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Botanical supplements and herbal products are widely used by consumers for various purported health benefits, and their popularity is increasing. Some of these natural products can have adverse effects on liver function and/or interact with prescription and over-the-counter (OTC) medications. Ensuring the safety of these readily available products is a crucial public health concern; however, not all regulatory authorities require premarket safety review and/or testing. To address and discuss these and other emerging needs related to botanical safety, a symposium was held at the Society of Toxicology Annual Meeting in Salt Lake City (UT) on March 11, 2024. The symposium addressed the latest research on botanical-induced liver toxicity and botanical-drug interactions, including new approach methods to screen for toxicity, challenges in assessing the safety of botanicals, and relating human adverse events to specific products. The presentations and robust panel discussion between the speakers and audience highlighted the need for further research and collaboration to improve the safety of botanical supplements and herbal products, with the ultimate goal of protecting consumer health. Although utility of many of the modern tools presented in the symposium requires further study, the synergistic efforts of diverse experts hold promise for effective prediction and evaluation of botanical-induced hepatotoxicity and botanical-drug interaction potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The following author initials are employed by the private sector: AR., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Patients with heart disease often use or substitute their treatment with natural remedies, but the evidence for their cardiovascular effects, side effects, and interactions is generally weak. Many preparations have no documented cardiovascular benefits, while some have documented or potential harmful effects. Treating physicians should therefore be considerate of patients' potential usage of natural remedies, and actively engage with patients on this topic, as argued in this review., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: Herbal medicines (HMs) are extensively used by consumers/patients worldwide. However, their safety profiles are often poorly reported and characterized. Previous studies have documented adverse events (AEs) associated with HMs, such as hepatotoxicity, renal failure, and allergic reactions. However, the prevalence rate of AEs related to HMs has been reported to be low. To date, no systematic review and meta-analysis has comprehensively analyzed the AEs of HMs using published data acquired from pharmacovigilance (PV) databases., Objective: This study aimed to (1) estimate the reporting rate of the AEs of HMs using PV databases and (2) assess the detailed data provided in AE reports., Methods: In this systematic review and meta-analysis, MEDLINE/PubMed, SCOPUS, EMBASE, and CINAHL were systematically searched for relevant studies (until December 2023). The DerSimonian-Laird random effects model was used for pooling the data, and subgroup analyses, the meta-regression model, and sensitivity analysis were used to explore the source of heterogeneity. Crombie's checklist was used to evaluate the risk of bias (ROB) of the included studies., Results: In total, 26 studies met the eligibility criteria. The reporting rate of the AEs of HMs ranged considerably, from 0.03% to 29.84%, with a median overall pooled estimate of 1.42% (IQR 1.12%-1.72%). Subgroup analyses combined with the meta-regression model revealed that the reporting rate of the AEs of HMs was associated with the source of the reporter (P=.01). None of the included studies provided full details of suspected herbal products, only the main ingredients were disclosed, and other potentially harmful components were not listed., Conclusions: This systematic review and meta-analysis highlighted risks related to HMs, with a wide range of reporting rates, depending on the source of the reporter. Continuous efforts are necessary to standardize consumer reporting systems in terms of the reporting form, education, and follow-up strategy to improve data quality assurance, aiming to enhance the reliability and utility of PV data for monitoring the safety of HMs. Achieving effective monitoring and reporting of these AEs necessitates collaborative efforts from diverse stakeholders, including patients/consumers, manufacturers, physicians, complementary practitioners, sellers/distributors, and health authorities., Trial Registration: PROSPERO (Prospective International Register of Systematic Reviews) CRD42021276492., (©Chuenjid Kongkaew, Dang Thuc Anh Phan, Prathan Janusorn, Pajaree Mongkhon. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 29.08.2024.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ofelia Loani Elvir Lazo reports financial support, administrative support, statistical analysis, and writing assistance were provided by Cedars-Sinai Medical Center., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022. Published by Elsevier B.V.)

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., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

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., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier Ltd.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Herbal compounds including those already well-established in traditional Chinese medicine have been increasingly tested in the treatment of various diseases. Recent studies have shown that herbal compounds can be of benefit also for pulmonary silicosis as they can diminish changes associated with silica-induced inflammation, fibrosis, and oxidative stress. Due to a lack of effective therapeutic strategies, development of novel approaches which may be introduced particularly in the early stage of the disease, is urgently needed. This review summarizes positive effects of several alternative plant-based drugs in the models of experimental silicosis with a potential for subsequent clinical investigation and use in future.

Acute interstitial nephritis can result due to exposure to any medication, toxins, infections or malignancy. In the midst of this Coronavirus (COVID-19) pandemic, there has been a race for finding remedies to prevent the spread of and control the complications due to Severe Acute Respiratory Syndrome Coronavirus 2. Certain Indian medicinal herb concoctions like kabasura kudineer and nilavembu kudineer are being widely publicized to boost immunity and reduce the risk of developing COVID-19. Little knowledge exists about the adverse effects of these herbal remedies. We report two patients who presented to us with vague complaints following the ingestion of kabasura kudineer and we diagnosed them with acute tubulointerstitial nephritis (ATIN). The temporal relationship of ingestion of these remedies to the development of ATIN calls for vigilance and caution with regular monitoring of renal functions especially in those with chronic kidney disease., (© 2021 Asian Pacific Society of Nephrology.)

