scholarly journals Endophytic Fungal Community of Huperzia serrata: Diversity and Relevance to the Production of Huperzine A by the Plant Host

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 892
Author(s):  
Lingli Cui ◽  
Hamza Armghan Noushahi ◽  
Yipeng Zhang ◽  
Jinxin Liu ◽  
Andreea Cosoveanu ◽  
...  

As the population ages globally, there seem to be more people with Alzheimer’s disease. Unfortunately, there is currently no specific treatment for the disease. At present, Huperzine A (HupA) is one of the best drugs used for the treatment of Alzheimer’s disease and has been used in clinical trials for several years in China. HupA was first separated from Huperzia serrata, a traditional medicinal herb that is used to cure fever, contusions, strains, hematuria, schizophrenia, and snakebite for several hundreds of years in China, and has been confirmed to have acetylcholinesterase inhibitory activity. With the very slow growth of H. serrata, resources are becoming too scarce to meet the need for clinical treatment. Some endophytic fungal strains that produce HupA were isolated from H. serrate in previous studies. In this article, the diversity of the endophytic fungal community within H. serrata was observed and the relevance to the production of HupA by the host plant was further analyzed. A total of 1167 strains were obtained from the leaves of H. serrata followed by the stems (1045) and roots (824). The richness as well as diversity of endophytic fungi within the leaf and stem were higher than in the root. The endophytic fungal community was similar within stems as well as in leaves at all taxonomic levels. The 11 genera (Derxomyces, Lophiostoma, Cyphellophora, Devriesia, Serendipita, Kurtzmanomyces, Mycosphaerella, Conoideocrella, Brevicellicium, Piskurozyma, and Trichomerium) were positively correlated with HupA content. The correlation index of Derxomyces with HupA contents displayed the highest value (CI = 0.92), whereas Trichomerium showed the lowest value (CI = 0.02). Through electrospray ionization mass spectrometry (ESI-MS), it was confirmed that the HS7-1 strain could produce HupA and the total alkaloid concentration was 3.7 ug/g. This study will enable us to screen and isolate the strain that can produce HupA and to figure out the correlation between endophytic fungal diversity with HupA content in different plant organs. This can provide new insights into the screening of strains that can produce HupA more effectively.

Author(s):  
Nguyen Thi Thu Hoai ◽  
Nguyen Thuy Duong ◽  
Bui Thanh Tung ◽  
Dao Thi Vui ◽  
Dang Kim Thu

