Studies On The Chemical Constituents And Bioactivities Of Arctii Fructus

Arctium lappa L. is a biennial herbaceous plant distributed mainly throughout China and Japan. Arctii Fructus, named "niu bang zi" in Chinese, is the dried mature fruits of Arctium lappa L.. It is a very important traditional medicine to treat the measles, constipation, sore throat, and facial nerve paralysis. The preliminary bioassay showed that it has antioxidant and hepatoprotective activity. In order to further clarify the active substance of Arctii Fructus, we performed the chemical investigation of Arctii Fructus by using various chromatographic separation technologies,51 compounds inclouding 18 new compounds were isolated and identified on the basis of spectroscopic and chemical methods. The new compounds were marked "*". Compound 1* is a novel rare butyrolactone lignan with a 6-carboxyl-2-pyrone moiety. The 6-carboxyl-2-pyrone was potentially formed from 3,4-dihydroxy phenyl moiety through the oxidative cleavage, oxidation, and esterification. The structures of these compounds were characterized as follows:arctiidilactone (1*), (8R,7’R,8’R)-rafanotrachelogenin-4-O-β-D-glucopyranoside (2*), (8R,7’S,8’R)-rafanotrachelogenin-4-O-β-D-glucopyranoside (3*),(8R,7’R,8’R)-4,4’,7’-trihydroxy-3,3’-dimethoxy-9-oxo dibenzylbutyrolactone lignan-4-O-β-D-gluco-pyranoside (4),(7S,8S,8’R)-4,7-dihydroxy-3,3’,4’-trimethoxy-9-oxo dibenzylbutyro-lactone lignan (5*),(7S,8S,8’R)-4,7-dihydroxy-3,3’,4’-trimethoxy-9-oxo dibenzylbutyro-lactone lignan-4-O-β-D-glucopyranoside (6*), (7R,8S,8’R)-4,7-dihydroxy-3,3’,4’-trimethoxy-9-oxo dibenzylbutyrolactone lignan-4-O-β-D-glucopyranoside (7*), (7R,8S,8’R)-4,7,4’-trihydroxy-3,3’-dimethoxy-9-oxo dibenzylbutyrolactone lignan-4-0-β-D-glucopyranoside (8*), arctigenin-4-O-α-D-galactopyranosyl-(1â†'6)-O-β-D-glucopyranoside (9*), arctigenin-4-O-β-D-apiofuranosyl-(1â†'6)-O-β-D-glucopyranoside (10*),5’-propanediolmatairesinoside (11*), arctiinorlignan A (12*), matairesinol-4,4’-di-O-β-D-glucopyranoside (13), arctiin (14), arctigenin-4-O-β-D-gentiobioside (15), styraxlignolide E (16), styraxlignolide D (17), (7S,8R)-4,7,9,9’-tertahydroxy-3,3’-dimethoxy-8-4’-oxyneolignan-9’-O-β-D-apiofuranosyl-(1â†'6)-O-β-D-glucopyrano-side(18*), (8R)-4,9,9’-trihydroxy-3,3’-dimethoxy-7-oxo-8-4’-oxyneolignan-4-O-β-D-glucopyranoside (19*), (7R,8R)-4,7,9,9’-tertahydroxy-3,3’-dimethoxy-8-4’-oxyneolignan (20), (7R,8R)-7,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan-4-O-β-D-glucopyrano-side (21), (7R,8R)-4,7,9,9’-tetrahydroxy-3,3’-dimethoxy-8-O-4’-neolignan-9’-O-β-D-glucopyranoside (22), (7R,8R)-4,7,9,9’-tetrahydroxy-3,3’-dimethoxy-8-4’-oxyneolign-7’-ene-9’-O-β-D-glucopyranoside (23), (8S,7’S,8R)-4,4’,9’-trihydroxy-3,3’-dimethoxy-7’,9-epoxylignan-7-oxo-4-O-β-D-glucopyranoside (24*), (8S,7’S,8’R)-4,4’,9’-trihydroxy- 3,3’-dimethoxy-7’,9-epoxylignan-7-oxo-4’-O-β-D-glucopyranoside (25), (7R,SS)-dihydrode-hydrodiconiferyl alcohol-7’-oxo-4-O-β-D-glucopyranoside (26*), (7S,8R)-dihydrode-hydrodiconiferyl alcohol-4-O-β-D-glucopyranoside (27), (7S,8R,7’R,8’R)-pinoresinol-4,4’-di-O-β-D-glucopyranoside (28), (7S,8R,7’R,8’R)-epipinoresinol-4’-O-β-D-glucopyranoside (29), secoisolariciresinol-4-O-β-D-glucopyranoside (30), arctiisesquineolignan A (31*), arctiisesquineolignan B (32*), lappaol H (33), 1-O-β-D-xylosfuranosyl-(1â†'6)-O-β-D-glucopyranosyl-4-hydroxy-3,5-dimethoxyphenol (34*),1-O-β-D-xylopyranosyl-(1â†'6)-O-β-D-glucopyranoside-2-methoxy-4-hydroxy-phenol (35), 1-O-β-D-xylopyranosyl-(1â†'6)-O-β-D-glucopyranoside-3-methoxy-4-hydroxyphenol (36),4-O-β-D-xylopyranosyl-(1â†'6)-O-β-D-glucopyranoside-4-hydroxy-3-methoxybenzyl alcohol (37),2-azanyl-8,9-dimethxyl-5H-purin-6-one (38), 2’-deoxyguanosine (39), guanosine (40), thymine (41), thymine deoxyriboside (42), 4-O-caffeoylquinic acid (43),3-O-caffeoylquinic acid (44),5-O-caffeoylquinic acid (45),3,5-di-O-caffeoylquinic acid (46),4,5-di-O-caffeoylquinic acid (47), 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethxyl-quinoxaline (48), tryptophan (49), 3-benzyl-2,5-piperazinedione (50),2-phenethyl β-primeveroside (51).Bioactivities of fractions and compounds from Arctii Fructus were screened by various pharmaceutical models. The results showed that, the macroporous resin 30% ethanol elution of the water fraction of EtOH extract of Arctii Fructus extracted by EtOAc exibited obvious antioxidant activities against Fe2+-Cysteine induced toxicity at 10 μg/mL and some hepatoprotective effects against D-galactosamine-induced toxicity in WB-F344.The macroporous resin 95% ethanol elution of the water fraction also show some inhibitory effects on nitric oxide production by BV2 stimulated with LPS. Compouds 33 and 34* showed significant DPPH radical scavenging activities at the concentraction of 1×10-5M (Inhibition:50.1% and 44.4%, respectively. Positive control: 44.0%). Compouds 11* and 12* showed significant hepatoprotective activities against APAP-induced toxicity in HepG2 at the concentraction of 2×10-5 M (Inhibition:53.9% and 53.6%, respectively. Positive control:53.9%), and compouds 6*,8*,18* also showed some hepatoprotective activities.Compouds 1*,3*,5*,11*, and 17 showed obvious inhibitory effects on nitric oxide production by BV2 stimulated with LPS at the concentraction of 1×10-5M (Inhibition:96.34%,87.77%,63.31%,71.59%, and 66.67%, respectively. Positive control:53.00%). Cytotoxicity studies revealed that all compounds exhibit inactivity against all cancer cell lines (ICso> 10μM).