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[An experimental study of acute toxicity and pharmacology of fermented Platycodonis Radix]
Yan-Li Meng1, Nan-Nan Liu1, Yan Jiang1
1Heilongjiang Academy of Chinese Medicine Sciences Harbin 150036, China.
Abstract:
This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 μL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.
Insights
Fermented Platycodonis Radix demonstrates no acute toxicity in mice. It effectively suppresses cough by reducing the expression of TRPA1, CGRP, and SP in lung tissue, indicating its therapeutic potential.
Area of Science:
- Pharmacology
- Traditional Chinese Medicine
- Respiratory Medicine
Context:
- Mycoplasma pneumoniae infection is a common cause of respiratory illness and cough.
- Fermented Platycodonis Radix is a traditional herbal medicine with potential therapeutic properties.
- Understanding the mechanisms of cough suppression is crucial for developing effective treatments.
Purpose:
- To evaluate the acute toxicity of fermented Platycodonis Radix in mice.
- To investigate the efficacy of fermented Platycodonis Radix in suppressing cough in a mouse model of Mycoplasma pneumoniae infection.
- To elucidate the molecular mechanisms underlying the anti-tussive effects of fermented Platycodonis Radix.
Summary:
- Acute toxicity studies showed no adverse effects or mortality in mice treated with fermented Platycodonis Radix.
- Pharmacological experiments revealed that fermented Platycodonis Radix significantly reduced cough latency and count in mice infected with Mycoplasma pneumoniae.
- Histopathological examination and molecular analysis (qRT-PCR, immunohistochemistry) indicated that fermented Platycodonis Radix suppressed the expression of transient receptor potential A1 (TRPA1), calcitonin gene-related peptide (CGRP), and substance P (SP) in lung tissues.
Impact:
- Fermented Platycodonis Radix exhibits a favorable safety profile.
- The study identifies fermented Platycodonis Radix as a potential natural remedy for cough associated with respiratory infections.
- The findings provide mechanistic insights into the anti-tussive action of fermented Platycodonis Radix by targeting TRPA1, CGRP, and SP pathways.
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