Abstract
Ophiocordyceps sinensis is one of the most sought-after medicinal fungi used to treat various medical conditions such as respiratory diseases, liver and kidney dysfunctions. In China, it is widely used for alleviation of frequent urination where patients treated with O. sinensis have shown improvement in nocturia, which is the most common symptom of overactive bladder (OAB). Many studies have reported its anticancer, anti-inflammatory, anti-oxidative, hypoglycaemic and vasorelaxation properties. These properties are attributable to the presence of bioactive components such as polysaccharides, proteins and nucleosides. This mini-review highlights the medicinal potential of O. sinensis in alleviating OAB, which is a debilitating condition with a profound impact on the quality of life in a high proportion of older people. Four possible mechanisms of action of O. sinensis are suggested. Firstly, the relaxation of bladder smooth muscle through calcium dynamic, production of nitric acid (NO) and adenosine triphosphate (ATP). A second mechanism proposed is through the suppression of micturition reflex. The unequivocal properties of O. sinensis as anti-inflammatory and anti-oxidant, are two other plausible explanations, as both chronic inflammation and accumulation of oxidative stress molecules are associated with OAB exacerbation. With the recent success in cultivation of O. sinensis and the positive results from toxicity studies, a better understanding of its pharmacological actions can be further substantiated, including its use for relieving OAB.
References
Abrams, P., Kelleher, C. J., Kerr, L. A., & Rogers, R. G. (2000). Overactive bladder significantly affects quality of life. American Journal of Managed Care, 6(11 SUPPL.). Retrieved from https://pubmed.ncbi.nlm.nih.gov/11183901/
Alexandre, E. C., Calmasini, F. B., de Oliveira, M. G., Silva, F. H., da Silva, C. P. V., André, D. M., … Antunes, E. (2016). Chronic treatment with resveratrol improves overactive bladder in obese mice via antioxidant activity. European Journal of Pharmacology, 788, 29-36.
https://doi.org/10.1016/j.ejphar.2016.06.017
Apodaca, G., Kiss, S., Ruiz, W., Meyers, S., Zeidel, M., & Birder, L. (2003). Disruption of bladder epithelium barrier function after spinal cord injury. American Journal of Physiology - Renal Physiology, 284(5 53-5).
https://doi.org/10.1152/ajprenal.00359.2002
Athanasopoulos, A., & Giannitsas, K. (2011). An overview of the clinical use of antimuscarinics in the treatment of overactive bladder. Advances in Urology.
https://doi.org/10.1155/2011/820816
Azadzoi, K. M., Radisavljevic, Z. M., Golabek, T., Yalla, S. V., & Siroky, M. B. (2010). Oxidative Modification of Mitochondrial Integrity and Nerve Fiber Density in the Ischemic Overactive Bladder. Journal of Urology, 183(1), 362-369.
https://doi.org/10.1016/j.juro.2009.08.103
Bao, Z. D., Wu, Z. G., & Zheng, F. (1994). Amelioration of aminoglycoside nephrotoxicity by Cordyceps sinensis in old patients. Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban, 14(5).
Boland, B., Himpens, B., Paques, C., Casteels, R., & Gillis, J. M. (1993). ATP induced‐relaxation in the mouse bladder smooth muscle. British Journal of Pharmacology, 108(3), 749-753.
https://doi.org/10.1111/j.1476-5381.1993.tb12872.x
Brading, A. F. (1997). A myogenic basis for the overactive bladder. Urology, 50(6 SUPPL. A), 57-67.
https://doi.org/10.1016/S0090-4295(97)00591-8
Chatterjee, R., Srinivasan, K. S., & Maiti, P. C. (1957). Cordyceps sinensis (Berkeley) Saccardo: Structure of Cordycepic Acid. Journal of the American Pharmaceutical Association (Scientific Ed.), 46(2), 114-118.
https://doi.org/10.1002/jps.3030460211
Chen, H., Li, S., Wang, P., Yan, S., Hu, L., Pan, X., … Leung, G. P. (2014). Endothelium-dependent and -independent relaxation of rat aorta induced by extract of Schizophyllum commune. Phytomedicine, 21(11), 1230-1236.
