scholarly journals Regulatory Perspectives of Pyrrolizidine Alkaloid Contamination in Herbal Medicinal Products

Planta Medica ◽  
2021 ◽  
Author(s):  
Jacqueline Wiesner
Keyword(s):  
Animal Studies ◽  
Pyrrolizidine Alkaloids ◽  
Pyrrolizidine Alkaloid ◽  
European Medicines Agency ◽  
Medicinal Products ◽  
Herbal Medicinal Products ◽  
Herbal Medicinal ◽  
National Competent Authorities

AbstractThe toxicity of plants containing certain pyrrolizidine alkaloids has long been recognized in grazing animals and humans. Genotoxicity and carcinogenicity data from in vitro and in vivo (animal) studies were published over the last few decades for some of the 1,2-unsaturated pyrrolizidine alkaloids, leading to regulatory action on herbal medicinal products with pyrrolizidine alkaloid-containing plants more than 30 years ago. In recent years, it has become evident that in addition to herbal medicinal products containing pyrrolizidine alkaloid-containing plants, these products may also contain pyrrolizidine alkaloids without actually including pyrrolizidine alkaloid-containing plants. This is explained by contamination by accessory herbs (weeds). The national competent authorities of the European member states and the European Medicines Agency, in this case, the Committee on Herbal Medicinal Products, reacted to these findings by setting limits for all herbal medicinal products. This review article will briefly discuss the data leading to the establishment of thresholds and the regulatory developments and consequences, as well as the current discussions and research in this area.

Quantitative Removal of Pyrrolizidine Alkaloids from Essential Oils by the Hydrodistillation Step in Their Manufacturing Process

Planta Medica ◽  
2021 ◽  
Author(s):  
David S. Giera ◽  
Michael Preisitsch ◽  
Hugues Brevard ◽  
Jörn Nemetz
Keyword(s):  
Essential Oils ◽  
Manufacturing Process ◽  
Pyrrolizidine Alkaloids ◽  
Pyrrolizidine Alkaloid ◽  
Medicinal Products ◽  
Herbal Medicinal Products ◽  
Naturally Occurring ◽  
Herbal Medicinal ◽  
Set Up ◽  
Theoretical Considerations

AbstractPyrrolizidine alkaloids are naturally occurring toxins produced by certain weeds that can, if accidentally co-harvested, contaminate plant-based food, feed, and herbal medicinal products. Focusing on herbal medicinal products, the presence of pyrrolizidine alkaloids is restricted by regulatory prescribed thresholds to assure patient safety. Among the multitude of different herbal active substances utilized in herbal medicinal products, the class of pharmaceutically effective essential oils is considered to exhibit a negligible contribution to pyrrolizidine alkaloid contamination. Within the present investigation, this hypothesis should be scientifically scrutinized. For this purpose, an experimental set-up was chosen that reproduces the typical manufacturing step of hydrodistillation. Essential oils of eucalyptus and lemon were selected exemplarily and spiked with 3 representative pyrrolizidine alkaloids (retrorsine, retrorsine-N-oxide, and lycopsamine), whereupon hydrodistillation was performed. Analysis of the resulting distillates by LC-MS/MS proved that artificially added pyrrolizidine alkaloids were removed completely. Moreover, quantitative pyrrolizidine alkaloid recovery in the aqueous phases was observed. Hence, it was experimentally confirmed that herbal medicinal products employing hydrodistilled essential oils of pharmaceutical quality are intrinsically free of pyrrolizidine alkaloids due to the particularities of their manufacturing process. Furthermore, it can be concluded from theoretical considerations that essential oils produced by cold pressing have a negligible risk of carrying pyrrolizidine alkaloid contamination. Our findings provide a strong indication that the requirement for analytical pyrrolizidine alkaloid testing of essential oils for pharmaceutical use should be fundamentally reconsidered.

