Evaluation of the effects of notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF (CNS) on the activities of cytochrome P450 enzymes using a cocktail method in rats.

Notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF, namely CNS, are used for the treatment of cardiovascular diseases in clinic. This study developed a cocktail assay involving seven cytochrome P450 (CYP) enzymes to elucidate the effect of NS, SF, and CNS on CYP enzymes and to explore the synergistic effect of CNS in terms of CYP enzymes. Ultra-performance liquid chromatography-MS and reverse-transcription polymerase chain reaction were applied to detect the activities and mRNA expression levels of CYP enzymes. SF exhibited inhibitory effects on CYP1A2, 2B1, 2E1, and 2C11 and induction effects on CYP2C19 and 2D4. NS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C11, 2C19, and 2D4. CNS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C19, and 2D4 and inhibitory effects on CYP3A1 in vivo. Moreover, mRNA expression results were consistent with pharmacokinetic results. Potential herb-drug interactions should be studied closely when SF, NS, or CNS with clinical drugs are metabolized by CYP1A2, 2B1, 2E1, 2C11, 2C19, 2D4, and 3A1. CNS could change the inhibition or induction effects of CYP compared to the NS group, which might be one of the causes for the synergistic effects of the combination of NS and SF.

A new prenylated coumarin diglycoside with insulin-release promoting activity from Clausena dunniana.

A new prenylated coumarin diglycoside, 6-prenylcoumarin-7-O-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside (1) and five known flavonoid glycosides (2-6) were isolated from the leaves and stems of Clausena dunniana. The structures of these isolates were elucidated based on comprehensive MS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. Compounds 2-6 are obtained from the title plant for the first time. All these isolates were evaluated for their insulin-release promoting effects, and compounds 1, 2, and 4 exhibited significant activities (2.0 to 3.3-fold higher in comparison with the control, p < 0.01) at 40 µM.[Formula: see text].

Highly selective inhibition of IMPDH2 provides the basis of antineuroinflammation therapy.

Inosine monophosphate dehydrogenase (IMPDH) of human is an attractive target for immunosuppressive agents. Currently, small-molecule inhibitors do not show good selectivity for different IMPDH isoforms (IMPDH1 and IMPDH2), resulting in some adverse effects, which limit their use. Herein, we used a small-molecule probe specifically targeting IMPDH2 and identified Cysteine residue 140 (Cys140) as a selective druggable site. On covalently binding to Cys140, the probe exerts an allosteric regulation to block the catalytic pocket of IMPDH2 and further induces IMPDH2 inactivation, leading to an effective suppression of neuroinflammatory responses. However, the probe does not covalently bind to IMPDH1. Taken together, our study shows Cys140 as a druggable site for selectively inhibiting IMPDH2, which provides great potential for development of therapy agents for autoimmune and neuroinflammatory diseases with less unfavorable tolerability profile.

Three new compounds from Dictamnus dasycarpus and their anti-inflammatory activities.

Three new compounds (1-3), named dasycarine G (1), dasycarether (2), and dasycarester (3), along with seven known compounds (4-10) obtained from the genus Dictamnus for the first time, were isolated from the root bark of Dictamnus dasycarpus. Their structures were elucidated on the basis of spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, and CD). In the in vitro assay, compounds 1, 5, 6, 9, and 10 exhibited NO inhibitory effects of LPS-induced BV-2 cells with IC50 values in the range of 10.4 µM to 27.2 µM.

Nitric Oxide Inhibitory Sesquiterpenoids and Its Dimers from Artemisia freyniana.

Two new disesquiterpenoids (1 and 2) and 11 new (3-13) and 10 known (14-23) sesquiterpenoids were isolated from the whole plants of Artemisia freyniana. Their structures were elucidated by spectroscopic data analysis and comparison with published NMR data. The absolute configurations of the new isolates (1-13) were assigned based on single-crystal X-ray diffraction data and comparison of the experimental and calculated ECD data. The eremophilane derivatives 8 and 9 possess an unprecedented 2-isopropyl-3,7,7a-trimethyl-2,4,5,6,7,7a-hexahydro-1 H-indene scaffold, and a putative biosynthetic pathway for these compounds is proposed. Compounds 4, 5, and 9 exhibited inhibitory effects against LPS-stimulated nitric oxide (NO) production in RAW 264.7 macrophage cells with IC50 values of 10.8, 12.6, and 11.7 µM, respectively.

