Ophiocordyceps sinensis and Pharmaceutical Industry

Abstract

Fungus has ever since been of great interest to science. Among the group of eukaryotic organisms, fungi are of great importance and use. The very amazing kingdom Fungi includes few important organisms. Out of those few important organisms, one such is the cordyceps species which is of great interest to the mycologists from the time of their discovery. The reason behind being popular among mycologists is because of its bioactivity. There are a lot of bioactive compounds that are found in cordyceps species that proves to be a boon for pharmaceutical industry. This review article includes short discussion on Ophiocordyceps sinensis and the bioactive compound that they possess.

Keywords

Bioactivity, Cordyceps, Therapeutic, Antitumor, Antifungal

Introduction

Fungi show an exceptional level of basic and utilitarian differing qualities with an expected 1 to 5 million surviving species, out of which around 100,000 fungal species have so far been depicted. The quantity of species distinguished keeps on rising prompting to expanding wellspring of biomolecules to be investigated for food, health, natural & environmental applications [1-10]. Current comprehension of contagious science has given a chance to recognize the extensive variety of exercises valuable for industrial, therapeutic, agricultural and environmental applications [8,10].

Among these, the caterpillar fungus is of great importance. The caterpillar fungus popularly known as Cordyceps sinensis is an entomopathogenic fungus that parasitize insect larvae like arthropods and other related fungi [11-15]. In English it is known as 'Caterpillar Fungus’ whereas in different geographic regions it is variously known as ‘yarsa gumba’ a Tibetan name [winter= (yarsa; summer=gumba], ‘gunba’ or ‘gonba’ or ‘gumba’. In the Indian mountainous region it is popular as ‘keera jhar’ (insect herb), while in Chinese it is famous as ‘Dong Chong Xia Cao’ (meaning ‘winter worm, summer plant’) [16-20].

The regular natural fruiting body of Cordyceps has been known and utilized as a part of customary Chinese drug for a considerable length of time. Because of its little size and confined development, it is hard to acquire them in simple way. They are for the most part found at high elevation extending from 4,600–5,000 m asl and they show up every year in Himalayan locale of India, Nepal, and Tibet. In view of late developmental studies [21-27], the terminology has been changed to Ophiocordyceps Petch and the present name of this fungus is Ophiocordyceps sinensis (Berk.) Sung et al. Thus in the future Cordyceps sinensis will be referred to as Ophiocordyceps sinensis (O. sinensis) [28].

The O. sinensis fruiting body esteemed as an herbal medicine is found in mountainous locales of Nepal, Tibet and India. The fungus causes infection in the living larva, which eventually executes and embalms it, and afterward the stalk-like fruiting body rises up out of the carcass [28-37]. Ophiocordyceps sinensis is a very much depicted cure utilized as a part of conventional restorative framework in India, Nepal and china. The wild fungus, which has a plant-like fruiting body, grows from dead caterpillar loaded with mycelia [38-45]. O. sinensis is a slow developing fungus that grows at lower temperature, i.e., beneath 21°C. Both, temperature and development rate are vital calculates recognizing O. sinensis from other comparable fungi Figure 1 [45-55].

Figure 1: Ophiocordyceps sinensis.

Bioactive Compounds in Ophiocordyceps sinensis

In recent years, different medicines and other health-care products obtained from O. sinensis are extremely popular in diverse forms which include capsules, oral liquids, drinks etc. Due to immense medicinal properties that this fungus possesses, the wild fungus is highly priced. The cost of one kg of O. sinensis varies from about 3000 USD to 21000 USD in India, and approximately 1500 USD to 17000 USD in Nepal. Sources clarified that the price of the fungus depends upon the condition and colour of the collected wild samples [55-65]. As stated, the fungus can be used in the development of various medicines and other health-care products, Table 1. Includes the list of some bioactive compounds obtained from O. sinensis:

Table 1. List of Bioactive Compounds obtained from Ophiocordyceps sinensis.

