Anti-Food Allergic Alkaloids from the Lotus Seed Pot.

Lotus seed pod (LSP) has been used as traditional herbal cuisine to modulate immunity. From the AcOEt-soluble extract of LSP, one new aporphine alkaloid, N-[2-(2H-phenanthro[3,4-d][1,3]dioxol-5-yl)ethyl]acetamide (nelunucine A, 1) was obtained along with 19 known ones. Their structures were established by detailed analysis of the 1D-, 2D-NMR, and HR-ESI-MS data. N-Nornuciferine (9) and lirinidine (10) showed potent in vitro anti-food allergic activity with IC50 values of 40.0 and 55.4 µM, respectively, compared to 91.4 µM for loratadine, the positive control.

Anti-adipogenicadamantane type polycyclic polyprenylated acylphloroglucinols from Hypericum subsessile.

Hypersubones D-H (1-5), five new polycyclic polyprenylated acylphloroglucinols (PPAPs) type metabolites with intriguing adamantane and homo-adamantane skeletons, were characterized from aerial parts of Hypericum subsessile. Compounds 1-2 were elucidated to share an adamantane core with 28,29-expoxide moiety, while 3-5 were homo-adamantane type PPAPs sharing a1,2-dioxepane ring system. Their structures were determined on the basis of comprehensive NMR and MS spectroscopic data.The anti-adipogenesis activities of these isolates were evaluated through employing 3T3-L1 cells as an in vitro system using oil red O staining, and compounds 1, 2 and 5 were able to significant inhibit the adipocyte differentiation, which implied that these compounds possessed anti-adipogenic activity.

[Binding interaction of harpagoside and bovine serum albumin: spectroscopic methodologies and molecular docking].

Scrophularia ningpoensis has exhibited a variety of biological activities and been used as a pharmaceutical product for the treatment of inflammatory ailment, rheumatoid arthritis, osteoarthritis and so on. Harpagoside (HAR) is considerer as a main bioactive compound in this plant. Serum albumin has important physiological roles in transportation, distribution and metabolism of many endogenous and exogenous substances in body. It is of great significance to study the interaction mechanism between HAR and bovine serum albumin (BSA). The mechanism of interaction between HAR and BSA was investigated using 2D and 3D fluorescence, synchronous florescence, ultraviolet spectroscopy and molecular docking. According to the analysis of fluorescence spectra, HAR could strongly quench the fluorescence of BSA, and the static quenching process indicated that the decrease in the quenching constant was observed with the increase in temperature. The magnitude of binding constants (KA) was more than 1×105 L·mol⁻¹, and the number of binding sites(n) was approximate to 1. The thermodynamic parameters were calculated through analysis of fluorescence data with Stern-Volmer and Van't Hoff equation. The calculated enthalpy change (ΔH) and entropy change (ΔS) implied that the main interaction forces of HAR with BSA were the bonding interaction between van der Waals forces and hydrogen. The negative values of energy (ΔG) demonstrated that the binding of HAR with BSA was a spontaneous and exothermic process. The binding distance(r) between HAR and BSA was calculated to be about 2.80 nm based on the theory of Frster's non-radiation energy transfer, which indicated that energy is likely to be transfer from BSA to HAR. Both synchronous and 3D florescence spectroscopy clearly revealed that the microenvironment and conformation of BSA changed during the binding interaction between HAR and BSA. The molecular docking analysis revealed HAR is more inclined to BSA and human serum albumin (HSA) in subdomain ⅡA (Sudlow's site I). This study will provide valuable information for understanding the action mechanism of HAR.

Two new secoiridoids and other anti-hepatitis B virus active constituents from Swertia patens.

Two new secoiridoids, swerpatic acid (1) with an unusual C8 skeleton and swerpalactone (2), were isolated along with ten known compounds (3-12) from the whole plants of Swertia patens. Their structures were elucidated by comprehensive spectroscopic analyses. Eight compounds were evaluated for their anti-hepatitis B virus (HBV) activities on Hep G 2.2.15 cell line in vitro. Compounds 4 and 10 showed moderate inhibitory activities on the secretion of HBsAg with IC50 values of 1.96 and 0.50 mM.

