Spasmolytic and anti-inflammatory effects of constituents from Hertia cheirifolia

A sesquiterpenoid Bakkenolide (1), and two steroids, (3β, 22E)-Stigmasta-5, 22-diène-3-ol (Stigmasterol) (2) and stigmasterol 3β-glucoside (3), isolated from the Hertia cheirifolia (L.) chloroform extract, were evaluated respectively for their spasmolytic and anti-inflammatory activities. We note that these natural products were isolated and purified for the first time from the specie Hertia cheirifolia. Their structures have been established by spectroscopy (1 and 2D NMR experiences) and mass spectrometry. Chloroform-, ethyl acetate- and methanol-extracts were also tested for their spasmolytic and anti-inflammatory activities. Spasmolytic and anti-inflammatory screening were based respectively on the contractile response effects on rat isolated smooth muscles and on the dose-related carrageenan induced paw edema in rats. screening of the crude extracts showed spasmolytic and anti-inflammatory positive results. The antispasmodic effect of Bakkenolide was found in the same range as that of Alverine, a standard musculotropic spasmolytic agent.     

Secondary metabolites from Calotropis procera (Aiton)

Three new metabolites, 5-hydroxy-3,7-dimethoxyflavone-4′-O-β-glucopyranoside (1), 2β,19-epoxy-3β,14β-dihydroxy-19-methoxy-5α-card-20(22)-enolide (4) and β-anhydroepidigitoxigenin-3β-O-glucopyranoside (5), along with two known compounds, uzarigenine (2) and β-anhydroepidigitoxigenin (3), were isolated from Calotropis procera (Asclepiadaceae). The structure elucidation was accomplished mainly by nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric methods. To examine putative antimicrobial or cytotoxic activities, various bioassays were performed. Uzarigenine (2) demonstrated moderate cytotoxicity.     

Triterpene glycosides from red ginseng marc and their anti-inflammatory activities

Three new triterpene glycosides ursan-3β,19α,22β-triol-3-O-β-d-glucopyranosyl (2′→1″)-β-d-glucopyranoside (1), ursan-3α,11β-diol-3-O-α-d-glucopyranosyl-(6′→1″)-α-d-glucopyranosyl-(6″→1‴)-α-d-glucopyranosyl-(6‴→1‴′)-α-d-glucopyranoside (2) and lanost-5,24-dien-3β-ol-3-O-β-d-glucopyranosyl-(6′→1″)-β-d-glucopyranosyl-(6″→1‴)-β-d-glucopyranoside (3), together with one known compound were isolated and identified from the marc of red ginseng. Their structures were elucidated by spectroscopic data analysis. Compounds (1–3) were investigated for anti-inflammatory effects using the RAW 264.7 macrophage cell line. In the cell proliferation assay, lipopolysaccharide stimulation decreased cell proliferation of RAW 264.7 macrophage cells, but the suppression of cell proliferation was significantly protected by treatment with compounds 2 and 3. Compounds 2 and 3 had a suppressive effect on the production of nitric oxide (NO), and they inhibited mRNA expression of proinflammatory mediators such as inducible nitric oxide synthase, and cyclooxygenase-2, and proinflammatory cytokines such as two interleukins and tumor necrosis factor-α. These findings suggest that compounds 2 and 3 have potential anti-inflammatory activities.     

Two new spirostanol saponins from the the roots and rhizomes of Tupistra chinensis

Two new spirostanol saponins (1) and (2), together with three known saponins (3–5), were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as (20S, 22R)-spirost-25(27)-en-1β, 3β, 4β, 5β-tetraol-5-O-β-d-glucopyranoside (1) and (20S, 22R)-spirost-25(27)-en-1β, 3β, 5β-triol-5-O-β-d-glucopyranoside (2), (20S, 22R)-spirost-25(27)-en-1β, 2β, 3β, 4β, 5β-pentaol-5-O-β-d-glucopyranoside (3), Δ²⁵⁽²⁷⁾-pentrogenin (4) and ranmogenin A (5) on the basis of physicochemical properties and spectral analysis. The isolated compounds were evaluated for their cytotoxic activities against A549 and H1299 tumor cell lines in vitro. Among them, compound 2 showed cytotoxicities against A549 cells (IC₅₀ 52.66 ± 3.12 μmol L⁻¹) and H1299 cells (IC₅₀ 57.29 ± 2.51 μmol L⁻¹), respectively.     

