27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression: A key target potentially linking zearalenone and cancer.

Zearalenone (ZEN) is a mycotoxin that extensively contaminates food and feed, posing a significant threat to public health. However, the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear. In this study, Sprague-Dawley (SD) rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w. for a duration of 14 days. The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine. Furthermore, ZEN exposure caused a significant reduction in the levels of apolipoprotein E (ApoE) and liver X receptor (LXR) (P < 0.05). Conversely, it upregulated the levels of myeloid-derived suppressor cells (MDSCs) markers (P < 0.05) and decreased the presence of 27-hydroxycholesterol (27-HC) in the intestine (P < 0.05). It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN. Additionally, a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal, breast, and lung cancers. These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine. Notably, ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.

Zearalenone-14-glucoside specifically promotes dysplasia of Gut-Associated Lymphoid Tissue: A natural product for constructing intestinal nodular lymphatic hyperplasia model.

INTRODUCTION: Zearalenone-14-glucoside (Z14G) is a modified mycotoxin that widely contaminates food across the world. Our preliminary experiment showed that Z14G degrades to zearalenone (ZEN) in the intestine exerting toxicity. Notably, oral administration of Z14G in rats induces intestinal nodular lymphatic hyperplasia. OBJECTIVES: To investigate the mechanism of Z14G intestinal toxicity and how it differs from ZEN toxicity. We conducted a precise toxicology study on the intestine of rats exposed to Z14G and ZEN using multi-omics technology. METHODS: Rats were exposed to ZEN (5 mg/kg), Z14G-L (5 mg/kg), Z14G-H (10 mg/kg), and pseudo germ free (PGF)-Z14G-H (10 mg/kg) for 14 days. Histopathological studies were performed on intestines from each group and compared. Metagenomic, metabolomic, and proteomic analyses were performed on rat feces, serum, and intestines, respectively. RESULTS: Histopathological studies showed that Z14G exposure resulted in dysplasia of gut-associated lymphoid tissue (GALT) compared to ZEN exposure. The elimination of gut microbes in the PGF-Z14G-H group alleviated or eliminated Z14G-induced intestinal toxicity and GALT dysplasia. Metagenomic analysis revealed that Z14G exposure significantly promoted the proliferation of Bifidobacterium and Bacteroides compared to ZEN. Metabolomic analysis showed that Z14G exposure significantly reduced bile acid, while proteomic analysis found that Z14G exposure significantly reduced the expression of C-type lectins compared to ZEN. CONCLUSIONS: Our experimental results and previous research suggest that Z14G is hydrolyzed to ZEN by Bifidobacterium and Bacteroides promoting their co-trophic proliferation. This leads to inactivation of lectins by hyperproliferative Bacteroides when ZEN caused intestinal involvement, resulting in abnormal lymphocyte homing and ultimately GALT dysplasia. It is noteworthy that Z14G is a promising model drug to establish rat models of intestinal nodular lymphatic hyperplasia (INLH), which is of great significance for studying the pathogenesis, drug screening and clinical application of INLH.

A comprehensive review on the pretreatment and detection methods of neonicotinoid insecticides in food and environmental samples.

In recent years, the residues of neonicotinoid insecticide in food and environmental samples have attracted extensive attention. Neonicotinoids have many adverse effects on human health, such as cancer, chronic disease, birth defects, and infertility. They have substantial toxicity to some non-target organisms (especially bees). Hence, monitoring the residues of neonicotinoid insecticides in foodstuffs is necessary to guarantee public health and ecological stability. This review aims to summarize and assess the metabolic features, residue status, sample pretreatment methods (solid-phase extraction (SPE), Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS), and some novel pretreatment methods), and detection methods (instrument detection, immunoassay, and some innovative detection methods) for neonicotinoid insecticide residues in food and environmental samples. This review provides detailed references and discussion for the analysis of neonicotinoid insecticide residues, which can effectively promote the establishment of innovative detection methods for neonicotinoid insecticide residues.

Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by ß-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells.

