Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloids
Background: Areca catechu is distributed in Southeast Asia, and its nut is called “Binrouji” in Japanese. A. nut contains alkaloids typified by arecoline (1), which are reported to exhibit nicotine-like activities such as parasympathetic nerve excitatory activity. A. nut alkaloids, 1, arecaidine (2)...
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Elsevier
2022-08-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S266703132200077X |
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| author | Yoshiyuki Hirata Hinata Nishino Tsutomu Sasaki Yasuo Nagaoka Shinichi Uesato Masahiko Taniguchi |
| author_facet | Yoshiyuki Hirata Hinata Nishino Tsutomu Sasaki Yasuo Nagaoka Shinichi Uesato Masahiko Taniguchi |
| author_sort | Yoshiyuki Hirata |
| collection | DOAJ |
| description | Background: Areca catechu is distributed in Southeast Asia, and its nut is called “Binrouji” in Japanese. A. nut contains alkaloids typified by arecoline (1), which are reported to exhibit nicotine-like activities such as parasympathetic nerve excitatory activity. A. nut alkaloids, 1, arecaidine (2), guvacoline (3) and guvacine (4), have a basic skeleton similar to nicotinamide (5) which inhibits nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases [sirtuins (SIRTs)], epigenetic enzymes involved in an acquired gene modification. We therefore hypothesized that the A. nut alkaloids might have an inhibitory activity against SIRTs as does nicotinamide (5). Purpose: The present study aimed to examine the potency of these alkaloids as SIRT inhibitors by the methods involving the assays of enzymatic inhibition, cellular acetylated lysine (Ac-Lys) accumulation, chemical pull-down and Western blot, as well as the test of neurite outgrowth. Methods: Inhibitory activity of the A. nut alkaloids against SIRT1–3 was measured utilizing the fluorometric SIRT1, 2, or 3 deacetylase assay. Pull down of SIRT1 from the lysate of the neuron-like cell, Neuro 2a, was conducted using arecaidine (2) immobilized with magnetic FG-NH2 beads as bait. The effect of arecoline (1) on the accumulation of acetylated histone was evaluated using an anti-Ac-Lys-antibody. The neurite outgrowth activity of arecoline (1) was assessed by using microscope. Results: Arecoline (1) and arecaidine (2) showed an inhibitory activity stronger than and equal to the representative SIRT inhibitor, nicotinamide (5), respectively. In support for this finding, SIRT1 was pulled down from the Neuro 2a lysate with arecaidine (2) immobilized on the FG NH2-beads, and accumulated acetyl-lysine was detected from the lysate of arecoline (1)-incubated Neuro 2a cells. Additionally, alkaloid 1 showed a neurite outgrowth effect though at the concentration range which did not inhibit SIRT1–3. Conclusion: We found out that arecoline (1) had the SIRT1–3 inhibition activities higher than the typical SIRT inhibitor, nicotinamide (5), while arecaidine (2) had the activities comparable to those of 5. Additionally, we disclosed that alkaloid 1 has another beneficial effect, the neurite outgrowth activity, though not related to SIRT inhibitory activity. |
| first_indexed | 2024-12-12T05:32:22Z |
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| institution | Directory Open Access Journal |
| issn | 2667-0313 |
| language | English |
| last_indexed | 2024-12-12T05:32:22Z |
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| spelling | doaj.art-14a5db2e666640e1bd642e31ce0faa0a2022-12-22T00:36:17ZengElsevierPhytomedicine Plus2667-03132022-08-0123100294Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloidsYoshiyuki Hirata0Hinata Nishino1Tsutomu Sasaki2Yasuo Nagaoka3Shinichi Uesato4Masahiko Taniguchi5Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan; Corresponding author.Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, JapanDepartment of Neurology, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, JapanDepartment of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, JapanFaculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan; Kansai University Center for Innovation and Creativity, 3-3-35, Yamate-cho, Suita, Osaka 564-8680, JapanFaculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan; Corresponding author.Background: Areca catechu is distributed in Southeast Asia, and its nut is called “Binrouji” in Japanese. A. nut contains alkaloids typified by arecoline (1), which are reported to exhibit nicotine-like activities such as parasympathetic nerve excitatory activity. A. nut alkaloids, 1, arecaidine (2), guvacoline (3) and guvacine (4), have a basic skeleton similar to nicotinamide (5) which inhibits nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases [sirtuins (SIRTs)], epigenetic enzymes involved in an acquired gene modification. We therefore hypothesized that the A. nut alkaloids might have an inhibitory activity against SIRTs as does nicotinamide (5). Purpose: The present study aimed to examine the potency of these alkaloids as SIRT inhibitors by the methods involving the assays of enzymatic inhibition, cellular acetylated lysine (Ac-Lys) accumulation, chemical pull-down and Western blot, as well as the test of neurite outgrowth. Methods: Inhibitory activity of the A. nut alkaloids against SIRT1–3 was measured utilizing the fluorometric SIRT1, 2, or 3 deacetylase assay. Pull down of SIRT1 from the lysate of the neuron-like cell, Neuro 2a, was conducted using arecaidine (2) immobilized with magnetic FG-NH2 beads as bait. The effect of arecoline (1) on the accumulation of acetylated histone was evaluated using an anti-Ac-Lys-antibody. The neurite outgrowth activity of arecoline (1) was assessed by using microscope. Results: Arecoline (1) and arecaidine (2) showed an inhibitory activity stronger than and equal to the representative SIRT inhibitor, nicotinamide (5), respectively. In support for this finding, SIRT1 was pulled down from the Neuro 2a lysate with arecaidine (2) immobilized on the FG NH2-beads, and accumulated acetyl-lysine was detected from the lysate of arecoline (1)-incubated Neuro 2a cells. Additionally, alkaloid 1 showed a neurite outgrowth effect though at the concentration range which did not inhibit SIRT1–3. Conclusion: We found out that arecoline (1) had the SIRT1–3 inhibition activities higher than the typical SIRT inhibitor, nicotinamide (5), while arecaidine (2) had the activities comparable to those of 5. Additionally, we disclosed that alkaloid 1 has another beneficial effect, the neurite outgrowth activity, though not related to SIRT inhibitory activity.http://www.sciencedirect.com/science/article/pii/S266703132200077XSIRT inhibitionAreca catechu nut alkaloidArecolineArecaidineChemical pull-down |
| spellingShingle | Yoshiyuki Hirata Hinata Nishino Tsutomu Sasaki Yasuo Nagaoka Shinichi Uesato Masahiko Taniguchi Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloids Phytomedicine Plus SIRT inhibition Areca catechu nut alkaloid Arecoline Arecaidine Chemical pull-down |
| title | Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloids |
| title_full | Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloids |
| title_fullStr | Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloids |
| title_full_unstemmed | Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloids |
| title_short | Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloids |
| title_sort | sirtuin inhibition and neurite outgrowth effect as new biological activities for areca catechu nut alkaloids |
| topic | SIRT inhibition Areca catechu nut alkaloid Arecoline Arecaidine Chemical pull-down |
| url | http://www.sciencedirect.com/science/article/pii/S266703132200077X |
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