In vivo and in vitro chemical composition and biological activity of traditional vs. dispensing granule decoctions of Coptidis Rhizoma: A comparative study.

Coptidis Rhizoma (CR) holds significant clinical importance. In this study, we conducted a comparative analysis of CR's dispensing granule decoction (DGD) and traditional decoction (TD) to establish a comprehensive evaluation method for the quality of DGD. We selected nine batches of DGD (three from each of manufacturers A, B and C) and 10 batches of decoction pieces for analysis. We determined the content of representative components using high-performance liquid chromatography and assessed the content of blood components in vivo post-administration using ultra-performance liquid chromatography-mass spectrometry. The antibacterial activity was measured using the drug-sensitive tablet method. To evaluate the overall consistency of DGD and TD, we employed the CRITIC method and Grey relational analysis method. Our CRITIC results indicated no significant difference between the CRITIC scores of DGD-B and TD, with DGD-B exhibiting the highest consistency and overall quality. However, DGD-A and DGD-C showed variations in CRITIC scores compared with TD. After equivalent correction, the quality of DGD-A and DGD-C approached that of TD. Furthermore, our Grey relational analysis results supported the findings of the CRITIC method. This study offers a novel approach to evaluate the consistency between DGD and TD, providing insights into improving the quality of DGD.

Research on rapid quality identification method of Panax notoginseng powder based on artificial intelligence sensory technology and multi-source information fusion technology.

Panax notoginseng powder (PNP) has high medicinal value and is widely used in the medical and health food industries. However, the adulteration of PNP in the market has dramatically reduced its efficacy. Therefore, this study intends to use artificial intelligence sensory (AIS) and multi-source information fusion (MIF) technology to try to establish a quality evaluation system for different grades of PNP and adulterated Panax notoginseng powder (AD-PNP). The highest accuracy rate reached 100% in identifying PNP grade and adulteration. In the prediction of adulteration ratio and total saponin content, the optimal determination coefficients of the test set were 0.9965 and 0.9948, respectively, and the root mean square errors were 0.0109 and 0.0123, respectively. Therefore, the grade identification method of PNP and the evaluation system of AD-PNP based on AIS and MIF technology can rapidly and accurately evaluate the quality of PNP.

Quality consistency evaluation of chemical composition and pharmacology of Shaoyao-Gancao decoction dispensing granules and traditional decoction.

Dispensing granules of Chinese medicine (DGCM) have emerged as a more convenient alternative to traditional decoction (TD) of Chinese medicine, gaining popularity in recent years. However, the debate surrounding the consistency of DGCM compared to TD remains unresolved. In this study, three batches of Baishao and Gancao DGCM were obtained from manufacturers A, B, and C, and 15 batches of crude drugs were procured from hospital pharmacies for the preparation of dispensing granule decoction (DGD) and TD of Shaoyao-Gancao decoction (SGD). The HPLC-UV method was employed to determine the levels of gallic acid, paeoniflorin, albiflorin, liquiritin, liquiritin apioside, isoliquiritin apioside, isoliquiritin, glycyrrhizic acid, and isoliquiritigenin. The analgesic and antispasmodic effects were assessed using the hot plate and acetic acid writhing test in mice. To evaluate the consistency of chemical constituents and pharmacological effects between the two decoctions, the Criteria Importance Though Intercriteria Correlation (CRITIC) method combined with chemometrics was employed. Grey relation analysis (GRA) was used to assess the comprehensive quality consistency of the two decoctions. The CRITIC results revealed certain differences in chemical constituents and pharmacological effects between the selected DGCM and TD. Notably, DGD-A/C exhibited a significant difference from TD (p > 0.05), whereas DGD-B demonstrated no significant difference from TD (p > 0.05). The GRA analysis demonstrated that the overall quality consistency between DGD-B and TD was the highest among the three manufacturers. This study presents a method for evaluating the quality consistency of DGCM and TD of SGD, offering novel insights into the evaluation of consistency between DGCM and TD.