Four new lanostane-type triterpenoids from Inonotus obliquus

Four new lanostane-type triterpenoids, inonotsuoxodiol B (1), inonotsuoxodiol C (2), epoxyinonotsudiol (3), and methoxyinonotsutriol (4), were isolated from the sclerotia of Inonotus obliquus. Their structures were determined to be 3β,22R-dihydroxylanosta-9(11),24-dien-7-one (1), 3β,22R-dihydroxylanosta-7,24-dien-11-one (2), 9α,11α-epoxy-lanosta-7,24-diene-3β,22R-diol (3), and 7β-methoxylanosta-8,24-diene-3β,11α,22R-triol (4) on the basis of NMR spectroscopy, including 1D and 2D (¹H–¹H-COSY, NOESY, HMQC, HMBC) NMR spectra, and EIMS.     

A new ursane-type triterpenoid glycoside from Centella asiatica leaves modulates the production of nitric oxide and secretion of TNF-α in activated RAW 264.7 cells

One new ursane-type triterpenoid glycoside, asiaticoside G (1), five triterpenoids, asiaticoside (2), asiaticoside F (3), asiatic acid (4), quadranoside IV (5), and 2α,3β,6β-trihydroxyolean-12-en-28-oic acid 28-O-[α-l-rhamnopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl] ester (6), and four flavonoids, kaempferol (7), quercetin (8), astragalin (9), and isoquercetin (10) were isolated from the leaves of Centella asiatica. Their chemical structures were elucidated by mass, 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy. The structure of new compound 1 was determined to be 2α,3β,23,30-tetrahydroxyurs-12-en-28-oic acid 28-O-[α-l-rhamnopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl] ester. The anti-inflammatory activities of the isolated compounds were investigated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Asiaticoside G (1) potently inhibited the production of nitric oxide and tumor necrosis factor-α with inhibition rates of 77.3% and 69.0%, respectively, at the concentration of 100 μM.     

Anti-inflammatory iridoid glycosides from fruits of Cornus officinalis

Three undescribed iridoid glycosides, cyc(7β-O-6′)-morroniside (1), 6′-methyl succinate-7β-O-methylmorroniside (2), and 7β-O-methyl phenyllactate morroniside (3) were isolated from 50% ethanol extract of Cornus officinalis fruits. The structures of the isolated compounds were determined by HRESIMS, ¹D NMR, ²D NMR, UV and IR spectroscopic methods. Compounds 1-3 exhibited moderate anti-inflammatory activities in vivo in a CuSO₄-induced zebrafish inflammation model (when evaluated at 50 μM).     

Isolation of hopane triterpenes and other constituents from Machaerium brasiliense vogel (Fabaceae)

Phytochemical study of Machaerium brasiliense leaves extract afforded three hopane triterpenes 3,4-seco-21β-H-hop-22 (29)-en-3-oic acid (1), hopenone B (2), hopene B (3). In addition, lupeol (4), stigmasterol (5), β-sitosterol (6), daucosterol (7), uracil (8), allantoin (9) and trans-4-hydroxy-N-methylproline (10) were isolated. The structures of these compounds were established based on spectroscopic data in comparison to those described in literature. Considering the chemotaxonomic relevance of the isolated compounds, this is the first report of triterpenes 1, 2 and 3 in Fabaceae family and compounds 7, 8 and 9 in the genus Machaerium. Besides, preliminary screening on antiproliferative and antioxidant activities was performed for MBEB and its fractions.     

