NF-κB Inhibitory Activities of Glycosides and Alkaloids from <i>Zanthoxylum schinifolium</i> Stems

Abstract

Zanthoxylum schinifolium is an aromatic shrub, the pericarp and leaves of which are widely used in culinary applications in East Asian countries. In the present study, one new neolignan glycoside, zanthoxyloside A (1) together with 16 known glycosides (2-12) and alkaloids (13-17), were isolated from methanol extract of the stems of Z. schinifolium. The absolute configuration of one known monoterpenoid glycoside (2) was determined. The structures of the isolated compounds were established by one dimensional (1D), 2D NMR and mass spectrometry. The nuclear factor-κB (NF-κB) inhibitory activities of the isolated compounds stimulated with tumor necrosis factor alpha (TNFα) were measured using a luciferase reporter system. Compounds 1, 5, 16, and 17 exhibited significant inhibition of NF-κB activation in a dose-dependent manner. Furthermore, compounds 1, 5, 16, and 17 inhibited TNFα-induced expression of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) mRNA and dose-dependent inhibition of iNOS promoter activity.Key words Zanthoxylum schinifolium; Rutaceae; glycoside; alkaloid; nuclear factor-κB (NF-κB) inhibitory activity Zanthoxylum schinifolium SIEB. & ZUCC., which belongs to the Rutaceae family, is an aromatic plant, widely used as a pungent condiment and seasoning in Korea, China, Japan and other East Asian countries because of its unique aroma and taste.1) The leaves and seeds of Z. schinifolium have been used primarily for treatment of various types of pain, the common cold, diarrhea, and jaundice in traditional Chinese medicine. Pharmacological research on Z. schinifolium has focused on its inhibitory effect on monoamine oxidase and its anti-platelet, anti-diabetes, and anti-inflammatory activities. 2-4)Phytochemical studies on Z. schinifolium indicated the main constituents to be coumarins, essential oils, triterpenoids, monoterpenoids, steroids, and flavonoids. [5][6][7] Coumarins were shown to have significant platelet aggregation activity. Essential oils were found to have antioxidant activity and are used in skin care products. Alkaloids have various bioactivities such as antimicrobial effects. 8) Although there have been many investigations of the active constituents of Z. schinifolium, there have been no detailed reports of the isolation and structural elucidation of glycosides and alkaloids from the stems of this plant or their bioactivities.Nuclear factor-κB (NF-κB) represents a family of Rel domain-containing proteins, which includes five NF-κB units that can form 15 transcription factors through homo-and heterodimerization. NF-κB plays an important role in the transcriptional regulation of numerous cytokines and adhesion molecules. It is the most extensively studied transcription factor in the immune system. Known inducers of NF-κB activity are highly variable and include reactive oxygen species (ROS), tumor necrosis factor alpha (TNFα), interleukin (IL)-1β, bacterial lipopolysaccharides (LPS), isoproterenol, cocaine, and ionizing radiation. The activation of NF-...

Biologically active quinoline and quinazoline alkaloids part II

“…173 However, skimmianine, haplopine, and glycohaplopine from Zanthoxylum schinifolium did not inhibit NF- κ B. 174…”

“…In addition, a new compound, 2‐[(6Z,9Z)‐pentadeca‐6,9‐dienyl]quinolin‐4(1H)‐one ( 202 ) from Tetradium ruticarpum and evodol inhibited fMLP/CB‐induced elastase release with IC 50 values lower than 14.4 μM, while rutaecarpine, evodiamine, and skimmianine inhibited O − 2 generation (IC 50 ≤ 20.9 μM) by human neutrophils in response to N ‐formyl‐ l ‐methionyl‐ l ‐leucyl‐ l ‐phenylalanine/cytochalasin B (fMLP/CB) . However, skimmianine, haplopine, and glycohaplopine from Zanthoxylum schinifolium did not inhibit NF‐κB …”

Progress of Plant Medicine Derived Extracts and Alkaloids on Modulating Viral Infections and Inflammation

“…Furthermore, these compounds inhibited TNF-α-induced expression of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 mRNA, and dose-dependent inhibition of iNOS promoter activity. 107 A Matrine-Type Alkaloid Oxymatrine ( 15) is a major active compound of Sophora root. 108 Oxymatrine had excellent anti-influenza A virus activity against eight strains in vitro.…”

Comparative Study of Bioactivity and Safety Evaluation of Ethanolic Extracts of Zanthoxylum schinifolium Fruit and Pericarp

“…However, it can cure leprosy, strengthen teeth, and prevent hair fall. Moreover, it can brighten the eyes, relieve stomach ache, and prevent dysentery caused by cold [ 21 , 22 , 23 , 24 ]. There are several phytochemical compounds that are obtained from ZS and possess beneficial bioactivities.…”

“…There are several phytochemical compounds that are obtained from ZS and possess beneficial bioactivities. For example, the anti-KSHV activity of megastigmane sesquiterpenoids; NF-κB inhibitory activity of glycosides and alkaloids; radio-sensitizing effects of 4-quinolinone derivatives; as well as the anticancer activity, apoptogenic activity, monoamine oxidase inhibitory, and antiplatelet aggregation activities of coumarins derived from ZS have been investigated [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Additionally, the vascular smooth muscle proliferation inhibitory effect, antioxidant, cytotoxicity, antibacterial, anti-melanogenic, anti-inflammatory, and insecticidal activities have been reported in ZS extracts [ 29 , 30 , 31 , 32 , 33 ].…”