As one of the most important conjugated mycotoxins, zearalenone-14-glucoside (Z14G) has received widespread attention from researchers. Although the metabolism of Z14G in animals has been extensively studied, the intracellular toxicity and metabolic process of Z14G are not fully elucidated. In this study, the cytotoxicity of Z14G to human ovarian granulosa cells (KGN) and the metabolism of Z14G in KGN cells were determined. Furthermore, the experiments of co-administration of ß-glucosidase and pre-administered ß-glucosidase inhibitor (Conduritol B epoxide, CBE) were used to clarify the mechanism of Z14G toxicity release. Finally, the human colon adenocarcinoma cell (Caco-2) metabolism model was used to verify the toxicity release mechanism of Z14G. The results showed that the IC50 of Z14G for KGN cells was 420 µM, and the relative hydrolysis rate of Z14G on ZEN was 35% (25% extracellular and 10% intracellular in KGN cells). The results indicated that Z14G cannot enter cells, and Z14G is only hydrolyzed extracellularly to its prototype zearalenone (ZEN) by ß-glucosidase which can exert toxic effects in cells. In conclusion, this study demonstrated the cytotoxicity of Z14G and clarified the toxicity release mechanism of Z14G. Different from previous findings, our results showed that Z14G cannot enter cells but exerts cytotoxicity through deglycosylation. This study promotes the formulation of a risk assessment and legislation limit for ZEN and its metabolites.

Simultaneous detection of 93 anabolic androgenic steroids in dietary supplements using gas chromatography tandem mass spectrometry.

In recent years, anabolic androgenic steroids (AASs) have been frequently detected as undeclared ingredients in dietary supplements, where the adverse analytical findings (AAFs) were obtained from analysis of athletes' urine samples after ingestion. In our present study, a GC-MS/MS method for simultaneous detection of 93 anabolic steroids was developed. The chromatographic and mass spectrometric conditions were optimized, and selective reaction monitoring (SRM) mode was adopted to obtain the necessary sensitivity. The whole sample analysis process was completed within 23 min, and the limit of detection (LOD) was 0.5-4 ng.g-1 for solid samples and 0.1-0.8 ng.mL-1 for liquid samples. This method was verified according to World Anti-Doping Agency (WADA) regulations. In addition, the method was found to be specific, accurate. The developed method was then applied to a routine analysis of more than 300 liquid and solid dietary supplements, and one testosterone-positive sample was found. Three suspected drugs, (4-hydroxyandrostenedione, DHEA, and 6-Br androstenedione) were found in three dietary supplements obtained from the Internet through the pretreatment method of this study. This study provides a high-throughput method for screening and monitoring the ingredients of supplements and their subsequent harm to public health.

[Residual status, toxicity, and analytical method of banned pesticides in traditional Chinese medicines].

A total of 33 pesticides have been banned from Chinese medicinal materials and decoction pieces(plants) according to Chinese Pharmacopoeia(2020 edition). According to the chemical structures, they are mainly divided into seven categories: organophosphorus compounds, organochlorines, carbamates, amidines, sulfonylureas, phenylpyrazoles, and ethers. These banned pesticides exhibit neurotoxicity, reproductive toxicity, immune system toxicity, teratogenicity, carcinogenesis, and mutagenesis, seriously damaging human and animal health. They affect not only the quality and safety of traditional Chinese medicines and resulting products, but also their competitiveness in the international market. Due to the numerous varieties of traditional Chinese medicines and their complex substrates, it is necessary to establish a universal and highly sensitive method for pesticide residue detection. This review systematically summarized the residual status, toxicity, and analytical methods of banned pesticides in traditional Chinese medicines, and forecasted the prospects of different analytical techniques, so as to provide reference for further safety and risk assessment of banned pesticide residues in traditional Chinese medicines, thus ensuring the safe production of traditional Chinese medicines.

Development of a sensitive indirect competitive enzyme-linked immunosorbent assay for high-throughput detection and risk assessment of aflatoxin B1 in animal-derived medicines.