Dark tea, a unique tea fermented primarily in China, has numerous potential beneficial effects. However, harmful substances present in dark tea have provoked significant concern. To conduct a quantitative benefit-risk assessment of dark tea for Chinese residents and provide guidance on rational consumption, a framework of Benefit-Risk Analysis for Foods (BRAFO) and meta-analysis was applied to construct a disability-adjusted life year (DALY). Based on the BRAFO-tiered approach, a reference scenario (no intake) and an alternative scenario (intake of 3 cups/day) were determined. The overall health impacts of dark tea were simulated by comparing the risks of fluoride and AF with benefits of reduced-risk to coronary heart disease (CHD) and diabetes in different scenarios. Three cups of fermented tea consumed per day decreased risks of CHD and diabetes by 8.16% and 12.77% respectively. After quantitative integration of information, the ultimate net health effect was found to be -1958.827 illustrating that the benefits of drinking three cups of dark tea per day outweigh the risks. However, considering the uncertainties in the process, decision-makers should proceed with caution, consulting additional well-conducted studies and further managing harmful substances in dark tea., (Copyright © 2021. Published by Elsevier Ltd.)

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., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

This review is an updated and expanded version published in this journal in 2016. Warfarin pharmacotherapy is extremely complex, since in addition to being a low therapeutic index drug, it does not follow the dose-response pattern and has characteristics that predispose the occurrence of interactions, such as high binding rate to plasma proteins, metabolization by cytochrome P450 enzymes, further to acting in the complex process of blood coagulation, platelet activation, and inflammation. For these reasons, warfarin has great potential for interaction with drugs, foods, and herbal medicines. Herb-warfarin interactions, however, are still not very well studied; thus, the objective of this update is to present new information on the subject aiming to provide a scientific basis to help health professionals in the clinical management of these interactions. A literature review was performed from May to June 2021 in multiple databases and articles published in 2016 to 2021 were included. A total of 59 articles describing 114 herbal medicines were reported to interact with warfarin. Of the plants mentioned, 84% had the potential to increase warfarin effect and the risk of bleeding. Targets possibly involved in these interactions include the processes of blood coagulation, platelet activation, and inflammation, in addition to the pharmacokinetics and pharmacodynamics of warfarin. Despite these alarming numbers, however, the clinical management of interactions is known to be effective. Thus, it is important that the use of these herbal medicines be done with caution in anticoagulated patients and that studies of herb-drug interactions be encouraged in order to generate information to support the clinical management of patients., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Algorithms can have several purposes in the clinical practice. There are different scales for causality imputation in DILI (Drug-Induced Liver Injury), but the applicability and validity of these for the HILI (Herb-Induced Liver Injury) evaluation is questionable for some scales. The purpose of the study was to determine the clinical and demographic profile of the patients with HILI, and the main algorithmic scales used in its causality assessment. The methodology was a systematic review of articles in English, Spanish, or Portuguese language, from 1979 to 2019, involving humans, with descriptors related to HILI. Qualitative and quantitative statistical analysis were performed. As a result, from a total of 60 articles, 203 HILI reports were selected: 59.9% were women, similar with other studies, and the average age was 45.8 years. Jaundice was the most frequent symptom and regarding the type of lesion, the hepatocellular was the most frequent. In regard to HILI severity, 3.0% were severe and 7.6% were fatal or required liver transplantation. In 72.3% of the cases, the most used algorithm was RUCAM (Roussel Uclaf Causality Assessment Method). The conclusion of the study is that RUCAM was the most used algorithm for causality assessment in HILI. The patients were predominantly female, jaundice was the main symptom, and HILI is reversible in the majority of cases., Competing Interests: Conflicts of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Ethnopharmacological Relevance: The recognized challenges to access conventional antimalarial medicines could have contributed to the extensive use of Aristolochia bracteolata Lam. (Aristolochiaceae)to manage malaria in South Sudan traditionally. However, the use and acquired experiences are notwell documented., Aim of the Study: This study aimed to document the traditional use of A. bracteolata for malaria treatment and experiences among the local communities in Jubek State of South Sudan., Methods: We performed a cross-sectional study in four counties in Jubek State and interviewed 396 community members, including traditional healers, using a semi-structured questionnaire. Four focused group discussions (FGDs) were also conducted using the interviewer guide. The inclusion criteria were; adults 18 years and older, men andwomen participants, at least one year residing in the study area before the study, and those with a history of medicinal plant use. Data were summarized and presented as proportions. Qualitative data were analyzed using a thematic content approach. The major themes that emerged were discussed. We applied the Pearson Chi-Square test at α = 0.05 to test the study's significant differences in responses. The statistical package for social sciences version 21 software was used for data analysis., Results: Women accounted for 208 (52.5%) of participants, with the majority 321 (81.1%) were between 18 and 45 years. Interestingly, most 312 (78.8%) had formal education. Moreover, about 208 (52.5%) participants collect the plant in their vicinity, where leaves were the most commonly used part 277 (46.4%), followed by the roots, seeds, and stems at 245(41.0%), 71 (11.9%), and 4 (0.7%), respectively. Furthermore, about 63 (15.9%) of the participants experienced side effects, including early abortions, heartburns, sweating, and stomach discomforts. Conversely, a total of 387 (96.0%) reported getting cured of malaria. Generally, the quantity of medicine taken per day differs concerning parts of the plant, with leaves ranging from 1 to 10 pieces, roots at 0.4-1 g, and seeds at 0.1-0.5 g. The locals used these plant parts to prepare infusion and decoction traditional dosage forms for oral use., Conclusion: The documented medicinal plant's therapeutic uses provided critical information on the traditional use of A. bracteolata by the community in Jubek state of South Sudan to treat malaria. Although most users reported getting cured of malaria, a notable proportion of them experienced side effects, including early-stage abortion and stomach discomforts. Thus, the use of A. bracteolata preparations, particularly in pregnant women, should be avoided. Finally, further studies are needed to devise a strategy to neutralize the toxic compounds and create community awareness on best practices to minimize side effects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Although a number of systematic reviews and meta-analyses of saffron (Crocus sativus L.) have been published, no study has comprehensively summarized the clinical evidence from meta-analyses, or assessed the reporting or methodological quality of these reviews., Purpose: The present meta-research study was designed to fill the gaps in knowledge to inform future studies and allow enhanced clinical decision-making on saffron., Methods: The PubMed, Cochrane Library, Embase, and CNKI databases were systematically searched from inception to April 3 rd, 2021, for meta-analyses of clinical trials that assessed the efficacy and safety of saffron. PRISMA 2009 and AMSTAR-2 were employed to assess the reporting and methodological quality of meta-analyses identified in the search, respectively. The present study was registered on PROSPERO with registration number CRD42020220274., Results: Nineteen eligible systematic reviews with meta-analyses published in English were identified from 235 records. These meta-analyses were published in 12 peer-reviewed journals from 2013 to 2021. The heterogeneous results indicated that saffron significantly reduced fasting blood glucose, waist circumference, diastolic blood pressure, concentrations of total cholesterol and low-density lipoprotein cholesterol, and improved symptoms of depression, cognitive function and sexual dysfunction compared with controls (mainly placebos). Common side effects of saffron consumption included nausea, dry mouth, poor appetite, and headache, but no serious adverse reactions were reported. Primary analysis and sensitivity analysis confirmed that the reporting and methodological quality of reviews included in the study were highly correlated (p < 0.001). The quality of meta-analyses of saffron requires improvement by including a structured abstract, a prospective protocol and registration, explanation of the study designs within each study that is reviewed, the searches, risk of bias assessment, literature selection, and reporting of funding sources., Conclusion: The available evidence indicates that saffron is a safe plant for administration as a medicine and can improve diverse clinical outcomes, but the scientific quality of the published systematic reviews needs to be improved. Moreover, the clinical effects of saffron need to be confirmed through high-quality randomized trials in multiple countries with large sample sizes., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Objective: To evaluate the safety and tolerability of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids (Warmi®, Lima Perú;) in otherwise healthy adult women., Methods: This was a phase-I, randomized parallel three arms, double-blinded, and a placebo-controlled clinical trial. A total of 55 participants aged 18-40 were randomly assigned to one of three groups to receive for three months: (1) an oral herbal supplement of 1650 mg/day; (2) an oral herbal supplement of 3300 mg/day; or (3) an oral placebo 3300 mg/day. The primary endpoints were oral safety and tolerability of the supplement. The secondary endpoint was its effect on vital functions, anthropometrics, and laboratory tests. We used an exploratory approach by covariance analysis (ANCOVA) adjusted for the variables' baseline value for the secondary outcomes., Results: All women completed three months of follow-up, reporting no side effects. Our exploratory analysis revealed that treatment with the herbal supplement of 1650 mg/day was associated with increased glucose and uric acid levels. In comparison, the herbal supplement 3300 mg/day was associated with reduced breathing rate, increased basal temperature, and systolic blood pressure, both compared to the placebo group. However, despite significant differences, none of these was clinically significant., Conclusion: The oral herbal supplement had a favorable safety and tolerability profile in studied women. There is a need to study its potential as an option to treat menopausal symptoms.

