The basic chemical substances of three medicinal parts from Rhododendron molle G. Don.

Rhododendron Molle G. Don belongs to Ericaceae family. As a toxic traditional Chinese medicine, its roots, flowers, and fruit are often mixed and substituted arbitrarily to treat rheumatoid arthritis in clinic. To clarify the main chemical basis of each medicinal part, and provide sufficient scientific basis for clinical application, analysis using HPLC-ELSD of the roots, flowers, and fruit from R. molle was established, and characteristic chemical constituents of them were separated by tracking. The structures were determined by NMR methods. Finally, 16, 21, and 18 compounds were obtained from the roots, flowers, and fruit, respectively. Overall, 49 compounds were obtained, of which 25 were identified for the first time in R. molle. Meanwhile, among the obtained compounds, 12, 11, and 6 characteristic peaks were identified from the roots, flowers, and fruit, respectively. Thus, the basic chemical substances of the medicinal parts of R. molle were determined initially.

Two new xanthones, a new lignin, and twenty phenolic compounds from Smilax china and their NO production inhibitory activities.

Two new xanthones smilone A (1), smilone B (2), and a new lignin smilgnin A (3) were isolated from the rhizomes of Smilax china L., together with three known xanthones (4-6), four lignins (7-10), two flavones (11, 12), two stilbenoids (13, 14), and ten organic phenoloids (15-24). Of them, compounds 4-6 were isolated from the genus Smilax for the first time. The structures of 1-24 were elucidated by the extensive analysis of spectral data and compared with the literature. All compounds were evaluated for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 24 exhibited significant inhibitory activity against NO production (IC50 = 1.26 µM), while compounds 3, 6, and 7 showed weak activities at the concentration of 50 µM.[Formula: see text].

Chemical constituents from the fibrous root of Ophiopogon japonicus, and their effect on tube formation in human myocardial microvascular endothelial cells.

In an effort to identify novel active constituents on the cardiovascular system, a systematic study on macroporous resin adsorption of extracts from the fibrous root of Ophiopogon japonicus was performed in a human myocardial microvascular endothelial cell line (HMMEC) based assay. One novel spirostan, named ophiogenin (1), together with six known spirostans (4-8, 10), and one new sesquiterpene glycoside, named ophioside A (2), together with one known monoterpene glycoside (9) were isolated from the active fractions, and the aglycone of compound 2 that was a new natural compound was obtained from the acid hydrolysis of 2, named ophiopogonol (3). Their structures were determined by spectral and chemical analyses. Furthermore, their effect on HMMEC tube formation was also determined. Our results indicated that compounds 4 and 8 could significantly improve the tube formation and 2 showed moderate increasing effect, while compound 5 exhibited potent inhibitory effect.

[In vivo antitumor effect of canstatin gene on human esophageal carcinoma xenografts in nude mice].

BACKGROUND AND OBJECTIVE: Canstatin is a newly discovered endogenous inhibitor of angiogenesis. Previous study has shown that canstatin can efficiently suppress the growth of human cancers, even more potent than endostatin. This study was to investigate the antitumor effects of canstatin gene on human esophageal carcinoma xenografts. METHODS: Tumor xenografts were induced with KYSE150 cells in BALB/c nude mice, and randomized into three groups: PBS, adenovirus green fluorescent protein (Ad-GFP), and Ad-GFP-canstatin groups. During treatment, tumor size was measured. The mice were killed 30 days later to observe tumor morphology. The expression of vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), caspase-3 and microvessel density (MVD) were detected by immunohistochemistry. RESULTS: Compared with that in Ad-GFP and PBS groups, tumor growth in Ad-GFP-canstatin group was significantly suppressed in the first week after gene transfection. The inhibition rate of tumor growth was up to 61% at the sixth day. Necrotic regions were observed in all groups, especially in Ad-GFP-canstatin group. Compared with those in Ad-GFP and PBS groups, caspase-3 expression in Ad-GFP-canstatin group was higher (P<0.05), while Flk-1 expression and MVD was lower (P<0.05). There was no obvious difference in VEGF expression among the three groups. CONCLUSION: Canstatin can inhibit the growth of human esophageal carcinoma by suppressing angiogenesis via down-regulating Flk-1 expression.

Safflower extracts functionally regulate monoamine transporters.

