| In vitro: |
| J Pharmacobiodyn. 1985 Apr;8(4):257-63. | | Calcium antagonist-like actions of coumarins isolated from [Pubmed: 2411906] | The effects of coumarins on anaphylactic mediator release from rat mast cells were investigated. Since Pd-Ia (3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin) causes relaxation of smooth muscle by inhibiting calcium influx, and since mediator release is a calcium-dependent process, studies were made on whether coumarins block calcium influx into rat mast cells stimulated by concanavalin A.
METHODS AND RESULTS:
Pd-Ia isolated from Peucedanum praeruptorum Dunn and related compounds, named Pd-C-II, Pd-C-III and Pd-C-IV, from Peucedanum decursivum Maxim., (Angelica decursiva Fr. et Sav.) inhibited anaphylactic mediator release from purified mast cells induced by concanavalin A with phosphatidylserine; their IC50 values were 79, 100, 102 and 73 microM, respectively. Pd-III, decursidin and water-soluble analogues of Pd-Ia (Pd-Ia-OH, Pd-Ia-OCH2CH3) did not inhibit the release. | | Arch Pharm Res. 2016 Jan;39(1):115-26. | | Coumarins from Angelica decursiva inhibit lipopolysaccharide-induced nitrite oxide production in RAW 264.7 cells.[Pubmed: 26474585 ] | Angelica decursiva has long been used in Korean traditional medicine as an antitussive, analgesic, antipyretic, and cough remedy.
METHODS AND RESULTS:
In this study, the anti-inflammatory activity of 9 coumarin derivatives isolated from a 90 % methanol fraction was evaluated via inhibition of production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Among the tested compounds, edulisin II (1) exhibited the most potent NO production inhibitory activity, followed by decursidin (2), Pd-C-III (3), 4-hydroxy Pd-C-III (4), Pd-C-I (5), and Pd-C-II (6). In contrast, (+)-trans-decursidinol (7) did not exhibit NO suppressive effects on LPS-stimulated RAW 264.7 cells. Structure-activity relationships revealed that esterification of the hydroxyl at C-3' or C-4' of 7 with an angeloyl/senecioyl/acetyl group is essential for its inhibitory activity against NO production, while the number of angeloyl or senecioyl groups, and their positions greatly affect the potency of these coumarins. Coumarins 1-6 also inhibited TNF-α production and iNOS protein expression, while compounds 1-4 inhibited COX-2 protein expression in LPS-stimulated RAW 264.7 cells.
CONCLUSIONS:
These results suggest that coumarins isolated from A. decursiva might be used as potential leads for the development of therapeutic agents for inflammation-associated disorders. |
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