Structures of New Phenylbutanoids and Nitric Oxide Production Inhibitors from the Rhizomes of Zingiber cassumunar

Abstract

The Zingiberaceae plant, Zingiber cassumunar (Z. cassumunar), is widely distributed in the Southeast Asian countries and was called as "phlai" in Thailand. The rhizomes of this plant are used as a spice and also used for treatment of asthma, bronchitis, gastrointestinal distress, etc., in traditional Thai medicine. Recently, several chemical and biological studies on Z. cassumunar have been reported. [1][2][3][4][5] For example, several phenylbutanoids isolated from Z. cassumunar were reported to possess P-glycoprotein inhibitory, 1) cyclooxygenase-2 inhibitory, 4) and anti-inflammatory 5) effects. During the course of our characterization studies on Zingiberaceae natural medicines, [6][7][8][9][10][11][12][13][14][15][16] the MeOH extract from the rhizomes of Z. cassumunar was found to show inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages. From the MeOH extract, six new phenylbutanoids named phlains I-VI were isolated together with 16 known constituents. Furthermore, we examined the inhibitory effects of principal constituents on NO production induced by LPS in mouse peritoneal macrophages. In this paper, we describe the isolation and structure elucidation of the new constituents (1-6) and the NO production inhibitory effects of principal constituents from the rhizomes of Z. cassumunar.The rhizomes of Z. cassumunar were extracted with MeOH. The MeOH extract (24.1% from the rhizomes) was partitioned into an EtOAc-H 2 O (1 : 1, v/v) mixture to furnish an EtOAc-soluble fraction (16.7%) and an aqueous phase (7.4%). The MeOH extract (IC 50 ϭ11 mg/ml) and the EtOAc- Structures of New Phenylbutanoids and Nitric Oxide Production Inhibitors from the Rhizomes of Zingiber cassumunar

Prasaplai: An essential Thai traditional formulation for primary dysmenorrhea treatment

“…In addition, curcumin, which was found as a minor compound in Z. cassumunar, has an ability to suppress the expression of COX-2 (Surh and Kundu, 2007). Other mechanisms include the inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, experimented in mouse peritoneal macrophages in which DMPBD, TMPBD, and cassumunaquinone showed IC 50 of 69, 83, and 47 μM, respectively (Nakamura et al, 2009). In addition, Chaiwongsa and co-workers reported an anti-inflammatory activity of compound D against the IL-1 induced catabolic gene expression involved in cartilage degeneration (Chaiwongsa et al, 2013).…”

Invasion Inhibitors of Human Fibrosarcoma HT 1080 Cells from the Rhizomes of <i>Zingiber cassumunar</i>: Structures of Phenylbutanoids, Cassumunols

“…34) As a continuing study, effects of the principal constituents from the rhizomes of Z. cassumunar on the invasion of HT1080 cells through Matrigel-coated filters were examined (Table 3). Among them, phlain I (9) and III (10) (12), and (Ϫ)-b-sesquiphellandrene (22) showed anti-invasion effects. Particularly, 12 significantly inhibited the invasion [inhibition (%) 46.8Ϯ7.2 (pϽ0.05) at 30 mg/ml].…”

“…In the course of our studies on bioactive constituents from Zingiberaceae plant, [1][2][3][4][5][6][7][8][9][10][11][12] we previously reported that the methanolic extract from the rhizomes of Zingiber (Z.) cassumunar showed inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages.…”

“…cassumunar showed inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages. 12) From the extract, then new conjugated phenylbutanoids named phlains I-VI were isolated and their structures as well as the inhibitory activities on NO production were characterized. As a continuing study, the methanolic extract and its EtOAc-soluble fraction from the rhizomes of Z. cassumunar were found to inhibit invasion of human fibrosarcoma HT 1080 cells through Matrigel-coated filters in vitro.…”

“…The methanolic extract and EtOAc-soluble fraction were found to show potent inhibitory effects on the invasion of HT 1080 cells through Matrigel-coated filters (Table 1), whereas the H 2 O-soluble fraction showed no activity. The EtOAc-soluble fraction was subjected to normal phase and reversed-phase column chro- matographies, and finally HPLC to give cassumunols A (1, 0.0093% from the dried rhizomes), B (2, 0.0026%), C (3, 0.0016%), D (4, 0.013%), E (5, 0.0044%), F (6, 0.017%), G (7, 0.0021%), and H (8, 0.024%) together with phlasins I (9), 12) II, 12) III (10), 12) IV, 12) V, 12) and VI, 12) (E)-1-(3,4-dimethoxyphenyl)buta-1,3-diene (11), 12,13) (E)-1-(2,4,5-trimethoxyphenyl)buta-1,3-diene (12), 12,13) (Z)-1-(2,4,5-trimethoxyphenyl)buta-1,3-diene (0.0057%), 14) (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-ol (13), 12,15) (E)-4-(3,4-dimethoxyphenyl)but-3-enyl acetate (14), 12,16) (E)-4-(3,4-dimethoxyphenyl)but-3-ene-1,2-diol (15, 0.021%), 16) (E)-1-(3,4-dimethoxyphenyl)but-1-ene (16), 12,17) (E)-1-(2,4,5-trimethoxyphenyl)but-1-ene (17), 12,17) 12,17) (Ϯ)-cis-3-(2,4,5-trimethoxyphenyl)-4-[(E)-2,4,5-trimethoxystyryl]cyclohex-1-ene (19), 12,17) (Ϯ)-trans-3-(3,4-dimethoxy- 18) (E)-3-(2.4, 5-trimethoxyphenyl)propenal (0.0012%), 19) cassumunaquinones 1 12,20) and 2, 12,20) curcumin, 12,21,22) cassumunarins A (0.0080%) …”