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09.11.2019 | Original Paper

BBB-permeable aporphine-type alkaloids in Nelumbo nucifera flowers with accelerative effects on neurite outgrowth in PC-12 cells

verfasst von: Mamiko Yano, Souichi Nakashima, Yoshimi Oda, Seikou Nakamura, Hisashi Matsuda

Erschienen in: Journal of Natural Medicines

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Abstract

Blood–brain barrier (BBB)-permeable components in the methanolic extract of Nelumbo nucifera flowers showed accelerative effects on neurite outgrowth in PC-12 cells. Among the constituents isolated from N. nucifera flowers in our previous study, aporphine-type alkaloids, lirinidine, asimilobine, N-methylasimilobine, and pronuciferine, showed accelerative effects. Lirinidine, N-methylasimilobine, and an alkaloid-rich diethyl ether fraction at low concentrations increased the expression of mRNAs coding for TrkA, Vav3, and Rac1. In addition, good permeability of asimilobine and N-methylasimilobine was confirmed using an in vitro BBB model. Asimilobine and N-methylasimilobine are considered to be suitable as seed compounds of drugs for Alzheimer’s disease, because of their activity and BBB permeability.

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Nakamura S, Nakashima S, Tanabe G, Oda Y, Yokota N, Fujimoto K, Matsumoto T, Sakuma R, Ohta T, Ogawa K, Nishida S, Miki H, Matsuda H, Muraoka O, Yoshikawa M (2013) Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells. Bioorg Med Chem 21:779–787CrossRef

Agnihotri VK, ElSohly HN, Khan SI, Jacob MR, Joshi VC, Smillie T, Khan I, Walker LA (2008) Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity. Phytochem Lett 1:89–93CrossRef

Ma C, Wang J, Chu H, Zhang X, Wang Z, Wang H, Li G (2014) Purification and characterization of aporphine alkaloids from leaves of Nelumbo nucifera Gaertn and their effects on glucose consumption in 3T3-L1 adipocytes. Int J Mol Sci 15:3481–3494CrossRef

Liu CM, Kao CL, Wu HM, Li WJ, Huang CT, Li HT, Chen CY (2014) Antioxidant and anticancer aporphine alkaloids from the leaves of Nelumbo nucifera Gaertn. cv Rosa-plena. Molecules 19:17829–17838CrossRef

Castilla-Ortega E, Ladrón de Guevara-Miranda D, Serrano A, Pavón FJ, Suárez J, Rodríguez de Fonseca F, Santín LJ (2017) The impact of cocaine on adult hippocampal neurogenesis: potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder. Biochem Pharmacol 141:100–117CrossRef

Ma T, Gong K, Yan Y, Zhang L, Tang P, Zhang X, Gong Y (2013) Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Res 1506:35–43CrossRef

Mezeiova E, Korabecny J, Sepsova V, Hrabinova M, Jost P, Muckova L, Kucera T, Dolezal R, Misik J, Spilovska K, Pham NL, Pokrievkova L, Roh J, Jun D, Soukup O, Kaping D, Kuca K (2017) Development of 2-methoxyhuprine as novel lead for alzheimer’s disease therapy. Molecules 22:1265CrossRef

Rizk P, Salazar J, Raisman-Vozari R, Marien M, Ruberg M, Colpaert F, Debeir T (2006) The alpha2-adrenoceptor antagonist dexefaroxan enhances hippocampal neurogenesis by increasing the survival and differentiation of new granule cells. Neuropsychopharmacol 31:1146–1157CrossRef

Zhang YN, Yang YF, Yang XW (2018) Blood–brain barrier permeability and neuroprotective effects of three main alkaloids from the fruits of Euodia rutaecarpa with MDCK-pHaMDR cell monolayer and PC-12 cell line. Biomed Pharmacother 98:82–87CrossRef

10.

Imamura S, Tabuchi M, Kushida H, Nishi A, Kanno H, Yamaguchi T, Sekiguchi K, Ikarashi Y, Kase Y (2011) The blood–brain barrier permeability of geissoschizine methyl ether in Uncaria hook, a galenical constituent of the traditional Japanese medicine yokukansan. Cell Mol Neurobiol 31:787–793CrossRef

11.

Oda Y, Nakashima S, Nakamura S, Yano M, Akiyama M, Imai K, Kimura T, Nakata A, Tani M, Matsuda H (2016) New potent accelerator of neurite outgrowth from Lawsonia inermis flower under non-fasting condition. J Nat Med 70:384–390CrossRef

12.

Oda Y, Nakashima S, Kondo E, Nakamura S, Yano M, Kubota C, Masumoto Y, Hirao M, Ogawa Y, Matsuda H (2018) Comparison of lawsone contents among Lawsonia inermis plant parts and neurite outgrowth accelerators from branches. J Nat Med 72:890–896CrossRef

13.

Matsumoto T, Nakamura S, Nakashima S, Ohta T, Yano M, Tsujihata J, Tsukioka J, Ogawa K, Fukaya M, Yoshikawa M, Matsuda H (2016) γ-Lactam alkaloids from the flower buds of daylily. J Nat Med 70:376–383CrossRef

14.

Ohta T, Nakamura S, Nakashima S, Oda Y, Matsumoto T, Fukaya M, Yano M, Yoshikawa M, Matsuda H (2016) Chemical structures of constituents from the whole plant of Bacopa monniera. J Nat Med 70:404–411CrossRef

15.

Morikawa T, Kitagawa N, Tanabe G, Ninomiya K, Okugawa S, Motai C, Kamei I, Yoshikawa M, Lee I, Muraoka O (2016) Quantitative determination of alkaloids in Lotus flower (flower buds of Nelumbo nucifela) and their melanogenesis inhibitory activity. Molecules 21:930CrossRef

Titel: BBB-permeable aporphine-type alkaloids in Nelumbo nucifera flowers with accelerative effects on neurite outgrowth in PC-12 cells
verfasst von: Mamiko Yano
Souichi Nakashima
Yoshimi Oda
Seikou Nakamura
Hisashi Matsuda
Publikationsdatum: 09.11.2019
Verlag: Springer Singapore
Erschienen in: Journal of Natural Medicines
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-019-01368-7

Springer Medizin

Abstract

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