1.Banxia Xiexin Tang Ameliorates Cognitive Dysfunction in Rat Model of Vascular Dementia via AGE/RAGE Pathway
Shuzhi LIANG ; Zhongmin ZHAO ; Suyu HOU ; Dandan LUO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):10-21
ObjectiveTo explore the mechanism by which Banxia Xiexin Tang (BXT) regulates the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia (VD). MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry(UPLC-Q-Orbitrap-MS/MS), and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries (2-VO) method. The successfully modeled rats were randomly allocated into the model, low-, medium-, and high-dose (3.748 5, 7.497, 14.994 g·kg-1) BXT (BXT-L, BXT-M, and BXT-H), and nimodipine (NMP, 0.002 7 g·kg-1) groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage, and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze, Y-maze, and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin (HE) staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE, RAGE, and phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry (IHC). The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze, Y maze, and novel object recognition tests showed that compared with the sham group, the model group demonstrated prolonged successful latency and decreases in number of platform crossings, alternation rate, number of entries into the new arm, preference index, and discrimination index (P0.01). Compared with the model group, the BXT-H and BXT-M groups showed shortened successful latency (P0.01) and increases in number of platform crossings (P0.05), alternation rate (P0.01), number of entries into the new arm (P0.05), preference index (P0.01), and discrimination index (P0.01). HE results showed that compared with the sham group, the cells of model rats were loosely and disorderly arranged, and the nuclei were condensed. Compared with the model group, the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group, the model group presented up-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 in the hippocampus (P0.01), and compared with the model group, the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 (P0.01). Western blot results showed that compared with the sham group, the model group presented up-regulated expression of AGE, RAGE, p-NF-κB p65, and tumor necrosis factor-α (TNF-α) (P0.05), and compared with the model group, the BXT-H group presented down-regulated expression of AGE, RAGE, p-NF-κB p65, and TNF-α (P0.05). IHC results showed that compared with the sham group, the model group had increased expression of RAGE (P0.01), and compared with the model group, the BXT-H and BXT-M groups had reduced expression of RAGE (P0.01). ELISA results showed that compared with the sham group, the model group exhibited elevated levels of TNF-α and Interleukin-1β (IL-1β) and declined levels of acetylcholine (ACh) and dopamine (DA) in the serum (P0.01). Compared with the model group, the BXT-L, BXT-M, and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum (P0.05) and elevated levels of ACh and DA (P0.05). ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway, reducing neuroinflammatory responses, and regulating neurotransmitter levels.
2.Herbal Textual Research on Inulae Flos in Famous Classical Formulas
Caixia LIU ; Yue HAN ; Yanzhu MA ; Lei GAO ; Sheng WANG ; Yan YANG ; Wenchuan LUO ; Ling JIN ; Jing SHAO ; Zhijia CUI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):210-221
In this paper, by referring to ancient and modern literature, the textual research of Inulae Flos has been conducted to clarify the name, origin, production area, quality evaluation, harvesting, processing and others, so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research, it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties, Xuanfuhua has been taken as the official name, and it also has other alternative names such as Jinfeicao, Daogeng and Jinqianhua. The period before the Song and Yuan dynasties, the main origin of Inulae Flos was the Asteraceae plant Inula japonica, and from the Ming and Qing dynasties to the present, I. japonica and I. britannica are the primary source. In addition to the dominant basal species, there are also regional species such as I. linariifolia, I. helianthus-aquatili, and I. hupehensis. The earliest recorded production areas in ancient times were Henan, Hubei and other places, and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower, the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months, and dried in the sun, and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom, in order to remove impurities, dry in the shade or dry in the sun. In addition, the roots, whole herbs and aerial parts are used as medicinal materials. In ancient times, there were no records about the quality of Inulae Flos, and in modern times, it is generally believed that the quality of complete flower structure, small receptacles, large blooms, yellow petals, long filaments, many fluffs, no fragments, and no branches is better. Ancient processing methods primarily involved cleaning, steaming, and sun-drying, supplemented by techniques such as boiling, roasting, burning, simmering, stir-frying, and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties, ancient texts describe it as salty and sweet in taste, slightly warm in nature, and mildly toxic. Modern studies characterize it as bitter, pungent, and salty in taste, with a slightly warm nature. Its therapeutic effects remain consistent across eras, including descending Qi, resolving phlegm, promoting diuresis, and stopping vomiting. Based on the research results, it is recommended that when developing famous classical formulas containing Inulae Flos, either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements, where no processing instructions are specified, the raw products may be used after cleaning.
