Systematic Analysis of the Mechanism of Polygoni Multiflori Caulis in Improving Depressive Disorder in Mice via Network Pharmacology Combined with Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Exactive Orbitrap Mass Spectrometer.

BACKGROUND AND OBJECTIVE: Depressive disorder (DD) is a common chronic and highly disabling disease. Polygoni Multiflori Caulis (PMC), a traditional Chinese medicine, has been listed in the 2020 edition of the Chinese Pharmacopoeia. Here, the antidepressant effects and mechanisms of PMC were explored for the first time. METHODS: We observed the safety of PMC at a 10-fold clinically equivalent dose. Depressed mice were induced by chronic unpredictable mild stress (CUMS) and were used to evaluate the antidepressant effects of PMC via the sucrose preference test and the tail suspension test. The composition of PMC was identified by ultra-high performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometer, and the active components, important targets, and potential mechanism of PMC in DD treatment were predicted via network pharmacology. Investigation included active compounds and DD-related targets screening, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, PMC-compound-target-pathway- DD network construction, and Molecular docking. RESULTS: In the safety evaluation of PMC, no toxic side effects or deaths occurred. There were no significant differences in liver function (ALT, AST, and TP; P > 0.05) and kidney function (BUN, CRE, and UA; P > 0.05) in each group of mice. Compared to the control group, the model group of mice showed significantly decreased sucrose preference and significantly increased immobility time (P < 0.01 or P < 0.05). Compared with the model group, the mice in the PMC low, medium, and high dose groups showed a significant decrease in immobility time and a significant increase in sucrose preference. In the PMC-Compound-Target-Pathway-DD network, 54 active compounds, 83 common targets, and 13 major signaling pathways were identified for the treatment of DD. Molecular docking verified that the active compounds could effectively bind with the hub targets. CONCLUSION: PMC is a relatively safe antidepressant herbal medicine with its potential mechanism involving multiple compounds, targets, and pathways.

Herbal Textual Research on Polygoni Multiflori Radix and Polygoni Multiflori Caulis in Famous Classical Formulas / 中国实验方剂学杂志

By reviewing ancient materia medica， medical books， prescription books and modern literature， this paper conducted a systematic research on name， origin， medicinal parts， producing area， quality， harvesting and processing methods， functions and toxicity of Polygoni Multiflori Radix（PMR） and Polygoni Multiflori Caulis（PMC） in famous classical formulas. It was found that the name of Heshouwu was first found in the Biography of Heshouwu and originated from its discoverer， and then still in use today. Since the Song dynasty， Heshouwu has been included in the materia medica with Fallopia multiflora as the mainstream origin. Since the Ming dynasty， in addition to F. multiflora， Cynanchum bungei， C. wilfordii， C. auriculatum have been used as the origin of Heshouwu. Heshouwu is widely distributed， the production areas recorded in ancient times are mainly Luchuan， Guangxi and Ganzhou， Jiangxi， and in modern times， Deqing， Guangdong and other places are respected as the geo-authentic habitats. Its origin processing is mostly dug out， washed， sliced and dried in the sun. Modern literature concludes that the quality of PMR is better in terms of weight， solid quality and powder， while PMC is better in terms of uniformity and purplish-red skin. In the Qing dynasty and before that， it was recorded in the materia medica that PMR was harvested mainly in late spring， mid-summer and early autumn， in modern times， it was harvested mainly in spring and autumn， while PMC was harvested in autumn. In Song dynasty， the processing method of PMR was mainly soaked with rice-washed water， the Ming dynasty for black bean steaming method， the Qing dynasty for steaming followed by black bean juice maceration， while in modern times， it is mostly sliced and steamed with black bean juice and yellow rice wine until the juice is absorbed. PMC is prepared by removing impurities， washing or moistening， and cutting into sections to dry. During the five dynasties， PMR was used to treat infertility as well as gastrointestinal diseases and blood in the stool caused by wind chill， and during the Song dynasty， it was mostly used raw products for the treatment of scrofula and carbuncles， and in the Yuan and Ming dynasties， raw and processed products were used， and Polygoni Multiflori Radix Praeparata was used to treat hemorrhoids， waist and knee soreness. PMC is mainly used for treating insomnia， fatigue and sweating， wind sores and scabies， etc. In the Song dynasty， the ancients considered that PMR was non-toxic， but its toxicity was gradually discovered after the Ming dynasty， and the toxicity mechanism has not been clearly analyzed yet. Based on the results of the textual research， it is recommended that F. multiflora be used as the base for development of famous classical formulas containing PMR， and from the safety perspective， it is recommended to use raw products with caution， oral administration must be used processed products. PMC is recommended to use raw products.

Beware of the Potential Risks for Polygoni Multiflori Caulis-Induced Liver Injury.

Background: Reynoutria multiflora (Thunb.) Moldenke (PM) is a widely-used medicinal plant in China, whose root and stem are included in the Chinese Pharmacopoeia as Polygoni Multiflori Radix (RPM), Polygoni Multiflori Radix Preparata (PMP), and Polygoni Multiflori Caulis (PMC). The hepatotoxicity of RPM and PMP is concerned by the public, while the risk of PMC is ignored. Purpose: Here, we investigate the potential risks for PMC-induced liver injury from clinical, chemical, and animal features. Study design: First, we analyzed the 12-month usage of RPM, PMP, and PMC in Longhua Hospital. Second, we determined the contents of gallic acid, cis-2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (cis-SG), trans-2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (trans-SG), emodin-8-O-ß-D-glucoside (EG), physcion-8-O-ß-D-glucoside (PG), emodin, and physcion in the water extracts from 15 batches of RPM, PMP, and PMC. Third, we probed the hepatotoxic effect of RPM, PMP, and PMC in mice and explored the mechanism of cis-SG and trans-SG causing the liver injury at the dosages based on our results from the first and second parts. Results: PMC had nearly five times the amount of usage in both outpatient prescriptions and inpatient orders than RPM and PMP. Overall, 68% dosage of PMC was 30 g. The contents of cis-SG, trans-SG, and emodin in PMC water extracts were significantly lower than those in RPM and PMP water extracts. PMC induced milder idiosyncratic liver injury for its lower content of cis-SG and trans-SG than its root counterparts. Conclusion: The potential risks for PMC-induced liver injury should be fully aware of.