Animal-derived medicine is an important part of traditional Chinese medicine (TCM). Studies have shown that many animal-derived medicinal products are susceptible to contaminate of aflatoxins, nevertheless, the rapid detection for animal-derived medicine is prone to be ignored. Here we developed a sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) for rapid screening of aflatoxin B1 (AFB1) in ground beetle, cockroach, silkworm and earthworm. The sensitivity of the icELISA method was significantly enhanced. The IC50 for the four animal-derived medicinal samples ranged from 0.092 to 0.135 ng mL-1; the limit of detection (LOD) was 0.008-0.020 ng mL-1. To obtain high accuracy, the extraction solution and time were evaluated. By using this method, a total of 138 samples were investigated, and the detection rates of AFB1 in ground beetle and earthworm samples were 26.6% and 16.7%, respectively. The result was validated by liquid chromatography combined with tandem mass spectrometry, and an excellent correlation was observed between the two datasets, with a R2 value of 0.999. Our results indicate that the proposed method can be used for the rapid detection of AFB1 in animal-derived medicine. Furthermore, the quantitative risk assessment was conducted for ground beetle and earthworm based on the results, demonstrating that the intake of AFB1 in ground beetle had a slight threat to the risk of cancer.

Illicium verum essential oil, a potential natural fumigant in preservation of lotus seeds from fungal contamination.

The antifungal properties of Illicium verum essential oil (IV-EO) against a toxigenic strain of Aspergillus flavus (A. flavus) were analyzed in order to determine its use in the preservation of lotus seeds. GC/MS analysis of IV-EO revealed that its main components are trans-anethole (91.32%), D-Limonene (2.0%) and estragole (2.0%). The antifungal activity of IV-EO against A. flavus infection was analyzed in vitro upon A. flavus with the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) determined to be 2.0 and 4.0 µL/mL, respectively. IV-EO exhibited strong inhibitory effects on the mycelial growth and spore production of A. flavus, and caused a significant reduction in dry mycelium weight and aflatoxin B1 and B2 (AFB1 and AFB2) biosynthesis. Complete inhibition was observed at an IV-EO concentration of 3.6 µL/mL. Analysis in an in vivo (food system) demonstrated that IV-EO inhibited AFB1 and AFB2 accumulation in lotus seeds to varying degrees depending on its concentration, and completely inhibited aflatoxin production at concentrations above 6.0 µL/g. Morphological studies carried out using SEM revealed that ultra-structural changes in the hyphae and conidiophore structures following IV-EO treatment. Therefore, IV-EO has demonstrated its practical efficacy as a new biological fumigant in the preservation of lotus seeds.

Comprehensive assessment for the residual characteristics and degradation kinetics of pesticides in Panax notoginseng and planting soil.

Incorrect and excess usage of pesticides during crop cultivation poses a serious threat to human health and ecosystems. In this study, we tested for the presence of 201 pesticide residues in 90 batches of Panax notoginseng (P. notoginseng) and 10 batches of planting soil. Pesticide residue characteristics and the relationship between pesticides present in P. notoginseng and the soil were discussed. Twenty-nine pesticides were detected in P. notoginseng samples and 15 pesticides were found in the soil samples. In P. notoginseng samples, the 68.9% of the identified pesticides were fungicides, and six fungicides (procymidone, iprodione, pyrimethanil, propiconazole, dimethomorph and tebuconazole) were found in >90% of the samples. Nine insecticides were found, with one insecticide, chlorpyrifos, detected in 93.3% of the P. notoginseng samples. The residual concentrations of 17 pesticides were found at levels exceeded the "non-Chinese" maximum residue levels (MRLs) for Ginseng and 17 pesticides were found at levels exceeding the MRLs set by China for "pollution-free" P. notoginseng. We observed no significant differences in pesticide residues were found on P. notoginseng from different cultivation areas. We also analyzed the degradation kinetics of pesticides in the soil, as well as their bioconcentration factors (BCFs), and found that the fungicides iprodione and myclobutanil displayed strong uptake from the soil to the root of P. notoginseng. Together, our data suggest that fungicides should be considered as key monitoring substances in P. notoginseng and planting soil.

[Safety evaluation of heavy metals contaminated Astragalus membranaceus using health risk assessment model].

