Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety.

AREAS COVERED: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and Caenorhabditis elegans. These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and C. elegans assays evaluate neurobehavioral responses. The paper also provides an account of the selection of botanical case studies based on expert judgment and existing neuroactivity/toxicity information. The proposed battery of assays will be tested with these case studies to evaluate their utility for neurotoxicity screening. EXPERT OPINION: The complexity of botanicals necessitates the use of multiple NAMs for effective neurotoxicity screening. This paper discusses the evaluation of methodologies to develop a robust framework for evaluating botanical safety, including complex neuronal models and key neurodevelopmental process assays. It aims to establish a comprehensive screening framework.

Herbal remedies as a potential cause of hypoadrenalism.

A 37-year-old woman presented with nausea, vomiting and headache. She was found to be profoundly hyponatraemic with a sodium of 121 mmol/L, which deteriorated following a fluid challenge. An initial hyponatraemia screen identified adrenal insufficiency, with cortisol of 48 nmol/L. History confirmed she had been taking the herbal plant, ashwagandha. After 3 days of fluid restriction and steroid replacement, her sodium returned to normal (139 mmol/L). This article reviews the possible harmful effects of over-the-counter herbal remedies and highlights the importance of considering a wide differential diagnosis in patients presenting with non-specific symptoms.

Adverse events of herbal decoction: A systematic review and meta-analysis over past 10 years.

BACKGROUND: Herbal decoctions (HDs) are the oldest and most common herbal medicine formulations. Different HDs exist, and some consumers are concerned that they may become contaminated during manufacturing. Therefore, the need for a safety assessment of HDs has been raised. This study aimed to investigate the adverse events (AEs) associated with HDs by comprehensively analyzing randomized controlled trials (RCTs) using systematic reviews and meta-analyses. METHODS: A systematic search was conducted on PubMed, Embase, and the Cochrane Library for articles published up to November 2022. The included RCTs compared HDs with other treatments published between 2013 and 2022, and the risk of bias was assessed using RevMan 5.4. Meta-analyses of the number of AEs associated with HDs reported in the included RCTs were also performed. RESULTS: The systematic review included 26 RCTs, and the meta-analysis included 17 RCTs that reported AEs. The meta-analysis comparing HDs with active controls showed that both the number of AEs (14 studies; risk ratio (RR)= 0.50 cases, 95 % confidence interval (CI) [0.29, 0.88]; I2 = 42 %) and the number of patients who complained of AEs (seven studies; RR=0.51 patients, 95 % CI [0.28, 0.94]; I2 =9 %) were fewer in the HDs group than in the active control groups. CONCLUSION: This study showed that HDs are safer than other conventional medications based on the results of qualitative and quantitative syntheses of RCTs.

Use of herbal medication in the perioperative period: Potential adverse drug interactions.

Use of herbal medications and supplements has experienced immense growth over the last two decades, with retail sales in the USA exceeding $13 billion in 2021. Since the Dietary Supplement Health and Education Act (DSHEA) of 1994 reduced FDA oversight, these products have become less regulated. Data from 2012 shows 18% of U.S. adults used non-vitamin, non-mineral natural products. Prevalence varies regionally, with higher use in Western states. Among preoperative patients, the most commonly used herbal medications included garlic, ginseng, ginkgo, St. John's wort, and echinacea. However, 50-70% of surgical patients fail to disclose their use of herbal medications to their physicians, and most fail to discontinue them preoperatively. Since herbal medications can interact with anesthetic medications administered during surgery, the American Society of Anesthesiologists (ASA) and the American Association of Nurse Anesthetists (AANA) recommend stopping herbal medications 1-2 weeks before elective surgical procedures. Potential adverse drug effects related to preoperative use of herbal medications involve the coagulation system (e.g., increasing the risk of perioperative bleeding), the cardiovascular system (e.g., arrhythmias, hypotension, hypertension), the central nervous system (e.g., sedation, confusion, seizures), pulmonary (e.g., coughing, bronchospasm), renal (e.g., diuresis) and endocrine-metabolic (e.g., hepatic dysfunction, altered metabolism of anesthetic drugs). During the preoperative evaluation, anesthesiologists should inquire about the use of herbal medications to anticipate potential adverse drug interactions during the perioperative period.