3.Traditional Chinese Medicine Against Insomnia by Regulating PI3K/Akt Signaling Pathway: A Review
Suyu HOU ; Dandan LUO ; Xiangye GAO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):284-293
Insomnia is a sleep disorder characterized by difficulty in falling asleep, sleep maintenance disorder and impaired daytime function. Its pathological mechanism involves multiple factors such as nerve excitability, circadian rhythm, cell apoptosis, oxidative stress injury. As a classical tyrosine kinase signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) triggers Akt phosphorylation cascade, inducing inflammatory response, apoptosis, autophagy, oxidative damage, nerve excitability, and circadian rhythm imbalance. Traditional Chinese medicine(TCM) can improve sleep by targeting the PI3K/Akt pathway. Based on this, this paper systematically reviews the research progress on the regulation of PI3K/Akt pathway by traditional Chinese medicine(TCM) for insomnia at home and abroad. These drugs can regulate neuronal excitability by regulating the PI3K/Akt pathway, affect the circadian rhythm, alleviate inflammation, apoptosis, autophagy and oxidative stress, and thus regulate sleep-wake. Furthermore, literature review indicates that the PI3K/Akt signaling pathway may represent a specific pathway underlying phlegm-turbidity disturbing the upper Jiao-type insomnia.
4.Banxia Xiexin Tang Ameliorates Cognitive Dysfunction in Rat Model of Vascular Dementia via AGE/RAGE Pathway
Shuzhi LIANG ; Zhongmin ZHAO ; Suyu HOU ; Dandan LUO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):10-21
ObjectiveTo explore the mechanism by which Banxia Xiexin Tang (BXT) regulates the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia (VD). MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry(UPLC-Q-Orbitrap-MS/MS), and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries (2-VO) method. The successfully modeled rats were randomly allocated into the model, low-, medium-, and high-dose (3.748 5, 7.497, 14.994 g·kg-1) BXT (BXT-L, BXT-M, and BXT-H), and nimodipine (NMP, 0.002 7 g·kg-1) groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage, and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze, Y-maze, and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin (HE) staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE, RAGE, and phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry (IHC). The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze, Y maze, and novel object recognition tests showed that compared with the sham group, the model group demonstrated prolonged successful latency and decreases in number of platform crossings, alternation rate, number of entries into the new arm, preference index, and discrimination index (P<0.01). Compared with the model group, the BXT-H and BXT-M groups showed shortened successful latency (P<0.01) and increases in number of platform crossings (P<0.05), alternation rate (P<0.01), number of entries into the new arm (P<0.05), preference index (P<0.01), and discrimination index (P<0.01). HE results showed that compared with the sham group, the cells of model rats were loosely and disorderly arranged, and the nuclei were condensed. Compared with the model group, the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group, the model group presented up-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 in the hippocampus (P<0.01), and compared with the model group, the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 (P<0.01). Western blot results showed that compared with the sham group, the model group presented up-regulated expression of AGE, RAGE, p-NF-κB p65, and tumor necrosis factor-α (TNF-α) (P<0.05), and compared with the model group, the BXT-H group presented down-regulated expression of AGE, RAGE, p-NF-κB p65, and TNF-α (P<0.05). IHC results showed that compared with the sham group, the model group had increased expression of RAGE (P<0.01), and compared with the model group, the BXT-H and BXT-M groups had reduced expression of RAGE (P<0.01). ELISA results showed that compared with the sham group, the model group exhibited elevated levels of TNF-α and Interleukin-1β (IL-1β) and declined levels of acetylcholine (ACh) and dopamine (DA) in the serum (P<0.01). Compared with the model group, the BXT-L, BXT-M, and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum (P<0.05) and elevated levels of ACh and DA (P<0.05). ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway, reducing neuroinflammatory responses, and regulating neurotransmitter levels.
