Planta medica [journal]
- Trypanocidal Activity of Flavokawin B, a Component of Polygonum ferrugineum Wedd. [JOURNAL ARTICLE]
- Planta Med 2016 Jul 21.
The trypanocidal potential of the natural chalcone flavokawin B, which was isolated from the hexanic extract of Polygonum ferrugineum Wedd., is reported here. Although flavokawin B is widespread, this is the first report about its trypanocidal properties on both Trypanosoma cruzi (IC50 = 9.5 µM, IC50 = 34.7 µM benznidazol, Y strain) epimastigotes and Trypanosoma brucei (IC50 = 4.8 µM, IC50 = 6.4 µM pentamidine, 29-13 strain) procyclic forms, which was also corroborated on T. brucei strain 427 (IC50 = 6.2 µM). In order to learn more about its properties, unspecific cytotoxicity on Hep G2 cells was investigated as well as the trans-splicing inhibitory potential on T. brucei cells. The results shown here point to flavokawin B as a candidate in the search for new agents. It is also cheaper and less toxic than the available drugs to treat trypanosomiasis with a special focus on sleeping sickness disease.
- Special Issue dedicated to Prof. Dr. Dres. h. c. mult. Kurt Hostettmann. [Journal Article]
- Planta Med 2016 Jul; 82(11-12):919.
- Chemical Composition, Anticonvulsant Activity, and Toxicity of Essential Oil and Methanolic Extract of Elettaria cardamomum. [JOURNAL ARTICLE]
- Planta Med 2016 Jul 19.
Elettaria cardamomum is an aromatic spice (cardamom) native to the humid Asian areas, which contains some compounds with a potential anticonvulsant activity. Various pharmacological properties such as anti-inflammatory, analgesic, antioxidant, and antimicrobial effects have been related to this plant. This research was conducted to examine the probable protective impact of the essential oil and methanolic extract of E. cardamomum against chemically (pentylentetrazole)- and electrically (maximal electroshock)-induced seizures in mice. In addition, neurotoxicity, acute lethality, and phytochemistry of the essential oil and methanolic extract were estimated. The TLC method showed the presence of kaempferol, rutin, and quercetin in the extract, and the concentration of quercetin in the extract was 0.5 µg/mL. The major compounds in the essential oil were 1,8-cineole (45.6 %), α-terpinyl acetate (33.7 %), sabinene (3.8 %), 4-terpinen-4-ol (2.4 %), and myrcene (2.2 %), respectively. The extract and essential oil showed significant neurotoxicity in the rotarod test at the doses of 1.5 g/kg and 0.75 mL/kg, respectively. No mortalities were observed up to the doses of 2 g/kg and 0.75 mL/kg for the extract and essential oil. The essential oil was effective in both the pentylentetrazole and maximal electroshock models; however, the extract was only effective in the pentylentetrazole model. The study suggested that E. cardamomum methanolic extract had no significant lethality in mice. Both the essential oil and methanolic extract showed movement toxicity. Anticonvulsant effects of E. cardamomum were negligible against the seizures induced by pentylentetrazole and maximal electroshock.
- Effects of Inonotus hispidus Extracts and Compounds on Human Immunocompetent Cells. [JOURNAL ARTICLE]
- Planta Med 2016 Jul 18.
Inonotus hispidus is used as a traditional medicine in China. Previous investigations revealed promising immunomodulatory activity of fruit body extracts of I. hispidus. Bioactivity-guided fractionation showed that hispolon and hispidin were active substances.In this study, we analysed the effects of I. hispidus extract and selected constituents on different types of human immune cells and investigated the potential of I. hispidus extract as a medicinal mushroom. The influence of I. hispidus extract on activity and maturation of human T cells, purified natural killer cells, and dendritic cells was analysed using cytometric-based surface marker expression. The cell division characteristics of the activated T cells were assessed by membrane permeable dye, and the function of natural killer cells was investigated by a degranulation CD107a assay. Apoptosis induction was assessed by surface staining of phosphatidylserine, and camptothecin and cyclosporine A were used individually as controls. Phytochemical analysis, using TLC chromatograms and HPLC analysis, was conducted to characterise the I. hispidus extract. I. hispidus extract increased the activation and diminished the proliferation of activated human T cells in the presence of apoptosis. Natural killer cell activity and function were dose-dependently increased. Surface marker expression of dendritic cells demonstrated that I. hispidus extract has the potential to induce maturation. TLC and HPLC analyses showed that the extract contained hispidin and hispolon. Investigations using hispidin and hispolon demonstrated similar, albeit noncongruent, results with extracts on measured parameters.The results indicate that extracts from I. hispidus and their constituents, hispidin and hispolon, interfere with the function of multiple immune cells, thus providing a rationale for their potential as a medicinal mushroom.
- Sesquiterpene Coumarins from Ferula sinkiangensis Act as Neuroinflammation Inhibitors. [JOURNAL ARTICLE]
- Planta Med 2016 Jul 15.
Neuroinflammation mediated by microglia cells plays a critical role in the development of Alzheimer's disease. To identify novel natural neuroinflammation inhibitors, a bioactivity-guided phytochemical research was performed on the traditional Chinese medicine "Awei", that exhibited a significant inhibitory effect on nitric oxide production in over-activated microglia cells. The research identified sixteen bioactive sesquiterpene coumarins (two new and fourteen known ones) in the effective extract of Ferula sinkiangensis. Further, the anti-neuroinflammatory activities in BV-2 microglial cells were evaluated by monitoring LPS-induced nitric oxide production. In conclusion, the major constituent, (3'S, 5'S, 8'R, 9'S, 10'R)-kellerin (1.5 %, w/w), should be responsible for the anti-neuroinflammatory effect exhibited by Awei. Furthermore, it might be a potential natural therapeutic agent for Alzheimer's disease. The research indicated moreover, that its primary mechanism is the inhibition of mRNA expression of the inflammatory cytokines nitric oxide, tumor necrosis factor-α, cyclooxygenase-2, interleukin-6 and interleukin-1β.
