(2):102-114. doi:10.1016/j.joim.2024.03.004,PMID:38494355.

[10] Winkler D. Yartsa Gunbu (Cordyceps sinensis) and the Fungal Commodification of Tibet’s Rural Economy. Economic Botany 2008; 62(3):291-305. doi:10.1007/s12231-008-9038-3.

[11] Zhou X, Gong Z, Su Y, Lin J, Tang K. Cordyceps fungi: natural products, pharmacological functions and developmental products. J Pharm Phar-macol 2009; 61(3):279-291. doi:10.1211/jpp/61.03.0002,PMID:19222900.

[12] Xu J, Huang Y, Chen XX, Zheng SC, Chen P, Mo MH. The Mecha-nisms of Pharmacological Activities of Ophiocordyceps sinensis Fungi. Phytother Res 2016; 30(10):1572-1583. doi:10.1002/ptr.5673,PMID:27373780.

[13] Jędrejko KJ, Lazur J, Muszyńska B. Cordyceps militaris: An Overview of Its Chemical Constituents in Relation to Biological Activity. Foods 2021; 10(11):2634. doi:10.3390/foods10112634,PMID:34828915.

[14] Tan W, Wang Y, Dai H, Deng J, Wu Z, Lin L, et al. Potential Thera-peutic Strategies for Renal Fibrosis: Cordyceps and Related Products. Front Pharmacol 2022;13:932172. doi:10.3389/fphar.2022.932172,PMID:35873549.

[15] Zhang J, Wang N, Chen W, Zhang W, Zhang H, Yu H, et al. Integrated metabolomics and transcriptomics reveal metabolites difference between wild and cultivated Ophiocordyceps sinensis. Food Res Int 2023;163:112275. doi:10.1016/j.foodres.2022.112275,PMID:36596185.

[16] Zhang B, Li B, Men XH, Xu ZW, Wu H, Qin XT, et al. Proteome se-quencing and analysis of Ophiocordyceps sinensis at different culture periods. BMC Genomics 2020; 21(1):886. doi:10.1186/s12864-020-07298-z,PMID:33308160.

[17] Liu QH, Tang JW, Ma ZW, Hong YX, Yuan Q, Chen J, et al. Rapid dis-crimination between wild and cultivated Ophiocordyceps sinensis through comparative analysis of label-free SERS technique and mass spectrometry. Curr Res Food Sci 2024;9:100820. doi:10.1016/j.crfs.2024.100820, PMID:39263205.

[18] Yue K, Ye M, Lin X, Zhou Z. The artificial cultivation of medicinal Cater-pillar Fungus, Ophiocordyceps sinensis (Ascomycetes): a review. Int J Med Mushrooms 2013; 15(5):425-434. doi:10.1615/intjmedmushr.v15.i5.10,PMID:24266368.

[19] Li Y, Wang XL, Jiao L, Jiang Y, Li H, Jiang SP, et al. A survey of the geograph-ic distribution of Ophiocordyceps sinensis. J Microbiol 2011; 49(6):913-919. doi:10.1007/s12275-011-1193-z, PMID:22203553.

[20] Paterson RR. Cordyceps: a traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry 2008; 69(7):1469-1495. doi:10.1016/j.phytochem.2008.01.027,PMID:18343466.

[21] Zhou XW, Li LJ, Tian EW. Advances in research of the artificial cul-tivation of Ophiocordyceps sinensis in China. Crit Rev Biotechnol 2014; 34(3):233-243. doi:10.3109/07388551.2013.791245,PMID:23875938.

[22] Ko YF, Liau JC, Lee CS, Chiu CY, Martel J, Lin CS, et al. Isolation, Culture and Characterization of Hirsutella sinensis Mycelium from Caterpillar Fungus Fruiting Body. PLoS One 2017; 12(1):e0168734. doi:10.1371/journal.pone.0168734,PMID:28046129.

[23] Jang SH, Kim SH, Lee HY, Jang SH, Jang H, Chae SW, et al. Immune-Modulating Activity of Extract Prepared from Mycelial Culture of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomy-cetes). Int J Med Mushrooms 2015; 17(12):1189-1199. doi:10.1615/intjmedmushrooms.v17.i12.90,PMID:26854106.