Safflower (HH), the dry flower of Carthamus tinctorius L., has long been used to empirically treat neuropsychological disorders such as stroke and major depression in traditional Chinese medicine, and recently been proven effective for regulating levels of dopamine and serotonin in new-born rat brain. The present study assessed whether HH would be bioactive for functionally regulating monoamine transporters using in vitro drug-screening cell lines. Our current results showed that all solvent-extracted HH fractions, in different degrees, markedly increased both dopamine uptake by Chinese hamster ovary (CHO) cells stably expressing dopamine transporter (DAT) and norepinephrine uptake by CHO cells expressing norepinephrine transporter (NET), and also showed that chloroform (HC), ethyl acetate (HE), and n-butyl alcohol extract strikingly depressed serotonin uptake by CHO cells expressing serotonin transporter (SERT); wherein, the potencies of ethanol extract, HC, HE, and aqueous extract to up-regulate dopamine/norepinephrine uptake and potency of HE to inhibit serotonin uptake were relatively stronger. Further investigation revealed that the enhancement of dopamine/norepinephrine uptake by HC and HE was dependent of DAT/NET activity, and the HE-induced inhibition of serotonin uptake was typical of competition. Thus, HH extracts are novel monoamine transporter modulators functioning as DAT/NET activators and/or SERT inhibitors, and would likely improve neuropsychological disorders through regulating monoamine-transporter activity.

Dopamine transporter inhibitory and antiparkinsonian effect of common flowering quince extract.

Common flowering quince (FQ) is the fruit of Chaenomeles speciosa (Sweet) Nakai. FQ-containing cocktails have been applied to the treatment of neuralgia, migraine, and depression in traditional Chinese medicine. The present study assessed whether FQ is effective in dopamine transporter (DAT) regulation and antiparkinsonism by utilizing in vitro and in vivo assays, respectively. FQ at concentrations of 1-1000 microg/ml concentration-dependently inhibited dopamine uptake by Chinese hamster ovary (CHO) cells stably expressing DAT (D8 cells) and by synaptosomes. FQ had a slight inhibitory action on norepinephrine uptake by CHO cells expressing the norepinephrine transporter and no inhibitory effect on gamma-aminobutyric acid (GABA) uptake by CHO cells expressing GABA transporter-1 or serotonin uptake by the serotonin transporter. A viability assay showed that FQ mitigated 1-methyl-4-phenylpyridinium-induced toxicity in D8 cells. Furthermore, in behavioral studies, FQ alleviated rotational behavior in 6-hydroxydopamine-treated rats and improved deficits in endurance performance in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Furthermore, immunohistochemistry revealed that FQ markedly reduced the loss of tyrosine hydroxylase-positive neurons in the substantia nigra in MPTP-treated mice. In summary, FQ is a selective, potent DAT inhibitor and has antiparkinsonian-like effects that are mediated possibly by DAT suppression. FQ has the potential to be further developed for Parkinson's disease treatment.

Bakuchiol analogs inhibit monoamine transporters and regulate monoaminergic functions.

Monoamine transporters play key roles in controlling monoamine levels and modulating monoamine reuptake. The objective of the present study was to identify monoamine transporter inhibitors from herbal sources. We discovered that bakuchiol analogs isolated from Fructus Psoraleae inhibited monoamine transporter uptake to differing degrees. The bakuchiol analog, Delta3,2-hydroxybakuchiol was the most potent and efficacious reuptake blocker and was thus selected as the candidate target. Monoamine transporter inhibition by Delta3,2-hydroxybakuchiol was more selective for the dopamine transporter (DAT) (IC50=0.58+/-0.1 microM) and norepinephrine transporter (NET) (IC50=0.69+/-0.12 microM) than for the serotonin transporter (SERT) (IC50=312.02+/-56.69 microM). Delta3,2-Hydroxybakuchiol exhibited greater potency (pEC50 for DAT and NET) than bupropion and exhibited similar efficacy (E(max) for DAT and/or NET) to bupropion and GBR12,935. Pharmacokinetically, Delta3,2-hydroxybakuchiol competitively inhibited DAT and NET with partial reversibility and occupied cocaine binding sites. Moreover, Delta3,2-hydroxybakuchiol counteracted 1-methyl-4-phenylpyridinium-induced toxicity in cells expressing DAT with similar efficacy to GBR12,935. In vivo studies showed that Delta3,2-hydroxybakuchiol increased the activity of intact mice and improved the decreased activity of reserpinized mice. In the conditioned place preference test, preference scores in intact mice were unaffected by Delta3,2-hydroxybakuchiol treatment. Bakuchiol analogs, especially Delta3,2-hydroxybakuchiol, are monoamine transporter inhibitors involved in regulating dopaminergic and noradrenergic neurotransmission and may have represented potential pharmacotherapies for disorders such as Parkinson's disease, depression, and cocaine addiction.