Topic Editors

1. Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8370292, Chile
2. Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara 06330, Turkey

Safety and Toxicological Risks of Medicinal Plants and Natural Products: Mechanistic Insights

Abstract submission deadline
closed (15 January 2024)
Manuscript submission deadline
closed (15 April 2024)
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Topic Information

Dear Colleagues,

The plant kingdom comprises a high number of species, producing a variety of bioactive compounds with different chemical scaffolds. According to earlier appraisals, various plant species have been systematically examined pharmacologically and phytochemically. Though currently, the percentage of well characterized species is possibly higher owing to continuing research efforts, it is still possible that there is a huge number of plant compounds that are not well investigated pharmacologically in the plant species described so far. The revived scientific interest in plant-derived drug discovery is paralleled with major scientific and technological advances in significant research fields, with better understanding of diseases and their fundamental mechanisms, advances in screening methods and analytical equipment, increasing number of targets available for testing, and better possibilities for optimization of natural leads using synthetic modification strategies. However, it is clear that the current challenges regarding herbal products must be overcome. These challenges generally include the difficulty of cultivating certain species, unconscious overuse of medicinal and aromatic herbs, purity of herbal drugs, loss of endangered plant species, deforestation and urbanization, quality, safety, efficacy, dosage, and standardization.

Several supporters of medicinal plants contend that products with a long history of popular use are usually safe when used correctly at common therapeutic doses. A critical question is the extent to which the absence of evidence of toxicity could be taken as evidence of safety of medicinal plants or the absence of toxicity. Whether the absence of archives of adverse effects is an indication of lack of toxicity depends on the type of toxic effect and the probability of perceiving such an adverse effect under the environments prevailing in the traditional usage. Acute symptoms and short-term toxic effects are likely to be recognized and associated with medicinal plants. Consequently, the absence of such observations provides some evidence of safety in these certain endpoints. Long-term adverse effects are unlikely to be related to the popular use of a medicine, without an adequately designed epidemiology study is undertaken. Therefore, the absence of evidence of these adverse effects in the context of traditional usage of medicinal plants is not evidence of the absence of the possibility to cause them. As far as drugs are concerned, safety is expected only when the null hypothesis has not been invalidated after being challenged by a correctly designed and comprehensive set of preclinical and clinical studies, which have plenty of statistical power to reject false hypotheses.

We welcome authors from all parts of the world to contribute with articles that evaluate mechanistic insights into preclinical studies for safety assessment and potential toxicity of natural products. We are particularly interested in articles that describe the assessment of toxicological activities in vitro, in vivo, in silico, and cell-based assays and compile this effect using active molecules from natural sources.

This Research Topic provides a venue for authors from various disciplines to disseminate crucial information about the effect of medicinal plants and natural products with safety assessment and potential toxicity. The subtopics to be covered within this collection are listed below, but not limited to:

  • Perspectives (based on systematic reviews) such as predictions, estimations, comparisons;
  • In vivo, in vitro, in silico, and cell-based assays on plants;
  • Clarification of the toxic effect mechanism;
  • Evidenced-based research and clinical trials on natural products related to safety assessment and toxicological properties;
  • Drug delivery systems prepared with natural compounds that reduce side effects and provide targeting and also increase efficiency in cancer studies.

Prof. Dr. Eduardo Sobarzo-Sánchez
Prof. Dr. Esra Küpeli Akkol
Topic Editors

Keywords

  • drug development
  • natural product
  • in vivo
  • in vitro
  • in silico
  • cell-based assay
  • toxicity

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomolecules
biomolecules
5.5 8.3 2011 16.9 Days CHF 2700
Current Issues in Molecular Biology
cimb
3.1 2.4 1999 13.5 Days CHF 2200
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.3 Days CHF 2900
Marine Drugs
marinedrugs
5.4 9.6 2003 14 Days CHF 2900
Molecules
molecules
4.6 6.7 1996 14.6 Days CHF 2700
Plants
plants
4.5 5.4 2012 15.3 Days CHF 2700

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Published Papers (3 papers)

