N-alkylamides from Litsea cubeba (Lour.) Pers. with potential anti-inflammatory activity.

Six amides, including a new N-alkylamide (1), four known N-alkylamides (2-5) and one nicotinamide (6) were isolated from Litsea cubeba (Lour.) Pers., which is a pioneer herb traditionally utilized in medicine. Their structures were elucidated on the basis of 1D and 2D NMR experiments and by comparison of their spectroscopic and physical data with the literature values. Cubebamide (1) is a new cinnamoyltyraminealkylamide and possessed obvious anti-inflammatory activity against NO production with IC50 values of 18.45 µM. Further in-depth pharmacophore-based virtual screening and molecular docking were carried out to reveal the binding mode of the active compound inside the 5-LOX enzyme. The results indicate that L. cubeba, and the isolated amides might be useful in the development of lead compounds for the prevention of inflammatory diseases.

Heterodimers with a cucurbitane-type triterpenoid skeleton from the branches of Elaeocarpus dubius.

Four undescribed and two known cucurbitane-type triterpenoids, including two heterodimers, elaeocarpudubins A and B, were isolated from the branches of Elaeocarpus dubius (Elaeocarpaceae). The chemical structures of these undescribed isolates were determined by analyses of 1D and 2D NMR and MS data, electronic circular dichroism (ECD) calculations, and chemical transformation. Biogenetically, elaeocarpudubins A and B might be derived from cucurbitacin F through Michael addition with vitamin C and (-)-catechin, respectively. These six isolates were evaluated for their cytotoxic activities against human leukemia HL-60, human lung adenocarcinoma A549, human hepatoma SMMC-7721, human breast cancer MCF-7, human colon cancer SW480, and paclitaxel-resistant A549 (A549/Taxol) cell lines, for their antioxidant properties using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, and for their differentiation effects on nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells. Cucurbitacins F (IC50 of 4.98-38.11 µM) and D (IC50 of 0.03-4.40 µM) showed growth-inhibitory activities against these six cancer cell lines. Elaeocarpudubin B (IC50 of 61.04 µM) and elaeocarpudoside B (IC50 of 6.93 µM) showed antioxidant activities. Elaeocarpudubin B and elaeocarpudoside B also showed neurite outgrowth-promoting activities in PC12 cells at a concentration of 10 µM.

5-Demethoxy-10'-ethoxyexotimarin F, a New Coumarin with MAO-B Inhibitory Potential from Murraya exotica L.

Rutaceae plants are known for being a rich source of coumarins. Preliminary molecular docking showed that there was no significant difference for coumarins in Clausena and Murraya, both of which had high scoring values and showed good potential inhibitory activity to the MAO-B enzyme. Overall, 32 coumarins were isolated from Murraya exotica L., including a new coumarin 5-demethoxy-10'-ethoxyexotimarin F (1). Their structures were elucidated on the basis of a comprehensive analysis of 1D and 2D NMR and HRMS spectroscopic data, and the absolute configurations were assigned via a comparison of the specific rotations and the ECD exciton coupling method. The potential of new coumarin (1) as a selective inhibitor of MAO-B was initially evaluated through molecular docking and pharmacophore studies. Compound (1) showed selectivity for the MAO-B isoenzyme and inhibitory activity in the sub-micromolar range with an IC50 value of 153.25 ± 1.58 nM (MAO-B selectivity index > 172).

Sesquiterpenoids and 2-(2-Phenylethyl)chromone Derivatives from the Resinous Heartwood of Aquilaria sinensis.

One novel spirolactone, aquilarisinolide (1), three new sesquiterpenoids, (2R,4S,5R,7R)-2-hydroxyeremophila-9,11-dien-8-one (2), (1R,4S,5S,7R,11R)-13-hydroxyepidaphnauran-9-en-8-one (3), and (4R,5S,7R,8S,10S,13R)-8,13-dihydroxyrotunda-1,11-dien-3-one (4), together with 13 known compounds (5-17) were isolated from the resinous heartwood of Aquilaria sinensis (Thymelaeaceae). The structures of the new compounds were elucidated based on the analysis of NMR and MS data and theoretical calculations their ECD spectra. The isolated compounds were evaluated for their protective activities against PC12 cell injury induced by corticosterone (CORT) and 1-methyl-4-phenylpyridine ion (MPP+), as well as inhibitory activities against BACE1. Compound 4, 5,6-dihydroxy-2-(2-phenylethyl)chromone (5), daphnauranol B (7), 6-methoxy-2-[2-(3-methyoxyphenyl)ethyl]chromone (10), isoagarotetrol (14), and 1-hydroxy-1,5-diphenylpentan-3-one (16) showed significant protective effects on CORT-induced injury in PC12 cells at a concentration of 20 µM (P < 0.001). Isoagarotetrol (14) showed a significant protective effect on MPP+-induced injury in PC12 cells at a concentration of 20 µM (P < 0.001), while compound 4 showed a moderate activity (P < 0.01). The BACE1-inhibitory activities of all tested compounds were very weak with less than 30% inhibition at a concentration of 20 µM.