Pyrrolizidine Alkaloid Contamination in Medicinal Plants: Regulatory Requirements and Their Impact on Production and Quality Control of Herbal Medicinal Products

Planta Medica ◽  
2021 ◽  
Author(s):  
Barbara Steinhoff
Keyword(s):  
Pyrrolizidine Alkaloids ◽  
Pyrrolizidine Alkaloid ◽  
Daily Intake ◽  
Herbal Drugs ◽  
Herbal Extracts ◽  
Medicinal Products ◽  
Plant Materials ◽  
Herbal Medicinal Products ◽  
Code Of Practice ◽  
Herbal Medicinal

AbstractAgainst the background of potential contamination of medicinal plant materials with pyrrolizidine alkaloids caused by weeds, suppliers of herbal drugs and manufacturers of herbal medicinal products have taken action by establishing a Code of Practice by monitoring potential contamination and by collection of data. In August 2020, the Herbal Medicinal Products Committee, in its new draft public statement, proposed a daily intake of 1.0 µg of pyrrolizidine alkaloids per day for adults in general, also including contaminations of herbal medicinal products. Over the past years, the results of data collections showed a remarkable reduction of the pyrrolizidine alkaloid burden in herbal drugs and herbal extracts. Meanwhile, a stable situation has been achieved for herbal drugs, while further improvement can be observed for herbal extracts. The results indicate that the implemented measures have been efficient and contribute to a continuous and sustainable reduction of pyrrolizidine alkaloid contamination. A permanent limit of 1.0 µg of pyrrolizidine alkaloids per day is considered appropriate to guarantee sufficient availability of batches used for the production of herbal medicinal products. The new Ph.Eur. general chapter 2.8.26 describes, as an example, an analytical procedure suitable for the determination of target pyrrolizidine alkaloids.

scholarly journals In vitro screening of herbal medicinal products for their supportive curing potential in the context of SARS-CoV-2

2021 ◽  
Author(s):  
Hoai Tran ◽  
Philipp Peterburs ◽  
Jan Seibel ◽  
Dimitri Abramov-Sommariva ◽  
Evelyn Lamy
Keyword(s):  
Symptom Relief ◽  
A549 Cells ◽  
Spike Protein ◽  
In Vitro Screening ◽  
Medicinal Products ◽  
Binding Interaction ◽  
Herbal Medicinal Products ◽  
Ifn Γ ◽  
Herbal Medicinal

Background: Herbal medicinal products have a long-standing history of use in the therapy of common respiratory infections. In the COVID-19 pandemic, they may have the potential for symptom relief in non-severe or moderate disease cases. Here we describe the results derived by in vitro screening of five herbal medicinal products with regard to their potential to i) interfere with the binding of the human Angiotensin-converting enzyme 2 (ACE2) receptor with the SARS-CoV-2 Spike S1 protein, ii) modulate the release of the human defensin HBD1 and cathelicidin LL-37 from human A549 lung cells upon Spike S1 protein stimulation and iii) modulate the release of IFN-γ from activated human peripheral blood mononuclear cells (PBMC). The investigated extracts were: Sinupret extract (SINx), Bronchipret thyme-ivy (BRO TE), Bronchipret thyme-primrose (BRO TP), Imupret (IMU), and Tonsipret (TOP). Methods: The inhibitory effect of the herbal medicinal products on the binding interaction of Spike S1 protein and the human ACE2 receptor was measured by ELISA. The effects on intracellular IFN-γ expression in stimulated human PBMCs were measured by flow cytometry. Regulation on HBD1 and LL-37 expression and secretion was assessed in 25d long-term cultured human lung A549 epithelial cells by RT-PCR and ELISA. Results: IMU and BRO TE concentration-dependently inhibited the interaction between spike protein and the ACE2 Receptor. However, this effect was only observed in the cell-free assay at a concentration range which was later on determined as cytotoxic to human PBMC. SINx, TOP and BRO TP significantly upregulated the intracellular expression of antiviral IFNγ from stimulated PBMC. Co-treatment of A549 cells with IMU or BRO TP together with SARS-CoV-2 spike protein significantly upregulated mRNA expression (IMU) and release (IMU and BRO TP) of HBD1 and LL-37 (BRO TP). Conclusions: The in vitro screening results provide first evidence for an immune activating potential of some of the tested herbal medicinal extracts in the context of SARS-CoV-2. Whether these could be helpful in prevention of SARS-CoV-2 invasion or supportive in recovery from SARS-CoV-2 infection needs deeper understanding of the observations.

