RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. AIM OF THE STUDY: NLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD. MATERIALS AND METHODS: BALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting. RESULTS: XQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1ß and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome. CONCLUSIONS: The representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.
Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Rinite Alérgica , Camundongos , Animais , Inflamassomos/metabolismo , Interleucina-13 , Camundongos Endogâmicos BALB C , Piroptose , Interleucina-4 , Interleucina-5 , Simulação de Acoplamento Molecular , Rinite Alérgica/tratamento farmacológico , Modelos Animais de Doenças , OvalbuminaRESUMO
OBJECTIVE: To investigate the effect of Sarcandra glabra Thunb on prevention and treatment of thrombocytopenia after chemotherapy with a large dosage. METHODS: The Babl/c mice model of thrombocytopenia was made by intraperitoneal injection of 5-FU at a large dosage. All mice were poured Sarcandra glabra Thunb dilution to the mice's stomach once daily from the beginning of the experiment. Then the effect was analyzed by measuring peripheral blood cell counts of the mice on the 2nd day, the 4th day and the 7th day after chemotherapy. On the end of 7th day, all mice were killed, and then bone marrow biopsy was employed to investigate the hemapoietic condition. RESULTS: Before the chemotherapy, the platelet counts of mice treated by Sarcandra glabra Thunb were higher than that in the control group (P < 0.05). After chemotherapy with 5-FU, the platelet counts were not significantly decreased in two all experimental groups compared with negative control group (P < 0.05), while there was not significantly different between two experimental groups (P > 0.05). Moreover the marrow biopsy showed that bone marrow hyperplasia was active in two intervention study groups with some megaryocytes in the medullary cavity of bone while bone marrow hyperplasia was low in the control group without any megaryocyte in the medullary cavity of bone. CONCLUSION: The Sarcandra glabra Thunb had obvious activity in treatment to therombocytopenia and can prevent thrombocytopenia by 5-FU.