당삼, 황매목, 고본, 사인에서 분리한 화합물의 알레르기성 염증반응 억제효과 Chemical Constituents Isolated from Codonopsis Pilosulae Radix, Linderae Ramulus, Angelicae Tenuissimae Radix, and Amomi Fructus along with Their Anti-allergic Inflammatory Activity원문보기
Allergic diseases are the result of inappropriate responses of human body against innocuous environmental substances. The prevalence and severity of allergic diseases has increased during the last decade in developed countries. The discovery of candidates for the treatment of allergic inflammatory d...
Allergic diseases are the result of inappropriate responses of human body against innocuous environmental substances. The prevalence and severity of allergic diseases has increased during the last decade in developed countries. The discovery of candidates for the treatment of allergic inflammatory diseases is important in public health. Plant still remains as the important sources of pharmacologically active compounds that lead to the development of innovative drug. For selection of effective plants, we tested the plants extract and found inhibition of histamine release, and down-regulation of TNF-α, and IL-6 gene expression. Among the four tested plant extracts, Codonopsis Pilosulae Radix, Linderae Ramulus, Angelicae Tenuissimae Radix, and Amomi Fructus showed strong effect reducing the gene expression of cytokines and release of histamine. In this study, seventy-seven compounds were isolated from Codonopsis Pilosulae Radix, Linderae Ramulus, Angelicae Tenuissimae Radix, and Amomi Fructus, including seven new compounds, iso-lobetyolin (1), cis-lobetyolin (2), linderin A (20) and (3R,8S)-heptadeca-1-en-4,6-diyne-3,8-diol (42), lobetyol (3), lobetyolin (4), and cordifolioidyne B (5), along with seventy known compounds (6-19, 21-41, and 43-77). Compounds 1-19 were isolated from Codonopsis Pilosulae Radix, and their structures were identified to be (+)-lariciresinol (6), dihydrodehydrodiconiferyl alcohol (7), (-)-(2R,3R)-secoisolariciresinol (8), secoisolariciresinol C-5 dimer (9), linolenic acid (10), methyl linolenate (11), palmitic acid (12), linoleic acid (13), methyl linoleate (14), 2,3-dihydroxypropyl linoleate (15), β-stigmastenol (16), spinasterol (17) , creoside IV (18), and hexyl β-sophoroside (19). Compounds 20-41 were isolated from Linderae Ramulus, and their structures were idendified to be (+)-xanthoxyol (21), pluviatilol (22), actiforin (23), (+) syringaresinol (24), (+)-(7S,8R,8'R)-acuminatolide (25), (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (26), lynoside (27), and nudiposide (28), (-)-catechin (29), (-)-epicatechin (30), 5.7,3'-trihydroxy-flavanone-4'-O-β-D-glucopyranoside (31), quercitrin (32), hyperoside (33), tachioside (34), isotachioside (35), koaburaside (36), 2,6-dimethoxy-4-hydroxy-1-O-β-D-glucopyranoside (37), 4,6-dihydroxy-2-methoxyphenyl-1-O-β-D-glucopyranoside (38), (6-hydroxymethyl) -1-O-β-D-glucopyranoside (39), salidroside (40), and erigeside C (41). Compounds 43-63 were isolated from Angelicae Tenuissimae Radix, and their structures were identified to be falcarindiol (43), oplopandiol (44), butylidenephthalide (45), senkyunolide C (46), senkyunolide B (47), (Z)-ligustilde (48), ligusilidiol (49), senkyunolide H (50), (Z)-6-hydroxy-7-methoxy dihydroligustilide (51), levistolide A (52), fraxetol (53), demethylsuberosin (54), (+)-marmesinin (55), (-)-marmesinin (56), 3'(S)-O-β-D-glucopyranosyl-30,40-dihydroxanthyletin (57), 3'(S)-O-β-D-glucopyranosyl-30,40-dihydroxanthyletin (58), isopraeroside (59), 1,2,3-propanetriol (60), ferulic acid (61), 3,(3,4-dihydroxyphenyl)-2-propenoic acid (62), 3-hydroxy-2-methoxy-benzoic acid (63). Compounds 64-77 were isolated from Amomi Fructus, and their structures were identified to be 4-hydroxy-benzaldehyde (64), 3,4-dihydroxy-benzaldehyde (65), 3,5-dimethoxy-4methyl-benzaldehyde (66), syringic aldehyde (67), benzoic acid (68), 3,4-dihydroxy benzoic acid (69), vanillic acid (70), 3-hydroxy-2-methoxybenzoic acid (71), o-vanillic acid (72), benzeneacetic acid (73), tyrosol (74), pyrocatechol (75), 1,2,4,5-tetramethoxybenzene (76), and 3,3',5,5'-tetramethoxybiphenyl-4,4'-diol (77). To verify the anti-allergic effects, we evaluated the inhibitory effects of all the isolates (1-77) on histamine release and gene expression of IL-6 and TNF- α in human mast cells. Among tested compounds, Acetylenes (1-5, and 42-44), lignans (20-28), and phtalides (45-57) significantly inhibited the expression of pro-inflammatory cytokines and release of histamine. In particular, phenolic glycosides (34-41) isolated from Linderae Ramulus showed strong anti-allergic inflammation activity. Compounds 36, 37, and 41 inhibited histamine release 66.9, 68.1, and 65.7% at a concentration of 10 μM, respectively, whereas gallic acid (the positive control, which has been reported to inhibit histamine release and pro-inflammatory cytokine production in mast cells) inhibited histamine generation by 65.7% at a concentration of 10 μM. Additionally, 41 significantly inhibited the expressions of IL-6 and TNF-α in mast cells.