[24] Kaushik V, Arya A, Sindhu A, Singh A. Identification, and Optimization of Culture Conditions, Bioactive Potential of Chinese Caterpillar Mushroom Ophiocordyceps sinensis (Ascomycetes) Mycelium Iso-lated from Fruiting Body. Int J Med Mushrooms 2019; 21(9):931-942. doi:10.1615/IntJMedMushrooms.2019031841,PMID:32450031.

[25] Chen L, Liu Y, Guo Q, Zheng Q, Zhang W. Metabolomic compari-son between wild Ophiocordyceps sinensis and artificial cultured Cordyceps militaris. Biomed Chromatogr 2018; 32(9):e4279. doi: 10.1002/bmc.4279,PMID:29752731.

[26] Li WJ, Dong CH, Liu XZ, Li QP, Xia JM, Liang L. Research advanc-es in artificial cultivation of Chinese cordyceps. Mycosystema 2016; 35(4):375-387. doi:10.13346/j.mycosystema.160003.

[27] Zhou Y, Wang M, Zhang H, Huang Z, Ma J. Comparative study of the composition of cultivated, naturally grown Cordyceps sinen-sis, and stiff worms across different sampling years. PLoS One 2019; 14(12):e0225750. doi:10.1371/journal.pone.0225750,PMID:31800596.

[28] Zhang X, Liu Q, Zhou W, Li P, Alolga RN, Qi LW, et al. A compara-tive proteomic characterization and nutritional assessment of nat-urally- and artificially-cultivated Cordyceps sinensis. J Proteomics 2018; 181:24-35. doi:10.1016/j.jprot.2018.03.029,PMID:29609095.

[29] Sharma A, Ranout AS, Nadda G. Insights into cultivation strategies, bioactive components, therapeutic potential, patents, and market products of Ophiocordyceps sinensis: A comprehensive review. S Afr J Bot 2024; 171:546-570. doi:10.1016/j.sajb.2024.06.036.

[30] Lu C, Wang Q, Jiang Y, Zhang M, Meng X, Li Y, et al. Discovery of a novel nucleoside immune signaling molecule 2′-deoxyguanosine in microbes and plants. J Adv Res 2023; 46:1-15. doi:10.1016/j.jare.2022.06.014, PMID:35811061.

[31] Pandita D, Pandita A. Mushrooms Nutraceuticals and Functional Foods. Boca Raton, FL: CRC Press; 2023.

[32] Yan JK, Wang WQ, Wu JY. Recent advances in Cordyceps sinensis polysaccharides: Mycelial fermentation, isolation, structure, and bioactivities: A review. J Funct Foods 2014; 6:33-47. doi:10.1016/j.jff.2013.11.024, PMID:32362940.

[33] Li SP, Su ZR, Dong TT, Tsim KW. The fruiting body and its caterpillar host of Cordyceps sinensis show close resemblance in main constitu-ents and anti-oxidation activity. Phytomedicine 2002; 9(4):319-324. doi:10.1078/0944-7113-00134,PMID:12120813.

[34] Cai Y, Guo J, Kang Y. Future prospect of polysaccharide as a poten-tial therapy in hepatocellular carcinoma: A review. Int J Biol Macro-mol 2024; 270(Pt 1):132300. doi:10.1016/j.ijbiomac.2024.132300,PMID:38735616.

[35] Bai C, Su F, Zhang W, Kuang H. A Systematic Review on the Re-search Progress on Polysaccharides from Fungal Traditional Chi-nese Medicine. Molecules 2023; 28(19):6816. doi:10.3390/mole-cules28196816,PMID:37836659.

[36] Ohta Y, Lee JB, Hayashi K, Fujita A, Park DK, Hayashi T. In vivo anti-influenza virus activity of an immunomodulatory acidic polysaccha-ride isolated from Cordyceps militaris grown on germinated soy-beans. J Agric Food Chem 2007; 55(25):10194-10199. doi:10.1021/jf0721287,PMID:17988090.

[37] Koh JH, Kim JM, Chang UJ, Suh HJ. Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps sinensis. Biol Pharm Bull 2003; 26(1):84-87. doi:10.1248/bpb.26.84,PMID:12520179.

