Identification of chemical components and network pharmacology of Huanglian Decoction based on UPLC-Q-TOF-MS/MS technology / 中国中药杂志

The chemical components of Huanglian Decoction were identified by ultra-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) technology. The gradient elution was conducted in Agilent ZORBAX Extend-C_(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the MS data were collected under the scanning range of m/z 100-1 500. Through high-resolution MS data analysis, combined with literature comparison and confirmation of reference substances, this paper identified 134 chemical components in Huanglian Decoction, including 12 alkaloids, 23 flavonoids, 22 terpenes and saponins, 12 phenols, 7 coumarins, 12 amino acids, 23 organic acids, and 23 other compounds, and the medicinal sources of the compounds were ascribed. Based on the previous studies, 7 components were selected as the index components. Combined with the network pharmacology research and analysis me-thods, the protein and protein interaction(PPI) network information of the intersection targets was obtained through the STRING 11.0 database, and 20 core targets of efficacy were screened out. In this study, UPLC-Q-TOF-MS/MS technology was successfully used to comprehensively analyze and identify the chemical components of Huanglian Decoction, and the core targets of its efficacy were discussed in combination with network pharmacology, which laid the foundation for clarifying the material basis and quality control of Huanglian Decoction.

Material basis and mechanism of Kazakh classic prescription Wuzdekh in the treatment of enteritis / 中国药房

OBJECTIVE To explore the material basis and potential mechanism of Kazakh classic prescription Wuzdekh （WZDK） in the treatment of enteritis. METHODS LC-MS/MS technology was used to analyze the chemical components in WZDK. Through network pharmacology and molecular docking technology， the main chemical components of WZDK were screened and the target was predicted； therapeutic effect and target of WZDK on acute enteritis were verified through in vivo experiments. The acute enteritis model of mice was induced by dextran sulfate sodium salt； the general condition of the mice was observed during administration and the disease activity index （DAI） score was calculated； pathological changes of the intestine and mRNA expression of core target were validated by HE staining and quantitative real-time PCR. RESULTS A total of 316 chemical components were obtained by LC-MS/MS. The core targets of network pharmacological analysis mainly included interleukin 1β（IL- 1β）， protein kinase B1 （AKT1）， tumor protein p53 （TP53）， IL-6， tumor necrosis factor （TNF） and so on. The results of molecular docking showed that chemical components such as mairin， lappadilactone， costunolide and dehydrocostus lactone were stable in binding to the core target. The results of in vivo experiment showed that， compared with model group， high dose （5.00 g/kg） of WZDK could significantly reduce the DAI score （P＜0.05）， improve inflammatory cell infiltration and mucosal tissue damage of colon tissue， and significantly down-regulated mRNA expressions of IL-6， TNF-α， IL-1β and TP53 in colon tissue（P＜ 0.05 or P＜0.01）. CONCLUSIONS Chemical components of WZDK such as mairin， lappadilactone， costunolide and dehydrocostus lactone may play the role of improving the imbalance of local inflammatory factors in the intestine and repairing damage of colonic mucosal tissue by down-regulating mRNA expressions of TNF-α， IL-6， IL-1β and TP53 in colon tissue.

Historical Evolution and Textual Research on Classic Prescription Danggui Buxuetang / 中国实验方剂学杂志

Danggui Buxuetang， derived from Clarifying Doubts about Damage from Internal and External Causes （Volume 2）： Treatise on Heat Injury to Stomach Qi（《内外伤辨惑论卷中·暑伤胃气论》） by LI Dongyuan in the Jin and Yuan dynasties， is a classic and famous formula for tonifying qi and generating blood that has been inherited and promoted by successive generations of medical practitioners and has been included in the "Catalogue of Ancient Classical Prescriptions （First Batch）" published by the National Administration of Traditional Chinese Medicine in 2018. The paper analyzed the historical origin， composition， dosage， processing， preparation， decocting， and taking methods， efficacy， and application of the classic formula Danggui Buxuetang by consulting ancient and modern literature and combining the key information examination principles of ancient classic prescriptions. A total of 604 pieces of information on relevant ancient literature were collected， including 186 ancient Chinese medical books， of which 40 （five in the Jin and Yuan dynasties， 19 in the Ming Dynasty， and 16 in the Qing Dynasty） had detailed records of composition， processing， and dosage. Danggui Buxuetang is mainly comprised of Astragali Radix and Angelicae Sinensis Radix. According to the ancient and modern dose conversion， there are 37.3-38.1 g of Astragali Radix and 7.5-7.6 g of Angelicae Sinensis Radix in the formula. Astragali Radix is preferably fried with honey and Angelicae Sinensis Radix with wine. Astragali Radix and Angelicae Sinensis Radix are decocted with 600 mL of water to 300 mL， and taken warm before meals. The main effect of this formula are described in ancient books as blood deficiency and fever， with symptoms of muscle fever， dryness and heat， irritability and thirst， red eyes and face， sleeplessness in daytime and night， and surging and feeble pulse which is weak under hard pressing， and it is a famous formula for replenishing qi and generating blood. Modern research shows that Danggui Buxuetang is commonly used in the treatment of various kinds of anemia， diabetic nephropathy， tumors， and cardiovascular and cerebrovascular diseases. The above research results can provide a reference for the subsequent development and research on the classic formula Danggui Buxuetang.

