New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Clerodane diterpenoids with in-vitro anti-neuroinflammatory activity from the tuberous root of Tinospora sagittata (Menispermaceae).

Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.

New enantiomeric lignans and new meroterpenoids with nitric oxide release inhibitory activity from Piper puberulum.

Six new lignans with various type of linkage between two C6-C3 fragments (1a, 1b, 2a, 2b, 3, 4), two new meroterpenoids (5, 6) and 24 known compounds (7-30) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of enantiomers 1a and 1b were determined by single-crystal X-ray diffraction analysis, 2a and 2b were determined by comparing their calculated and experimental ECD spectra. Biogenetically, all the new lignans may come from the polymerization of two molecules of hydroxychavicol (30). In the anti-neuroinflammation activity assay, the IC50 values of fifteen compounds were lower than those of the positive control minocycline, and compound 1a showed good activity, but its enantiomer 1b showed no activity. Compound 1a have notable anti-neuroinflammatory activity, and can significantly decrease mRNA levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) in a dose-dependent manner.

Flavonol glycosides and phenylpropanoid glycosides with inhibitory effects on microglial nitric oxide production from Neoshirakia japonica.

Five new flavonol glycosides (1-5), one new phenylpropanoid glycoside (6), and nine known glycosides (7-15) were isolated from the stems and leaves of Neoshirakia japonica. The structures of the new compounds were determined by detailed analysis of spectroscopic data (HRESIMS, 1D and 2D NMR) and acid hydrolysis experiment. The antineuroinflammatory effects of all the isolates were evaluated by inhibiting NO production against LPS-induced BV-2 microglial cells. Compounds 1, 8, and 9 showed more potent inhibitory activities with IC50 values of 2.7, 5.5, and 4.1 µM, respectively, than that of the positive control minocycline (IC50 = 15.6 µM), while compounds 7 (IC50 = 17.0 µM) and 10 (IC50 = 24.3 µM) also displayed inhibitory activities to a certain degree.

Diterpenoids and triterpenoids from Triadica rotundifolia and their effects on microglial nitric oxide production.

Four new diterpenoids (1-4), three new triterpenoids (12-14), and seven known diterpenoids (5-11) were obtained from an aqueous EtOH extract of the aerial parts of Triadica rotundifolia. The structures of new compounds were determined by spectroscopic techniques. Their absolute configurations were verified via single-crystal X-ray diffraction data, Mo2(OAc)4 induced electronic circular dichroism (ECD), and ECD calculations. The antineuroinflammatory effects of the isolates were assessed by inhibiting NO production in LPS-induced BV-2 microglial cells. Compared with the positive control minocycline (IC50 = 16.1 µM), compounds 3, 8, 11 showed moderate inhibitory activities with IC50 values of 35.9, 17.0, 31.5 µM, respectively.

Isolation, Absolute Configuration, and Biological Activities of Chebulic Acid and Brevifolincarboxylic Acid Derivatives from Euphorbia hirta.

Twenty new chebulic acid and brevifolincarboxylic acid derivatives, including eight optically pure or achiral compounds (1-7 and 14) and six pairs of enantiomers (8a/8b-13a/13b), along with nine known analogues (15-23), were isolated from an EtOH extract of the aerial parts of Euphorbia hirta. The absolute configurations of the new compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD data. Racemic or scalemic mixtures of 8-13 were isolated, and their enantiomers were analyzed by chiral-phase HPLC-ECD measurements. Compound 12 possesses an unprecedented 2H-cyclopenta[de]chromene-2,5(4H)-dione scaffold. Compounds 12, 20, and 23 displayed moderate inhibitory effects against lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, while all the isolates exhibited significant DPPH radical scavenging activities with EC50 values of 2.2-15.8 µM.

Anti-inflammatory activity of isobutylamides from zanthoxylum nitidum var. tomentosum.

Inflammation is a very common and important basic pathological process. There is still a great need for the isolation of effective anti-inflammatory agents from plants. In this paper, five new isobutylamides, zanthoxylumamides E-I (1-5), and four known isobutylamides (6-9) were isolated from Zanthoxylum nitidum var. tomentosum (Rutaceae). Chiral resolution of seven racemic isobutylamides (1-4 and 6-8) was successfully performed, and the absolute configurations of two stereoisomers of 1-4 were validated by ECD and NMR. The obtained isobutylamides were evaluated in vitro anti-inflammatory activity with the lipopolysaccharide (LPS)-stimulated production of nitric oxide (NO) in murine macrophage RAW264.7 cells. Compound 8 exhibited significant inhibition of LPS-induced NO production. The underlying molecular mechanisms of the anti-inflammatory activity of 8 revealed that it suppressed the NO production through the modulation of myeloid differentiation factor 88 (MyD88) and interferon regulatory factor 3 (IRF3) signaling pathways.

Sesquiterpenes and diterpenes from Euphorbia thymifolia.

One new pseudoguaianolide (1), one new megastigmane (6), and one new ent-abietane diterpene (9), together with seven known compounds (2-5, 7, 8, and 10) were isolated from the aerial parts of Euphorbia thymifolia. The structures of the new compounds and their relative configurations were determined by spectroscopic data analysis. The absolute configurations of compounds 1, 6, and 9 were determined by single-crystal X-ray crystallographic analysis, modified Mosher's method and calculated ECD experiment, respectively. All compounds were tested for their inhibitory effects against LPS-induced NO production in BV-2 microglial cells, and pseudoguaianolides (1-5) showed significant activity with IC50 values of 0.41-15.32 µM.

