Study On The Chemical Constituents From Pogostemon Cablin And Their Biological Activities

Pogostemon cablin（Lamiaceae）is a traditional aromatic herb.Traditional Chinese medicine believes that P.cablin is mild bitter and pungent in taste,lukewarm in nature and it is attributed to lung,spleen and stomach meridians.The aerial parts of this herb have been used as stomachic tonic to eliminate dampness,improve dyspepsia and soothe vomiting and diarrhea,and also used for the treatment of influenza,headache,fever and nausea.Patchouli alcohol,one of the main ingredients of P.cablin,has been reported with anti-influenza virus activity.These findings hint that patchoulol-type sesquiterpenoids would play an important role in the active components with anti-influenza virus activity of P.cablin.In an effort to find out more active compounds and enrich the knowledge of the material foundation of P.cablin,the constituents isolated from the petroleum ether and ethyl acetate soluble fraction of the aerial parts of P.cablin were systematically studied in this investigation.In addition,the anti-influenza virus and anti-inflammatory activities of isolated sesquiterpenoids were evaluated.By means of several chromatographic techniques,such as silica gel,Sephadex LH-20 gel,MPLC,semi-preparative and preparative HPLC,and preparative TLC,along with comprehensive utilization of 1D-NMR,2D-NMR,HRESIMS and other methods,in combination with the quantum chemical calculation methods containing ECD and ¹³C-NMR computational methods,a total of 62 compounds were isolated and identified from P.cablin.Among them,16 undescribed sesquiterpenoids（1-5,7-9,11,13,16,17,20,29,30 and 32）,coupled with 4 new natural compounds（21,27,28 and 40）were reported here.62 isolates consisted largely of sesquiterpenoids,containing 4 sesquiterpenoids（1-4）owning novel carbon skeleton,15 guaiane-type ones（5-19）,9 patchoulol-type ones（20-28）,1 seychellene-type one（29）,2 caryolane-type ones（30 and 31）,2 cadinane-type ones（32 and 33）,4 eudesmane-type ones（34-37）,together with 2 nor-monocyclofarnesol-type ones（38 and 39）.Additionally,other terpenoids（40-45）,6 steroids（46-51）,5 flavonoids（52-56）,3 lignans（57-59）,2 benzene derivatives（60 and 61）and 1 octanediol（62）were separated and elucidated.It’s worth to note that pogocablene A（1）and pogocablene B（2）,owning bicyclo[4.3.1]decanone skeleton,were a pair of C₂ isomers.Through ring expansion with the rearrangement from the angular methyl of eudesmane-type sesquiterpenoid,pogocablene C（3）possessed a unique sesquiterpenoid skeleton owning bicyclo[5.4.0]undecane with a peroxy hemiacetal moiety.Moreover,pogocablene D（4）was the first example of 9,1-guaiane-type sesquiterpenoid in nature.Last but not least,pogocablene E（5）was a 4,5-seco-guaiane-type sesquiterpenoid with a peroxy hemiacetal moiety and a spirocyclic skeleton.The isolated sesquiterpenoids were evaluated for anti-influenza virus activity with influenza strains WSN and PR8 on MDCK cells.Valeriananoid A（22）and（5R）-5-hydroxypatchoulol（25）,two patchoulol-type sesquiterpenoids,exhibited anti-influenza virus activity.Compound 22showed obvious inhibitory activity against PR8 virus with the EC₅₀ value of 1.48±0.47μM,while25 performed protective inhibitory activity against PR8 and WSN virus with the EC₅₀ values of3.06 and 49.6μM,respectively.Unfortunately,all compounds did not show anti-inflammatory activity.