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., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

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., Competing Interests: The authors declare no competing interests., (Copyright: Nadia El Orfi et al.)

This review summarizes the four processes of wound healing in the human body (hemostasis, inflammatory, proliferation, and remodeling) and the most current research on the most important factors affecting cutaneous wound healing and the underlying cellular and/or molecular pathways. Local factors, including temperature, oxygenation, and infection, and systemic factors, such as age, diabetes, sex hormones, genetic components, autoimmune diseases, psychological stress, smoking and obesity are also addressed. A better understanding of the role of these factors in wound repair could result in the development of therapeutics that promote wound healing and resolve affected wounds. Additionally, natural products obtained from plants and animals are critical targets for the discovery of novel biologically significant pharmacophores, such as medicines and agrochemicals. This review outlines the most recent advances in naturally derived targeted treatment for wound healing. These are plant-derived natural products, insect-derived natural products, marine-derived natural products, nanomaterial-based wound-healing therapeutics (metal- and non-metal-based nanoparticles), and natural product-based nanomedicine to improve the future direction of wound healing. Natural products extracted from plants and animals have advanced significantly, particularly in the treatment of wound healing. As a result, the isolation and extraction of bioactive compounds from a variety of sources can continue to advance our understanding of wound healing. Undescribed bioactive compounds or unexplored formulations that could have a role in today's medicinal arsenal may be contained in the abundance of natural products and natural product derivatives., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Ethnopharmacological Relevance: There are plant species used in the Mexican traditional medicine for the empirical treatment of anxiety and depression., Aim of the Study: This work assessed the prevalence of self-medication with medicinal plants and the prevalence of the concomitant use of prescribed psychiatric drugs and medicinal plants for treating symptoms associated with anxiety and depression during the Covid-19 lockdown in Mexico., Materials and Methods: The suspected adverse reactions associated with drug-herb interactions were assessed. The factors associated with self-medication, the concomitant use of herb-drug combinations, and the presence of adverse reactions due their combined use is also reported. The study was descriptive and cross-sectional using an online questionnaire conducted among population with symptoms associated with anxiety and depression (n = 2100) from seven states of central-western Mexico., Results: The prevalence of the use of herbs (61.9%) and the concomitant use of drug-herb combinations (25.3%) were associated with being diagnosed with mental illness [OR:2.195 (1.655-2.912)] and the use of psychiatric medications [OR:307.994 (178.609-531.107)], respectively. The presence of adverse reactions (n = 104) by the concomitant use of drug-herb combinations was associated with being unemployed [p = 0.004, OR: 3.017 (1.404-6.486)]., Conclusion: Health professionals should be aware if their patients concomitantly use medicinal plants and psychiatric drugs. Public health campaigns should promote the possible adverse reactions that might produce the concomitant use of drug-herb combinations for mental illnesses., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Negative psychological and physiological consequences of neurodegenerative disorders represent a high social and health cost. Among the neurodegenerative disorders Alzheimer's disease (AD) is recognized as a leading neurodegenerative condition and a primary cause of dementia in the elderlys. AD is considered as neurodegenerative disorder that progressively impairs cognitive function and memory. According to current epidemiological data, about 50 milLion people worldwide are suffering from AD. The primary symptoms of AD are almost inappreciable and usually comprise forgetfulness of recent events. Numerous processes are involved in the development of AD, for example oxidative stress (OS) mainly due to mitochondrial dysfunction, intracellular the accumulation of hyperphosphorylated tau (τ) proteins in the form of neurofibrillary tangles, excessive the accumulation of extracellular plaques of beta-amyloid (Aβ), genetic and environmental factors. Running treatments only attenuate symptoms and temporarily reduce the rate of cognitive progression associated with AD. This means that most treatments focus only on controlLing symptoms, particularly in the initial stages of the disease. In the past, the first choice of treatment was based on natural ingredients. In this sense, diverse natural products (NPs) are capable to decrease the symptoms and alleviate the development of several diseases including AD attracting the attention of the scientific community and the pharmaceutical industry. Specifically, numerous NPs including flavonoids, gingerols, tannins, anthocyanins, triterpenes and alkaloids have been shown anti-inflammatory, antioxidant, anti-amyloidogenic, and anti-choLinesterase properties. This review provide a summary of the pathogenesis and the therapeutic goals of AD. It also discusses the available data on various plants and isolated natural compounds used to prevent and diminish the symptoms of AD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The increasing national prevalence of diabetes mellitus (DM) and its complications have overstretched the health care system in Tanzania and influenced patients to use herbal medicines as alternative therapeutic strategies. Therefore, an urgent need exists to validate the safety and efficacy of plants used locally., Aim of the Study: To identify plants used for the management of DM in Tanzania and analyses their pharmacological, phytochemistry, and safety evidence with a special focus on the mechanism of action., Methods: Researchers searched Medline, web of science, and Scopus for published articles. Also, specialized herbarium documents of Muhimbili Institute of traditional medicine were reviewed. Articles were assessed for relevance, quality, and taxonomical accuracy before being critically reviewed., Results: We identified 62 plant species used locally for DM management. Moringa oleifera Lam. and Cymbopogon citratus (D.C) stapf were the most mentioned. Fifty-four phytochemicals from 13 species had DM activities. These were mainly; polyphenolics, phytosterols, and triterpenoids. Extracts, fractions, and pure compounds from 18 species had in vitro antidiabetic activities of which 14 had α-glucosidase and α-amylase inhibition effects. The most studied -Momordica charantia L. increased; glucose uptake and adiponectin release in 3T3-L1 adipocytes, insulin secretion, insulin receptor substrate-1 (IRS-1), GLUT-4 translocation, and GLP-1 secretion; and inhibited protein tyrosine phosphatase 1 B (PTP1B). Preclinical studies reported 30 species that lower plasma glucose with molecular targets in the liver, skeletal muscles, adipose tissues, pancreases, and stomach. While three species; Aspilia mossambiscensis (Oliv.) Willd, Caesalpinia bonduc (L.) Roxb, and Phyllanthus amarus Schumach. & Thonn. had mild toxicity in animals, 33 had no report of their efficacy in DM management or toxicity., Conclusion: Local communities in Tanzania use herbal medicine for the management of DM. However, only a fraction of such species has scientific evidence. A. mossambiscensis, C. bonduc., and P. amarus had mild toxicity in animals. Together, our findings call for future researches to focus on in vitro, in vivo, and phytochemical investigation of plant species for which their use in DM among the local communities in Tanzania have not been validated., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose of Review: To assess the effects of herbal medicine (HM) therapy in various durations and analyze the effects of HM separately by mechanism of action in the treatment of allergic rhinitis (AR)., Recent Findings: Thirty-two studies were included (2,697 patients, mean age 34.6 years). For the ≤ 4 weeks of treatment duration, HM brought greater benefits over placebo in reduction of total nasal symptoms score (standardized mean difference (SMD) -0.68; 95% confidence interval (CI) -0.98, -0.38; p <0.01) and improvement in Rhinoconjunctivitis Quality of Life Questionnaire score (SMD -0.53; 95% CI -0.81, -0.25; p <0.01). For the 4-12 weeks duration, total nasal symptoms score (SMD -0.22; 95%CI -0.4, -0.05; p =0.01) and Rhinoconjunctivitis Quality of Life Questionnaire score (SMD -0.48; 95% CI -0.89, -0.06; p =0.03) favored the HM. However, HM therapy for longer than 12 weeks was related to tachyphylaxis and showed no benefit over placebo in any outcomes. There was no difference between the HM and standard treatment on symptoms improvement. Anti-allergic effect, anti-inflammatory effect, anti-leukotriene effect, and anti-histaminic effect of HM were revealed. HM was safe and their adverse effects were comparable placebo. HM therapy is safe and provides better results than placebo in improving nasal symptoms and disease-specific quality of life in patients with AR. Its beneficial effects are demonstrated only in less than 12 weeks of treatment., Trial Registration: PROSPERO ID: CRD42020168367.