Chemical constituents of Swertia delavayi and their anti-hepatitis B virus activity.

Fifteen known compounds were isolated from Swertia delavayi by silica gel, Sephadex LH-20 and Rp-18 column chromatographies. Based on extensive spectroscopic analysis (MS, 1H, 13C-NMR), their structures were identified aserythrocentaurin (1), erythrocentaurindimethylacetal (2), sweroside (3), swertiamarin (4), gentiopicroside (5), swertiakoside A (6), 2'-O-acetylswertiamarin (7), 4'-O-[(Z) -coumaroyl] swertiamarin (8), 1,5,8-trihydroxy-3-methoxyxanthone (9), 8-O-ß-D-glucopyranosyl-1-hydroxy-2,3, 5-trimethoxyxanthone (10), 8-O-[ß-D-xyl- opyranosyl-(1 --> 6)-ß-D-glucopyranosyl]-7,8-dihydroxy-3-methoxyxanthone (11), isovitexin (12), ß-sitosterol (13), daucosterol (14), and oleanolic acid (15). Among them, ten ones (14, 7-11, 13) were obtained from S. delavayi for the first time. The isolates were evaluated for their anti-HBV activities in HepG 2. 2. 15 cell line in vitro. The results showed that compound 1, 2, 6, 7, 9 and 12 exhibited significant inhibitory activity on HBV DNA replication with IC50 values from 0.05 to 1.46 mmol x L(-1).

Isolation, synthesis and anti-hepatitis B virus evaluation of p-hydroxyacetophenone derivatives from Artemisia capillaris.

p-Hydroxyacetophenone (p-HAP), as a main hepatoprotective and choleretic constituent of Artemisia capillaris, was revealed with anti-hepatitis B virus (HBV) effects in recent investigation. In addition to p-HAP, four derivatives of p-HAP were also isolated from A. capillaris by various chromatographic methods. Subsequent structural modification on p-HAP and its glycoside led to the synthesis of 28 additional derivatives, of which 13 compounds showed activity inhibiting hepatitis B surface antigen (HBsAg) secretion; and 18 compounds possessed inhibition on HBV DNA replication. The primary structure-activity relationships (SARs) suggested that the conjugated derivatives of p-HAP glycoside and substituted cinnamic acids (2a-2i) obviously enhanced the activity against HBV DNA replication with IC50 values ranged from 5.8 to 74.4 µM.

Chemical constituents of Swertia mussotii and their anti-hepatitis B virus activity.

Three new secoiridoid aglycones of (-)-swermusic acid A (1) and B (3), and (-)-swerimuslatone A (2), and four new secoiridoid glycosides of 6'-O-formylsweroside (4), 6'-O-formylgentiopicroside (5), 6'-O-acetylamarogentin (6) and 6'-O-acetylamaronitidin (7), along with 40 known compounds (8-47) were isolated from Swertia mussotii. Their structures were elucidated on the basis of extensive spectroscopic analyses including MS, IR, UV, 1D- and 2D-NMR. Forty-five compounds from S. mussotii were evaluated for their anti-HBV activity on the HepG 2.2.15 cell line in vitro inhibiting the secretions of HBsAg and HBeAg, as well as HBV DNA replication. Six of the nine phenols 26-29, 31 and 32 exhibited activities inhibiting HBsAg and HBeAg secretion with IC50 values from 0.23 to 5.18mM, and HBV DNA replication with IC50 values from <0.06 to 2.62mM. Moreover, isooriention (45) displayed significant anti-HBV activities against secretions of HBsAg and HBeAg with IC50 value of 0.79 and 1.12mM, as well as HBV DNA replication with IC50 value of 0.02mM.

[Chemical constituents of Swertia patens].