Novel bioconversion products of andrographolide by Aspergillus ochraceus and their cytotoxic activities against human tumor cell lines

Andrographolide (1), a major labdane diterpenoidal constituent of a famous traditional Chinese of Andrographis paniculata, exhibits a wide spectrum of biological activities including antibacterial, anti-inflammatory, and antitumor properties. Bioconversion of andrographolide (1) by Aspergillus ochraceus (ATCC 1008) was investigated. Five bioconversion products were isolated and identified. Their structures were identified to be 8β-hydroxy-8(17)-dihydroandrographolide (2), 8β-hydroxy-8(17)-dihydro-14-deoxy-11,12-didehydroandrographolide (3), 8β-hydroxy-8(17)-dihydro-14-deoxy-11,12-didehydroandrographolide 19-oic acid (4), 14-deoxy-11,12-didehydroandrographolide (5), and 14-deoxy-11,12-didehydroandrographolide 19-oic acid (6). Metabolites 2–4 were novel compounds. The proposed biosynthetic pathways of andrographolide by A. ochraceus were drawn. Most bioconversion products showed potential cytotoxic activities against human breast cancer (MCF-7), human colon cancer (HCT-116) and leukemia (HL-60) cell lines.     

Sesquiterpenes and triterpenoids from the rhizomes of Alisma orientalis and their pancreatic lipase inhibitory activities

Five new terpenoids, including three sesquiterpenes 11-hydroxy-8-ox-alismoxide (1), 11-oxo-13-nor-alismol (2), and 1β,11-dihydroxy-β-cyperone (3), and two protostane-type triterpenoids 16β-acetoxy alisol B (4) and 16α-acetoxy alisol B (5) were isolated from the rhizomes of Alisma orientalis together with 11 known compounds. Their structures were established using 1D and 2D NMR and HRESIMS spectroscopic analyses. The isolated compounds were assayed for their inhibitory activities against pancreatic lipase. Compounds 6 and 13 showed inhibitory effects with IC₅₀ values of 64.4 and 45.5 μM, respectively.     

Thiophenes,polyacetylenes and terpenes from the aerial parts of Eclipata prostrata

One new bithiophenes, 5-(but-3-yne-1,2-diol)-5′-hydroxy-methyl-2,2′-bithiophene (2), two new polyacetylenic glucosides, 3-O-β-d-glucopyranosyloxy-1-hydroxy-4E,6E-tetradecene-8,10,12-triyne (8), (5E)-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-d-glucopyranoside (9), six new terpenoid glycosides, rel-(1S,2S,3S,4R,6R)-1,6-epoxy-menthane-2,3-diol-3-O-β-d-glucopyranoside (10), rel-(1S,2S,3S,4R,6R)-3-O-(6-O-caffeoyl-β-d-glucopyranosyl)-1,6-epoxy menthane-2,3-diol (11), (2E,6E)-2,6,10-trimethyl-2,6,11-dodecatriene-1,10-diol-1-O-β-d-glucopyranoside (12), 3β,16β,29-trihydroxy oleanane-12-ene-3-O-β-d-glucopyranoside (13), 3,28-di-O-β-d-glucopyranosyl-3β,16β-dihydroxy oleanane-12-ene-28-oleanlic acid (14), 3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl oleanlic-18-ene acid-28-O-β-d-glucopyranoside (15), along with fifteen known compounds (1, 3–7, and 16–24), were isolated from the aerial parts of Eclipta prostrata. Their structures were established by analysis of the spectroscopic data. The isolated compounds 1–9 were tested for activities against dipeptidyl peptidase IV (DPP-IV), compound 7 showed significant antihyperglycemic activities by inhibitory effects on DPP-IV in human plasma in vitro, with IC₅₀ value of 0.51 μM. Compounds 10–24 were tested in vitro against NF-κB-luc 293 cell line induced by LPS. Compounds 12, 15, 16, 19, 21, and 23 exhibited moderate anti-inflammatory activities.     

