Studies On The Chemical Constituents And Biological Activities Of Zanthoxylum Armatum DC.and Asafetida

Zanthoxylum armatum DC.,also known as“Wanhuazhen”,“Baizongguan”,“Zhuyezongguan”（Jiangxi,Hunan）,“Shanhuajiao”（Guangxi）,“Goujiao”,“Yehuajiao”（Henan,Guizhou,Yunnan）,“Yajiao”,“Qinjiao”,and“Shujiao”are perennial dicotyledonous shrubs of the genus Zanthoxylum in the Rutaceae family,which have the same medicinal and food sources.The roots,stems,leaves,fruits,and seeds of bamboo leaf pepper are all used as medicinal herbs.The fruit has a spicy taste and a warm nature.In Chinese traditional medicine and Indian Ayurveda medicine,Zanthoxylum armatum DC.,is used to treat various diseases,such as toothache,headache,diabetes,eczema,diarrhea,cough,inflammation and cancer.In this paper,using lipophilic organic solvent extraction,normal phase silica gel ODS column chromatography,reversed phase C18 column chromatography,Sephadex LH-20 column chromatography,preparation liquid pre-HPLC,preparation thin layer chromatography（PTLC）and other separation methods.Twenty-two compounds were isolated from twig of Z.armatum,and their structures were identified by ¹H NMR,¹³C NMR,HMBC,HMQC,COSY and HRESIMS,including ten phenolic acids,a steroid and eleven lignans.The isolated compounds were identified as trans-ferulic acid（1）,methyl ferulate（2）,3,4,5-tri-methoxy benzoic acid（3）,3,4,5-tri-methoxy cinnamic acid（trans）（4）,methyl（E）-p-hydroxycinnamate（5）,methyl syringate（6）,eugenol（7）,（1S,2S）-1,2,3-trihydroxy-l-（3,4-methylenedioxyphenyl）propane（8）,vanillic（9）,β-sitosterol（10）,（-）-phillygenin（11）,（-）-fargesin（12）,（-）-kobusin（13）,（-）-asarinin（14）,（-）-epipinoresin（15）,（-）-eudesmin（16）,xanthoxylol（17）,（-）-epieudesmin（18）,（-）-pinoresinol（19）,pinoresinol monome ether（20）,（-）-praderin（21）,and dibutyl phthalate（22）.Among them,compounds 1-7,15,17,18 and 21 were isolated from Z.armatum for the first time,and compounds 1-3,7 and 21 were also first reported from Rutaceae.The results showed that compounds 2,3,5,7,8,12 and 14 had potential anti-hypoxia activities and could significantly reverse the decline in viability of PC12 cells under hypoxic conditions.At the same time,the anti-pancreatic cancer activities of the compounds were evaluated by using human pancreatic cancer Ca PAN-2 cell lines.The results of MTT assay showed that compounds 1,5,8 and 14 had good anti-pancreatic cancer activity on Ca PAN-2 cells.It can significantly inhibit the survival rate of cancer cells.Asafetida,is a gelatinous resin obtained by cutting the roots of the plant of the genus Umbelliferae,which is native to Central Asia,Afghanistan and Iran.It is not only used as a flavouring agent in food,but also as a traditional medicine in India.In addition,the 30 compounds were isolated from the plant by various chromatographic separation techniques.The structures of 14 compounds were determined by 1D and 2D NMR,and the absolute configurations of some compounds were determined by physical techniques such as X-ray single crystal diffraction.Compounds were obtained as follows:famesiferol C（AWJ-1）,galbanic acid（AWJ-2）,methyl galbanate（AWJ-3）,farnesiferol A（AWJ-4）,asimafoetida（AWJ-5）,kellerin（AWJ-6）,szowitsiacoumarin A（AWJ-7b）,（3’R,8’S,9’S,10’R）-drimane-5’,6’-en-11’-7-ether-coumarin（AWJ-8）,farnesiferone A（AWJ-9）,canferone（AWJ-10）,lehmannolone（AWJ-11）,farnesiferon B（AWJ-12）,badrakemin acetate（AWJ-13）and conferol acete（AWJ-14）,they are class of sesquiterpene coumarin compounds,and structural feature is that the 7 hydroxyl group of 7-hydroxycoumarin is linked to the sesquiterpene by ether bond.Compounds AWJ-1,AWJ-2,AWJ-3,AWJ-5,and AWJ-12 are coumarins with monocyclic sesquiterpene substitutions,while the other compounds are coumarins with bicyclic sesquiterpene substitutions.Among them,compound AWJ-8 is a new structure,and the absolute configuration of compound AWJ-9 was first determined by X-ray single crystal diffraction.AWJ-6 was found to inhibit the growth of CFPAC-1,Ca PAN-2 and PANC-1 pancreatic cancer cell lines.The inhibition rate of AWJ-6 was less than 50%.AWJ-4 can inhibit the growth of CFPAC-1 pancreatic cancer cells.