Limonoids and alkaloids from Tetradium austrosinense (Hand.-Mazz.) T.G.Hartley.

A pair of new enantiomeric indolopyridoquinazoline-type alkaloids, (+)-1,7S,8R- and (-)-1,7R,8S-trihydroxyrutaecarpine (3a and 3b), and a new limonoid-tyrosamine hybrid, austrosinin (8), along with six known alkaloids and limonoids, were isolated from the stems with leaves of Tetradium austrosinense. Their structures were elucidated on the basis of analysis of MS, NMR, ECD and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations, as well as proposed biosynthetic pathway. An anti-inflammatory bioassay in vitro showed 8 had significant immunosuppressive effect against the production of pro-inflammatory cytokine TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

B-seco Limonoids with anti-inflammatory activity from Tetradium fraxinifolium (Hook.) T.G.Hartley.

Fraxinifolines A-F (1-6), six new B-seco limonoids, together with four known A,D-di-seco ones, were isolated from the twigs with leaves of Tetradium fraxinifolium. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR, single-crystal X-ray diffraction and biogenetic pathway. An anti-inflammatory bioassay in vitro showed limonoids 1-3 had significant immunosuppressive effect against the production of pro-inflammatory cytokines (IL-1ß and/or TNF-α) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Structurally diverse polycyclic polyprenylated acylphloroglucinols with protective effect on human vein endothelial cells injured by high-glucose from Hypericum acmosepalum N. Robson.

Hyperacmotone A, a polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented skeleton, along with five undescribed congeners and eleven reported ones, was isolated from Hypericum acmosepalum. Hyperacmotone A possesses a unique monocyclic ring skeleton based on a cyclopent-4-ene-1,3-dione acylphloroglucinol core. Their structures were elucidated by extensive analysis of HRESIMS, NMR, biogenetic pathway, and quantum-chemical calculations. In addition, hypercohone G exhibited significant protective effects on high-glucose-injured HUVECs.

Monoterpene indole alkaloids from Melodinus cochinchinensis (Lour.) Merr.

Melodicochinines A - D (1-4), four new monoterpene indole alkaloids (MIAs), along with 21 known ones, were isolated from the stems and twigs of Melodinus cochinchinensis. Their structures were elucidated on the basis of extensive spectroscopic analysis. A ubiquitin-rhodamine 110 assay showed that 11-methyloxytabersonine had potential inhibitory effect against ubiquitin-specific protease 7 (USP7).

Acmoxanthones A-E, New Lavandulated Xanthones from Hypericum acmosepalum N. Robson.

Acmoxanthones A-E (1-5), five new lavandulylated xanthones, were isolated from the aerial parts of Hypericum acmosepalum, together with four known xanthones. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR and chiroptical properties. A bioassay against high glucose-induced damage on human umbilical vein endothelial cells (HUVECs) showed ananixanthone (6) and osajaxanthone (7) had potential antioxidative damage activity with EC50 values of 10.5 µg/mL and 7.6 µg/mL, respectively, while 3-hydroxy-2,4-dimethoxyxanthone (8) exhibited cytotoxic effect on the damaged cells with IC50 values of 7.1 µg/mL.

Structurally diverse polyprenylated acylphloroglucinols from Hypericum uralum Buch.-Ham. ex D. Don.

Uralins A - D, four undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) featuring an unprecedented fused hexacyclic architecture, a unique monocyclic tetra-seco-tetranor-b-PPAP, an oxidative b-PPAP and a rare norspiroindane-type m-PPAP, respectively, were isolated from the aerial parts of Hypericum uralum, along with ten known PPAPs. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques (MS, NMR, [α]D, CD), conceivable biogenetic pathways and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Biological assays showed three b-PPAPs had moderate antioxidative damage activities, while spiroindanes exhibited moderate cytotoxic effects.

Polycyclic polyprenylated acylphloroglucinols from Hypericum choisianum.

Twenty-one polycyclic polyprenylated acylphloroglucinols, including three new compounds named as hyperichoisins A (3), B (14) and C (21), were isolated from the aerial parts of Hypericum choisianum. The structures of those new compounds were elucidated by analysis of mass, NMR data, and chiroptical properties. A bioassay showed that otogirinin B had significant inhibitory effect on cell proliferation of A549.

Polyprenylated acylphloroglucinols as deubiquitinating protease USP7 inhibitors from Hypericum hookerianum.