Neuroprotective compounds from the resinous heartwood of Aquilaria sinensis.

Six undescribed compounds, including three sesquiterpenoids [(4S,5S,7S,8S,11R)-7-hydroxyguai-1(10)-en-8,12-olide, aquilarisinone, and 2Z,7(13),9E-humulatrien-12-ol-5-one], one diphenylpentanone [1-(2-hydroxyphenyl)-5-phenylpentan-3-one], and two 2-(2-phenylethyl)chromones (6-epiagarotetrol and triepoxyhexahydrochromone A), along with 15 known compounds, were isolated from the resinous heartwood of Aquilaria sinensis (Thymelaeaceae). Their structures were determined by mass (MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configuration of (4S,5S,7S,8S,11R)-7-hydroxyguai-1(10)-en-8,12-olide was confirmed by X-ray diffraction analysis, and the configurations of (4S,7S,8S,10R,11R)-7,10-epoxyguai-1(5)-en-8,12-olide, aquilarisinone, 6-epiagarotetrol, and triepoxyhexahydrochromone A were confirmed by electronic circular dichroism (ECD) calculations. The neuroprotective activities of the compounds were evaluated using models of BACE1 inhibition and PC12 cells with corticosterone- and 1-methyl-4-phenylpyridine ion (MPP+)-induced damage. At concentrations of 1, 2, and 5 µM, triepoxyhexahydrochromone A, (+)-(7R,10R)-selina-4,11(13)-diene-12,15-dial, (-)-(5R,7R,10R)-12,15-dioxo-α-selinene, and (+)-(1R,4S,5R)-1ß-hydroxyeremophila-7(11),9-dien-8-one exerted significant protective effects (p < 0.01) on PC12 cell injury induced by corticosterone, while triepoxyhexahydrochromone A and (-)-(5R,7R,10R)-12,15-dioxo-α-selinene exerted significant protective effects (p < 0.01) on MPP+-induced PC12 cell injury at concentrations of 1, 2, and 5 µM. No compounds produced significant inhibitory effects on BACE1, with inhibition rates of less than 20% observed at a concentration of 20 µM.

Carbazole Alkaloids from Clausena anisum-olens: Isolation, Characterization, and Anti-HIV Evaluation.

Two new carbazole alkaloids (1,2) and six known carbazole alkaloids (3-8) were isolated from Clausena anisum-olens. Their structures were elucidated based on extensive spectroscopic analysis. All isolated compounds (1-8) were evaluated for their anti-HIV effects on virus replication in MT-4 lymphocytes infected by HIV-1NL4-3 Nanoluc-sec virus, and new carbazole alkaloid 1 exhibited anti-HIV activity with an EC50 value of 2.4 µg/mL and SI of 7.1.

Anisucoumaramide, a Bioactive Coumarin from Clausena anisum-olens.

A new coumarin, anisucoumaramide (1), and a new δ-truxinate derivative, anisumic acid (2), were isolated from Clausena anisum-olens. Their structures were elucidated from extensive NMR and MS data. The absolute configurations of the coumarins were assigned using the experimental and calculated electronic circular dichroism data. Anisucoumaramide (1) represents the first example of a naturally occurring coumarin of which the terpenoidal side chain does not comply with the biosynthesis isoprene rule due to the presence of an unprecedented acetamido motif directly connected with the terpenoidal side chain. The δ-truxinate derivative was isolated from Clausena species for the first time. Compound 1 showed high selectivity for the MAO-B isoenzyme and inhibitory activity in the nanomolar range. Putative biosynthesis pathways toward 1 and 2 are proposed.