[38] Zeng P, Li J, Chen Y, Zhang L. The structures and biological functions of polysaccharides from traditional Chinese herbs. Prog Mol Biol Transl Sci 2019; 163:423-444. doi:10.1016/bs.pmbts.2019.03.003,PMID:31030757.

[39] Wang J, Nie S, Chen S, Phillips AO, Phillips GO, Li Y, et al. Structural characterization of an α-1, 6-linked galactomannan from natural Cordyceps sinensis. Food Hydrocoll 2018; 78:77-91. doi:10.1016/j.foodhyd.2017.07.024.

[40] Ying M, Yu Q, Zheng B, Wang H, Wang J, Chen S, et al. Cultured Cordyceps sinensis polysaccharides attenuate cyclophosphamide-in-duced intestinal barrier injury in mice. J Funct Foods 2019;62:103523. doi:10.1016/j.jff.2019.103523.

[41] Wang J, Kan L, Nie S, Chen H, Cui SW, Phillips AO, et al. A comparison of chemical composition, bioactive components and antioxidant ac-tivity of natural and cultured Cordyceps sinensis. LWT-Food Sci Tech-nol 2015; 63(1):2-7. doi:10.1016/j.lwt.2015.03.109.

[42] Guan J, Zhao J, Feng K, Hu DJ, Li SP. Comparison and characteriza-tion of polysaccharides from natural and cultured Cordyceps using saccharide mapping. Anal Bioanal Chem 2011; 399(10):3465-3474. doi:10.1007/s00216-010-4396-y,PMID:21152906.

[43] Nie S, Cui SW, Xie M, Phillips AO, Phillips GO. Bioactive polysaccha-rides from Cordyceps sinensis: Isolation, structure features and bioac-tivities. Bioact Carbohydr Diet Fibre 2013; 1(1):38-52. doi:10.1016/j.bcdf.2012.12.002.

[44] Zhu ZY, Liu XC, Tang YL, Dong FY, Sun HQ, Chen L, et al. Effects of cultural medium on the formation and antitumor activity of polysac-charides by Cordyceps gunnii. J Biosci Bioeng 2016; 122(4):494-498. doi:10.1016/j.jbiosc.2016.03.015,PMID:27074949.

[45] Liu QH, Zhang YD, Ma ZW, Qian ZM, Jiang ZH, Zhang W, et al. Frac-tional extraction and structural characterization of glycogen particles from the whole cultivated caterpillar fungus Ophiocordyceps sin-ensis. Int J Biol Macromol 2023; 229:507-514. doi:10.1016/j.ijbio-mac.2022.12.319,PMID:36603712.

[46] Liu Y, Wang J, Wang W, Zhang H, Zhang X, Han C. The Chemical Constituents and Pharmacological Actions of Cordyceps sinen-sis. Evid Based Complement Alternat Med 2015; 2015:575063. doi:10.1155/2015/575063,PMID:25960753.

[47] Li X, Liu Q, Li W, Li Q, Qian Z, Liu X, et al. A breakthrough in the ar-tificial cultivation of Chinese cordyceps on a large-scale and its im-pact on science, the economy, and industry. Crit Rev Biotechnol 2019; 39(2):181-191. doi:10.1080/07388551.2018.1531820,PMID:30394122.

[48] Duan X, Yang H, Wang C, Liu H, Lu X, Tian Y. Microbial synthesis of cordycepin, current systems and future perspectives. Trends Food Sci Technol 2023; 132:162-170. doi:10.1016/j.tifs.2023.01.006.

[49] Zhou Y, Schneider DJ, Blackburn MR. Adenosine signaling and the regulation of chronic lung disease. Pharmacol Ther 2009; 123(1):105-116. doi:10.1016/j.pharmthera.2009.04.003, PMID:19426761.

[50] Kim J, Shin JY, Choi YH, Lee SY, Jin MH, Kim CD, et al. Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adeno-sine Receptor Mediated Wnt/β-Catenin Pathway Stimulation by Reg-ulating GSK3b Activity. Int J Mol Sci 2021; 22(11):5571. doi:10.3390/ijms22115571,PMID:34070360.