Mahuang Shengmatang Based on Five Depression Syndromes in Huangdi Neijing / 中国实验方剂学杂志

Mahuang Shengmatang was first recorded in the chapter "Reverting Yin Diseases" in the Treatise on Cold Damage （《伤寒论》）. Whether it is a classic prescription created by ZHANG Zhong-jing is controversial among scholars and physicians due to its distinctiveness in contexts and drug composition. In fact， its proven efficacy in a number of clinical cases cannot be denied， and it is rather biased to judge that Mahuang Shengmatang is a fallacy of later generations. The present study pointed out that Mahuang Shengmatang was a representative in the Treatise on Cold Damage in the treatment of diseases with complicated syndromes. In this formula， although the compatibility of drugs effective in dispersion， astringing， nourishing Yin， assisting Yang， clearing heat， dissipating cold， ascending， floating， sinking， and descending seems complex， it follows certain therapeutic principles. Five depression syndromes in the Huangdi Neijing （《黄帝内经》） highly reflect the Five Elements losing the nature， and embody multiple characteristics of the five elements， such as the movement forms， functions， and disease nature. Furthermore， the corresponding treatment methods were pointed out in the Plain Questions · Major Discussion on the Progress of the Six Climatic Changes of Huangdi′s Internal Classic， including "stagnation of wood should be treated by smoothing， stagnation of fire by dispersing， stagnation of earth by attacking， stagnation of metal by dredging， and stagnation of water by inhibiting"， aiming to restore the physiological conditions of the five elements. The indicated syndromes of Mahuang Shengmatang are complex in superior-inferior， asthenia-sthenia， and cold-heat. The five depression syndromes and their treatment methods recorded in the Huangdi's Internal Classic can reflect the key syndrome pathogenesis and therapeutic principles， which are conducive to analyzing the syndrome differentiation and formulating principles of Mahuang Shengmatang. In the disease progression， impaired Yang Qi in greater Yin and inward invasion of cold pathogens in reverting Yin happen in the initial stage of indicated syndromes of Mahuang Shengmatang， with characteristics of water stagnation， earth stagnation， and wood stagnation. Furthermore， mental stagnation and fire stagnation triggered by Yang Qi accumulation in greater Yang and Yang brightness are the secondary consequences. The compatibility of five types of drugs in Mahuang Shengmatang can act on five depression syndromes in a targeted manner. Based on the five-depression theory in the Huangdi′s Internal Classic and available literature， the present study summarized syndrome pathogenesis and medication characteristics of Mahuang Shengmatang， clarified the correlation between formula and syndrome， and reviewed clinical reports in recent years， which is expected to provide references for the clinical application of Mahuang Shengmatang.

UPLC-Q-TOF-MS analysis of chemical constituents of classical prescription Yiguanjian standard decoction / 中国中药杂志

An UPLC-Q-TOF-MS method was employed to characterize and classify the chemical components of the standard decoction of Yiguanjian, a classical famous recipe. Chromatographic separation was performed on an Acquity HSS T3(2.1 mm ×100 mm, 1.8 μm) column with a mobile phase of 0.1% formic acid water-0.1% formic acid acetonitrile using gradient elution. The flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry was performed on electrospray ionization source(ESI) with positive and negative ion scanning modes. The potential compounds were identified by comparing the reference compounds, analyzing the mass spectrometry data and matching the published articles on Masslynx 4.1 software and SciFinder database. Finally, a total of 113 compounds, including 11 amino acids, 19 terpenoids, 13 phthalides, 11 steroidal saponins, 10 coumarins, 9 alkaloids, 7 flavonoids, 8 phenylethanoid glycosides, 8 organic acids and 17 other categories were identified. The established method systematically and accurately characterized the chemical components in Yiguanjian, which could provide experimental evidences for the subsequent studies on the pharmacodynamical material basis and quality control of Yiguanjian.