Hookerianones A - E (1-5), five new polyprenylated acylphloroglucinols (PPAPs), along with six known ones, were isolated from the aerial parts of Hypericum hookerianum. Their structures were elucidated by analyses of MS, NMR, chiroptical properties, biogenetic pathway, and/or single crystal X-ray diffraction. A ubiquitin-rhodamine 110 assay showed that furohyperforin and hypercalin C, two representative PPAPs in this plant, inhibited more than 90% USP7 at the concentration of 10 µM.

Alopecines A-E, five chloro-containing matrine-type alkaloids with immunosuppressive activities from the seeds of Sophora alopecuroides.

Alopecines A-E (1-5), five unusual matrine-type alkaloids featuring with an additional dichlorocyclopropane (1-3) or a di/tri-chloromethyl (4/5) attached on the D ring, were isolated from the seeds of Sophora alopecuroides. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques, and X-ray diffraction analyses or time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Alkaloid 4 exhibited potent inhibitory effects on the proliferation of ConA-induced T lymphocytes or LPS-induced B cells with IC50 value of 3.98 or 3.74 µM, respectively.

Aspergillolide, a new 12-membered macrolide from sea cucumber-derived fungus Aspergillus sp. S-3-75.

A new 12-membered macrolide, aspergillolide (1), along with nine known compounds (2-10), were isolated from the fungus Aspergillus sp. S-3-75 associated with the sea cucumber Holothuria nobilis Selenka. The structure and absolute stereochemistry of 1 were elucidated on the basis of extensive spectroscopic methods and single crystal X-ray diffraction analysis.

Sodium rutin ameliorates Alzheimer's disease-like pathology by enhancing microglial amyloid-ß clearance.

The accumulation of aggregated amyloid-ß (Aß) in the brain is the first critical step in the pathogenesis of Alzheimer's disease (AD), which also includes synaptic impairment, neuroinflammation, neuronal loss, and eventual cognitive defects. Emerging evidence suggests that impairment of Aß phagocytosis and clearance is a common phenotype in late-onset AD. Rutin (quercetin-3-rutinoside) has long been investigated as a natural flavonoid with different biological functions in some pathological circumstances. Sodium rutin (NaR), could promote Aß clearance by increasing microglial by increasing the expression levels of phagocytosis-related receptors in microglia. Moreover, NaR promotes a metabolic switch from anaerobic glycolysis to mitochondrial OXPHOS (oxidative phosphorylation), which could provide microglia with sufficient energy (ATP) for Aß clearance. Thus, NaR administration could attenuate neuroinflammation and enhance mitochondrial OXPHOS and microglia-mediated Aß clearance, ameliorating synaptic plasticity impairment and eventually reversing spatial learning and memory deficits. Our findings suggest that NaR is a potential therapeutic agent for AD.

Diverse lignans with anti-inflammatory activity from Urceola rosea.

Seventeen structurally diverse lignans, comprising six new compounds, ecdysanols A (1), B (11), C - E (13-15), and F (17), were isolated from the caulis of Urceola rosea. The structures and absolute configurations of these new compounds were elucidated by means of extensive analysis of mass and NMR data, as well as chiroptical properties. A bioassay in vitro showed that all lignans possessed anti-inflammatory effects by inhibiting the production of TNF-α, NO and/or IL-6 in LPS-stimulated RAW264.7 cells. Ecdysanol F (17) showed the most strongly effect against NO and IL-6 levels.

Flueggenoids A - E, new dinorditerpenoids from Flueggea virosa.

A phytochemical investigation on the twigs and leaves of Flueggea virosa (Euphorbiaceae) led to the isolation of flueggenoids A - E (1-5), five new 13-methyl-ent-podocarpanes, together with eleven known compounds (6-16). Their structures and absolute configurations were elucidated on the basis of extensive MS and NMR data analysis, and/or single-crystal X-ray diffraction, time-dependent density functional theory (TDDFT)-based electronic circular dichroism (ECD) calculations, and chemical transformation. All isolates were evaluated for anti-HCV activity, the results showed that terpenoids of F. virosa had nonnegligible contribution for the anti-HCV activity.

Triterpenoids, megastigmanes and hydroxycinnamic acid derivatives from Anisomeles indica.

