Natural iridoids from Patrinia heterophylla showing anti-inflammatory activities in vitro and in vivo.

Inflammation, especially chronic inflammation, has been found to be closely related to the pathology of many diseases and the discovery of bioactive natural products to inhibit NO production is one of strategies to treat inflammation. In our continuous search for bioactive natural substances as potential anti-inflammatory agents, five new compounds (1-5) were extracted and purified from Patrinia heterophylla. The NMR and MS data analysis, along with electronic circular dichroism (ECD) calculations, led to the identification of these isolates, which were new iridoids. Using cell and zebrafish models, the in vitro and in vivo anti-inflammatory effects were conducted to evaluate the potency of anti-inflammation of these compounds. The preliminary mechanism was explored using molecular docking and Western blotting experiments.

Bioactive triterpenoids from Lantana camara showing anti-inflammatory activities in vitro and in vivo.

Bioactive natural products play an important role in the research and development of new drugs. In our search for bioactive natural substances as potential lead compounds for inflammation, four new (1-4) and six known (6-10) triterpenoids were acquired from Lantana camara. Using NMR and MS techniques and electronic circular dichroism (ECD) calculations, these isolates were characterized and the new compounds (1-4) were found to be euphane-type triterpenoids. The in vitro anti-inflammatory effects of all the isolates were evaluated and the more bioactive compounds were selected for the investigation of preliminary mechanism using molecular docking and Western blotting experiments, as well as the in vivo anti-inflammatory evaluation using a zebrafish model.

Diterpenoids from the leaves of Casearia kurzii showing cytotoxic activities.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new and two known clerodane diterpenoids from the leaves of Casearia kurzii. Their structures were elucidated using NMR techniques and electronic circular dichroism (ECD) calculations. The subsequent biological cytotoxicity evaluation of these isolates toward human lung cancer A549, human cervical cancer HeLa, human chronic myeloid leukemia K562, and human hepatocellular carcinoma HepG2 was carried out. The most active compound 4 with an IC50 value of 9.7 µM against HepG2 cells was selected to examine the cytotoxic mechanism, which induced the apoptosis and arrested the HepG2 cell cycle at S stage. The in vivo zebrafish experiments revealed that compound 4 had the property of inhibiting tumor proliferation and migration.

Bioactive Diterpenoids from the Stems of Euphorbia royleana.

Two ingenane- (1 and 2), two ent-atisane- (3 and 4), two ent-kaurane- (5 and 6), two ent-abietane- (7 and 8), and one ent-isopimarane-type (9) diterpenoid and 12 known analogues have been isolated from the methanolic extract of the stems of Euphorbia royleana. Their structures, including absolute configurations, were determined by extensive spectroscopic methods and ECD data analysis. The nitric oxide inhibitory activities of those diterpenoids were examined biologically in lipopolysaccharide-stimulated BV-2 cells, with compounds 1, 2, 5-7, 10, and 12 having IC50 values lower than 40 µM. Molecular docking was used to investigated the possible mechanism of compounds 1, 2, 5-7, 10, and 12.

Withanolides from Physalis peruviana showing nitric oxide inhibitory effects and affinities with iNOS.

A phytochemical study to obtain new nitric oxide (NO) inhibitors resulted in the isolation of five new withanolides from the whole plants of Physalis peruviana. The structures were determined on the basis of extensive NMR spectroscopic data analysis as well as the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The NO inhibitory effects were examined by inhibiting NO release in lipopolysaccharide-stimulated murine microglial BV-2 cells. Molecular docking studies showed the strong interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein, revealing the potential mechanism of NO inhibition of bioactive compounds.

Bioactive terpenoids from Euonymus verrucosus var. pauciflorus showing NO inhibitory activities.