Safety Aspects of Herb Interactions: Current Understanding and Future Prospects.

BACKGROUND: The use of herbal medicines is on the rise throughout the world due to their perceived safety profile. However, incidences of herb-drug, herb-herb and herb-food interactions considering safety aspects have opened new arenas for discussion. OBJECTIVE: The current study aims to provide comprehensive insights into the various types of herb interactions, the mechanisms involved, their assessment, and historical developments, keeping herbal safety at the central point of discussion. METHODS: The authors undertook a focused/targeted literature review and collected data from various databases, including Science Direct, Wiley Online Library, Springer, PubMed, and Google Scholar. Conventional literature on herbal remedies, such as those by the WHO and other international or national organizations. RESULTS: The article considered reviewing the regulations, interaction mechanisms, and detection of herb-herb, herb-drug and herb-food interactions in commonly used yet vital plants, including Glycyrrhiza glabra, Mentha piperita, Aloe barbadensis, Zingiber officinale, Gingko biloba, Withania somnifera, etc. The study found that healthcare professionals worry about patients not informing them about their herbal prescriptions (primarily used with conventional treatment), which can cause herb-drug/herb-food/herb-herb interactions. These interactions were caused by altered pharmacodynamic and pharmacokinetic processes, which might be explained using in-vivo, in-vitro, in-silico, pharmacogenomics, and pharmacogenetics. Nutrivigilance may be the greatest method to monitor herb-food interactions, but its adoption is limited worldwide. CONCLUSION: This article can serve as a lead for clinicians, guiding them regarding herb-drug, herb-food, and herb-herb interactions induced by commonly consumed plant species. Patients may also be counseled to avoid conventional drugs, botanicals, and foods with a restricted therapeutic window.

Changing Trends Towards Herbal Supplements: An Insight into Safety and Herb-drug Interaction.

Herbs have been used as sustenance and medicine for a very long time, often in conjunction with other prescribed medications. Even though they are thought to be natural and secure, many of these herbs can interact with other medications and cause potentially dangerous adverse effects or decrease the benefits of the medication. The complex and diverse pharmacological functions carried out by the active ingredients in herbs unavoidably alter the pharmacokinetics of chemical drugs when administered in vivo. Drug transporter expression has a direct impact on how medications are absorbed, distributed, metabolized, and excreted in living organisms. Changes in substrate pharmacokinetics can affect the effectiveness and toxicity of a drug when the active ingredients of a herb inhibit or stimulate the expression of transporters. By reviewing published clinical and preclinical studies, this review aims to raise awareness of herbdrug interactions and discuss their evidence-based mechanisms and clinical consequences. More clinical information on herb-drug interactions is required to make choices regarding patient safety as the incidence and severity of herb-drug interactions are rising due to an increase in the use of herbal preparations globally.This review seeks to increase understanding of herb-drug interactions and explore their evidence-based mechanisms and clinical implications by reviewing published clinical and preclinical studies. The incidence and severity of herb-drug interactions are on the rise due to an increase in the use of herbal preparations worldwide, necessitating the need for more clinical data on these interactions in order to make decisions regarding patient safety. Healthcare workers and patients will become more alert to potential interactions as their knowledge of pharmacokinetic herb-drug interactions grows. The study's objective is to raise readers' awareness of possible interactions between herbal supplements and prescription medications who regularly take them.

["Herbalist" supplements maliciously expanding from Mexico to the world. Artriking and company]. / Complementos "herbolarios" expandiéndose maliciosamente de México para el mundo. Artriking y compañíal.