Ethnobotany, phytochemistry, and pharmacology of the genus Litsea: An update.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Litsea is one of the most diverse genera of evergreen trees or shrubs belong to Lauraceae, and comprises roughly 400 species of tree that are distributed abundantly throughout tropical and subtropical Asia, North and South America. Litsea species have been used globally in traditional medicine for the treatment of various diseases including influenza, stomach aches, diarrhea, diabetes, vomiting, bone pain, inflammation, illness related to the central nervous system and other ailments. The purpose of this review is to provide updated, comprehensive and categorized information on the ethnobotany, phytochemistry and pharmacological research of Litsea species in order to explore their therapeutic potential and evaluate future research opportunities. MATERIALS AND METHODS: All the available information on Litsea species was actualised by systematically searching the scientific literatures including Chinese, Korean, Japanese, Indian, and South American herbal classics, library catalogs and scientific databases (PubMed, SciFinder, Web of Science, Google Scholar, VIP and Wanfang). The Plant List, International Plant Name index and Scientific Database of China Plant Species were used to validate scientific names. RESULTS: 407 secondary metabolites have been reported from Litsea species. Litsea Species are sources of secondary metabolites with interesting chemical structures (alkaloids, lactones, sesquiterpenes, flavonoids, lignans, and essential oils) and significant bioactivities. Crude extracts, fractions and phytochemical constituents isolated from Litsea show a wide spectrum of in vitro and in vivo pharmacological activities including anticancer, anti-inflammatory, antimicrobial, antioxidant, antidiabetic, anti-HIV, insecticidal, etc. CONCLUSIONS: From data collected in this review, the genus Litsea comprises a wide range of therapeutically promising and valuable plants, and has attracted much attention owing to its multiple functions. Many traditional uses of Litsea species have now been validated by modern pharmacology research. Deep and systematic phytochemical investigation of the genus Litsea and the pharmacological properties, especially its mechanism of action and toxicology, to illustrate its ethnomedicinal use, explore the therapeutic potential and support further health-care product development will undoubtedly be the focus of further research. Therefore, detailed and extensive studies and clinical evaluation of Litsea species should be carried out in future for the safety approval of therapeutic applications.

In vitro extraction of intra-corneal iron using reverse iontophoresis and vitamin C.

PURPOSE: The aim of this study was to optimize reverse iontophoretic (RI) extraction of ferric/ferrous ions from the cornea. METHODS: Group I consisted of the right eye corneas from 20 normal rabbits. Corneal blood staining was induced in 60 right eyes. The corneal depths from the endothelium to the epithelium layers were divided into three groups by slit-lamp examination: Group II, one-third corneal thickness; Group III, one-half corneal thickness; Group IV, full corneal thickness. RI was performed using vertical diffusion cells. The lower chamber was loaded with glutathione bicarbonate Ringer's buffer (GBR; pH 7.0) or vitamin C (12.5 mg/mL) and GBR (pH 7.0), while the upper chamber was filled with 1 mL GBR. Progress of corneal blood staining removal was evaluated. RESULTS: Application of 1.5 mA to the cornea increased flux by 1.72- and 2.19-fold in Groups III and IV, respectively, but not in Groups I or II, compared to the control. When vitamin C was included, we observed significant flux increases in the controls (1.5-, 2.06-, 2.60-, and 4.59-fold) for Groups I, II, III, and IV, and under RI conditions for Groups III and IV. Following RI, the corneal endothelia appeared similar to corneas from untreated control rabbits, while Draize scores were zero. CONCLUSIONS: These results suggested that extracellular ferric/ferrous ions could be extracted from the cornea in vitro by RI, and that vitamin C reduced Fe(3+) to Fe(2+) in the cornea and altered its permselectivity, thus increasing the RI contribution to iron extraction.

Five-year incidence of retinal microvascular abnormalities and associations with arterial hypertension: the Beijing Eye Study 2001/2006.

PURPOSE: To describe the 5-year incidence of retinal microvascular abnormalities and analyze their associations with arterial hypertension in nondiabetic elderly Chinese subjects in urban and rural Beijing in a follow-up of the original Beijing Eye Study 2001. DESIGN: Population-based study. PARTICIPANTS: The Beijing Eye Study 2006 included 3251 subjects who had participated in the Beijing Eye Study 2001 and returned for reexamination. METHODS: By using fundus photographs, we determined the 5-year incidence and change (progression or regression) of retinal microvascular abnormalities, including focal narrowing (FN) of retinal arterioles, arteriovenous nicking (AVN), and retinopathy. Arterial hypertension was graded as controlled treated arterial hypertension, uncontrolled treated arterial hypertension, and untreated arterial hypertension. MAIN OUTCOME MEASURES: Incidence of retinal microvascular abnormalities. RESULTS: After excluding patients with diabetes mellitus or any retinal or optic nerve disease, 2058 subjects (1409 women [68.5%]) were included in the study. The mean age of subjects was 53.8 ± 9.5 years, and the mean refractive error was -0.24 ± 2.04 diopters. The 5-year accumulated incidence of FN, AVN, and retinopathy was 4.1%, 1.4%, and 3.3%, respectively. Adjusted for age, gender, and region of habitation, the 5-year incidence of FN, AVN, and retinopathy increased 1.58 times (95% confidence interval [CI], 1.24-2.00; P<0.001), 1.55 times (95% CI, 1.04-2.32; P = 0.03), and 1.46 times (95% CI, 1.12-1.91; P = 0.005), respectively, for every 10 mmHg increase in mean arterial blood pressure. After adjusting for age, gender, and region of habitation, the rate of regression of FN decreased by 28% with every increase in the grade of the arterial hypertension classification. Correspondingly, the rate of regression of FN was significantly higher in the group with controlled arterial hypertension (44.4%) than in the uncontrolled (22.6%) and untreated (11.5%) groups (P = 0.01). CONCLUSIONS: Arterial hypertension was strongly associated with the incidence and longitudinal change of retinal microvascular abnormalities in nondiabetic subjects. Better control of arterial hypertension was correlated with a decreased incidence of retinal microvascular abnormalities and an increased rate of regression of FN. This suggests that retinal FN as potentially the first step of retinal microvascular abnormalities is reversible if arterial hypertension is controlled. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