Six triterpenoids (1-6), four megastigmanes (7-10) and five hydroxycinnamic acid derivatives (11-15) were isolated from the aerial part of Anisomeles indica (Lamiaceae). Of these components, compound 1 was identified to be a new triterpenoid with the structure of 2α,3α,19α-trihydroxyurs-12,20(30)-dien-28-oic acid based on extensive analysis of MS, 1D and 2D NMR spectroscopic data, while compounds 2-13 were obtained for the first time from Anisomeles species.

Anti-inflammatory constituents from Perilla frutescens on lipopolysaccharide-stimulated RAW264.7 cells.

Perilla frutescens (L.) Britt. (Lamiaceae) is a traditionally medicinal herb in East Asian countries to treat various diseases. In present study, the low-polarity constituents of the aerial parts of P. frutescens were investigated and their anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated RAW264.7 cells were assayed. Three new furanoid monoterpenoids, named as frutescenones A - C (1-3), together with thirteen known compounds (4-16) were isolated and identified on the basis of extensive spectroscopic analysis and a single-crystal X-ray diffraction study. Among these components, 1 is an unusual monoterpenoid with 2,3'-bifuran skeleton, and 3 is a rare perillaketone-adenine hybrid heterodimer, while the revised NMR arrangements of 4 were reported at the first time. Furthermore, monoterpenoid 4 and alkaloid 15 showed remarkably inhibitory effect on the production of inflammatory mediator (NO) and pro-inflammatory cytokines (TNF-α and/or IL-6) in LPS-stimulated RAW264.7 cells.

Limonoids from the fruits of Swietenia macrophylla with inhibitory activity against H2O2-induced apoptosis in HUVECs.

The fruits of Swietenia macrophylla (skyfruits) are commercially used as healthcare products to improve blood circulation. An investigation of active ingredients of skyfruits led to the isolation of four new limonoids, swietemacrolides A-D (1-4), together with ten known limonoids (5-14) and one proto-limonoid (15). Their structures were elucidated on the basis of MS and NMR data analysis. Swietemacrolide C (3) at the concentration of 10 µM showed significant protective effect on H2O2-induced apoptosis in human umbilical vascular endothelial cells (HUVECs), while swieteliacate D (5) displayed moderate anti-apoptotic activity.

Mexicanolide-type limonoids from the seeds of Swietenia macrophylla.

Three new mexicanolide-type limonoids, 3-O-propionylproceranolide (1), 6-O-acetylswietenin B (2), and 6-deoxyswietemahonin A (3), together with 15 known limonoids, were isolated from the seeds of Swietenia macrophylla (Meliaceae). The structures of those new compounds were established by extensive analysis of MS, 1D, and 2D NMR spectral data.

Highly oxygenated and structurally diverse diterpenoids from Euphorbia helioscopia.

A phytochemical investigation on the aerial part of Euphorbia helioscopia (Euphorbiaceae) led to the isolation of 22 highly oxygenated diterpenoids with structural types of ent-abietane, ent-kaurane, lathyrane, ent-atisane and ingenane. 17 of them, named euphelionolides A - N, 16-epi-18-hydroxy-abbeokutone, as well as eupheliotriols A and B, were identified to be previously undescribed compounds by extensive analysis of spectroscopic data. The stereostructures of euphelionolides A - K were determined by single crystal X-ray diffraction combined with analysis of substituent effects and comparison of optical characteristics. Eupheliotriol B is the first example of natural occurring lathyrol with 12Z-ene, while ent-atisanes are the first reported from the title plant. Furthermore, euphelionolides F and L exhibited significant cytotoxicity against MCF-7 and PANC-1 cell lines.

The synthesis of dendroflorin.

The first synthesis of dendroflorin has been achieved in 10 steps with an overall yield of 5.5%. The key step in the synthesis features the biphenyl structure is built through Suzuki-Miyaura reaction. In addition, the ortho-localization effect induced by aromatic substituent during the bromination of intermediate 8 is also observed and discussed.

Triterpenoids from the barks of Terminalia chebula.

Two new triterpenoids, termichebuloside A (1), an unusual dimeric triterpenoid saponin, and termichebulolide (2), an oleanolic acid-type lactone, along with 11 known triterpenoids, were isolated from MeOH extract of the barks of Terminalia chebula. The structures of 1 and 2 were elucidated to be arjunglucoside I-(3-O-19',23-O-19')-18,19-seco-19-hydroxyarjunglucoside I (1) and 2α,3ß,23-trihydroxyolean-11,13(18)-dien-28,19ß-olide (2), respectively, on the basis of spectroscopic evidences and biogenetic consideration.