Exploring the medication rules and related pharmacological analysis of traditional Chinese medicine in the treatment of allergic rhinitis based on data mining, network pharmacology, and experimental verification
Allergic rhinitis (AR), also known as allergic rhinitis, is a chronic non infectious inflammation of the nasal mucosa caused by the release of inflammatory factors (histamine, leukotrienes, prostaglandins, platelet activating factors, etc.) mediated by immunoglobulin E (IgE) after exposure to allergens in atopic individuals, and involving multiple immune active cells and immune factors. Inflammatory factors cause edema and exudation of the local nasal mucosa, stimulating the nasal sensory nerves, resulting in typical symptoms such as paroxysmal and recurrent nasal itching, sneezing, and watery nasal discharge. It may also be accompanied by nasal congestion, decreased sense of smell, asthma, and other symptoms. AR is closely related to genetic factors, regional climate, air pollution, neurological and psychological factors, and socio-economic factors in addition to allergens. AR belongs to the category of “nasal congestion” in traditional Chinese medicine. Traditional Chinese medicine believes that this disease is the result of the combined action of internal and external factors. The internal factors are mostly organ deficiency and insufficient positive qi, while the external factors are mostly wind, cold, or foreign qi invasion, with the clash of evil and positive qi, and the inability to release lung qi, resulting in nasal congestion. In clinical practice, antihistamines and nasal corticosteroids are mainly used to treat AR, but long-term use has poor efficacy and is prone to recurrence. Traditional Chinese medicine treats AR through oral administration, nasal flushing of Chinese herbal decoctions or acupoint application, Chinese herbal fumigation, nebulization, and other methods. This article uses data mining methods to analyze the medication patterns of traditional Chinese medicine in the treatment of AR, and uses network pharmacology and in vivo pharmacology verification methods to predict and verify the potential mechanism of action of high-frequency traditional Chinese medicine in the treatment of AR, providing rational reference and scientific theoretical basis for its clinical treatment of AR.

 

In the frequency analysis of traditional Chinese medicine used to treat AR, the top five most frequently used herbs are Xinyi, Huangqi, Fangfeng, Licorice, and Cang’er Zi. Xinyi, as the most frequently used traditional Chinese medicine, has a warm nature, can dispel wind and cold, and promote nasal opening. Its main components are volatile oils, lignans, and alkaloids, which have a wide range of pharmacological effects such as protecting mucous membranes, improving local blood circulation, anti-inflammatory, antibacterial, anti allergic, antioxidant, and relaxing smooth muscles. Xinyi is often used as a royal medicine in the treatment of various rhinitis and nasal diseases, such as Xinyi Rhinitis Pills, Biyan Kang Tablets, Biyuan Pills, Tongqiao Rhinitis Granules, Xinfang Rhinitis Capsules, Xinyi Powder, Xinyi Pills, Xinyi Ointment, Sinus Infusion Fluid, etc. Li Shizhen also recorded in the Compendium of Materia Medica that “Xinyi can warm the middle and treat diseases of the head, face, nose, and nine orifices”.
Through research, it has been found that among 252 traditional Chinese medicine prescriptions, the drug classification is mainly based on surface clearing drugs (such as Xinyi, Fangfeng, Xixin, Baizhi, Guizhi, etc.) and deficiency tonifying drugs (such as Huangqi, Licorice, Atractylodes macrocephala, etc.). The medicinal properties are mostly focused on warming, and the medicinal flavors are mainly spicy and sweet. Warm herbs have the effects of warming the middle and dispelling cold, tonifying fire and assisting yang. Spicy herbs can dispel wind and cold, promote qi and blood circulation. Sweet herbs have the effects of harmonizing medicinal properties, nourishing the middle, and regulating the meridians of the lungs, spleen, and liver. Based on comprehensive analysis, the single traditional Chinese medicine used to treat AR is mostly Xinyi, Fangfeng, Cang’er Zi, Xixin, Baizhi, Guizhi, etc., which are mainly used for wind and cold manifestations such as chills, fever, headache, sweating, limb soreness, runny nose, nasal congestion, thin and white fur, throat itching and cough, and floating pulse.
In the analysis of association rules, the core drug combinations with high support are Huangqi Atractylodes macrocephala Radix Atractylodes macrocephala Radix Atractylodes macrocephala Radix Atractylodes macrocephala Radix Atractylodes macrocephala Radix Atractylodes macrocephala Radix Atractylodes macrocephala Radix Atractylodes macrocephala Radix Atractylodes macrocephala Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylodes Radix Atractylo. Except for Schisandra chinensis, Cicada molt, and peppermint, the commonly used doses of other high-frequency drugs are within the dosage range specified in the Chinese Pharmacopoeia.