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13 pages, 1701 KiB  
Article
Effect of the Aqueous Extract of Chrysobalanus icaco Leaves on Maternal Reproductive Outcomes and Fetal Development in Wistar Rats
by Natalie Emanuelle Ribeiro Rodrigues, Alisson Rodrigo da Silva Oliveira, Sandrine Maria de Arruda Lima, Daniel Medeiros Nunes, Priscilla Barbosa Sales de Albuquerque, Maria das Graças Carneiro da Cunha, Almir Gonçalves Wanderley, Flavio Manoel Rodrigues da Silva Júnior, José Bruno Nunes Ferreira Silva, Álvaro Aguiar Coelho Teixeira and Teresinha Gonçalves da Silva
Curr. Issues Mol. Biol. 2023, 45(9), 7617-7629; https://doi.org/10.3390/cimb45090479 - 19 Sep 2023
Cited by 1 | Viewed by 932
Abstract
Toxicological studies on medicinal plants are essential to ensure their safety and effectiveness in treating various diseases. Despite the species Chrysobalanus icaco L. being popularly used in the treatment of several diseases due to the pharmacological properties of its bioactive compounds, there are [...] Read more.
Toxicological studies on medicinal plants are essential to ensure their safety and effectiveness in treating various diseases. Despite the species Chrysobalanus icaco L. being popularly used in the treatment of several diseases due to the pharmacological properties of its bioactive compounds, there are few studies in the literature regarding its toxicity regarding reproduction. Therefore, the purpose of this study was to assess the potential embryotoxic and teratogenic effects of the aqueous extract of C. icaco leaves (AECi) on Wistar rats. Animals were given AECi at doses of 100, 200, and 400 mg/kg during the pre-implantation and organogenesis periods. Data were analyzed using ANOVA followed by Tukey’s test and Kruskal–Wallis. Pregnant rats treated during the pre-implantation period showed no signs of reproductive toxicity. Rats that received AECi at 100, 200, and 400 mg/kg during organogenesis did not exhibit any signs of maternal systemic toxicity or significant differences in gestational and embryotoxic parameters. Some skeletal changes were observed in the treated groups. Therefore, it can be suggested that AECi at doses of 100, 200, and 400 mg/kg is safe for treated animals and does not induce reproductive toxicity under the experimental conditions applied, but it also caused low systemic toxicity. Full article
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15 pages, 3049 KiB  
Article
Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function
by Swapna Kannothum Kandy, Madhura Milind Nimonkar, Suravi Sasmita Dash, Bhupesh Mehta and Yogananda S. Markandeya
Mar. Drugs 2022, 20(10), 645; https://doi.org/10.3390/md20100645 - 18 Oct 2022
Cited by 7 | Viewed by 2839
Abstract
Excitotoxicity is known to associate with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, as well as aging, stroke, trauma, ischemia and epilepsy. Excessive release of glutamate, overactivation of glutamate receptors, calcium overload, mitochondrial dysfunction and excessive [...] Read more.
Excitotoxicity is known to associate with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, as well as aging, stroke, trauma, ischemia and epilepsy. Excessive release of glutamate, overactivation of glutamate receptors, calcium overload, mitochondrial dysfunction and excessive reactive oxygen species (ROS) formation are a few of the suggested key mechanisms. Astaxanthin (AST), a carotenoid, is known to act as an antioxidant and protect neurons from excitotoxic injuries. However, the exact molecular mechanism of AST neuroprotection is not clear. Thus, in this study, we investigated the role of AST in neuroprotection in excitotoxicity. We utilized primary cortical neuronal culture and live cell fluorescence imaging for the study. Our results suggest that AST prevents neuronal death, reduces ROS formation and decreases the abnormal mitochondrial membrane depolarization induced by excitotoxic glutamate insult. Additionally, AST modulates intracellular calcium levels by inhibiting peak and irreversible secondary sustained calcium levels in neurons. Furthermore, AST regulates the ionotropic glutamate subtype receptors NMDA, AMPA, KA and mitochondrial calcium. Moreover, AST decreases NMDA and AMPA receptor protein expression levels, while KA remains unaffected. Overall, our results indicate that AST protects neurons from excitotoxic neuronal injury by regulating ionotropic glutamate receptors, cytosolic secondary calcium rise and mitochondrial calcium buffering. Hence, AST could be a promising therapeutic agent against excitotoxic insults in neurodegenerative diseases. Full article
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9 pages, 1803 KiB  
Article
In Vitro Toxicity Evaluation of Carrageenan on Cells and Tissues of the Oral Cavity
by Babatunde Y. Alli, Akshaya Upadhyay, Yuli Zhang, Belinda Nicolau and Simon D. Tran
Mar. Drugs 2022, 20(8), 502; https://doi.org/10.3390/md20080502 - 03 Aug 2022
Cited by 1 | Viewed by 1781
Abstract
Carrageenan is a highly potent anti-human papillomavirus (HPV) agent with the potential for formulation as a mouthwash against oral HPV infection. However, its toxic effect on tissues of the oral cavity is currently unknown. This study aims to evaluate the safety of carrageenan [...] Read more.
Carrageenan is a highly potent anti-human papillomavirus (HPV) agent with the potential for formulation as a mouthwash against oral HPV infection. However, its toxic effect on tissues of the oral cavity is currently unknown. This study aims to evaluate the safety of carrageenan on human cells and tissues of the oral cavity. Human salivary gland cells and reconstructed human oral epithelium (RHOE) were used for this in vitro study. The cells were subjected to 0.005–100 µg/mL of carrageenan for 4, 12, and 24 h in quadruplicate. RHOE were exposed to 100 µg/mL of carrageenan for 24 h in triplicate and stained with hematoxylin/eosin for histological analyses. All experiments had saline and 1% sodium dodecyl sulphate (SDS) as negative and positive controls, respectively. Carrageenan tissue toxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to quantify cell viability. Tissue toxicity was further evaluated histologically by an oral pathologist to assess morphological changes. Our data showed that carrageenan did not significantly decrease cell and tissue viability when compared to the positive control. The histological evaluation of the RHOE also showed no loss of viability of the carrageenan-treated sample compared to untreated tissue. In contrast, 1% SDS-treated RHOE showed extensive tissue destruction. Our experiments suggest that carrageenan is safe for use in the oral cavity. Full article
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