https://doi.org/10.1016/j.phymed.2014.06.008
Chiou, W. F., Chang, P. C., Chou, C. J., & Chen, C. F. (2000). Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis. Life Sciences, 66(14), 1369-1376.
https://doi.org/10.1016/S0024-3205(00)00445-8
Chughtai, B., Kavaler, E., Lee, R., Te, A., Kaplan, S. A., & Lowe, F. (2013). Use of herbal supplements for overactive bladder. Reviews in Urology, 15(3), 93-96. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24223020%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3821987
Chung, H. C., Lee, C. K., Park, K. H., & Jeong, S. W. (2015). Bladder outlet obstruction causes up-regulation of nicotinic acetylcholine receptors in bladder-projecting pelvic ganglion neurons. Brain Research, 1602(C), 111-118.
https://doi.org/10.1016/j.brainres.2015.01.026
Coyne, K. S., Zhou, Z., Bhattacharyya, S. K., Thompson, C. L., Dhawan, R., & Versi, E. (2003). The prevalence of nocturia and its effect on health-related quality of life and sleep in a community sample in the USA. BJU International, Vol. 92, pp. 948-954.
https://doi.org/10.1111/j.1464-410X.2003.04527.x
De Groat, W. C. (1997). Neurologic basis for the overactive bladder. Urology, 50(6 SUPPL. A), 36-52.
https://doi.org/10.1016/S0090-4295(97)00587-6
de Groat, W. C., & Yoshimura, N. (2012). Plasticity in reflex pathways to the lower urinary tract following spinal cord injury. Experimental Neurology, Vol. 235, pp. 123-132.
https://doi.org/10.1016/j.expneurol.2011.05.003
Dong, C. H., & Yao, Y. J. (2008). In vitro evaluation of antioxidant activities of aqueous extracts from natural and cultured mycelia of Cordyceps sinensis. LWT - Food Science and Technology, 41(4), 669-677.
https://doi.org/10.1016/j.lwt.2007.05.002
Endeshaw, Y. W., Schwartz, A. V., Stone, K., Caserotti, P., Harris, T., Smagula, S., & Satterfield, S. (2016). Nocturia, insomnia symptoms and mortality among older men: The health, aging and body composition study. Journal of Clinical Sleep Medicine, 12(6), 789-796.
https://doi.org/10.5664/jcsm.5870
Fung, S. Y., Cheong, P. C. H., Tan, N. H., Ng, S. T., & Tan, C. S. (2018). Nutrient and chemical analysis of fruiting bodies of a cultivar of the Chinese caterpillar mushroom, Ophiocordyceps sinensis (Ascomycetes). International Journal of Medicinal Mushrooms, 20(5), 459-469. h
https://doi.org/10.1615/IntJMedMushrooms.2018026252
Fung, S. Y., Lee, S. S., Tan, N. H., & Pailoor, J. (2017). Safety assessment of cultivated fruiting body of Ophiocordyceps sinensis evaluated through subacute toxicity in rats. Journal of Ethnopharmacology, 206, 236-244.
https://doi.org/10.1016/j.jep.2017.05.037
Ghoniem, G., Faruqui, N., Elmissiry, M., Mahdy, A., Abdelwahab, H., Oommen, M., & Abdel-Mageed, A. B. (2011). Differential profile analysis of urinary cytokines in patients with overactive bladder. International Urogynecology Journal, 22(8), 953-961.
https://doi.org/10.1007/s00192-011-1401-8
Giuliano, F., Ückert, S., Maggi, M., Birder, L., Kissel, J., & Viktrup, L. (2013). The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. European Urology, Vol. 63, pp. 506-516.
https://doi.org/10.1016/j.eururo.2012.09.006
Hanna-Mitchell, A. T., Kashyap, M., Chan, W. V., Andersson, K. E., & Tannenbaum, C. (2014). Pathophysiology of idiopathic overactive bladder and the success of treatment: A systematic review from ICI-RS 2013. Neurourology and Urodynamics, Vol. 33, pp. 611-617.
https://doi.org/10.1002/nau.22582
He, Q., Wang, Z., Liu, G., Daneshgari, F., MacLennan, G. T., & Gupta, S. (2016). Metabolic syndrome, inflammation and lower urinary tract symptoms: Possible translational links. Prostate Cancer and Prostatic Diseases, 19(1), 7-13.