In our continuous search for new nitric oxide (NO) inhibitory compounds as potential anti-inflammatory agents or lead compounds for inflammatory diseases, the chemical constituents of Euonymus verrucosus var. pauciflorus were investigated, leading to the isolation of eleven terpenoids including six new diterpenoids, designated as euonymupenes A-F. The structures were elucidated on the basis of NMR and ECD data analysis. Euonymupenes A, C, and F feature rare labdane-type norditerpenoid skeletons. The NO inhibitory effects were evaluated and all of the isolates were found to inhibit lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells. Western blotting analysis indicated that the most active compound (5) can regulate iNOS (inducible nitric oxide synthase) expression. The further molecular docking studies exhibited the affinities of bioactive compounds with iNOS.

NO inhibitory phytochemicals as potential anti-inflammatory agents from the twigs of Trigonostemon heterophyllus.

Studies on the relationship of nitric oxide (NO) and inflammation have revealed that compounds with NO inhibitory effects are potentially useful for inflammation and related inflammatory disorders. A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of two new cleistanthane diterpenoids (1 and 2) and 11 known terpenoids (3-13) from Trigonostemon heterophyllus. The structures of these terpenoids were established by analysis of their NMR, MS, and electronic circular dichroism (ECD) data. Compounds 1 and 2 possess rare 3,4-seco-cleistanthane diterpenoid skeletons. All of the isolates were evaluated biologically for their NO inhibitory effects in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells and compounds 1, 6, and 8-10 showed strong NO inhibitory effects with IC50 values less than 40 µM. Using Western blotting experiments and molecular docking, the possible mechanism of NO inhibition was investigated.

Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new clerodane diterpenoids, designated as kurzipenes A-F (1-6), from the leaves of Casearia kurzii. Their structures were elucidated on the basis of NMR spectroscopic data analysis and the absolute configurations were confirmed by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The cytotoxic activities of compounds 1-6 were evaluated against human lung cancer A549 cell line, human cervical cancer Hela cell line, and human hepatocellular carcinoma HepG2 cell line. Most diterpenoids showed potent cytotoxicities against the three selected cancer cell lines. The preliminary mechanism studies revealed that the most active compound 2, with an IC50 value of 5.3 µM against Hela cells, induced apoptosis and arrested the Hela cell cycle at the G0/G1 stage to exert cytotoxic effects.

Nitric oxide inhibitory limonoids as potential anti-neuroinflammatory agents from Swietenia mahagoni.

Recent studies have revealed that there is a close relationship between neuroinflammation and Alzheimer's disease (AD) and compounds with anti-neuroinflammatory effects are potentially useful for the treatment of AD. A phytochemical investigation to obtain new neuroinflammatory inhibitors resulted in the isolation of four new and three known limonoids from Swietenia mahagoni. The structures of these limonoids were established by NMR, MS, and electronic circular dichroism (ECD) data analysis. Compounds 1-3 feature complicated polycyclic caged structures of limonoid orthoester and represent new examples of phragmalin-type limonoids. All of the isolates showed anti-neuroinflammatory activities by inhibiting nitric oxide (NO) release in LPS-induced murine microglial BV-2 cells with compounds 1 and 3-6 having IC50 values of 26.8, 26.1, 26.0, 37.1, and 16.5 µM, respectively. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.

Cytotoxic diterpenoids as potential anticancer agents from the twigs of Casearia kurzii.

A search for bioactive natural products as anticancer lead compounds has led to the isolation of five new clerodane diterpenoids (1-5) from the twigs of Casearia kurzii. Their structures were elucidated by extensive analysis of their NMR, IR, and HRESIMS data, and the absolute configurations were determined by experimental and calculated electronic circular dichroism (ECD) data analysis. The isolates were biologically evaluated and showed cytotoxic activities toward human lung cancer cells (A549), human cervical cancer cells (HeLa), and human hepatocellular carcinoma cells (HepG2). The most active compound (5) with an IC50 value of 5.3 µM against HeLa cells, was found to induce apoptosis and arrest the HeLa cell cycle at G0/G1 stage to exert cytotoxic effects.

NO inhibitory constituents as potential anti-neuroinflammatory agents for AD from Blumea balsamifera.