Allergic diseases are the result of inappropriate responses of human body against innocuous environmental substances. The prevalence and severity of allergic diseases has increased during the last decade in developed countries. The discovery of candidates for the treatment of allergic inflammatory diseases is important in public health. Plant still remains as the important sources of pharmacologically active compounds that lead to the development of innovative drug. For selection of effective plants, we tested the plants extract and found inhibition of histamine release, and down-regulation of TNF-α, and IL-6 gene expression. Among the four tested plant extracts, Codonopsis Pilosulae Radix, Linderae Ramulus, Angelicae Tenuissimae Radix, and Amomi Fructus showed strong effect reducing the gene expression of cytokines and release of histamine. In this study, seventy-seven compounds were isolated from Codonopsis Pilosulae Radix, Linderae Ramulus, Angelicae Tenuissimae Radix, and Amomi Fructus, including seven new compounds, iso-lobetyolin (1), cis-lobetyolin (2), linderin A (20) and (3R,8S)-heptadeca-1-en-4,6-diyne-3,8-diol (42), lobetyol (3), lobetyolin (4), and cordifolioidyne B (5), along with seventy known compounds (6-19, 21-41, and 43-77). Compounds 1-19 were isolated from Codonopsis Pilosulae Radix, and their structures were identified to be (+)-lariciresinol (6), dihydrodehydrodiconiferyl alcohol (7), (-)-(2R,3R)-secoisolariciresinol (8), secoisolariciresinol C-5 dimer (9), linolenic acid (10), methyl linolenate (11), palmitic acid (12), linoleic acid (13), methyl linoleate (14), 2,3-dihydroxypropyl linoleate (15), β-stigmastenol (16), spinasterol (17) , creoside IV (18), and hexyl β-sophoroside (19). Compounds 20-41 were isolated from Linderae Ramulus, and their structures were idendified to be (+)-xanthoxyol (21), pluviatilol (22), actiforin (23), (+) syringaresinol (24), (+)-(7S,8R,8'R)-acuminatolide (25), (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (26), lynoside (27), and nudiposide (28), (-)-catechin (29), (-)-epicatechin (30), 5.7,3'-trihydroxy-flavanone-4'-O-β-D-glucopyranoside (31), quercitrin (32), hyperoside (33), tachioside (34), isotachioside (35), koaburaside (36), 2,6-dimethoxy-4-hydroxy-1-O-β-D-glucopyranoside (37), 4,6-dihydroxy-2-methoxyphenyl-1-O-β-D-glucopyranoside (38), (6-hydroxymethyl) -1-O-β-D-glucopyranoside (39), salidroside (40), and erigeside C (41). Compounds 43-63 were isolated from Angelicae Tenuissimae Radix, and their structures were identified to be falcarindiol (43), oplopandiol (44), butylidenephthalide (45), senkyunolide C (46), senkyunolide B (47), (Z)-ligustilde (48), ligusilidiol (49), senkyunolide H (50), (Z)-6-hydroxy-7-methoxy dihydroligustilide (51), levistolide A (52), fraxetol (53), demethylsuberosin (54), (+)-marmesinin (55), (-)-marmesinin (56), 3'(S)-O-β-D-glucopyranosyl-30,40-dihydroxanthyletin (57), 3'(S)-O-β-D-glucopyranosyl-30,40-dihydroxanthyletin (58), isopraeroside (59), 1,2,3-propanetriol (60), ferulic acid (61), 3,(3,4-dihydroxyphenyl)-2-propenoic acid (62), 3-hydroxy-2-methoxy-benzoic acid (63). Compounds 64-77 were isolated from Amomi Fructus, and their structures were identified to be 4-hydroxy-benzaldehyde (64), 3,4-dihydroxy-benzaldehyde (65), 3,5-dimethoxy-4methyl-benzaldehyde (66), syringic aldehyde (67), benzoic acid (68), 3,4-dihydroxy benzoic acid (69), vanillic acid (70), 3-hydroxy-2-methoxybenzoic acid (71), o-vanillic acid (72), benzeneacetic acid (73), tyrosol (74), pyrocatechol (75), 1,2,4,5-tetramethoxybenzene (76), and 3,3',5,5'-tetramethoxybiphenyl-4,4'-diol (77). To verify the anti-allergic effects, we evaluated the inhibitory effects of all the isolates (1-77) on histamine release and gene expression of IL-6 and TNF- α in human mast cells. Among tested compounds, Acetylenes (1-5, and 42-44), lignans (20-28), and phtalides (45-57) significantly inhibited the expression of pro-inflammatory cytokines and release of histamine. In particular, phenolic glycosides (34-41) isolated from Linderae Ramulus showed strong anti-allergic inflammation activity. Compounds 36, 37, and 41 inhibited histamine release 66.9, 68.1, and 65.7% at a concentration of 10 μM, respectively, whereas gallic acid (the positive control, which has been reported to inhibit histamine release and pro-inflammatory cytokine production in mast cells) inhibited histamine generation by 65.7% at a concentration of 10 μM. Additionally, 41 significantly inhibited the expressions of IL-6 and TNF-α in mast cells.
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