[51] Vincenzi F, Pasquini S, Contri C, Cappello M, Nigro M, Travagli A, et al. Pharmacology of Adenosine Receptors: Recent Advance-ments. Biomolecules 2023; 13(9):1387. doi:10.3390/biom13091387,PMID:37759787.

[52] Kitakaze M, Hori M. Adenosine therapy: a new approach to chronic heart failure. Expert Opin Investig Drugs 2000; 9(11):2519-2535. doi:10.1517/13543784.9.11.2519,PMID:11060817.

[53] Nakav S, Chaimovitz C, Sufaro Y, Lewis EC, Shaked G, Czeiger D, et al. Anti-inflammatory preconditioning by agonists of adenosine A1 receptor. PLoS One 2008; 3(5):e2107. doi:10.1371/journal.pone.0002107, PMID:18461129.

[54] Zong SY, Han H, Wang B, Li N, Dong TT, Zhang T, et al. Fast Simultane-ous Determination of 13 Nucleosides and Nucleobases in Cordyceps sinensis by UHPLC-ESI-MS/MS. Molecules 2015; 20(12):21816-21825. doi:10.3390/molecules201219807,PMID:26690105.

[55] Wu G. Amino acids: metabolism, functions, and nutrition. Amino Acids 2009; 37(1):1-17. doi:10.1007/s00726-009-0269-0,PMID:19301095.

[56] Torres N, Tobón-Cornejo S, Velazquez-Villegas LA, Noriega LG, Alemán-Escondrillas G, Tovar AR. Amino Acid Catabolism: An Overlooked Area of Metabolism. Nutrients 2023; 15(15):3378. doi:10.3390/nu15153378,PMID:37571315.

[57] Zhao J, Shi T, Zhu W, Chen L, Guan Y, Jin C. Quality control method of sterols in fermented Cordyceps sinensis based on combined finger-print and quantitative analysis of multicomponents by single marker. J Food Sci 2020; 85(10):2994-3002. doi:10.1111/1750-3841.15412,PMID:32918296.

[58] Matsuda H, Akaki J, Nakamura S, Okazaki Y, Kojima H, Tamesada M, et al. Apoptosis-inducing effects of sterols from the dried powder of cultured mycelium of Cordyceps sinensis. Chem Pharm Bull (Tokyo) 2009; 57(4):411-414. doi:10.1248/cpb.57.411,PMID:19336939.

[59] Yuan JP, Wang JH, Liu X, Kuang HC, Zhao SY. Simultaneous determi-nation of free ergosterol and ergosteryl esters in Cordyceps sinensis by HPLC. Food Chem 2007; 105(4):1755-1759. doi:10.1016/j.food-chem.2007.04.070.

[60] Zhao YY, Shen X, Chao X, Ho CC, Cheng XL, Zhang Y, et al. Ergosta-4,6,8(14),22-tetraen-3-one induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Bio-chim Biophys Acta 2011; 1810(4):384-390. doi:10.1016/j.bbagen.2010.12.005,PMID:21241775.

[61] Zhabinskii VN, Drasar P, Khripach VA. Structure and Biological Activity of Ergostane-Type Steroids from Fungi. Molecules 2022; 27(7):2103. doi:10.3390/molecules27072103,PMID:35408501.

[62] Wang FX, Zhu N, Zhou F, Lin DX. Natural Aporphine Alkaloids with Po-tential to Impact Metabolic Syndrome. Molecules 2021; 26(20):6117. doi:10.3390/molecules26206117,PMID:34684698.

[63] Xue Y, Wu L, Ding Y, Cui X, Han Z, Xu H. A new nucleoside and two new pyrrole alkaloid derivatives from Cordyceps militaris. Nat Prod Res 2020; 34(3):341-350. doi:10.1080/14786419.2018.1531861,PMID:30580621.

[64] Han X, Liu LH, Fang XY, Jiang ST, Zhao H, Qian ZM, et al. Cordythiazole A, the first member of thiazole alkaloids from Chinese cordyceps, with α-glucosidase inhibitory activity. J Nat Med 2023; 77(4):986-991. doi:10.1007/s11418-023-01732-8,PMID:37515674.

