Isobutylhydroxyamides from Zanthoxylum bungeanum and Their Suppression of NO Production

Abstract

Abstract:Four new unsaturated aliphatic acid amides, named zanthoamides A-D (1-4), and eight known ones-tetrahydrobungeanool (5), ZP-amide A (6), ZP-amide B (7), ZP-amide C (8), ZP-amide D (9), ZP-amide E (10), bugeanumamide A (11), and (2E,7E,9E)-N-(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide (12)-were isolated from the pericarps of Zanthoxylum bungeanum. The structures of these compounds were elucidated by extensive use of spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses and comparison with previously reported data. Compound 4 contained a rare C 6 fatty acid unit with an acetal group. Results revealed that compounds 1, 5, 6, and 12 showed inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with IC 50 values of 48.7 ± 0.32, 27.1 ± 1.15, 49.8 ± 0.38, and 39.4 ± 0.63 µM, respectively, while the other compounds were inactive (IC 50 > 60 µM). They could contribute to the anti-inflammatory effects of Z. bungeanum by suppression of NO production.

Zanthoxylum bungeanum Maxim. (Rutaceae): A Systematic Review of Its Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics, and Toxicology

“…Apart from these, some compounds isolated from the pericarps of Z. bungeanum were found to exhibit notable anti-inflammatory effects by the suppression of nitric oxide (NO) production. Results revealed that the compounds ZP-amide D, ZP-amide E, ZP-amide F, and ZP-amide G showed inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with IC 50 values of 48.7 ± 0.32, 27.1 ± 1.15, 49.8 ± 0.38, and 39.4 ± 0.63 μM, respectively [ 38 ].…”

Identification of the candidate genes related to sanshool biosynthesis in Zanthoxylum bungeanum by comparative RNA sequencing analysis

“…Due to their potential economic value, many studies have focused on separating sanshools and their analogues, identifying their chemical structures 9 , artificially synthesising sanshools, and exploring their pharmacological effects 10,11 . However, due to the lack of genomic information, molecular synthesis pathways and the related genes remain to be elucidated.…”

Isolation, Structural Characterization and Neurotrophic Activity of Alkylamides from Zanthoxylum bungeanum

“…Red huajiao, the pericarps of the fruits of Z. bungeanum have been utilized as a pungent foodstuff and also as a kind of traditional Chinese medicine for treatment of vomiting, toothache, stomachache, abdominal pain, and diarrhea [11]. Phytochemical investigation of this plant afforded terpenoids, aliphatic acid amides (also known as sanshools), alkaloids, flavonoids, and lignans [12][13][14][15][16]. These compounds showed various pharmacological effects, such as antitumor [17], anti-inflammation [14], neurotrophic activity [18] and anesthetic properties [10].…”

“…To date, nearly all aliphatic acid amide compounds from the Zanthoxylum species have been isolated as a racemic, and their absolute configurations have not yet to be determined [12,14,25]. Herein, limited experiments are unable to determine the absolute configuration of new compounds.…”

“…Herein, limited experiments are unable to determine the absolute configuration of new compounds. In addition, the seven known compounds (3−9), including ZP-amide A (3), ZP-amide B (4), ZP-amide C (5), ZP-amide D (6), ZP-amide E (7), tetrahydrobungeanool (8) and (2E,7E,9E)-N-(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide (9) were obtained by previously reported methods [14].…”