Chemical constituents of Swertia patens. The whole plant of air-dried Swertia patens was extracted with 90% EtOH. The water extract was suspended in H2O and extracted with petroleum ether, EtOAc and n-BuOH, successively. The compounds were isola- ted and purified by column chromatography from the EtOAc fraction, and identified based on spectral analyses (MS, ¹H-NMR, ¹³C- NMR). Eighteen compounds were isolated and elucidated as 3, 4-dihydro-1H,6H,8H-naptho [1,2-c:4,5-c', d'dipyrano-1, 8-dione (1), angelone (2), gentiogenal (3), erythricin (4), erythrocentaurin (5), gentianine (6), swertiakoside B (7), swertiamarin (8), 2'-O-actylswertiamarin (9), amarogentin (10), 1, 3, 5-trihydroxyxanthone (11), 1, 3-dihydroxy-5-methoxyxanthone (12), 1-hydroxy- 2, 3, 5-trimethoxyxanthone (13), gentiocrucine (14), 3-hydroxyphenylketone (15), n-hexacosyl ester 4-hydroxy-trans-cinnamate (16), n-hexacosyl ester 4-hydroxy-cis-cinnamate (17), and cholest-4-en-3-one (18). Compounds 1-7, 9-18 were obtained from S. patens for the first time.

[Chemical constituents of Swertia kouitchensis Franch].

This study is to investigate the chemical constituents of Swertia kouitchensis. The whole plants of air-dried Swertia kouitchensis was extracted with 90% EtOH. The water extract was suspended in H2O and extracted with petroleum ether, EtOAc and n-BuOH, successively. The compounds were isolated and purified by column chromatography from the EtOAc fraction, and their structures were identified based on spectral analyses (MS, 1H-NMR, 13C-NMR). Twenty-eight compounds were obtained, and characterized as erythrocentaurin (1), erythrocentaurin dimethylacetal (2), swertiamarin (3), vogeloside (4), 2'-O- actylswertiamarin (5), swertianoside D (6), gentiocrucines A-B (7-8), gentiocrucine (9), 1-hydroxy-3, 7, 8-trimethoxyxanthone (10), 1-hydroxy-3, 5, 6-trimethoxyxanthone (11), 3-epitaraxerol (12), erythrodiol 3-O-palmitate (13), (+) -syringaresinol (14), caffeic acid (15), trans-coniferyl aldehyde (16), trans-coniferyl alcohol (17), 3, 4-dihydroxybenzoic acid (18), 4-hydroxy-3-methoxybenzoic acid (19), 3, 4-dihydroxybenzoic aldehyde (20), 2, 3-dihydroxybenzoic acid (21), 4-hydroxybenzoic acid (22), 3-acetoxybenzoic acid (23), 3-hydroxybenzoic acid (24), 3-hydroxybenzoic alcohol (25), nicotinic acid (26), 2-furoic acid (27), and uracil (28). Compounds 1-4, 6-28 were obtained from S. kouitchensis for the first time.

[Chemical constituents of Swertia angustifolia].

This present work is to study the chemical constituents of Swertia angustifolia. The whole plants of air-dried Swertia angustifolia was extracted with 90% EtOH. The water extract was suspended in H2O and extracted with petroleum ether, EtOAc and nBuOH, successively. The compounds were isolated and purified by column chromatography from the EtOAc fraction, and identified based on spectral analyses (MS, 1H-NMR, 13C-NMR). Fourteen compounds were isolated and characterized as 1, 8-dihydroxy-3, 7-dimethoxyxanthone (1), 1, 8-dihydroxy-3, 5, 7-trimethoxyxanthone (2), 7-hydroxy-3, 8-dimethoxyxanthone-1-O-ß-D-glucopyranoside (3), 8-0-[ß-D-xylopyranosyl-(1-6) -ß-D-glucopyranosyl] -1, 7-dihydroxy-3-methoxyxanthone (4), (+) -syringaresinol (5), ferulic acid (6), trans-coniferyl aldehyde (7), sinapaldehyde (8), trans-coniferyl alcohol (9), 3, 4-dihydroxybenzoic acid (10), 2-hydroxybenzoic acid (11), isophthalic acid (12), 2-furoic acid (13), and 2-methyl-4(3H)-quinazolinone(14). Compounds 2-14 were obtained from this plant for the first time.