Anti-Inflammatory Prenylated Phenylpropenols and Coumarin Derivatives from Murraya exotica.

Three new prenylated phenylpropenols, exotiacetals A-C (1-3), 10 new coumarin derivatives, exotimarins A-I (4-13), and 35 known analogues (14-48) were isolated from the roots of Murraya exotica. The absolute configurations of the new compounds were assigned via comparison of their specific rotations, single-crystal X-ray diffraction data, Mosher's method, the ECD exciton coupling method, comparison of experimental and calculated ECD data, and the ECD data of the in situ formed transition metal complexes. Compounds 1-3, which possess an unprecedented hexahydro-1H-isochromen-1-ol system, are presumably biosynthesized from two prenylated p-coumaryl alcohol moieties via Diels-Alder [4+2] cycloaddition and cyclic hemiacetal formation reactions. Compounds 1, 28, 33, and 35 demonstrated inhibition against LPS-induced NO production in BV-2 microglial cells with IC50 values of 8.6 ± 0.3, 11.8 ± 0.9, 15.5 ± 0.9, and 16.9 ± 1.0 µM, respectively.

LC-MS-Guided Isolation of Insulin-Secretion-Promoting Monoterpenoid Carbazole Alkaloids from Murraya microphylla.

Fifteen new structurally unique monoterpenoid carbazole alkaloids, including two pairs of epimers (1/2 and 3/4), three pairs of enantiomers (6a/6b, 7a/7b, and 8a/8b), and five optically pure analogues (5, 9-12), were obtained from a 95% aqueous EtOH extract of Murraya microphylla by a combination of bioassay- and LC-MS-guided fractionation procedures. Their structures were established based on NMR and HRESIMS data interpretation. The absolute configuration of compound 1 was determined via X-ray crystallographic data analysis and for all compounds by comparison of experimental and calculated ECD data. Compounds 1-5 were assigned as five new thujane-carbazole alkaloids, and compounds 6-12 as 10 new menthene-carbazole alkaloids linked through an ether or carbon-carbon bond. Compounds 1-12 promoted insulin secretion in the HIT-T15 cell line, 1.9-3.1-fold higher than the gliclazide control at 100 µM.

Pyrrolo[2,1-a]isoquinoline and pyrrole alkaloids from Sinomenium acutum.

Two pyrrolo[2,1-a]isoquinolines (1 and 2) and three pyrrole alkaloids (3-5), including three new ones, named sinopyrines A-C (1-3), were isolated from the 95% EtOH extract of the stems and rhizomes of Sinomenium acutum (Thumb.) Rehd. et Wils. The structures of the new compounds were elucidated on the basis of spectroscopic data. This is the first report of pyrrole-bearing natural compounds from the family Menispermaceae.

Three new indole alkaloid derivatives from the roots of Murraya paniculata.

Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs (4‒9) were isolated from the roots of Murraya paniculata. The structures were elucidated on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature. The absolute configurations of new compounds were assigned via the determination of specific optical rotation, Mosher's method, and ECD spectra. Compound 3 is the first heterodimer of C-N linked indole and coumarin derivatives.

[Four new cis-phenylethanoid glycosides from stems of Cistanche deserticola cultured in Tarim desert].

In order to clarify the chemical constituents of Cistanche deserticola cultured in Tarim desert, a systematically phytochemical investigation was carried out. The chemical constituents were isolated by column chromatography, such as silica gel, Sephadex LH-20, MCI gel, ODS and semi-preparative HPLC, and their structures were determined on the basis of MS, NMR spectroscopic analysis, and comparison with literature data. Four compounds were isolated from the 85% ethanol extract of the stems of C. cultured in Tarim desert. Their structures were identified as cis-tubuloside (1), cis-cistanoside (2), cis-cistanoside J (3), and cis-isocistanoside C(4). Compounds 1-4 were four new cis-phenylethanoid glycosides. Herein, we firstly report the ¹H, ¹³C-NMR data of the new compounds(1-4) for the first time. This study will provide the scientific evidence for comprehensively analyzing the chemical constituents of C. deserticola cultured in Tarim desert.

