Kava extract, an herbal alternative for anxiety relief, potentiates acetaminophen-induced cytotoxicity in rat hepatic cells

The widely used over-the-counter analgesic acetaminophen (APAP) is the leading cause of acute liver failure in the United States and due to this high incidence, a recent FDA Advisory Board recommended lowering the maximum dose of APAP. Kava herbal dietary supplements have been implicated in several human liver failure cases leading to the ban of kava-containing products in several Western countries. In the US, the FDA has issued warnings about the potential adverse effects of kava, but kava dietary supplements are still available to consumers. In this study, we tested the potential of kava extract to potentiate APAP-induced hepatocyte cytotoxicity. In rat primary hepatocytes, co-treatment with kava and APAP caused 100% loss of cell viability, while the treatment of kava or APAP alone caused ∼50% and ∼30% loss of cell viability, respectively. APAP-induced glutathione (GSH) depletion was also potentiated by kava. Co-exposure to kava decreased cellular ATP concentrations, increased the formation of reactive oxygen species, and caused mitochondrial damage as indicated by a decrease in mitochondrial membrane potential. In addition, similar findings were obtained from a cultured rat liver cell line, clone-9. These observations indicate that kava potentiates APAP-induced cytotoxicity by increasing the magnitude of GSH depletion, resulting in oxidative stress and mitochondrial dysfunction, ultimately leading to cell death. These results highlight the potential for drug-dietary supplement interactions even with widely used over-the-counter drugs.     

Green synthesized nanoparticles in the fight against mosquito-borne diseases and cancer—a brief review

Nanobiomedicine and parasitology are facing a number of key challenges, which mostly deal with the paucity of effective preventive and curative tools against mosquito-borne diseases and cancer. In this scenario, the employ of botanical and invertebrate extracts as reducing, stabilizing and capping agents for the synthesis of nanoparticles is advantageous over chemical and physical methods, since it is one-pot, cheap, and does not require high pressure, energy, temperature, or the use of highly toxic chemicals. Considering the overlooked connection between mosquito vector activity and the spread of cancer in USA, this review focused on the current knowledge available about green synthesized nanoparticles with efficacy against mosquito-borne diseases and cancer. Green fabricated metal nanoparticles showed antiplasmodial activity that often encompasses the efficacy of currently marked drugs for malaria treatment. They have been also reported as growth inhibitors against dengue virus (serotype DEN-2), with moderate cytotoxicity on mammalian cells. However, this feature is strongly dependent to the botanical agents employed during nanosynthesis. In addition, green nanoparticles have been successfully used to reduce mosquito young instar populations in the field. The final section focuses on some issues for future research, with special reference to the chemical standardization of the botanical extracts used for nanosynthesis and the potential effects on green fabricated nanoparticles on non-target organisms.     

Molecular breeding of switchgrass for use as a biofuel crop

Switchgrass (Panicum virgatum L.) is projected to become one of the main herbaceous, biofuel crops in United States. This status was the result of several years of research; much it sponsored by the United States Department of Energy (DOE). Literature documenting fundamental aspects of switchgrass taxonomy, genetics, breeding, management, physiology, and use is now available and form the basis for protocols to establish and manage the crop, as well as efforts to develop improved cultivars. Future improvement will include production of high yielding hybrids and the use of genomic and transgenic biotechnologies to enhance both productivity and chemical composition. Reducing bioconversion recalcitrance via reduction of lignin content is an example of projected future research in this area.     

Hallucinogenic botanicals of America: a growing need for focused drug education and research

Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and dissociative drugs harvested from nature or that are openly and legally cultivated in the United States. Examples of harmful outcomes reported in the media are contrasted with existing responsible ingestion by others, some of whom have the protected right to do so for traditional or sacramental religious purposes. Despite an ongoing and expensive effort to warn people of the potential harms of recreational drug use, little is known about the extent of use of these psychoactive botanicals, and the recent explosion of information available via the Internet could herald a storm of morbidity to come. Mounting more targeted research and educational efforts today may reduce later use and abuse, inform society about the special circumstances of religious use, and better prepare clinicians and other health care providers about the issues involved when people choose to indigenously source psychoactive drugs for human consumption.     