[65] Zhang J, Zhong X, Li S, Zhang G, Liu X. Metabolic characterization of natural and cultured Ophicordyceps sinensis from different origins by 1H NMR spectroscopy. J Pharm Biomed Anal 2015; 115:395-401. doi:10.1016/j.jpba.2015.07.035,PMID:26279370.

[66] Krishna KV, Ulhas RS, Malaviya A. Bioactive compounds from Cordyceps and their therapeutic potential. Crit Rev Biotechnol 2024; 44(5):753-773. doi:10.1080/07388551.2023.2231139,PMID:37518188.

[67] Wang T, Tang C, Xiao M, Cao Z, He H, He M, et al. Analysis of meta-bolic spectrum characteristics of naturally and cultivated Ophio-cordyceps sinensis based on non-targeted metabolomics. Sci Rep 2024; 14(1):17425. doi:10.1038/s41598-024-68306-w,PMID:39075220.

[68] Yang L, Chen J, Lu H, Lai J, He Y, Liu S, et al. Present and Pueraria lobata for Diabetes Mellitus: Past, Future. Am J Chin Med 2019; 47(7):1419-1444. doi:10.1142/S0192415X19500733,PMID:31659910.

[69] Zhang Z, Zhang L, Xu H. Effect of Astragalus polysaccharide in treat-ment of diabetes mellitus: a narrative review. J Tradit Chin Med 2019; 39(1):133-138. PMID:32186034.

[70] Baska A, Leis K, Gałązka P. Berberine in the Treatment of Diabetes Mellitus: A Review. Endocr Metab Immune Disord Drug Targets 2021; 21(8):1379-1386. doi:10.2174/1568026620666201022144405,PMID:33092516.

[71] An X, Xu Y, Gui D. Combination of Astragalus membranaceus and Panax notoginseng as Main Components in the Treatment of Diabetic Nephropathy: A Systematic Review and Meta-Analy-sis. Evid Based Complement Alternat Med 2023; 2023:2945234. doi:10.1155/2023/2945234,PMID:37101717.

[72] Sun H, Yu X, Li T, Zhu Z. Structure and hypoglycemic activity of a novel exopolysaccharide of Cordyceps militaris. Int J Biol Macromol 2021; 166:496-508. doi:10.1016/j.ijbiomac.2020.10.207,PMID:33129900.

[73] Wang Y, Wang M, Ling Y, Fan W, Wang Y, Yin H. Structural determination and antioxidant activity of a polysaccharide from the fruiting bodies of cultured Cordyceps sinensis. Am J Chin Med 2009; 37(5):977-989. doi:10.1142/S0192415X09007387,PMID:19885957.

[74] Wu F, Yan H, Ma X, Jia J, Zhang G, Guo X, et al. Comparison of the structural characterization and biological activity of acidic polysac-charides from Cordyceps militaris cultured with different media. World J Microbiol Biotechnol 2012; 28(5):2029-2038. doi:10.1007/s11274-012-1005-6,PMID:22806024.

[75] Zhao H, Lai Q, Zhang J, Huang C, Jia L. Antioxidant and Hypoglycemic Effects of Acidic-Extractable Polysaccharides from Cordyceps militaris on Type 2 Diabetes Mice. Oxid Med Cell Longev 2018; 2018:9150807. doi:10.1155/2018/9150807,PMID:30595798.

[76] Xu RH, Peng XE, Chen GZ, Chen GL. Effects of cordyceps sinensis on natural killer activity and colony formation of B16 melanoma. Chin Med J (Engl) 1992; 105(2):97-101. PMID:1597083.

[77] Rong L, Li G, Zhang Y, Xiao Y, Qiao Y, Yang M, et al. Structure and immunomodulatory activity of a water-soluble α-glucan from Hir-sutella sinensis mycelia. Int J Biol Macromol 2021; 189:857-868. doi:10.1016/j.ijbiomac.2021.08.185,PMID:34464642.

[78] Bi S, Jing Y, Zhou Q, Hu X, Zhu J, Guo Z, et al. Structural elucida-tion and immunostimulatory activity of a new polysaccharide from Cordyceps militaris. Food Funct 2018; 9(1):279-293. doi:10.1039/c7fo01147d,PMID:29168868.

