Seventeen undescribed iridoid derivatives with anti-inflammatory effects from Hedyotis diffusa and their structure-activity relationships.

Seventeen undescribed iridoid derivatives (1-17) and four known compounds (18-21) were isolated from the whole plant of Hedyotis diffusa Willd. Their structures were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, CD, and 1D and 2D NMR). It is noteworthy that compounds 1-8, which possess unique long-chain aliphatic acid moiety, were reported for the first time among the iridoid natural products. All compounds were evaluated for their anti-inflammatory activities in lipopolysaccharide-induced RAW 264.7 cells. Compounds 2, 4, and 6 showed significant suppression effects on nitric oxide production, with IC50 values of 5.69, 6.16, and 6.84 µM, respectively. The structure-activity relationships of these compounds indicated that long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. The therapeutic properties of these iridoid derivatives could give an insight into utilizing H. diffusa as a natural source of anti-inflammatory agents.

Six undescribed lavandulylated flavonoids with PTP1B inhibition from the roots of Sophora flavescens.

Six undescribed lavandulylated flavonoids (1-6) were isolated from the roots of Sophora flavescens. Remarkably, compounds 1 and 2, which were composed of a flavane unit and a phloroglucinol unit, were the first reported dimers. Compounds 3 and 4 were the first reported neoflavonoids with lavandulyl units. Compounds 5 and 6 were chalcone with oxidized lavandulyl units. Their structures were fully characterized by cumulative analyses of UV, IR, HRESIMS, NMR and ECD spectroscopic data, along with computational calculations through density functional theory. Compounds 1 and 2 showed significant protein tyrosine phosphatase-1B inhibitory activities with IC50 values of 2.669 and 3.596 µM, respectively.

Synthesis of 4-thiosubstituted flavan derivatives and their hypoglycemic activities.

A series of 4-thiosubstituted flavan derivatives (1-44) were designed and synthesized. The target compounds were assayed for inhibitory activity against α-glucosidase in vitro, and the results indicated that all compounds displayed significant effects in the range of IC50 = 1.03-7.48 µM compared to that of acarbose, the positive control drug. Structure-activity relationship (SAR) studies indicated that the hydroxyl groups in the flavan B ring, the electron withdrawing groups, and the length of the alkyl chains are important for this biological activity. In addition, some compounds were tested for their tolerance to sucrose in mice, and compound 44 exhibited activity comparable to that of acarbose. Docking analysis indicated that compound 44 binds to the enzyme in a pocket close to the catalytic site, similar to acarbose.

The phenolic acids from the plant of Salvia miltiorrhiza.

Seven new phenolic acids, 7, 8-epiblechnic acid (1), 8-epiblechnic acid 9-ehthyl-9'-methyl ester (2), 9'-ehyl-isolithospermate (3), 9''-methyl-isolithospermate (4), 9'-ethyl-9''-methyl-isolithospermate (5), 9', 9''-dimethyl-isolithospermate (6), sebesteniod E (7), were isolated from the roots of Salvia miltiorrhiza. Their structures were elucidated by detailed spectroscopic means including UV, IR, HRESIMS, and NMR data spectra. The bioactive assays of compounds 1-7 against neuroprotection activities were determined. The results suggested that compound 4 exhibited a moderate glutamate-induced neuroprotective activity and the cell survival rate was 24.0% (10-5 mol/L), while compound 2 showed weak activity (survival rate: 7.58%, 10-5 mol/L), using PHPB (survival rate: 7.56%, 10-5 mol/L) as positive control.

The triterpenoids and sesquiterpenoids from the plant of Agrimonia pilosa.

