Multi-mycotoxin detection and human exposure risk assessment in medicinal foods.

Mycotoxin contamination in medicinal foods has attracted increasing global attention. In this study, a simple and sensitive ultrasonication assisted one-step extraction based ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous detection of multi-mycotoxins in five kinds of medicinal foods rich in starch. Under optimal conditions, the developed technique displayed excellent analytical performances. Limits of detection and quantitation for the six mycotoxins were 0.04-0.25 ng/mL and 0.10-0.67 ng/mL, respectively. Average recoveries at three fortified levels ranged from 75.33 % to 118.0 %. Real-world application in 103 batches of medicinal foods displayed that 58 samples were positive with one or more mycotoxins at an occurrence rate of 56.31 % (58/103). Coix seed gave the highest positive rate of 96.15 %, followed by Lily (90 %), Chinese yam (50 %), Lotus seed (34.04 %) and Malt (30 %). Zearalenone had the highest positive rate of 28.16 % with contents in 5 Coix seeds exceeding the maximum residue limit (MRL), followed by aflatoxin B1 of 27.18 % (28/103) with contents in 7 Coix seed and 10 Lotus seeds over its MRL, and ochratoxin A (OTA) of 11.65 % with contents in 1 Lotus seed and 5 Lily samples greater than its MRL. Exposure risk assessment indicated that Coix seed and Lotus seeds that were susceptible to aflatoxins posed great threats to human health. Long-term consumption of Lily that was easily contaminated with OTA were also harmful. This work provides a robust platform for multi-mycotoxin monitoring in medicinal foods to protect the consumers from potential health risks.

Genome-Wide Association Study of Body Weight Trait in Yaks.

The yak is the largest meat-producing mammal around the Tibetan Plateau, and it plays an important role in the economic development and maintenance of the ecological environment throughout much of the Asian highlands. Understanding the genetic components of body weight is key for future improvement in yak breeding; therefore, genome-wide association studies (GWAS) were performed, and the results were used to mine plant and animal genetic resources. We conducted whole genome sequencing on 406 Maiwa yaks at 10 × coverage. Using a multiple loci mixed linear model (MLMM), fixed and random model circulating probability unification (FarmCPU), and Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK), we found that a total of 25,000 single-nucleotide polymorphisms (SNPs) were distributed across chromosomes, and seven markers were identified as significantly (p-values < 3.91 × 10−7) associated with the body weight trait,. Several candidate genes, including MFSD4, LRRC37B, and NCAM2, were identified. This research will help us achieve a better understanding of the genotype−phenotype relationship for body weight.

Development of an economic ultrafast liquid chromatography with tandem mass spectrometry method for trace analysis of multiclass mycotoxins in Polygonum multiflorum.

Rapid, economic, and highly effective determination of multiple mycotoxins in complex matrices has given huge challenges for the analytical method. In this study, an economic analytical strategy based on sensitive and rapid ultrafast liquid chromatography coupled to hybrid triple quadrupole/linear ion trap mass spectrometry technique was developed for the determination of seven mycotoxins of different chemical classes (aflatoxin B1 , B2 , G1 , and G2 , ochratoxin A, T-2 toxin, and HT-2 toxin) in Polygonum multiflorum. Target mycotoxins were completely extracted using a modified quick, easy, cheap effective, rugged, and safe method without additional clean-up steps. The types of extraction solvents and adsorbents for the extraction procedure were optimized to achieve high recoveries and reduce coextractives in the final extracts. Due to significant matrix effects for all analytes (≤68.9% and ≥110.0%), matrix-matched calibration curves were introduced for reliable quantification, exploring excellent linearity for the seven mycotoxins with coefficients of determination >0.9992. The method allowed high sensitivity with limit of detection in the range of 0.031-2.5 µg/kg and limit of quantitation in the range of 0.078-6.25 µg/kg, as well as satisfactory precision with relative standard deviations lower than 8%. Recovery rates were between 74.3 and 119.8% with relative standard deviations below 7.43%. The proposed method was successfully applied for 24 batches of P. multiflorum samples, and six samples were found to be positive with aflatoxin B1 , B2 , G1 , or ochratoxin A. The method with significant advantages, including minimum analytical time, low time and solvent consumption, and high sensitivity, would be a preferred candidate for economic analysis of multiclass mycotoxins in complex matrices.

The Scientific Basis and Advantage of Human Experiential Assessment in the quality control of Chinese Herbal Medicines exampling as Schisandrae Chinensis Fructus.