In cluster analysis, a group of traditional Chinese medicines mainly focus on tonifying deficiency and relieving exterior symptoms. Among them, the main active ingredient of Astragalus membranaceus, Astragalus polysaccharides, can alleviate symptoms such as sneezing, scratching the nose, and runny nose in AR rats. It can reduce the inflammation of AR rat nasal mucosal tissue by upregulating the expression of T-bet and IFN – γ mRNA, downregulating the expression of GATA-3 and IL-4 mRNA, and promote the recovery of AR by reducing the levels of inflammatory factors such as serum IL-4, IL-6, IL1 β, IgE, TNF – α, etc. Windproof has the effects of dispelling wind, relieving surface dampness, and relieving itching. Windproof polysaccharides have been proven to have good anti allergic effects through in vitro experiments. Windproof alcohol extracts can exert anti allergic effects by reducing the expression of PAR-2 in in vitro cells. Guizhi has the effects of sweating and relieving muscle, warming and promoting meridians, helping yang transform qi, and dispersing external wind pathogens. Ju Er Cang Er Zi has the effects of dispersing wind and cold, promoting nasal opening, and dispelling wind and dampness. It is used for treating wind and cold headaches, nasal congestion and runny nose, nasal congestion, nasal sinuses, rheumatism and itching, and damp stagnation and spasms; The n-butanol extract of Fructus Xanthii can alleviate nasal mucosal inflammation in AR guinea pigs, reduce white blood cell count, eosinophil percentage, and serum SIgE levels; The water extract of Atractylodes macrocephala can alleviate symptoms such as nasal mucosal detachment, tissue edema, and inflammatory cell infiltration in AR guinea pigs, and reduce the expression levels of inflammatory cytokines IgE, IL-4, and IFN – γ in serum.
This article searched the TCMSP database and supplemented the literature, and found a total of 48 active ingredients in the Huangqi Xinyi medicine pair, corresponding to 306 target points. Each ingredient is used for multiple targets. To further illustrate the relationship between target points and components, a “component target disease” network was constructed by taking the intersection of component targets and disease targets. The main components, kaempferol and quercetin, were found to have the highest correlation with the targets and may be the key components of Huangqi Xinyi in treating AR, playing important pharmacological roles. Studies have shown that kaempferol can reduce the occurrence of intestinal inflammation by improving the integrity of the intestinal barrier, and has significant anti hyperglycemic and antioxidant effects; Quercetin can significantly reduce atherosclerotic inflammation by inhibiting the binding of galectin-3 and NLRP3. Further analysis of the KEGG pathway revealed that the neuroactive ligand receptor interaction pathway, calcium ion signaling pathway, steroid hormone biosynthesis pathway, and cancer pathway are the main pathways through which Huangqi Xinyi exerts its anti AR effects, involving 34 active ingredients and 39 core targets. By analyzing the “component target pathway disease” relationship, we found that PTGS2, HSP90, NOS2, CALM1, CHRM1, CYP1B1, and other target proteins play a major role in the pathway. PTGS2 is involved in pathological reactions such as inflammation or tumors, and is a target of nonsteroidal anti-inflammatory drugs. It can be highly induced by pro-inflammatory cytokines and growth factors to secrete inflammatory factors, triggering an inflammatory response. HSP90 is an ATP dependent molecular chaperone that can assist client proteins in completing correct spatial folding and participating in cell cycle regulation. Studies have shown that HSP90 can regulate lymphocyte activation, promote lymphocyte migration to infection sites, and facilitate local inflammatory responses under physiological stress in the body. NOS2 is an inducible nitric oxide synthase expressed after injury in the body, which can utilize the oxidative stress of nitric oxide to participate in immune regulation and inflammatory response in the body. CALM1 is a calmodulin protein, and overexpression of CALM1 can abnormally activate cellular calcium ion signaling channels, ultimately leading to inflammatory reactions and a certain degree of liver damage in the body. CHRM1 is a parasympathetic receptor, and studies have shown that CHRM1 agonists can regulate neuronal differentiation by enhancing cellular calcium ion activity. In molecular docking validation, they have low binding energy to kaempferol and can trigger the release of inflammatory cytokines by regulating the activation of calcium ion channels. CYP1B1 is a major protein involved in the steroid hormone synthesis pathway. Steroids have significant anti-inflammatory and anti allergic immune regulatory effects, and have shown good and stable binding ability to quercetin and kaempferol in molecular docking validation. From the above analysis, it can be seen that the main components in Huangqi Xinyi may act on the neuroactive ligand receptor interaction pathway, calcium ion signaling pathway, steroid hormone biosynthesis pathway, and cancer pathway through targets such as PTGS2, HSP90, NOS2, CALM1, CHRM1, CYP1B1 to exert therapeutic effects on AR. In order to further verify the reliability of the above prediction results, an AR mouse model induced by ragweed pollen was constructed for in vivo experimental verification. The research results showed that Huangqi Xinyi medicine could reduce the protein expression of PTGS2, HSP90, and NOS2 in AR mice, inhibit the expression levels of inflammatory factors histamine, IgE, TNF – α, and IL-6 in AR mouse serum, nasal lavage fluid, and bronchoalveolar lavage fluid, increase the expression of anti-inflammatory factor IL-10, significantly alleviate AR mouse scratching and sneezing symptoms, and reveal that Huangqi Xinyi medicine may inhibit the occurrence and development of inflammatory reactions by inhibiting the HSP90/PTGS2/NOS2 pathway, thereby achieving the effect of intervening in AR.
In summary, the medication rules for clinical treatment of AR were summarized through data mining statistical analysis and network pharmacology techniques, and the molecular mechanism of high-frequency drug combination Huangqi Xinyi in treating AR was deeply studied. Molecular docking simulation verified the multi-component, multi-target, and multi pathway characteristics of Huangqi Xinyi, and in vivo experiments confirmed that Huangqi Xinyi drugs may inhibit the occurrence of inflammatory reactions, alleviate AR symptoms in mice, and ultimately achieve the effect of treating AR by inhibiting the HSP90/PTGS2/NOS2 pathway. The results of this study can provide a scientific theoretical basis for the rational use of Xinyi Huangqi medicine in clinical practice, and further promote the application of traditional Chinese medicine in the treatment of allergic rhinitis.