Herbal extract, rich with natural compounds, has been used for medicinal purpose such as treating neurological disorders such as cognitive defection for a long period of time, often without significant adverse effects. We compared AChE and BuChE – inhibition effect of total extracts and fractions of Huperzia serrata (Thunb.) Trevis. with alcaloid-rich extract. Our samples were subjected under supersonic extraction with ethanol 50o as solvent and fractionally extracted with n-hexane, EtOAc and n-butanol, respectively; alcaloid-rich extract was collected simutaneously. Ellman’s method was used to assay AChE and BuChE inhibition activity. Results: Alcaloid-rich extraction proved to be the superior AChE inhibiting agent, its activity nearly 6 fold of the most active Huperzia serrata extraction with IC50 value of 7.93 (5.43-10.98) µg/ml. While the fractions as well as the total extract did not provide any BuChE inhibition activity, alcaloid-rich extract showed weak ability (IC50 at 76.67 (64.78 – 91.84) µg/ml). Overall, the superior enzyme inhibition effect of alcaloid-rich extract might open a new approach in preventing and treating neurological disorders such as alzheimer’s. Keywords Huperzia serrata (Thunb.) Trevis, alcaloid, Acetylcholinesrerase inhibitors (AChE); butyrylcholinesterase (BuChE), Alzheimer. References [1] Dos Santos Picanco, Leide C et al., Alzheimer's disease: A review from the pathophysiology to diagnosis, new perspectives for pharmacological treatment, Current medicinal chemistry 25(26) (2018) 3141 - 3159. https://doi.org/10.2174/0929867323666161213101126.[2] B.M. McGleenon, K.B. Dynan, A.P. Passmore, Acetylcholinesterase inhibitors in Alzheimer's disease, British journal of clinical pharmacology 48(4) (1999) 471-480. https://10.1046/j.1365-2125.1999.00026.x.[3] Agneta Nordberg, Clive Ballard, Roger Bullock, Taher Darreh-Shori, Monique Somogyi, A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease, The primary care companion for CNS disorders 15(2) (2013). https://10.4088/PCC.12r01412.[4] N.M. Ha, V.V. Dung et al., Report on the review of Vietnam’s wildlife trade policy, 2007.[5] D.H. Bich, et al., Medicinal plants and medicinal animals in Viet Nam. Science and Technics Publishing House 1 (2011) 896-897 (in Vietnamese).[6] Jia-Sen Liu, Yuan-Long Zhu, Chao-Mei Yu, You-Zuo Zhou, Yan-Yi Han, Feng-Wu Wu, Bao-Feng Qi, The structures of huperzine A and B, two new alkaloids exhibiting marked anticholinesterase activity. Canadian Journal of Chemistry 64(4) (1986) 837-839. https://doi.org/10.1139/v86-137.[7] Takuya Ohba, Yuta Yoshino et al., Japanese Huperzia serrata extract and the constituent, huperzine A, ameliorate the scopolamine-induced cognitive impairment in mice, Bioscience biotechnology and biochemistry 79(11) (2015) 1838-1844. https://doi.org/10.1080/09168451.2015.1052773.[8] Ju-Yeon Park, Hyuck Kim et al., Ethanol Extract of Lycopodium serratum Thunb. Attenuates Lipopolysaccharide-Induced C6 Glioma Cells Migration via Matrix Metalloproteinase-9 Expression, Chinese Journal of Integrative Medicine 24(11) (2018) 860-866. https://doi.org/10.1007/s11655-017-2923-9.[9] M. Maridass, G. Raju, Investigation of phytochemical and antimicrobial activity of Huperzia species, Pharmacologyonline 3 (2009) 688-692.[10] George.L.Ellman, K.Diane Courtney, et al., A new and rapid colorimetric determination of acetylcholinesterase activity, Biochemical Pharmacology 7(2) (1961) 88-95. https://doi.org/10.1016/0006-2952(61)90145-9.[11] Paul T Francis, et al., The cholinergic hypothesis of Alzheimer’s disease: a review of progress. Journal of Neurology, Neurosurgery & Psychiatry, 66(2) (1999) 137-147. http://dx.doi.org/10.1136/jnnp.66.2.137.[12] Prerna Upadhyaya, Vikas Seth, Mushtaq Ahmad, Therapy of Alzheimer’s disease: An update, African Journal of Pharmacy and Pharmacology 4(6) (2010) 408-421.[13] Hachiro Sugimoto, Hiroo Ogura, et al., Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor, The Japanese journal of pharmacology 89(1) (2002) 7-20.[14] N.T.K. Thu, et al., Acetylcholinesterase and butyrylcholinesterase inhibition effect of fractions extract of Huperzia serrata (Thunb.) Trevis. The journal of Pharmeceutical 56(11) 49-53 (in Vietnamese).[15] Xiaoqiang Ma, Changheng Tan, et al, Is there a better source of huperzine A than Huperzia serrata? Huperzine A content of Huperziaceae species in China. J Agric Food Chem, 53(5) (2005)1393-8. https://doi.org/10.1021/jf048193n.[16] Ya-Bing Yang, Xue-Qiong Yang, et al., A New Flavone Glycoside from Huperzia serrata. Chinese Journal of Natural Medicines 6(6) (2008) 408-410.[17] G.T. Ha, R.K. Wong, Y. Zhang, Huperzine a as potential treatment of Alzheimer's disease: an assessment on chemistry, pharmacology, and clinical studies, Chemistry & biodiversity 8(7) (2011) 1189-1204. https://doi.org/10.1002/cbdv.201000269.[18] H.Y. Zhang, X.C. Tang, Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease, Trends in pharmacological sciences 27(12) (2006) 619-625. https://doi.org/10.1016/j.tips.2006.10.004.[19] Y. Wang, X.C. Tang, H.Y. Zhang, Huperzine A alleviates synaptic deficits and modulates amyloidogenic and nonamyloidogenic pathways in APPswe/PS1dE9 transgenic mice, Journal of neuroscience research 90(2) (2012) 508-517. https://doi.org/10.1002/jnr.22775.[20] C.Y. Wang, et al., Huperzine A activates Wnt/β-catenin signaling and enhances the nonamyloidogenic pathway in an Alzheimer transgenic mouse model, Neuropsychopharmacology 36(5) (2011) 1073-1089. https://doi.org/10.1038/npp.2010.245.[21] R.K. Gordon, et al., The NMDA receptor ion channel: a site for binding of Huperzine A, Journal of applied toxicology 21(S1) (2001) S47-S51. https://doi.org/10.1002/jat.805.[22] M. Rafii, et al., A phase II trial of huperzine A in mild to moderate Alzheimer disease, Neurology 76(16) (2011) 1389-1394. https://doi.org/10.1212/WNL.0b013e318216eb7b.[23] N.H. Greig, et al., A new therapeutic target in Alzheimer's disease treatment: attention to butyrylcholinesterase, Current medical research and opinion 17(3) (2001)1 59-165.[24] A. Ferreira, et al., Huperzine A from Huperzia serrata: a review of its sources, chemistry, pharmacology and toxicology, Phytochemistry reviews 15(1) (2016) 51-85. https://doi.org/10.1007/s11101-014-9384-y.


