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Andropogon virginicus is an invasive weed that seriously threatens agricultural production and economics worldwide. In this research, dried aerial parts of A. virginicus were extracted, applying Soxhlet and liquid-liquid phase methods to acquire the total crude (T-Anvi), hexane (H-Anvi), ethyl acetate (E-Anvi), butanol (B-Anvi), and water (W-Anvi) extracts, respectively. In which, T-Anvi contains the highest total phenolic and flavonoid contents (24.80 mg gallic acid and 37.40 mg rutin equivalents per g dry weight, respectively). Via anti-radical (ABTS and DPPH), and reducing power assays, E-Anvi exhibits the most potent activities (IC50 = 13.96, 43.59 and 124.11 µg/mL, respectively), stronger than butylated hydroxytoluene (BHT), a standard antioxidant, while the lipid peroxidation inhibitory effect of E-Anvi (LPI = 90.85% at the concentration of 500 µg/mL) is close to BHT. E-Anvi shows the most substantial inhibition (IC50 = 2.58 mg/mL) on tyrosinase. Notably, α-amylase is significantly suppressed by H-Anvi (IC50 = 0.72 mg/mL), over twice stronger than the positive control, palmitic acid. In the cytotoxic assay, E-Anvi is the strongest extract inhibiting K562 cells (IC50 = 112.01 µg/mL). Meanwhile, T-Anvi shows the highest prevention on Meg-01 expansion (IC50 = 91.40 µg/mL). Dominant compounds detected in E-Anvi by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) are identified as flavonoids. However, among four major compounds identified in H-Anvi by gas chromatography-mass spectrometry (GC-MS), palmitic acid and phytol are the most abundant compounds with peak areas of 27.97% and 16.42%, respectively. In essence, this is the first report describing that A. virginicus is a potential natural source of antioxidants, tyrosinase and α-amylase inhibitors, and anti-chronic myeloid leukemia (CML) agents which may be useful in future therapeutics as promising alternative medicines.
RUCAM (Roussel Uclaf Causality Assessment Method) or its previous synonym CIOMS (Council for International Organizations of Medical Sciences) is a well established tool in common use to quantitatively assess causality in cases of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI). Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report. Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. We now present the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality assessment as a common basic tool.
Among the causality assessment methods used for the diagnosis of drug-induced liver injury (DILI), Roussel Uclaf Causality Assessment Method (RUCAM) remains the most widely used not only for individual cases but also for prospective and retrospective studies worldwide. This first place is justified by the characteristics of the method such as precise definition and classification of the liver injury, which determines the right scale in the scoring system, precise definition of the seven criteria, and the validation approach based on cases with positive rechallenge. RUCAM is used not only for any types of drugs but also for herbal medicines causing herb-induced liver injury, (HILI) and dietary supplements. In 2016, the updated RUCAM provided further specifications of criteria and instructions to improve interobserver variability. Although this method was criticized for criteria such as the age and alcohol consumption, recent consensus meeting of experts has recognized their value and recommended their incorporation into any method. While early studies searching for DILI in large databases especially in electronic medical records were based on codes of diseases or natural language without causality assessment, the recommendation is now to include RUCAM in the search for DILI/HILI. There are still studies on DILI detection or the identification of biomarkers that take into consideration the cases assessed as “possible,” although it is well known that these cases reduce the strength of the association between the cases and the offending compound or the new biomarker to be validated. Attempts to build electronic RUCAM or automatized application of this method were successful despite some weaknesses to be corrected. In the future, more reflections are needed on an expert system to standardize the exclusion of alternative causes according to the clinical context. Education and training on RUCAM should be encouraged to improve the results of the studies and the day-to-day work in pharmacovigilance departments in companies or in regulatory agencies. It is also expected to improve RUCAM with biomarkers or other criteria provided that the validation process replaces expert opinion by robust standards such as those used for the original method.
Herb induced liver injury (HILI) and drug induced liver injury (DILI) share the common characteristic of chemical compounds as their causative agents, which were either produced by the plant or synthetic processes. Both, natural and synthetic chemicals are foreign products to the body and need metabolic degradation to be eliminated. During this process, hepatotoxic metabolites may be generated causing liver injury in susceptible patients. There is uncertainty, whether risk factors such as high lipophilicity or high daily and cumulative doses play a pathogenetic role for HILI, as these are under discussion for DILI. It is also often unclear, whether a HILI case has an idiosyncratic or an intrinsic background. Treatment with herbs of Western medicine or traditional Chinese medicine (TCM) rarely causes elevated liver tests (LT). However, HILI can develop to acute liver failure requiring liver transplantation in single cases. HILI is a diagnosis of exclusion, because clinical features of HILI are not specific as they are also found in many other liver diseases unrelated to herbal use. In strikingly increased liver tests signifying severe liver injury, herbal use has to be stopped. To establish HILI as the cause of liver damage, RUCAM (Roussel Uclaf Causality Assessment Method) is a useful tool. Diagnostic problems may emerge when alternative causes were not carefully excluded and the correct therapy is withheld. Future strategies should focus on RUCAM based causality assessment in suspected HILI cases and more regulatory efforts to provide all herbal medicines and herbal dietary supplements used as medicine with strict regulatory surveillance, considering them as herbal drugs and ascertaining an appropriate risk benefit balance.