Batch-to-Batch Quality Consistency Evaluation of Botanical Drug Products Using Multivariate Statistical Analysis of the Chromatographic Fingerprint

Botanical drug products have batch-to-batch quality variability due to botanical raw materials and the current manufacturing process. The rational evaluation and control of product quality consistency are essential to ensure the efficacy and safety. Chromatographic fingerprinting is an important and widely used tool to characterize the chemical composition of botanical drug products. Multivariate statistical analysis has showed its efficacy and applicability in the quality evaluation of many kinds of industrial products. In this paper, the combined use of multivariate statistical analysis and chromatographic fingerprinting is presented here to evaluate batch-to-batch quality consistency of botanical drug products. A typical botanical drug product in China, Shenmai injection, was selected as the example to demonstrate the feasibility of this approach. The high-performance liquid chromatographic fingerprint data of historical batches were collected from a traditional Chinese medicine manufacturing factory. Characteristic peaks were weighted by their variability among production batches. A principal component analysis model was established after outliers were modified or removed. Multivariate (Hotelling T ² and DModX) control charts were finally successfully applied to evaluate the quality consistency. The results suggest useful applications for a combination of multivariate statistical analysis with chromatographic fingerprinting in batch-to-batch quality consistency evaluation for the manufacture of botanical drug products.     

Do lakes feel the burn? Ecological consequences of increasing exposure of lakes to fire in the continental United States

Wildfires are becoming larger and more frequent across much of the United States due to anthropogenic climate change. No studies, however, have assessed fire prevalence in lake watersheds at broad spatial and temporal scales, and thus it is unknown whether wildfires threaten lakes and reservoirs (hereafter, lakes) of the United States. We show that fire activity has increased in lake watersheds across the continental United States from 1984 to 2015, particularly since 2005. Lakes have experienced the greatest fire activity in the western United States, Southern Great Plains, and Florida. Despite over 30 years of increasing fire exposure, fire effects on fresh waters have not been well studied; previous research has generally focused on streams, and most of the limited lake‐fire research has been conducted in boreal landscapes. We therefore propose a conceptual model of how fire may influence the physical, chemical, and biological properties of lake ecosystems by synthesizing the best available science from terrestrial, aquatic, fire, and landscape ecology. This model also highlights emerging research priorities and provides a starting point to help land and lake managers anticipate potential effects of fire on ecosystem services provided by fresh waters and their watersheds.     

Environmental Contaminants in the Botanical Dietary Supplement Ginseng and Potential Human Risk

Botanical dietary supplements have a long history of use in Europe and Asia, but the use of these products is becoming increasing popular in the United States. Because these products are classified as dietary supplements, the U.S. Food and Drug Administration does not routinely monitor them for environmental contaminants. Ginseng served as a model botanical dietary supplement and was purchased from suppliers in the United States, Europe, and Asia. Samples were analyzed for metals (e.g., cadmium, nickel) and chlorinated pesticides (e.g., PCNB, DDT, and metabolites). Flame and furnace atomic absorption spectrophotometry were utilized for analysis of metals, while gas chromatography (GC) and GC-mass spectrophotometry were utilized for analysis of chlorinated pesticides. Because no formalized guidelines exist to determine risk of botanical dietary supplements, U.S. Environmental Protection Agency guidelines for protection of human health were used. Metals and chlorinated organics were found in Ginseng samples, but the concentrations posed no noncarcinogenic hazard; however, a 1000?mg/d dose for 350?d/yr resulted in 1 × 10^?6 carcinogenic risk in 19% of the Ginseng samples analyzed. At a lower usage rate (42?d/yr), no samples exceeded 1 × 10^?6 risk. Chlorinated organics, such as aldrin and heptachlor epoxide, accounted for the carcinogenic risk (1 X 10-6) in the Ginseng samples.     

Indian Podophyllum

Since Indian Podophyllum is very rich in a resin of cathartic action, it has been the subject of several botanical, chemical and pharmacological investigations, and has been admitted to the British Pharmacopoeia but not yet to that of the United States.     

