Agreement between self-reported illicit drug use and biological samples: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies often rely upon self-report and biological testing methods for measuring illicit drug use, although evidence for their agreement is limited to specific populations and self-report instruments. We aimed to examine comprehensively the evidence for agreement between self-reported and biologically measured illicit drug use among all major illicit drug classes, biological indicators, populations and settings. METHODS: We systematically searched peer-reviewed databases (Medline, Embase and PsycINFO) and grey literature. Included studies reported 2 × 2 table counts or agreement estimates comparing self-reported and biologically measured use published up to March 2022. With biological results considered to be the reference standard and use of random-effect regression models, we evaluated pooled estimates for overall agreement (primary outcome), sensitivity, specificity, false omission rates (proportion reporting no use that test positive) and false discovery rates (proportion reporting use that test negative) by drug class, potential consequences attached to self-report (i.e. work, legal or treatment impacts) and time-frame of use. Heterogeneity was assessed by inspecting forest plots. RESULTS: From 7924 studies, we extracted data from 207 eligible studies. Overall agreement ranged from good to excellent (> 0.79). False omission rates were generally low, while false discovery rates varied by setting. Specificity was generally high but sensitivity varied by drug, sample type and setting. Self-report in clinical trials and situations of no consequences was generally reliable. For urine, recent (i.e. past 1-4 days) self-report produced lower sensitivity and false discovery rates than past month. Agreement was higher in studies that informed participants biological testing would occur (diagnostic odds ratio = 2.91, 95% confidence interval = 1.25-6.78). The main source of bias was biological assessments (51% studies). CONCLUSIONS: While there are limitations associated with self-report and biological testing to measure illicit drug use, overall agreement between the two methods is high, suggesting both provide good measures of illicit drug use. Recommended methods of biological testing are more likely to provide reliable measures of recent use if there are problems with self-disclosure.

Mifepristone (RU-486®) as a Schedule IV Controlled Drug-Implications for a Misleading Drug Policy on Women's Health Care.

BACKGROUND: Mifepristone (RU-486) has been approved for abortion in Taiwan since 2000. Mifepristone was the first non-addictive medicine to be classified as a schedule IV controlled drug. As a case of the "misuse" of "misuse of drugs laws," the policy and consequences of mifepristone-assisted abortion for pregnant women could be compared with those of illicit drug use for drug addicts. METHODS: The rule-making process of mifepristone regulation was analyzed from various aspects of legitimacy, social stigma, women's human rights, and access to health care. RESULTS AND DISCUSSION: The restriction policy on mifepristone regulation in Taiwan has raised concerns over the legitimacy of listing a non-addictive substance as a controlled drug, which may produce stigma and negatively affect women's reproductive and privacy rights. Such a restriction policy and social stigma may lead to the unwillingness of pregnant women to utilize safe abortion services. Under the threat of the COVID-19 pandemic, the US FDA's action on mifepristone prescription and dispensing reminds us it is time to consider a change of policy. CONCLUSIONS: Listing mifepristone as a controlled drug could impede the acceptability and accessibility of safe mifepristone use and violates women's right to health care.

Validation study of a new reconstructed human epidermis model EPiTRI for in vitro skin irritation test according to OECD guidelines.

Following the global trend of reducing animal testing, various reconstructed human epidermis (RHE) models for skin irritation test (SIT) have been developed, verified, validated and included in OECD TG 439. We developed a new RHE called EPiTRI and a SIT method using EPiTRI (EPiTRI-SIT model) following the OECD guidelines. EPiTRI possesses morphological, biochemical and physiological properties similar to human epidermis with well-differentiated multilayered viable cells with barrier function. The EPiTRI-SIT model was tested for 20 reference chemicals in Performance Standard of OECD TG 439 (GD 220), showing good predictive capacity with 100% sensitivity, 70% specificity and 85% accuracy. EPiTRI had sensitivity in detecting di-n-propyl disulphate, as an irritant chemical (UN GHS Category 2), whereas most validated reference methods detected it as a non-irritant. An international validation study of EPiTRI-SIT was conducted in four laboratories to confirm the within- and between-laboratory reproducibility, as well as predictive capacity. The phase I/II within-laboratory and between-laboratory reproducibility was 100%/95% and 95%, respectively. The overall sensitivity, specificity and accuracy of EPiTRI-SIT was 96%, 70% and 83%, respectively, which fulfilled the OECD criteria. Thus, EPiTRI, meets the criteria of Performance Standards of OECD TG 439 (GD 220) and is suitable for screening irritating chemicals in vitro.