https://doi.org/10.1038/pcan.2015.43
Hegele, A., Knippschild, S., Frohme, C., Hänze, J., Olbert, P., & Hofmann, R. (2014). Changes in prostaglandin E2 in patients with idiopathic overactive bladder syndrome after botulinum toxin type A treatment: Is there a clinical benefit? BMC Urology, 14(1).
https://doi.org/10.1186/1471-2490-14-85
Hsu, T. H., Shiao, L. H., Hsieh, C., & Chang, D. M. (2002). A comparison of the chemical composition and bioactive ingredients of the Chinese medicinal mushroom DongChongXiaCao, its counterfeit and mimic, and fermented mycelium of Cordyceps sinensis. Food Chemistry, 78(4), 463-469.
https://doi.org/10.1016/S0308-8146(02)00158-9
Hu, Z., Lee, C. Il, Shah, V. K., Oh, E. H., Han, J. Y., Bae, J. R., … Oh, K. W. (2013). Cordycepin increases nonrapid eye movement sleep via adenosine receptors in rats. Evidence-Based Complementary and Alternative Medicine, 2013.
https://doi.org/10.1155/2013/840134
Ji, N. F., Yao, L. S., Li, Y., He, W., Yi, K. S., & Huang, M. (2011). Polysaccharide of Cordyceps sinensis enhances cisplatin cytotoxicity in non-small cell lung cancer H157 cell line. Integrative Cancer Therapies, 10(4), 359-367.
https://doi.org/10.1177/1534735410392573
Jia, J. M., Ma, X. C., Wu, C. F., Wu, L. J., & Hu, G. S. (2005). Cordycedipeptide A, a new cyclodipeptide from the culture liquid of Cordyceps sinensis (BERK.) SACC. Chemical and Pharmaceutical Bulletin, 53(5), 582-583.
https://doi.org/10.1248/cpb.53.582
Khan, M. S., Parveen, R., Mishra, K., Tulsawani, R., & Ahmad, S. (2015). Determination of nucleosides in Cordyceps sinensis and Ganoderma lucidum by high performance liquid chromatography method. Journal of Pharmacy and Bioallied Sciences, 7(4), 264-266.
https://doi.org/10.4103/0975-7406.168022
Kitta, T., Chancellor, M. B., De Groat, W. C., Kuno, S., Nonomura, K., & Yoshimura, N. (2014). Roles of adenosine A1 and A2A receptors in the control of micturition in rats. Neurourology and Urodynamics, 33(8), 1259-1265.
https://doi.org/10.1002/nau.22487
Lee, M. K., Li, X., Yap, A. C. S., Cheung, P. C. K., Tan, C. S., Ng, S. T., … Fung, S. Y. (2018). Airway relaxation effects of water-soluble sclerotial extract from Lignosus rhinocerotis. Frontiers in Pharmacology, 9(MAY), 461.
https://doi.org/10.3389/fphar.2018.00461
Leiria, L. O. S., Mõnica, F. Z. T., Carvalho, F. D. G. F., Claudino, M. A., Franco-Penteado, C. F., Schenka, A., … Antunes, E. (2011). Functional, morphological and molecular characterization of bladder dysfunction in streptozotocin-induced diabetic mice: Evidence of a role for L-type voltage-operated Ca 2+ channels. British Journal of Pharmacology, 163(6), 1276-1288.
https://doi.org/10.1111/j.1476-5381.2011.01311.x
Lemack, G. E., Zimmern, P. E., Vazquez, D., McConnell, J. D., & Lin, V. K. (2000). Altered response to partial bladder outlet obstruction in mice lacking inducible nitric oxide synthase. Journal of Urology, 163(6), 1981-1987.
https://doi.org/10.1016/S0022-5347(05)67614-8
Li, S. P., Li, P., Dong, T. T. X., & Tsim, K. W. K. (2001). Anti-oxidation activity of different types of natural Cordyceps sinensis and cultured Cordyceps mycelia. Phytomedicine.
