School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China.
School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
Drug Des Devel Ther. 2023 Aug 11;17:2355-2368. doi: 10.2147/DDDT.S419626. eCollection 2023.
In China, herbal preparation is commonly administered transdermally for treating pediatric diarrhea. However, few studies have probed into their antidiarrheal mechanisms. This study was designed to investigate the antidiarrheal effect of Renzhu ointment (Renzhuqigao, RZQG) and its underlying mechanisms via transdermal administration.
The main components of RZQG were confirmed by gas chromatography-mass spectrometry (GC-MS). The effect of RZQG on L-type voltage-dependent calcium channel (L-VDCC) was evaluated by CaCl- and ACh-induced contraction in isolated colon. The antidiarrheal efficacy of RZQG was further investigated by the senna-induced diarrhea mice based on the frequency of loose stools, diarrhea rate and index, fecal moisture content, and the basal tension of the colon. Additionally, the protein expression of CACNA1C, CACNA1D, cAMP, and PKA were detected with Western blot and immunohistochemistry (IHC).
GC-MS analysis determined 14 components in RZQG. In vitro, RZQG relaxed the CaCl- and ACh-induced tension, while nifedipine (a L-VDCC inhibitor) and H-89 (a PKA inhibitor) decreased the relaxation. In vivo, animal model showed that transdermal administration of RZQG exhibited a significant reduction in the frequency of loose stools, diarrhea rate and index, fecal moisture content and the basal tension. Compared to the model group, the colon of mice treated with RZQG showed lower expression of CACNA1C, CACNA1D, cAMP, and PKA. IHC results showed that cAMP was downregulated in colonic smooth muscle after RZQG treatment.
RZQG improved diarrhea symptoms and down-regulated the expression of CACNA1C and CACNA1D via transdermal administration, which is closely associated with the cAMP/PKA signaling pathway in colonic smooth muscle.
在中国，草药制剂常用于经皮治疗小儿腹泻。然而，很少有研究探讨其止泻机制。本研究旨在通过经皮给药探讨仁珠膏（仁珠脐高，RZQG）的止泻作用及其机制。
采用气相色谱-质谱联用（GC-MS）法确定 RZQG 的主要成分。通过氯化钙和乙酰胆碱诱导的分离结肠收缩评价 RZQG 对 L 型电压依赖性钙通道（L-VDCC）的作用。基于番泻叶诱导的腹泻小鼠的稀便频率、腹泻率和指数、粪便水分含量和结肠基础张力，进一步研究 RZQG 的止泻作用。此外，采用 Western blot 和免疫组织化学（IHC）检测 CACNA1C、CACNA1D、cAMP 和 PKA 的蛋白表达。
GC-MS 分析确定 RZQG 中有 14 种成分。体外，RZQG 松弛了氯化钙和乙酰胆碱诱导的张力，而硝苯地平（L-VDCC 抑制剂）和 H-89（PKA 抑制剂）降低了松弛作用。体内，动物模型表明，经皮给予 RZQG 可显著减少稀便频率、腹泻率和指数、粪便水分含量和结肠基础张力。与模型组相比，RZQG 治疗组小鼠的结肠 CACNA1C、CACNA1D、cAMP 和 PKA 表达降低。IHC 结果显示，RZQG 处理后结肠平滑肌中 cAMP 下调。
RZQG 通过经皮给药改善腹泻症状，并下调 CACNA1C 和 CACNA1D 的表达，这与结肠平滑肌中 cAMP/PKA 信号通路密切相关。