Pharmaceutical Assessment Suggests Locomotion Hyperactivity in Zebrafish Triggered by Arecoline Might Be Associated with Multiple Muscarinic Acetylcholine Receptors Activation.

Arecoline is one of the nicotinic acid-based alkaloids, which is found in the betel nut. In addition to its function as a muscarinic agonist, arecoline exhibits several adverse effects, such as inducing growth retardation and causing developmental defects in animal embryos, including zebrafish, chicken, and mice. In this study, we aimed to study the potential adverse effects of waterborne arecoline exposure on zebrafish larvae locomotor activity and investigate the possible mechanism of the arecoline effects in zebrafish behavior. The zebrafish behavior analysis, together with molecular docking and the antagonist co-exposure experiment using muscarinic acetylcholine receptor antagonists were conducted. Zebrafish larvae aged 96 h post-fertilization (hpf) were exposed to different concentrations (0.001, 0.01, 0.1, and 1 ppm) of arecoline for 30 min and 24 h, respectively, to find out the effect of arecoline in different time exposures. Locomotor activities were measured and quantified at 120 hpf. The results showed that arecoline caused zebrafish larvae locomotor hyperactivities, even at a very low concentration. For the mechanistic study, we conducted a structure-based molecular docking simulation and antagonist co-exposure experiment to explore the potential interactions between arecoline and eight subtypes, namely, M1a, M2a, M2b, M3a, M3b, M4a, M5a, and M5b, of zebrafish endogenous muscarinic acetylcholine receptors (mAChRs). Arecoline was predicted to show a strong binding affinity to most of the subtypes. We also discovered that the locomotion hyperactivity phenotypes triggered by arecoline could be rescued by co-incubating it with M1 to M4 mAChR antagonists. Taken together, by a pharmacological approach, we demonstrated that arecoline functions as a highly potent hyperactivity-stimulating compound in zebrafish that is mediated by multiple muscarinic acetylcholine receptors.

New psychoactive substances in Taiwan: The current situation and initiative for rational scheduling.

Use of New Psychoactive Substances (NPS) has posed a global threat to public health and the security of the population. As of December 2019, the NPS items identified in total have outnumbered by three to one the controlled substances listed in the 1961 and 1971 UN Drug Conventions. However, most of these NPS have not been scheduled by the United Nations because of their easy modification on the chemical structures to shun control. Currently, the scheduling and control of NPS is mostly at the national level and a rational scheduling of NPS by objective assessments is essential but often lacking. To rationally schedule NPS, the NPS misuse situation was firstly estimated with the Taiwanese Substance Misuse Monitoring and Reporting Systems (SMMRS) from 2006 through 2019. Then, the assessment of drug-related harms with an expert Delphi procedure for drug scheduling was performed. The epidemiological analysis revealed that among 37 substances commonly misused in Taiwan, heroin posed the highest risk, followed by (meth)amphetamine and ketamine. Of note, misuse of NPS, such as ketamine, synthetic cannabinoids (JWHs, AM-2201, XJR-11), synthetic cathinones (MDPV, bk-MDMA, 4 -MMCetc.), phenethylamines (PMMA, FMA, 2C-B, 2C-E etc.), piperazines (BZP, TFMPP) and tryptamines (5-MeO-DIPT) has been on the rise. Though perceived drug-related harms differed among experts with different professional backgrounds, the differences were not significant. Four dimensions of drug-related harms- addiction, misuse, social harm and physical harm- integrated from Nutt's model and scheduling criteria of Taiwan's Statute for the Prevention and Control of Illicit Drugs (SPCID), were further divided into 11 indicators and applied to assess harms of the 37 substances. Among the 11 indicators that corresponded to the four dimensions, 7 had significant prediction capabilities. Additionally, prevalence of misuse nationally was an important predictor of harm assessment. These indicators of harm assessment of drug misuse can help develop a proper scheduling system for the management of controlled/illicit drugs. In conclusions, drug scheduling is the first step toward proper management of drug use problems. Facing the threats of NPS, it is imperative to implement a rational and effective scheduling system for appropriate management. This study provides a mechanism to scrutinize, and improve, the current evaluation process for NPS scheduling.

New psychoactive substances in Taiwan: challenges and strategies.