UFLC/MS-IT-TOF guided isolation of anti-HBV active chlorogenic acid analogues from Artemisia capillaris as a traditional Chinese herb for the treatment of hepatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatitis B induced by HBV is a serious health problem. Artemisia capillaris (Yin-Chen) has long been used to treat hepatitis in traditional Chinese medicine. Coumarins, flavonoids and organic acids were revealed as its hepatoprotective and choleretic components, but its anti-HBV active components remain unknown. This current study focused on its anti-HBV active constituents by various chromatographic methods. MATERIAL AND METHODS: LC/MS and bioassay-guided fractionation on the active extract of Artemisia capillaris led to the isolation of nine chlorogenic acid analogues. Structures of the isolates were elucidated by MS/MS and NMR techniques. Anti-HBV assay was performed on HepG 2.2.15 cell line in vitro: reduction of HBsAg and HBeAg secretions was measured by an ELISA method; inhibition of HBV DNA replication was monitored by real-time quantitative PCR and cellular toxicity was assessed by a MTT method. RESULTS: The 90% ethanol extract of Artemisia capillaris (Fr. AC) showed significantly inhibitory activity on HBV DNA replication with an IC50 value of 76.1 ± 3.9 µg/mL and low cytotoxic effects (SI>20.1). To clarify its active constituents, the extract was further separated into 3 sub-fractions (AC-1, AC-2 and AC-3), of which Fr. AC-2 was the most active fraction against HBeAg secretion and HBV DNA replication with IC50 values of 44.2 ± 2.8 and 23.2 ± 1.9 µg/mL. Nine chlorogenic acid analogues were detected from the active part (Fr. AC-2) by a LC/MS technique and further separated by a HPLC method. The isolates were determined as chlorogenic acid (1), cryptochlorogenic acid (2), neochlorogenic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), chlorogenic acid methyl ester (7), cryptochlorogenic acid methyl ester (8), neochlorogenic acid methyl ester (9). Compounds 1-6 possessed potent activity against HBV DNA replication with IC50 values in the range of 5.5 ± 0.9-13.7 ± 1.3 µM. Di-caffeoyl analogues (4-6) also exhibited activity against the secretions of HBsAg and HBeAg. Esterified analogues (7-9) showed dramatically decreased anti-HBV activity, indicating that carboxyl group is closely associated to the anti-HBV activity. CONCLUSIONS: This investigation was focused on the active fractions of Artemisia capillaris and their active compositions, which showed that Fr. AC-2 was the main active section of Artemisia capillaris and chlorogenic acid analogues were the main constituents contributing to its anti-HBV activity. These results support the ethnopharmacological use of Artemisia capillaris as anti-HBV agents.

Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris.

Three new polyacetylenes, 8-(Z)-decene-4, 6-diyne-1, 3, 10-triol (1), 1, 3S, 8S-trihydroxydec-9-en-4, 6-yne (2), 3S, 8S-dihydroxydec-9-en-4, 6-yne 1-O-ß-D-glucopyranoside (3), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-ß-D-glucopyranose (4), together with 34 known compounds were isolated from Artemisia capillaris. The structures of the new compounds were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRESIMS, [α]D and CD experiments. Among them, 19 compounds showed activity inhibiting HBsAg secretion; 20 compounds showed activity inhibiting HBeAg secretion; and 25 compounds possessed inhibitory activity against HBV DNA replication according to our anti-HBV assay on HepG 2.2.15 cell line in vitro. The most active compound 12 could inhibit not only the secretions of HBsAg and HBeAg, but also HBV DNA replication with IC50 values of 15.02 µM (SI=111.3), 9.00 µM (SI=185.9) and 12.01 µM (SI=139.2).

[Chemical structure of capsicuoside A from fruits of Capsicum annuum].

