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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Toxicology and Public Health".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 28937

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Dr. Oliver Grundmann

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Guest Editor

Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
Interests: forensic & clinical toxicology; natural products pharmacology & toxicology; dietary supplement quality & safety; pharmacology & toxicology of psychoactive drugs; epidemiology of drug use & abuse
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Special Issue Information

Dear Colleagues,

The use of medicinal plants as part of traditional medical systems remains a staple of healthcare in many developing and developed countries to this day. Despite the contributions and advances of Western medical practices, both traditional systems of medicine and herbal supplements remain popular and readily accessible to the general public. In many cases, they form the basis of medical practice in regions where Western conventional medicine is not affordable. In its most recent report, the World Health Organization acknowledges a lack of policy and regulatory oversight of complementary and traditional medicines, including herbal medicines. As such, the risk of toxicity associated with the use of medicinal plants and herbal supplements often is unknown based on a lack of safety, quality, and effectiveness.

In addition, the traditional and modern uses of herbal medicines and supplements are often used in conjunction with Western pharmacotherapy, leading to potential drug–herb interactions. Some of these interactions have been studied in vitro, although their clinical relevance often remains unknown.

This Special Issue is focused on the toxicity associated with medicinal plants and herbal supplements, with an emphasis on particular mechanisms and associated compounds, clinical relevance, and potential improvement of quality to resolve specific adverse effects. Clinical investigations are of particular interest, but pre-clinical in vitro and in vivo experiments with direct implications and translational value are also welcome. Analytical research that provides insights into improving the quality of herbal medicines and supplements to establish Good Manufacturing Practices (GMPs) are of interest if they include descriptions of validated methods. Reviews will be considered upon inquiry by the authors with the Guest Editor.

Prof. Dr. Oliver Grundmann
Guest Editor

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Keywords

herbal supplements
medicinal plants
herb–drug interactions
toxicity and adverse effects

Published Papers (6 papers)

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Research

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11 pages, 22097 KiB

Open AccessArticle

BST204 Protects Dexamethasone-Induced Myotube Atrophy through the Upregulation of Myotube Formation and Mitochondrial Function

by Ryuni Kim, Hyebeen Kim, Minju Im, Sun Kyu Park, Hae Jung Han, Subin An, Jong-Sun Kang, Sang-Jin Lee and Gyu-Un Bae

Int. J. Environ. Res. Public Health 2021, 18(5), 2367; https://doi.org/10.3390/ijerph18052367 - 01 Mar 2021

Cited by 6 | Viewed by 3128

Abstract

BST204 is a purified ginseng dry extract that has an inhibitory effect on lipopolysaccharide-induced inflammatory responses, but its effect on muscle atrophy is yet to be investigated. In this study, C2C12 myoblasts were induced to differentiate for three days followed by the treatment of dexamethasone (DEX), a corticosteroid drug, with vehicle or BST204 for one day and subjected to immunoblotting, immunocytochemistry, qRT-PCR and biochemical analysis for mitochondrial function. BST204 alleviates the myotube atrophic effect mediated by DEX via the activation of protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling. Through this pathway, BST204 suppresses the expression of muscle-specific E3 ubiquitin ligases contributing to the enhanced myotube formation and enlarged myotube diameter in DEX-treated myotubes. In addition, BST204 treatment significantly decreases the mitochondrial reactive oxygen species production in DEX-treated myotubes. Furthermore, BST204 improves mitochondrial function by upregulating the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in DEX-induced myotube atrophy. This study provides a mechanistic insight into the effect of BST204 on DEX-induced myotube atrophy, suggesting that BST204 has protective effects against the toxicity of a corticosteroid drug in muscle and promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy. Full article

(This article belongs to the Special Issue Toxicity of Medicinal Plants and Herbal Supplements)

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17 pages, 7747 KiB

Open AccessArticle

Indol-3-Carbinol and Quercetin Ameliorate Chronic DSS-Induced Colitis in C57BL/6 Mice by AhR-Mediated Anti-Inflammatory Mechanisms

by Sina Riemschneider, Maximilian Hoffmann, Ulla Slanina, Klaus Weber, Sunna Hauschildt and Jörg Lehmann

Int. J. Environ. Res. Public Health 2021, 18(5), 2262; https://doi.org/10.3390/ijerph18052262 - 25 Feb 2021

