Isolation, Structural Characterization and Neurotrophic Activity of Alkylamides fromZanthoxylum bungeanum

Abstract

Two new fatty acid amides, zanthoamides E (1) and F (2), were isolated from the pericarps of Zanthoxylum bungeanum. The structures of the two sanshool compounds were elucidated by analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). All isolated compounds (1-9) were evaluated for nerve growth factor (NGF)-potentiating activity using PC-12 cells, and the results indicated that compound 8 (tetrahydrobungeanool) showed the strongest neurotrophic activity.

Chemistry and Pharmacology of Alkylamides from Natural Origin

“…Two new alkylamides, zanthoamides E (40) and F (41), along with seven known ones (ZP-amide A (42), ZP-amide B (43), ZP-amide C (44), ZP-amide D (45), Z P -a m i d e E (4 6 ) , t e t r ah y d r o b un g ea n o ol ( 4 7) , (2E,7E,9E)-N-(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide (48)) were isolated from the pericarps of Z. bungeanum and structures determined by analysis of spectroscopic data (IR, UV, HRESIMS, 1D, and 2D NMR) (Wang et al 2017). Abdubakiev et al (2019) isolated sixteen known Nalkylamides from the dried fruits of P. longum.…”

“…Z. bungeanum , popularly called “toothache tree” and widely distributed in China and Southeast Asian countries, is used as a condiment and in traditional medicine as anesthetic and analgesic for toothache and sore throats (Rong et al 2016 ). The pericarps from the fruits of Z. bungeanum are used in traditional medicine for the treatment of vomiting, toothache, stomachache, abdominal pain, and diarrhea (Wang et al 2017 ). Acmella oleracea (L.) R.K. Jansen, Asteraceae, is used in ethnomedicine to relieve toothache (Dallazen et al 2018 ).…”

“…All the nine compounds gave an increase in neurite-bearing cells with compound 47 (tetrahydrobungeanool) having the highest neurite outgrowth-promoting activity while compounds 45 , 46 , and 48 showed moderate activities. The neurotrophic mimicking activity of these alkylamides may be the basis for their use in the management of neurodegenerative diseases such as Alzheimer’s disease (Wang et al 2017 ).…”

“…seedlings showed that N -isobutyl-decanamide, a C:10 saturated alkylamide, was the most active compound in inhibiting primary root growth and stimulating lateral root formation (Méndez-Bravo et al 2010 ). Wang et al ( 2017 ) reported that tetrahydrobungeanool, having a non-oxygenated unsaturated long fatty acid chain, had the highest neurite outgrowth-promoting activity, thus suggesting that the non-oxygenated unsaturated long carbon chain appears to play an important role in the neurite outgrowth-promoting activity of the tested alkylamides. Further studies on the SAR of alkylamides would provide more insight into their various observed pharmacological activities.…”

Zanthoxylum Species: A Comprehensive Review of Traditional Uses, Phytochemistry, Pharmacological and Nutraceutical Applications

“…Wang et al [ 126 ] isolated nine alkylamides, including tetrahydrobungeanool, zanthoamides E and F, ZP-amides A-E and (2 E ,7 E ,9 E )- N -(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide, from Z. bungeanum pericarps. In vitro neuritogenic test using rat pheochromocytoma PC-12 showed that the nine compounds enhanced neurite outgrowth, indicating that they have neuritogenic activity, without apparent cytotoxicity.…”