Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects.

To understand the material foundation and liver injury mechanism of STR.

Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot.

A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment.

The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

Traditional, complementary, and integrative medicine (TCIM) modalities are widely employed. However, TCIM, specifically herbal and non-herbal dietary supplements, can pose challenges in the context of organ transplantation. In this review, we discuss common supplements used for psychiatric purposes and highlight important considerations for candidates and recipients of liver transplants.

Ashwagandha, kava kava, green tea extract, skullcap, turmeric, and valerian have known idiosyncratic hepatotoxic potential and may complicate the liver transplantation course. Multiple supplements reportedly carry a lower risk of hepatotoxicity, though evidence for widespread use in those at risk for or with hepatic impairment is limited. Psychiatrists caring for candidates and recipients of liver transplants must recognize that patients may find supplements helpful in alleviating psychiatric symptoms, despite an overall limited evidence base. Evaluating benefit versus risk ratios and reviewing drug-drug interactions is essential to promote transplant candidacy and mitigate the possibility of native or graft liver dysfunction.

Since usnic acid was first isolated in 1844 as a prominent secondary lichen metabolite, it has been used for various purposes worldwide. Usnic acid has been claimed to possess numerous therapeutic properties, including antimicrobial, anti-inflammatory, antiviral, anti-proliferative, and antipyretic activities. Approximately two decades ago, crude extracts of usnic acid or pure usnic acid were marketed in the United States as dietary supplements for aiding in weight loss as a "fat-burner" and gained popularity in the bodybuilding community; however, hepatotoxicity was documented for some usnic acid containing products. The US Food and Drug Administration (FDA) received numerous reports of liver toxicity associated with the use of dietary supplements containing usnic acid, leading the FDA to issue a warning letter in 2001 on a product, LipoKinetix. The FDA also sent a recommendation letter to the manufacturer of LipoKinetix, resulting in the withdrawal of LipoKinetix from the market. These events triggered investigations into the hepatotoxicity of usnic acid and its mechanisms. In 2008, we published a review article titled "Usnic Acid and Usnea Barbata Toxicity". This review is an updated version of our previous review article and incorporates additional data published since 2008. The purpose of this review is to provide a comprehensive summary of the understanding of the liver toxicity associated with usnic acid, with a particular focus on the current understanding of the putative mechanisms of usnic acid-related hepatotoxicity.

The consumption of dietary supplements (DS) has resulted in a significant and escalating number of cases involving liver injury. It is crucial for clinicians and consumers to be well informed about the adverse effects of such products, leading to their discontinuation and timely reporting of any harmful cases. This article delves into the clinical perspective of DS-related hepatotoxicity, highlighting key concepts such as a systematic diagnostic approach. The discussion extends to notable examples of both currently popular and potential future dietary supplements, such as garcinia cambogia, turmeric, and ashwagandha, accompanied by an overview of recent findings. Causality assessment tools play a crucial role in establishing a connection between these products and instances of liver injury, with consideration of the advantages and disadvantages associated with their use. Fostering a comprehensive understanding of regulatory standards, coupled with a solid foundation of knowledge of DS, will prove instrumental in preventing DS-related hepatotoxicity. Achieving this goal requires collaborative efforts from both consumers and clinicians.

The general population widely uses herbal medicines, as they are regarded as effective and safe. St. John's wort, which is an effective herbal antidepressant, exhibits both pharmacokinetic and pharmacodynamic interactions with several drugs. The aim of this review was to highlight the clinically significant interactions of St. John's wort with drugs that require to be monitored to assess their therapeutic effect.

Published literature was searched using electronic databases, such as MEDLINE, PubMed, and Elsevier ScienceDirect using terms such as "herbal medicine," "herbal toxicity," "legislation herbal medicine," "drug-herb interactions," "St. John's wort," and "St. John's wort-drug interactions." Searches were limited to the English language, and there was no restriction on the date of publication.

