New C9 -Monoterpenoid Alkaloids Featuring a Rare Skeleton with Anti-Inflammatory and Antiviral Activities from Forsythia suspensa.

Forsyqinlingines C (1) and D (2), two C9 -monoterpenoid alkaloids bearing a rare skeleton, were isolated from the ripe fruits of Forsythia suspensa. Their structures, including absolute configurations, were fully elucidated by extensive spectroscopic data and ECD experiments. The plausible biogenetic pathway for compounds 1 and 2 was also proposed. In vitro, two C9 -monoterpenoid alkaloids showed anti-inflammatory activity performed by the inhibitory effect on the release of ß-glucuronidase in rat polymorphonuclear leukocytes (PMNs), as well as antiviral activity against influenza A (H1N1) virus and respiratory syncytial virus (RSV).

Anti-inflammatory and anti-viral labdane diterpenoids from the fruits of Forsythia suspensa.

Eight labdane diterpenoids, including two new labdane diterpenoids, named forsyshiyanins A-B (2-3), along with six known ones (1, 4-8), were isolated from the fruits of Forsythia suspensa. The new structures including their absolute configurations were elucidated by extensive spectroscopic analyses, X-ray diffraction and computational calculation. In vitro, eight labdane diterpenoids showed anti-inflammatory activities, with the inhibition rates of release of ß-glucuronidase from polymorphonuclear leukocytes of rats being in the range 46.8-51.0% at concentrations of 10 µM, as well as anti-viral activities against influenza A (H1N1) virus and respiratory syncytial virus (RSV), with the IC50 values in the range 18.4-26.2 µM and EC50 values in the range 10.5-14.4 µM, respectively.

New Flavonoid Glucuronate Esters with Anti-inflammatory Activities from Scutellaria regeliana.

Two new flavonoid glucuronate esters, named scuregeliosides A and B (1 and 2), as well as three known ones, chrysin-7-O-ß-d-glucuronic acid methyl ester (3), 5,7,4'-trihydroxyflavone-8-O-ß-d-glucuronic acid methyl ester (4) and apigenin-7-O-ß-d-glucuronic acid ethyl ester (5), were isolated from the ethanolic extract of the whole plant of Scutellaria regeliana. Their chemical structures were elucidated on the basis of comprehensive spectroscopic analyses. Five compounds were screened for anti-inflammatory activity in vitro. As the results, the inhibition rates of release of ß-glucuronidase from rat polymorphonuclear leukocytes were in the range of 42.2 - 47.1% at a concentration of 10 µm.

[Studies on flavonoids from Scutellaria moniliorrhiza].

By means of preparative HPTLC and column chromatography over silica gel and Sephadex LH-20, nineteen flavonoids were isolated and purified from the whole plants of Scutellaria moniliorrhiza. Based on the physico-chemical properties and spectral data, their structures were identified as： apigenin (1), luteolin (2), wogonin (3), oroxylin A (4), 6-methoxynaringein (5), 5,7,4'-trihydroxy-6,8-dimethoxyflavone (6), 5,7,8-trimethoxyflavone (7), 3,5,6,7-tetramethoxyflavone (8), 7-hydroxy-4',5,6,8-tetramethoxyflavone (9), 5,7,2'-trihydroxy-6-methoxyflavanone (10), 5,7,4'-trihydroxy-6-methoxyflavone (11), 5,7-dihydroxy-6,8-dimethoxy -flavone (12), 5,2',6'-trihydroxy-7,8-dimethoxyflavone (13), 5,7,2'-trihydroxy-8-methoxyflavone (14), 5,2'-dihydroxy-7,8-dimethoxyflavanone (15), 2'-hydroxy-5,7,8-trimethoxyflavone (16), 5-hydroxy-7,8-dimethoxyflavone (17), 5,2'-dihydroxy-7,8-dimethoxyflavone (18), and 5-hydroxy-6,7,8-trimethoxyflavone (19). For the first time, compounds 1-19 were isolated from S. moniliorrhiza, and compounds 6, 8, 9, 12, 19 were isolated from the Scutellaria genus.

