28 research outputs found
Johanniskraut - von Inhaltsstoffen und anderen Unwägbarkeiten
Die Depression gehÜrt zu den häufigsten Volkskrankheiten. Derzeit sind rund vier Millionen Deutsche an einer behandlungsbedßrftigen Depression erkrankt. Die Erkrankung verläuft typischerweise in Form von Episoden, die Wochen bis Monate, manchmal auch Jahre anhalten kÜnnen. Wenn die Erkrankung unbehandelt bleibt, kann sie wiederkehren und einen chronischen Verlauf nehmen. Rund 75 Prozent der Betroffenen erleiden nach einer Ersterkrankung innerhalb von fßnf Jahren mindestens eine neue depressive Phase. Zudem werden mit steigender Episodenzahl die episodenfreien Zwischenzeiten immer kßrzer. Es gilt heute als unstrittig, dass mehr als die Hälfte aller Depressionen nicht diagnostiziert und allenfalls ein Fßnftel adäquat behandelt werden. Das verursacht nicht nur enorme Kosten fßr die Volkswirtschaft, sondern ist fßr die Betroffenen auch mit erheblichem Leid und Lebensgefahr verbunden
Phytochemical analysis of Ficus carica L. active compounds possessing anticonvulsant activity
The anticonvulsant potential of Ficus carica methanol-extract (Fc) has been studied. It was found that Fc most active fraction is rich in oligosaccharides (OFG). 1H, 13C NMR and Nano-ESI, MALDI MS, and LC-MS techniques proved that OFG contains alpha-glucopyranoside oligomer in high amounts. Both Fc and OFG reduced strychnine (STR) convulsion-action. Fc and OFG fully protected the experimental-animals from STR-lethality. The intracerebroventricular-administration (ICV) of Fc or OFG in combination with glycine in ethanol-treated mice caused a dose-dependent returning to a 2nd-loss of righting-reflex (LORR), and was antagonized by STR. FC and OFG ICV injection counteracted STR-inhibition, confirming that Fc/OFG anticonvulsant mechanism of action was mediated by potentiation of glycine receptor. These results support Fc and OFG potential anticonvulsant-activity with good safety-profile. Keywords: Ficus carica, Moraceae, Nano-ESI MS, MALDI MS, Intracerebroventricular, Anticonvulsant activity
Combined approach of backbone amide linking and on-resin n-methylation for the synthesis of bioactive and metabolically stable peptides
Rhabdopeptides are a large class of nonribosomal peptides from the bacteria Xenorhabdus and Photorhabdus with low micromolar activity against different protozoa, which are the causative agents of several tropical diseases. The development of a facile and flexible synthesis combining backbone amide linking with on-resin peralkylation for the synthesis of permethylated rhabdopeptides is described. This strategy allows the fast generation of permethylated naturally occurring and artificial rhabdopeptides for a structure-activity study. Furthermore, in vitro experiments revealed their superior properties regarding their stability and passive membrane diffusion
Combined Approach of Backbone Amide Linking and On-Resin NâMethylation for the Synthesis of Bioactive and Metabolically Stable Peptides
Rhabdopeptides
are a large class of nonribosomal peptides from
the bacteria <i>Xenorhabdus</i> and <i>Photorhabdus</i> with low micromolar activity against different protozoa, which are
the causative agents of several tropical diseases. The development
of a facile and flexible synthesis combining backbone amide linking
with on-resin peralkylation for the synthesis of permethylated rhabdopeptides
is described. This strategy allows the fast generation of permethylated
naturally occurring and artificial rhabdopeptides for a structureâactivity
study. Furthermore, in vitro experiments revealed their superior properties
regarding their stability and passive membrane diffusion
MH84 improves mitochondrial dysfunction in a mouse model of early Alzheimerâs disease
Abstract Background Current approved drugs for Alzheimerâs disease (AD) only attenuate symptoms, but do not cure the disease. The pirinixic acid derivate MH84 has been characterized as a dual gamma-secretase/proliferator activated receptor gamma (PPARÎł) modulator in vitro. Pharmacokinetic studies in mice showed that MH84 is bioavailable after oral administration and reaches the brain. We recently demonstrated that MH84 improved mitochondrial dysfunction in a cellular model of AD. In the present study, we extended the pharmacological characterization of MH84 to 3-month-old Thy-1 AβPPSL mice (harboring the Swedish and London mutation in human amyloid precursor protein (APP)) which are characterized by enhanced AβPP processing and cerebral mitochondrial dysfunction, representing a mouse model of early AD. Methods Three-month-old Thy-1 AβPPSL mice received 12 mg/kg b.w. MH84 by oral gavage once a day for 21 days. Mitochondrial respiration was analyzed in isolated brain mitochondria, and mitochondrial membrane potential and ATP levels were determined in dissociated brain cells. Citrate synthase (CS) activity was determined in brain tissues and MitoTracker Green fluorescence was measured in HEK293-AβPPwt and HEK293-AβPPsw cells. Soluble Aβ1â40 and Aβ1â42 levels were determined using ELISA. Western blot analysis and qRT-PCR were used to measure protein and mRNA levels, respectively. Results MH84 reduced cerebral levels of the β-secretase-related C99 peptide and of Aβ40 levels. Mitochondrial dysfunction was ameliorated by restoring complex IV (cytochrome-c oxidase) respiration, mitochondrial membrane potential, and levels of ATP. Induction of PPARÎł coactivator-1Îą (PGC-1Îą) mRNA and protein expression was identified as a possible mode of action that leads to increased mitochondrial mass as indicated by enhanced CS activity, OXPHOS levels, and MitoTracker Green fluorescence. Conclusions MH84 modulates β-secretase processing of APP and improves mitochondrial dysfunction by a PGC-1Îą-dependent mechanism. Thus, MH84 seems to be a new promising therapeutic agent with approved in-vivo activity for the treatment of AD
Combined Approach of Backbone Amide Linking and On-Resin NâMethylation for the Synthesis of Bioactive and Metabolically Stable Peptides
Rhabdopeptides
are a large class of nonribosomal peptides from
the bacteria <i>Xenorhabdus</i> and <i>Photorhabdus</i> with low micromolar activity against different protozoa, which are
the causative agents of several tropical diseases. The development
of a facile and flexible synthesis combining backbone amide linking
with on-resin peralkylation for the synthesis of permethylated rhabdopeptides
is described. This strategy allows the fast generation of permethylated
naturally occurring and artificial rhabdopeptides for a structureâactivity
study. Furthermore, in vitro experiments revealed their superior properties
regarding their stability and passive membrane diffusion