Cited by 35 | Viewed by 5119

Abstract

Inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, are multifactorial inflammatory disorders of the gastrointestinal tract, characterised by abdominal cramps, bloody diarrhoea, and anaemia. Standard therapies, including corticosteroids or biologicals, often induce severe side effects, or patients may develop resistance to those therapies. Thus, new therapeutic options for IBD are urgently needed. This study investigates the therapeutic efficacy and safety of two plant-derived ligands of the aryl hydrocarbon receptor (AhR), quercetin (Q), and indol-3-carbinol (I3C), using a translationally relevant mouse model of IBD. Q and I3C are administered by gavage to C57BL/6 wild-type or C57BL/6 Ahr^-/- mice suffering from chronic colitis, induced by dextran sulphate sodium (DSS). The course of the disease, intestinal histopathological changes, and in-situ immunological phenotype are scored over 25 days. Our results show that both Q and I3C improved significantly clinical symptoms in moderate DSS colitis, which coincides with a significantly reduced histopathological score. Even in severe DSS colitis I3C, neither Q nor the therapy control 6-thioguanine (6-TG) can prevent a fatal outcome. Moreover, treatment with Q or I3C restored in part DSS-induced loss of epithelial integrity by induction of tight-junction proteins and reduced significantly gut inflammation, as demonstrated by colonoscopy, as well as by immunohistochemistry revealing lower numbers of neutrophils and macrophages. Moreover, the number of Th17 cells is significantly reduced, while the number of Treg cells is significantly increased by treatment with Q or I3C, as well as 6-TG. Q- or I3C-induced amelioration of colitis is not observed in Ahr^-/- mice suggesting the requirement of AhR ligation and signalling. Based on the results of this study, plant-derived non-toxic AhR agonists can be considered promising therapeutics in IBD therapy in humans. However, they may differ in terms of efficacy; therefore, it is indispensable to study the dose-response relationship of each individual AhR agonist also with regard to potential adverse effects, since they may also exert AhR-independent effects. Full article

(This article belongs to the Special Issue Toxicity of Medicinal Plants and Herbal Supplements)

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13 pages, 673 KiB

Open AccessArticle

Nutritional and 13-Week Subchronic Toxicological Evaluation of Lignosus rhinocerotis Mycelium in Sprague-Dawley Rats

by I-Chen Li, Bi-Hua Yang, Jing-Yi Lin, Shan Lin and Chin-Chu Chen

Int. J. Environ. Res. Public Health 2021, 18(3), 1271; https://doi.org/10.3390/ijerph18031271 - 31 Jan 2021

Cited by 3 | Viewed by 2559

Abstract

Lignosus rhinocerotis (Tiger’s Milk mushroom) is a novel mushroom with sclerotium belonging to the Polyporaceae family and has been reported widely to possess anti-cancer, anti-cough, antioxidant, gastro-protective, immuno-modulating, and neurite-stimulating properties. As numerous studies have proven the tremendous medicinal values of L. rhinocerotis, it is necessary to understand its nutrition as well as its safety for the recipient. Previous research on L. rhinocerotis has mainly focused on the naturally occurring sclerotium and may have overlooked mushroom mycelia from submerged liquid fermentation, which ensures a high uniform quantitative biomass production as well as a high biological value. Hence, this is the first report on the evaluation of nutrition and 13-week repeated oral toxicity of L. rhinocerotis mycelium (LRM). The LRM powder contained 9.0 ± 4.2% moisture, 1.9 ± 1.3% ash, 1.6 ± 2.2% crude lipid, 8.4 ± 5.3% crude protein, 79.3 ± 4.6% carbohydrate, and 364 kcal/100 g energy. The total free amino acid ranged from 349 to 5636 mg/100 g and the umami index of freeze-dried LRM powder was 0.37. For safety assessment, ninety-six rats were divided into four groups, each consisting of twelve male and twelve female rats. Test articles were administered by oral gavage to rats at 850, 1700, and 3400 mg/kg body weight/day for 13 weeks and reverse osmosis water was used as the control. All animals survived to the end of the study. During the experiment period, no abnormal changes were observed in clinical signs, body weight, or ophthalmological examinations. No adverse or test article-related differences were found in urinalysis, hematology, or serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. According to the above results, the no-observed-adverse-effect level (NOAEL) of L. rhinocerotis was identified to be greater than 3400 mg/kg body weight (BW)/day in Sprague–Dawley rats. Full article

(This article belongs to the Special Issue Toxicity of Medicinal Plants and Herbal Supplements)

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13 pages, 533 KiB

Open AccessArticle

Evaluation of the Mitragynine Content, Levels of Toxic Metals and the Presence of Microbes in Kratom Products Purchased in the Western Suburbs of Chicago

by Walter C. Prozialeck, Joshua R. Edwards, Peter C. Lamar, Balbina J. Plotkin, Ira M. Sigar, Oliver Grundmann and Charles A. Veltri

Int. J. Environ. Res. Public Health 2020, 17(15), 5512; https://doi.org/10.3390/ijerph17155512 - 30 Jul 2020

