Anti-inflammatory Water-soluble Constituents Of Oxybaphus Himalaicus

Oxybaphus himalaicus Edgew（Nyctaginaceae）,formerly known as Mirabilis himalaica（Edgew.）Heim.,is a kind of commonly used Tibetan medicinal plant.The dry root of O.himalaicus is named‘Bazhu’and used to warm kidney,regenerate tissue,be diuretic,remove calculus,and dry‘yellow water’in Tibetan medicine classics and clinical application.Previous studies focus on the constituents of flavonoids,especially rotenoids and their anti-tumor bioactivity.A phenylpropionate ester also exhibits anti-tumor activity on Hep G2 cells during S phase,with IC₅₀ 15.12μg/m L.In addition,a few amides,sugar esters and lignans have been reported to have weak anti-tumor,antibacterial and antioxidant activities.In clinical practice,most of the diseases treated with‘Bazhu’are related to inflammation,such as nephritis,edema,and arthralgia.Preliminary anti-inflammatory activity screening showed that the water-soluble components had significant activity.Therefore,the isolation,structure identification and anti-inflammatory activity of water-soluble constituents were carried out.Through the application of diversified chromatographic packings(MCI Gel CHP-20P,HPLCone,ODS C₁₈,Sephadex LH-20,π-NAP and HILIC)in open column,medium pressure or high pressure liquid chromatography separation,twenty-two compounds were isolated from the water-soluble part of O.himalaicus.Their chemical structures were identified as five amides（1,9,13,17 and 18）,five lignans（6,7,10,11 and 14）,eight sugar esters（2,3,4,5,15,19,20 and 21）,two flavonoid glucosides（16 and 22）and two other kind of compounds（8 and 12）based on the comprehensive spectral analyses（HRESIMS,1D and 2D NMR,UV,IR,XRD and ECD,etc.）.Among them,six compounds（1-6）were obtained for the first time,and compound 1 was a pair of benzofuranε-caprolactams featuring a unique 7/6/5 fused tricyclic framework with p-glucosyl-O-phenyl units,which was separated by chiral chromatography.The possible biosynthetic pathway of 1 was proposed.Anti-inflammatory assay showed compounds 1,5 and 10 had significant inhibitory effects against NO production,with IC₅₀ 11.9±1.9,8.9±3.5 and 13.6±0.8μM,and compounds 2,3,5,6 and 16 had potential inhibitory ability to TNF-αsecretion,with IC₅₀ 9.2±0.6,14.8±0.4,12.8±1.3,17.4±1.3 and 15.4±1.5μM,respectively.The results of this research will provide a scientific basis for the clinical application of Tibetan material medica Bazhu and the discovery of anti-inflammatory components with potential development value from O.himalaicus and related plants.