Development of a variety and quality evaluation method for Amomi fructus using GC, electronic tongue, and electronic nose.

Amomi fructus is rich in volatile components and valuable as a medicine and edible spice. However, the quality of commercially available A. fructus varies, and issues with mixed sources and adulteration by similar products are common. In addition, due to incomplete identification methods, rapid detection of the purchased A. fructus quality is still an issue. In this study, we developed qualitative and quantitative evaluation models to assess the variety and quality of A. fructus using GC, electronic tongue, and electronic nose to provide a rapid and accurate variety and quality evaluation method of A. fructus. The models performed well; the qualitative authenticity model had an accuracy of 1.00 (n = 64), the accuracy of the qualitative origin model was 0.86 (n = 44), and the quantitative model was optimal on the sensory fusion data from the electronic tongue and electronic nose combined with borneol acetate content, with R 2 = 0.7944, RMSEF = 0.1050, and RMSEP = 0.1349. The electronic tongue and electronic nose combined with GC quickly and accurately evaluated the variety and quality of A. fructus, and the introduction of multi-source information fusion technology improved the model prediction accuracy. This study provides a useful tool for quality evaluation of medicine and food.

Authenticity and species identification of Fritillariae cirrhosae: a data fusion method combining electronic nose, electronic tongue, electronic eye and near infrared spectroscopy.

This paper focuses on determining the authenticity and identifying the species of Fritillariae cirrhosae using electronic nose, electronic tongue, and electronic eye sensors, near infrared and mid-level data fusion. 80 batches of Fritillariae cirrhosae and its counterfeits (including several batches of Fritillaria unibracteata Hsiao et K.C. Hsia, Fritillaria przewalskii Maxim, Fritillaria delavayi Franch and Fritillaria ussuriensis Maxim) were initially identified by Chinese medicine specialists and by criteria in the 2020 edition of Chinese Pharmacopoeia. After obtaining the information from several sensors we constructed single-source PLS-DA models for authenticity identification and single-source PCA-DA models for species identification. We selected variables of interest by VIP value and Wilk's lambda value, and we subsequently constructed the three-source fusion model of intelligent senses and the four-source fusion model of intelligent senses and near-infrared spectroscopy. We then explained and analyzed the four-source fusion models based on the sensitive substances detected by key sensors. The accuracies of single-source authenticity PLS-DA identification models based on electronic nose, electronic eye, electronic tongue sensors and near-infrared were respectively 96.25%, 91.25%, 97.50% and 97.50%. The accuracies of single-source PCA-DA species identification models were respectively 85%, 71.25%, 97.50% and 97.50%. After three-source data fusion, the accuracy of the authenticity identification of the PLS-DA identification model was 97.50% and the accuracy of the species identification of the PCA-DA model was 95%. After four-source data fusion, the accuracy of the authenticity of the PLS-DA identification model was 98.75% and the accuracy of the species identification of the PCA-DA model was 97.50%. In terms of authenticity identification, four-source data fusion can improve the performance of the model, while for the identification of the species the four-source data fusion failed to optimize the performance of the model. We conclude that electronic nose, electronic tongue, electronic eye data and near-infrared spectroscopy combined with data fusion and chemometrics methods can identify the authenticity and determine the species of Fritillariae cirrhosae. Our model explanation and analysis can help other researchers identify key quality factors for sample identification. This study aims to provide a reference method for the quality evaluation of Chinese herbs.

Study on the taste-masking effect and mechanism of Acesulfame K on berberine hydrochloride.

