Patent application of intelligent quality control technology in traditional Chinese medicine production process: a review / 中国中药杂志

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.

Effects and evaluation of different processing and drying methods on components in Paeoniae Radix Alba / 中国中药杂志

The present study evaluates different processing and drying methods and investigates their effects on the chemical components in Paeoniae Radix Alba via content determination. The fresh medicinal materials of Paeoniae Radix Alba collected from Bozhou of Anhui province were processed(boiled and peeled) and dried(hot air-dried, infrared-dried, and microwave-dried) at different temperatures(40, 50, 60 and 70 ℃), and the 11 components(monoterpene glycosides, polyphenols, tannin, and benzoic acid) in Paeoniae Radix Alba were determined by ultra-performance liquid chromatography coupled to triple quadrupole with electrospray tandem mass spectrometry(UPLC-TQ-MS). Then the compounds in processed and dried samples were analyzed by partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA), and the contribution rates of differential components were evaluated by variable important in projection(VIP). The results indicated that the samples obtained by different processing and drying methods could be distinguished. Albiflorin, gallic acid, 1,2,3,4,6-pentakis-O-galloyl-β-D-glucose, and benzoic acid were the common differential components in boiled Paeoniae Radix Alba. Benzoic acid was the common differential component in peeled Paeoniae Radix Alba. Gallic acid was the common differential component in Paeoniae Radix Alba dried by different methods. The samples could not be distinguished after drying at different temperatures due to the lack of common differential components. This study is expected to provide a reference for the selection of processing and drying methods and the optimization of processing parameters.

Comparative study on differences of Paeonia lactiflora from different habitats based on fingerprint and chemometrics / 中国中药杂志

This study aims to compare the differences of Paeonia lactiflora from different habitats by establishing fingerprint. The fingerprint of P. lactiflora was established by UPLC. The samples collected from Sichuan,Hebei,Henan,Shanxi and Anhui were analyzed. The common peaks were identified by UPLC-Q-TOF/MS. The relative peak area of the common peaks was analyzed through similarity evaluation system( 2012 edition) for chromatographic fingerprint of traditional Chinese medicine developed by the National Pharmacopoeia Commission. Twelve common peaks were obtained and ten components were identified by reference substance and literature comparison. The similarity of each sample to the reference fingerprint is greater than 0. 900. However,all samples were clearly divided into 5 groups according to habitats after PLS-DA analysis. The peaks 2,6( ethyl gallate),10( galloypaeoniflorin) and 12( benzoyl paeoniflorin) were found to be the main difference components between the samples from five different habitats through the VIP value map. The study found that the variety of ingredients in the different areas are basically similar. But there are some differences in the content of the four components. The results of this study can provide reference at choosing and utilizing P. lactiflora from different places comprehensively.

Identification of metabolites of Reduning injection in rat plasma, bile, urine and feces after intravenous administration / 药学学报

This study was designed to determine the metabolites of Renduining injection in rats. The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometric (UHPLC-LTQ-Orbitrap-MS) and mass defect filter techniques were applied to analyze the metabolites of Reduning injection in rat plasma, bile, urine and feces. As a result, we determined 14 metabolites of geniposide, including oxidation, dehydration, hydroxymethylene loss, hydrolysis, ring-opened, cysteine conjugation and glucuronidation conjugation of aglycone; 9 metabolites of geniposidic acid, consisting of dehydration, ring-opened, double-bond reduction and cysteine conjugation; 6 metabolites of secoxylogain including hydrolysis, hydroxymethylene loss, hydroxylation and ethylation; 12 metabolites of chlorogenic acid, containing decarboxylation, hydrolysis, methylation, acetylation, cysteinylglycine conjugation and glutathione conjugation. It provided information for the therapeutic effect of Reduning in vivo.