Role in Pharmaceutical Industry

Cordyceps is considered for various positive viewpoints as far as pharmacological impacts and thought to be sheltered. Other than a little contrarily distributed information, it is generally thought to be a non-dangerous therapeutic mushroom. This medicinal fungus came in the spotlight amid Chinese National Games in 1993, when a gathering of women athletes won nine world records, had conferred that they had been taking Cordyceps routinely. It has been reported that Cordyceps likewise upgrades physical stamina making it extremely helpful for the elderly individuals and competitors. Latest writings further affirm that Cordyceps improves cell vitality as ATP (adenosine tri-phosphate) [78-85].

After the underlying revelation of some chemical constituents, center had been moved toward this ponder and wild growth, and plenty of substance mixes have been segregated and utilized for different purposes. O. sinensis is referred to in the west as a therapeutic mushroom. It is utilized for the treatment of diseases like cancer and fatigue [86-91]. Here is a list of bioactive compounds along with their bioactivity Table 2.

Table 2. Bioactivity of compounds isolated from Ophiocordyceps sinensis.

Conclusion

Entomopathogenic fungus has ever since been the center of research for mycologists. Ophiocordyceps sinensis is an interesting fungus which is yet to be explored in terms of science. There are several countries that use it as a traditional medicine [90-94]. There is a major need of planned study in reference to this fungus. Since, there are several compounds that can be isolated out of this fungus; attempts towards its molecular study must be made. As slowly this fungus is getting into picture and as the climate and environment is rapidly changing; steps must be taken in order to preserve the fungus. Different gene banks can be made, where the fungus can be preserved which can be used later for morphological and molecular studies. More focus on specific fungi will help in getting better results. Moreover, if an initiative can be taken keeping in mind only few fungi variety, it will be very much beneficial to science and to mankind as well. Advanced molecular studies of Ophiocordyceps sinensis is also very important. In various laboratories it has been found that samples collected from different regions had variations in their molecular structures. Best way to pursue the studies on Ophiocordyceps sinensis will be studying it morphologically first, identifying the associated fungi growth as the associated fungi are also very important and then at the same time going for the molecular studies. As it has been found that the fungus is a hub for pharmaceuticals. Studies on this regard can be very beneficial.

