2 research outputs found
Best practice in the chemical characterisation of extracts used in pharmacological and toxicological researcht - the ConPhyMP-guidelines
BACKGROUND : Research on medicinal plants and extracts derived from them differs
from studies performed with single compounds. Extracts obtained from plants,
algae, fungi, lichens or animals pose some unique challenges: they are
multicomponent mixtures of active, partially active and inactive substances,
and the activity is often not exerted on a single target. Their composition
varies depending on the method of preparation and the plant materials used.
This complexity and variability impact the reproducibility and interpretation of
pharmacological, toxicological and clinical research.
OBJECTIVES : This project develops best practice guidelines to ensure
reproducibility and accurate interpretations of studies using medicinal plant
extracts. The focus is on herbal extracts used in pharmacological, toxicological, and clinical/intervention research. Specifically, the consensus-based statement
focuses on defining requirements for: 1) Describing the plant material/herbal
substances, herbal extracts and herbal medicinal products used in these studies,
and 2) Conducting and reporting the phytochemical analysis of the plant
extracts used in these studies in a reproducible and transparent way.
THE PROCESS AND METHODS : We developed the guidelines through the following
process: 1) The distinction between the three main types of extracts (extract
types A, B, and C), initially conceptualised by the lead author (MH), led the
development of the project as such; 2) A survey among researchers of medicinal
plants to gather global perspectives, opportunities, and overarching challenges
faced in characterising medicinal plant extracts under different laboratory
infrastructures. The survey responses were central to developing the
guidelines and were reviewed by the core group; 3) A core group of
9 experts met monthly to develop the guidelines through a Delphi process;
and. 4) The final draft guidelines, endorsed by the core group, were also
distributed for feedback and approval to an extended advisory group of
20 experts, including many journal editors.
OUTCOME : The primary outcome is the “Consensus statement on the
Phytochemical Characterisation of Medicinal Plant extracts“ (ConPhyMP)
which defines the best practice for reporting the starting plant materials and
the chemical methods recommended for defining the chemical compositions
of the plant extracts used in such studies. The checklist is intended to be an
orientation for authors in medicinal plant research as well as peer reviewers and
editors assessing such research for publication.Willmar Schwabe GmbH & Co. KG, Germany.https://www.frontiersin.org/journals/pharmacologydm2022Paraclinical Science
In vitro degradation and antitumor activity of oxime bond-linked daunorubicin-GnRH-III bioconjugates and DNA-binding properties of daunorubicin-amino acid metabolites.
Bioconjugates with receptor-mediated tumor-targeting functions and carrying cytotoxic agents should enable the specific delivery of chemotherapeutics to malignant tissues, thus increasing their local efficacy while limiting the peripheral toxicity. In the present study, gonadotropin-releasing hormone III (GnRH-III; Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH(2)) was employed as a targeting moiety to which daunorubicin was attached via oxime bond, either directly or by insertion of a GFLG or YRRL tetrapeptide spacer. The in vitro antitumor activity of the bioconjugates was determined on MCF-7 human breast and HT-29 human colon cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Their degradation/stability (1) in human serum, (2) in the presence of cathepsin B and (3) in rat liver lysosomal homogenate was analyzed by liquid chromatography in combination with mass spectrometry. The results show that (1) all synthesized bioconjugates have in vitro antitumor effect, (2) they are stable in human serum at least for 24Â h, except for the compound containing an YRRL spacer and (3) they are hydrolyzed by cathepsin B and in the lysosomal homogenate. To investigate the relationship between the in vitro antitumor activity and the structure of the bioconjugates, the smallest metabolites produced in the lysosomal homogenate were synthesized and their binding to DNA was assessed by fluorescence spectroscopy. Our data indicate that the incorporation of a peptide spacer in the structure of oxime bond-linked daunorubicin-GnRH-III bioconjugates is not required for their antitumor activity. Moreover, the antitumor activity is influenced by the structure of the metabolites (daunorubicin-amino acid derivatives) and their DNA-binding properties