https://doi.org/10.1078/0944-7113-00030
Li, S. P., Zhang, G. H., Zeng, Q., Huang, Z. G., Wang, Y. T., Dong, T. T. X., & Tsim, K. W. K. (2006). Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia. Phytomedicine.
https://doi.org/10.1016/j.phymed.2005.02.002
Li, Shao P., Zhao, K. J., Ji, Z. N., Song, Z. H., Dong, T. T. X., Lo, C. K., … Tsim, K. W. K. (2003). A polysaccharide isolated from Cordyceps sinensis, a traditional Chinese medicine, protects PC12 cells against hydrogen peroxide-induced injury. Life Sciences, 73(19), 2503-2513.
https://doi.org/10.1016/S0024-3205(03)00652-0
Li, X., Liu, Q., Li, W., Li, Q., Qian, Z., Liu, X., & Dong, C. (2019). A breakthrough in the artificial cultivation of Chinese cordyceps on a large-scale and its impact on science, the economy, and industry. Critical Reviews in Biotechnology, 39(2), 181-191.
https://doi.org/10.1080/07388551.2018.1531820
Li, Yan, Li, K., Mao, L., Han, X., Zhang, K., Zhao, C., & Zhao, J. (2016). Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc. PeerJ Life and Environment, 2016(5).
https://doi.org/10.7717/peerj.1992
Li, Yi, Wang, X. L., Jiao, L., Jiang, Y., Li, H., Jiang, S. P., … Yao, Y. J. (2011). A survey of the geographic distribution of Ophiocordyceps sinensis. Journal of Microbiology, 49(6), 913-919.
https://doi.org/10.1007/s12275-011-1193-z
Liu, H. P., Chen, G. L., Liu, P., & Xu, X. P. (2009). Amlodipine alone or combined with terazosin improves lower urinary tract disorder in rat models of benign prostatic hyperplasia or detrusor instability: Focus on detrusor overactivity. BJU International, 104(11), 1752-1757.
https://doi.org/10.1111/j.1464-410X.2009.08659.x
Liu, Y., Wang, J., Wang, W., Zhang, H., Zhang, X., & Han, C. (2015). The chemical constituents and pharmacological actions of Cordyceps sinensis. Evidence-Based Complementary and Alternative Medicine, 2015, 12.
https://doi.org/10.1155/2015/575063
Lo, H. C., Hsieh, C., Lin, F. Y., & Hsu, T. H. (2013). A systematic review of the mysterious caterpillar fungus Ophiocordyceps sinensis in Dong-ChongXiaCao (Dōng Chóng Xià Cǎo) and related bioactive ingredients. Journal of Traditional and Complementary Medicine, Vol. 3, pp. 16-32.
https://doi.org/10.1016/S2225-4110(16)30164-X
Lu, W. J., Chang, N. C., Jayakumar, T., Liao, J. C., Lin, M. J., Wang, S. H., … Sheu, J. R. (2014). Ex vivo and in vivo studies of CME-1, a novel polysaccharide purified from the mycelia of Cordyceps sinensis that inhibits human platelet activation by activating adenylate cyclase/cyclic AMP. Thrombosis Research, 134(6), 1301-1310.
https://doi.org/10.1016/j.thromres.2014.09.023
Mamta, Mehrotra, S., Amitabh, Kirar, V., Vats, P., Nandi, S. P., … Misra, K. (2015). Phytochemical and antimicrobial activities of Himalayan Cordyceps sinensis (Berk.) Sacc. Indian Journal of Experimental Biology, 53(1), 36-43.
Mattiasson, A., Ekstrom, B., & Andersson, K. E. (1989). Effects of intravesical instillation of verapamil in patients with detrusor hyperactivity. Journal of Urology.
https://doi.org/10.1016/S0022-5347(17)40635-5
McVary, K. (2006). Lower urinary tract symptoms and sexual dysfunction: Epidemiology and pathophysiology. BJU International, 97(SUPPL. 2), 23-28.
https://doi.org/10.1111/j.1464-410X.2006.06102.x
Meena, H., Singh, K. P., Negi, P. S., & Ahmed, Z. (2013). Sub-acute toxicity of cultured mycelia of Himalayan entomogenous fungus Cordyceps sinensis (Berk.) Sacc. in rats. Indian Journal of Experimental Biology, 51(5), 381-387.