References

1. Zhang Q, et al. The Strategies for Increasing Cordycepin Production of Cordyceps Militaris by Liquid Fermentation. Fungal Genom Biol. 2016;6:134.
2. Hsu JH, et al. Healthcare Functions of Cordyceps cicadae. J Nutr Food Sci. 2015;5:432.
3. Liu JH, et al. Structural Elucidation and Antioxidant Activity of a Polysaccharide from Mycelia Fermentation of Hirsutella sinensis Isolated from Ophiocordyceps sinensis. J Bioprocess Biotech. 2014;4:183
4. Sampath KA, et al. Structural, Magnetic and In Vitro Bioactivity of Co-Cu Ferrite and Bioglass Composite for Hyperthermia in Bone Tissue Engineering. Bioceram Dev Appl. 2016; 6:91
5. Amin AMM, et al. Zirconia Effect on the Bioactivity and the Mechanical Properties of Calcium Magnesium Silicate Ceramics at (Cao+Mgo)/SiO2 Molar Ratio Close to Unity. Bioceram Dev Appl. 2016;6:88.
6. Tanwar A, et al. Targeting Antibiotic Resistant Salmonella enterica: Bio-matrix Based Selection and Bioactivity Prediction of Potential Nutraceuticals. Biochem Anal Biochem. 2015;4:217.
7. Hejazi MS, et al. Effect of Alumina Amount on the Bioactivity of Dense Magnesium Fluorapatite/Alumina Composite in Simulated Body Fluid (SBF) using Taguchi Method. J Bioprocess Biotech. 2015;5:219
8. Wang L, et al. Mini Review on Antimicrobial Activity and Bioactive Compounds of Moringa oleifera. Med Chem (Los Angeles). 2016;6:578-582.
9. Anjugam M, et al. Antibiofilm Competency of Portunus pelagicus Haemolymph and Identification of its Bioactive Compounds. J Aquac Res Development. 2016;7:444.
10. Alara OR and Olalere OA. A Critical Overview on the Extraction of Bioactive Compounds from Phaleria macrocarpa(Thymelaceae). Nat Prod Chem Res. 2016;4:232.
11. Borges KC, et al. Fresh and Spray Dried Pitanga (Eugenia uniflora) and Jambolan (Syzygium cumini) Pulps are Natural Sources of Bioactive Compounds with Functional Attributes. J Prob Health. 2016;4:145.
12. Ali SA, et al. Understanding the Challenges of Melanogenesis: Key Role of Bioactive Compounds in the Treatment of Hyperpigmentory Disorders. Pigmentary Disorders. 2015;2:223.
13. Shaikh MH, et al. Synthetic Strategies for 1,2,3-Triazole Based Bioactive Compounds. Organic Chem Curr Res. 2015;4:e140.
14. Durgadevi KB, et al. Optimization of Cultural Parameters for Cost Effective Production of Kojic Acid by Fungal Species Isolated from Soil. Fermentol Techno. 2015;4:119.
15. Godheja J and Shekhar SK. Biodegradation of Keratin from Chicken Feathers by Fungal Species as a Means of Sustainable Development. J Bioremed Biodeg. 2014; 5:232
16. Baral B and Maharjan. Nepal Academy of Science and Technology (NAST). 2012.
17. Chatterjee R, et al. Cordyceps sinensis: structure of cordycepic acid. J. Am. Pharm. Assoc. 46, 114–118.
18. Hattori M, Isomura S, Yokoyama E, Ujita M, and Hara A (2005). Extracellular trypsin-like protease produced by Cordyceps militaris. J Biosci Bioeng. 1957;100:631-636.
19. Hobbs C (1995) Medicinal mushrooms: an exploration of tradition, healing, and culture. Santa Cruz (CA): Botanica Press.
20.  Srivastava M, et al. To Develop Strain Specific Molecular Marker for Easy and Proper Identification of Fungal Species Based on Molecular Characters: A Review. J Mol Biomark Diagn. 2014;5:172.
21. Abdelfattah EA. Biomolecules Oxidation and Antioxidant Enzymes Response as a Result of Injection of Oxidative Stressor into 5th Instar of Schistocerca Gregaria (Orthoptera, Acrididae). Entomol Ornithol Herpetol. 2016;5:181.
22. Heidari A. Pharmacokinetics and Experimental Therapeutic Study of DNA and Other Biomolecules Using Lasers: Advantages and Applications. J Pharmacokinet Exp Ther. 2016;1:e005
23. Fischer WB. Classics and Hybrids - Approaches to Modeling the Dynamics of Biomolecules. J Bioanal Biomed. 2016;8: e138
