Sub-chronic and developmental toxicity of transdermal delivery of Renzhu ointment in young SD rats

Yang, Fuzhen; Cao, Mengfei; Zhong, Lei; Xiao, Ni; Chen, Guanfeng; Cao, Qian; Huang, Fengke; Zhang, Jun; He, Huifen

doi:10.1080/15569527.2022.2088781

Cited by 1 publication

(1 citation statement)

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“…The sub-chronic toxicity testing in rats showed that the no observed adverse effect level (NOAEL) of RZQG was 0.3 g/kg/day (equivalent to 30 times the clinically planned dose and 4.92 times the human equivalent dose). 42 According to the sub-chronic toxicity and the efficacy tests, RZQG presented promising perspectives. Electrolyte and water imbalance were also involved in the pathogenesis of diarrhea.…”

Section: Discussionmentioning

confidence: 99%

Renzhu Ointment Regulates L-Type Voltage-Dependent Calcium Channel in Mice Model of Senna-Induced Diarrhea by Transdermal Administration

Zhong¹,

Cao²,

Li³

et al. 2023

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Purpose 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. Methods 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 2 - 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). Results GC-MS analysis determined 14 components in RZQG. In vitro, RZQG relaxed the CaCl 2 - 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. Conclusion 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.

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Section: Discussionmentioning

confidence: 99%