Background and Aim. Spontaneous bacterial peritonitis (SBP) is one of the most common complications of liver cirrhosis. Antibiotics are the main treatment regimen of SBP. Traditional Chinese medicine Xuebijing injection has been used in such patients. Our study aimed to overview the efficacy of Xuebijing injection combined with antibiotics for the treatment of SBP.
Method. We searched the PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang databases. The search items included "Xuebijing", "peritonitis", "liver cirrhosis", and "random" to identify all relevant randomized controlled trials (RCTs). The Cochrane risk of bias tool was used to assess the study quality. The odd ratios (ORs) with 95% confidence intervals (CIs) were calculated by using a random-effect model. Heterogeneity was also calculated.
Results. A total of 9 RCTs were included. The study quality was unsatisfied. The overall (OR = 2.95, 95% CI = 1.97–4.42, p<0.00001) and complete (OR = 2.18, 95% CI = 1.57–3.04, p<0.00001) responses were significantly higher in the Xuebijing injection combined with antibiotics group than the antibiotics alone group. The incidence of cirrhosis related complications, including hepatic encephalopathy and hepatorenal syndrome, was lower in the Xuebijing injection combined with antibiotics group than the antibiotics alone group. No significant heterogeneity was observed among studies.
Conclusion. Additional use of Xuebijing injection may improve the efficacy of antibiotics for the treatment of SBP in liver cirrhosis. However, due to a low level of current evidence, we did not establish any recommendation regarding the use of Xuebijing injection for the treatment of SBP.
Efficacy from different extractions for chemical profile and biological activities of rice husk
(2018)
Rice husk is a by-product produced abundantly in rice production but it has low commercial value and causes environmental pollution. This study was conducted to examine different extracting solvents and conditions to optimize the efficacy of antioxidant and antimicrobial potentials, and chemical components in rice husk. By the use of distilled water at 100 °C, the ethyl acetate (EtOAc) extract was potent in both total phenolic content (TPC), total flavonoid content (TFC), and DPPH scavenging activity. The treatment of either ethyl acetate (100 °C, 1 h), combined with MeOH 100%, showed the highest percent of lipid peroxidation inhibition (LPI) (86%), meaning that the strongest antioxidant activity was by the β-carotene bleaching method. The treatment of distilled water at room temperature possessed the strongest antioxidant activity in the assay of the reducing power. The use of dried samples at 100 °C for 2 h, combined with methanol (MeOH) 10%, provided the most potent antimicrobial activities against Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Bacillus subtilis, and Proteus mirabilis. The results suggested that the EtOAc extract from rice husk could be a potential source of natural antioxidants. In general, the use of temperature 100 °C for 2 h, combined with either EtOAc or 10% MeOH, can optimize chemical components and antioxidant and antimicrobial capacities in rice husk. Principal constituents putatively identified by gas chromatography–mass spectrometry (GC–MS) revealed the presence of momilactones A and B (MA and MB, respectively), phenols, phenolic acids, and long-chain fatty acids, although yields of these compounds varied among extracts. The bioactive MA and MB were found in most of the extracts, except distilled water and MeOH ≤ 50%, at any temperature. Findings of this study provided optimal conditions for future production at an industrial scale for rice husk to exploit its potent biological properties. It thus helps to increase the economic value and reduce the disposal burden and environmental troubles caused by rice husk.
Momilactones A and B (MA and MB, respectively) are phytoalexins and plant growth inhibitors available in rice husks. However, to date, the isolation and purification of the two compounds have been complicated, laborious, and less effective. The present study was conducted to establish a protocol to simplify and optimize quantities of MA and MB by combinations of ethyl acetate (EtOAc), distilled water, methanol (MeOH), temperature, and pressure for extractions. At a temperature of 100 °C, combined with EtOAc and MeOH 100%, MA and MB were enriched in greater quantities than non-treated rice husks, of which MB was much augmented than MA. The EtOAc extract obtained from samples dried at 100 °C for 1 h, then placed in MeOH 100% for 1 week, provided maximum yields of MA [58.76 µg/g dry weight (DW)] and MB (104.43 µg/g DW). The use of pressure effectively enhanced yields of MA (17.90–26.26 µg/g DW) and MB (40.78–71.0 µg/g DW). The actual purified amounts of MA and MB increased by 5 and 15 folds, respectively. The use of either sole distilled water or MeOH ≤ 50% at any temperature did not successfully isolate both MA and MB. The yield optimization aids to easier and more productive purification of the two compounds, and thus extends researches on biological activities of MA and MB, including pharmaceutical and medicinal properties.
