Enantiomeric pairs of macrocyclic acylphloroglucinols from Syzygium szemaoense.

Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively.

Rhodomeroterpene alleviates macrophage infiltration and the inflammatory response in renal tissue to improve acute kidney injury.

Inflammation is broadly recognized as an important factor in the pathogenesis of acute kidney injury (AKI), but pharmacological approaches to alleviate inflammation in AKI have not been proved successful in clinical trials. Macrophage infiltration into renal tissue promotes inflammatory responses that contribute to the pathogenesis of AKI. Suppression of renal tissue inflammatory responses is postulated to improve renal injury of patients and animals. Rhodomeroterpene (RMT) is a novel meroterpenoid isolated from the Rhododendron genus that was shown to exert anti-inflammatory action in vivo or in vitro in this study. We investigated the treatment effects of RMT on LPS-induced sepsis and two different AKI models. The results showed that pretreatment with RMT (30 mg kg-1  d-1 , ip, for 3 days) significantly inhibited acute inflammatory responses in LPS-induced septic mice. In both renal ischemia-reperfusion injury (I/R) and sepsis-induced AKI models, RMT (30 mg kg-1  d-1 , ip, for 3 days) ameliorated renal function and injury and alleviated inflammation by reducing the infiltration of immune cells, including macrophages and neutrophils. Furthermore, our study demonstrated that RMT inhibits inflammatory responses in macrophages. The anti-inflammatory effects of RMT may be due to the inactivation of the IKK/NF-κB and PI3K/PDK1/Akt inflammatory signaling pathways in macrophages. Collectively, our findings indicate that RMT ameliorates renal injury and alleviates the renal inflammatory state in different AKI models, suggesting that RMT may be a potential agent for the treatment of AKI.

Dimeric sesquiterpenoids and anti-inflammatory constituents of Sarcandra glabra.

Three novel dimeric sesquiterpenoids named sarglanoids A-C (1-3), two undescribed monomeric sesquiterpenoids named sarglanoids D (4) and E (5), and seven known compounds (6-12), were isolated and characterized from Sarcandra glabra. Compound 1 represents the first heterodimeric sesquiterpenoid composed of a eudesmane and an eremophilane moiety. Compound 2 possesses two eremophilane monomers featuring an undescribed dimerization pattern. Compound 3 is a symmetric eudesmane dimer with a rare 1,4-epoxy bridge. The structures of 1-5 were fully identified by spectroscopic methods and single-crystal X-ray diffraction experiments. Compounds 3 and 6 suppressed the LPS-triggered inflammatory responses in RAW 264.7 cells.

Two New Cytotoxic Maytansinoids Targeting Tubulin from Trewia nudiflora.

Two new maytansinoids, N-methyltreflorine (1: ) and methyltrewiasine (2: ), were isolated from the dried fruits of Trewia nudiflora, together with three known congeners (3:  - 5: ). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1: and 2: was determined by X-ray crystallographic analysis. Compounds 1:  - 5: exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4 - 11, and MCF-7, with IC50 values ranging from 0.12 to 11 nM. Compounds 1: and 4: also showed inhibitory activity against the MCF-7/ADR cell line with IC50 values of 13 and 28 nM, respectively. Compounds 1: and 2: significantly inhibited tubulin polymerization in vitro with IC50 values of 3.6 and 3.2 µM, respectively.

Dimeric clerodane diterpenoids and antiviral constituents of Dodonaea viscosa.

Three unprecedented dimeric clerodane diterpenoids, dodovisdimers A-C (1-3), along with six known clerodane monomers (4-9), were isolated from Dodonaea viscosa. Compounds 1-3 may be biosynthetically formed via an intermolecular Diels-Alder [4+2] cycloaddition between the coexisting monomers 4-7. The structures of these clerodanes were characterized by spectroscopic techniques, X-ray crystallographic study, and ECD calculations. Some isolates exerted antiviral effects on human influenza A virus (H3N2) in vitro.

Two New Oleanane-Triterpenoid Saponins from Clinopodium gracile.

Two new oleanane-triterpenoid saponins, clinograsaponins A (1) and B (2), together with twelve known ones (3-14), were isolated from the whole herb of Clinopodium gracile (Bentham) Matsumura. Their structures were determined by spectroscopic analysis and chemical method. All the isolated compounds were evaluated for their activities against ATP-citrate lyase (ACLY) and nuclear factor kappa B (NF-κB).

[Studies on alkaloid constituents of Fritillaria yuminensis].

Twelve alkaloids were isolated from the bulbs of Fritillaria yuminensis by column chromatography over silica gel, ODS, and Sephadex LH-20, as well as RP-HPLC. Their structures were identified mainly by NMR and MS analyses as yubeinine(1), imperialine(2), delavinone(3), tortifoline(4), hupehenizioiside(5), imperialine-ß-D-glucoside(6), kuroyurinidine(7), pengbeisine A(8), walujewine A(9), peimisine-3-O-ß-D-glucopyranoside(10), solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside(11), and solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)]-ß-D-glucopyranoside(12). Compounds 4-12 were obtained from F. yuminensis for the first time.