To evaluate the safety of heavy metals contaminated Astragalus membranaceus,an appropriate protocol was established to study the heavy metals pollution level by health risk assessment. This study provided a detailed procedure to assess the medicinal herbs in quality control and safety evaluation,and expected to create awareness among the public on the safety of consuming of A. membranaceus or any other kinds of medicinal herbs. The heavy metals content of Cu,As,Cd,Pb and Hg in a total of 45 batches of A. membranaceus were carefully analyzed with a developed inductively coupled plasma mass spectrometry( ICP-MS). Besides,the heavy metal contamination level was further evaluated through 4 main assessment parameters,including maximum residue limit( MRL) set by International Standard Organization,estimated daily intake( EDI) set by IUPAC,target hazard quotients( THQ) and Total THQ set by USEPA and total THQs in raw herbs of A. membranaceus. In addition,the recommended MRLs of 5 main heavy metals aimed to A. membranaceus were calculated based on the regulated consumption quantity. The result showed that,under the ISO international standard of Chinese medicine-Chinese herbal medicine heavy metals,the unqualified rate was 8. 89% for A. membranaceus,which including 4 batches of A. membranaceus exceeded the MRL of As. Here,the standard THQ value of A. membranaceus was firstly proposed as 0. 02 and 0. 011 25 for adults and children,respectively,which were calculated with the recommended consumption quantity of 30 g and 9 g for adults and children. Furthermore,the values of THQ for As and total THQs in adults and children were exceeded the standard THQ in A. membranaceus,and the recommended MRLs of Pb,Cd,Hg and Cu in above medicinal materials that calculated based on health risk assessment model were higher than the regulated MRLs that set by ISO and Chinese Pharmacopeia. The research showed that the contents of heavy metals in A. membranaceus were not in the safe range and the certain non-carcinogenic risks to human body cannot be neglected. Based on above investigation result,it is easily known that the common evaluation method for raw herbs based on the comparison of MRL of heavy metals was not precise enough,and the international model of health risk assessment should be built for each medicinal herb. Above all,this study provided a more realistic research approach for safety evaluation of any other kinds of heavy metals contaminated medicinal herbs,including the establishment of heavy metals standard limit in a specified medicinal herb under recommended consumption quantity,and it is expected to create awareness among the public on the safety of consuming any other medicinal herbs.

A comprehensive analysis of 201 pesticides for different herbal species-ready application using gas chromatography-tandem mass spectrometry coupled with QuEChERs.

Developing an analysis of multi-pesticide residues for different herbal species-ready applications is a challenge. In the present work, a comprehensive analysis was proposed for rapid detection of 201 pesticides in various medicinal herbs. Samples were extracted and cleaned up with a high throughput pretreatment approach (modified QuEChERS), and then detected by gas chromatograph coupled to an electron impact ionization triple quadrupole mass spectrometer (GC-EI-MS/MS). The clean-up procedure has been optimized using four types of representative medicinal herbs with different primary or secondary metabolites. Moreover, a mixture of analyte protectants (APs) was to improve the peak shape and intensity of some compounds. The performance of the method was validated according to the European Union SANTE/11813/2017 regulatory guidelines. The limit of quantification (LOQ) was determined to be ≤10 ng mL-1, and the recovery was between 70.0%-120.0%, with ≤20% RSD for the majority of pesticides. Sixty samples belonging to different species of medicinal herbs (such radix, flos, cortex, fructus, and seeds) were analyzed to evaluate the applicability of the optimized method. High frequency of chlorpyrifos was found in Citri reticulatae pericarpium, Crataegi fructus and Cuscutae semen samples.

[Effect of Ferula ferulaeoides on growth and apoptosis of human gastric cancer MGC-803 transplantation tumor in nude mice].

In this paper,the effects of active fractions of Ferula ferulaeoides on the growth and apoptosis of human gastric cancer cell MGC-803 transplantation tumor were systematically studied. The subcutaneous ectopic transplantation tumor model was established in human gastric cancer MGC-803 nude mice by cell suspension implantation method. The anti-tumor rate and organ index were used to evaluate the anti-tumor effect of the active fractions of F. ferulaeoides on the tumor-bearing nude mice. HE staining,TUNEL staining,RT-PCR,Western-blot and ELISA were used for pathological examination,apoptosis observation,and detection of apoptosis-related genes,proteins and cytokines expression. The results showed that as compared with the model group,the low,medium and high doses of the active fraction of F. ferulaeoides had inhibitory effects on xenografts in nude mice,respectively,in a dose-dependent manner; the apoptotic ratio was increased with the increase of drug concentration. As compared with the model group,F. ferulaeoides could down-regulate the expression of survivin mRNA in nude mice,and the protein expression levels of Bax,Bcl-2,caspase-3 and caspase-9 in tumor tissues of nude mice could be increased to different degrees in F. ferulaeoides groups. The contents of IL-10 and TGF-ß1 in plasma of nude mice were decreased in high dose group of F. ferulaeoides active fractions. The results indicated that F. ferulaeoides can significantly inhibit the growth of human gastric cancer MGC-803 subcutaneously transplanted tumor,and its mechanism may be related with down-regulating the expression of survivin mRNA,and up-regulating the expression of apoptosis-related proteins Bax,caspase-3 and caspase-9.