[The protective effects of ginkgo biloba extract on cultured human retinal ganglion cells].

OBJECTIVE: This study was designed to investigate the protective effects of ginkgo biloba extract (EGb) 761 on human retinal ganglion cells (RGC). METHODS: It was an experimental study. Cultured human retinal cells were separated for four groups: control group, glutamate group, EGb761 group and EGb761+glutamate group. RGC survival rate was determined by immune Flow cytometry using Thy-1 as a special fluorescent antibody of RGC. RGC survival rate in Multi groups were analysed by repetitive measure analysis of variance (ANOVA), and the differences between groups were analysed by LSD t test. RESULTS: The effects of EGb761 on cultured human RGC were different under different interfere factors. The RGC survival rate was (61.94±7.75)% in control group, (44.59±4.19)% in glutamate group, (75.05±3.90)% in EGb761 group, and (63.19±9.44)% in EGb761+glutamate group. There were significant difference in different groups on survival rates of RGC (F=13.329, P<0.01). Compared with the control group, the survival rate of RGC in glutamate group was significantly decreased (P=0.010), while the EGb761 group was significantly increased (P=0.019), and the EGb761+glutamate group had no significant difference (P=0.801). Compared with the glutamate group, the survival rate of RGC in the EGb761 group and the EGb761+glutamate group was significantly increased (P=0.000, 0.020). There was no significant difference in the percentage of the large RGC in all groups. But compared with the control group (36.69±2.92)%, the percentage of large RGC in dead RGC in the EGb761 group (24.63±7.21)% and the EGb761+glutamate group (25.99±5.05)% was significantly decreased (P=0.001, 0.002). Compared with the glutamate group (40.78±3.34)%, the death rate of the large RGC in the EGb761 group and the EGb761+glutamate group was also significantly decreased (P=0.000, 0.000). CONCLUSION: EGb761 can protect RGC against glutamate induced neurotoxicity, and it has significant protective effect on cultured human RGC.

Coumarins from Clausena anisum-olens Merr.

Seven coumarins, including a new O-terpenoidal coumarin, named anisumarin (1), were isolated from Clausena anisum-olens Merr. The structure of this new coumarin was identified as 7-{(E)-4-[(4-acetoxymethyl-1,5-dihydro-5-oxo)-2H-furylium-2-yl]-3-methyl-2-butenoxy}-8-methoxycoumarin on the basis of an extensive spectroscopic analysis.

Triterpenes from Stachyurus himalaicus var. himalaicus Hook. f. et Thoms. ex Benth.

Four triterpenes 1-4, including a new naturally occurring oleanane-type triterpene 1, were isolated by a multi-step chromatography procedure from the leaves and twigs of Stachyurus himalaicus var. himalaicus Hook. f. et Thoms.ex Benth. The structures of the compounds were elucidated by spectroscopic methods, including HRESIMS, 1H- NMR, 13C-NMR, DEPT, HMQC, HMBC and NOESY spectra. All the isolated compounds were evaluated for their in vitro cytotoxic activities against human Hela cell line.

A new 2'-oxygenated flavone glycoside from Litsea glutinosa (Lour.) C. B. Rob.

A new 2'-oxygenated flavone glycoside, named glutin, was isolated from Litsea glutinosa (Lour.) C. B. Rob. along with four known compounds. The structure was identified as 2',5,7-trihydroxy-6-methoxyflavone 2'-O-beta-D-glucopyranoside (1) on the basis of extensive spectroscopic analysis.