[Flavonoids with PTP1B inhibition from Broussonetia papyrifera].

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) µmol·L-1.

Enantiomeric Pairs of Meroterpenoids with Diverse Heterocyclic Systems from Rhododendron nyingchiense.

Eight enantiomeric pairs of new meromonoterpenoids (1a/1b-8a/8b) and four known compounds (9-12) were isolated from Rhododendron nyingchiense. Their structures were established by spectroscopic methods, quantum chemical calculations, and X-ray crystallography. The enantiomeric pairs were acquired from scalemic mixtures by chiral-phase HPLC and showed diverse heterocyclic frameworks. Compounds 1a/1b possess a rare 6/7/5/5 heterocyclic system, and 2a/2b incorporate a new 6/6/3/5 heterocyclic system featuring a quinone motif. Compounds 3a/3b represent the first meroterpenoids with a 6/6/5 ring system from the Rhododendron genus. Putative biosynthetic pathways of these compounds are proposed. Compounds 1b, 2a-4a, 8a, 8b, and 11 exhibited weak inhibitory effects on PTP1B, with IC50 values ranging from 5.7 ± 0.5 to 61.0 ± 4.8 µM.

5,4'-Dihydroxy-7,8-dimethoxyflavanone and Aliarin from Dodonaea viscosa Are Activators of PPARγ.

PPARγ agonists are widely used medications in diabetes mellitus therapy. Their role in improving adipose tissue function contributes to antidiabetic effects. The extracts of Dodonaea viscosa have been reported to exert antidiabetic activity. However, the effective mediators and the underlying mechanisms were largely unknown. In this study, we investigated the action on PPARγ transactivation and adipocyte modulation of two typical flavonoid constituents from D. viscosa, 5,4'-dihydroxy-7,8-dimethoxyflavanone and aliarin. Our results showed that 5,4'-dihydroxy-7,8-dimethoxyflavanone and aliarin were potential partial PPARγ agonists. The compounds induced adipogenesis in 3T3-L1 cells, with an upregulated adiponectin mRNA level and enhanced insulin sensitivity. The favorable effects of 5,4'-dihydroxy-7,8-dimethoxyflavanone, aliarin, and other flavonoid constituents on adipocytes might contribute to the antidiabetic efficacy of D. viscosa.

Vistriterpenoids A and B, Two New 24-Nor-oleanane Triterpenoids from Dodonaea viscosa.

Two new triterpenoids, vistriterpenoids A (1) and B (2), and four known ones, were acquired from Dodonaea viscosa. Compounds 1 and 2 represent the 24-nor-oleanane triterpenoids isolated from the genus Dodonaea for the first time. Their structures were identified based on extensive spectroscopic methods. Compounds 1, 2, 5, and 6 exerted inhibitory activities against PTP1B in vitro.

Isoprenylated phenolic compounds with tyrosinase inhibition from Morus nigra.

A new isoprenylated sanggenon-type flavanone, nigrasin K (1), together with three known analogs (2-4) and five known Diels-Alder adducts (5-9), were isolated from the twigs of Morus nigra. Their structures were elucidated by spectroscopic methods. Sanggenon M (2), chalcomoracin (5), sorocein H (6), kuwanon J (7), sanggenon C (8), and sanggenon O (9) showed significant inhibitory effects on mushroom tyrosinase.

Five Pairs of Meroterpenoid Enantiomers from Rhododendron capitatum.

Chemical investigation on the aerial parts of Rhododendron capitatum resulted in the discovery of five enantiomeric pairs of new meroterpenoids, (+)-/(-)-rhodonoids C (1a and 1b), E (3a and 3b), F (4a and 4b), and (-)-/(+)-rhodonoids D (2a and 2b) and G (5a and 5b). These enantiomeric pairs existed as partial racemates in a plant and were obtained by chiral HPLC separation. Their structures with absolute configurations were assigned by spectroscopic data, single-crystal X-ray diffraction, and ECD analysis. Compounds 1a and 1b are the first pair of meromonoterpenes incorporating an unprecedented 6/6/6/5 ring system, and 1a showed antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Compounds 2a and 2b are the first examples of meromonoterpenes featuring a unique 6/6/5/5 ring system.

New Cytotoxic Alkylated Chalcones from Fatoua villosa.

Three new alkylated chalcones, villosins A - C (1 - 3), five known analogues, together with ten known coumarins, were isolated from Fatoua villosa. The structures of the new compounds were elucidated by extensive spectroscopic analysis, including 1D-, 2D-NMR, and MS data. Compounds 1 - 3 showed cytotoxicity against five kinds of human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC50 values ranging from 1.4 ± 0.1 to 5.7 ± 0.3 µm.

New Alkaloids and α-Glucosidase Inhibitory Flavonoids from Ficus hispida.