[Current situation of heavy metal pollution,detection and removal techniques in medicinal marine organisms in China].

As an important branch of traditional medicines,medicinal marine organisms have many advantages,including biological diversity,remarkable biological activity,especial for the treatment of anti-cancer,anti-virus,anti-coagulation,analgesia,anti-bacterial,cardiovascular and cerebrovascular diseases. In recent years,with the continuous exploration of marine organisms by human beings,many marine organisms with specific biological activities and medicinal prospects have been found,which have attracted great attention around the world and thus called " new hope" to solve human health problems. However,due to the rapid development of modern industry,heavy metal pollution not only poses a great threat to medicinal marine living resources,but also hinders the development of marine biomedical industry and threatens human health. In view of this,this paper introduced the development trend of medicinal marine organisms and the current situation of heavy metal pollution and focusing on the analysis technology and chemical removal technology of heavy metals in medicinal marine organisms,which is to provide reference for the heavy metals control in marine medicines and the development and utilization of marine medicines.

[Establishment of health risk assessment model for assessing medicinal and edible plants contaminated by heavy metals--take Astragali Radix,Codonopsis Radix and Laminariae Thallus as examples].

With the improvement of living standard,the theory of " medicine and food homology" has developed rapidly in the field of diet,medicine and health preservation. In recent years,many literatures have been reported on the active ingredients and pharmacological effects of medicinal and edible plants,but relatively few reports have been reported on their safety investigation. Therefore,to further evaluate the quality and safety of medicinal and edible plants,Astragali Radix,Codonopsis Radix and Laminariae Thallus were selected as our research objects in this study. Moreover,the pollution level and the potential health risk of heavy metals were deeply assessed in different types of medicinal and edible plants. Especially,the contents of chromium,copper,arsenic,cadmium,mercury and lead in these three herbs were determined by inductively coupled plasma mass spectrometry( ICP-MS),and their health risk level was evaluated by target hazard coefficient method. The results showed that under the international heavy metal limit standard( ISO 18664-2015,GB 2762-2017),the over-standard rates were 25%,77% and 100% in 16 batches of Astragali Radix,26 batches of Codonopsis Radix and 9 batches of Laminariae Thallus,respectively. Besides,the values of target hazard quotients( THQ) for adults and children are 0. 028 244,0. 063 505 and 0. 014 485,0. 032 568 in Astragalus membranaceus and Codonopsis pilosula,respectively,which were higher than the standard values of 0. 02 and 0. 011 25. While,the total heavy metals THQ values for adults and children are 0. 023 734 and 0. 020 287 in Laminariae Thallus,which were much higher than the standard values of 0. 008 0 and 0. 007 5. However,the CR values of As,Cd and Pb in the three herbs were lower than 1×10~(-6). Above results indicated that those six harmful elements have certain health hazards to the exposed population,but there is no potential carcinogenic effect. It can be seen that,there were still presence of the pollution of harmful elements,and it is necessary to establish the reasonable limit standards and quality control methods of medicinal and edible plants in time.

[Safety evaluation of heavy metals contaminated Xiaochaihu Tang using health risk assessment model].