[79] Zhang J, Yu Y, Zhang Z, Ding Y, Dai X, Li Y. Effect of polysaccharide from cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed to 60Co. Int Immunopharma-col 2011; 11(12):2251-2257. doi:10.1016/j.intimp.2011.09.019,PMID:22001898.

[80] Gu L, Yu T, Liu J, Lu Y. Evaluation of the mechanism of cordyceps polysaccharide action on rat acute liver failure. Arch Med Sci 2020; 16(5):1218-1225. doi:10.5114/aoms.2020.94236,PMID:32864011.

[81] Lee BH, Chen CH, Hsu YY, Chuang PT, Shih MK, Hsu WH. Polysaccha-rides Obtained from Cordyceps militaris Alleviate Hyperglycemia by Regulating Gut Microbiota in Mice Fed a High-Fat/Sucrose Diet. Foods 2021; 10(8):1870. doi:10.3390/foods10081870,PMID:34441649.

[82] Lei J, Wei Y, Song P, Li Y, Zhang T, Feng Q, et al. Cordycepin inhib-its LPS-induced acute lung injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol 2018; 818:110-114. doi:10.1016/j.ejphar.2017.10.029, PMID:29054740.

[83] Kim HG, Shrestha B, Lim SY, Yoon DH, Chang WC, Shin DJ, et al. Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur J Pharmacol 2006; 545(2-3):192-199. doi:10.1016/j.ejphar.2006.06.047,PMID:16899239.

[84] Liu Y, Guo ZJ, Zhou XW. Chinese Cordyceps: Bioactive Components, Antitumor Effects and Underlying Mechanism-A Review. Molecules 2022; 27(19):6576. doi:10.3390/molecules27196576,PMID:36235111.

[85] Tan L, Liu S, Li X, He J, He L, Li Y, et al. The Large Molecular Weight Polysaccharide from Wild Cordyceps and Its Antitumor Activity on H 22 Tumor-Bearing Mice. Molecules 2023; 28(8):3351. doi:10.3390/molecules28083351,PMID:37110586.

[86] He W, Zhang MF, Ye J, Jiang TT, Fang X, Song Y. Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules. J Zheji-ang Univ Sci B 2010; 11(9):654-660. doi:10.1631/jzus.B1000081,PMID:20803769.

[87] Yuan Q, Xie F, Tan J, Yuan Y, Mei H, Zheng Y, et al. Extraction, structure and pharmacological effects of the polysaccharides from Cordyceps sinensis: A review. J Funct Foods 2022;89:104909. doi:10.1016/j.jff.2021.104909.

[88] Wen Z, Du X, Meng N, Li Y, Mi R, Li X, et al. Tussah silkmoth pu-pae improve anti-tumor properties of Cordyceps militaris (L.) Link by increasing the levels of major metabolite cordycepin. RSC Adv 2019; 9(10):5480-5491. doi:10.1039/c8ra09491h,PMID:35515955.

[89] Ma S, Sun Y, Wang F, Mi R, Wen Z, Li X, et al. Effects of tussah im-munoreactive substances on growth, immunity, disease resistance against Vibrio splendidus and gut microbiota profile of Apostichopus japonicus. Fish Shellfish Immunol 2017; 63:471-479. doi:10.1016/j.fsi.2017.02.045, PMID:28254498.

[90] Shweta, Abdullah S, Komal, Kumar A. A brief review on the me-dicinal uses of Cordyceps militaris. Pharmacol Res - Mod Chin Med 2023;7:100228. doi:10.1016/j.prmcm.2023.100228.

[91] Dong CH, Yao YJ. In vitro evaluation of antioxidant activities of aque-ous extracts from natural and cultured mycelia of Cordyceps sin-ensis. Lebensm Wiss Technol 2008; 41(4):669-677. doi:10.1016/j.lwt.2007.05.002, PMID:32287390.

[92] Wang BS, Lee CP, Chen ZT, Yu HM, Duh PD. Comparison of the hepato-protective activity between cultured Cordyceps militaris and natural Cordyceps sinensis. J Funct Foods 2012; 4(2):489-495. doi:10.1016/j.jff.2012.02.009.