New cytotoxic neo-clerodane diterpenoids from Scutellaria strigillosa.

Three new neo-clerodane diterpenoids, named scutestrigillosins A-C (1-3), were isolated from the whole plant of Scutellaria strigillosa. Their chemical structures including absolute configurations were established on the basis of detailed physical data analyses. In vitro, the isolated three new compounds exhibited significant cytotoxic activities against four tumor cell lines (HONE-1, P-388, MCF7 and HT29), and gave IC50 values in the range 3.5-7.7µM.

New neo-clerodane diterpenoids from Scutellaria strigillosa with cytotoxic activities.

Two new neo-clerodane diterpenoids, named scutestrigillosins D and E (1 and 2), were isolated from the whole plant Scutellaria strigillosa. Their structures were established on the basis of detailed physical data analyses. In vitro, two new compounds exhibited cytotoxic activities against four tumor cell lines (HONE-1, P-388, MCF7, and HT29), and gave IC50 values in the range of 3.4-8.9 µΜ.

[neo-Clerodane diterpenoids from Scutellaria galericulata].

By means of preparative HPTLC and column chromatography over silica gel and Sephadex LH-20, fourteen diterpenoids were isolated and purified from the whole plants of Scutellaria galericulata. Based on the physico-chemical properties and spectral data, their structures were elucidated and identified as：scutebarbatine D(1), scutolide A(2), scutolide K(3), scutebata J(4), scutebata I(5), 6-O-acetylscutehenanine A(6), barbatin C(7), scutolide E(8), barbatine C(9), scutebarbatine Y(10), scutebarbatine B(11), scutestrigillosin A(12), scutebata O(13), scutolide B(14). Compounds 1-14 were isolated from S. galericulata for the first time.

[Studies on sesquiterpenes from Solanum septemlobum].

By means of preparative HPTLC and column chromatography over silica gel and Sephadex LH-20, ten sesquiterpenes were isolated and purified from the whole plants of Solanum septemlobum Bunge. Based on the physico-chemical properties and spectral data, their structures were elucidated and identified as: lyratol D(1), solajiangxin B(2), 1 ,2-dehydrocyperone(3), solanerianone A (4), dehydrocarissone(5), ligucyperonol(6), nardoeudesmol A(7), solajiangxin F(8), and lyratol B(9), solajiangxin D(10). For the first time, compounds 1-10 were isolated from Solanum septemlobum, and compounds 5-7 were obtained from the genus Solanum.

[Diterpenoids from Scutellaria strigillosa].

By means of preparative HPTLC and column chromatography over silica gel and Sephadex LH-20, nine diterpenoids were isolated and purified from the whole plants of Scutellaria strigillosa. Based on the physico-chemical properties and spectral data, their structures were elucidated as: 6-O-acetyl-7-O-nicotinoylscutebarbatine G(1), 6-O-nicotinoyl-7-O-acetylscutebarbatine G(2), 6,7-di-O-nicotinoylscutebarbatine G(3), scutebarbatine K(4), scutebarbatine B(5), 6-O-acetylscutehenanine A(6), 6-O-nicotinoylbarba- tin A(7), 6,7-di-O-acetoxylbarbatin A(8), scutebarbatine F(9). Compound 1 is a new diterpenoid, and compounds 2-9 were isolated from Scutellaria strigillosa for the first time.

New sesquiterpenoid derivatives from Solanum lyratum and their cytotoxicities.

Three new sesquiterpenoid isopropylidene derivatives, named solajiangxins H and I (1 and 2) and 7-hydroxylsolajiangxin I (3), were isolated from the whole plant of Solanum lyratum. Their structures were elucidated on the basis of integrated spectroscopic techniques, mainly HR-FAB-MS, 1D NMR, and 2D NMR ((1)H-(1)H COSY, HMQC, HMBC, and NOESY). In vitro, compounds 1-3 were found to show significant cytotoxicity against three cancer cells (P-388, HONE-1, and HT-29), and gave IC50 values in the range of 3.2-7.7 µM.

