Comparative Study on the Pharmacodynamics of Xiangzhu Fanggan Formula （香术防感方） by Sniffing and Nasal Drops for Prevention of Influenza A H1N1 Virus Infection in Mice
10.13288/j.11-2166/r.2024.12.014
- VernacularTitle:香术防感方吸嗅与滴鼻给药方式预防甲型流感H1N1模型小鼠的药效学比较研究
- Author:
Yue ZHANG
1
;
Yizhi DONG
1
;
Haoyue LI
2
;
Xinxin WU
1
;
Xiaolei LI
1
;
Jing ZHAO
1
Author Information
1. Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， Beijing， 100700
2. International Cooperation Department， China Academy of Chinese Medical Sciences
- Publication Type:Journal Article
- Keywords:
influenza A;
H1N1 virus;
Xiangzhu Fanggan Formula （香术防感方）;
sniffing;
nasal drops;
antiviral;
inflammatory factor
- From:
Journal of Traditional Chinese Medicine
2024;65(12):1279-1286
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo compare the effectiveness and mechanism of Xiangzhu Fanggan Formula （香术防感方） by sniffing and nasal drops for preventing influenza A H1N1flu. MethodsFifty-six BALB/c mice were randomly divided into normal group， model group， zanamivir group， high-concentration sachet group， low-concentration sachet group， high-concentration nasal drops group， and low-concentration nasal drops group， with 8 mice in each group. In the low- and high-concentration sachet groups， 15 g and 30 g of Xiangzhu Fanggan Formula sachet were used for sniffing for 24 h per day； while in the low- and high-concentration nasal drops groups， nasal drops of Xiangzhu Fanggan Formula were given at a concentration of 0.11 and 0.22 g/ml， 20 μl each time， twice a day； in the zanamivir group， zanamivir was given at a concentration of 1.025 mg/ml of 20 μl each time， twice a day； in the normal group and the model group， nasal drops of normal saline were given at 20 μl each time， twice a day. Each group was given prophylactic intervention for 5 days. On day 5， 1 h after the administration of the drug， the mice in all groups except the normal group received 35 μl of 50 LD50 A/PR/8/34/H1N1 viral solution as nasal drops to prepare influenza A H1N1 model mice. The body mass of the mice was recorded and the rate of change of body mass was calculated daily from day 5 to day 9 of the experiment， and the general status was observed. The mice were sampled on day 9， and the lung index and the inhibition rate of lung index were calculated； HE staining was used to detect pathological changes in lung tissues and to score lung tissue lesions； RT-qPCR was used to detect viral load in lung tissues； and ELISA was used to detect secretory immunoglobulin A （sIgA） and serum tumour necrosis factor α （TNF-α） and interleukin 2 （IL-2）， interleukin 6 （IL-6）， and interferon γ （IFN-γ） in the lavage fluid of the upper respiratory tract. ResultsOn days 7， 8 and 9 of the experiment， the rate of change in body mass of mice in the model group significantly lower than that in the normal group at the same time points （P＜0.05 or P＜0.01）. On days 8 and 9 of the experiment， the rate of change in body mass of mice in the zanamivir group and the high-concentration nasal drops group increased when compared with the model group （P＜0.05 or P＜0.01）. Compared with the normal group， mice in the model group had significantly higher lung index， lung tissue lesion score， lung tissue viral load， significantly higher serum TNF-α， IL-6， IL-2， IFN-γ levels， and significantly lower sIgA levels in the upper respiratory lavage fluid （P＜0.01）. Compared with the model group， the lung index and lung tissue viral load reduced， serum IFN-γ， TNF-α， IL-2， IL-6 levels reduced， and sIgA levels increased in the zanamivir group and the high-concentration nosal drops group （P＜0.05 or P＜0.01）； except for low-concentration sachet group， lung tissue lesion scores of the drug intervention groups reduced compared with those of the model group （P＜0.01）. Compared with the zanamivir group， the lung index increased in the low-concentration sachet group and the low- and high-concentration nasal drops groups， and the serum TNF-α and IL-2 levels increased in all Xiangzhu Fanggan Formula intervention groups （P＜0.05 or P＜0.01）. Compared with high-concentration nasal drops group， serum TNF-α and IFN-γ levels elevated in the high-concentration increased group， and lung tissue viral load elevated in the low-concentration nasal drops group （P＜0.05 or P＜0.01）. The lung index inhibition rate was 80.84% in the zanamivir group， 41.61% and 17.90% in the high- and low-concentration sachet groups， and 35.40% and 25.40% in the high- and low-concentration nasal drops groups， respectively. HE staining showed that the lung tissues of the model group showed thickening of alveolar septa， alveolar collapse， and infiltration of inflammatory cells； whereas， in each drug intervention group， the inflammation of the lung tissues of the mice and the damage reduced， and the most obvious improvement was in the zanamivir group and the high-concentration nasal drops group. ConclusionXiangzhu Fanggan Formula by sniffing and nasal drops could both prevent influenza A H1N1 virus infection， with antiviral and anti-inflammatory effects， also could improve the pathological damage of lung tissue， and improve the immunity of respiratory mucosa. The nasal drops may be better than sachets in inhibiting inflammatory response， especially the high-concentration nasal drops showed more effective.