New terpenoids and thiophene derivatives from the aerial parts of Artemisia sieversiana.

One new highly oxygenated nortriterpene, named sieverlactone (1), one new sesquiterpene, 1ß,10ß-epoxy-8α-acetoxyachillin (2), one new natural product, 5-propinyl-thiophene-2-carboxylic acid (3), and one new thiophene, 3-hydroxy-5-propinyl-2-acetyl-thiophene (4), together with 10 other known compounds (5-14), were isolated from the dried aerial parts of Artemisia sieversiana. Their structures were elucidated by a combination of extensive spectroscopic analysis, including 1D, 2D NMR spectroscopic and mass spectrometric data. Meanwhile, the stereochemistry of 1 and 2 was confirmed by single-crystal X-ray diffraction technique using Cu radiation. All the isolates were evaluated for their anti-neuroinflammatory effects on the lipopolysaccharide-induced nitric oxide production in BV-2 murine microglial cells. Compounds 2, 5, and 6 exhibited the significant activities with IC50 values of 6.5 ±â€¯0.5, 11.9 ±â€¯0.7, and 10.1 ±â€¯0.3 µM, respectively, comparable to the positive control, quercetin, with an IC50 value of 16.3 ±â€¯0.4 µM.

Ruticarpsides A-C, three new ester glycosides from the fruits of Tetradium ruticarpum.

In the course of our ongoing phytochemical investigation on the n-butanol extract of the fruits of Tetradium ruticarpum (Rutaceae), three new compounds, ruticarpsides A-C (1-3), were obtained and their structures were elucidated by a comprehensive analysis of NMR and MS data. Compound 3 showed a weak inhibition effect on nitric oxide production in BV-2 microglial cells stimulated with lipopolysaccharide.

A new prenylated flavone from Pleione bulbocodioides.

A new prenylated flavone, 3,5,7,3'-tetrahydroxy-8,4'-dimethoxy-6-(3-methylbut-2- enyl)flavone (1), together with three known flavone derivatives (2-4), two known dihydrophenanthrenes (5-6), two known lignin derivatives (7-8), and three known phenolic glycoside compounds (9-11) were isolated from the n-BuOH extract of Pleione bulbocodioides. High-resolution electrospray ionization mass spectroscopy (HRESIMS), FTIR spectroscopy, and NMR techniques were used to elucidate the structures of these compounds. Biological investigations showed that compound 5, 4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene, exhibited potent anti-inflammatory activity on LPS-stimulated NO production in BV-2 microglial cells, with IC50 value of 5.44 µM.

[Sesquiterpenoids from aerial parts of Artemisia myriantha].

The present study is to investigate the chemical constituents from the aerial parts of Artemisia myriantha. The chemical constituents were isolated by column chromatographies over silica gel, Sephadex LH-20, ODS and Semi-prep HPLC, and the structures were identified by NMR and MS data. Thirteen known compounds were isolated and identified as: blumenol A (1),(+)-dehydrovomifoliol (2),(+)-3-hydroxy-ß-ionone (3),(3R, 6R, 7E)-3-hydroxy-4, 7-megastigmadien-9-one (4),(-)-10-oxo-isodauc-3-en-15-oic acid (5),isoerivanin (6),eudesmafraglaucolide (7), artanomalide A (8),13-acetoxy-3ß-hydroxy-germacra-1(10) E,4E,7(11)-trien-12,6α-olide (9),13-acetoxy-3ß-tigloyl-germacra-1(10) E, 4E, 7(11)-trien-12, 6α-olide (10),13-acetoxy-3ß-(3-methylbutanoyl)-germacra-1(10)E, 4E, 7(11)-trien-12, 6α-olide (11),3,9-diacetoxy-13-hydroxy-1(10), 4, 7(11)-germacratrien-12,6α-olide (12), and 8α-angeloyloxycostunolide (13). Compounds 1-6 and 13 were obtained from the genus Artemisia for the first time, and 7-9 and 12 were isolated from this plant for the first time. Compound 8 exhibited selective cytotoxicity against human colon cancer (HCT-8) and human gastric cancer (BGC-823) with IC50 values of 2.33 and 4.53 µmol•L ⁻¹, respectively.