[Sesquiterpenoids from Solanum lyratum].

Ten compounds were isolated and purified by column chromatography over silica gel, preparative TLC, and Sephadex LH-20 from the whole plant of Solanum lyratum. The structures were elucidated on the basis of physico-chemical properties and spectral data as 1beta-hydroxy-1 ,2-dihydro-alpha-santonin (1) , boscialin (2) , blumenol C (3), 3beta-hydroxy-5alpha, 6alpha-epoxy-7-megastigmen-9-one(4), dehydrovomifoliol(5) , blumenol A(6), (1'S,2R,5S, 10R) -2-(1', 2'-dihydroxy-l1'-methylethyl) -6,10-dimethylspiro[4,5] dec-6-en-8-one(7) , (1'R,2R,5S,10R)-2-( 1',2'-dihydroxy-l '-methylethyl) -6,1 l0-dimethylspiro[4,5]dec-6-en-8-one( 8) , 2-(1',2'-dihydroxy-1 '-methylethyl) -6,1 0-dimethyl-9-hydroxyspiro [4,5] dec-6-en-8-one (9) , and grasshopper ketone (10). Compounds 1-10 were isolated from this plant for the first time.

New ursane-type triterpene with NO production suppressing activity from Nauclea officinalis.

Two new ursane-type triterpenes, named as 3ß, 19α, 23, 24-tetrahydroxyurs-12-en-28-oic acid (1) and 2ß, 3ß, 19α, 24-tetrahydroxyurs-12-en-28-oic acid (2), together with two known triterpenoids, 3-oxo-urs-12-ene-27, 28-dioic acid (3) and quinovic acid-3-ß-rhamnopyranoside (4), were isolated from the stems (with barks) of Nauclea officinalis. The structures of 1 and 2 were determined by the combined use of single-crystal X-ray diffraction and spectroscopic data analysis. The inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells were examined, and compound 1 was found to inhibit NO production, with the IC(50) value of 4.8 µM.

New abietane norditerpenoid from Salvia miltiorrhiza with cytotoxic activities.

One new abietane-type norditerpenoid, named militibetin A (1), was isolated from the dry roots of Salvia miltiorrhiza, along with two known diterpenoids, yunnannin A (2) and ferruginol (3). Their structures were established by means of extensive spectroscopic analyses. In vitro, compounds 1-3 were found to show cytotoxicities against selected cancer cells, including P-388, HONE-1, and HT-29, and gave ED(50) values in the range of 2.9-5.4 µg ml(- 1).

Two new C13-norisoprenoids from Solanum lyratum.

Two new C(13)-norisoprenoids, named lyratols E and F (1-2), were isolated from the whole plant of Solanum lyratum Thunb, and their structures were elucidated by extensive spectroscopic analyses. In vitro, two new compounds were found to show significant cytotoxicity against selected cancer cells including P-388 and HT-29.

Trinorlabdane diterpenoid alkaloids featuring an unprecedented skeleton with anti-inflammatory and anti-viral activities from Forsythia suspensa.

Two unique trinorlabdane diterpenoid alkaloids, forsyqinlingines A (1) and B (2), were isolated from the ripe fruits of Forsythia suspensa. Their structures, including absolute stereochemical configurations, were fully elucidated from extensive spectroscopy experiments, single-crystal X-ray diffraction, and electronic circular dichroism (ECD). In addition, a plausible biosynthetic pathway for the formation of compounds 1 and 2 in Forsythia suspensa was also proposed. In vitro, the two C17-labdane diterpenoid alkaloids exhibited anti-inflammatory activities by inhibiting the release of ß-glucuronidase in rat polymorphonuclear leukocytes (PMNs), and antiviral activities against influenza A (H1N1) virus and respiratory syncytial virus (RSV).

