Effective Substance And Mechanism Of Hyssopus Cuspidatus Boriss.in Treating Asthma

Uigur medicine Zufa is the dry aerial parts of Hyssopus cuspidatus Boriss,a genus of herbaceous or semi-woody plants in Lamiaceae family,native from the east Mediterranean to central Asia as far east as Mongolia,which was originally recorded in the Uyghur medicine monograph"Yi He Ti Ya La Ti Baidiyi".It has many pharmacological effects such as anti-inflammatory,anti-asthma,preventing cough and eliminating phlegm,and it is mainly used to treat pneumonia,acute asthma,long-term cough,etc.Many studies have demonstrated that the extracts of Zufa and related plants have the confirmed anti-asthmatic effect,although the principle active ingredients have not been identified.The anti-asthmatic activity of the extracts of Zufa was evaluated by an ovalbumin（OVA）-induced allergic asthma mouse model.The result showed that the extracts decreased the total inflammatory cells,eosinophils and lymphocytes in BALF,and reduced the inflammatory infiltration around airways and lung tissues dose-dependently.The extracts also substantially inhibited the production of IL-4,IL-13,IL-17 and promoted the production of IFN-γand IL-10 in BALF to improve the imbalance of Th1/Th2 immune response.These findings demonstrated the significant anti-asthmatic effect of Zufa.In order to further explore the effective substance of Zufa in treating asthma,twenty-three compounds were isolated and identified from the 95%EtOH extracts of Zufa by a combination using of silica gel,ODS,Toyopearl HW-40C,Sephadex LH-20and semi-preparative HPLC.Among them,compound 1（7-epi-3-eudesmene-1β,11-diol）and compound 2（（7S,10R）-11-hydroxy-4,5-seco-guai-1-ene-4-one）were new compounds,compound 3（11-hydroxy-1-oxo-4β,5β,7β,10β-eremophilane）was a new natural product,and compound 1²2 were isolated from the plants of Hyssopus genus for the first time.Nitric oxide（NO）is a kind of small molecular medium that is widely present in living organisms and has complex biological activities.In the pathogenesis of asthma,a large amount of NO will expand airway blood vessels,stimulate glandular secretion,and induce the release of a variety of inflammatory mediators to aggravate airway inflammation and tissue damage.Fifteen compounds isolated from Zufa were tested for their inhibitory effects against NO production in lipopolysaccharide（LPS）-induced RAW264.7 cells.The results showed that compared with the positive reference dexamethasone(IC₅₀=70.35±2.04μM),（3S,5R,6S,7E）-3,5,6-trihydroxy-7-megastigmen-9-one（compound 17）and spathulenol（compound 18）expressed a moderate inhibitory activity with IC₅₀0 values of 105.86±2.68μM and 89.04±2.82μM,respectively;other compounds showed no significant inhibitory activity.The anti-inflammatory and anti-asthmatic substances and molecular mechanisms of Zufa need to be further studied.