Experiential quality assessment(EQA) is an important sensory analysis for judging herbal quality grades. Because of the high empirical utility of expert experience, the consistency, science and inheritance of such experience are continuously in dispute. To explore the scientific evidence for this subjective method, we designed a Delphi expert investigation coupled with chemical analysis to evaluate the quality of Schisandrae Chinensis Fructus (SCF). Initially, 13 experts were invited to independently evaluate the grades of 11 batches of SCF. After screening the consistency and repeatability of the evaluation results, typical samples of all quality levels were identified. Seven significant physical characters were detected; colour and size were found to be the key parameters for identifying SCF quality. Based on this correlation, a decision tree model was ultimately established and converted to a quality evaluation card. Over 80% consistency in a novice test demonstrated the technical advantages and application characteristics of the model. Further correlation analysis revealed that EQA quality grades of SCF were positively correlated to the content of polysaccharides and polyphenols, while negatively correlated to the content of lignans. Biological activities were also approving it. In summary, our study proves that subjective EQA is consistency, repeatability and could be inherited.

Quality Assessment of Panax notoginseng from Different Regions through the Analysis of Marker Chemicals, Biological Potency and Ecological Factors.

Panax notoginseng (Burk.) F.H. Chen, called Sanqi in China, is a perennial herb that has been used as a medicinal herb in traditional Chinese medicine for more than 400 years. Because notoginseng is included in many proprietary Chinese medicines, the quality of notoginseng directly affects its efficacy and safety. However, considering the complex and special growth environment requirements of notoginseng, it is insufficient to evaluate its quality based solely on the analysis of marker chemicals. Thus, in this study, we tried to evaluate the quality of notoginseng with integrated indicators: (1) the concentration of five marker chemicals, notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd; (2) the anticoagulant activity (ACA); and (3) twenty-one ecological factors (e.g., longitude, latitude, elevation and soil data). Using these 27 parameters, notoginseng from different regions could be distinguished effectively, indicating a remarkable divergence of quality. A correlation analysis showed that variations of the ecological factors were closely associated with the saponins content and biopotency. For instance, the total nitrogen (TN), alkali hydrolysis nitrogen (AHN) and rapidly available potassium (RAPT) were significantly correlated with ACA, and RAPT was significantly correlated with the content of ginsenoside Rd and notoginsenoside R1. The results demonstrated that the high-quality notoginseng was produced from the emerging regions such as Kunming, Qujing and Honghe, which had higher ACA and saponin content than the notoginseng produced in traditional regions such as Wenshan and Baise.

[Precision medicine-oriented safety assessment strategy for traditional Chinese medicines: disease-syndrome-based toxicology].

Drug toxicity is commonly divided into intrinsic and idiosyncratic types. The former can be generally uncovered in the preclinical safety evaluation stage by conventional toxicological experiments, while the latter is usually found only in the clinical evaluation stage, which is the main cause of severe adverse reactions and withdrawal of post-marketing drugs. Assessment and prediction of idiosyncratic toxicity is a challenging problem worldwide, and is an essential in the development of translational toxicology and precision medicine. Since traditional Chinese medicines (TCMs) have been applied for thousands of years with long experience in clinical efficacy and safety, idiosyncratic toxicity is regarded as an important factor for traditional "non-toxic" medicines and is associated with multiple individual states including different diseases, syndromes, habitus, etc. However, these individual conditions related to disease are often difficult to be resolved in conventional toxicological experiments, leading to insufficient translation of the experimental results into clinical application. We took an approach of systematic analysis of the differences and similarities in toxic property, medication rule and evaluating requirement between TCMs and chemical synthetic medicines. We present a novel and clinic-associated safety assessment strategy, namely as "disease-syndrome-based toxicology", for TCMs. The strategy is able to access the relativity, susceptibility and controllability of the toxicity of TCMs. The new strategy provides a theoretical and methodological guidance to practice and development of the TCM in favor of precision medicine.

[Study on dosage-toxicity/efficacy relationship of prepared rhubarb on basis of symptom-based prescription theory].

