Chemical Constituents And Biological Activities Of Halenia Corniculata (L.) Cornaz

Halenia corniculata(L.) Cornaz is an annual plant belongs to the family of Gentianaceae that distributed throughout Russia,Mongolia.In China,it is concentrated on east and north of China,Shaanxi,and so on.H.corniculata is mostly used to be a traditional plant drug which indicated liver diseases in Mongolia and Tibetan medicine in China.This paper summarized the pharmacogonasy characters of it and the chemical constituents and pharmacological research of Halenia.It was found that the chloroform and n-butanol extracts of H.corniculata significantly inhibited the chemical injury on liver of mouse.Thus,the chemical constituents of this two extracts and the relation between H.corniculata and liver injury were researched in the present study.Additionally,the inhibitory activity against osteoporosis in vivo and vitro of H.corniculata and components from it were also explained.It was determined by using the chemical and immunity liver injury model that the chloroform and n-butanol fractions of H.corniculata showed significant inhibitory activity. Through the bioactivity-guided fractionation,twenty two compounds(1-22) were isolated from this two parts by means of many different chromatographic methods.By physico-chemical data and spectral methods,these compounds were identified as 1-hydroxy-2, 3,4,5-tetramethoxyxanthone(1),1-hydroxy-2,3,4,7-tetramethoxyxanthone(2), 1-hydroxy-2,3,4,5,7-pentamethoxyxanthone(3),1-hydroxy-2,3,5-trimethoxyxanthone(4), 1,3-dihydroxy-4,5-dimethoxyxanthone(5),1-hydroxy-3,5-dimethoxyxanthon(6),1, 8-dihydroxy-3,5-dimethoxyxanthone(7),1,3-dihydroxy-4,7-dimethoxyxanthone(8),2,3, 5-trimethoxy-1-O-primeverosyloxyxanthone(9),2,3,4,5-tetramethoxy- 1-O-primeverosyloxyxanthone (10),2,3,4,7-tetramethoxy-1-O-primeverosyloxyxanthone(11), luteolin(12),apigenin(13),cinaroside(14),(7S)-7-caffeoyloxysweroside(15),epi-vogeloside (16),sweroside(17),8-hydroxy-2-methylchromone(18),1-hydroxy-2,3,7-trimethoxyl--xanthone (19),1,3,5-trihydroxyxanthone(20),ursolic acid(21),β-sitosterol(22).Among them,compounds 9,16,17,19,21 and 22 were isolated from the plant for the first time.Four xanthones(compounds 5,6,8 and 20) were found for the first time in genus Halenia. Compound 7,15 were isolated from the family of Gentianaceae for the first time.And compound 18 was determined to be a novel natural product.According to the experiments of anti CCl₄-induced liver injury on mouse in vivo, compounds 1,2,9,11 showed inhibitory activities,in which 9,11 were more active than 1,2 and compound 9 was the most potent.The structure-activity relationship showed that the presence of glycosyl group and the absence of methoxyl group in the molecular might have the important role in inhibiting liver injury.The effect on HBV,HCV of H.corniculata and components from it in vitro mostly showed negative results.Above all,it is concluded that H. corniculata can not inhibit the growth and copy of HBV and HCV virus,but it affected the liver diseases by repairing the liver cells injury.Screening by co-culture system of mouse osteoblastic calvarial cells and bone marrow cells in amounts of nature plants,the chloroform and n-butanol extracts of H.corniculata were found to be effective on inhibition of osteoclastogenesis.They also showed strong activity in vivo experiment on OVX rats.They increased the uterus index and reduced the body weight,increased the serum E2 and reduced the serum ALP,also prevented the decrease of BMD of the femoral diaphysis and improved the biomechanical properties significantly.So it was further investigated of the compounds isolated from the two extracts.Repeated experiments resulted that most of the xanthones and flavonoids showed inhibitory effect on the osteoclast differentiation.Compounds 1-4,7 and 12 were the most potent.The structure-activity relationship showed that the presence of 1-hydroxy group of xanthones might have the important role in inhibiting osteoclastogenesis,but 3-hydroxy group reduced this activity.Five of the above six compounds were also evaluated to be effective on bone resorption through an osteoclastic bone resorption assay and an osteoclastic survival assay, only except for compound 7.Additionally,the six compounds showed the stimulatory activity on osteoblast through the assay of ALP activity of osteoblasts and compounds 1,4 and 7 improved the formation of mineralized bone nodule,which indicated the effect on stimulating the bone formation of these compounds.