- Protective Effects of Puerarin against Aβ 1-42-Induced Learning and Memory Impairments in Mice. [JOURNAL ARTICLE]
- Planta Med 2016 Jul 15.
Puerarin is a major isoflavone glycoside from the root of Pueraria lobata. It has been reported that puerarin can protect neurons from oxidative stress-induced apoptosis. Emerging evidence suggests that oxidative damage is associated with Aβ-induced neuronal death. In the current study, we evaluated the effect of puerarin on Alzheimer's disease induced by Aβ and explored the potential mechanisms underlying this effect. We found that the escape latency of the Morris water maze was decreased in groups treated with puerarin compared to the model group (p < 0.01). In addition, there were significant differences between treated groups and the model group mice in a Y-maze test (p < 0.01). Furthermore, puerarin recovered the levels of brain-derived neurotrophic factor, phosphorylated tau, malondialdehyde, acetylcholine esterase, glycogen synthase kinase-3beta, and the activity of superoxide dismutase to some extent in the hippocampus and cerebral cortex. Shrinkage of nuclei and swollen and eccentrically dispersed neuronal bodies were observed in the hippocampus of Aβ-treated mice. These data demonstrate that puerarin might protect against cognitive deficits, oxidative stress, and neurodegeneration induced by Aβ 1-42.
- The Plant-Derived Naphthoquinone Droserone Inhibits In Vitro Measles Virus Infection. [JOURNAL ARTICLE]
- Planta Med 2016 Jul 15.
The naphthoquinone droserone (1) is a natural product occurring in dicotyledonous plants. We have now observed that the addition of 1 during infection of tissue culture cells with measles virus considerably reduced the infection. Interestingly, the infection was inhibited only when droserone (1) was added during virus entry, but not when added to the cells prior to virus uptake or after virus uptake. These findings suggest that 1 interacts with viral particles to reduce infectivity. The formation of progeny measles virus particles was inhibited to 50 % by droserone (1) at a concentration (IC50) of approximately 2 µM with a half-maximal cytotoxicity (CC50) of about 60 µM for Vero cells. Other tested naphthoquinone derivatives, among them the likewise natural plumbagin (2), but also synthetic analogs, were either more cytotoxic or not as effective as 1. Thus, our data do not support the development of naphthoquinone derivatives into antiviral compounds, but suggest that they may be interesting research tools to study measles virus entry into cells.
- Caco-2 Permeability Studies and In Vitro hERG Liability Assessment of Tryptanthrin and Indolinone. [JOURNAL ARTICLE]
- Planta Med 2016 Jul 15.
Tryptanthrin and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-inflammatory and antiallergic alkaloids, and shown to inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations. To assess their suitability for oral administration, we screened the compounds in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compounds, validated UPLC-MS/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coefficient > 32.0 × 10(-6) cm/s) across the cell monolayer. The efflux ratio below 2 (< 1.12) and unchanged apparent permeability coefficient values in the presence of the P-glycoprotein inhibitor verapamil (50 µM) indicated that tryptanthrin was not involved in P-glycoprotein interactions. For indolinone, a low recovery was found in the human colon adenocarcinoma cell assay. High-resolution mass spectrometry pointed to extensive phase II metabolism of indolinone (sulfation and glucuronidation). Possible cardiotoxic liability of the compounds was assessed in vitro by measurement of an inhibitory effect on human ether-a-go-go-related gene tail currents in stably transfected HEK 293 cells using the patch clamp technique. Low human ether-a-go-go-related gene inhibition was found for tryptanthrin (IC50 > 10 µM) and indolinone (IC50 of 24.96 µM). The analysis of compounds using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-a-go-go-related gene potassium channel at micromolar concentrations.
- Triterpenoid Saponins from the Caryophyllaceae Family Modulate the Efflux Activity of the P-Glycoprotein in an In Vitro Model of Intestinal Barrier. [JOURNAL ARTICLE]
- Planta Med 2016 Jul 15.
The oral bioavailability of drugs is often limited due to the presence of the P-glycoprotein, an efflux pump strongly expressed on the luminal side of the intestinal barrier. In an attempt to circumvent drug efflux, strategies consisting in the coadministration of drugs with surface-active agents have been found to be promising. In this context, the role of saponins on the intestinal permeability of a P-glycoprotein substrate was investigated. The P-glycoprotein inhibition activity of three triterpenoid saponins extracted from several plants of the Caryophyllaceae family was evaluated using an intestinal barrier model comprised of Caco-2 cell lines. The results showed a strong effect of two saponins on P-glycoprotein-mediated transport. At a concentration of 15 µM, the efflux ratio was close to 1 for both saponins, thus suggesting a total inhibition of the efflux pump in contrast to verapamil HCl, a conventional P-glycoprotein inhibitor. In addition, measurements of the transepithelial electrical resistance revealed that the integrity of the monolayers was not altered at such concentrations, thereby reducing potential adverse effects. The presence of acetylated sugars in the saponin structure could possibly facilitate interactions with the efflux pump by an ATP-dependent mechanism or by fluidization of cell membranes.