24. Dakubo GD. Enigmatic Biomolecules from the Mitochondrial Genome. Biol syst Open Access. 2015;4:137.
25. Hirumavalavan M and Lee JF. A Short Review on Chitosan Membrane for Biomolecules Immobilization. J Mol Genet Med. 2015;9:178
26. Trincone A. Marine Biomolecules. Oceanography. 203;1:e104.
27. Rajkumar R and Takriff MS. Prospects of Algae and their Environmental Applications in Malaysia: A Case Study. J Bioremed Biodeg. 2016;7:321.
28. Sung GH, et al. Phylogenetic classification of Cordyceps and the clavicipitaceous fungi. Studies on Mycology. 2007;57:5-59.
29. Ragaei A, et al. Therapeutic Potential of Mesenchymal Stem Cells and Vitamin E on Experimental Hepatocellular Carcinoma. J Stem Cell Res Ther. 2016;6:362
30. Bakeer MSM. Coagulation System: New Concepts for Novel Therapeutics. J Clin Exp Cardiolog. 2016;7:471.
31. Oryan A and Alemzadeh E. Therapeutic Options of Cutaneous Leishmaniasis. Air Water Borne Dis. 2016;5:129.
32.  Assavedo CRA, et al. Epidemiological, Clinical and Therapeutic Aspects of Orbital Diseases in Ophthalmologic Hospital of Saint André de Tinré (OHSAT), in Benin Republic. J Med Surg Pathol. 2016;1:134.
33. Ahmed SM and Mohamed DA. Possible Therapeutic Role of Mesenchymal Stem Cells on Colostomy Induced Myenteric Plexus Histological Changes in Different GIT Levels in Adult Male Albino Rats: Histological and Immunohistochemical Study. J Stem Cell Res Ther. 2016;6:360.
34. Heuer TS. De Novo Palmitate Synthesis Supports Oncogenic Signalling and Tumor Growth Through Diverse Mechanisms: Implications for FASN-Targeted Therapeutics. J Cell Signal. 2016;1:124.
35. Ayano G. Bipolar Disorders and Carbamazepine: Pharmacokinetics, Pharmacodynamics, Therapeutic Effects and Indications of Carbamazepine: Review of Articles. J Neuropsychopharmacol Ment Health. 2016;1:112
36. Kauczor HU, et al. Dynamic Quantitative Contrast-enhanced Ultrasound for Assessment of Cilostazol Induced Pro-angiogenic Therapeutic Effects on Skeletal Muscle Microcirculation in Peripheral Arterial Disease. J Vasc Med Surg. 2016;4: 284.
37. Herrera-Arellano A, et al. Therapeutic Effectiveness of an Herbal Medicinal Product of Hibiscus sabdariffa in Hypertensive Patients: A 16 Week Controlled and Randomized Clinical Study. Med Aromat Plants (Los Angel). 2016;5:265.
38. Ikemoto K. Perspective of D-Neuron (Trace Amine Neuron) Research: From Novel Therapeutic Strategies. J Neurol Disord. 2016;4:286.
39.  Polo F and Toffoli G. Point-of-Care for Therapeutic Drug Monitoring of Antineoplastic Drugs. Med chem (Los Angeles). 2016;6:e108.
40. Kopsky DJ. Extending the Therapeutic Scope for the Treatment of Neuropathic Pain with Topical Analgesics. J Pain Relief. 2016;5:251.
41. Ganapathy M and Bhunia S. Nutraceuticals: The New Generation Therapeutics. Adv Tech Biol Med.2016;4:179.
42. Navin R and Kim SM. Therapeutic Interventions Using Ursolic Acid for Cancer Treatment. Med chem (Los Angeles). 2016;6: 339-344.
43. Yu G. Metformin as an Anticancer Drug: A Commentary on the Potential Therapeutic Strategy and Underlying Mechanism of Metformin in Gastric Cancer. Chemo Open Access. 2016;5:202.
44. Shiberu T, et al. Evaluation of Some Botanicals and Entomopathogenic Fungi for the Control of Onion Thrips (Thrips tabaci L.) in West Showa, Ethiopia. J Plant Pathol Microb. 2013;4:161.
45. Sansinenea E. The Role of Entomopathogenic Bacillus thuringiensis: Is It Only Insect Pathogen?. Biochem Pharmacol. 2012;1:e136.
46. Revathi N, et al. Pathogenicity of Three Entomopathogenic Fungi against Helicoverpa armigera. J Plant Pathol Microbiol. 2011;2:114.
47. Reddy HA and Venkatappa B. Effect of Staphylococcus aureus Infection on Biochemical and Antioxidant Activities of Fifth Instar Silkworm Larvae (Bombyx mori L.). J Bacteriol Parasitol. 2016;7:286.