5.Herbal Textual Research on Inulae Flos in Famous Classical Formulas
Caixia LIU ; Yue HAN ; Yanzhu MA ; Lei GAO ; Sheng WANG ; Yan YANG ; Wenchuan LUO ; Ling JIN ; Jing SHAO ; Zhijia CUI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):210-221
In this paper, by referring to ancient and modern literature, the textual research of Inulae Flos has been conducted to clarify the name, origin, production area, quality evaluation, harvesting, processing and others, so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research, it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties, Xuanfuhua has been taken as the official name, and it also has other alternative names such as Jinfeicao, Daogeng and Jinqianhua. The period before the Song and Yuan dynasties, the main origin of Inulae Flos was the Asteraceae plant Inula japonica, and from the Ming and Qing dynasties to the present, I. japonica and I. britannica are the primary source. In addition to the dominant basal species, there are also regional species such as I. linariifolia, I. helianthus-aquatili, and I. hupehensis. The earliest recorded production areas in ancient times were Henan, Hubei and other places, and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower, the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months, and dried in the sun, and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom, in order to remove impurities, dry in the shade or dry in the sun. In addition, the roots, whole herbs and aerial parts are used as medicinal materials. In ancient times, there were no records about the quality of Inulae Flos, and in modern times, it is generally believed that the quality of complete flower structure, small receptacles, large blooms, yellow petals, long filaments, many fluffs, no fragments, and no branches is better. Ancient processing methods primarily involved cleaning, steaming, and sun-drying, supplemented by techniques such as boiling, roasting, burning, simmering, stir-frying, and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties, ancient texts describe it as salty and sweet in taste, slightly warm in nature, and mildly toxic. Modern studies characterize it as bitter, pungent, and salty in taste, with a slightly warm nature. Its therapeutic effects remain consistent across eras, including descending Qi, resolving phlegm, promoting diuresis, and stopping vomiting. Based on the research results, it is recommended that when developing famous classical formulas containing Inulae Flos, either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements, where no processing instructions are specified, the raw products may be used after cleaning.
6.Traditional Chinese Medicine Against Insomnia by Regulating PI3K/Akt Signaling Pathway: A Review
Suyu HOU ; Dandan LUO ; Xiangye GAO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):284-293
Insomnia is a sleep disorder characterized by difficulty in falling asleep, sleep maintenance disorder and impaired daytime function. Its pathological mechanism involves multiple factors such as nerve excitability, circadian rhythm, cell apoptosis, oxidative stress injury. As a classical tyrosine kinase signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) triggers Akt phosphorylation cascade, inducing inflammatory response, apoptosis, autophagy, oxidative damage, nerve excitability, and circadian rhythm imbalance. Traditional Chinese medicine(TCM) can improve sleep by targeting the PI3K/Akt pathway. Based on this, this paper systematically reviews the research progress on the regulation of PI3K/Akt pathway by traditional Chinese medicine(TCM) for insomnia at home and abroad. These drugs can regulate neuronal excitability by regulating the PI3K/Akt pathway, affect the circadian rhythm, alleviate inflammation, apoptosis, autophagy and oxidative stress, and thus regulate sleep-wake. Furthermore, literature review indicates that the PI3K/Akt signaling pathway may represent a specific pathway underlying phlegm-turbidity disturbing the upper Jiao-type insomnia.