St. John's wort exhibits a number of pharmacokinetic and pharmacodynamic interactions with drugs. The most dangerous interactions occurred when used concurrently with the immunosuppressants, cyclosporine, and tacrolimus (treatment failure or organ rejection) or warfarin (treatment failure resulting in thromboembolic events) or antiretroviral agents (treatment failure and the emergence of new viral variants that are resistant to conventional drugs).

Patients should consult their health care providers before consuming herbal supplements, especially St. John's wort, to avoid potentially dangerous drug-herb interactions.

In the last couple of decades, we have experienced increased use of nutraceuticals worldwide with a demand for organic foods, which has been elevated to an extent probably unmatched with other periods of our civilization. One of the nutraceuticals that gained attention is epigallocatechin gallate (EGCG), a polyphenol in green tea. It has been suggested that diseases of the central nervous system can benefit from consuming some antioxidants, despite current results showing little evidence for their use in preventing and treating these diseases. ECGC may be beneficial in delaying the neurodegeneration of the substantia nigra regardless of the origin of Parkinson's disease (PD). This review covers the effect of EGCG on vitro and animal models of PD, the potential mechanisms of neuroprotection involved and summaries recent clinical trials in human PD. This review also aims to provide an investigative analysis of the current knowledge in this field and to identify putative crucial issues. Environmental factors such as dietary habits, drug use and social interaction are all factors that influence the evolution of neurodegenerative diseases. Therefore, the use of nutraceuticals requires further investigation.

The use of herbal supplements and alternative medicines has been increasing in the last decades. Despite popular belief that the consumption of natural products is harmless, herbs might cause injury to various organs, particularly to the liver, which is responsible for their metabolism in the form of herb-induced liver injury (HILI).

To identify herbal products associated with HILI and describe the type of lesion associated with each product.

Studies were retrieved using Medical Subject Headings Descriptors combined with Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE, BIREME, LILACS, Cochrane Library for Systematic Reviews, SciELO, Embase, and Opengray.eu. Languages were restricted to English, Spanish, and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. To access causality, the Maria and Victorino System of Causality Assessment in Drug Induced Liver Injury was used. Simple descriptive analysis were used to summarize the results.

The search strategy retrieved 5918 references. In the final analysis, 446 references were included, with a total of 936 cases reported. We found 79 types of herbs or herbal compounds related to HILI. He-Shou-Wu, Green tea extract, Herbalife, kava kava, Greater celandine, multiple herbs, germander, hydroxycut, skullcap, kratom, Gynura segetum, garcinia cambogia, ma huang, chaparral, senna, and aloe vera were the most common supplements with HILI reported. Most of these patients had complete clinical recovery (82.8%). However, liver transplantation was necessary for 6.6% of these cases. Also, chronic liver disease and death were observed in 1.5% and 10.4% of the cases, respectively.

HILI is normally associated with a good prognosis, once the implied product is withdrawn. Nevertheless, it is paramount to raise awareness in the medical and non-medical community of the risks of the indiscriminate use of herbal products.

Safety data on commonly used herbal medicinal (HM) products (HMPs) and marketed in Ghana are scarce. We assessed the sub-chronic toxicity of three most-patronised commercial antimalarial HMPs in Kumasi, Ghana.

Top three HMPs (designated as herbal products 'A' (HPA), 'B' (HPB) and 'C' (HPC)) were selected after a mini-survey and sub-chronic toxicity evaluation conducted in accordance with Organisation for Economic Co-operation and Development (OECD) 407 guidelines. Control rats received clean water while test groups received daily adult human dose (DAHD), 5× DAHD or 10× DAHD of either HPA, HPB or HPC for 30 days. Rats were killed on day 31 to obtain biochemical, haematology and histology samples for analysis. Data were analysed by one-way analysis of variance (ANOVA) and post hoc Tukey's test.