Quality value transfer of substance benchmarks in Sanpian Decoction / 中国中药杂志

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

General screening principles and inheritance paths of classic prescriptions in Tibetan medicine / 中国中药杂志

Due to the profound theoretical rationale, perfect diagnosis and treatment system, and characteristic medicinal resources, Tibetan medicine has been passed down to the present day as one of the four traditional medicine systems all over the world. With the development of modern society and the change in people's concept of seeking medical services, Tibetan medicine has gradually attracted wide attention by virtue of its natural, green and safe diagnosis and treatment characteristics, which enables it to be vigo-rously developed and inherited. There are numerous ancient books on Tibetan medicine, covering a large number of ancient prescriptions, which has laid a solid foundation for later scholars to thoroughly investigate the diagnosis and treatment rules in Tibetan medicine and apply them to modern clinical practice. Screening the classic prescriptions that meet modern clinical needs from those numerous ancient books is a new direction in the inheritance and development of Tibetan medicine. On the basis of historical origin and current application status of ancient prescriptions in Tibetan medicine, this paper preliminarily elaborated the definition of classic prescriptions of Tibetan medicine and their general screening principles and precautions, and also discussed the modern inheritance paths of classic prescriptions in Tibetan medicine from basic research, post-marketing evaluation, and the development of novel preparations. Considering the shortcomings in the present study, the key technical issues mentioned need to be more deeply explored and analyzed in future studies.

Methods and key points of literature collation and mining of classic prescriptions in ethnic medicine / 中国中药杂志

The systematic collation and mining of ethnic medicine literature is the key to the screening and textual research of classic prescriptions. This study focused on the textual research of such key issues as the source of prescriptions, the translation of minority languages into Chinese characters and their corresponding medical terms, the original plants of drugs, and the standard dosage. It is believed that the methods and experience of textual research of classic prescriptions in traditional Chinese medicine(TCM) can be utilized by the ethnic medicine. At the same time, the prominent problems unique to ethnic medicine cannot be neglected.(1)Attention should be paid to extraterritorial traditional medical literature in the textual research of the source of prescriptions. For instance, Indian medical literature is the source of many classic prescriptions in Tibetan medicine, Ibn Sina's Canon of Medicine the source of those in Uygur and Hui medicine, and ancient Indian Buddhist classics the source of those in Dai medicine.(2)The translation and comparison of medical terms in different language systems requires the cooperation of linguists, historians, and medical experts, the combination of historical research, historical linguistics and clinical research methods, and the use of cross-language comparison. In recent years, the related research achievements like multiple translated and annotated versions of classical literature in ethnic medicine and their respective terminology standards have been constantly emerging.(3)In textual research of the original plants of drugs, the following two points deserve attention: one is that the same drug is used in different ethnic medical systems, but there are differences in the understanding of drug properties and active parts; the other is that the original plants of the same drug vary in different ethnic medical systems.(4)The derivation of some classic prescriptions in ethnic medicine from foreign classics results in the difference among measurement systems. In addition, the detailed dosage fails to be covered in some ethnic literature, so the dosage standard should be determined depending on clinical practice and expert consensus.

Study on determination and quantity transfer of multi index components in Wenjing Decoction / 中国中药杂志

Based on the textual research on literature, the key information of Wenjing Decoction were tested and identified, and 15 batches of lyophilized powder samples of Wenjing Decoction were prepared. The specific components, including paeoniflorin, glycyrrhizin, ginsenosides(Rg_1, Re and Rb_1), glycyrrhizic acid, and paeonol, were used as indexes to establish the HPLC method for quantitative evaluation, and the content ranges and transfer rates of these components were determined. The results showed that the contents of paeoniflorin, glycyrrhizin, ginsenosides Rg_1 + Re, ginsenoside Rb_1, glycyrrhizic acid, and paeonol in the 15 batches of samples were 0.62%-0.86%, 0.25%-0.76%, 0.14%-0.30%, 0.07%-0.21%, 0.63%-1.16%, and 0.09%-0.25%, respectively, and their transfer rates from the decoction pieces to the reference materials were 14.99%-19.42%, 28.11%-40.93%, 25.92%-61.88%, 25.03%-64.06%, 23.43%-35.53%, and 5.34%-10.44%, respectively. The consistency of the transfer rates between batches indicated that the preparation process was stable. It is suggested that the contents of paeoniflorin, glycyrrhizin, ginsenosides Rg_1 + Re, ginsenoside Rb_1, glycyrrhizic acid, and paeonol in Wenjing Decoction should not be less than 0.52%, 0.35%, 0.15%, 0.10%, 0.63%, and 0.12%, respectively. In this study, we determined the contents and analyzed the quantity transfer process of the index components in Wenjing Decoction, which can provide a basis for the follow-up development of Wenjing Decoction and the quality control of related preparations.