A new O-terpenoidal coumarin from Clausena anisum-olens Merr.

A new O-terpenoidal coumarin 1, named hekumarone, was isolated from the leaves and twigs of Clausena anisum-olens Merr.(Rutaceae) collected in Hekou County in Yunnan Province, P.R. China. Structure elucidation and unambiguous NMR assignments for the title compound was carried out on the basis of 1D and 2D NMR experiments.

New monoterpenoid coumarins from Clausena anisum-olens.

Two new monoterpenoid coumarins: anisucumarin A (1) and B (2), a pair of epimers, were isolated from Clausena anisum-olens. Their structures were established based on extensive spectroscopic analyses.

New cytotoxic steroid from Stachyurus imalaicus var. himalaicus.

A phytochemical study of the ethanolic extract of Stachyurus imalaicus var. himalaicus was undertaken and as a result a new polyoxygenated steroid, named stachsterol ((20S)-20, 25-dihydroxy-4-cholesten-3-one, 1) and three known ecdysteroids, 20-hydroxyecdysone (2), 20-hydroxyecdysone-20, 22-monoacetonide (3) and polypodine B-20,22-monoacetonide (4), were isolated. Their structures were elucidated by spectroscopic methods, including UV, NMR, MS and HR-MS. The purified product 1 was found to have in vitro cytotoxic activity against human Hela cell lines with an IC50 value of 2.5 microg/mL. This is the first time that phytoecdysteroids have been found in the genus Stachyurus.

Isolation, X-ray crystallography, and computational studies of calydaphninone, a new alkaloid from Daphniphyllum calycillum.

[structure: see text]. A new hexacyclic alkaloid, calydaphninone (1), containing a 4-azatricyclo[5.2.2.0(1,4)]undecan ring system, has been isolated from the leaves and twigs of Daphniphyllum calycillum (Daphniphyllaceae). Its structure was elucidated by spectral and crystallographic means. Furthermore, conformations of calydaphninone (1) in solution are discussed on the basis of NMR spectral analysis and computational (B3LYP/6-31G*) results.

Retinal vascular abnormalities in adult Chinese in rural and urban Beijing: the Beijing Eye Study.

OBJECTIVE: To assess retinal vascular abnormalities, including focal and generalized arteriolar narrowing, arteriovenous nicking, and arteriolar sheathing, in adult Chinese in rural and urban Beijing, and their associations with self-reported diagnosis of cardiovascular and cerebrovascular diseases. DESIGN: Population-based cross-sectional cohort study. PARTICIPANTS: The study included 4439 subjects out of 5324 subjects invited to participate (response rate, 83.4%) with an age of > or =40 years. It was divided into a rural part (n = 1973 [44.4%]) and an urban part (n = 2466 [55.6%]). Mean age was 56.2+/-10.6 years (range, 40-101 years). METHODS: Color optic disc photographs were morphometrically examined. One eye of each participant was randomly selected. Generalized and focal arteriolar narrowing, arteriovenous nicking (arteriovenous crossing abnormalities), and arteriolar sheathing were assessed. Self-reported histories of cardiovascular and cerebrovascular diseases and habits of smoking and alcohol drinking were obtained from questionnaires. MAIN OUTCOME MEASURES: Frequency of generalized and focal arteriolar narrowing, arteriovenous nicking, and arteriolar sheathing. RESULTS: Optic disc photographs were available for 4228 (95.2%) subjects. Focal arteriolar narrowing was found in 6.3%, arteriovenous nicking in 6.6%, arteriolar sheathing in 4.8%, and generalized narrowing in 4.3% of the subjects. Abnormalities were more common in the temporal quadrant; they were rare in the inferior nasal quadrant. Frequencies and severities of all retinal microvascular abnormalities examined increased with age (P<0.05). The microvascular abnormalities were detected more frequently in the rural population than in the urban population (P<0.05). After controlling for age, gender, area, and habit of drinking alcohol, generalized arteriolar narrowing (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.64, 4.22), focal arteriolar narrowing (OR, 1.51; 95% CI, 1.00, 2.29), and arteriolar sheathing (OR, 1.71; 95% CI, 1.08, 2.71) were significantly associated with the self-reported diagnosis of arterial hypertension. The microvascular abnormalities were not significantly associated with the self-reported diagnosis of coronary heart disease or stroke. CONCLUSIONS: Retinal vascular abnormalities in adult Chinese increase with age and are more commonly found in people living in rural areas. Retinal vascular abnormalities are associated with the self-reported diagnosis of arterial hypertension, and are not related to self-reported diagnosis of coronary heart disease or previous cerebrovascular events such as stroke.