This letter aims to inform the medical community about herbal supplements that have steroidal and non-steroidal drugs hidden in their formulation, entailing risks to the health of consumers, in addition to the fact that they are not regulated at the local level and the producers of these supplements try to sell them internationally, which would bring serious consequences, since it would become a serious global health problem; these supplements have provoked Cushing's syndrome, diabetes mellitus, sepsis, pneumonitis and invasive helminthiasis.

La presente carta pretende informar a la comunidad médica sobre los complementos herbolarios que tienen de manera oculta en su formulación fármacos esteroideos y no esteroideos, lo cual conlleva riesgos a la salud de los consumidores, además de que no hay una regulación de los mismos a nivel local y quienes los producen buscan que se diseminen en forma global, lo cual traería consecuencias graves, dado que se convertiría en un problema de salud pública mundial; estos complementos han condicionado síndrome de Cushing, diabetes mellitus, sepsis, neumonitis y helmintiasis invasivas.

[Dangerous herbal preparations being sold by web shops]. / Gevaarlijke kruidenpreparaten te koop via de webshops.

BACKGROUND: A large number of herbal preparations are offered on the internet. Some of these may contain substances not listed on the label. When these are illegal "regular" drugs, this can lead to serious side effects. CASE DESCRIPTION: In January 2021, The Netherlands Pharmacovigilance Centre Lareb received 4 reports of side effects after using the herbal preparation Montalin® from Indonesia. Laboratory analysis showed that effective amounts of paracetamol and meloxicam were also present in this herbal preparation. These have been added illegally and are not listed on the packaging. The five web shops that sold this product were ordered to immediately stop trading by order of the Dutch Food and Consumer Product Safety Authority (NVWA). CONCLUSION: Consumers should be careful when purchasing herbal preparations over the internet. It is not always clear what is in it. Certainly if a clear effect is experienced, it may be that (illegally) effective amounts of pharmacologically active substances have been added.

Consumption of nephrotoxic plants among chronic hemodialysis patients in the Eastern region of Morocco: A multicentric cross-sectional study.

ETHNOPHARMACOLOGICAL RELEVANCE: The consumption of nephrotoxic plants is quite frequent in Morocco and could explain the high prevalence of indeterminate nephropathy in patients with End-Stage Kidney Disease (ESKD). AIM OF THE STUDY: to determine, in a population of chronic hemodialysis (CHD) patients and before the occurrence of ESKD, the prevalence of the use of nephrotoxic plants, in particular, Aristolochia longa L. (Bereztam) and the etiological role of plants in the rapid progression of known and unknown nephropathy toward the end stage of chronic hemodialysis. MATERIALS AND METHODS: This was a multicentric cross-sectional study spread over 12 months (May 2019-May 2020), carried out in public hemodialysis centers in the eastern region of Morocco. Clinical data were collected from medical records. Herbal and sociodemographic data were collected from a detailed and precise interview with each enrolled CHD patient. RESULTS: A total of 404 CHD patients participated in the study. 71.5%, had used medicinal plants before the occurrence of ESKD and 32.9% had indeterminate nephropathy. Among the plants consumed, we identified plants whose kidney toxicity was well demonstrated, mainly Rhamnus alaternus L. (Mlilas) in 66.7%, Artemisia herba alba Asso (Chih) in 54.32%, Aristolochia longa L.(Bereztam) in 52.6%, and Rubia tinctorum L. (Fowa) in 47.4%. 27.7% of CHD patients had presented complications following the use of the plants before the occurrence of ESKD. In multivariate analysis, the use of plants to treat digestive disorders (OR 9.57; 95%CI [4.49-20.37], P < 0.001) and asthenia associated with anemia (OR 8.59; 95%CI [3.92-18.81], P < 0.001), as well as side effects observed after taking the plants (OR 4; 95%CI [1.09, 14.7], P = 0.03), were identified as significant risk factors for the occurrence of severe indeterminate nephropathy. CONCLUSIONS: This study showed the high prevalence of consumption of nephrotoxic herbs which may be the root cause of chronic renal failure in CHD patients.