In order to further improve the quality and safety evaluation standards of traditional Chinese medicine compound preparation,Xiaochaihu Tang compound preparations were selected to analyze the pollution level of heavy metals deeply,and the potential health risks were evaluated under taking such kind of compound preparations. In this study,the contents of copper( Cu),arsenic( As),cadmium( Cd),mercury( Hg),and lead( Pb) in different Xiaochaihu Tang compound preparations were determinated by the method of inductively coupled plasma mass spectrometry( ICP-MS). Moreover,combined with target hazard coefficient method and in vitro artificial system,the bioaccessibility and health risk level was investigated in three main consumption ways including powder,decoction and granule. The result was showed that,under the maximum residual limit set by International Standard Organization,only one batch of raw herb was eight times exceeded the Hg MRL,however,in water decoctions and granules,the heavy metal residue rate was reduced to 2. 02%( Hg in granules)-42. 85%( Cd in granules). So,the heavy metal pollutions and health risks can be reduced to safe region in spite of the serious pollution in raw herbs. Besides,the THQ and CR values of the three consumption methods were lower than the standard values of non-carcinogenic and carcinogenic risks of each heavy metal. It can be seen that even if the heavy metals in the raw herbs exceed the standard,the use of Xiaochaihu Tang decoction and granules can reduce the harm of heavy metals to the human body. Above all,the establishment of this health risk assessment model can be provided experimental basis and reference value for improving the safety evaluation standard of other heavy metals contained traditional Chinese medicine( TCM) compound preparations,and further improving the quality control methods of other different toxic compounds in clinical use.

[Survey on pesticide use in Crataegi Fructus and analysis of pesticide residues based on LC-ESI-MS/MS].

In order to study the pesticide residues of the medicinal Crataegi Fructus,this study aims to establish an analysis method for pesticide residues( mainly containing insecticides and fungicides) suitable for the actual situation of medicinal Crataegi Fructus based on the survey of the pesticides of the Crataegi Fructus base,combined with the blind screening results of the LC-ESI-MS/MS pesticide screening platform established by the research team in the early stage. Then,the pesticide residues in medicinal Crataegi Fructus from Shandong,Hebei,Henan,Shanxi,and Liaoning( main cultivation areas) were analyzed. The samples were pretreated by the modified Qu ECh ERS method,i.e.,extracted with acetonitrile-water( 9 ∶1),purified by PSA,C_(18),GCB,silica gel. The detection of pesticides was performed by LC-MS/MS. The ion source was ESI with positive scanning mode,and the linearity of 11 kinds of pesticides in the range of 5-300 µg·kg~(-1) was acceptable( R~2>0. 996 9). All the recoveries of pesticides were within 70. 02%~(-1)12. 0% in the low,medium and high levels,with RSD≤17%. The results showed that the detection rate of carbendazim,chlorpyrifos and difenoconazole is 79%,82%,56%,respectively. Besides,the prohibition pesticide carbofuran were detected in some of the batches,indicating the security risk. This study provides methodological references and basic data for risk assessment of Crataegi Fructus and government regulation.

[Estimation of bioaccessibility and risk assessment of heavy metals in decoction pieces of Bupleuri Radix].

This project was launched to study on the overall residual status of heavy metals of comprehensive understanding in decoction pieces of Bupleuri Radix (DPBR) from different habitats and risk assessment. In this study, inductively coupled plasma mass spectrometry was used to determine the heavy metals of 30 batches of Bupleuri Radix in different producing areas. Simulated gastrointestinal fluid method was used to determine the dissolution rate of heavy metals in the simulated gastrointestinal fluid and the average daily intake Average Daily Dose (ADD) and Hazard Quotient (HQ) index were used to assess the risk of heavy metals in DPBR. The results showed that the contents of copper (Cu), lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg) in the 30 batches of DPBR didn't exceed the limit of Chinese Pharmacopeia, however, the chromium (Cr) in DPBR exeeded the limit set by NSF in USA and the limit for herbal ingredients in Canada. The mean bioaccessible heavy metal concentrations decreased from Cu (5.27 mg·kg⁻¹)>Cr (4.67 mg·kg⁻¹)>As (0.18 mg·kg⁻¹)>Pb (0.12 mg·kg⁻¹)>Cd (0.06 mg·kg⁻¹), and Hg was not detected in this test. In addition, cumulative non-carcinogenic health risks (HI) for adults and children were 0.799 and 0.714, respectively. Both HI values in adults and children for combined trace element and heavy metal element exposures were below the value of 1 (HI<1), indicating very low carcinogenic health risk. Heavy metals toxicity in herbal medicines and its health risk to humans would be overestimated when assessed only by the total concentrations without considering the bioaccessibility. Therefore, bioaccessibility has great significance for evaluating the human health risks induced by heavy metals.

