Journal of Natural Products VoI. 58, No. I , pp. 140-144, Januav I995
140
ANTI-INFLAMMATORY ACTIVITY OF SAIKOSAPONINS FROM HETEROMORPHA TRlFOLIATA MARIA DEL CARMEN RECIO, MARIA JOSE JUST, ROSAMARIA SALVADOR U Z ,JOSE LUISk O S , *
GINER,
Departament de Farmacologia, Facultat de Farmicia, Uniwrsitat de Valktcia, Avah. Vicent And& Estellii sln, E-461 00 Burjassot, Valhcia, Spain and KURTHOSTET~A”
Institut de Pbarmacognosie et Pbytochimie, Ecole de Pbarmacie, Uniwrsite’de Luusanne, CH-I 015 Luusanne-Dwigny, Switzerland AaSmcr.-By means of activity-directed chromatographic fractionation using the 12-0tetradecanoylphorbol acetate (TPA)-induced edema test, two saikosaponins were isolated from the MeOH extract of Hetermotpba trgoliata leaves. They were identified as 16P,23-dihydroxy13,28-epoxyolean-l l-en-3P-yl-[P-D-glucopyranosyl(1+2)1-[P-D-glucopyranosyl (1+3)f-f!D-fucopyranoside E l f and 16P,23,28-trihydroxy-l la-methoxyolean-12-en-3f!-yl-[~-Dglucopyranosyl (1+2)]-[P-~glucopyranosyl (1+3)f-P-D-fucopyranoside 121. Compound 1 showed activity in the TPA and ethylphenylpropiolate (EPP) mouse ear edema and the serotonin paw edema tests, whereas compound 2 was active only in the mouse ear edema model. Both substances had only a slight effect against a carrageenan paw edema model. The anti-inflammatory action of compound 1 was notably decreased by the mRNA and protein synthesis inhibitors actinomycin D and cycloheximide.
Hetermotpha trifoliata Eckl. & Zeyh. (Umbelliferae) is a bush growing in Central and East Africa that is used in traditional medicine for its antimalarial and antiscabies activities (1,2). Two antifungal products, the polyine falcarindiol and the allylbenzene sarisan, have been isolated from a petroleum ether extract of the leaves (1). We have recently examined the anti-inflammatory activity of its MeOH extract, and found it to reduce TPA-induced ear edema and carrageenaninduced paw edema in mice by 88% and 4456, respectively (unpublished data). We report herein the isolation of its active anti-inflammatory principles. Fractionation of the MeOH extract of H . trifoliata on a Sephadex LH-20 column yielded six fractions. The first of these, which contained crude saponins, decreased the TPA-induced edema by 92%. Further purification by chromatographic techniques yielded compounds 1 and 2. ’H-and 13C-nmrspectral interpretation indicated that these compounds had identical sugar moieties. Acid hydrolysis of the compounds gave glucose and fucose as sugar components. The
aglycones in 1 and 2 were identified as saikogenin F and that of saikosaponin B,, respectively. Because their ‘H- and 13Cnmr spectra are identical to those reported in the literature (3,4), compound 1wascharacterizedas 16P,23-dihydroxy13,28-epoxyolean-11-en-3P-yl-[P-Dglucopyranosyl( 1+2)}-{P-D-glucopyranosyl (1+3)}-P-D-fucopyranoside and compound 2 as 16P,23,28-trihydroxy- 1la-methoxyolean-12-en-3P-yl{~-D-glucopyranosyl(1+2)}-{~-~-glucopyranosyl( 1+3)]-P-D-fucopyranoside. Saponin 1 was identified for the first time in Budilejajaponica Hemsl. (Buddlejaceae) (3) and named buddlejasaponin IV.Recently, both saponins have been described in a species of Bupleurum (Umbelliferae) (4), a genus related to Hetwommpha. The identity and the sequence of sugar units in the trisaccharide attached at C-3 were determined by different spectroscopic techniques. Both saponins 1 and 2 showed a marked topical activity against TPAinduced edema, with a significant inhibition of 89 and 87% (p