The Food and Drug Administration (FDA) classifies herbal preparations as food supplements. New herbal supplements and products are not governed by the strict FDA drug approval process and there is no premarket approval required. The FDA prohibits manufacturers and distributors from marketing adulterated or misbranded products but does not rigorously define safe practices. Scientific evidence related to herbal supplements is limited. Herbal supplements have been associated with adverse reactions and herbal-drug interactions. Information and precautions for 20 common herbal supplements, including St. John's wort, ginseng, echinacea, and ginkgo, are reviewed. Resources for consumers and health care professionals are highlighted., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In recent decades, ritualistic use of ayahuasca has spread throughout the world. Retrospective studies have suggested a good psychological safety profile, but prospective studies involving ceremony ayahuasca-naive participants are lacking., Methods: We conducted the study using a subsample from a previous study, for which first-time ceremony ayahuasca participants were recruited. The subsample consisted of 7 subjects who experienced acute and challenging psychological reactions. The semistructured Mini-International Neuropsychiatric Interview and psychometric questionnaires were administered before participants attended the ayahuasca ceremony and at 1 and 6 months after exposure. Subjective experiences were also recorded., Results: Seven subjects from a sample of 40 reported having experienced intense challenging psychological effects during the ayahuasca ceremony. Four of those 7 subjects met the diagnostic criteria for 1 or more psychiatric disorder before the ayahuasca ceremony. One month after the ceremony, 2 of those subjects no longer showed psychiatric symptoms, whereas the symptoms of the other 2 were reduced considerably. Those results persisted at the 6-month follow-up. Inappropriate setting/context (poor guiding skills and screening) contributed to some of the challenging reactions. Most of the participants (6 of 7) did not take ayahuasca again during the study period., Conclusions: Based on the cases reported here, we suggest that although it is possible that participating in ayahuasca ceremonies may entail acute psychological negative reactions, those challenging experiences can also have positive long-term effects. Prospective research on the safety profile of ayahuasca and how it is affected by the context of different practices and safety strategies is therefore necessary., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Ethnopharmacological Relevance: Plumula Nelumbinis, the green embryo of the mature seeds of Nelumbo nucifera Gaertn, has a medical history of over 400 years. It is widely used for clearing the heart and heat, calming the mind, and promoting astringent essence and hemostasis in traditional Chinese medicine. Moreover, it usually dual use as food and medicine. This review aimed to evaluate the therapeutic potential of Plumula Nelumbinis by summarizing its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety., Methods: This review summarized published studies on Plumula Nelumbinis in the Chinese Pharmacopoeia and literature databases including PubMed, Web of Science, Baidu Scholar, Wiley and China Knowledge Resource Integrated Database (CNKI), and limits the different research articles in botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety about Plumula Nelumbinis., Results: Plumula Nelumbinis is used to treat hypertension, arrhythmia, severe aplastic anemia, insomnia, encephalopathy and gynecological disease in traditional Chinese medicine and clinical studies. More than 130 chemicals have been isolated and identified from Plumula Nelumbinis, including alkaloids, flavonoids, polysaccharides and volatile oil. In addition, pharmacological effects, such as protective effects against cardiovascular diseases, neurological diseases, lung and kidney injury, anti-inflammatory and anticancer activities, were also evaluated by in vitro and in vivo studies. Moreover, the potential signaling pathways regulated by Plumula Nelumbinis in cardiovascular and neurological diseases and perspectives on Plumula Nelumbinis research were discussed., Conclusion: Plumula Nelumbinis, a commonly used Chinese medicine, has a variety of traditional and modern therapeutic uses. Some traditional uses, especially the treatment of cardiovascular and neurological diseases, have been verified by pharmacological investigation. However, the pharmacological molecular mechanisms, pharmacokinetics and toxicology of Plumula Nelumbinis are still incomplete. In the future, a series of systematic studies on active compounds identification, pharmacological mechanism clarification, quality and safety evaluation are necessary., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This review focuses on four new product categories of food supplements: pre-workout, fat burner/thermogenic, brain/cognitive booster, and hormone/testosterone booster. Many food supplements have been shown to be contaminated with unauthorized substances. In some cases, the ingredients in the new categories of dietary supplements were medicinal products or new synthetic compounds added without performing clinical trials. Some of the new ingredients in dietary supplements are plant materials that are registered in the pharmacopoeia as herbal medicines. In other cases, dietary supplements may contain plant materials that have no history of human use and are often used as materials to 'camouflage' stimulants. In the European Union, new ingredients of dietary supplements, according to European Food Safety Authority or unauthorized novel food. Furthermore, selected ingredients in dietary supplements may be prohibited in sports and are recognized as doping agents by World Anti-Doping Agency., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Migraine is a chronic paroxysmal incapacitating neurological disorder, which endangers the health of human worldwide ranking as the third most prevalent medical condition. There are no comprehensive estimates of treatments for migraine. We will conduct this systematic review and Bayesian network meta-analysis (NMA) to synthesis quantitative and comparative evidence on the efficacy and