2020 ◽  
Author(s):  
Han Wen-Xia ◽  
Han Zhong-Wen ◽  
Jia Min ◽  
Zhang Han ◽  
Li Wei-Ze ◽  
...  

Abstract Background Huperzine A is an important drug for treating Alzheimer's disease and mainly extracted from the Huperzia serrata . Nevertheless, the content of Huperzine A in Huperzia serrata is very low of 0.007% with growing circle of 8 to 10 years, and the chemical synthesis of Huperzine A still has some insurmountable limitations in the industrialized production. So, the available resources of Huperzine A for clinical treatment of Alzheimer's disease are scarce. The purpose of this work was to construct a biosynthesis platform based on the endophytic fungi from Huperzia serrata . Methods Based on the morphological characteristics and nuclear ribosomal DNA ITS sequences of endophytic fungi to complete the strain identification. Combined alkaloid precipitation with acid dye colorimetry, thin layer chromatography, high-performance liquid chromatography, liquid chromatography-tandem mass spectrometry analysis and inhibition activity of acetylcholinesterase determination model to determine the physicochemical properties of the biosynthetic products. Compare the biosynthetic HupA with the listed APIs of HupA by the test of AChE inhibition ability and cytotoxicity in vitro. Results In this work, five endophytic fungi Mucor racemosus NSH-D, Mucor fragilis NSY-1, Fusarium verticillioides NSH-5, Fusarium oxysporum NSG-1 and Trichoderma harzianum NSW-V were firstly found and isolated from the Chinese folk medicine Qian Ceng Ta ( Huperzia serrata (Thunb.) Trevis. (Lycopodiaceae)), which were identified according to their morphological characteristics and nuclear ribosomal DNA ITS sequences. These fungi could effectively biosynthesize huperzine A in liquid culture of 100-400 mg/L which were 1 000 times higher than that of other reported conventional endophytic fungi. Moreover, these fungi with higher hereditary stability could possess the initial express ability of HupA after 40 generations, and the expressed HupA from these biosynthesis systems has the prior physicochemical properties, better inhibition activity of acetylcholinesterase and lower cytotoxicity compared to the listed APIs of HupA. Conclusions These results indicate that the endophytic fungi in this work provide a promising alternative platform for producing HupA at industrial scale by biosynthesis for the treatment of Alzheimer's disease.


2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.


2008 ◽  
Vol 175 (1-3) ◽  
pp. 396-402 ◽  
Author(s):  
Hai Yan Zhang ◽  
Chun Yan Zheng ◽  
Han Yan ◽  
Zhi Fei Wang ◽  
Li Li Tang ◽  
...  

2008 ◽  
Vol 4 ◽  
pp. T192-T192
Author(s):  
Hongmei Wu ◽  
Jun Li ◽  
RongLe Zhou ◽  
Guanjian Liu ◽  
Birong Dong

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