Two new pyrrolidine alkaloids, ficushispimines A (1) and B (2), a new ω-(dimethylamino)caprophenone alkaloid, ficushispimine C (3), and a new indolizidine alkaloid, ficushispidine (4), together with the known alkaloid 5 and 11 known isoprenylated flavonoids 6 - 16, were isolated from the twigs of Ficus hispida. Their structures were elucidated by spectroscopic methods. Isoderrone (8), 3'-(3-methylbut-2-en-1-yl)biochanin A (11), myrsininone A (12), ficusin A (13), and 4',5,7-trihydroxy-6-[(1R*,6R*)-3-methyl-6-(1-methylethenyl)cyclohex-2-en-1-yl]isoflavone (14) showed inhibitory effects on α-glucosidase in vitro.

(2S)-7,4'-dihydroxy-8-prenylflavan stimulates adipogenesis and glucose uptake through p38MAPK pathway in 3T3-L1 cells.

Adipose tissue plays a key role in the development of obesity and diabetes. Natural products are one of the main sources for discovering new lead compounds. In the present study, (2S)-7,4'-dihydroxy-8-prenylflavan (DHPF), a natural prenylated flavan isolated from Morus yunnanensis, was found to significantly promote adipogenesis and increase glucose uptake in 3T3-L1 cells. Real-time PCR results showed that DHPF increased the expression of glucose and lipid metabolism-related genes (C/EBPα, PPARγ, aP2, GLUT4 and adiponectin) and decreased the expression of inflammatory cytokine TNF-α. Western blotting further revealed that DHPF activated p38 MAPK at the initial stage of 3T3-L1 preadipocyte differentiation. DHPF-induced activation of p38, adipogenesis and glucose uptake were effectively blocked by SB203580, a specific p38 inhibitor. These results indicate that DHPF could stimulate adipogenesis and increase glucose uptake through the p38 MAPK pathway, and DHPF may be useful for the prevention and treatment of obesity-associated disorders such as type 2 diabetes (T2D).

Inhibitory Effects of (2'R)-2',3'-dihydro-2'-(1-hydroxy-1-methylethyl)-2,6'-bibenzofuran-6,4'-diol on Mushroom Tyrosinase and Melanogenesis in B16-F10 Melanoma Cells.

(2'R)-2',3'-Dihydro-2'-(1-hydroxy-1-methylethyl)-2,6'-bibenzofuran-6,4'-diol (DHMB) is a natural compound extracted from Morus notabilis. It was found that DHMB acts as a competitive inhibitor against mushroom tyrosinase with a Ki value of 14.77 µM. Docking results further indicated that it could form strong interactions with one copper ion with a distance of 2.7 Å, suggesting the mechanism of inhibition might be due to chelating copper ions in the active site. Furthermore, melanin production in B16-F10 murine melanoma cells was significantly inhibited by DHMB in a concentration-dependent manner without cytotoxicity. The results of western blotting also showed that DHMB decreased 3-isobuty-1-methxlzanthine-induced mature tyrosinase expression. Taken together, these findings indicated that DHMB may be a new promising pigmentation-altering agent for agriculture, cosmetic, and therapeutic applications.

New Isoprenylated Phenolic Compounds from Morus laevigata.

Two new isoprenylated flavonoids, laevigasins A and B (1 and 2, resp.), and one new isoprenylated 2-arylbenzofuran, leavigasin C (3), together with eight known compounds, 4-11, were isolated from the twigs of Morus laevigata. Their structures were elucidated by spectroscopic methods. Laevigasin A (1) showed significant inhibitory effect on α-glucosidase in vitro. Notabilisin E (5), taxifolin (10), and hultenin (11) inhibited PTP1B phosphatase activity in vitro.

[Phenolic compounds from Rhododendron phaeochrysum var. agglutinatum].

Eight phenolic compounds were isolated from Rhododendron phaeochrysum var. agglutinatum and their sructures were identified as phaeochrysin (1), (2R)-4-(3',4'-dihydroxyphenyl) -2-butanol (2), (-) -rhododendrol (3), rhododendrin (4), (+) -isolariciresinol (5), (-) -lyoniresinol (6), lyoniresinol-9'-O-ß-D-xylopyranoside (7), and dihydrodehydrodiconiferyl-3a-O-α-L-rhamnopyranoside (8). Compound 1 is new, and compounds 2, 5-8 were isolated from this plant for the first time.

Cardiac glycosides from Streblus asper with potential antiviral activity.

Ten undescribed cardiac glycosides, strasperosides A-J, together with twelve known analogues, were isolated from Streblus asper Lour. Their structures were elucidated on the basis of spectroscopic analysis, electronic circular dichroism data, and chemical methods. These cardiac glycosides showed diversity in steroid skeleton and sugar moiety. Strasperosides A and B are a pair of unusual stereoisomers featuring different orientation of the lactone motif. Ten cardiac glycosides demonstrated potent antiviral effects on HSV-1 in vitro with the IC50 values from 0.19 ± 0.08 to 1.03 ± 0.25 µM and the therapeutic indices from 66.61 ± 5.08 to 326.75 ± 11.75.