Network-assisted mechanism investigation of Yaobitong Capsules on lumbar intervertebral discs / 中成药

AIM To explore analgesic mechanism of Yaobitong Capsules (Notoginseng Radix et Rhizoma,Chuanxiong Rhizoma,Corydalis Rhizoma,etc.) on lumbar intervertebral discs.METHODS An array of data mining,molecular docking and network analysis were employed to investigate the active compounds and key target protein.RESULTS Among the forty-six active hits identified by virtual screening,most compounds displayed good oral bioavailability and might confer an optimal CNS exposure.And eleven molecules (coptisine,diligustilide,corypalmine,chuanxiongterpene,etc.) were further confirmed to alleviate lumbar intervertebral discs through their targeting at nineteen proteins (such as p38,CGRP,MMPs,TNFα) to inhibit the inflammatory response and the infiltration of microvasculature,to reduce the nociceptors sensitivity,and to modulate the balance of Collagen and proteoglycans in catabolic and anabolic responses.CONCLUSION Yaobitong Capsules' clear molecular working mechanism and the key active compounds are revealed by this network-assisted investigation highlight the subsequent experiments on targets and active compounds.

HTRF-based high-throughput PGE2 release prohibition model and application in discovering traditional Chinese medicine active ingredients / 中国中药杂志

Prostaglandin (PG) E2 is an active substance in pathological and physiological mechanisms, such as inflammation and pain. The in vitro high-throughput assay for screening the inhibitors of reducing PEG2 production is a useful method for finding out antiphlogistic and analgesic candidates. The assay was based on LPS-induced PGE2 production model using a homogeneous time-resolved fluorescence(HTRF) PGE2 testing kit combined with liquid handling automation and detection instruments. The critical steps, including the cell density optimization and IC50 values determination of a positive compound, were taken to verify the stability and sensibility of the assay. Low intra-plate, inter-plate and day-to-day variability were observed in this 384-well, high-throughput format assay. Totally 5 121 samples were selected from the company's traditional Chinese medicine(TCM) material base library and used to screen PGE2 inhibitors. In this model, the cell plating density was 2 000 cells for each well; the average IC₅₀ value for positive compounds was (7.3±0.1) μmol; the Z' factor for test plates was more than 0.5 and averaged at 0.7. Among the 5 121 samples, 228 components exhibited a PGE2 production prohibition rate of more than 50%, and 23 components exhibited more than 80%. This model reached the expected standards in data stability and accuracy, indicating the reliability and authenticity of the screening results. The automated screening system was introduced to make the model fast and efficient, with a average daily screening amount exceeding 14 000 data points and provide a new model for discovering new anti-inflammatory and analgesic drug and quickly screening effective constituents of TCM in the early stage.

Monitor on influence of quality standard improvement upon Guizhi Fuling capsules efficacy / 中国中药杂志

In 2012, the preparation process and quality standard for Guizhi Fuling capsule were improved. To compare the effects and differences of capsules before (2011) and after(2012-2014) the improvement, evaluation models for intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma were applied in rats. Models were induced by oxytocin, liqiud bacteria mixture and estrogen loading, respectively. The capsules (12 batchs/year, 48 bathcs in all), sampled randomly in 2011-2014, the effects were assessed using the three models. In anti-dysmenorrhea models, remarked reduction of writhing frequency, ET-1 and PGF2α content in uterus could be detected, as well as extension of writhing latency. In pelvic inflammation rats, depression of TNF-α and raise of IL-2 were induced by earh batch of capsules. In hysteromyoma model, uterine weight and smooth muscle proliferation, including E2 and P level in plasma, were lowered obviously by all batchs of capsules. Secondly, Guizhi Fuling capsules produced in 2012-2014 revealed better effectiveness than the ones manufactured in 2011. Moreover, pharmacodynamics indexes of the samples made in 2011 differed significantly between groups, which could not be observed in the ones ot 2012-2014. After tne preparation process and quality standard improvement, the effectiveness and homogeneity of Guizhi Fuling capsules were enhanced.

Main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule / 中国中药杂志

Guizhi Fuling capsule is a traditional Chinese medicine composed of five kinds of medicinal plants, Cinnamomi Ramulus, Poria, Moutan Cortex, Persicae Semen, and Paeoniae Radix Alba. Pharmacology studies have shown that Guizhi Fuling capsule has many activities: anti-inflammatory, analgesic, anti-tumor, regulating smooth muscle, endocrine regulation and enhancing immunity. It achieved obvious effects in the treatment of uterine fibroids, pelvic inflammatory disease, dysmenorrheal, endometriosis, ovarian cysts, breast hyperplasia and other gynecological diseases. This paper reviewed the main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule in recent years.