Our continuous search for new nitric oxide (NO) inhibitory substances as anti-neuroinflammatory agents for AD resulted in the isolation of one new labdane diterpenoid and three new guaiane sesquiterpenoids, as well as ten known compounds from Blumea balsamifera. Their structures were elucidated by NMR spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The anti-neuroinflammatory effects were examined by inhibiting NO release in LPS-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein.

Nitric oxide inhibitors with a spiro diterpenoid skeleton from Scutellaria formosana: Structures, NO inhibitory effects, and interactions with iNOS.

A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of five new spiro diterpenoids (1 -5) from the aerial parts of Scutellaria formosana. The structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The nitric oxide (NO) inhibitory effects were evaluated and all of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The possible mechanism of NO inhibition of bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein.

NO inhibitors function as potential anti-neuroinflammatory agents for AD from the flowers of Inula japonica.

The extensive pathology studies revealed that Alzheimer's disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. Inula japonica is a member of the Asteraceae plant family and its flowers have been used as a healthy tea and a traditional Chinese medicine. Our continuous search for new nitric oxide (NO) inhibitory substances as anti-neuroinflammatory agents for AD resulted in the isolation of two new sesquiterpenes and ten known terpenes from the flowers of I. japonica. Their structures were established on the basis of extensive analysis of NMR and MS spectroscopic data, as well as calculated and experimental electronic circular dichroism (ECD) spectra. Among these isolates, compound 1 is a new sesquiterpene with a rare tricyclic fused skeleton, and 2 processes a 1,10-seco-eudesmane skeleton. The anti-neuroinflammatory effects were examined by inhibiting NO release in LPS-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the iNOS protein. The present study disclosed that the flowers of I. japonica as a healthy tea are potentially useful for AD and related neuroinflammatory diseases.

Phytochemicals with NO inhibitory effects and interactions with iNOS protein from Trigonostemon howii.

A phytochemical investigation to obtain new NO inhibitors led to the isolation of nine compounds including one new guaiane-type sesquiterpenoid (1) and two new cleistanthane diterpenoids (2 and 3) from the stems of Trigonostemon howii. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of new compounds 1-3 were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 3 possess a rare 3,4-seco-cleistanthane diterpenoid skeleton. All of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The further molecular docking studies indicated the strong interactions between some bioactive compounds with the iNOS protein, which revealed the possible and potential mechanism of NO inhibition of bioactive compounds.

Nitric oxide inhibitory daphnane diterpenoids as potential anti-neuroinflammatory agents for AD from the twigs of Trigonostemon thyrsoideus.

The extensive pathology studies revealed that Alzheimer's disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. A continuous search for new nitric oxide (NO) inhibitory compounds as anti-neuroinflammatory agents for AD resulted in the isolation of four new (1-4) and eight known (5-12) daphnane diterpenoids from the twigs of Trigonostemon thyrsoideus. Their structures were elucidated on the basis of extensive nuclear magnetic resonance (NMR) spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Compounds 1-4 represent new examples of daphnane diterpenoid orthoesters and 4 features a rare and complex macroring diterpenoid structure. The anti-neuroinflammatory effects were examined by inhibiting NO release in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.

Polycyclic phloroglucinols as PTP1B inhibitors from Hypericum longistylum: Structures, PTP1B inhibitory activities, and interactions with PTP1B.

Protein tyrosine phosphatase 1B (PTP1B) has been regarded asa target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A-D (1-4) from the aerial parts of Hypericum longistylum. The structures of 1-4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1-4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes.

Bioactive Diterpenoids from the Leaves of Callicarpa macrophylla.

A phytochemical investigation of the leaves of Callicarpa macrophylla led to the isolation of five new diterpenoids (1-5), macrophypenes A-E, and nine known analogues (6-14). The structures of 1-5 were established on the basis of extensive analysis of NMR spectroscopic data, X-ray diffraction data, and experimental and calculated electronic circular dichroism spectra. Compound 1 is a spiroditerpenoid with a novel skeleton, and compound 5 is a rare ent-abietane diterpenoid possessing a peroxide bridge. Compounds 1, 5-7, and 11-14 stimulate nerve growth factor mediated neurite outgrowth from PC12 cells.