OBJECTIVE: In our previous taste-masking study, we found that Acesulfame K (AK) had a better taste-masking effect than other high-efficiency sweeteners for several representative bitter natural drugs in aqueous decoction. Furthermore, we performed a preliminary taste-masking study of AK for representative bitter API Berberine Hydrochloride (BH) and found that it had a good taste-masking effect. We also found that flocculent precipitation was generated in the BH solution, but it was not clear whether it was related to the good taste-masking effect. This study was conducted to explore the taste-masking effect and mechanism of AK on BH. METHODS: The taste-masking effect of AK on BH was evaluated based on the Traditional Human Taste Panel Method and the electronic tongue evaluation method. DSC, XRD, and molecular simulation techniques were used to explore the mechanism of AK on BH, from the macro level and molecular level, respectively. RESULTS: When evaluating the taste-masking effect, we found that 0.1% AK had the best taste-masking effect on BH, while higher concentrations had a worse taste-masking effect. DSC and XRD revealed that the flocculent precipitation was a complex AK-BH. Finally, by simulating the binding of AK, BH, and TAS2R46 receptors, we found the unique taste-masking mechanism of AK. CONCLUSION: The sweet taste stimulus of AK can mask the bitter taste stimulus of BH, and AK can generate AK-BH with BH to reduce the contact between BH and bitter taste receptors. Additionally, it could block the expression of the TAS2R46 receptors.

Identification of Bletilla striata and related decoction pieces: a data fusion method combining electronic nose, electronic tongue, electronic eye, and high-performance liquid chromatography data.

Introduction: We here describe a new method for distinguishing authentic Bletilla striata from similar decoctions (namely, Gastrodia elata, Polygonatum odoratum, and Bletilla ochracea schltr). Methods: Preliminary identification and analysis of four types of decoction pieces were conducted following the Chinese Pharmacopoeia and local standards. Intelligent sensory data were then collected using an electronic nose, an electronic tongue, and an electronic eye, and chromatography data were obtained via high-performance liquid chromatography (HPLC). Partial least squares discriminant analysis (PLS-DA), support vector machines (SVM), and back propagation neural network (BP-NN) models were built using each set of single-source data for authenticity identification (binary classification of B. striata vs. other samples) and for species determination (multi-class sample identification). Features were extracted from all datasets using an unsupervised approach [principal component analysis (PCA)] and a supervised approach (PLS-DA). Mid-level data fusion was then used to combine features from the four datasets and the effects of feature extraction methods on model performance were compared. Results and Discussion: Gas chromatography-ion mobility spectrometry (GC-IMS) showed significant differences in the types and abundances of volatile organic compounds between the four sample types. In authenticity determination, the PLS-DA and SVM models based on fused latent variables (LVs) performed the best, with 100% accuracy in both the calibration and validation sets. In species identification, the PLS-DA model built with fused principal components (PCs) or fused LVs had the best performance, with 100% accuracy in the calibration set and just one misclassification in the validation set. In the PLS-DA and SVM authenticity identification models, fused LVs performed better than fused PCs. Model analysis was used to identify PCs that strongly contributed to accurate sample classification, and a PC factor loading matrix was used to assess the correlation between PCs and the original variables. This study serves as a reference for future efforts to accurately evaluate the quality of Chinese medicine decoction pieces, promoting medicinal formulation safety.

[Main characteristics and practical discussions of national drug standards for 196 kinds of Chinese medicine formula granules].

As China is implementing the policy of "Announcement on Ending the Pilot Work of Chinese medicine formula gra-nules", the standard of Chinese medicine formula granules has gradually become the focus of industry development. Up to now, 196 national drug standards for Chinese medicine formula granules have been published by China, which guaranteed the production quality of Chinese medicine formula granules. However, there are still several challenges such as the rational application of national drug standards and the enrichment and improvement of varieties. The basic content of the issued national drug standards for Chinese medicine formula granules was analyzed and compared with the quality standard provisions of the corresponding decoction pieces in the Chinese Pharmacopoeia(2020 edition) in this paper. This paper discussed the main characteristics of paste-forming rate of each medicinal raw materials, "quantity-quality" transformation, equivalent ratio, and so on, and clarified the characteristics of the national standard for Chinese medicine formula granules. This paper provided references for achieving the unified quality control and meeting the overall quality requirements of Chinese medicine formula granules.

Study on Masking the Bitterness of Chinese Medicine Decoction-Mate.