Cited by 24 | Viewed by 5515

Abstract

Kratom (Mitragyna speciosa, Korth) is a tree-like plant that is indigenous to Southeast Asia. Kratom leaf products have been used in traditional folk medicine for their unique combination of stimulant and opioid-like effects. Kratom is being increasingly used in the West for its reputed benefits in the treatment of pain, depression and opioid use disorder. Recently, the United States Food and Drug Administration and Centers for Disease Control have raised concerns regarding the contamination of some kratom products with toxic metals (Pb and Ni) and microbes such as Salmonella. To further explore this issue, eight different kratom products were legally purchased from various “head”/”smoke” shops in the Western Suburbs of Chicago and then tested for microbial burden, a panel of metals (Ni, Pb, Cr, As, Hg, Cd), and levels of the main psychoactive alkaloid mitragynine. All of the samples contained significant, but variable, levels of mitragynine (3.9–62.1 mg/g), indicating that the products were, in fact, derived from kratom. All but two of the samples tested positive for the presence of various microbes including bacteria and fungi. However, none of the samples tested positive for Salmonella. Seven products showed significant levels of Ni (0.73–7.4 µg/g), Pb (0.16–1.6 µg/g) and Cr (0.21–5.7 µg/g) while the other product was negative for metals. These data indicate that many kratom products contain variable levels of mitragynine and can contain significant levels of toxic metals and microbes. These findings highlight the need for more stringent standards for the production and sale of kratom products. Full article

(This article belongs to the Special Issue Toxicity of Medicinal Plants and Herbal Supplements)

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18 pages, 953 KiB

Open AccessArticle

Acute and Subchronic Oral Toxicity of Oil Palm Puree in Sprague–Dawley Rats

by Zaida Zainal, Augustine Ong, Choo Yuen May, Sui Kiat Chang, Afiqah Abdul Rahim and Huzwah Khaza’ai

Int. J. Environ. Res. Public Health 2020, 17(10), 3404; https://doi.org/10.3390/ijerph17103404 - 13 May 2020

Cited by 11 | Viewed by 3172

Abstract

Palm puree is rich in antioxidants and is produced via blending various proportions of mesocarp fibre and crude palm oil. The aim of this study was to assess the acute and subchronic toxicity of palm puree in male and female Sprague–Dawley rats. For the acute toxicity study, animals administered single palm-puree doses (2000 mg kg⁻¹) by gavage were observed daily for 14 d. For the subchronic toxicity study, the rats were administered 500, 1000, or 2000 mg kg⁻¹ palm puree daily for 28 d. We evaluated body and organ weights; performed haematological, biochemical, and histopathological analyses of blood and organ samples during and after treatment; and calculated the oral no-observed-adverse-effect level (NOAEL). The toxicity studies showed no signs of toxicity or mortality. The haematological, biochemical, and histopathological analyses and body and organ weights indicated no evidence of substantial toxicity at any dose of palm puree. The oral lethal dose and NOAEL for the palm puree were greater than 2000 mg kg⁻¹ d⁻¹ over 28 d. To the best of our knowledge, the present study is the first to confirm the safety of palm puree as a novel functional food. These encouraging results warrant further studies to elucidate its potential for pharmaceutical formulations. Full article

(This article belongs to the Special Issue Toxicity of Medicinal Plants and Herbal Supplements)

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Review

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20 pages, 468 KiB

Open AccessReview

African Herbal Medicines: Adverse Effects and Cytotoxic Potentials with Different Therapeutic Applications

by Kunle Okaiyeto and Oluwafemi O. Oguntibeju

Int. J. Environ. Res. Public Health 2021, 18(11), 5988; https://doi.org/10.3390/ijerph18115988 - 02 Jun 2021

Cited by 42 | Viewed by 7691

Abstract

The African continent is naturally endowed with various plant species with nutritional and medicinal benefits. About 80% of the people in developing countries rely on folk medicines to treat different diseases because of indigenous knowledge, availability, and cost-effectiveness. Extensive research studies have been conducted on the medicinal uses of African plants, however, the therapeutic potentials of some of these plants has remained unexploited. Over the years, several studies have revealed that some of these African floras are promising candidates for the development of novel drugs. Despite the plethora of studies on medicinal plant research in Africa, there is still little scientific data supporting the folkloric claims of these plants. Besides, safety in the use of folk medicines has been a major public health concern over the year. Therefore, it has become mandatory that relevant authority should take measures in safeguarding the populace on the use of herbal mixtures. Thus, the present review extracted relevant information from different scientific databases and highlighted some problems associated with folk medicines, adverse effects on reproductive systems, issue about safety due to the toxicity of some plants and their toxicity effects with potential therapeutic benefits are discussed. Full article

(This article belongs to the Special Issue Toxicity of Medicinal Plants and Herbal Supplements)

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