Miyata, Y., Matsuo, T., Mitsunari, K., Asai, A., Ohba, K., & Sakai, H. (2019). A review of oxidative stress and urinary dysfunction caused by bladder outlet obstruction and treatments using antioxidants. Antioxidants, 8(5).
https://doi.org/10.3390/antiox8050132
Nakagomi, H., Yoshiyama, M., Mochizuki, T., Miyamoto, T., Komatsu, R., Imura, Y., … Koizumi, S. (2016). Urothelial ATP exocytosis: Regulation of bladder compliance in the urine storage phase. Scientific Reports, Vol. 6.
https://doi.org/10.1038/srep29761
National Institute For Health and Care, & Excellence. (2015). Urinary incontinence | Guidance and guidelines | NICE. National Institute of Health and Clinical Evidence. Retrieved from https://www.nice.org.uk/guidance/cg171
Nomiya, M., Andersson, K. E., & Yamaguchi, O. (2015). Chronic bladder ischemia and oxidative stress: New pharmacotherapeutic targets for lower urinary tract symptoms. International Journal of Urology.
https://doi.org/10.1111/iju.12652
Park, J. S., Jung, H. Do, Cho, Y. S., Jin, M. H., & Hong, C. H. (2018). Neonatal bladder irritation is associated with vanilloid receptor TRPV1 expression in adult rats. International Neurourology Journal, 22(3), 169-176.
https://doi.org/10.5213/inj.1836020.101
Peng, Y., Tao, Y., Wang, Q., Shen, L., Yang, T., Liu, Z., & Liu, C. (2014). Ergosterol is the active compound of cultured mycelium cordyceps sinensis on antiliver fibrosis. Evidence-Based Complementary and Alternative Medicine, 2014.
https://doi.org/10.1155/2014/537234
Qi, W., Zhang, Y., Yan, Y. B., Lei, W., Wu, Z. X., Liu, N., … Fan, Y. (2013). The protective effect of cordymin, a peptide purified from the medicinal mushroom Cordyceps sinensis, on diabetic osteopenia in alloxan-induced diabetic rats. Evidence-Based Complementary and Alternative Medicine, 2013.
https://doi.org/10.1155/2013/985636
Qian, G. M., Pan, G. F., & Guo, J. Y. (2012). Anti-inflammatory and antinociceptive effects of cordymin, a peptide purified from the medicinal mushroom Cordyceps sinensis. Natural Product Research, 26(24), 2358-2362.
https://doi.org/10.1080/14786419.2012.658800
Rahnama'i, M. S., van Koevringe, G. A., & Van Kerrebroeck, P. E. (2013). Overactive bladder syndrome and the potential role of prostaglandins and phosphodiesterases: An introduction. Nephro-Urology Monthly, 5(4), 933-944.
https://doi.org/10.5812/numonthly.14087
Searl, T. J., Dynda, D. I., Alanee, S. R., El-Zawahry, A. M., McVary, K. T., & Silinsky, E. M. (2016). A1 Adenosine Receptor-Mediated Inhibition of Parasympathetic Neuromuscular Transmission in Human and Murine Urinary Bladder. The Journal of Pharmacology and Experimental Therapeutics, 356(1), 116-122.
https://doi.org/10.1124/jpet.115.228882
Seo, M. J., Kim, M. J., Lee, H. H., Park, J. U., Kang, B. W., Kim, G. Y., … Jeong, Y. K. (2013). Effect of cordycepin on the expression of the inflammatory cytokines TNF-alpha, IL-6, and IL-17a in C57bL/6 mice. Journal of Microbiology and Biotechnology, 23(2), 156-160.
https://doi.org/10.4014/jmb.1211.11032
Silva, I., Costa, A. F., Moreira, S., Ferreirinha, F., Magalhães-Cardoso, M. T., Calejo, I., … Correia-de-Sá, P. (2017). Inhibition of cholinergic neurotransmission by β3-adrenoceptors depends on adenosine release and A1-receptor activation in human and rat urinary bladders. American Journal of Physiology - Renal Physiology, 313(2), F388-F403.