A phytochemistry of the whole plant of Agrimonia pilosa led to the discovery of two new nortriterpenoids, agrimonorterpenes A and B (1 and 2), together with one known triterpenoid fupenzic acid (3) and seven known sesquiterpenoids (4-10). The new structures were determined as 19α-hydroxy-2-oxo-nor-A (3)-urs-11,12-dien-28-oic acid (1) and 2, 19ß-dihydroxy-3-oxo-23-noroleana-1, 4, 12-trien-28-oic acid (2) by the spectroscopic data of UV, IR, HR-ESI-MS, and NMR. Notably, the structure of 1 possessed a rare five-membered A- ring. And this is the first time to discover the sesquiterpenoids (4-10) from A. pilosa. Compound 3 displayed the selective cytotoxicity against HCT116, BGC823, and HepG2 cell lines with the IC50 values of 16.31 µM, 21.94 µM, and 23.40 µM, respectively.

Neuroprotective and anti-inflammatory phenylethanoidglycosides from the fruits of Forsythia suspensa.

Neuroinflammation is emerging as a crucial reason of major neurodegenerative diseases in recent years. Increasingly evidences have supported that bioactive natural products from traditional Chinese medicines have efficiency for neuroinflammation. Forsythia suspensa, a typical medicinal herb, showed potential neuroprotective and anti-inflammatory properties in previous pharmacological studies. In our research to obtain neuroprotective and anti-inflammatory natural products, three unprecedented C6-C7'/C6-C16' linked phenylethanoidglycoside dimers (1-3), three new phenylethanoidglycosides (4-6), and six known compounds (7-12) were isolated from the fruits of Forsythia suspensa. Their structures were determined by comprehensive spectroscopic data and comparison to the literature data. All isolated compounds were evaluated their neuroprotective and anti-inflammatory activities. Compounds 1 and 10 exhibited significant neuroprotective activities with the cell viability values of 75.24 ± 8.05% and 93.65 ± 10.17%, respectively, for the serum-deprivation and rotenone induced pheochromocytoma (PC12) cell injury. Meanwhile, compound 1 exhibited excellent anti-inflammatory activity against tumor necrosis factor (TNF)-α expression in LPS induced RAW264.7 cells with the IC50 value of 1.30 µM. This study revealed that the bioactive phenylethanoidglycosides may attenuate neuroinflammation through their neuroprotective and anti-inflammatory activities.

Bioactive amides from Polygonum cuspidatum.

One pair of new amides enantiomers (1a and 1b) and two known amides were isolated from the rhizomes of Polygonum cuspidatum. Their structures were established using UV, IR, HRESIMS, and NMR data. Notably, compound 1 possesses unique C-C connection between feruloyltyramine and resveratrol. Their absolute configurations were determined by the ECD method. All compounds were evaluated for their α-glucosidase inhibitory activity and compounds 2 and 3 showed significant inhibitory activity with IC50 values of 2.82 and 13.06 µmol/L, respectively (positive control acarbose, IC50 385 µmol/L).

Three new compounds from the rhizome of Ligusticum chuanxiong and their anti-inflammation activities.

Phytochemical investigation of the rhizome of Ligusticum chuanxiong Hort led to the isolation and identification of three new compounds, chuanxiongoside A, (2E,4E)-8-(6-O-inositolyl)-8-oxo-2,7-dimethyl-octadienoic acid (2), chuanxiongoside C (3). The structures of these compounds were unambiguously established by HR-ESI-MS, UV, IR, CD, NMR spectral data and comparison to reported data. All the isolated compounds (1-3) were investigated for their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells. All compounds showed excellent inhibition of NO production stronger than curcumin. [Formula: see text].

Bioactive phenylpropanoid esters of sucrose and anthraquinones from Polygonum cuspidatum.

Four new compounds including two new phenylpropanoid esters of sucrose, polygonusucroside A (1) and B (2); two new anthraquinones, 8-O-ß-d-(6'-galloyl)-glucopyranoside (3) and polyanthraquinoside A (4), together with six known compounds were isolated from Polygonum cuspidatum. Their structures were established using UV, IR, HRESIMS, and NMR data. All compounds were evaluated for their α-glucosidase inhibitory activities and neuroprotective effects. Compounds 5, 7 and 9 showed significant α-glucosidase inhibitory activities with IC50 values of 27.30, 5.51, and 1.09 µmol/L, respectively (acarbose as positive control, IC50 = 6.17 µmol/L). In addition, the assessment of neuroprotective effect showed that compound 3 exhibited remarkable effect against PC12 cells injured by serum-deprivation and compounds 2, 7, and 9 exhibited moderate effects against PC12 cells injured by rotenone.