Steroidal constituents of Solanum xanthocarpum

From the extract of the fruits of Solanum xanthocarpum (Solanaceae), five new steroidal compounds were isolated and characterized: 4α-methyl-24ξ-ethyl-5α-cholest-7-en-3β,22ξ-diol (1), 3β,22ξ-dihydroxy-4α-methyl-24ξ-ethyl-5α-cholest-7-en-6-one (2), 3β-benzoxy-14β,22ξ-dihydroxy-4α-methyl-24ξ-ethyl-5α-cholest-7-en-6-one (3), 3β-benzoxy-14α,22ξ-dihydroxy-4α-methyl-24ξ-ethyl-5α-cholest-7-en-6-one (4) and 3β-(p-hydroxy)-benzoxy-22ξ-hydroxy-4α-methyl-24ξ-ethyl-5α-cholest-7-en-6-one (5).     

Three new phenolic glycosides from the whole plant of Aconitum tanguticum (Maxim.) Stapf

Three new phenolic glycosides 2-(3-O-β-d-glucopyranosyl-4-hydroxyphenyl) ethanol 1-O-β-d-glucopyranoside (1), 2-(4-O-β-d-fructopyranosylphenyl) ethanol 1-O-β-d-galactopyranoside (2) and 3-methoxy-4-O-β-d-allopyranosyl acetophenone (3), along with nine known compounds (4–12), were isolated from the ethanol extract of the whole plant of Aconitum tanguticum (Maxim.) Stapf. Their structures were elucidated by analysis of spectroscopic data including 1D-, 2D-NMR and HRESIMS, and the reported literature data comparison. All the compounds were evaluated for their potential anti-inflammatory effects by the inhibition of TNF-α production on LPS-stimulated RAW264.7 macrophages. Compounds 1, 3, 5 and 7–9 showed certain inhibition activity and their IC₅₀ values were 38.18, 27.64, 3.25, 84.45, 12.76 and 18.44 μg/mL, respectively.     

Three new compounds isolated from the bulbs of Fritillaria pallidiflora Schrenk and their anti-inflammatory activity

Three new compounds, 17β-cevanin-6-oxo-5α,20β-diol yibeinine (1), 2-(tetrahydro-5-(2-hydroxyphenyl)-2H-pyran-3-yl) phenol (2), 1,3-O-diferuloyl-2-methoxypropane diol (3), as well as four known compounds (4–7), have been isolated from the ethanol extract of dried bulbs of Fritillaria pallidiflora Schrenk. All structures were determined based on their spectroscopic data (1D and 2D NMR (including ¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMBC, HSQC, HSQC-TOCSY, and NOESY experiments), and MS). Biological evaluation showed that compounds 1–4 inhibited the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells with IC₅₀ values of 18.0, 38.7, 29.5, and 47.1 μM, respectively. These results indicated that compound 1 has potential anti-inflammatory activity.     

Cytotoxicity of cardenolides and cardenolide glycosides from Asclepias curassavica

A new cardenolide, 12β,14β-dihydroxy-3β,19-epoxy-3α-methoxy-5α-card-20(22)-enolide (6), and a new doubly linked cardenolide glycoside, 12β-hydroxycalotropin (13), together with eleven known compounds, coroglaucigenin (1), 12β-hydroxycoroglaucigenin (2), calotropagenin (3), desglucouzarin (4), 6′-O-feruloyl-desglucouzarin (5), calotropin (7), uscharidin (8), asclepin (9), 16α-hydroxyasclepin (10), 16α-acetoxycalotropin (11), and 16α-acetoxyasclepin (12), were isolated from the aerial part of ornamental milkweed, Asclepias curassavica and chemically elucidated through spectral analyses. All the isolates were evaluated for their cytotoxic activity against HepG2 and Raji cell lines. The results showed that asclepin (9) had the strongest cytotoxic activity with an IC₅₀ value of 0.02 μM against the two cancer cell lines and the new compound 13 had significant cytotoxic activity with IC₅₀ values of 0.69 and 1.46 μM, respectively.     

