[Optimization of prediction model for personalized water pills based on semantic analysis of traditional Chinese medicine materials].

This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y_1=-4.172+3.63X_A+15.057X_B+1.838X_C-0.997X_D(adhesive concentration of 10% when Y_1<0, and 20% when Y_1>0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y_2=6.051+94.944X_A~(1.5)+161.977X_B+70.078X_C~2+12.016X_D~(0.3)+27.493X_E~(0.3)-2.168X_F~(-1)(R~2=0.954, P<0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.

Synthesis and application of clinically approved small-molecule drugs targeting androgen receptor.

Androgen receptor (AR) plays a crucial role in various physiological processes. Dysregulation of AR signaling has been implicated in several diseases, such as prostate cancer and androgenetic alopecia. Therefore, the development of drugs that specifically target AR has gained significant attention in the field of drug discovery. This review provides an overview of the synthetic routes of clinically approved small molecule drugs targeting AR and discusses the clinical applications of these drugs in the treatment of AR-related diseases. The review also highlights the challenges and future perspectives in this field, including the need for improved drug design and the exploration of novel therapeutic targets. Through an integrated analysis of the therapeutic applications, synthetic methodologies, and mechanisms of action associated with these approved drugs, this review facilitates a holistic understanding of the versatile roles and therapeutic potential of AR-targeted interventions. Overall, this comprehensive review serves as a valuable resource for medicinal chemists interested in the development of small-molecule drugs targeting AR.

[Classification optimization of traditional Chinese medicine materials based on additive physical properties of powder].

According to the method of predicting the physical properties of oily powder based on the additive physical properties of Chinese medicinal powder, Dioscoreae Rhizoma and calcined Ostreae Concha with high sieve rate and good fluidity were mixed and crushed with Persicae Semen, Platycladi Semen, Raphani Semen, Ziziphi Spinosae Semen, and other typical oily materials with high fatty oil content in proportion to obtain 23 mixed powders. Fifteen physical properties such as bulk density, water absorption, and maximum torque force were measured, and the physical properties of typical oily powders were predicted. When the mixing and grinding ratio was in the range of 5∶1-1∶1, the r value in the correlation equation between the weighted average score of the mixed powder and the powder proportion ranged from 0.801 to 0.986, and the linearity was good, indicating that the method of predicting the physical properties of oily powder based on the additive physical properties of traditional Chinese medicine(TCM)powder was feasible. The results of cluster analysis showed that the classification boundaries of the five kinds of TCM materials were clear, and the similarity of the physical fingerprints of powdery and oily materials decreased from 80.6% to 37.2%, which solved the problem of fuzzy classification boundaries of powdery and oily materials due to the lack of representativeness of oily material model drugs. The classification of TCM materials was optimized, laying a foundation for optimizing the prediction model of the prescription of personalized water-paste pills.

[Material classification of decoction pieces based on physical properties of powder].

Chinese medicinals feature different medicinal parts and enriched components, which makes their powders show obvious microscopic identification characteristics and specific physical properties. On this basis, the commonly used Chinese medicinals can be divided into several categories, such as powdery, fibrous, sugar, oil, and brittle materials, which is of great importance to the research and development of personalized Chinese medicinal preparation technology. However, the existing classification methods are highly subjective and thus difficult to meet the requirements for the development of personalized Chinese medicinal preparations with high quality. In this study, 55 representative Chinese medicinals, such as Dioscoreae Rhizoma and Leonuri Herba, were selected, and the physical properties of their powders were systematically characterized by comprehensive powder tester, torque rheometer, texture analyzer, etc., based on which a data set encompassing physical properties of these powders was built. The typical physical fingerprints of powders from the above 5 categories were established by multivariate statistical analysis. Then, the Chinese medicinals were classified according to the Euclidean distance between each of them and the typical value in the PCA score plot. For those with multiple material properties, whose classification boundary was fuzzy, the proportions of different types of materials were calculated with the combination of Euclidean distance, powder properties, microscopic identification characteristics, and chemical composition, so as to achieve the multivariate quantitative classification of Chinese medicinals. This lays the foundation for the further creation of intelligent personalized Chinese medicinal preparation technology.

[Establishment of prediction model for personalized water-paste pills based on classification of traditional Chinese medicine materials].

The purpose of the present study was to investigate the relationship of the classification of traditional Chinese medicine(TCM) materials with the suitable binder concentration and dosage in the preparation of personalized water-paste pills and establish a model for predicting the binder concentration and dosage. Five representative TCM materials were selected, followed by mixture uniform design. The water-paste pills were prepared by extrusion and spheronization with hypromellose E5(HPMC E5) as the binder. The quality of intermediates and final products was evaluated, and the resulting data were subjected to multivariate statistical analysis. The prediction models for binder concentration and dosage were established as follows: binder concentration: Y_1=0.378 6 + 0.570 1X_A + 2.271 2X_B-0.894 5X_C-0.458 2X_D-1.145 4X_E(when Y_1 < 0, 10% HPMC E5 was required; when Y_1 > 0, 20% HPMC E5 was required), with the accuracy reaching up to 100%; binder dosage: Y_2=32.38 + 0.25X_A + 1.85X_B-0.013X_B~2-0.002 5X_C~2(R~2=0.932 6, P < 0.001). The results showed that the binder concentration and dosage were correlated positively with the proportion of fiber material but negatively with the proportions of sugar material and brittle material. Then the validation experiments were conducted with the prediction models and all the prescriptions could be successfully prepared at one time. These demonstrated that following the classification of TCM materials and the calculation of their proportions in the prescription, the established mathematical model could be adopted for predicting the binder concentration and dosage required in the preparation of personalized water-paste pills, which contributed to reducing the pre-formulation research and guiding the actual production of personalized water-paste pills.