Application of traditional Chinese medicine in prevention and treatment of COVID-19 / 中草药

The outbreak of COVID-19 in Wuhan Province of China is highly contagious, rapid transmission and widespread, which has aroused great concern at home and abroad. WHO declared COVID-19 as an international public health emergency of concern. In the face of major epidemic situation, our hospital has carried out investigation and analysis on the use of traditional Chinese medicine in the prevention and treatment of COVID-19, and summarized the direction of diagnosis and treatment of traditional Chinese medicine and the main points of use of antiviral traditional Chinese medicine, classic prescriptions and Chinese patent medicine, in order to provide reference for diagnosis and treatment of COVID-19 and rational drug selection in medical institutions.

Study on optimization of UPLC fingerprint of classic prescription of Shentong Zhuyu Decoction based on principle of information entropy maximization / 中草药

Objective: To optimize the condition of the fingerprint of the classic prescription Shentong Zhuyu Decoction (SZD) by the principle of information entropy maximization. Methods: The chromatographic fingerprint was obtained with Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) and gradient eluted with acetonitrile and 0.4% phosphoric acid aqueous solution; The flow rate was 0.6 mL/min, and the column temperature was maintained at 40 ℃; The detection wavelengths were set at 190-400 nm, and the injection volume was 1 μL, and calculate the information entropy to optimize the wavelength of maximizing the information entropy of the fingerprint of SZD, under the optimal wavelength, investigate the mobile phase, column temperature, flow rate, sample volume, select the optimal conditions based on the principle of maximizing the information entropy, and carry out the fingerprint study of 15 batches of SZD under the optimal conditions. Results : Under the principle of information entropy maximization, the optimal conditions of the fingerprint of SZD were as follows: the detection wavelength was 235 nm, and gradient eluted with acetonitrile and 0.4% phosphoric acid aqueous solution; The flow rate was 0.4 mL/min, and the column temperature was maintained at 40 ℃, the injection volume was 3 μL; The absolute and relative entropy was the largest. The total statistical moment similarity of 15 batches of SZD fingerprints ranged from 0.882 8 to 0.995 3. The RSD values of the total first-order moment and information entropy of the total amount were 5.40% and 2.25% respectively, all of which were less than 10%, indicating that the imprinting effect of the overall chemical structure of the multi-component system of traditional Chinese medicine was stable. Conclusion: When the number and area of chromatographic peaks reach the best characterization, the information entropy is the largest. At this time, the number of peaks is high, the shape of peaks is better, the resolution is good, the number of theoretical plates is higher, and the best condition of fingerprint can be determined. The principle of information entropy maximization can provide scientific basis for fingerprint optimization of traditional Chinese medicine and its compound prescription, and lay a foundation for quality control of classical formulas.

Study on specific chromatogram and content determination of multi-index components about material reference of classic prescription of Huaganjian / 中草药

Objective: To establish the UPLC specific chromatogram and HPLC content determination methods of multi-index components about the material reference of classical Huaganjian and build its quality control system. Methods: According to the ancient books and combining with the previously inspected process, 18 batches of Huaganjian material reference from different origins were prepared. The specific chromatogram was established by using UPLC. Similarity was calculated by using TCM Chromatographic Fingerprint Similarity Evaluation Software (2012). Combining with orthogonal partial least squares discriminant analysis, we excavated the main components that affected the quality of Huaganjian material reference from different batches and origins. Three of these index components (paeoniflorin, hesperidin, paeonol) from prescription sovereign drug, minister drug, and assistant drug were selected and used as indicators for content determination of Huaganjian material reference. HPLC content determination methods were established and the content of 18 batches of samples was determined respectively. Results: The similarity of the specific chromatogram was ≥ 0.989. Thirty-three common peaks were calibrated, and eight common peaks were identified by chemical composition (gallic acid, geniposide, paeoniflorin, hesperidin, didymin, paeonol, sinensetin, and 3,5,6,7,8,3',4'- heptamethoxyflavone). Nine index components that affected the stability between batches were found out (Peak 31, 20, 11, 13, 22, 33, 21, 29, 1). Paeoniflorin, hesperidin, and paeonol were selected as content determination indicators. The content range of these components in material reference was 1.28%-1.95% paeoniflorin, 0.91%-1.02% hesperidin, 0.48%-0.57% paeonol. Conclusion: The quality control method of the material reference of classic prescription Huaganjian was established preliminarily through the UPLC specific chromatogram and HPLC content determination of index components. This method was rapid, simple, feasible, reproducible, stable and could provide a theoretical basis for the subsequent development and quality control of Huaganjian preparations.