Microbial transformation of acetyl-11-keto-β-boswellic acid and their inhibitory activity on LPS-induced NO production

The capabilities of 20 strains of fungi to transform acetyl-11-keto-β-boswellic (AKBA) were screened. And biotransformation of AKBA by Cunninghamella blakesleana AS 3.970 afforded five metabolites (1–5), while two metabolites (6, 7) were isolated from biotransformation of Cunninghamella elegans AS 3.1207. The chemical structures of these metabolites were identified by spectral methods including 2D NMR and their structures were elucidated as 7β-hydroxy-3-acety-11-keto-β-boswellic acid (1), 21β-dihydroxy-3-acety-11-keto-β-boswellic acid (2), 7β,22α-dihydroxy-3-acety-11-keto-β-boswellic acid (3), 7β,16α-dihydroxy-3-acety-11-keto-β-boswellic acid (4), 7β,15α-dihydroxy-3-acety-11-keto-β-boswellic acid (5); 7β,15α,21β-trihydroxy-3-acety-11-keto-β-boswellic acid (6) and 15α,21β-dihydroxy-3-acety-11-keto-β-boswellic acid (7). All these products are previously unknown. Their primary structure–activity relationships (SAR) of inhibition activity on LPS-induced NO production in RAW 264.7 macrophage cells were evaluated.     

Ent-kaurene diterpenoids and lignan from Leontopodium leontopodioides and their inhibitory activities against cyclooxygenases-1 and 2

Two new ent-kaurene diterpenoids, 13α,15α-dihydroxy-18-carboxy-19-nor-ent-kaur-16-ene-2β-O-(2′-angelate)-β-d-glucopyranoside (leontocin A, 1), 13α,15α-dihydroxy-18-carboxy-19-nor-ent-kaur-16-ene-2β-O-(2′-angelate-6′-acetyl)-β-d-glucopyranoside (leontocin B, 2), and one new lignan, 2,3-bis[(3,4-di-hydroxyphenyl)methylene]-monoethyl ester-butanedioic acid (leontolignan A, 3), together with three known phenolic acids (4-6) were isolated from the aerial parts of Leontopodium leontopodioides (Asteraceae). Their structures were elucidated by chemical and spectroscopic methods. All isolates were evaluated for their anti-inflammatory activities by measuring their inhibitory effects against cyclooxygenase-1 and 2 in vitro.     

Synthesis of quercetin glycosides and their melanogenesis stimulatory activity in B16 melanoma cells

4′-O-β-d-Glucopyranosyl-quercetin-3-O-β-d-glucopyranosyl-(1→4)-β-d-glucopyra-noside (3) was isolated from Helminthostachys zeylanica root extract as a melanogenesis acceleration compound and was synthesized using rutin as the starting material. Related compounds were also synthesized to understand the structure–activity relationships in melanin biosynthesis.Melanogenesis activities of the glycosides were determined by measuring intracellular melanin content in B16 melanoma cells. Among the synthesized quercetin glycosides, quercetin-3-O-β-d-glucopyranoside (1), quercetin-3-O-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (2), and 3 showed more potent intracellular melanogenesis acceleration activities than theophyline used as positive control in a dose-dependent manner with no cytotoxic effect.     

Phenolic glycosides from Alangium salviifolium leaves with inhibitory activity on LPS-induced NO,PGE2, and TNF-α production

Three new phenolic glycosides, salviifosides A?C (13), and three known compounds salicin (4), kaempferol (5), and kaempferol 3-O-β-d-glucopyranoside (6) were isolated from the leaves of Alangium salviifolium (L.f.) Wangerin (Alangiaceae). The structures of the new metabolites were determined on the basic of spectroscopic analyses including two dimensional NMR. The anti-inflammatory activities of new compounds (1?3) were investigated on lipopolysaccharide (LPS)-induced murine macrophage cells line, RAW 264.7. Salviifoside B (2) potentially inhibits the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor-α (TNF-α).