tolerability of all the known pharmacological and non-pharmacological interventions for migraine., Method: We will perform the systematic electronic search of the literature utilizing MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing & Allied Health (CINAHL), and PsycINFO. We will only include randomized controlled trials (RCTs) of high quality which appraise the efficacy or safety of any potential pharmacological or non-pharmacological interventions in the treatment of patients with migraine. The traditional pairwise meta-analyses will be performed to anticipate the heterogeneities and publication bias and the NMA will be conducted within a Bayesian hierarchical model framework to obtain estimates for all valuable treatments for migraine. The entire heterogeneity will be quantified by Q statistic and I2 index. Other analyses included sensitivity analyses, meta-regression, and subgroup analyses will also be conducted. The whole process will be conducted using in R-3.6.0 software., Results: This study will obtain the efficacy and tolerability of all potential treatments for migraine, aiming at providing consolidated evidence to help make the best choice of interventions. The results will be published in a peer-reviewed journal., Discussion: This Bayesian network meta-analysis may be the first attempt to quantitatively synthesize the efficacy and tolerability of all potential treatments for migraine. And this method can ensure us to fully utilize both the direct and indirect evidence as well as gain the comparative estimates displayed in the derived hierarchies. Besides, we have registered this protocol on the international prospective register of systematic review (PROSPERO) (CRD42020157278)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aging is a natural biological progress accompanied by the gradual decline in physiological functions, manifested by its close association with an increased incidence of human diseases and higher vulnerability to death. Those diseases include neurological disorders, cardiovascular diseases, diabetes, and cancer, many of which are currently without effective cures. Even though aging is inevitable, there are still interventions that can be developed to prevent/delay the onset and progression of those aging-associated diseases and extend healthspan and/or lifespan. Here, we review decades of research that reveals the molecular pathways underlying aging and forms the biochemical basis for anti-aging drug development. Importantly, due to the vast chemical space of natural products and the rich history of herb medicines in treating human diseases documented in different cultures, natural products have played essential roles in aging research. Using several of the most promising natural products and their derivatives as examples, we discuss how natural products serve as an inspiration resource that helped the identification of key components/pathways underlying aging, their mechanisms of action inside the cell, and the functional scaffolds or targeting mechanisms that can be learned from natural products for drug engineering and optimization. We argue that natural products might eventually provide a solution to aging and aging-associated diseases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: To explore the ethnobiological wisdom of the tribals of three western districts of West Bengal, India against poisonous and non-poisonous bites and stings, a quantitative approach was adopted. These age-old yet unexplored knowledge can be utilized in finding lead-molecules against poisonous and non-poisonous animal-bites. Further, an evidence-based approach is needed to assess the venom-neutralization ability of plants by experimental studies., Materials and Methods: During 2008-2009 and 2012-2017, 11 ethnomedicinal surveys were carried out to explore the use of medicinal flora and fauna via conducting open semi-structured interviews with 47 traditional healers (THs) or informants. The retrieved dataset was statistically evaluated using seven quantitative-indexes: use-value (UV), informants'-consensus-factor (ICF), fidelity-level (FL), relative-importance (RI), cultural importance-index (CI), index of agreement on remedies (IAR) and cultural agreement-index (CAI). Anti-phospholipaseA2 (PLA2) properties of selected plant extracts were also examined. In addition, the cytotoxicity and genotoxicity of the water extract of the plants showing high FL as well as significant PLA2 inhibitory potential were investigated using Allium cepa root tip assay., Results: A total of 41 traditional-formulations (TFs) containing 40 plant species (of 39 genera from 28 families) and 3 animal species were prescribed by the THs. Fabaceae exhibited most number of medicinal plants. Piper nigrum (1.78) and Apis cerana indica and Crossopriza lyoni (both 0.21) exhibited the highest UV among the plants and the animals respectively. Stinging of centipede and dog/cat/hyena bite displayed highest ICF (1.00 each). Among the plants, the maximum RI (0.91) and CI (4.98) values were observed for Aristolochia indica. IAR (1.00) was recorded maximum for Achyranthes aspera, Gloriosa superba, Lycopodium cernuum, Smilax zeylanica and Streblus asper. Maximum CAI value was noted for Piper nigrum (5.5096). Among the animals, Apis cerana indica (0.31) and Crossopriza lyoni (1.52) displayed the highest RI and CI values respectively. Crossopriza lyoni (0.99) and Apis cerana indica (1.3871) exhibited maximum IAR and CAI values respectively. Plants showing higher FL exhibited higher anti-PLA2 activity via selective inhibition of human-group PLA2. In addition, Allium cepa root tip assay has indicated the safety and/or toxicity of the plant parts prescribed by the THs. Root water extracts of Aristolochia indica and Gloriosa superba exhibited significant genotoxicity and cytotoxicity., Conclusions: Three western districts of West Bengal is the natural abode for many tribal and non-tribal communities. A noteworthy correlation was established between the plants used against poisonous-bites and their anti-PLA2 activity. A few plant parts used by the THs also exhibited high toxicity. Such alternative medical practices serve as the only option in these underprivileged and backward areas during medical-exigencies., Competing Interests: The authors have declared that no competing interests exist.