7.Characterization and Application of Moisture Absorption Kinetics of Traditional Chinese Medicines Based on Double Exponential Model:A Review
Yanting YU ; Lei XIONG ; Yan HE ; Wei LIU ; Jing YANG ; Yao ZHANG ; Jiali CHEN ; Xiaojian LUO ; Xiaoyong RAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):340-346
Hygroscopicity research has long been a key focus and hot topic in Chinese materia medica(CMM). Elucidating hygroscopic mechanisms plays a vital role in formulation design, process optimization, and storage condition selection. Hygroscopic models serve as essential tools for characterizing CMM hygroscopic mechanisms, with various types available. The double exponential model is a kinetic mathematical model constructed based on the law of conservation of energy and Fick's first law of diffusion, tailored to the physical properties of CMM extracts. In recent years, this model has been extensively applied to simulate the dynamic moisture absorption behavior of CMM extracts and solid dosage forms under varying humidity conditions. It has revealed the correlation between moisture absorption kinetic parameters and material properties, offering a new perspective for characterizing the moisture uptake behavior of CMM. This paper systematically reviews the application progress of this model in the field of CMM, analyzes its advantages, disadvantages, and challenges in this domain, and explores its potential application trends in other fields. It aims to provide references for elucidating the moisture absorption mechanisms of CMM and researching moisture-proofing technologies, while also offering insights for its broader application in food and polymer materials.
8.Serum Metabolomics of Simulated Weightless Rats Treated with Taikong Yangxin Pills
Xiaodi LIU ; Xuemei FAN ; Yiming WANG ; Mengjia YAN ; Yongzhi LI ; Jiaping WANG ; Junlian LIU ; Guoan LUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):147-153
ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground, the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows: out-of-capsule control, in-capsule control, model, and high (3.0 g·kg-1) and low (1.5 g·kg-1) doses of Taikong Yangxin Pills, and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The obtained data were processed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group, the in-capsule control group showed elevated levels of thirteen metabolites, including 14-hydroxyhexadecanoic acid, linoleic acid, and α-linolenic acid (P<0.05), which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group, the model group showed lowered levels of fourteen metabolites, including 4-imidazolone-5-propionic acid, isocitric acid/citric acid, and L-tyrosine (P<0.05), which were recovered after the treatment with Taikong Yangxin pills (P<0.05). The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine, tyrosine, and tryptophan biosynthesis, tyrosine metabolism, histidine metabolism, and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.
9.Rapid Identification of Different Parts of Nardostachys jatamansi Based on HS-SPME-GC-MS and Ultra-fast Gas Phase Electronic Nose
Tao WANG ; Xiaoqin ZHAO ; Yang WEN ; Momeimei QU ; Min LI ; Jing WEI ; Xiaoming BAO ; Ying LI ; Yuan LIU ; Xiao LUO ; Wenbing LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):182-191
ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi, so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GC-MS) combined with Smart aroma database and National Institute of Standards and Technology(NIST) database were used to characterize the aroma components in different parts of N. jatamansi, and the aroma components were quantified according to relative response factor(RRF) and three internal standards, and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis(OPLS-DA) and cluster thermal analysis based on variable importance in the projection(VIP) value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose, and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data, and the rapid identification model of different parts of N. jatamansi was established by principal component analysis(PCA), discriminant factor alysis(DFA), soft independent modeling of class analogies(SIMCA) and statistical quality control analysis(SQCA). ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi, of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components, the contents of five components(ethyl isovalerate, 2-pentylfuran, benzyl alcohol, nonanal and glacial acetic acid,) in the aboveground part of N. jatamansi were significantly higher than those in the underground part(P<0.01), the contents of β-ionone, patchouli alcohol, α-caryophyllene, linalyl butyrate, valencene, 1,8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part(P<0.01). Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82, and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted, respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%, the validation score of the SIMCA model for discrimination of the two parts was 99, and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose(PCA, DFA, SIMCA and SQCA) can realize the rapid identification of different parts of N. jatamansi. Combining the two results, it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.