OBJECTIVE: To investigate the dosage-efficacy/toxicity relationship of prepared rhubarb, in order to explore the bidirectional effects in hepatoprotection and hepatotoxicity of prepared rhubarb and the objective authenticity for attenuating toxicity by processing. METHOD: Normal and pathological animals were adopted simultaneous to investigate the effect of total extracts from prepared rhubarb within a high dose range (2.0, 5.4, 14.7, 40.0 g x kg(-1) x d(-1)) on normal state, biochemical index and histopathology of experimental animals. The factor analytic approach was used to analyze the dosage-efficacy/toxicity relationship of prepared rhubarb. RESULT: The factor analytic approach was used to extract two common factors from the nine biochemical indexes. The firs common factor was mainly dominated by HA, LN and TGF-ß1, and could be explained as fibrotic factors. The second common factor was mainly dominated by ALT, AST and ALP, and could be explained as cellular factor. The results of the factor analysis suggested that prepared rhubarb showed significant bidirectional effects in hepatoprotection and hepatotoxicity, which could protect liver in CC14 injured chronic hepatic injury, but had a certain hepatotoxic effect to normal animals. The pathological examination showed consistent results with the factor analysis. Under comparable dosages, prepared rhubarb showed a stronger liver protecting effect than crude rhubarb, with a lower toxicity. CONCLUSION: Although prepared rhubarb has a certain hepatotoxic effect to normal animals, it has also a significant therapeutic effect to animals with liver injury. The results proved the symptom-based prescription theory and the scientificity of the symptom-based medication. The symptom-based prescription theory is important to correctly realize the dosage-efficacy/toxicity relationship of traditional Chinese medicines and guide the symptom-based medication.

Needle-free injection of insulin powder: delivery efficiency and skin irritation assessment.

Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection (PNI) device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors (gas pressure, cylinder volume, and nozzle distance) were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs.

[Novel method for dynamic monitoring and early-warning on wild resources of traditional Chinese medicines based on price ratio between drug and foodstuff].

OBJECTIVE: To probe into the new idea along with establishment of a novel method for dynamic monitoring and early-warning on the wild resources of traditional Chinese medicines (TCMs). METHOD: The alterations of wild traditional Chinese medicinal resources were assessed through the price ratio between drug and foodstuff (PRDF) indicating the balance between supply and demand of the specific TCMs, referred to the price ration between pork to foodstuff which is used in national monitoring to the balance between pork supply and demand. RESULT: Since the price of rice was tightly controlled by government, it was selected as a relatively stable reference to build the PRDF in order to take away the non-marketing influence to TCMs price such as CPI and inflation rate. The modified relative alteration trend of TCMs price had been researched through comparing different formulae to build PRDF, including absolute average month price of TCMs, month average price ratio of TCMs to foodstuff (rice) , month-on-month change of TCMs to rice, year-on-year change of TCMs to rice, and difference in value of period-on-period change (DVPPC). In the research, Cordyceps, Glycyrrhiza and totally five herbs were selected as model drugs and the price data were collected from 2002 to 2008. The results showed that DVPPC calculated of relative long time window was more sensitive and stable to reflect the relative alteration trend of TCMs price. For instance, the DVPPC of Ligustici showed continuously increase trend in recent years. This suggested appearance of unbalance between supply and demand of Ligustici, and forced policy intervention to maintain reasonable and continuable utilization of Ligustici resource. CONCLUSION: The proposed method and the formula of DVPPC revealed some useful guidance for dynamic monitoring the wild resources of TCMs.

Assessment of the renal protection and hepatotoxicity of rhubarb extract in rats.

AIM OF THE STUDY: Rhubarb is well used to treat chronic renal failure (CRF) in China and Japan, but recent studies reported that the anthraquinone derivatives contained in rhubarb had nephrotoxicity. In this investigation an attempt was made to assess the value and toxic potential of rhubarb to treat CRF. MATERIALS AND METHODS: Histopathologic and biochemical tests combined with toxicokinetic analysis were performed to investigate the nephrotoxic potential and protective effect of rhubarb extract. RESULTS: In normal rat groups, no death was observed and no renal lesion was found after repetitive administration of rhubarb for 3 weeks. The survival rate, pathologic conditions and biochemical indexes of CRF rats treated with rhubarb at two dosages were all improved and significant amelioration was found in the low dosage group compared to the untreated CRF group. Rhein was the mainly absorbable anthraquinone derivative into systemic circulation after oral administration and the area under curve of rhein in CRF groups was lower than that in normal groups at same dosage. CONCLUSIONS: After 3 weeks of administration of rhubarb extract, there was evidence of protective effect to CRF rats, while incidences of hepatotoxicity with minimal to mild hyaline droplets were also observed in normal rats.