[Exploratory study on preparation of high drug loading granules with traditional Chinese medicine raw powder as carriers].

With Sangtang Yin granule as model drug,and based on the strategy of " unification of medicines and excipients",the feasibility of preparing high drug loading granules with traditional Chinese medicine( TCM) raw powder as carrier was explored. The powder yield,particle size and particle size distribution,fillibility,flowability,hygroscopicity,reconstituability and other key physical properties relating to preparations of 8 herbs( Dioscoreae Rhizoma,Euryales Semen,Atractylodis Macrocephalae Rhizoma,Coicis semen,Poria,Puerariae Lobatae Radix,Puerariae Thomsonii Radix and Coicis Semen by stir-frying with bran) were studied after being smashed,and the feasibility of taking them as excipients of TCM granules was evaluated by co-spray drying,dry granulation and other preparation techniques. According to the results of the physical properties of raw powders,raw powders of Dioscoreae Rhizoma,Euryales Semen and Puerariae Thomsonii Radix had a high powder yield,uniform particle size distribution,good fillibility,poor hygroscopicity and good reconstitutability,with the feature of assisting granule forming. Compared with the prescription of spray dry powder Sangtang Yin without any excipient,the co-sprayed powder had a high yield,good fillibility and compressibility. The yield of dry granules prepared by co-spraying dry powder was increased by more than 10%,and the particles had a uniform color,good fluidity and dissolubility with the drug-loading rate up to 100%. Based on the physical characteristics of TCM raw powder combined with the analysis of the preparation process,Dioscoreae Rhizoma and Puerariae Thomsonii Radix raw powder were selected as the carriers of granule preparations,and Sangtang Yin granule without any excipient was successfully prepared. The findings provide a feasible idea for the preparation of TCM granules with a high drug loading capacity.

[Physiochemical property variation in traditional Chinese medicine decoction before or after precipitation in alcohol and its relationship with wall stickiness in spray drying].

To explore the relationship between the variations of the physiochemical properties of traditional Chinese medicine(TCM) decoction before or after precipitation in alcohol and the wall stickiness in spray drying. In this study, widely used TCMs in clinic were selected to determine the physiochemical properties of TCM decoction before or after precipitation in alcohol separately.Afterwards, the principle component analysis(PCA),Hierarchical cluster analysis(HCA),and orthogonal partial least squares-discriminate analysis(OPLS-DA) were used to evaluate the relationship between the variations of those liquid before or after precipitation in alcohol and hot-melt stickiness in spray drying.Three types of statistical analysis methods all indicated that ethanol precipitation affected physiochemical properties of TCM decoction, and the variations of physical properties showed significant association with hot-melt stickiness in spray drying.The results of PCA-X and HCA suggested that the dynamic surface tension(DST) was impacted most by the alcohol deposition treatment,at the same time,the other 5 physiochemical properties were also affected.OPLS-DA verified that PCA-X and HCA results, and revealed that DST,equilibrium surface tension(EST) and pH were significantly affected by alcohol deposition treatment,and the order of the affecting factors from high to low was DST,EST and pH.Therefore,the downward trend of DST and pH were the important factors that directly affected the hot-melt stickiness of TCM after precipitation in alcohol,which would be probably caused by losing macromolecules alcoholic insoluble components and increasing relative proportions of organic acid and small molecule sugar.

[Correlation between chemical compositions of traditional Chinese medicine extracts and phenomenon of wall stickiness in spray drying].

To explore the correlation between chemical compositions (organic acids, small molecule sugars, protein and others) of traditional Chinese medicine extracts and the wall stickiness in spray drying. In this study, 55 types of most common used Chinese herbs were selected to determine the content of 7 chemical components such as citric acid and fructose from plant extraction. The status of wall stickiness was observed during the drying process. The principle component analysis (PCA-X), hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were then used to evaluate the correlation between each chemical compositions and wall stickiness, so as to look for the essential chemical compositions associated with the wall stickiness. All of the above 3 statistical analysis methods showed significant results in distinguishing the two groups (sticky or non-sticky). PCA-X score chart and HCA clustering scatter plot suggested that the small molecular substance was the main factor causing wall stickiness, which was then proved by the reality where some of the traditional herb extracts were in non-sticky state after drying but in sticky state after alcohol precipitation. OPLS-DA results revealed that L-malic acid, citric acid, fructose and glucose were the difference factors for the wall stickiness of the extracts. Under small molecular components, L-malic acid, citric acid, fructose and glucose were the crucial factors that directly led to the hot melt sticky wall of the herbal extracts, and macromolecular substances might ameliorate the function of wall stickiness.

