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Anticholinesterase, antioxidant, and beta-amyloid aggregation inhibitory constituents from Cremastra appendiculata

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Abstract

The tubers of Cremastra appendiculata (D. Don) Makino (Orchidaceae) are used in traditional Chinese medicine for the treatment of cancer and bacterial infections. Its 95% ethanol extract was found to display potent inhibitory activities on butyrylcholinesterase (BChE) (IC50 = 23.66 µg/mL) and β-amyloid peptide aggregation (74.09% at 100 μg/mL). Active ethyl acetate extract afforded one bibenzyl (1), four phenanthrenes (2–5), and one rotenoid (6) by a bioassay-guided isolation. Compounds 2, 3, and 5 exhibited potent BChE inhibitory effects with IC50 values of 19.66, 32.80, and 37.79 µM, respectively. Kinetic studies indicated that both 2 and 3 were mixed-type BChE inhibitors. Their strong binding affinities to BChE were further confirmed by fluorescence quenching analysis. Meanwhile, 2 and 3 showed the effective DPPH and ABTS radical scavenging activities (EC50 < 11 μM) and inhibition effect on β-amyloid peptide aggregation (64.49 and 29.50% at 20 μM, respectively), suggesting they could serve as multifunctional potential agents for AD drugs development. This paper revealed the potential medicinal and economic values of C. appendiculata and its chemical constituents in AD prevention/treatment.

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References

  • Broering TJ, Morrow GW (1999) Oxygenated dihydrophenanthrenes via quinol acetals: a brief synthesis of orchinol. Synth Commun 29:1135–1142

    Article  CAS  Google Scholar 

  • Brus B, Kosak U, Turk S, Pišlar A, Coquelle N, Kos J, Stojan J, Colletier JP, Gobec S (2014) Discovery, biological evaluation, and crystal structure of a novel nanomolar selective butyrylcholinesterase inhibitor. J Med Chem 57:8167–8179

    Article  CAS  PubMed  Google Scholar 

  • Coban G, Carlino L, Tarikogullari AH, Parlar S, Sarıkaya G, Alptüzün V, Alpan AS, Güneş HS, Erciyas E (2016) 1H-benzimidazole derivatives as butyrylcholinesterase inhibitors: synthesis and molecular modeling studies. Med Chem Res 25:2005–2014

    Article  CAS  Google Scholar 

  • Cummings JL (2004) Alzheimer’s disease. N Engl J Med 351:56–67

    Article  CAS  PubMed  Google Scholar 

  • Fang L, Gou S, Fang X, Cheng L, Fleck C (2013) Current progresses of novel natural products and their derivatives/analogs as anti-Alzheimer candidates: an update. Mini Rev Med Chem 13:870–887

    Article  CAS  PubMed  Google Scholar 

  • Furukawa-Hibi Y, Alkam T, Nitta A, Matsuyama A, Mizoguchi H, Suzuki K, Moussaoui S, Yu QS, Greig NH, Nagai T, Yamada K (2011) Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice. Behav Brain Res 225:222–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Godyń J, Jończyk J, Panek D, Malawska B (2016) Therapeutic strategies for Alzheimer’s disease in clinical trials. Pharmacol Rep 68:127–138

    Article  PubMed  Google Scholar 

  • Greig NH, Utsuki T, Ingram DK, Wang Y, Pepeu G, Scali C, Yu Q, Mamczarz J, Holloway HW, Giordano T, Chen D, Furukawa K, Sambamurti K, Brossi A, Lahiri DK (2005) Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent. Proc Natl Acad Sci USA 102:17213–17218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han SH, Mook-Jung I (2014) Diverse molecular targets for therapeutic strategies in Alzheimer’s disease. J Korean Med Sci 29:893–902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang L, Su T, Li X (2013) Natural products as sources of new lead compounds for the treatment of Alzheimer’s disease. Curr Top Med Chem 13:1864–1878

    Article  CAS  PubMed  Google Scholar 

  • Ikeda Y, Nonaka H, Furumai T, Igarashi Y (2005) Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata. J Nat Prod 68:572–573

    Article  CAS  PubMed  Google Scholar 

  • Krautwurst KD, Tochtermann W (1981) Polycyclische Verbindungen, XX1) Eine einfache Orchinol-Synthese. Chem Ber 114:214–219

    Article  CAS  Google Scholar 

  • Kumar A, Singh A (2015) A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol Rep 67:195–203

    Article  CAS  PubMed  Google Scholar 

  • Leong YW, Kang CC, Harrison LJ, Powell AD (1997) Phenanthrenes, dihydrophenanthrenes and bibenzyls from the orchid Bulbophyllum vaginatum. Phytochemistry 44:157–165

    Article  CAS  Google Scholar 

  • Li Q, Tu Y, Zhu C, Luo W, Huang W, Liu W, Li Y (2017) Cholinesterase, β-amyloid aggregation inhibitory and antioxidant capacities of Chinese medicinal plants. Ind Crops Prod 108:512–519

    Article  CAS  Google Scholar 

  • Libro R, Giacoppo S, Rajan TS, Bramanti P, Mazzon E (2016) Natural phytochemicals in the treatment and prevention of dementia: an overview. Molecules 21:518

