| Objective:First of all,this study aims to evaluate the clinical efficacy of Biyan Tongqiao powder in the treatment of allergic rhinitis(AR)with deficient cold of lung Qi syndrome.Secondly,Biyan Tongqiao powder contains multiple pungent herbs.Pungent herbs are similar to capsaicin and have the effect of activating the TRPV1 pathway.Therefore,we will use a network pharmacology approach to explore the common targets and signaling pathways between Biyan Tongqiao powder and capsaicin in the treatment of AR,in order to investigate the common pharmacological mechanism of Biyan Tongqiao powder and capsaicin in the treatment of AR.Finally,based on the different roles of capsaicin,vasoactive intestinal peptide(VIP)and dendritic cell(DC)in allergic rhinitis,we investigated the effects of capsaicin,which has a similar pharmacological mechanism to that of Biyan Tongqiao powder,in modulating immunerelated mechanisms in AR rats subjected to different DC interventions.Research content:1.Clinical observation of Biyan Tongqiao powder in treatment of AR with deficient cold of lung Qi syndromeThe medical records of 68 AR patients with deficient cold of lung Qi syndrome who met the criteria were retrospectively collected and divided into treatment group and control group according to the patients' previous medications.The treatment group was treated with Biyan Tongqiao powder,while the control group was treated with rupatadine fumarate tablets and mometasone furoate aqueous nasal spray.The main outcome measures were the total nasal symptom score(TNSS)and the individual nasal symptom score(INSS);the secondary outcome measures were the scores of rhinoconjunctivitis quality of life questionnaire(RQLQ)to evaluate the improvement of clinical symptoms and quality of life of AR patients after treatment,and to provide a basis for further multicenter clinical trials with large samples.Results:(1)The two groups of patients were comparable in terms of total symptom and sign scores before treatment.(2)Comparing the symptom-sign scores of the treatment group after treatment revealed that there was a highly significant difference in terms of improvement of sneezing,runny nose,nasal congestion and nasal itching(p<0.01),and a significant difference in terms of improvement of sleep(p<0.05).In the control group,there was a highly significant difference in improving the symptoms of nasal congestion and sneezing(p<0.01);there was a significant difference in improving the symptoms of runny nose and nasal itching(p<0.05).(3)Comparison of the two groups after treatment showed that the treatment group was more effective than the control group in improving nasal congestion(p<0.01).There was no significant difference in improving the quality of life between the treatment group and the control group(p>0.05).2.Network pharmacological study on the common targets of Biyan Tongqiao powder and capsaicin in the treatment of ARThe active components of Biyan Tongqiao Powder were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)with standards of Absorption,Distribution,Metabolism,and Excretion(ADME),and the related target proteins were predicted.The target protein of capsaicin was predicted in the TCMSP database by the compound name of capsaicin.Uni Prot database was used to standardize the gene names of these target proteins,and Gene Cards database was used to screen the related targets of AR.The obtained targets of Biyan Tongqiao Powder,capsaicin and AR were imported into the Venny website to obtain their common targets.Then,these common targets were input into STRING online database to generate proteinprotein interaction(PPI)network,which were visualized and arranged according to the degree value by Cytoscape 3.7.1 software to screen out the core targets and key active components of Biyan Tongqiao powder and capsaicin in the treatment of AR.To explore the pharmacological mechanism of Biyan Tongqiao powder and capsaicin on AR,Metascape database was used for GO and KEGG enrichment analysis of common targets.Results:(1)Eleven Chinese herbal medicines of Biyan Tongqiao Powder contained 200 compounds and 272 target genes from TCMSP database.It is predicted that there are 36 target proteins in capsaicin from TCMSP database.(2)A total of 524 AR-related targets were screened from Gene Cards database.(3)In the Venn diagram generated by Venny website,Biyan Tongqiao powder,capsaicin and AR have 9 common targets.(4)According to the degree values,kaempferol,quercetin,luteolin,beta-sitosterol,and naringenin were the top five key compounds.The nine common targets were listed in descending order according to their degree values as AKT1,MAPK1,VEGFA,PTGS2,HMOX1,ALOX5,MMP1,RELA,and BCL2.