[Lignans from stems of Cistanche deserticola cultured in Tarim desert].

In order to clarify the chemical constituents of Cistanche deserticola cultured in Tarim desert, a systematically phytochemical investigation was carried out. The chemical constituents were isolated by column chromatography, such as silica gel, Sephadex LH- 20, MCI gel, ODS and semi-preparative HPLC, and their structures were determined on the basis of MS, NMR spectroscopic analysis and/or comparison with literature data. Eleven lignans were isolated from the 85% ethanol extract of the stems of C. deserticola cultured in Tarim desert. Their structures were identified as (+)-syringaresinol-4'-O-ß-D-glucopyranoside (1), (+)-isoeucommin A (2), eucommin A (3), (+)-pinoresinol monomethylether ß-D-glucoside (4), lariciresinol 4'-O-ß-D-glucopyranoside (5), lariciresinol 4-O-ß-D-glucopyranoside (6), conicaoside (7), dehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside (8), dehydrodiconiferyl alcohol γ'-O-ß-D-glucoside (9), citrusin A (10), and alaschanioside A (11). Compounds 1, 3-7, 10 and 11 were isolated from this genus for the first time, and compounds 2, 8 and 9 were obtained from this species for the first time.

Three new triterpene saponins from Clematis chinensis.

Three new triterpene saponins, clematochinenosides H-J (1-3), were isolated from the roots and rhizomes of Clematis chinensis. Their structures were elucidated on the basis of spectroscopic means including 1D and 2D NMR experiments and hydrolysis products.

Two new phenolic compounds from the heartwood of Caesalpinia sappan L.

Two new phenolic compounds, epicaesalpin J and 7,10,11-trihydroxydracaenone, were isolated from the heartwood of Caesalpinia sappan L. Their structures were identified by spectroscopic analysis methods, such as 1D and 2D NMR, along with the high resolution mass spectral data. The NO inhibition activities of two new compounds and six known compounds were tested.

[Chemical constituents from stems of Cistanche deserticola cultured in Tarim desert].

In order to clarify the chemical constituents of Cistanche deserticola cultured in Tarim desert, a systematically phytochemical investigation was carried out. The chemical constituents were isolated by column chromatography, over silica gel, Sephadex LH-20, MCI gel, ODS and semi-preparative HPLC, and their structures were determined on the basis of MS, NMR spectroscopic data analysis, physicochemical properties and/or comparison with literature data Seventeen compounds were isolated from the 85% ethanol extract of the stems of C. deserticola cultured in Tarim desert. Their structures were identified as salsaside B (1), syringin (2), demethyl syrinyin (3), coniferin (4), (2E,6E)-3,7-dimethyl-8-hydroxyoctadien-1-O-beta-D-glucoside (5), (+)-syringaresinol (6), 2S,3S, 4S-trihydroxypentanoic acid (7), panaxytriol (8), beta-sitosterol-3-O-beta-D-xylopyranoside (9), androsin (10), 3-methyl-but-2-en-1-yl-beta-D-glucopyranoside (11), benzyl-glucopyranoside (12), 4-hydroxybenzyl-beta-D-glucoside (13), nicotinamide (14), p-hydroxybenzoic acid (15), 4-hydroxy-benzeneethanol (16), and galactitol (17). Compounds 3, 6-13 were isolated from this genus for the first time, and compounds 1, 4 and 5 were obtained from this species for the first time.

Bioactive abietane diterpenes and benzofuran neolignans from the resins of Toxicodendron vernicifluum.

Six new compounds (1-6), including two abietane diterpenes (1,2) and four benzofuran neolignans (3-6), along with five known compounds (7-11) were isolated and identified through phytochemical investigation on the resins of Toxicodendron vernicifluum (Toxicodendri Resina). The structures of the new compounds were fully elucidated by their 1D and 2D NMR, HRESIMS, UV, and IR spectroscopic data analyses. The absolute configurations of 1-4 were deduced by comparison of the experimental and calculated electronic circular dichroism (ECD) data. The inhibitory effects of the isolates on myocardial fibrosis induced by TGF-ß were examined, and compounds 1, 5, and 7-10 showed the anti-proliferation of myocardial fibroblasts at the concentrations of 10-40 µM in a dose-dependent manner.