Five compounds were isolated from Capsicum annuum by means of various chromatographic techniques (silica gel, Sephadex LH-20, MCI GEL CHP-20P and HPLC), and their structures were determined as luteolin-7-O-[2"-O-(5"-O-sinapoyl)-beta-D-apiofuranosyl]-beta-D-glucopyranoside (1), uridine (2), adenosine (3), 7-hydroxy-6-methoxy cinnamic acid ethyl ester (4) and 7-hydroxy cinnamic acid ethyl ester (5) by extensive spectroscopic analyses (UV, IR, MS, 1D- and 2D-NMR). Among them, compound 1 is a new flavone glycoside named as capsicuoside A, and cmpounds 2-5 are isolated for the first time from the fruits of C. annuum.

Chemical constituents of Swertia yunnanensis and their anti-hepatitis B virus activity.

Four new triterpenoids, sweriyunnangenin A (1), sweriyunnanosides A (2), B (3) and C (4), along with nineteen known compounds (5-23) were isolated from Swertia yunnanensis. Based on extensive spectroscopic analyses (1D- and 2D-NMR, HRESIMS, UV, IR, [α]D), the structures of sweriyunnangenin A (1), sweriyunnanosides A (2), B (3) and C (4) were elucidated as taraxer-14-ene-3α,6ß-diol, oleanolic acid 28-O-ß-D-glucopyranosyl-(1→2)-O-ß-D-glucopyranoside, 2α,3ß-di-hydroxyolean-12-en-28-oic acid 28-O-ß-D-glucopyranosyl(1→6)-ß-D-glucopyranosyl (1→6)-ß-D-glucopyranosyl(1→2)-ß-D-glucopyranoside and hederagenin 28-O-ß-D-glucopyranosyl(1→6)-ß-D-glucopyranosyl(1→6)-ß-D-glucopyranosyl(1→2)-ß-D-glucopyranoside, respectively. Twenty-two compounds were evaluated for their anti-HBV activities on the HepG 2.2.15 cell line in vitro, of which nine compounds showed potent anti-HBV activities. Compounds 1, 5-6, 14-16 and 19 showed activities against the secretion of HBsAg (IC50 values from 0.10 to 1.76 mM) and HBeAg (IC50 values from 0.04 to 1.41 mM), and compounds 11 and 13-16 exhibited significant inhibition on HBV DNA replication (IC50 values from 0.01 to 0.09 mM).

Xanthones with anti-hepatitis B virus activity from Swertia mussotii.

Two new xanthones, 8-O-ß-D-glucopyranosyl-1-hydroxy-2,3,5-trimethoxyxanthone (1) and 8-O-[ß-D-xylopyranosyl-(1 → 6)-ß-D-glucopyranosyl]-1-hydroxy-2,3,5-trimethoxyxanthone (2), along with eighteen known xanthones (3-20) were isolated from Swertia mussotii. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D- and 2D-NMR, HRESIMS, UV, IR, [α]D). All compounds were evaluated for their anti-hepatitis B virus activities on HepG 2.2.15 cells line in vitro, and compounds 3-10 exhibited significant activity inhibiting hepatitis B virus DNA replication with IC50 values from 0.01 mM to 0.13 mM. Compounds 3-5 showed remarkable activity with IC50 values of 0.77, > 0.98, and 0.21 mM for HBsAg, and < 0.62, 0.35, and 0.04 mM for HBeAg, respectively. Meanwhile, the effects of different substitutions on the anti-hepatitis B virus activity of xanthones from S. mussotii were discussed.

Seven new secoiridoids with anti-hepatitis B virus activity from Swertia angustifolia.

Seven new secoiridoids, swertianglide (1) and swertianosides A-F (2-7), together with fifteen known compounds, were isolated from the whole plants of Swertia angustifolia. Their structures were elucidated on the basis of extensive spectroscopic analyses ([α](D), UV, IR, MS, 1D- and 2D-NMR). Fourteen compounds were evaluated for their anti-hepatitis B virus (HBV) activities on the Hep G 2.2.15 cell line in vitro. Compound 2, an unusual secoiridoid glycoside dimer, showed significant activities inhibiting the secretion of HBsAg (IC50 0.18 mM, SI 3.11) and HBeAg (IC50 0.12 mM, SI 4.67).