48. Anne NW, et al. In Vitro Anti-Acetylcholinesterase Activity of Dichloromethane Leaf Extracts of Carphalea glaucescens in Chilo partellus Larvae. Biochem Anal Biochem. 2016;5:264.
49. Chandramouli K. The Importance of Next-generation Sequencing for Marine Larvae Research: Insight into Larvae Settlement and Anti-fouling. J Data Mining Genomics & Proteomics. 2016;7:e123.
50. Guidoli MG, et al. Administration of Three Autochthonous Bacillus subtilis Strains Induce Early Appearance of Gastric Glands and Vestiges of Pylorus in Piaractus mesopotamicus Larvae. J Bioprocess Biotech. 2016;6:271.
51. Harlina H, et al. Potential Study of Kopasanda (Chromolaena odorata L.) Leaves as Antibacterial Againsts Vibrio harveyi, Disease Causative Agent of Tiger Shrimp (Penaeus monodon Fabricius) Post Larvae. J Aquac Res Development. 2015;6:372.
52. ha C and Cohen AC. Effects of Anti-Fungal Compounds on Feeding Behavior and Nutritional Ecology of Tobacco Budworm and Painted Lady Butterfly Larvae. Entomol Ornithol Herpetol. 2014;3:120.
53. Susheela P. Laboratory Evaluation of the Biochemical Parameters in the Haemolymph of the Lepidopteran Larvae after Stinging by the Potter Wasp, Eumenes Conica (Insecta: Hymenoptera). Entomol Ornithol Herpetol. 2014;3:123.
54. Muhlestein JB, et al. Effect of the Chinese Drugs Nao Xintong and Dan Hong on Markers of Inflammation and the Lipid Profile in a Hypercholesterolemic Rabbit Model. J Clinic Experiment Cardiol. 2011;2:168.
55. Heim S and Keil A. Predicting Real-Life Cognitive Performance from Laboratory Data: A Case for Developmental Studies Using the Attentional Blink. Brain Disord Ther. 2016;5:210.
56. http//alohamedicinals.com
57. Hsieh C, et al. A Systematic Review of the Mysterious Caterpillar Fungus Ophiocordyceps sinensis in Dong-ChongXiaCao and Related Bioactive Ingredients. 2013;3:16-32.
58. Huang LF, et al. Simultaneous separation and determination of active components in Cordyceps sinensis and Cordyceps militaris by LC/ESI-MS. J Pharm Biomed Anal. 2003;33:1155-1162.
59. Iotti, M, et al. Morphological and molecular characterization of mycelia of ectomycorrhizal fungi in pure culture. Fungal Diversity. 2005;19:51-68.
60. Isaka M, et al. Bioxanthracenes from the insect pathogenic fungus Cordyceps pseudomilitaris BCC 1620. II. Structure elucidation. J Antibiot (Tokyo). 2001;54:36-43.
61. Jung EC, et al. A mushroom lectin from ascomycete Cordyceps militaris. BBA-Gen Subj. 2007;1770:833-841.
62. Kawaguchi N, et al. Occurrence of Gal beta (1–3) GalNAc-Ser/Thr in the linkage region of polygalactosamine containing fungal glycoprotein from Cordyceps ophioglossoides. Biochem Biophys Res Commun. 1986;140:350-356.
63. Kim JS, et al. A fibrinolytic enzyme from the medicinal mushroom Cordyceps militaris. J Microbiol. 2006;44:622-631.
64. Kobayasi Y. The genus Cordyceps and its allies. Sci Rep Tokyo, Bunrika Daigaku Sect B. 1941;84:53-260.
65. Krasnoff SB, et al. Cicadapeptins I and II: new Aib-containing peptides from the entomopathogenic fungus Cordyceps heteropoda. J Nat Prod. 2005;68:50-55.
66. Kumar A, et al. Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus. PLoS One. 2013;8:e71805.
67. Lee KH and Min TJ. Purification and characterization of a chitinase in culture media of Cordyceps militaris (L.) Link. Korean J Med Mycol. 2003;31:168-174.
68. Link JH. Handbuch zur Erkennung der Nutzbarsten und am Häufigsten Vorkommenden Gewächse. Part 3. Berlin: Haude und Spener. 1833;pp:346-349.
69. Mizuno T. Medicinal effects and utilization of Cordyceps (Fr.) Link (Ascomycetes) and Isaria Fr. (Mitosporic fungi) Chinese caterpillar fungi, “Tochukaso” (review). International Journal of Medicinal Mushroom. 1999;1:251-262.