https://doi.org/10.1152/ajprenal.00392.2016
Singh, M., Tulsawani, R., Koganti, P., Chauhan, A., Manickam, M., & Misra, K. (2013). Cordyceps sinensis increases hypoxia tolerance by inducing heme oxygenase-1 and metallothionein via Nrf2 activation in human lung epithelial cells. BioMed Research International, 2013, 1-13.
https://doi.org/10.1155/2013/569206
Siu, K. M., Mak, D. H. F., Chiu, P. Y., Poon, M. K. T., Du, Y., & Ko, K. M. (2004). Pharmacological basis of "Yin-nourishing" and "Yang-invigorating" actions of Cordyceps, a Chinese tonifying herb. Life Sciences, 76(4), 385-395.
https://doi.org/10.1016/j.lfs.2004.07.014
Srikrishna, S., Robinson, D., Cardozo, L., & Vella, M. (2007). Management of overactive bladder syndrome. Postgraduate Medical Journal, 83(981), 481-486.
https://doi.org/10.1136/pgmj.2007.057232
Steers, W. D. (2002). Pathophysiology of overactive bladder and urge urinary incontinence. Reviews in Urology, 4 Suppl 4, S7-S18. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16986023%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC1476015
Sui, G., Fry, C. H., Malone-Lee, J., & Wu, C. (2009). Aberrant Ca2+ oscillations in smooth muscle cells from overactive human bladders. Cell Calcium, 45(5), 456-464.
https://doi.org/10.1016/j.ceca.2009.03.001
Sun, X., Dong, Z., Li, N., Feng, X., Liu, Y., Li, A., … Zhao, Z. (2018). Nucleosides isolated from ophiocordyceps sinensis inhibit cigarette smoke extract-induced inflammation via the SIRT1-nuclear factor-κB/p65 pathway in RAW264.7 macrophages and in COPD mice. International Journal of COPD, 13, 2821-2832.
https://doi.org/10.2147/COPD.S172579
Tyagi, P. (2011). Pathophysiology of the urothelium and detrusor. Canadian Urological Association Journal, 5(5), S128-S130.
https://doi.org/10.5489/cuaj.11181
Tyagi, P., Barclay, D., Zamora, R., Yoshimura, N., Peters, K., Vodovotz, Y., & Chancellor, M. (2010). Urine cytokines suggest an inflammatory response in the overactive bladder: A pilot study. International Urology and Nephrology, 42(3), 629-635.
https://doi.org/10.1007/s11255-009-9647-5
Wang, N., Li, J., Huang, X., Chen, W., & Chen, Y. (2016). Herbal Medicine Cordyceps sinensis Improves Health-Related Quality of Life in Moderate-to-Severe Asthma. Evidence-Based Complementary and Alternative Medicine, 2016(6134593).
https://doi.org/10.1155/2016/6134593
Wang, Z., Cheng, Z., Cristofaro, V., Li, J., Xiao, X., Gomez, P., … Olumi, A. F. (2012). Inhibition of TNF-α improves the bladder dysfunction that is associated with type 2 diabetes. Diabetes, 61(8), 2134-2145.
https://doi.org/10.2337/db11-1763
Wang, Z. M., Peng, X., Lee, K. L. D., Tang, J. C. O., Cheung, P. C. K., & Wu, J. Y. (2011). Structural characterisation and immunomodulatory property of an acidic polysaccharide from mycelial culture of Cordyceps sinensis fungus Cs-HK1. Food Chemistry, 125(2), 637-643.
https://doi.org/10.1016/j.foodchem.2010.09.052
Wei, X., Hu, H., Zheng, B., Arslan, Z., Huang, H. C., Mao, W., & Liu, Y. M. (2017). Profiling metals in Cordyceps sinensis by using inductively coupled plasma mass spectrometry. Analytical Methods, 9(4), 724-728.
https://doi.org/10.1039/C6AY02524B
Winder, M., Tobin, G., Zupančič, D., & Romih, R. (2014). Signalling molecules in the urothelium. BioMed Research International, 2014.
https://doi.org/10.1155/2014/297295
Winkler, D. (2011). Caterpillar Fungus (Ophiocordyceps sinensis) Production and Sustainability on the Tibetan Plateau and in the Himalayas. Asian Medicine, 5(2), 291-316.