Herbal and Dietary Supplements-Induced Liver Injury in Latin America: Experience From the LATINDILI Network.

BACKGROUND: Herbal and dietary supplements (HDS) consumption, a growing cause of hepatotoxicity, is a common practice among Latin-American populations. OBJECTIVES: To evaluate clinical, laboratory features and outcome in HDS-hepatotoxicity included in the Latin America-Drug Induced Liver Injury (LATINDILI) Network. METHODS: A total of 29 adjudicated cases of HDS hepatotoxicity reported to the LATINDILI Network from October 2011 through December 2019 were compared with 322 DILI cases due to conventional drugs and 16 due to anabolic steroids as well as with other series of HDS-hepatotoxicity. RESULTS: From 367 DILI cases, 8% were attributed to HDS. An increasing trend in HDS-hepatotoxicity was noted over time (p = .04). Camellia sinensis, Herbalife® products, and Garcinia cambogia, mostly used for weight loss, were the most frequently adjudicated causative agents. Mean age was 45 years (66% female). Median time to onset was 31 days. Patients presented typically with hepatocellular injury (83%) and jaundice (66%). Five cases (17%) developed acute liver failure. Compared to conventional medications and anabolic steroids, HDS hepatotoxicity cases had the highest levels of aspartate and alanine transaminase (p = .008 and p = .021, respectively), had more re-exposure events to the culprit HDS (14% vs 3% vs 0%; p = .026), and had more severe and fatal/liver transplantation outcomes (21% vs 12% vs 13%; p = .005). Compared to other DILI cohorts, less HDS hepatotoxicity cases in Latin America were hospitalized (41%). CONCLUSIONS: HDS-hepatotoxicity in Latin-America affects mainly young women, manifests mostly with hepatocellular injury and is associated with higher frequency of accidental re-exposure. HDS hepatotoxicity is more serious with a higher chance of death/liver transplantation than DILI related to conventional drugs.

Garlic constituents for cancer prevention and therapy: From phytochemistry to novel formulations.

Garlic (Allium sativum L.) is one of the oldest plants cultivated for its dietary and medicinal values. This incredible plant is endowed with various pharmacological attributes, such as antimicrobial, antiarthritic, antithrombotic, antitumor, hypoglycemic, and hypolipidemic activities. Among the various beneficial pharmacological effects of garlic, the anticancer activity is presumably the most studied. The consumption of garlic provides strong protection against cancer risk. Taking into account the multi-targeted actions and absence of considerable toxicity, a few active metabolites of garlic are probably to play crucial roles in the killing of cancerous cells. Garlic contains several bioactive molecules with anticancer actions and these include diallyl trisulfide, allicin, diallyl disulfide, diallyl sulfide, and allyl mercaptan. The effects of various garlic-derived products, their phytoconstituents and nanoformulations have been evaluated against skin, prostate, ovarian, breast, gastric, colorectal, oral, liver, and pancreatic cancers. Garlic extract, its phytocompounds and their nanoformulations have been shown to inhibit the different stages of cancer, including initiation, promotion, and progression. Besides, these bioactive metabolites alter the peroxidation of lipid, activity of nitric oxide synthetase, nuclear factor-κB, epidermal growth factor receptor, and protein kinase C, cell cycle, and survival signaling. The current comprehensive review portrays the functions of garlic, its bioactive constituents and nanoformulations against several types of cancers and explores the possibility of developing these agents as anticancer pharmaceuticals.

Unpredictable adverse effects of herbal products.