PURPOSE OF REVIEW: Abuse of new psychoactive substances (NPS) has been a new global concern. So far, there has been no international consensus on legislative control of NPS. Scrutiny of Taiwan's illegal drug use history reveals that legislation and policy play an important role in tackling the drug issues. RECENT FINDINGS: Since the early 2000s, use of club drugs (mostly NPS) has become popular in local rave parties and dance clubs in Taiwan. Some NPS, such as ketamine, synthetic cathinones, and para-methoxymethamphetamine, have posed a risk to public health and a challenge to drug policy. SUMMARY: The illegal drug use history in Taiwan was firstly briefly reviewed, and the recent NPS use situation was depicted. Heroin and methamphetamine have been the most predominant drugs, but NPS such as ketamine and synthetic cathinones have become a new issue. The toxicological profiles of commonly abused NPS in Taiwan, although limited, were discussed. By comparison of the legislative mechanism for NPS control between Taiwan, South Korea, and Japan, it was found that timely and flexible legislative mechanism(s) is essential for early identification, surveillance, and comprehensive evaluation. In addition, researches on NPS epidemiology and toxicology are needed to firm up evidence-based strategies for effective prevention, treatment, and harm reduction measures.

Comparison of legislative management for new psychoactive substances control among Taiwan, South Korea, and Japan.

For decades, the three United Nations drug conventions have served as the basis for member states' obligations and international cooperation on drug control. However, the emergence of new psychoactive substances (NPSs) poses a new risk to public health and a challenge to drug policy because of their unknown toxicological effects and easy modification of chemical structures to shun legal control. So far, there is no international consensus on legislative control of NPSs. Therefore, we compared the legislative management on NPS control among Taiwan, South Korea, and Japan. Drug-related information was obtained from the authorities of these three countries. The results indicate that despite geographic proximity and similar legal attitudes toward illegal drug use, the legislative criteria, and responses for NPS control in these three countries were quite different. Ketamine has been the major used NPS in Taiwan but seldom found in South Korea and Japan. The difference in the number of controlled NPSs in Taiwan (91) and South Korea (245) might be due to the implementation of temporary designation systems and analog controls in South Korea. The recent surge of newly controlled NPSs in Japan was because of the promulgation of designated drug regulation and subsequent control of "dangerous drugs." Although NPS use has become a potential social and medical problem among these three countries, the outcomes of NPS legislation control remain to be scrutinized. To minimize harm from NPS use, development of legislative mechanism(s) on NPS scheduling is the first step for early identification and control of NPS problems.

HIV risk and the association with accessibility coverage to medical facilities and socioeconomic status among heroin users in Kaohsiung, Taiwan (2011-2015): A GIS approach.

Illegal drug use has caused considerable health and social costs. Access to medical treatment has been one of the most cost-effective interventions to reduce problematic drug use. Accessibility to treatment, which can be analyzed by the spatial approach such as geographic information system (GIS), has thus been utilized as a measure of the proportion of population that reaches appropriate health services. In this study, the association of accessibility coverage to medical facilities and socioeconomic status with human immunodeficiency virus (HIV) risk for heroin users was evaluated by GIS analysis in Kaohsiung, Taiwan. Data of 7890 heroin users were collected from 2011 to 2015 and categorized into five risk groups according to their income and distance to treatment settings. The results of this GIS-based analysis show that the areas with over 50% accessibility coverage rate had less amounts of HIV cases with statistical significance. Inconvenient access to medical facilities could result in poor treatment outcomes such as higher HIV incidences. Therefore, in order to effectively reduce HIV incidences among the heroin users, the accessibility coverage and locations of medical treatment facilities should meet the needs of drug users. It is also advised that the formulation of policies associated with illegal drug use problems should be evidence-based and geographical indicators could serve for this purpose from either prevention or intervention perspective.

New psychoactive substances of natural origin: A brief review.

Plant-based drugs of abuse are as old as recorded human history. Although traditional addictive substances, such as opium, cannabis and coca, have been controlled by the United Nations anti-drug conventions, many, if not most, natural plants with addictive or abuse liability remain elusive. Therefore, the United Nations Office on Drugs and Crime (UNODC) has warned the emerging threat from new psychoactive substances (NPS), which are mostly derived or modified from the constituents of natural origin. For example, synthetic cannabinoids and synthetic cathinones are derived from the cannabis and khat plant, respectively. In this review, we briefly discussed the chemistry, pharmacology and toxicology of five common NPS of natural origin, i.e., khat, kratom, salvia, magic mushroom and mandrake. Through the review, we hope that professionals and general public alike can pay more attention to the potential problems caused by natural NPS, and suitable control measures will be taken.