Streamlined approach for assessing embedded consumption of lithium and cobalt in the United States

In today's complex global supply chains, time and data intensive analyses are required to understand global flows of mineral commodities from mine to consumer, particularly for mineral commodities in products (electronics, automobiles, etc.) that contain multiple parts with many mineral commodities. National and regional analyses require additional time and data to incorporate international trade flows. However, data limitations and time constraints often prohibit global and national material flow analyses for minor metals. Here we present a methodological approach to circumvent these constraints by utilizing readily available industry-level global data from the United Nations Statistics Division and national industrial data to estimate total requirements for a mineral commodity. We apply this approach to lithium and cobalt use in the United States for the year 2018 and distinguish between apparent raw material consumption versus inferred embedded consumption of lithium and cobalt materials in all forms. The results show that more than half of the United States’ total requirements for both lithium and cobalt is in parts and products that were manufactured outside the United States. In large part, this is due to limited US manufacturing capability for lithium-ion battery materials and cells and the United States’ high import reliance for electronics that use those batteries.     

Herbal remedies for anxiety - a systematic review of controlled clinical trials.

Anxiety is a prominent indication for herbal medicine. This systematic review was therefore aimed at summarising the evidence for or against the anxiolytic efficacy of such treatments. Six databases were searched for all randomised clinical trials testing herbal monopreparations in the alleviation of anxiety. Seven such studies and one systematic review were located. Eight different herbals were studied. The herbal medicines, which, according to these data are associated with anxiolytic activity in humans, are Piper methysticum and Bacopa monniera. Only for kava were independent replications available. It was concluded that there is a lack of rigorous studies in this area and that only kava has been shown beyond reasonable doubt to have anxiolytic effects in humans.     

Mentors and role models for women in academic medicine.

Senior mentors and role models have a positive influence on the career advancement of junior professionals in law, business, and medicine. In medicine an increasing number of women are pursuing academic careers, but available senior mentors to provide career guidance are often lacking. We report on the results of a national survey of 558 full-time faculty women, aged 50 years and younger, in departments of medicine in the United States, regarding their experience with role models and mentors. Women with mentors report more publications and more time spent on research activity than those without mentors. Women with a role model reported higher overall career satisfaction. This report, with illustrative examples, may be helpful to other women pursuing academic careers and to physicians who serve as mentors or role models to others.     

Muthi to medicine

The limited commercial opportunity for bioprospecting for isolated pure natural compounds or their derivatives from plants for novel pharmaceuticals is discussed. A broad overview of the key research inputs involved in the commercialisation of indigenous medicinal plants as botanical medicines is given to assist young researchers in contextualising research from an industry perspective, and to encourage university-industry collaboration. Compliance with the Biodiversity Act of 2004, and the regulations under this Act is stressed. The chain of research and development (R&D) activities is briefly described including ethnobotanical research, raw material supply, identification of active compounds, extract development, absorption studies, formulation development, in vitro, in vivo, and clinical safety and efficacy studies, and protection of intellectual property. Ultimately obtaining international marketing authorization for a novel botanical medicine is a lengthy and costly undertaking, with high risk of failure. Elements of botanical medicine R&D can be applied to functional foods, novel foods and personal care products, which can reach the market faster and with less risk than botanical medicines.     

在美国进行植物药开发的路径、要求及策略探讨

近年来,越来越多药企开始在美国进行植物药的临床试验申请和新药申报,美国 FDA 日益重视植物药的开发,于 2016 年 12 月 发布并实施了修订版的《行业指南:植物药》,为植物药后期开发提供更多专业建议。结合 FDA 已经批准的 2 个植物药案例,详细介绍 植物药 CMC(化学、生产、控制)、临床前研究和过往人用历史方面的基本要求,浅谈 FDA 的申报要求、审评思想和申报策略,以期 为中国中药企业的国际化开发和注册提供参考。     

Environmental Impacts of Consumption in the European Union:High-Resolution Input-Output Tables with Detailed Environmental Extensions

For developing product policy, insight into the environmental effects of products is required. But available life-cycle assessment studies (LCAs) are hardly comparable between different products and do not cover total consumption. Input-output analysis with environmental extensions (EEIOA) of full consumption is not available for the European Union. Available country studies have a low sector resolution and a limited number of environmental extensions. This study fills the gap between detailed LCA and low-resolution EEIOA, specifying the environmental effects of household consumption in the European Union, discerning nearly 500 sectors, while specifying a large number of environmental extensions. Added to the production sectors are a number of consumption activities with direct emissions, such as automobile driving, cooking and heating, and a number of postconsumer waste management sectors. The data for Europe have been constructed by using the sparse available and coarse economic and environmental data on European countries and adding technological detail mainly based on data from the United States.
A small number of products score high on environmental impact per Euro and also have a substantial share of overall consumer expenditure. Several meat and dairy products, household heating, and car driving thus have a large share of the total environmental impact. Due to their sales volume, however, products with a medium or low environmental score per Euro may also have a substantial impact. This is the case with bars and restaurants, clothing, residential construction, and even a service such as telecommunications. The limitations in real European data made heroic assumptions necessary to operationalize the model. One conclusion, therefore, is that provision of data in Europe urgently needs to be improved, at least to the level of sector detail currently available for the United States and Japan.     