Background: Traditional Chinese medicine decoction (TCMD) is an oral liquid made by decocting crude medicinal compounds with water. It has complex compositions and diverse odor and taste, most of which have an unacceptable level of bitterness which seriously affects patients' medication compliance. To solve this problem, a variety of taste-masking pathways and different types of taste-masking excipients were combined, using the application of coffee-mate to mask the bitterness of coffee as an existing example. Three composite taste-masking adjuvants were developed to improve the taste of TCMD, referred to as the Chinese Medicine Decoction-Mate (CMD-M). However, whether CMD-M has a good taste-masking effect and whether it affects the chemical compositions and pharmacological effects of the medicine remain unclear. Method: The commonly used pediatric medicine Qingre Huazhi Decoction (QRHZD) and the personalized decoctions used in clinical practices were used as the masking research carriers. The taste-masking effect of CMD-M on QRHZD was evaluated by both healthy volunteers and an electronic tongue, and the personalized decoctions were evaluated by clinical subjects. The changes of chemical components of QRHZD before and after taste-masking were evaluated by HPLC. The changes in anti-inflammatory effects were evaluated by establishing mice as an acute inflammatory model. Results: The taste-masking effect evaluation results showed that the bitterness of QRHZD was significantly reduced after adding CMD-M. There was no significant difference in the relative peak areas change rate and total peak areas ratio of common peaks of QRHZD before and after taste-masking (P > 0.05), shown by HPLC analysis. The inhibitory rates of QRHZD on ear swelling in mice before and after taste-masking also showed no significant difference (P > 0.05). Conclusions: CMD-M can effectively mask the bitterness of decoctions while bringing no significant difference overall in chemical compositions and pharmacological effects before and after QRHZD masking.

[Chinese medicine dispensing granules: history, status quo, and development prospect in "post-pilot era"].

Chinese medicine dispensing granules, the result of the efforts to transform Chinese medicinal decoction pieces in China, features portability and ease of storage. Thus, it is destined to be an indispensible dosage form in the modernization drive of Chinese medicine. The Announcement on Ending the Pilot Project of Chinese Medicine Dispensing Granules was released in February 2021 and relevant regulations went into force in November 2021, which marks the a new journey for the development of Chinese medicine dispensing granules and the beginning of the "post-pilot era". However, it faces the challenges in quality and standard. This study reviewed the history of Chinese medicine dispensing granules, analyzed the technical progress, market, and main problems in development, and proposed suggestions and prospects for its development in the "post-pilot era", which is expected to serve as a reference for its industry development and rational use.

A comparative study of consistency between Paeonia rubra hort traditional decoction and dispensing granule decoctions from different sources.

OBJECTIVE: To compare the consistency between the decoction of Paeonia rubra hort dispensing granules from different manufacturers and traditional decoction (TD), and to provide a reference for the clinical application of Paeonia rubra hort dispensing granules. METHODS: Nine batches of Paeonia rubra hort dispensing granules (from three manufacturers, A, B, and C) and 20 batches of Paeonia rubra hort decoction pieces were collected. The contents of four active components in vivo and in vitro were determined by HPLC and UPLC-MS/MS, respectively. The consistency of the Paeonia rubra hort decoction pieces and dispensing granules were compared based on the Criteria Importance Though Intercrieria Correlation (CRITIC) weighting method and the equivalent correction suggestions (1 g of dispensing granule equals the same amount of Chinese herbal samples) were put forward for the dispensing granules. RESULTS: The total content of active ingredients in vivo and in vitro of manufacturer A was significantly lower than that of TD (p < 0.05), and the total content of active ingredients in vivo of manufacturer C was significantly lower than that of TD (p < 0.05); The equivalent of manufacturer A and manufacturer C should be corrected from 1:11 and 1:5 to 1:5 and 1:4, respectively. CONCLUSION: The quality of Paeonia rubra hort dispensing granule decoction from some manufacturers aligns that of TD, but the other is slightly inferior to that of TD. After appropriate equivalent correction, quality consistency can be achieved with TD.