    Article  PubMed  Google Scholar 

  • Liu L, Li J, Zeng KW, Jiang Y, Tu PF (2015) Five new benzylphenanthrenes from Cremastra appendiculata. Fitoterapia 103:27–32

    Article  CAS  PubMed  Google Scholar 

  • Majumder PL, Banerjee S (1988) Structure of flavanthrin, the first dimeric 9, 10-dihydrophenanthrene derivative from the orchid Eria flava. Tetrahedron 44:7303–7308

    Article  CAS  Google Scholar 

  • Ng YP, Or TCT, Ip NY (2015) Plant alkaloids as drug leads for Alzheimer’s disease. Neurochem Int 89:260–270

    Article  CAS  PubMed  Google Scholar 

  • Palmer AM (2011) Neuroprotective therapeutics for Alzheimer’s disease: progress and prospects. Trends Pharmacol Sci 32:141–147

    Article  CAS  PubMed  Google Scholar 

  • Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M (2016) World Alzheimer report 2016: improving healthcare for people living with dementia: coverage, quality and costs now and in the future. Alzheimer’s Disease International (ADI), London, UK

  • Shan WJ, Huang L, Zhou Q, Meng FC, Li XS (2011) Synthesis, biological evaluation of 9-N-substituted berberine derivatives as multi-functional agents of antioxidant, inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. Eur J Med Chem 46:5885–5893

    Article  CAS  PubMed  Google Scholar 

  • Shim JS, Kim JH, Lee J, Kim SN, Kwon HJ (2004) Anti-angiogenic activity of a homoisoflavanone from Cremastra appendiculata. Planta Med 70:171–173

    Article  CAS  PubMed  Google Scholar 

  • Singhal AK, Sharma RP, Baruah JN, Govindan SV, Herz W (1982) Rotenoids from roots of Millettia pachycarpa. Phytochemistry 21:949–951

    Article  CAS  Google Scholar 

  • Tu Y, Zhong Y, Du H, Luo W, Wen Y, Li Q, Zhu C, Li Y (2015) Anticholinesterases and antioxidant alkamides from Piper nigrum fruits. Nat Prod Res 30:1945–1949

    Article  PubMed  Google Scholar 

  • Unsal-Tan O, Ozadali-Sari K, Ayazgok B, Küçükkılınç TT, Balkan A (2017) Novel 2-arylbenzimidazole derivatives as multi-targeting agents to treat Alzheimer’s disease. Med Chem Res 26:1506–1515

    Article  CAS  Google Scholar 

  • Wang Y, Guan SH, Meng YH, Zhang YB, Cheng CR, Shi YY, Feng RH, Zeng F, Wu ZY, Zhang JX, Yang M, Liu X, Li Q, Chen XH, Bi KS, Guo DA (2013) Phenanthrenes, 9,10-dihydrophenanthrenes, bibenzyls, with their derivatives, and malate or tartrate benzyl ester glucosides from tubers of Cremastra appendiculata. Phytochemistry 94:268–276

    Article  CAS  PubMed  Google Scholar 

  • Williams P, Sorribas A, Howes MJR (2011) Natural products as a source of Alzheimer’s drug leads. Nat Prod Rep 28:48–77

    Article  CAS  PubMed  Google Scholar 

  • Wu D, Yan J, Wang J, Wang Q, Li H (2015) Characterisation of interaction between food colourant allura red AC and human serum albumin: multispectroscopic analyses and docking simulations. Food Chem 170:423–429

    Article  CAS  PubMed  Google Scholar 

  • Xia X, Cao J, Zheng Y, Wang Q, Xiao J (2014) Flavonoid concentrations and bioactivity of flavonoid extracts from 19 species of ferns from China. Ind Crops Prod 58:91–98

    Article  CAS  Google Scholar 

  • Xue Z, Li S, Wang S, Wang Y, Yang Y, Shi J, He L (2006) Mono-, bi-, and triphenanthrenes from the tubers of Cremastra appendiculata. J Nat Prod 69:907–913

    Article  CAS  PubMed  Google Scholar 

  • Yamaki M, Bai L, Inoue K, Takagi S (1989) Biphenanthrenes from Bletilla striata. Phytochemistry 28:3503–3505

    Article  CAS  Google Scholar 

  • Zuroff L, Daley D, Black KL, Koronyo-Hamaoui M (2017) Clearance of cerebral Aβ in Alzheimer’s disease: reassessing the role of microglia and monocytes. Cell Mol Life Sci 74:2167–2201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Financial support from the Science and Technology Department of Sichuan Province in China (No. 2016JY0062) is gratefully acknowledged.

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  1. School of Chemical Engineering, Sichuan University, 610065, Chengdu, China

    Yanbei Tu, Jiwu Huang & Yanfang Li

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  1. Yanbei Tu
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  2. Jiwu Huang
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  3. Yanfang Li
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Correspondence to Yanfang Li.

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Tu, Y., Huang, J. & Li, Y. Anticholinesterase, antioxidant, and beta-amyloid aggregation inhibitory constituents from Cremastra appendiculata . Med Chem Res 27, 857–863 (2018). https://doi.org/10.1007/s00044-017-2108-2

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  • DOI: https://doi.org/10.1007/s00044-017-2108-2

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