Abstract
Butylidenephthalide (Bdph, 30~300 μM), a constituent of Ligusticum chuanxiong Hort., significantly enhanced tension in isolated guinea-pig trachea. In this study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue. Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3 μM), and its tension changes were isometrically recorded. Cromakalim (3 μM), an ATP-dependent K+ channel opener, significantly antagonized the Bdph-induced enhancement of baseline tension. Bdph (300 μM) also significantly antagonized cromakalim-induced relaxation. Bdph (300 μM) did not significantly influence the antagonistic effects of glibenclamide (GBC, 1 μM) and tetraethylammonium (TEA, 8 mM) against the cromakalim-induced relaxation. However, Bdph (300 μM) and 4-aminopiridine (4-AP, 5 mM), a blocker of Kv1 family of K+ channels, in combination significantly rightward shifted the log concentration-relaxation curve of cromakalim. The antagonistic effect of the combination almost equals the sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers influenced neither the baseline tension nor antagonistic effect of Bdph against cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of Kv1 family of K+ channels, to enhance the baseline tension of guinea-pig trachea.
Highlights
IntroductionThe rhizomes of Ligusticum chuanxiong Hort. (previously named L. wallichii Franch.) and Angelica sinensis Diels. (Apiaceae) have been used by the Chinese for several thousand years
The rhizomes of Ligusticum chuanxiong Hort. and Angelica sinensis Diels. (Apiaceae) have been used by the Chinese for several thousand years
Other investigators reported that shimotsu-to, a prescription of traditional Chinese medicine (TCM), had antiproliferative effects in primary cultures of mouse aorta smooth muscle cells [2], mainly due to Cnidium rhizome-derived phthalides, such as senkyunolide, ligustilide, and Bdph [3]
Summary
The rhizomes of Ligusticum chuanxiong Hort. (previously named L. wallichii Franch.) and Angelica sinensis Diels. (Apiaceae) have been used by the Chinese for several thousand years. Other investigators reported that shimotsu-to, a prescription of traditional Chinese medicine (TCM), had antiproliferative effects in primary cultures of mouse aorta smooth muscle cells [2], mainly due to Cnidium rhizome-derived phthalides, such as senkyunolide, ligustilide, and Bdph [3]. Both antiplatelet and antiproliferative effects of these crude drugs benefit to prevent stroke. It is reported to maintain stem cell pluripotency by activating the Jak2/Stat pathway and increasing the efficiency of induced pluripotent stem cells generation [8] These results highlight the ability for these crude drugs to aid in the recovery from dyskinesia. Bdph was reported to inhibit growth of malignant brain tumor [9], lung adenocarcinoma [10], and glioblastomas [11] with a high therapeutic ratio [12]
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