[Change laws of water absorption in Chinese herbal pieces and prediction model of relative density for Chinese medicine decoction].

This study aims to explore the change laws of water absorption in Chinese herbal pieces and establish the prediction model of relative density for Chinese medicine compound decoction. Firstly, fitted equations of water absorption and decocting time was established by observing the change laws of water absorption in 36 kinds of Chinese herbal pieces in 12 groups(according to the drug-parts) with decocting time. The r value of the mineral group and other type group was 0.691 2 and 0.663 3, respectively. The r value of the remaining 10 groups was 0.802 2-0.925 4. All P values were less than 0.05(n=21). The formula of the amount of water added was optimized by combining the fitted equations with determined water absorption, and the liquid yield could be controlled in a range of 100%±10%. Secondly, it was determined that the liquid density tester could be used for the rapid determination of relative density of Chinese medicine decoction after methodological study and comparison with the pycnometer method. The linear regression equation between the corrected relative density(y) and extraction ratio(%, x) was built by measuring and analyzing the related parameters such as liquid yield, relative density and extraction ratio in 46 kinds of Chinese herbal pieces. The established equation was y=0.041 3x+1.003 7, r=0.930 9(P <0.01, n=46), with linear range of 1.94%-65.75%. Based on this, the prototype model for predicting relative density of Chinese medicine decoction was established, and the relative densities of 8 Chinese medicine decoctions were within the prediction interval of this model in verification. This study lays a foundation for database construction of Chinese medicine decoction, implementation of personalized decocting mode and rapid quality control of Chinese medicine decoction.

[A rapid identification of authenticity and specifications of Chinese medicine Fritillariae Cirrhosae Bulbus based on E-eye technology].

The quality of traditional Chinese medicine tablets is correlated with clinical efficacy and drug safety, and plays a great role in promoting the development of traditional Chinese medicine. However, the existing traditional artificial identification and modern instrument detection in terms of accuracy and timeliness have both advantages and disadvantages. Therefore, how to quickly and accurately identify the quality of traditional Chinese medicine tablets has become a high-profile issue. The purpose of this paper is to explore the feasibility of the application of electronic eye technology in the study of rapid identification of traditional Chinese medicine quality. A total of 80 batches of samples were collected and tested by Fritillariae Cirrhosae Bulbus for traditional empirical identification(M_1) and modern pharmacopeia(M_2). The optical data was collected from electronic eyes, and the chemical metrology was used to establish suitable discrimination models(M_3). Four authenticity and commodity specification models, namely identification analysis(DA), minimum bidirectional support vector machine(LS-SVM), partial minimum two-multiplier analysis(PLS-DA), main component analysis identification analysis(PCA-DA), were established, respectively. The accuracies of the authenticity identification models were 82.5%, 90.0%, 96.2% and 93.8%, while the accuracies of the commodity specification identification models were 89.3%, 96.0%, 90.7% and 97.3%, respectively. The models were well judged, the authenticity identification was based on the final identification model of PLS-DA, and the commodity specification was based on the final identification model of PCA-DA. There was no significant difference between its accuracy and M_1, and the time of determination was much shorter than M_2(P<0.01). Therefore, electronic-eye technology could be used for the rapid identification of the quality of Fritillariae Cirrhosae Bulbus.

[Study on superposition law of drug bitterness based on tongue taste evaluation and electronic tongue evaluation].