Kava lactones and the kava-kava controversy

Kava-kava is a traditional beverage of the South Pacific islanders and has had centuries of use without major side effects. Standardised extracts of kava-kava produced in Europe have led to many serious health problems and even to death. The extraction process (aqueous vs. acetone in the two types of preparations) is responsible for the difference in toxicity as extraction of glutathione in addition to the kava lactones is important to provide protection against hepatotoxicity. The Michael reaction between glutathione and kava lactones, resulting in opening of the lactone ring, reduces the side effects of the kava kava extracts. This protective activity was demonstrated using Acanthamoebae castellanii in which 100% cell death occurred with 100 mg ml(-1) kava lactones alone, and 40% cell death with a mixture of 100 mg ml (-1)glutathione and 100 mg ml (-1) kava lactones. A comparison of kava lactone toxicity with other pharmaceutical products is discussed and recommendations made for safe usage of kava-kava products     

美国生命科学两用性研究监管政策分析

目的:近年来高致病性禽流感H5N1病毒基因改造研究及美国国家生物安全科学咨询委员会的监管建议引起广泛争议,美国发布了生命科学两用性研究监管政策。本研究旨在通过对美国生命科学两用性研究监管政策进行分析,探讨两用性研究发展和监管趋势。方法:通过文献检索,获取生命科学两用性研究监管政策相关的情报源,对美国政府生命科学两用性研究监管的政策背景、主要内容、政策评论、政策动因进行系统梳理与分析。结果:美国政府出台的生命科学两用性研究监管政策,有助于美国对整个生命科学研究周期(从最初提交资助申请到研究结论和研究成果交流)潜在的误用风险进行管理。结论:美国生命科学两用性研究引发极大争议,两用性研究监管主要依靠生命科学团体的自我管理,政策具有指导性而非强制性。     

Driving following Kava Use and Road Traffic Injuries: A Population-Based Case-Control Study in Fiji (TRIP 14)

Objective

To investigate the association between kava use and the risk of four-wheeled motor vehicle crashes in Fiji. Kava is a traditional beverage commonly consumed in many Pacific Island Countries. Herbal anxiolytics containing smaller doses of kava are more widely available.

Methods

Data for this population-based case-control study were collected from drivers of ‘case’ vehicles involved in serious injury-involved crashes (where at least one road user was killed or admitted to hospital for 12 hours or more) and ‘control’ vehicles representative of ‘driving time’ in the study base. Structured interviewer administered questionnaires collected self-reported participant data on demographic characteristics and a range of risk factors including kava use and potential confounders. Unconditional logistic regression models estimated odds ratios relating to the association between kava use and injury-involved crash risk.

Findings

Overall, 23% and 4% of drivers of case and control vehicles, respectively, reported consuming kava in the 12 hours prior to the crash or road survey. After controlling for assessed confounders, driving following kava use was associated with a four-fold increase in the odds of crash involvement (Odds ratio: 4.70; 95% CI: 1.90–11.63). The related population attributable risk was 18.37% (95% CI: 13.77–22.72). Acknowledging limited statistical power, we did not find a significant interaction in this association with concurrent alcohol use.

Conclusion

In this study conducted in a setting where recreational kava consumption is common, driving following the use of kava was associated with a significant excess of serious-injury involved road crashes. The precautionary principle would suggest road safety strategies should explicitly recommend avoiding driving following kava use, particularly in communities where recreational use is common.     

Letter from RIKEN

Summary This is an excellent research laboratory for work in an important aspect of plant molecular biology. Generous fellowships, including travel funds for families, are available throughout the Science and Technology Agency; information in the United States is available from the National Science foundation. I can personally testify that living conditions at RIKEN are excellent, that the Japanese language is manageable with a little effort, that Japanese food is delicious, and that the people are gracious and helpful to foreign visitors. Of course, prices are extremely high by United States standards, but the RIKEN stipends are sufficiently generous to overcome even that difficulty.