https://doi.org/10.1163/157342109X568829
Winston, D., & Maimes, S. (2007). Adaptogens: Herbs for Strength, Stamina, and Stress Relief. In Healing Arts Press (1st ed.). Retrieved from http://www.holy-basil.com/6865.html
World Health Organization. (2017). Integrated Care for Older People: guidelines on community-level interentions to manage declines in intrinsic capacity. Retrieved from https://www.who.int/ageing/publications/guidelines-icope/en/
Yalin, W., Ishurd, O., Cuirong, S., & Yuanjiang, P. (2005). Structure analysis and antitumor activity of (1→3)-β-D-glucans (cordyglucans) from the mycelia of Cordyceps sinensis. Planta Medica, 71(4), 381-384.
https://doi.org/10.1055/s-2005-864111
Yamaguchi, O., Kakizaki, H., Homma, Y., Igawa, Y., Takeda, M., Nishizawa, O., … Kuroishi, K. (2015). Safety and efficacy of mirabegron as "add-on" therapy in patients with overactive bladder treated with solifenacin: A post-marketing, open-label study in Japan (MILAI study). BJU International, 116(4), 612-622.
https://doi.org/10.1111/bju.13068
Yamaguchi, Y., Kagota, S., Nakamura, K., Shinozuka, K., & Kunitomo, M. (2000). Antioxidant activity of the extracts from fruiting bodies of cultured Cordyceps sinensis. Phytotherapy Research, 14(8), 647-649.
https://doi.org/10.1002/1099-1573(200012)14:8<647::AID-PTR670>3.0.CO;2-W
Yang, F. Q., Li, D. Q., Feng, K., Hu, D. J., & Li, S. P. (2010). Determination of nucleotides, nucleosides and their transformation products in Cordyceps by ion-pairing reversed-phase liquid chromatography-mass spectrometry. Journal of Chromatography A, 1217(34), 5501-5510.
https://doi.org/10.1016/j.chroma.2010.06.062
Yang, L. Y., Chen, A., Kuo, Y. C., & Lin, C. Y. (1999). Efficacy of a pure compound H1-A extracted from Cordyceps sinensis on autoimmune disease of MRL lpr/lpr mice. Journal of Laboratory and Clinical Medicine, 134(5), 492-500.
https://doi.org/10.1016/S0022-2143(99)90171-3
Yang, M. L., Kuo, P. C., Hwang, T. L., & Wu, T. S. (2011). Anti-inflammatory principles from Cordyceps sinensis. Journal of Natural Products.
https://doi.org/10.1021/np100902f
Ye, M. Q., Hu, Z., Fan, Y., He, L., Xia, F. B., & Zou, G. L. (2004). Purification and characterization of an acid deoxyribonuclease from the cultured mycelia of Cordyceps sinensis. Journal of Biochemistry and Molecular Biology, 37(4), 466-473.
https://doi.org/10.5483/BMBRep.2004.37.4.466
Ying, X., Peng, L., Chen, H., Shen, Y., Yu, K., & Cheng, S. (2014). Cordycepin prevented IL-β-induced expression of inflammatory mediators in human osteoarthritis chondrocytes. International Orthopaedics, 38(7), 1519-1526.
https://doi.org/10.1007/s00264-013-2219-4
Zhang, Y. J., & Bai, Q. (2014). Urinary prostaglandins E2 correlates to overactive bladder symptoms in patients with benign prostatic hyperplasia. National Journal of Andrology, 20(3), 244-248. Retrieved from https://pubmed.ncbi.nlm.nih.gov/24738462/
Zhang, Z. J., Luo, H. L., & Li, J. S. (1997). Clinical and experimental studies on elimination of oxygen free radical of jinshuibao capsule in treating senile deficiency syndrome and its deoxyribonucleic acid damage repairing effects. Chinese Journal of Integrated Traditional and Western Medicine, 17(1), 35-38. Retrieved from https://pubmed.ncbi.nlm.nih.gov/9812650/

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Copyright (c) 2020 Li-Yin Pang, Chon-Seng Tan, Szu-Ting Ng, Kuan-Hon Lim, Sue-Mian Then, Ting Kang Nee
