[Sini Decoction inhibits TLR4/NF-κB signaling pathway to improve airway remodeling of allergic asthmatic mice]

Zhongguo Zhong Yao Za Zhi. 2022 Nov;47(22):6191-6198. doi: 10.19540/j.cnki.cjcmm.20220613.706.
[Article in Chinese]

Abstract

This study aims to explore the effect of Sini Decoction on Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) signaling pathway in the mice with allergic asthma(AA). Forty-eight SPF-grade BALB/c mice were randomly assigned into a blank control group, a model group, a dexamethasone group, and high-, medium-, and low-dose Sini Decoction groups, with 8 mice in each group. The sensitization solution made of ovalbumin and aluminum hydroxide powder was injected intraperitoneally in other groups except the blank control group which was injected with an equal volume of normal saline. The solution(or normal saline) was injected three times in total with an interval of 7 days. At the same time of sensitization, external cold stimulation and ice water were administered in a 4 ℃ climate box for 20 min every day. After modeling, the mice in each group were administrated with corresponding drugs by gavage for 3 weeks. At the end of administration, pentobarbital sodium(30 mg·kg~(-1)) was used for anesthesia, and then the samples were collected for the determination of various indexes. The phenol red test was conducted to evaluate tracheal excretion function. The histopathological changes of lung tissue were observed via hematoxylin-eosin(HE) staining. Masson staining was employed to reveal the deposition of blue collagen fibers around bronchi in lung tissue and the area occupied by blue collagen fibers was calculated. Immunofluorescence method was used to measure the expression of bronchial type Ⅰ collagen(Col-Ⅰ) and α-smooth muscle actin(α-SMA). The protein and mRNA levels of TLR4, NF-κB, cysteinyl aspartate specific proteinase-1(caspase-1), and interleukin-13(IL-13) were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction(real-time PCR), respectively. Compared with the model group, Sini Decoction significantly increased the phenol red excretion from trachea, lowered the lung inflammation score, reduced subepithelial collagen deposition, and decreased Col-Ⅰ and α-SMA levels. Furthermore, the decoction down-regulated the protein and mRNA levels of TLR4, NF-κB, caspase-1, and IL-13 in mouse lung tissue. In conclusion, Sini Decoction can improve air remodeling by inhibiting the TLR4/NF-κB signaling pathway.

Keywords: Sini Decoction; Toll-like receptor 4/nuclear factor-κB; airway remodeling; allergic asthma.

Publication types

  • English Abstract

MeSH terms

  • Airway Remodeling
  • Animals
  • Asthma* / drug therapy
  • Asthma* / genetics
  • Caspases
  • Interleukin-13 / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B* / genetics
  • NF-kappa B* / metabolism
  • Phenolsulfonphthalein / pharmacology
  • RNA, Messenger
  • Saline Solution / pharmacology
  • Signal Transduction
  • Toll-Like Receptor 4 / genetics

Substances

  • NF-kappa B
  • sini tang
  • Interleukin-13
  • Toll-Like Receptor 4
  • Saline Solution
  • Phenolsulfonphthalein
  • RNA, Messenger
  • Caspases
  • Tlr4 protein, mouse