Immunomodulatory Effects of Taiwanese Neolitsea Species on Th1 and Th2 Functionality.

Neolitsea species, medicinal plants belonging to Lauraceae, contain rich alkaloids, steroids, sesquiterpenoids, and triterpenoids which possess antimicrobial, antioxidant, and anti-inflammatory bioactivities. However, species differences in the immunomodulatory effects and evidence pertaining to the effects of Neolitsea species on adaptive immunity are scarce. This study aimed to evaluate the immunomodulatory properties of ten Taiwanese Neolitsea plants on T helper (Th) cell functionality, especially Th1 and Th2. Most of the 29 crude extracts of Neolitsea were not toxic to splenocytes, except N. buisanensis roots. N. aciculata and N. villosa leaf extracts possessed differential immunomodulatory effects on Th1/Th2 balance. N. aciculata var. variabillima and N. hiiranensis leaf extracts attenuated both Th1 and Th2 cytokines while N. konishii dramatically suppressed IFN-γ production. As N. aciculata var. variabillima and N. konishii leaf extracts significantly attenuated Th1 functionality, we further evaluated their effects on CD4 cells under CD3/CD28 stimulation. N. aciculata var. variabillima significantly suppressed IFN-γ, IL-10, and IL-17, demonstrating the broad suppressive effects on T helper cells; N. konishii significantly suppressed IFN-γ and IL-10 production, while the production of IL-17 was not altered. Collectively, these data demonstrated that leaf extracts of Taiwanese Neolitsea species contain phytochemicals with potentials to be developed as selective immunomodulators.

Prevalence of new psychoactive substances in Northeast Asia from 2007 to 2015.

The proliferation of new psychoactive substances (NPS) has been a global trend in drug abuse and its regulation has been a worldwide concern. There is no doubt that it is necessary to share information related to these emerging substances between countries and continents for the effective regulation of NPS. With efforts for the efficient regulation of NPS, many studies and information have been published for the prevalence of NPS in the United States and other countries in Europe and Oceania. However, there is lack of information available for the prevalence of NPS in Asian and African countries. Therefore, this research was focused on the investigation of legal status of certain NPS in Northeast Asian countries, including China, Japan, South Korea and Taiwan, in order to provide information on the prevalence and trend of emerging NPS in these countries. The results showed that a total of 940 NPS was reported in 4 Northeast Asian countries from 2007 to 2015. Among 940 NPS, 882 NPS are legally restricted in at least one country (94%) and 96 substances were not currently under control (6%) in these countries. The number of controlled NPS that are currently controlled in all 4 countries was only 25 (or 28%) out of 882 NPS. Each substance was categorized in 9 groups according to the classification proposed by the United Nations Office on Drugs and Crime (UNODC). In Northeast Asia, the most commonly controlled NPS were synthetic cannabinoids, synthetic cathinones, and phenethylamines. It was found that Japan is the most proactive country in terms of the NPS regulation with 41% of the total number of controlled NPS in Northeast Asia, followed by South Korea (21%), China (28%), Taiwan (10%). Comparing the number of NPS newly regulated in each country every year, NPS has been broadly scheduled in 2011 and the number of scheduled NPS has dramatically increased from 2013 to 2015. It was shown that Northeast Asia is also in danger of these emerging NPS and the effective regulation across countries is important for the prevention of NPS. Also, this study will bring attention to local law enforcement in the construction of local drug crime prevention network sharing information for these controlled substances.

Comparison of illegal drug use pattern in Taiwan and Korea from 2006 to 2014.