Herbal products are being increasingly used all over the world for preventive and therapeutic purposes because of the belief of their safety. They have become an important part of health care system in many countries since they can easily be purchased in the health food stores or online. However, the lack of sufficient study on their efficacy and toxicity, inadequate controls of their availability, reduce their safety. Unlike conventional drugs, herbal products are not regulated for purity and potency. Herbal products contain substances which can induce or inhibit enzymes that take part in drug metabolism. Therefore the concurrent use of drugs with some medicinal plants can cause serious adverse effects and can also decrease the efficacy of the therapy. Particularly, drugs with narrow therapeutic index and plants which can affect drug metabolizing enzymes when used together, may lead to unpredictable adverse reactions. Impurities, contaminants and adulterants found in the herbal products, are the most common malpractises in herbal raw-material trade. In this review the unpredictable adverse effects of herbal products due to their possible interactions with drugs and also due to the adulteration and contamination with prohibited chemicals will be discussed in detail.

Teacher plants - Indigenous Peruvian-Amazonian dietary practices as a method for using psychoactives.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous groups of the Amazon have developed intricate methods for the application of psychoactives, among which particularly the dieta or diet method of Peruvian-Amazonian traditional medicine stands out. It is a retreat-like intervention involving lengthy periods of social, behavioural, and alimentary restrictions, while ingesting specially prepared plant substances. The interplay of the dietary conditions and plants ingested sensitizes the dieter to receive healing, strength, guidance, and knowledge. From a clinical scientific point of view, the method has remained largely underexplored, but seems more pertinent than ever given the increasing interest in Amazonian psychoactive preparations including ayahuasca (Banisteriopsis caapi) and the burgeoning field of psychedelic-assisted therapies in general. AIM OF THE STUDY: This study offers a descriptive account and emic interpretation of the Peruvian-Amazonian dieta. More specifically we document in detail the procedure, its context and purpose of application, effects, modes of action, adverse effects, and risks, from the perspectives of a sample of Peruvian traditional healers. The Peruvian-Amazonian dieta is a multi-purpose method for making use of medicinal plants, many of which (but not all), are psychoactive; the current work especially focuses on its therapeutic applications in conjunction with psychoactives. METHODS: We interviewed 16 healers working in the Ucayali, San Martín, and Loreto provinces of Peru using a semi-structured interview approach. Interviews were audio-recorded and transcribed verbatim. The extensive data derived from these interviews were analysed by means of computer-assisted manifest qualitative content analysis using a theory-advancing approach. Over 500 coded text segments were categorized, resulting in 7 main theme clusters and corresponding sub-themes. RESULTS: The interviewed healers described a complex intervention with multifaceted applications (treatment, prevention, training) and effects in various domains (body, mind, spirit, energy). The process was portrayed as transformative, with benefits attributed to the effects of the so-called teacher plants in conjunction with the diet's conditions, along with the skill of the healer guiding the intervention. Further, a detailed risk assessment revealed sophisticated safety measures and tools designed to address adverse responses. The importance of adequate training of the healer that administers the diet was particularly highlighted in this context. CONCLUSIONS: The dieta is a central therapeutic concept and tool in Peruvian-Amazonian traditional medicine and a unique method for using psychoactive plants. Multidisciplinary health research that includes traditional treatment methods from Indigenous cultures, Amazonian and other, should not be neglected in the current global interest in psychedelic therapies; such research may in the long-term contribute to a more inclusive psychedelic research paradigm as well as healthcare practice in countries where rich traditional healing systems exist, and perhaps beyond. It may also contribute to the recognition of the Indigenous healers as not only historical forerunners, but also current leading experts in psychedelic medicine.

Potential propensity of traditional herbal materials ingested by collegiate athletes in South China for their consuming health care.