70. Paterson RM. Cordyceps – A traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry. 2008;69:1469-1495.
71. Pennycook SR. The genus Cordyceps and other names published in the cancellans issue of Fries’s observations Mycologicae, Pars secunda. Mycosystema, 32:462-8.
72. Petch T. Notes on entomogenous fungi. Trans Br Mycol Soc. 1931;16:55-75.
73. Raper BK and Fennell ID. The genus Aspergillus. The Williams & Wilkins Cop. Baltimore. 1965;pp:293-357.
74. Rogers DP. The genus Cordyceps and Fries’s observationes. Mycologia. 1954;46:248-53.
75. Rukachaisirikul V, et al. A cyclopeptide from the insect pathogenic fungus Cordyceps sp. BCC 1788. J Nat Prod. 2006;69:305-307.
76. Rukachaisirikul V, et al. 10- membered macrolides from the insect pathogenic fungus Cordyceps militaris BCC 2816. J Nat Prod. 2004;67:1953-1958.
77. Schroeter J. Kryptogamen-flora von schlesien halfte. In: Cohn F (ed.) Kryptogamen-Flora von Schlesien. Breslau: J.U. Kern’s Verlag1 1894;3:1-597.
78. Shrestha B, et al. A brief chronicle of the genus cordyceps fr., the oldest valid genus in cordycipitaceae (hypocreales, ascomycota). Mycobiology. 2014;42:93-99.
79. Unagul P, et al. Production of red pigments by the insect pathogenic fungus Cordyceps unilateralis BCC 1869. J Ind Microbiol Biot. 1869;32:135-140.
80. Wanga Z, et al. Purification and partial characterization of Cu, Zn containing superoxide dismutase from entomogenous fungal species Cordyceps militaris. Enzyme Microb Tech. 2005;36:862-869.
81. Watanabe N, et al. Entomogenous fungi that produce 2, 6-pyridine dicarboxylic acid (dipicolinic acid). J Biosci Bioeng. 2006;102:365-373.
82. Wonga JH, et al. Cordymin, an antifungal peptide from the medicinal fungus Cordyceps militaris. Phytomedicine. 2011;18:387-392.
83. Xiao JH, et al. Nutritional requirements for the hyperproduction of bioactive exopolysaccharides by submerged fermentation of the edible medicinal fungus Cordyceps taii. Biochem Eng J. 2010;49:241-249.
84. Zang M, et al. A new taxon in the genus Cordyceps from China. Mycotaxon. 1990;38:57-62.
85.  Liang JY, et al. Chemical Constituents and Insecticidal Activity of the Essential Oils Extracted from Artemisia giraldii and Artemisia rubripes against Two Stored Product Insects. Med Chem (Los Angeles). 2016;6:541-545.
86. Goswami P, et al. Chemical Constituents of Floral Volatiles of Plumeria rubra L. from India. Med Aromat Plants. 2016;S3:005.
87. Bekele D, et al. Bioactive Chemical Constituents from the Leaf of Oreosyce africana Hook.f (Cucurbitaceae) with Mosquitocidal Activities against Adult Anopheles arabiensis, the Principal Malaria Vector in Ethiopia. J Fertil Pestic. 2016;7:159.
88. Fadeyi OE, et al. Isolation and Characterization of the Chemical Constituents of Anacardium occidentale Cracked Bark. Nat Prod Chem Res. 2015;3:192.
89. Zhang X and Guan Y. Nuclear Receptor FXR: A Potential Therapeutic Target for the Treatment of Diseases with Impaired Urine Concentration. J Mol Biomarkers Diagn. 2016;7:278.
90. Kaiser k, et al. Content Validation of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale in Moderately to Highly Active Rheumatoid Arthritis. Rheumatology (Sunnyvale). 2016;6:193.
91. Hu JJ, et al. Cancer Related Fatigue and Clinical Outcome of Dendritic Cell Vaccine in Combination with Cytokine-Induced Killer Cell Therapy in Cancer Patients. J Immunooncol. 2016;2:104.
92. Abatta LR, et al. Analysis of the Fracture of Steel Reinforcing Bars under Low Cycle Fatigue. Biol Med (Aligarh). 2016;8:285.
93. Scovassi AI and Guamán Ortiz LM. Traditional Medicine: An Ancient Remedy Rediscovered. Biochem Pharmacol. 2013;2:110.
94. Eddouks M. Management of Diabetes in Africa: The Role of Traditional Medicines. Pharmaceut Reg Affairs. 2012;1:e111.