Sei-hai-to (TJ-90, Qing Fei Tang), a Chinese traditional medicine, increases ciliary beat frequency (CBF) and ciliary bend angle (CBA) mediated via cAMP (3′,5′-cyclic adenosine monophosphate) accumulation modulated by Ca²⁺-activated phosphodiesterase 1 (PDE1A). A high concentration of TJ-90 (≥40 μg/mL) induced two types of CBF increases, a transient increase (an initial increase, followed by a decrease) and a sustained increase without any decline, while it only sustained the CBA increase. Upon inhibiting increases in intracellular Ca²⁺ concentration ([Ca²⁺]_i) by 10 μM BAPTA-AM (Ca²⁺-chelator, 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) or Ca²⁺/calmodulin-dependent PDE1 by 8MmIBMX (a selective PDE1 inhibitor), TJ-90 (400 μg/mL) induced only the sustained CBF increase without any transient CBF increase. The two types of the CBF increase (the transient increase and the sustained increase) induced by TJ-90 (≥40 μg/mL) were mimicked by the stimulation with both procaterol (100 pM) and ionomycin (500 nM). Thus, TJ-90 stimulates small increases in the intracellular cAMP concentration ([cAMP]_i) and [Ca²⁺]_i in airway ciliary cells of mice. These small increases in [cAMP]_i and [Ca²⁺]_i cause inducing a transient CBF increase or a sustained CBF increase in an airway ciliary cells, depending on the dominant signal, Ca²⁺-signal, or cAMP-signal.

The effects of the isoflavone daidzein on the ciliary beat distance (CBD, which is a parameter assessing the amplitude of ciliary beating) and the ciliary beat frequency (CBF) were examined in ciliated human nasal epithelial cells (cHNECs) in primary culture. Daidzein decreased [Cl⁻]_i and enhanced CBD in cHNECs. The CBD increase that was stimulated by daidzein was mimicked by Cl⁻-free NO₃⁻ solution and bumetanide (an inhibitor of Na⁺/K⁺/2Cl⁻ cotransport), both of which decreased [Cl⁻]_i. Moreover, the CBD increase was inhibited by 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, a Cl⁻ channel blocker), which increased [Cl⁻]_i. CBF was also decreased by NPPB. The rate of [Cl⁻]_i decrease evoked by Cl⁻-free NO₃⁻ solution was enhanced by daidzein. These results suggest that daidzein activates Cl⁻ channels in cHNECs. Moreover, daidzein enhanced the microbead transport driven by beating cilia in the cell sheet of cHNECs, suggesting that an increase in CBD enhances ciliary transport. An [Cl⁻]_i decrease enhanced CBD, but not CBF, in cHNECs at 37 °C, although it enhanced both at 25 °C. Intracellular Cl⁻ affects both CBD and CBF in a temperature-dependent manner. In conclusion, daidzein, which activates Cl⁻ channels to decrease [Cl⁻]_i, stimulated CBD increase in cHNECs at 37 °C. CBD is a crucial factor that can increase ciliary transport in the airways under physiological conditions.