The three HMPs produced alterations in liver morphology predominantly characterised by prominent foci of fatty change with scattered hepatocytes containing intracytoplasmic fat globules and congested central veins and sinusoids. The lungs showed alveolar with evidence of inflammation and foci of epithelial sloughing. Alveolar spaces were also obscured by debris and inflammatory cells. HPA and HPC produced scattered intensely congested heart vessels while HPB(10) produced haemorrhage and amorphous exudates within the heart. All HMPs produced neither treatment-related deaths nor significant change in haematological and biochemical parameters, except for HPA and HPB which decreased (P<0.05) aspartate aminotransferase (AST) and HPB, which elevated (P<0.05) fasting blood glucose (FBG).

Data from the present study suggest the potential of the herbal products (HPs), HPA, HPB and HPC, to cause major organ-system dysfunction or damage. We advise cautious use of these products and recommend further safety evaluation in chronic toxicity models.

Dietary supplements are frequently used by healthy individuals and those with chronic medical conditions but may cause damage to the liver. The aim of this study was to examine the prevalence and attitudes of dietary supplement use, and the frequency of disclosure to healthcare providers among parents/caregivers for children with chronic liver disease.

We developed an anonymous survey for parents/caregivers of children (<18 years old) with chronic liver disease or liver transplant recipients and distributed the survey through social media groups organized around pediatric liver diseases.

The survey was completed by 101 parents/caregivers (48 without transplant and 53 posttransplant).Among respondents, 87% agreed they would use dietary supplements to help their child, but parents/caregivers of transplant recipients were less likely to consider use (77% vs 98%; P = 0.01). In the past 12 months, 83% reported dietary supplement use including 47% who used nonvitamin/mineral supplements. In two-thirds of parents/caregivers, use was initiated by their personal belief. Although 77% of respondents disclosed their use to their liver team, disclosure varied depending on the supplement with no individual that used cannabinoid products disclosing the use.

Dietary supplements are frequently used by children with liver disease and may exceed use in other pediatric conditions. Though most parents report use to their liver team, disclosure may vary depending on the specific supplement. Providers should take extra measures to review use of supplements with their patients and work to develop trust with their families to obtain accurate disclosure of use.

The use of nutraceuticals is considerably increasing worldwide with a demand for organic and clean foods in the last two decades, which is probably incomparable with other periods of our civilization. The consistent application of nutraceuticals and so-called "superfood" may have remarkable effects on the prevention of several chronic diseases, including cancer. Moreover, the increased rate of overweight and obesity in Western countries does not spare childhood and youth, and the number of parents using natural remedies for preventing pediatric illness is vastly increasing worldwide. However, the overwhelming effects on diseases often overshadow the side effects of such nutrition, particularly in societies without millennial experience with botanicals and natural elements. Thus, the final result may be disastrous for some individuals. The liver is the most important and conspicuous target organ of numerous molecular compounds, and the cell damage is particularly striking on the infantile and pediatric liver due to the immaturity of the hepatocytes. Here, we target some generic data on fulminant hepatic failure, the benefits, and toxicity of epigallocatechin-3-gallate, which is one of the major components of green tea, and the histopathology of the "green-tea"-associated liver disease.

MicroRNAs (miRNAs) are short regulatory RNAs that are involved in various biological processes that regulate gene expression posttranscriptionally. Changes in miRNA expression can be detected in many physiological and pathological events, such as liver injury. Drug induced liver injury is a life threatening condition that frequently requires organ transplantation. Hepatotoxicity is also one of the major causes of drug failure in clinical trials and of drug withdrawal from the market. The profiling of miRNA expression shows great promise in monitoring liver injury, in the prediction of outcome in patients, and in the identification of liver-reactive compounds in toxicological assessment. Recent studies have demonstrated organ-specificity of some miRNAs (i.e., miR-122), which are released into biological fluids as a result of hepatocyte damage. This attests to the potential of miRNAs as noninvasive biomarkers to detect liver toxicity. This review presents information on miRNA signatures of hepatotoxicity and on the application of promising miRNA biomarkers in preclinical safety assessment. We further discuss the technical challenges associated with these emerging biomarkers for early diagnosis and detection of hepatotoxicity.