The release of reactive oxygen species (ROS) and oxidative stress is associated with the development of many ailments, including cardiovascular diseases, diabetes and cancer. The causal link between oxidative stress and cancer is well established and antioxidants are suggested as a protective mechanism against cancer development. Recently, an increase in the consumption of antioxidant supplements was observed globally. The main sources of these antioxidants include fruits, vegetables, and beverage. Herbal infusions are highly popular beverages consumed daily for different reasons. Studies showed the potent antioxidant effects of plants used in the preparation of some herbal infusions. Such herbal infusions represent an important source of antioxidants and can be used as a dietary protection against cancer. However, uncontrolled consumption of herbal infusions may cause toxicity and reduced antioxidant activity. In this review, eleven widely consumed herbal infusions were evaluated for their antioxidant capacities, anticancer potential and possible toxicity. These herbal infusions are highly popular and consumed as daily drinks in different countries. Studies discussed in this review will provide a solid ground for researchers to have better understanding of the use of herbal infusions to reduce oxidative stress and as protective supplements against cancer development.

In 2019, ∼ 463 million people globally had diabetes mellitus (DM), with China (25.1%), India (16.6%), and the United States (6.69%) representing nearly 50% of that total. The primary objectives of this exploratory study were to assess the safety and potential efficacy of Nigella sativa and fenugreek seed supplemented chapatis in overweight (OW) and type 2 DM subjects. Forty subjects (15/OW; 9/DM; 16/DM/OW) consumed two chapatis twice a day 6 days/week for a daily dose of 5.45 g of an N. sativa /fenugreek combination over 12 weeks with no changes in lifestyle or medications. Anthropometric, glycemic, and vascular variables were recorded at baseline and after 6 and 12 weeks. Glycated hemoglobin (HbA1c), plasma lipids, and complete metabolic profile were measured at baseline and termination. Compliance, estimated during twice-daily individual delivery of precooked chapatis, was 100%, with no significant adverse effects. At termination, body weights, body mass index, waist and hip circumferences, index of central obesity, HbA1c, fasting blood glucose, 2-h postprandial blood glucose, estimated average glucose over 12 weeks, total cholesterol (TC), non-high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL), and triglycerides (TG) were decreased ( P  < .05) over all subjects. Subjects with HbA1c ≥7.0 exhibited greater improvements in all glycemic variables than HbA1c <7.0 subjects. In addition, the decrease in HbA1c was positively correlated with decreases in (1) hepatic enzymes alkaline phosphatase ( r  = 0.301, P  = .0067) and aspartate transaminase ( r  = 0.277, P  = .0129), (2) systolic blood pressure ( r  = 0.388, P  = .0004), and (3) number of diagnostic metabolic syndrome criteria exhibited per subject ( r  = 0.391, P  = .0005), cardiovascular risk score (CRS) ( r  = 0.281, P  = .0115), and hepatic steatosis index (HSI) ( r  = 0.223, P  = .0467). Atherogenic and diabetogenic indexes TC/HDL, low density lipoprotein/HDL, VLDL/HDL, and TG/HDL were all decreased ( P  < .05). Among all subjects, improvement ( P  < .05) was seen in CRS (-10.7%), fatty liver index (-19.8%), lipid accumulation product (-13.8%), and HSI (-7.53%). N. sativa /fenugreek supplemented chapatis present a safe and seamless dietary modification to address cardiometabolic risk.