[Chronic Disease Control among Rural Residents in Beijing Pinggu District].

OBJECTIVE: To analyze the composition and control status of chronic diseases among rural residents in a Beijing suburb district. METHODS: Rural residents aged 35 years or older were investigated by stratified random sampling in Pinggu District, Beijing. Each participant received questionnaire-based survey,physical examination,and laboratory tests including routine blood test,urine albumin creatinine ratio (ACR), liver and renal function,serum lipid, fasting blood glucose, and glycosylated hemoglobin. RESULTS: A total of 10 385 residents completed all items. Cerebrovascular disease was leading cause of hospitalization (accounting for 14.4%) and its incidence in the population was 9.6%. The incidences of hypertension,hyperlipidemia,diabetes mellitus,and gout/hyperuricemia,which were the main compositions related with metabolic diseases,were up to 64.4%,42.5%,24.4%, and 9.0%, respectively. The disease onset was significantly related with the age. The incidence of hypertension was gradually elevated with the increasing of age,while the peak age was 55-64 years for diabetes and 35-44 years for gout/hyperuricemia. The awareness rate of hypertension,diabetes,and chronic kidney disease was 60.2%, 55.1%,and 6.0%,respectively. The control rate of chronic disease was 19.2% and 28.8% in hypertensive and diabetic patients, respectively. CONCLUSIONS: Cerebrovascular diseases and metabolic-associated diseases are the main chronic diseases affecting rural residents in Pinggu district, Beijing. The awareness rate and control rate of chronic diseases needs to be further enhanced by strengthening health education and improving the community medical service.

[Saponins from roots of Securidaca inappendiculata with cytotoxic activities].

Seven acylated triterpene saponins were isolated from the roots of Securidaca inappendiculata by means of various chromatographic techniques such as silica gel, MPLC, preparative HPLC, and semi-preparative HPLC. Their chemical structures were identified as securioside A(1), securioside B(2), 3-O-ß-D-glucopyranosyl presenegenin 28-O-ß-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-[ß-D-glucopyranosyl-(1-->3)]-4-O-[(E)-3,4-dimethoxycinnamoyl]-ß-D-fucopyranosyl ester(3), 3-O-ß-D-glucopyranosyl presenegenin 28-O-ß-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-[ß-D-glucopyranosyl-(1-->3) ] -4-O-[(E/Z)-3, 4-dimethoxycinnamoyl]-ß-D-fucopyranosyl ester(3/4), 3-O-ß-D-glucopyranosyl presenegenin 28-O-α-L-arabinopyranosyl-(1-->3)-ß-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-4-O-[(E)-3,4-dimethoxycinnamoyl]-ß-D-fucopyranosyl ester(5), polygalasa- ponin XLV(6), and polygalasaponin XLVI (7) on the basis of spectroscopic data analysis and physicochemical properties. Among them, compounds 5-7 were isolated from the plants in genus Securidaca for the first time and compounds 3, 3/4 were isolated from the species for the first time. The cytotoxicity assay showed that compounds 2, 3/4, 5 have moderate cytotoxic activities against Lewis lung carcinoma LLC cells with IC50 values of 41.10, 38.17, and 48.92 µmol · L(-1), respectively; compound 2 exhibited moderate cytotoxic activities against human breast cancer MCF-7 cells with an IC50 value of 47.93 µmol · L(-1).

Bioactive clerodane diterpenoids from the twigs of Casearia balansae.

Eight new clerodane diterpenes, balanspenes A-H (1-8), along with two known analogues (9 and 10), were isolated from the twigs of Casearia balansae. The structures of 1-8 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of compounds 1, 4, and 7 were confirmed by comparing their experimental CD spectra with those calculated by the time-dependent density functional theory method. Compounds 4-7, 9, and 10 were found to possess the property of being able to stimulate NGF-mediated neurite outgrowth from PC12 cells.