Alkaloids bearing rare skeletons from Forsythia suspensa with anti-inflammatory and anti-viral activities in vitro.

Five alkaloids, including two previously undescribed alkaloids, named forsyshiyanines A and B, attributable to the rare skeletons 4b,5,6,7,8,8a,9,10-octahydrobenzo[f]quinoline and (6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)methyl, respectively, along with three known ones (3-5), were isolated from the ripe fruits of Forsythia suspensa. The chemical structures including absolute configurations of two undescribed compounds were established using integrated spectroscopic techniques, electronic circular dichroism calculations, and single-crystal x-ray diffraction analysis. In vitro, five alkaloids showed anti-inflammatory activities, with the inhibition rates of the release of ß-glucuronidase from polymorphonuclear leukocytes of rats being in the range 47.9%-56.0% at a concentration of 10 µM. Moreover, five compounds exhibited anti-viral activities against influenza A virus and respiratory syncytial virus, with IC50 values in the range of 7.3-32.5 µM and EC50 values in the range 3.7-14.1 µM.

New anti-inflammatory 4-hydroxyisoflavans from Solanum lyratum.

Three new 4-hydroxyisoflavans, named lyratin A (1), lyratin B (2) and lyratin C (3), along with a known compound, 4,7,2'trihydroxy-4'-methoxyisoflavan (4), were isolated from the whole plant of Solanum lyratum. Their structures were established by means of detailed physical data analyses. In vitro, four compounds showed anti-inflammatory activities with inhibitory ratios of release of beta-glucuronidase from polymorphonuclear leukocytes of rats in the range of 30.3-38.6% at 10 microM.

In vitro and in vivo pharmacokinetics of two novel 1,3-cyclic propanyl phosphate ester prodrugs of 18ß-glycyrrhetic acid in rats.

The in vitro metabolism of two novel phosphate prodrugs of glycyrrhetic acid (GA) was studied by the method of incubation in the rat liver microsome and the in vivo plasma pharmacokinetics after injecting intravenously (i.v.) into six rats was investigated, respectively. The prodrugs diminished gradually with time and most of the parent drugs were released in 30 min in vitro. In this paper, the in vivo plasma concentration data were analyzed by compartmental modeling. Both the prodrugs and the corresponding released parent drugs could be described by a two-compartment model, which existed for 48 h in rats. The t(1/2) increases remarkably after i.v. administration to rats when compared with injecting the parent drugs directly.

Two new cytotoxic ent-clerodane diterpenoids from Scutellaria barbata.

Two new ent-clerodane diterpenoids have been isolated from Scutellaria barbata, and their structures were established by detailed spectroscopic analyses as (13R)-6α,7ß-dihydroxy-8ß,13-epoxy-11ß-nicotinyloxy-ent-clerodan-3-en-15,16-olide (scutelinquanine D, 1) and (11E)-6α-acetoxy-7ß,8ß-dihydroxy-ent-clerodan-3,11,13-trien-15,16-olide (6-acetoxybarbatin C, 2). In vitro, the isolated two new compounds showed significant cytotoxic activities against three human cancer cell lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC(50) values in the range of 2.5-6.6 µM.

Labdane diterpenoids from Forsythia suspensa with anti-inflammatory and anti-viral activities.

Five previously undescribed labdane diterpenoids, named Forsypensins A-E, were isolated from the fruits of Forsythia suspensa. The structures and relative configurations of the compounds were elucidated via extensive spectroscopic methods, and their absolute configurations were fully confirmed by single crystal X-ray diffraction analyses using Cu Kα radiation and electronic circular dichroism data. The five labdane diterpenoids showed in vitro anti-inflammatory activity in rat polymorphonuclear leukocytes, inhibiting the rates of ß-glucuronidase release by 43.6%-49.2% at concentrations of 10 µM. The compounds also had anti-viral activity against influenza A (H1N1) virus and respiratory syncytial virus (RSV), with IC50 values in the range 21.8-27.4 µM, and EC50 values in the range 10.5-15.4 µM, respectively.