Two new lignans from the fruits of Forsythia suspensa.

Two new lignans, wikstronoside B (1) and forsysesquinorlignan (2), were isolated from the fruits of Forsythia suspensa, along with two known sesquineolignans, hedyotol A and hedyotol C (3 and 4). The structures of new compounds were established via extensive spectroscopy techniques, including UV, IR, HRESIMS, NMR, and ECD. Compounds 3 and 4 were isolated from this plant for the first time. Their anti-inflammatory effects were evaluated via a detection model with LPS-induced murine macrophage RAW264.7 cells, and compound 3 showed a moderate activity.

Anti-inflammatory phenylpropanoid glycosides from the fruits of Forsythia suspensa.

Five new phenylpropanoid glycosides, susaroysides A-E (1-5) were isolated from the fruits of Forsythia suspensa. Their structures were elucidated by comprehensive spectroscopic data analysis. The absolute configurations of their sugars were determined by GC analysis. Notably, susaroysides A-D possessed a sugar with an unsubstituted anomeric carbon, which is relatively rare in natural sources. Compound 1 exhibited significant anti-inflammatory activity against the lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α expression in macrophage cells with the IC50 value of 1.053 µM.

Eight new biflavonoids with lavandulyl units from the roots of Sophora flavescens and their inhibitory effect on PTP1B.

In the course of studying the components from the roots of Sophora flavescens, eight new unusual biflavonoids consisting of a flavanone fused with a dihydrochalcone skeleton were isolated. These new chemical structures were elucidated by means of UV, IR, HRESIMS, NMR and ECD spectroscopic data and a comparison of experimental ECD spectra with calculated ECD spectra. Some compounds were subjected to an antidiabetic bioassay on human recombinant PTP1B inhibition, and showed strong inhibitory activity.

Eight new triterpenoid saponins with antioxidant activity from the roots of Glycyrrhiza uralensis Fisch.

Eight new triterpenoid saponins (1-8), were isolated from the roots of Glycyrrhiza uralensis Fisch., together with 10 known triterpenoid saponins (9-18). Their structures were determined by analysis of their spectroscopic data and comparison with the reference. All of the compounds were evaluated for their antioxidant effects in the in vitro assay. Compounds 2 and 8 showed significant antioxidant activities against Fe2+/cysteine-induced liver microsomal lipid peroxidation at 0.1 µM.

Six new compounds from the flowers of Chrysanthemum morifolium and their biological activities.

Flower of Chrysanthemum morifolium is widely used in China and Japan as a folk medicine in treatment of many diseases. However, its active compounds remain largely unknown. In the present work, we have isolated, purified and characterized six new compounds (1-6), including two new arylnaphthalene lignans and four new phenolic glycosides, together with eight known compounds (7-14), from the flower of C. morifolium. Their structures and absolute configurations were elucidated in detail using 1D and 2D NMR, UV, IR, ORD, HRESIMS and ECD spectrometric data. In addition, compounds 1-3 possessed the significant neuroprotective activity against hydrogen peroxide-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.

Ferulic acid derivatives from Ligusticum chuanxiong.

Four new ferulic acid derivatives ligusticumacid A-C (1-3) and ligusticumaldehyde A (4), one new dimer ligusticumacid D (5), and two novel 8-8' lignans ligusticumacid E-F (6-7) were isolated from the rhizome of Ligusticum chuanxiong Hort. In particular, compounds 1-2, 5 were rarely phenylpropanoid phenolic acid dimers through different polymerization action in natural products. Their structures were established using UV, IR, HRESIMS, NMR data. The absolute configurations of 3 was determined by quantum ECD calculation and 4, 6-7 were determined by the ECD exciton chirality method. In addition, all compounds were evaluated for their neuroprotective effects on human neuroblastoma SH-SY5Y cell injury induced by H2O2. Compound 2 had a moderate neuroprotective activity and 7 had a weak neuroprotective activity on human neuroblastoma SH-SY5Y cell injury induced by H2O2 respectively.