[A new device for determination of adhesive force and its application in predicting hot-melt sticking in spray drying of traditional Chinese medicine].

A new device was designed to measure adhesive force and predict whether traditional Chinese medicine extracts would appear hot-melt sticking in spray drying process．Based on the physical property tester as fundamental test platform, the device was fixed with a camera, a temperature and humidity sensor probe and a set of equipment for hot air. This device could simulate the dry environment of spray dryer and analyze the variables of testing solutions' adhesiveness against drying time. To establish and validate a model of predicting hot-melt sticking in spray drying, data was collected by using data mining. The results of this study proved that the device could be used to predict the hot-melt sticking in spray drying based on the adhesive force of materials (testing solutions). In addition, the study also found that the adhesiveness of the hot-melt sticking materials gradually increased with the evaporation of water, while that of non-sticking materials first increased and then rapidly decreased.

[Discussion on research and development of new traditional Chinese medicine preparation process based on idea of QbD].

Traditional processes are mostly adopted in traditional Chinese medicine (TCM) preparation production and the quality of products is mostly controlled by terminal. Potential problems of the production in the process are unpredictable and is relied on experience in most cases. Therefore, it is hard to find the key points affecting the preparation process and quality control. A pattern of research and development of traditional Chinese medicine preparation process based on the idea of Quality by Design (QbD) was proposed after introducing the latest research achievement. Basic theories of micromeritics and rheology were used to characterize the physical property of TCM raw material. TCM preparation process was designed in a more scientific and rational way by studying the correlation among enhancing physical property of raw material, preparation process and product quality of preparation. So factors affecting the quality of TCM production would be found out and problems that might occur in the pilot process could be predicted. It would be a foundation for the R&D and production of TCM preparation as well as support for the "process control" of TCMIs gradually realized in the future.

A review of experimental research on herbal compounds in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease worldwide, leading to progressive muscle atrophy and paralysis. The limited success of conventional treatment for ALS has prompted investigations into complementary and alternative therapies. Herbal remedies provide good prospects of ALS prevention and treatment, with advantages such as multiple targets, multiple links, and few side effects. Studies in vitro and in vivo have shown that herbs have a great potential for treatment of ALS, with therapeutic effects against oxidative stress, excitatory amino acid toxicity, neuroinflammation, and calcium cytotoxicity. Active monomers or ingredients extracted from herbs are considered promising candidates for ALS. Therefore, we review recent experimental research on monomers and compounds isolated from herbal remedies for preventing and treating ALS.

[Multivariate analysis of relationships between material properties and hygroscopicity of Chinese medicine raw materials].

Material properties and hygroscopicity were determined. Principal component analysis and partial least squares regression were applied to evaluate relationships between material properties and hygroscopicity of Chinese medicine raw materials. The results showed that hygroscopicity was correlated with water content, particle size distribution, water soluble characteristic and cohesion. Balanced moisture content was positively correlated with water content, particle size distribution, water soluble characteristic and cohesion. Moisture absorption velocity was negatively correlated with particle size distribution, protruding degree and positively correlated with water soluble characteristic and cohesion. Moisture absorption acceleration was positively correlated with water content, particle size distribution and negatively correlated with water soluble characteristic and cohesion. Hygroscopicity of Chinese medicine raw materials is interpreted in terms of physics.

Effect of parthenolide on proliferation and apoptosis in gastric cancer cell line SGC7901.

OBJECTIVE: To investigate the effect of parthenolide (PAR) on proliferation and apoptosis in gastric cancer cell line SGC7901. METHODS: Human gastric cancer cell line SGC7901 cells were incubated with various concentration of PAR. After various periods of incubation, the proliferation of SGC7901 cells was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methyl thiazolyl tetrazolium (MTT) assay. Apoptosis was measured by the annexin V-fluorescein isothiocyanate fluoresceine isothiocyanate (FITC)/propidium iodide (PI) double labeled staining method and the morphology of the cell was observed under a fluorescent microscope. Mitochondrial potential was measured by flow cytometry after Rhodamine 123 staining. The expressions of cytochrome C and the Bcl-2 family of proteins, including Bcl-2, Bax, Bid and tBid were measured by Western blot. Caspase 3 and 8 activities were measured by enzyme-linked immunosorbent assay. RESULTS: Treatment with PAR induced apoptosis as confirmed by annexin V-FITC/PI assay. PAR-induced apoptosis was associated with intracellular events including the decline of mitochondrial potential, increased release of cytochrome C from the mitochondria, decreased expression of Bcl-2, increased expression of Bax, Bid and tBid and activation of caspase 3 and 8. CONCLUSION: These results suggest that possibly via activation of the mitochondrial pathway, PAR causes mitochondrial damage leading to the release of cytochrome C and by regulating the expression of the Bcl-2 family of proteins and activating caspases which leads to results in apoptotic cell death in SGC7901 cells. Our results might be helpful in formulating new therapeutic approaches using Chinese herbal medicine.