BACKGROUND: Illegal drug use has long been a global concern. Taiwan and Korea are geographically adjacent and both countries have experienced the illegal use problems of methamphetamine, a predominant prototype of New Psychoactive Substances (NPS). NPS, a term coined by the United Nations Office on Drugs and Crime (UNODC) in recent years, have not been scrutinized for their safety and may become a new threat to public health and security worldwide. To conduct evidence-based drug policy, it is imperative to estimate the trend and pattern of illegal drug use. Therefore, this study aims to analyze and compare the current status of drug-related seizures, arrests and illegal drug use, with a focus on methamphetamine and NPS, between Taiwan and Korea. METHODS: Data of illegal drug (including NPS)-related seizures and arrests were collected via anti-drug related agencies of both countries from 2006 through 2014.Since listing of NPS as controlled substances was a result of NPS abuse liability through official evaluation, the items of controlled NPS were used as an indicator of emerging use. These data obtained from Taiwan and Korea was then compared. RESULTS: The results showed that while methamphetamine remained as a predominant drug in both Taiwan and Korea for decades, different illegal drug use patterns have been observed in these two countries. In Taiwan, the major illegal drugs were methamphetamine, heroin, and ketamine, whereas in Korea those were methamphetamine and cannabis. By comparison of per capita illicit drug seizures, the illegal drug use situation in Taiwan was at a higher stake than that in Korea. In terms of NPS use, ketamine has been a major drug in Taiwan, but it was seldom found in Korea. Besides ketamine, the major type of NPS was synthetic cathinones in Taiwan whereas it was synthetic cannabinoids and phenethylamines in Korea. The difference in the numbers of controlled NPS items between Taiwan (23) and Korea (93) may be due to the implementation of temporary control on NPS in Korea since 2011. CONCLUSION: While the problem of methamphetamine still lingers, NPS have emerged as a new issue in both countries. However, the NPS pattern was different between Taiwan and Korea. Although the controlled NPS items in Taiwan were far less than those in Korea, the quantity of total NPS seizures, especially with ketamine, was much larger in Taiwan than in Korea. Different NPS pattern may also imply they were from different sources. Factors other than geographical proximity, such as drug policy and availability and accessibility to drugs, should be taken into account for the current status of illegal drug use in Korea and Taiwan.

Illegal use patterns, side effects, and analytical methods of ketamine.

In Asian countries, such as China, Taiwan, and Hong Kong, ketamine (KT) is one of the most prevalent illicit use drugs. KT is regulated by various drug-related laws in many countries, such as Korea, Taiwan, China, U.S.A, Netherlands, UK, Australia, Mexico, and Canada. This review research explored pharmacology and side effects of KT, the illicit use patterns of KT, the analytical methods of KT in biological samples, and the concentrations of KT from abusers and non-abusers. Many side effects of KT have been reported mental and physical problems. Although many studies conducted various analytical methods for KT, this research focused on the urine and hair analysis and compared some parameters of samples, instruments, columns, extraction methods, internal standards, LOD/LOQ levels, metabolites, NK/K ratio, cut off values, and m/z values. Our research also compared the concentrations of KT in biological samples from abusers and non-abusers. Many rapid and precise analytical methods for illegal KT use are needed to be developed and applied to real samples. To minimize and prevent harm from KT, the authorities and appropriate agencies require a careful assessment, evaluation, early identification, and surveillance of KT users in both clinical and social settings. In addition, there is a need to construct a stricter legislative management and provide preventive education to younger individuals because illegal KT use is relatively common among the young populations.

Identification of 1,2,3,4,6-Penta-O-galloyl-ß-d-glucopyranoside as a Glycine N-Methyltransferase Enhancer by High-Throughput Screening of Natural Products Inhibits Hepatocellular Carcinoma.

Glycine N-methyltransferase (GNMT) expression is vastly downregulated in hepatocellular carcinomas (HCC). High rates of GNMT knockout mice developed HCC, while overexpression of GNMT prevented aflatoxin-induced carcinogenicity and inhibited liver cancer cell proliferation. Therefore, in this study, we aimed for the identification of a GNMT inducer for HCC therapy. We established a GNMT promoter-driven luciferase reporter assay as a drug screening platform. Screening of 324 pure compounds and 480 crude extracts from Chinese medicinal herbs resulted in the identification of Paeonia lactiflora Pall (PL) extract and the active component 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranoside (PGG) as a GNMT inducer. Purified PL extract and PGG induced GNMT mRNA and protein expression in Huh7 human hepatoma cells and in xenograft tumors. PGG and PL extract had potent anti-HCC effects both in vitro and in vivo. Furthermore, PGG treatment induced apoptosis in Huh7 cells. Moreover, PGG treatment sensitized Huh7 cells to sorafenib treatment. Therefore, these results indicated that identifying a GNMT enhancer using the GNMT promoter-based assay might be a useful approach to find drugs for HCC. These data also suggested that PGG has therapeutic potential for the treatment of HCC.

Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core.

Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D2 gas generation were exploited to suppress undesired over-reactions and to maximize reaction rates simultaneously. The novel deuterium-containing chalcone derivatives may have interesting biological effects and improved metabolic properties as compared with the parent compounds.

Following "the Roots" of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries.

The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.