Study of effective components and molecular mechanism for Guizhi Fuling formula treatment of dysmenorrhea, pelvic inflammatory disease and uterine fibroids / 中国中药杂志

In this study, the active components and potential molecular .mechanism of Guizhi Fuling formula in treatment on dysmenorrhea, pelvic inflammation, and hysteromyoma were investigated using network pharmacological methods. Sterols and pentacyclic triterpenes, with high moleculal network degree, revealed promising effects on anti-inflammatory, analgesic, anti-tumor, and immune-regulation, according to D-T network analysis. On the other hand, the targets with high degree were involved in inflammatory, coagulation, angiopoiesis, smooth muscle contraction, and cell reproduction, which showed the novel function in anti-dysmenorrhea, pelvic inflammation, and hysteromyoma. Furthermore, the formula was indicated to play a key role in smooth muscle proliferation, inhibition of new vessels, circulation improvement, reduction of hormone secretion, alleviation of smooth muscle, block of arachidonic acid metabolism, and inflammation in uterus. Thus, the main mechanism of Guizhi Fuling formula was summarized. In conclusion, Guizhi Fuling formula was proven to alleviated dysmenorrhea, pelvic inflammation, and hysteromyoma by acting on multiple targets through several bioactive compounds, regulating 21 biological pathways.

Study on anti-inflammation and immunoloregulation effect of Guizhi Fuling capsule ingredients using high content screening / 中国中药杂志

The present study sought to investigate the anti-inflammation and immunoloregulation effect of 17 Guizhi Fuling capsule ingredients. The anti-inflammatory ingredients on LPS-induced RAW264. 7 cell injury were assessed with ELISA and immunofluorescence. The release of IL-1β, TNF-α, PGE2 were detected with ELISA and the expression of COX-2 was detected with immunofluorescence. The effects of them on promoting splenic lymphocyte proliferation were assessed with MTT and Hoechst 33342 staining method. The results showed that 15 ingredients had obviously anti-inflammatory activity on LPS- induced injury and play the immunoloregulation roles. This study suggested that the 15 ingredients may be the active ingredients on pelvic infection.

Effect of Phenobarbital on Bcl-2 and Bax expressions in brain tissue of young rats / 中华实用儿科临床杂志

Objective To study the effect of Phenobarbital (PB) on experimental rats,observe the histological changes of immature brain and the expressions of apoptosis-related proteins Bcl-2 and Bax in neurons detected by immunohistochemistry,and to explore the influence and mechanism of PB on brain damage at therapeutic levels to immature brain maturation of rat in order to provide the theoretical and experimental base for clinic.Methods A total of 40 healthy 18-day-old Sprague-Dawley(SD) rats (male or female) were randomly assigned into 2 groups:normal saline (NS) treated as control group(20 cases),PB group(20 cases).Each group was further randomly divided into longterm(4 weeks) treated group and short-term(2 weeks) treated group(10 rats in each group).The rats in PB group received intragastricadministration with PB (30 mg/kg).The rats in control group were handled by injection of NS into stomach and abdomen according to 4 mL/kg.All performances were undertaken for twice every day.At the end of the therapeutic period,body and brain weight were measured when the rats were sacrificed.Histological studies on the tissues of frontal lobes and hippocampus were performed by Hematoxylin-Eosin(HE) staining and Nissl staining.Expressions of apoptosis-related proteins Bcl-2 and Bax in neurons were detected by immunohistochemistry.Results There were no significant differences in body and brain weights or histological studies index among control group as well as PB group before and after treatment for short term(P ＞0.05).Remarkable reduction of brain weight was only observed in immature rats exposed to PB compared to control group for long period,and significant neurodegeneration,neuronal necrosis were observed in immature rats exposed to PB compared to control group(all P ＜ 0.01).The expression of Bax protein in the frontal lobe increased significantly in immature rats receiving PB for long period comparing with control (P＜0.01).In contrast,expression of Bcl-2 protein did not change at therapeutic level.The ratio of Bax/Bcl-2 was obviously increased.Conclusions Chronic treatment with PB will result in significant neuronal apoptosis and necrosis and persistent cognitive impairment and brain damage to immature rates.Brain damage of PB at therapeutic level to immature brain may be irreversible.The significant expression of Bax protein in the frontal lobe and the high rate of Bax/Bcl-2 are probably the main reasons which cause brain weight decreasing and brain damage by PB in immature brain tissue.