ABSTRACT: In south China, traditional herbal medicines have been widely used as functional foods or dietary supplements for daily health care. Many plant-derived chemical substances with biological activity are inadvertently ingested by collegiate athletes daily through canton-style herbal tea or herbal slow-cooked soup. In the view of the complexity of herbal ingredients, it is still no full survey reported for the sports risk of plant-derived sports doping. This research is firstly a descriptive statistical analysis. Collegiate athletes with different socio-economic characteristics from medical colleges in 3 different regions in China participated in the questionnaire survey. Three survey forms, including the oral interview, email inquiry, handing out and recovering the questionnaires in live, were developed and performed by researchers. It was first found that collegiate athletes resorted to some traditional herbal materials to protect their health care that there were regional differences (P < .01). Collegiate athletes with Health Fitness and Traditional Wushu as their sports expertise showed a higher frequency of recognition or ingestion in the use of traditional herbal materials (P < .01), while their different living types and cuisine preferences did not seem to be associated with the ingestion frequency of traditional herbal materials. In addition, in the view of the significant differences in the use of herbal preparations to relieve sports stress among young athletes in different regions (P < .01), the findings strongly suggested that athletes should strictly control their use of various herbal preparations during sports training and competition, including herbal wines, herbal oils, topical plasters, analgesic tablets.

Use of medicinal plants by cancer patients at the National Institute of Oncology, Rabat: a cross-sectional survey.

INTRODUCTION: the use of medicinal plants has increased significantly in recent years. According to the World Health Organization, 80% of the world's population uses medicinal plants to treat themselves. Our study aims to estimate the prevalence of medicinal plant use by cancer patients, list the different plants and identify their adverse effects cited by users and their reported efficacy. METHODS: this study was realised among 100 patients via a questionnaire with 14-items. Socio-economic and clinical characteristics have been analysed. The bivariate and multivariate analyses have been used to demonstrate the association between the socio-demographic characteristics of the participants, the duration of the disease and the use of medicinal plants. RESULTS: 45% of participants used medicinal plants. The most commonly reported reason for using medicinal plants was cancer cure (22%). During this study, 32 plants were identified. The Honey was the most commonly used (25%), thyme was also consumed at 15%, fenugreek at 13% and garlic at 7%. According to the multivariate analysis, the residence is predictor of medicinal plant use, urban residents used medicinal plants more than rural patients with an OR: 3,098, IC, 95%: [1,183-8,113] and P = 0,021. Fifty patients reported the moderate efficacy of the use of medicinal plants, and 20% described some side effects such as abdominal pain in 34%. CONCLUSION: in order to avoid any interaction with oncological drugs and to improve their effectiveness, a great importance must be given to information, education and awareness sessions.

[Pharmacokinetic interactions of fruit juices and herbal preparations]. / Jugos de fruta y productos herbáceos como perpetradores de interacciones farmacocinéticas mediadas por enzimas metabolizadoras y transportadores de membrana. Relevancia en clínica.

Drug disposition in the human body is strongly influenced by transporters and metabolizing enzymes expressed in key organs including intestine, liver and kidney. Since drugs and chemicals present in foods such as fruit juices and herb-based products are substrates of the above-mentioned proteins, there is a high probability of pharmacokinetic interactions. Findings from preclinical and clinical studies helped to characterize the mechanisms by which the components of fruit juices and herbs act as perpetrators of pharmacokinetic interactions. The aim of this review is to provide an overview of pharmacokinetic fruit juice- and herb-drug interactions that could be relevant in the clinical setting.

[Environmental toxicity and direct renal toxicity from drugs: herbs and plants].

Traditional medicine is a widespread treatment method in the world. Despite the WHO's confirmation of the progressive spread of national policies responsible for controlling the production and distribution of phytotherapy, the risk of toxic side effects is high even if the real incidence is not known. These risks largely result from the self-prescription supported by the assumption that what is natural is not dangerous to health. The phytotherapic industry turnover is progressively increasing, favored by the ease with which products can be purchased without prescription in pharmacies in some countries or online. In particular, Chinese herbs can be nephrotoxic and clinicians should consider the possibility of their role in some cases of AKI or CKD with unknown etiology. Furthermore, in the collection of the pharmacological history of patients with CKD or kidney transplantation it is necessary to exclude the use of some phytotherapics of common use that may be contraindicated for possible interactions with drugs of conventional medicine.