Introduction: Three major classes of natural products (NPs) for medicinal purposes or improving wellbeing are generally available in the US: conventional drugs of herbal origin, botanical drugs, and dietary supplements (DSs). Consumer consumption of DSs is growing annually. The U.S. FDA regulates conventional and botanical drugs for safety and efficacy; however, DSs are minimally regulated., Areas Covered: This article will: i) highlight the importance of NP as a significant source of prescription drugs; ii) discuss differences in the regulation of conventional drugs of NP product, botanical drugs, and DSs; iii) discuss the safety and efficacy of DSs and iv) make recommendations for improvement of safety for minimally regulated NPs., Expert Opinion: Toxicities associated with the use of NPs, including vitamins and DSs, are mainly due to excessive use and interactions with conventional drug(s) and may represent challenges for clinicians. Conventional and botanical-based prescription drugs are rarely associated with unknown toxicities. However, DSs are minimally regulated and can produce severe adverse effects. We believe that clinical pharmacologists can have a role in developing criteria for DS safety analysis. There is also the potential for a standardized NP stewardship program(s) and the development of NP policies and practices nationally and globally.

Objectives: Cancer patients are using medical cannabis (MC) to address symptoms; however, little data exist to guide clinicians when counseling patients. We seek to define the patterns of MC use among cancer patients, as well as efficacy and safety of MC., Materials and Methods: Cancer patients attending oncology office visits at Beaumont Hospital, Michigan from July to December 2018 were anonymously surveyed. The survey included data regarding demographics, diagnosis, treatment, symptom burden, and MC use. Patients who reported MC use since their cancer diagnosis completed a section on patterns of use, efficacy, and safety., Results: The response rate was 188 of 327 (57.5%). MC use was reported by 46 of 188 (24.5%). A median composite baseline symptom score ranging from 8 (best) to 32 (worst) was higher in patients using MC versus nonusers; 17.5 versus 14.4 (P<0.001). Pain was the symptom with the highest frequency of improvement 34/42 (81%), followed by appetite 34/44 (77.3%), and anxiety 32/44 (73%). MC improved the ability to tolerate treatment in 24/44 (54.5%). Cloudy thinking is the symptom that worsened the most 7/42 (16.7%), with decreased energy being experienced by 4/41 (9.8%) of the users., Conclusions: MC was utilized by a significant portion of cancer patients in this sample, across age, diagnosis, stage, and treatment. Patients with a higher severity of baseline symptoms were more likely to use MC and report a favorable efficacy profile of MC. Minimal toxicity was reported in this cohort. Prospective studies are needed to define the efficacy and safety of MC.