(5)A total of 108 KEGG pathways were enriched;two hundred and forty-two items were enriched with biological process(BP);five items were enriched with cell component(CC);six items were enriched with molecular function(MF).It is involved in response to oxidative stress,cellular response to oxidative stress,gland development,negative regulation of extrinsic apoptotic signaling pathway,regulation of extrinsic apoptotic signaling pathway,phosphatase binding,transcription factor binding,protein kinase binding,HIF-1 signaling pathway,NF-kappa B signaling pathway.Moreover,common targets have significant effects on nuclear membrane,secretory granule lumen,cytoplasmic vesicle lumen,and other regions.mechanisms in allergic rhinitis rats by different DC interventionExperiment?: Thirty healthy adult SD rats were randomly divided into three groups: group A(n = 10),group B(n = 10)and group C(n =10).The DCs were cultured in vitro,and a portion of DCs were activated by adding VIP.Finally,they were divided into VIP-activated DC(VIPDC)and DC.Then the nasal mucosa of rats in groups A,B and C were injected with VIP-DC supernatant,DC supernatant and normal saline,respectively.After injection,the AR models of rats in groups A,B and C were constructed based on the ovalbumin(OVA)sensitization method.Behavioral observations and scores were performed during the symptom provocation stage of the three groups.After construction of the AR rat model,the rats were executed and the nasal mucosa was taken for paraffin sectioning and hematoxylin-eosin staining(HE staining)to observe the tissue edema,vasodilatation,inflammatory cell infiltration and the integrity of the nasal mucosa epithelium.ELISA kits were applied to detect the levels of IL-4,IL-10 and TGF-? in the serum of rats in each group.Experiment?: Twenty healthy adult SD rats were randomly divided into two groups: group A(n = 10)and group B(n = 10).The AR models of rats in group A and group B were constructed based on the OVA sensitization method.After the completion of modeling,the nasal mucosa of rats in group A and group B were injected with VIP-DC and DC3.To study the regulatory effect of capsaicin on immune related supernatant,while nasal drops of OVA suspension were used to continuously induce allergic reactions.The nasal mucosa was injected 24 h later with capsaicin nasal drops for 15 days in group A and group B.Then behavioral observations and scores were made during the nasal mucosal injection phase and the completion phase of capsaicin nasal drops in the two groups,respectively.After 48 h of the completion phase of capsaicin nasal drops,the rats were executed and the nasal mucosa was extracted for HE staining to observe the tissue edema,vasodilation,inflammatory cell infiltration and the integrity of nasal mucosa epithelium.The supernatant extracted after centrifugation of blood was also used to detect the levels of IL-4,IL-10 and TGF-? in it by ELISA kit.Results:Experiment I:(1)The AR rat models were successfully modeled,and the rats showed typical symptoms of AR,such as sneezing,clear nasal discharge,scratching,and pale edema of nasal mucosa.(2)the allergic rhinitis symptoms of rats in group A were the most serious,and the immune response of rats in group C was more obvious than that in group B.(3)HE staining of nasal mucosa in three groups showed that the epithelium of nasal mucosa in each group was relatively complete;the degree of edema in group C was lighter than that in other groups;the degree of lymphocyte infiltration and edema in group A was the highest;and the degree of eosinophil infiltration in group B was more severe than that in other groups.(4)The levels of TGF-? and IL-10 in group A were lower.The level of IL-4 was higher in group A.The levels of TGF-? and IL-10 were higher in group B.The level of IL-4 in group B was lower.The levels of TGF-?,IL-10 and IL-4 in group C were moderate.Experiment?:(1)the AR models of rats in group A and B was established successfully.The total behavioral scores of rats in both groups decreased after capsaicin action.(2)HE staining of the nasal mucosa of rats in both groups suggested that the epithelium of the nasal mucosa was relatively complete in both groups;the degree of eosinophil infiltration in group A was more severe than that in group B;and the degree of lymphocyte infiltration and nasal mucosal edema in group B was higher than that in group A.(3)The results of ELISA showed that the levels of TGF-? and IL-4 were lower and IL-10 was higher in group A than in group B.Conclusion:1.Biyan Tongqiao powder can effectively improve the symptoms of nasal itching,nasal congestion,sneezing,runny nose and sleep in AR patients with deficient cold of lung Qi syndrome.2.Biyan Tongqiao powder and capsaicin have similar pathways of action in AR.Biyan Tongqiao powder is mainly involved in regulating immune and inflammation related signaling pathways and biological cellular processes through the binding of active ingredients such as kaempferol,quercetin,luteolin and common targets(AKT1,MAPK1,VEGFA,etc.),which ultimately achieve the purpose of treating allergic rhinitis.3.Im DC can help improve immune tolerance in the nasal mucosa of AR rats.VIP-treated imDC can intensify the anti-inflammatory response of nasal mucosa,improve the immune sensitivity of nasal mucosa,and reduce the tolerance of nasal mucosa to external antigens.4.Capsaicin attenuates allergic symptoms in AR rats subjected to different DC interventions. |
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