Traditional Chinese medicine( TCM) decoction contains complex bitterness. In this paper,the simple mixing of TCM monomer bitter substances is used as the entry point to study the law of bitterness superposition. With berberine hydrochloride( alkaloids),geniposide( terpenoids),and arbutin( glycosides) as mother liquor,sophoridine( alkaloids),gentiopicroside( terpenoids),and puerarin( glycosides) as additive substances,these different additive substances were mixed with different mother liquor according to concentration gradients to form different liquid mixtures. The bitterness of the additive solution and the mixtures was evaluated by traditional human taste panel method( THTPM) and electronic tongue; the bitterness-concentration fitting model of the additive solution and the liquid mixtures was established by Weibull and logarithmic curves. By comparing and analyzing the bitterness-concentration model and the bitterness difference( ΔI_0/ΔI_e) of the additive solution and the mixture,the influence of mother liquor on the bitterness of the mixture was investigated. The results showed that both the additive solution bitterness model and the liquid mixture bitterness model were consistent with the Weibull model and the logarithmic model( THTPM: R~2≥0. 887 0,P<0. 01; electronic tongue test:R~2≥0. 753 2,P<0. 05). The fitting degree of the Weibull model was generally higher than that of the logarithmic model; the bitterness difference( ΔI_0) was monotonously decreasing; the fitting equation of tongue bitterness and electronic tongue bitterness: R~2≥0. 874 2,P<0. 01. In this article,through the superposition of different kinds of TCM bitter substances,THTPM and electronic tongue test was combined. It was found that the bitterness after superposition was still in Weibull or logarithmic relationship with the concentration of additive substances; THTPM showed that the effect of bitter mother liquor on the bitterness of the mixture decreased with the increase of the concentration of the additive; the bitterness of the electronic tongue was obviously related to the bitterness of THTPM. However,further verification is needed later by optimizing the concentration gradient and expanding the sample size.

Optimization and validation of the protocol used to analyze the taste of traditional Chinese medicines using an electronic tongue.

Tools to define the active ingredients and flavors of Traditional Chinese Medicines (TCMs) are limited by long analysis times, complex sample preparation and a lack of multiplexed analysis. The aim of the present study was to optimize and validate an electronic tongue (E-tongue) methodology to analyze the bitterness of TCMs. To test the protocol, 35 different TCM concoctions were measured using an E-tongue, and seven replicate measurements of each sample were taken to evaluate reproducibility and precision. E-tongue sensor information was identified and classified using analysis approaches including least squares support vector machine (LS-SVM), support vector machine (SVM), discriminant analysis (DA) and partial least squares (PLS). A benefit of this analytical protocol was that the analysis of a single sample took <15 min for all seven sensors. The results identified that the LS-SVM approach provided the best bitterness classification accuracy (binary classification accuracy, 100%; ternary classification accuracy, 89.66%). The E-tongue protocol developed showed good reproducibility and high precision within a 6 h measurement cycle. To the best of our knowledge, this is the first study of an E-tongue being applied to assay the bitterness of TCMs. This approach could be applied in the classification of the taste of TCMs, and serve important roles in other fields, including foods and beverages.

Evaluation of the Bitterness of Traditional Chinese Medicines using an E-Tongue Coupled with a Robust Partial Least Squares Regression Method.

To accurately, safely, and efficiently evaluate the bitterness of Traditional Chinese Medicines (TCMs), a robust predictor was developed using robust partial least squares (RPLS) regression method based on data obtained from an electronic tongue (e-tongue) system. The data quality was verified by the Grubb's test. Moreover, potential outliers were detected based on both the standardized residual and score distance calculated for each sample. The performance of RPLS on the dataset before and after outlier detection was compared to other state-of-the-art methods including multivariate linear regression, least squares support vector machine, and the plain partial least squares regression. Both R² and root-mean-squares error (RMSE) of cross-validation (CV) were recorded for each model. With four latent variables, a robust RMSECV value of 0.3916 with bitterness values ranging from 0.63 to 4.78 were obtained for the RPLS model that was constructed based on the dataset including outliers. Meanwhile, the RMSECV, which was calculated using the models constructed by other methods, was larger than that of the RPLS model. After six outliers were excluded, the performance of all benchmark methods markedly improved, but the difference between the RPLS model constructed before and after outlier exclusion was negligible. In conclusion, the bitterness of TCM decoctions can be accurately evaluated with the RPLS model constructed using e-tongue data.