Eight new phenylethanoid glycoside derivatives possessing potential hepatoprotective activities from the fruits of Forsythia suspensa.

In our study to investigate components with hepatoprotective activities, eight new phenylethanoid glycoside derivatives (1-8) were isolated from the 75% EtOH-H2O extract of the fruits of Forsythia suspensa along with six known compounds (9-14). These new structures were elucidated through HRESIMS and extensive NMR spectroscopic techniques. The absolute configurations of their sugars were determined by GC analysis. The pharmacological assay showed that compounds 2, 3, and 9-11 displayed remarkable hepatoprotective activities against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage at the concentration of 10µM (Bicyclol as positive contrast).

Four new iridoid glucosides containing the furan ring from the fruit of Cornus officinalis.

Four new and rare iridoid glucosides, cornusfuroside A-D (1-4), containing the furan ring were identified from water extract of the fruit of Cornus officinalis. These new chemical structures were determined through extensive spectroscopic analysis, including 1D and 2D NMR, IR, HRESIMS, experimental and calculated electronic circular dichroism (ECD). Notably, this study is the first report on the isolation of four iridoid glucoside structures with acetal functions in the sugar moiety. The neuroprotective effects of these compounds were also evaluated in vitro.

Neuroprotective Caffeoylquinic Acid Derivatives from the Flowers of Chrysanthemum morifolium.

Three new caffeoylquinic acid derivatives, chrysanthemorimic acids A-C (1-3), and 11 known compounds (4-14) were isolated and characterized from the flowers of Chrysanthemum morifolium. Their structures were confirmed by spectroscopic data as well as by comparison of the experimental and calculated electronic circular dichroism spectra. Chrysanthemorimic acids A-C possess a rare 8-oxa-bicyclo[3.2.1]oct-3-en-2-one ring that is formed through a [5+2] cycloaddition of caffeoylquinic acid with a d-glucose derivative. Compounds 1-3, 6-8, 12, and 13 displayed significant effects against hydrogen peroxide-induced neurotoxicity in SH-SY5Y cells at 10 µM.

A novel ECG analog 4-(S)-(2,4,6-trimethylthiobenzyl)-epigallocatechin gallate selectively induces apoptosis of B16-F10 melanoma via activation of autophagy and ROS.

Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate autophagy. JP8 treatment had a stronger effect on apoptosis in B16-F10 melanoma cells than that in normal AML-12 hepatocytes. JP8 selectively resulted in reactive oxygen species (ROS) accumulation in B16-F10 cells, and this effect was associated with corresponding increases in key components of the ER stress-mediated apoptosis pathway. Pharmacological inhibition of ROS by N-acetyl-L-cysteine (NAC) attenuated JP8-induced autophagy and apoptosis, indicating an upstream role of ROS in JP8-induced autophagy. An in vivo study showed that JP8 had significant antitumor effects in a B16-F10 xenograft mouse model. Our results indicate that JP8 is a novel anticancer candidate with both autophagy and ROS induction activities.

Carthorquinosides A and B, Quinochalcone C-Glycosides with Diverse Dimeric Skeletons from Carthamus tinctorius.

Two novel quinochalcone C-glycosides, carthorquinosides A (1) and B (2), were isolated from the florets of Carthamus tinctorius. Their structures, including the absolute configurations, were established by analysis of NMR and MS data, together with chemical degradation and electronic circular dichroism spectra. Compound 1 has an unprecedented quinochalcone-flavonol structure linked via a methylene bridge, and compound 2 comprises two glucopyranosylquinochalcone moieties linked via the formyl carbon of an acyclic glucosyl unit. A potential biosynthesis pathway is also proposed. Compounds 1 and 2 exhibited anti-inflammatory activities in LPS-stimulated HUVEC cells by regulating IL-1, IL-6, IL-10, and IFN-γ mRNA expression at concentrations as low as 4 µM, and compound 2 also showed inhibitory activity against topoisomerase I at100 µM.