Comparisons of Japanese Kanpo medicine and Chinese patent medicine for medication guidance / 中草药

With the promulgation of the “Chinese Medicine Act”, the application of classic prescriptions has attracted the attention of various companies. At present, related researches mainly focus on industry, patents, quality, clinic and other aspects, lacking overall research on popularization and application, and the research on pharmaceutical instructions has received increasing attention as a link in applied research. Reviewing the existing literature on Chinese patent medicine specification research in China, we found that most studies are qualitative analysis, lack of targets, data comparison, and specific recommendations, so the specific improvement of the Chinese patent medicine specification is limited. In this paper, the 128-item Japanese Kampo preparation instructions and related medication instructions were studied. The specific differences between the Japanese Kampo preparations and Chinese patent medicines in the selection of traditional Chinese medicines, the contents of the specific manuals, and the contents of the index and guidance manual were analyzed. Preliminary analysis and suggestions were made on the establishment of the classic prescription name list, the contents of the drug instruction manual, the improvement of the indexing method, and the establishment of overall instruction manual and the application database, in order to provide references for the application and development of traditional Chinese medicine.

Background and overall design of Chinese medicine resources assessment / 中国中药杂志

This paper comprehensively analyses the background and meaning of The Technological Guiding Principle for Assessment of Chinese Medicine Resources enacted by the former CFDA ( China Food and Drug Administration), moreover, it also points out that the Chinese medicine resources assessment with the purpose of guaranteeing the sustainable supplying capacity of Chinese medicine resources is the premise of new drug development; the Chinese medicine resources assessment which takes quality guarantee as the core is a significant action to promote the fixing of place of origin and quality-management antedisplacement for the traditional Chinese medicine industry; in this regard, the Chinese medicine resources assessment which aims at realizing the whole-process traceability is the key to building the high-quality modern traditional Chinese medicine brand. The Chinese medicine resources assessment which takes the classical prescription as the entry point is the embodiment of the protection of traditional Chinese medicine resources and international vision of regulation, which aims at clarifying the thinking for the relevant enterprises to carry out the Chinese medicine resources assessment. Base on the general thinking of ensuring that the "total amount of Chinese medicine resources is fixed and the supply is guaranteed", this paper clarifies two methods of Chinese medicine resources assessment: "family property assessment" of Chinese medicine resources based on "fixed total amount", "supply and demand balance assessment" of Chinese medicine resources based on "supply guarantee". In this regard, the basic strategy of "supply and demand balance assessment" of Chinese medicine resources based on "guaranteed supply" is put forward and it is believed that the resources assessment will lead to the significant adjustment of traditional Chinese medicinal materials production. It becomes the only way for the development of various Chinese medicine production enterprises to realize the comprehensive improvement of Chinese medicine quality, brand construction, the establishment of preferential price mechanism.

Research Approaches on Discovery R&D of Innovative Drug of Chinese Materia Medica under New Situations / 世界科学技术-中医药现代化

In recent years,with the rapid development of life sciences,changes on the understanding and requirements for innovative drugs of Chinese materia medica (CMM) from the drug approval authorities have been made.In this paper,the discovery,research and development (R & D) approaches for innovative drugs of CMM under new situations were summarized and introduced in details from five aspects as follows.The discovery of innovative drugs from active components of CMMs,active fractions of CMMs and their compound preparations,famous classic prescription,clinically effective prescriptions as well as the famous Chinese patent drugs.This paper puts forward some new ideas for the pharmaceutical researches of innovative drugs of CMM,including the production process,chemical components,quality study,quality standard and stability.This paper provided references for the discovery,R & D of CMM.

Four proved cases of classic prescription / 中华中医药杂志

‘Typhoid fever and Miscellaneous Diseases’is well known as‘the origin of prescription’. Prescriptions in this book are reliable, exquisite and rigorous, can cure hard diseases using very few kinds of TCM. The principle of‘corresponding prescription to symptom’makes proved cases simple but highly effective to complex illnesses. This thesis introduced four proved cases of remedying miscellaneous internal medicine diseases under the guidance of determination of treatment based on syndrome differentiation, principle of correspondence of prescription and syndrome, the author used classic prescriptions, such as Wuzhuyu Decoction, Guizhi Shaoyao Zhimu Decoction, Guizhi and Houpo Xizi Decoction and Dachaihu Decocion.