Ethnopharmacological Relevance: Alopecia is a chronic condition that may cause emotional and psychological distress to patients, which may significantly impact a patient's quality of life. As conventional treatments have only a transient therapeutic effect and result in unwanted side effects, many patients have attempted to find therapeutic herbs or compounds that function as safer and more potent treatments for alopecia. Many such herbs have been used in complementary and alternative medicine (CAM) for centuries; however, there is a lack of information on the therapeutic mechanisms of herbs used for the treatment of alopecia., Aim of the Study: The aim of this review was to perform a critical assessment of the methods and results of experimental studies related to alopecia and to provide the potential mechanisms of action of herbs and their constituent compounds used in the identified studies, in particular, in relation to the stages of the cell cycle. We hope to better guide the clinical application and scientific research of herbs for the treatment of alopecia., Materials and Methods: We reviewed experimental studies to determine the methods used and the mechanism of action of the herbs and constituent compounds. Databases, including Medline (via PubMed), EMBASE, OASIS, and RISS, were searched for the following keywords: "medicinal plants," "alopecia," "alopecia areata," "androgenetic alopecia," "animal experiment," and "in vitro study." We also assessed the risks of bias, toxicity, and taxonomy to determine the quality of information., Results: C57BL/6 mice and human dermal papilla cells were the most commonly used models for in vivo and in vitro studies, respectively. Many herbs and their constituent compounds were used to treat alopecia by managing the hair cycle, keratinocyte proliferation, apoptosis, angiogenesis, hormones, and inflammation. These compounds prolong the anagen phase, shorten the transition from the telogen to phase anagen, and inhibit premature catagen phase., Conclusions: This review has further elucidated the therapeutic mechanisms of herbs and their constituent compounds that are relevant to alopecia and discussed the effectiveness of using herbal treatments. There is a need to develop evidence regarding the quality control, taxonomy, and toxicology of these compounds. Such improvements will provide a better quality of evidence to ensure the efficacy and safety of herbs and compounds used for the treatment of alopecia., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Unani system of medicine uses drugs from plants, minerals and animals (Mawaleed-e-salasa) origin. Most of the drugs used are believed to be safe, but some drugs may have toxins and produce harmful effects, so it is very important to remove the toxins or to minimize their harmful effects before using, so as to increase their therapeutic values and make easy for use., Aim of the Study: To explore the concept, aims and objectives of islah-e-advia (rectification/purification of drugs) in Unani system of medicine., Materials and Methods: A through literature survey was undertaken using the various online bibliographic databases like Pub Med, Google Scholar, Science Direct, Web of Science and Scopus. Classical Unani literature books which are translated in Urdu by CCRUM were used for Unani references. The keywords used for the search included "Tadbeer-e-Advia", "Islah-e-advia", Mudabbar process, detoxification and purification of drug., Results: The ancient Unani physicians were well aware of toxicity of the drugs and have divided drugs into four degrees (1°, 2°, 3° and 4°) according to the Mizaj (temperament) of drugs. The fourth degree drugs produce so strong effects that the physiological functions of the body get disturbed; such drugs are also considered to be poisonous drugs. Different methods of purification have been mentioned for drugs belonging to the third and fourth degree temperament and always recommended their use after subjecting them to certain Tadbeer (rectification/purification). Otherwise these drugs may destroy the physiological function of the body. After purification process the drugs become physically and chemically pure, therapeutically more effective and less toxic. Very few pharmacological and toxicity studies have been conducted., Conclusion: Third and fourth degree drugs and its formulations have been claimed by Unani scholars to be useful in the management of various diseases of the body. After purification toxicity has been reduced in comparison crude drug. However, further elaborate and comprehensive studies are required to validate such claims., Competing Interests: Declaration of competing interest There is no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There are trillions and trillions of microorganisms in the human gut, and these microorganisms and their metabolites are closely related to human health. Recent studies have found that the abundance of Akkermansia muciniphila is decreased in many diseases. Supplementation of A. muciniphila is used to treat many diseases, suggesting it as a probiotic. Herbal medicines are considered as valuable asset of traditional Chinese medicine. Recent studies have revealed traditional Chinese medicine as a potential prebiotic agent for the treatment of many diseases. Hence, in this review, we aimed to provide a plausible mechanistic basis for the interactions between herbal medicines and A. muciniphila, and therapeutic benefits on this interaction in various illnesses., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Bacterial biofilms widely exist in nature and seriously threaten global public health. Biofilms always cause persistent infection and seriously aggravate the occurrence of antibiotic resistance, which makes the treatment of bacterial infection difficult. Current conventional therapies, such as antibiotics, bacteriophages and quorum sensing inhibitors, are widely used to combat biofilms. However, these therapies are inadequate for the safe and effective treatment of biofilms. Antibiotics often produce resistance in treated bacteria, and antibacterial peptides are easily decomposed by proteases, so their efficacy is reduced. These results indicate that the treatment of biofilms needs further improvement. Increasing evidence has shown that natural medicine therapies have significant inhibitory effects on biofilms. This review summarized and analyzed the efficacy characteristics and corresponding mechanisms of conventional and natural medicine therapies combatting biofilms. By comparison, the advantages and disadvantages of those therapies have been classified and interpreted, so we have inferred that combined medication with natural medicines will be a more effective strategy against biofilms. This review lays a promising foundation for the development of antibiofilm agents and provides novel thinking for the treatment of bacterial biofilm infections., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Rationale: Excessive ingestion of licorice can cause pseudohyperaldosteronism. A few case reports in the available literature have described significant hypokalemia secondary to licorice consumption with clinical manifestations of muscle weakness, paralysis, or severe hypertension. To our knowledge, no report has discussed severe asymptomatic hypokalemia associated with licorice consumption., Patient Concerns: A 79-year-old man presented to the urology clinic with a several-month history of urinary frequency and a weak stream. Routine laboratory investigations revealed serum potassium (K) level of 1.8 mmol/L, and he was immediately admitted to the nephrology department., Diagnoses: He was in a good state of health, and systemic and neurological examinations were unremarkable. However, laboratory investigations revealed severe hypokalemia and metabolic alkalosis accompanied with renal K wasting and hypertension, suggesting a state of mineralocorticoid excess. Hormonal studies revealed low serum renin and aldosterone but normal serum cortisol levels. Detailed history taking revealed that he had used licorice tea daily during the preceding 18 months., Interventions and Outcome: The patient's serum K returned to normal levels after vigorous K replacement and discontinuation of licorice intake. He was also diagnosed with benign prostatic hyperplasia during hospitalization and was treated., Lessons: Chronic licorice ingestion can precipitate severe hypokalemia, although patients may remain asymptomatic. This case report indicates that the severity of a patient's clinical presentation depends on individual susceptibility, as well as the dose and duration of licorice intake.

Background: Most patients with contact allergy to Asteraceae plants are patch test positive to sesquiterpene lactone mix (SLM). There are several reports among these patients of a flare-up of hand eczema after ingestion of food and beverages originating from Asteraceae plants., Aim: To investigate whether German chamomile tea can elicit systemic allergic dermatitis., Patients and Methods: Individuals with or without contact allergy to SLM were patch tested with an extract of German chamomile tea. Six weeks later, they were provoked with capsules containing either freeze-dried German chamomile tea or placebo capsules containing lactose, in a double-blind, randomized study. A numerical rating scale (NRS) was used to ascertain the volunteers' opinion of their hand eczema status. The study individuals were examined to detect a possible flare-up of healed patch test reactions to chamomile., Results: None of the subjects had a flare-up of healed patch test reactions. According to the NRS, SLM-positive individuals experienced a significant worsening of hand eczema, independently of whether they received chamomile or lactose capsules., Conclusion: No evidence suggestive of systemic allergic dermatitis was found., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and the induction of oxidative damage in the cell. One effective strategy in reducing the toxic effects of As is the usage of chelating agents, which provide the formation of inert chelator-metal complexes with their further excretion from the body. This review discusses different aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic effect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium 2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent agents against As toxicity. The review also considers the possible role of flavonoids, trace elements, and herbal drugs as promising natural chelating and detoxifying agents.