scholarly journals The potential of herbal extracts to inhibit SARS-CoV-2: a pilot study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Michela Luisa De Pellegrin ◽  
Anette Rohrhofer ◽  
Philipp Schuster ◽  
Barbara Schmidt ◽  
Philipp Peterburs ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Quantitative Polymerase Chain Reaction ◽  
Herbal Medicines ◽  
Vero Cells ◽  
Cell Culture Supernatant ◽  
Herbal Extracts ◽  
Medicinal Products ◽  
Herbal Medicinal Products ◽  
Herbal Medicinal

Abstract Background Herbal medicinal products have a long-standing history of use in the therapy of common respiratory infections. We sought to assess the potential of five validated herbal extracts regarding their ability to restrict SARS-CoV-2 replication in vitro: Bronchipret thyme-ivy (BRO TI), Bronchipret thyme-primrose (BRO TP), Imupret (IMU), Sinupret extract (SINx) and Tonsipret (TOP). Methods Vero cells were incubated with different concentrations of herbal extracts and infected with SARS-CoV-2 for 48 hours. The inhibition of viral replication was assessed by determination of the viral RNA load in the cell culture supernatant using quantitative polymerase chain reaction (qPCR). Results SARS-CoV-2 RNA load was reduced by non-cytotoxic concentrations of BRO-TP (up to approximately 1,000-fold) and, to a lesser extent, IMU and TOP (approximately 10-fold). Conclusions Some herbal extracts showed a promising in vitro effectiveness against SARS-CoV-2, suggesting an antiviral potential of herbal medicinal products. The potential of herbal medicines to restrict SARS-CoV-2 and to treat COVID-19 should be investigated further in a clinical setting.

scholarly journals Novel Insights into Pyrrolizidine Alkaloid Toxicity and Implications for Risk Assessment: Occurrence, Genotoxicity, Toxicokinetics, Risk Assessment–A Workshop Report

Planta Medica ◽  
2021 ◽  
Author(s):  
Dieter Schrenk ◽  
Jörg Fahrer ◽  
Ashley Allemang ◽  
Peter Fu ◽  
Ge Lin ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pyrrolizidine Alkaloids ◽  
Liver Toxicity ◽  
Pyrrolizidine Alkaloid ◽  
International Workshop ◽  
Response Analysis ◽  
Medicinal Products ◽  
Widespread Occurrence ◽  
Animal Data

AbstractThis paper reports on the major contributions and results of the 2nd International Workshop of Pyrrolizidine Alkaloids held in September 2020 in Kaiserslautern, Germany. Pyrrolizidine alkaloids are among the most relevant plant toxins contaminating food, feed, and medicinal products of plant origin. Hundreds of PA congeners with widespread occurrence are known, and thousands of plants are assumed to contain PAs. Due to certain PAsʼ pronounced liver toxicity and carcinogenicity, their occurrence in food, feed, and phytomedicines has raised serious human health concerns. This is particularly true for herbal teas, certain food supplements, honey, and certain phytomedicinal drugs. Due to the limited availability of animal data, broader use of in vitro data appears warranted to improve the risk assessment of a large number of relevant, 1,2-unsaturated PAs. This is true, for example, for the derivation of both toxicokinetic and toxicodynamic data. These efforts aim to understand better the modes of action, uptake, metabolism, elimination, toxicity, and genotoxicity of PAs to enable a detailed dose-response analysis and ultimately quantify differing toxic potencies between relevant PAs. Accordingly, risk-limiting measures comprising production, marketing, and regulation of food, feed, and medicinal products are discussed.

Sign in / Sign up

Export Citation Format

Share Document