Coumarinolignoids and lignanoids from the stems and leaves of Sapium discolor.

Two new coumarinolignoids, sapiumins D (1) and E (2), a new lignanoid, lariciresinol 9'-benzoate (3), together with six known coumarinolignoids (4-9) and eight known lignanoids (10-17), were isolated from the stems and leaves of Sapium discolor. The structures of the isolated compounds were elucidated by extensive spectroscopic methods, including NMR, MS, and single crystal X-ray diffraction experiments. Compounds 5, 10, 11, and 13 significantly inhibited nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells, with IC50 values in the range of 2.13-11.37 µM.

New terpenoid and phenylpropanoid glycosides from Tinospora sinensis.

Two new cadinane sesquiterpene glucosides (1, 2), two new phenylpropanoid glycosides (3, 4), and two new diterpenoid glucosides (5, 6), as well as 6 known compounds were isolated from the stems of Tinospora sinensis. The structures of these compounds were elucidated by extensive spectroscopic analysis and chemical methods. The absolute configuration of compound 1 was determined by timedependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations and in situ dimolybdenum CD method. All the isolated compounds except for compounds 7, 11 and 12 were evaluated for their anti-neuroinflammatory effect by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine BV-2 microglial cells, and compound 4 showed anti-neuroinflammatory activity with IC50 values 42.90 µM in vitro assay.

Coumarinolignoids and Taraxerane Triterpenoids from Sapium discolor and Their Inhibitory Potential on Microglial Nitric Oxide Production.

Seventeen compounds, including three new pairs of coumarinolignoid enantiomers, (7' S,8' S)-sapiumins A-C (1a-3a) and (7' R,8' R)-sapiumins A-C (1b-3b), six new taraxerane triterpenoids, sapiumic acids A-F (4-9), and five known taraxerane triterpenoids (10-14), were isolated from an ethanol extract prepared from the stems and leaves of Sapium discolor. The structures of 1-9 and their relative configurations were determined by spectroscopic data analysis, and the absolute configurations of the coumarinolignoids 1a/1b-3a/3b and triterpenoids 6-9 were assigned using experimental and calculated ECD data. Compounds 1a/1b-3a/3b are the first coumarinolignoids to be reported from the genus Sapium. Among all the isolates, compounds 1b, 2a/2b, 3a/3b, and 6-9 inhibited nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells, with IC50 values of 1.7-15.3 µM.

[Chemical constitutes from Clerodendrum japonicum].

The chemical constituents from the ethanol extract of Clerodendrum japonicum were isolated by a combination of various chromatographic techniques including column chromatography over silica gel, sephadex LH-20, ODS and reversed phase HPLC. Sixteen compounds with a pair of epimers were elucidated through the application of physicochemical properties with modern spectral analysis technology as 7α-hydroxy syringaresinol (1), (-)-syringaresinol (2), (-)-medioresinol (3), 2″,3″-O-acetylmartyonside (4), 2″-O-acetyl-martyonside (5), martinoside (6), monoacetyl martinoside (7)，cytochalasin O (8), 9-epi-blumenol B (9), (6R, 9S) and (6R,9R)-9-hydroxy-4-megastigmen-3-one (10a，10b), (6R,9S)-3-oxo-α-ionol (11), (-)-dehydrovomifoliol (12)，megastigm-5-en-3,9-diol (13), (3R,6E,10S)-2,6,10-trimethyl-3-hydroxydodeca-6,11-diene-2,10-diol (14), (2R)-butylitaconic acid (15), 3-(3&-hydroxybutyl)-2,4,4-trimethylcyclohexa-2,5-dienone (16), (-)-loliolide (17), of which compound 1 and 15 are new natural product, the other compounds were isolated for the first time from Clerodendrum japonicum except for compounds 4, 6 and 7.

Oleanane-type triterpenoid saponins from Lysimachia fortunei Maxim.

Six previously undescribed oleanane-type triterpenoid saponins, fortunosides A-F, together with six known ones, were isolated from the aerial parts of Lysimachia fortunei Maxim. Their structures were established by spectroscopic data analyses (1D, 2D-NMR and HRESIMS) and chemical methods. All isolated triterpenoid saponins were evaluated for their cytotoxicity against four human liver cancer cell lines (SMMC-7721, Hep3B, HuH7, and SK-Hep-1). Three saponins with the aglycone protoprimulagenin A exhibited moderate cytotoxicity against all of the tested human cancer cell lines, with IC50 values ranging from 4.76 to 15.12 µM.

Isoprenylated Flavonoids with PTP1B Inhibition from Ficus tikoua.

Two new isoprenylated flavanones, ficustikousins A and B (1 and 2), together with seven known compounds (3-9) were isolated from the whole plant of Ficus tikoua (Moraceae). The structures of the new compounds were elucidated on the basis of spectroscopic methods. Compounds 1-7 exhibited moderate inhibitory activities against PTP1B in vitro.