Dual dispersive liquid-liquid microextraction for determination of phenylpropenes in oils by gas chromatography-mass spectrometry.

A novel, simple and quick sample preparation method was developed and used for pre-concentration and extraction of six phenylpropenes, including anethole, estragole, eugenol, methyl eugenol, safrole and myristicin, from oil samples by dual dispersive liquid-liquid microextraction. Gas chromatography-mass spectrometry was used for determination and separation of compounds. Several experimental parameters affecting extraction efficiency were evaluated and optimized, including forward-extractant type and volume, surfactant type and concentration, water volume, and back-extractant type and volume. For all analytes (10-1000ng/mL), the limits of detection (S/N≧3) ranged from 1.0 to 3.0ng/mL; the limits of quantification (S/N≧10) ranged from 2.5 to 10.0ng/mL; and enrichment factors ranged from 3.2 to 37.1 times. Within-run and between-run relative standard deviations (n=6) were less than 2.61% and less than 4.33%, respectively. Linearity was excellent with determination coefficients (r(2)) above 0.9977. The experiments showed that the proposed method is a simple, effective, and environmentally friendly method of analyzing phenylpropenes in oil samples.

Chemical constituents derived from Artocarpus xanthocarpus as inhibitors of melanin biosynthesis.

Twenty-four compounds, including the previously unknown artoxanthocarpuone A, artoxanthocarpuone B, hydroxylakoochin A, methoxylakoochin A, epoxylakoochin A, and artoxanthol, were isolated and characterized spectroscopically. Among them, artoxanthol is stilbene oligomer presumably constructed in a 5,11,12-triphenyl hexahydrochrysene scaffold by a Diels-Alder type of reaction, for which a biosynthetic pathway is proposed. Artoxanthol, alboctalol, steppogenin, norartocarpetin, resveratrol, oxyresveratrol, and chlorophorin potently inhibited mushroom tyrosinase activity with IC50 values from 0.9 to 5.7 µM that were all far stronger than the positive controls. Artoxanthocarpuone A, artoxanthocarpuone B, methoxylakoochin A, lakoochin A, cudraflavone C, artonin A, resveratrol, and chlorophorin reduced tyrosinase activity and inhibited α-melanocyte-stimulating hormone-induced melanin production in B16F10 melanoma cells without affecting cell proliferation. Collectively, the results suggest that the constituents of Artocarpus xanthocarpus have potential to be used as depigmentation agents.

Developing a QSAR model for hepatotoxicity screening of the active compounds in traditional Chinese medicines.

The perception that natural substances are deemed safe has made traditional Chinese medicine (TCM) popular in the treatment and prevention of disease globally. However, such an assumption is often misleading owing to a lack of scientific validation. To assess the safety of TCM, in silico screening provides major advantages over the classical laboratory approaches in terms of resource- and time-saving and full reproducibility. To screen the hepatotoxicity of the active compounds of TCMs, a quantitative structure-activity relationship (QSAR) model was firstly established by utilizing drugs from the Liver Toxicity Knowledge Base. These drugs were annotated with drug-induced liver injury information obtained from clinical trials and post-marketing surveillance. The performance of the model after nested 10-fold cross-validation was 79.1%, 91.2%, 53.8% for accuracy, sensitivity, and specificity, respectively. The external validation of 91 well-known ingredients of common herbal medicines yielded a high accuracy (87%). After screening the TCM Database@Taiwan, the world's largest TCM database, a total of 6853 (74.8%) ingredients were predicted to have hepatotoxic potential. The one-hundred chemical ingredients predicted to have the highest hepatotoxic potential by our model were further verified by published literatures. Our study indicated that this model can serve as a complementary tool to evaluate the safety of TCM.

TIPdb-3D: the three-dimensional structure database of phytochemicals from Taiwan indigenous plants.

The rich indigenous and endemic plants in Taiwan serve as a resourceful bank for biologically active phytochemicals. Based on our TIPdb database curating bioactive phytochemicals from Taiwan indigenous plants, this study presents a three-dimensional (3D) chemical structure database named TIPdb-3D to support the discovery of novel pharmacologically active compounds. The Merck Molecular Force Field (MMFF94) was used to generate 3D structures of phytochemicals in TIPdb. The 3D structures could facilitate the analysis of 3D quantitative structure-activity relationship, the exploration of chemical space and the identification of potential pharmacologically active compounds using protein-ligand docking. Database URL: http://cwtung.kmu.edu.tw/tipdb.