Green tea (GT) and green tea extracts (GTE) have been postulated to decrease cancer incidence. In vitro results indicate a possible effect; however, epidemiological data do not support cancer chemoprevention. We have performed a PubMED literature search for green tea consumption and the correlation to the common tumor types lung, colorectal, breast, prostate, esophageal and gastric cancer, with cohorts from both Western and Asian countries. We additionally included selected mechanistical studies for a possible mode of action. The comparability between studies was limited due to major differences in study outlines; a meta analysis was thus not possible and studies were evaluated individually. Only for breast cancer could a possible small protective effect be seen in Asian and Western cohorts, whereas for esophagus and stomach cancer, green tea increased the cancer incidence, possibly due to heat stress. No effect was found for colonic/colorectal and prostatic cancer in any country, for lung cancer Chinese studies found a protective effect, but not studies from outside China. Epidemiological studies thus do not support a cancer protective effect. GT as an indicator of as yet undefined parameters in lifestyle, environment and/or ethnicity may explain some of the observed differences between China and other countries.
The spectrum of alcoholic liver disease (ALD) is broad and includes alcoholic fatty liver, alcoholic steatohepatitis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatocellular carcinoma, best explained as a five-hit sequelae of injurious steps. ALD is not primarily the result of malnutrition as assumed for many decades but due to the ingested alcohol and its metabolic consequences although malnutrition may marginally contribute to disease aggravation. Ethanol is metabolized in the liver to the heavily reactive acetaldehyde via the alcohol dehydrogenase (ADH) and the cytochrome P450 isoform 2E1 of the microsomal ethanol-oxidizing system (MEOS). The resulting disturbances modify not only the liver parenchymal cells but also non-parenchymal cells such as Kupffer cells (KCs), hepatic stellate cells (HSCs), and liver sinusoidal endothelial cells (LSECs). These are activated by acetaldehyde, reactive oxygen species (ROS), and endotoxins, which are produced from bacteria in the gut and reach the liver due to gut leakage. A variety of intrahepatic signaling pathways and innate or acquired immune reactions are under discussion contributing to the pathogenesis of ALD via the five injurious hits responsible for disease aggravation. As some of the mechanistic steps are based on studies with in vitro cell systems or animal models, respective proposals for humans may be considered as tentative. However, sufficient evidence is provided for clinical risk factors that include the amount of alcohol used daily for more than a decade, gender differences with higher susceptibility of women, genetic predisposition, and preexisting liver disease. In essence, efforts within the last years were devoted to shed more light in the pathogenesis of ALD, much has been achieved but issues remain to what extent results obtained from experimental studies can be transferred to humans.
One of the most difficult challenges in clinical hepatology is the diagnosis of a drug-induced liver injury (DILI). The timing of the events, exclusion of alternative causes, and taking into account the clinical context should be systematically assessed and scored in a transparent manner. RUCAM (Roussel Uclaf Causality Assessment Method) is a well-established diagnostic algorithm and scale to assess causality in patients with suspected DILI. First published in 1993 and updated in 2016, RUCAM is now the worldwide most commonly used causality assessment method (CAM) for DILI. The following manuscript highlights the recent implementation of RUCAM around the world, by reviewing the literature for publications that utilized RUCAM, and provides a review of “best practices” for the use of RUCAM in cases of suspected DILI. The worldwide appreciation of RUCAM is substantiated by the current analysis of 46,266 DILI cases, all tested for causality using RUCAM. These cases derived from 31 reports published from 2014 to early 2019. Their first authors came from 10 countries, with China on top, followed by the US, and Germany on the third rank. Importantly, all RUCAM-based DILI reports were published in high profile journals. Many other reports were published earlier from 1993 up to 2013 in support of RUCAM. Although most of the studies were of high quality, the current case analysis revealed shortcomings in few studies, not at the level of RUCAM itself but rather associated with the work of the users. To ensure in future DILI cases a better performance by the users, a list of essential elements is proposed. As an example, all suspected DILI cases should be evaluated 1) by the updated RUCAM to facilitate result comparisons, 2) according to a prospective study protocol to ensure complete data sets, 3) after exclusion of cases with herb induced liver injury (HILI) from a DILI cohort to prevent confounding variables, and 4) according to inclusion of DILI cases with RUCAM-based causality gradings of highly probable or probable, in order to increase the specificity of the results. In conclusion, RUCAM benefits from its high appreciation and performs well provided the users adhere to published recommendations to prevent confounding variability.