10.The Effects of Qufeng Tongqiao Cough-Relieving Decoction (祛风通窍止咳方) on Cough Sensitivity,TRPV4 in Lung and Nasal Mucosal Tissues,and Neurogenic Inflammation in a Guinea Pig Model of Upper Airway Cough Syndrome
Jingshu LUO ; Jianling MA ; Liqing SHI ; Kun JI ; Song LIU ; Yuhan FAN ; Xianli LI ; Zhaodi GUO
Journal of Traditional Chinese Medicine 2025;66(5):518-525
ObjectiveTo investigate the potential mechanism of action of the Qufeng Tongqiao Cough-relieving Decoction (祛风通窍止咳方, QTCD) in the treatment of upper airway cough syndrome (UACS). MethodsTwenty-four guinea pigs were randomly divided into blank group, model group, traditional Chinese medicine (TCM) group, and inhibitor group, with six guinea pigs in each group. Except for the blank group, guinea pigs were sensitized with ovalbumin and aluminum hydroxide via intraperitoneal injection, followed by ovalbumin nasal drops combined with smoke exposure to establish the UACS model. After modeling, the TCM group was administered QTCD 0.9 g/(100 g·d) by gavage, the inhibitor group received the transient receptor potential vanilloid receptor 4 (TRPV4) inhibitor GSK2193874 1 mmol/L, 5 min by nebulisation, and the blank group and model group were given 2 ml/(100 g·d) normal saline by gavage once daily. After 7 days of treatment, a cough provocation test was performed using 0.4 mol/L citric acid. The levels of IgE in serum and inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8) in serum, bronchoalveolar lavage fluid (BALF), and nasal lavage fluid (NLF) were detected by enzyme-linked immunosorbent assay (ELISA). Histopathological changes in lung and nasal mucosal tissues were observed by hematoxylin-eosin (HE) staining. Immunohistochemistry was used to detect the protein levels of TRPV4, substance P (SP), and calcitonin gene-related peptide (CGRP) in lung and nasal mucosal tissues. Real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of TRPV4, SP, and CGRP in lung tissues. ResultsHE staining showed significant structural damage and infiltration of inflammatory cells in the lung and nasal mucosal tissues in the model group, while the TCM group and inhibitor group showed improved pathological changes. Compared with the blank group, the model group showed increased cough frequency, serum IgE level, and IL-6 and IL-8 levels in serum, BALF, and NLF. The protein levels of TRPV4, SP, and CGRP in lung and nasal mucosal tissues and their mRNA expression were elevated (P<0.05 or P<0.01). Compared with the model group, the TCM group and inhibitor group showed reduced cough frequency, serum IgE level, and TRPV4 and SP mRNA expression in lung tissues. The TCM group showed reduced IL-6 and IL-8 levels in serum, BALF, and NLF, and reduced TRPV4 and CGRP protein levels in lung and nasal mucosal tissues. The inhibitor group showed reduced IL-6 and IL-8 levels in serum, BALF, and NLF, reduced IL-6 in BALF, reduced IL-8 in NLF, and decreased TRPV4, SP, and CGRP protein levels in lung tissues and SP and CGRP protein levels in nasal mucosal tissues (P<0.05 or P<0.01). Compared with the TCM group, the inhibitor group had increased serum IgE, IL-6, and IL-8 levels, increased IL-6 level in BALF, and increased IL-8 levle in NLF, but decreased SP protein level in lung tissues and increased TRPV4 and SP mRNA expression in lung tissues (P<0.01). ConclusionQTCD effectively reduces cough frequency in the UACS guinea pig model. Its mechanism may involve inhibiting the activation of the TRPV4 pathway, improving airway neurogenic inflammation, alleviating inflammatory responses, and reducing cough hypersensitivity.

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