6'-Hydroxy Justicidin B Triggers a Critical Imbalance in Ca2+ Homeostasis and Mitochondrion-Dependent Cell Death in Human Leukemia K562 Cells.

Justicia procumbens (J. procumbens) is a traditional Chinese herbal medicine which was used for the treatment of fever, pain, and cancer. A compound 6'-hydroxy justicidin B (HJB) isolated from J. procumbens exhibits promising biological properties. However, the mechanism of action and the in vivo behavior of HJB remain to be elucidated. In this study, we investigated the mechanism of action of HJB on human leukemia K562 cells and its pharmacokinetic properties in rats. The results demonstrated that HJB significantly inhibited the proliferation of K562 cells and promoted apoptosis. Besides, HJB resulted in decreased mitochondrial membrane potential deltaPSIm, increased the level of the calcium homeostasis regulator protein TRPC6 and cytosolic calcium. The activity of caspase-8, caspase-9 and the expression of p53 were significantly increased after treatment with HJB. Additionally, HJB has rapid absorption rate and relative long elimination t1/2, indicating a longer residence time in vivo. The results indicate that HJB inhibited the proliferation of K562 cells and induced apoptosis by affecting the function of mitochondria and calcium homeostasis to activate the p53 signaling pathway. The pharmacokinetic study of HJB suggested it is absorbed well and has moderate metabolism in vivo. These results present HJB as a potential novel alternative to standard human leukemia therapies.

[Recent research progress on natural medicines in treatment of cadmium toxicity].

Cadmium contamination of environment is a subject of serious international concern. Bioaccumulation of cadmium occurs primarily through ingestion of contaminated water and food. Cadmium poisoning came into prominence with the "itai-itai" disease event in Japan in the 1950s. It could also cause damages to liver, kidney, lung and other organs. Thus, the treatment of cadmium poisoning has become a research hotspot. Researchers are trying their best to explore prophylactic and therapeutic medicines for prevention and treatment of cadmium-induced poisoning. So far, chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Natural medicines have a variety of advantages such as extensive sources, high safety, less adverse reactions, and thus have great potentials in treating cadmium poisoning. In this review, the progress in the antagonistic effects of natural drugs in cadmium poisoning and their therapeutic mechanisms were summarized in order to provide certain references for the future development and in-depth study of antagonistic substances.

Determination and pharmacokinetic study of guaiol in rat plasma by gas chromatography-mass spectrometry with selected ion monitoring.

Guaiol has been used for thousands of years as a traditional Uygur medicine and is the primary active component found in Ferula ferulaeoides (Steud.) Korov (F. ferulaeoides). In our present study, a rapid, selective, and sensitive method of monitoring selected ions was established based on gas chromatography-mass spectrometry. This method was optimized for the quantification and pharmacokinetic analysis of guaiol in rat plasma following oral administration of chloroform extract from Ferula ferulaeoides. Plasma was extracted using liquid-liquid extraction with ethyl acetate and was analyzed on a HP-5MS column (30 m × 250 µm × 0.25 µm) with a mass selective detector. Detection was carried out under selected ion monitoring mode, and three selected ion monitoring ions (m/z 59.1, 107.1, and 161.1 for guaiol) were used for the quantitative determination of that under investigation. The assay demonstrated excellent linearity in the range of 1-200 ng/mL (r = 0.9993, n = 8) in the case of guaiol measured in rat plasma. The limit of detection and the limit of quantification for guaiol in rat plasma were found to be 0.25 ng/mL and 1 ng/mL, respectively. Intra-day and inter-day precisions were expressed as the relative standard deviation for the method and were in the range of 97.49%-106.16% and 97.04%-105.91%, respectively. Extraction efficiencies were all determined to be >90%, and recoveries were ranged from 91.25% to 96.24%. This method has been successfully applied for the pharmacokinetic evaluation of chloroform extract isolated from F. ferulaeoides following a single oral administration dose (157.5 mg/kg) in rats. The guaiol pharmacokinetic study demonstrated that the half-life of guaiol was 9.18 ±â€¯3.75 h, the mean residence time was 9.07 ±â€¯3.86 h, the maximum guaiol concentration in the plasma was 28.63 ±â€¯6.82 ng/mL, and the maximum time guaiol was in the plasma was 0.50 h.