Rapid analysis and identification of dianthrone glycosides in Polygoni Multiflori Caulis based on enrichment of macroporous absorbent resin and UPLC-Q-TOF-MS/MS.

INTRODUCTION: Polygoni Multiflori Caulis (PMC) has been used as a traditional Chinese medicine for a long time in China. However, hepatotoxic events of PMC have been reported in recent years, but the potential toxic compounds have remained unclear. Dianthrones as the secondary plant metabolites were revealed to potential hepatotoxicity in a previous study. However, no reports focused on dianthrones in PMC. OBJECTIVE: In the quest for exploring potential hepatotoxic compounds in PMC, the aim of this work was to undertake a comprehensive characterisation of dianthrones in PMC. METHODS: A simple and effective macroporous absorbent resin column chromatography method was established in this study to enrich the minor dianthrones from PMC extracts. Exploration and characterisation of dianthrones in PMC was conducted by an ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) method and information dependent acquisition (IDA) mode. The aglycones of dianthrone glycosides were further verified by acid hydrolysis method. RESULTS: Seventy-two dianthrone glycosides and their five aglycones were discovered and tentatively characterised in PMC for the first time, of which 29 dianthrones were identified as potential new compounds. Dianthrone glycosides could be classified into three types according to their aglycone structures, and their fragmentation pathway rules and diagnosed ions were also summarised comprehensively. CONCLUSION: This was the first comprehensive investigation on dianthrones in PMC. The result would help to fully understand the phytochemical constituents and toxic components in PMC, and highlight the need for further toxicological investigations of the dianthrones in PMC due to their potential hepatotoxicity correlation.

Grade Evaluation of Polygoni Multiflori Caulis Based on Quality Constant Method / 中国实验方剂学杂志

Objective::To establish a scientific and reasonable grade evaluation standard for Polygoni Multiflori Caulis. Method::The quality constant method was used to conduct a grade evaluation study on Polygoni Multiflori Caulis. A total of 16 batches of samples were collected from Chinese herbal slices enterprises and medicinal materials markets. By measuring its appearance traits (average quality and average thickness of the decoction pieces) and the intrinsic quality indicators (content of 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-D-glucoside), then its quality constant and percentage quality constant were calculated comprehensively, finally, the grades of Polygoni Multiflori Caulis were classified by quality constant method. Result::The quality constant of 16 batches of the decoction pieces was 0.054-0.417, and the percentage quality constant was 12.98-100.00.If these samples were divided into three grades, the quality constant shall be ≥0.334 for the first-grade decoction pieces, the quality constant shall be <0.334 and ≥0.209 for the second-grade decoction pieces, while for the third-grade decoction pieces, the quality constant shall be <0.209. Conclusion::The grade evaluation method based on quality constant can overcome the shortcomings of traditional evaluation method for decoction pieces, and can realize scientific, objective and simple classification of Polygoni Multiflori Caulis. This study enriches the research data of modern grade evaluation of Polygoni Multiflori Caulis, and provides reference for grade evaluation and market circulation of other decoction pieces.

Drying model, kinetics, and stability of four rattan Chinese medicinal materials / 中草药

Objective: To establish the common model of four kinds of rattan traditional Chinese medicinal materials (TCMM) (Paederiae Scandens Caulis, Lonicerae Japonicae Caulis, Polygoni Multiflori Caulis, and Ipomoea batatas Caulis) determinate the drying kinetic parameters, and study the stability of active ingredients in the drying process. Methods: The experimental data of four rattan TCMM were fitted to the nine thin layer models (Page, Wang and Singh, Two-term exponential, Newton, Logarithmic, Aghbashlo, Two-term, Midilli, Diffusion approach) at the temperature of 40, 50, 60, and 70 ℃. R2, χ2, and RMSE were used as the criterion of fit. Fick diffusion law was used to calculate the drying dynamical parameters. Based on the principle of chemical kinetics, the stability of active ingredients in the drying process was studied. Results: Aghbashlo model was the best one to describe drying process of four rattan TCMM. The effective moisture diffusion coefficients D and activation energy Ea of four rattan TCMM were between 1 × 10−10 and 1 × 10−9 m2/s and 40—50 kJ/mol respectively. The degradation reactions of ursolic acid, THSG, and polysaccharide conformed to the first-order kinetic equation. The content of chlorogenic acid increased with the drying temperature and drying time increased. Conclusion: The drying dynamical parameters values of TCMM with different parts have different ranges, their drying process should be described by a common model. The quality of TCMM was affected greatly by drying process.

Rapid Characterization of the major chemical constituents from Polygoni Multiflori Caulis by liquid chromatography tandem mass spectrometry and comparative analysis with Polygoni Multiflori Radix.

Polygoni Multiflori Caulis is a traditional Chinese medicine that has been used for a long time to treat sleep disorders. However, the multiple chemical composition analysis has not been reported. In this study, a simple, rapid and effective ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was established to characterize the components of Polygoni Multiflori Caulis. In addition, a chemical comparative analysis was performed with Polygoni Multiflori Radix, another traditional Chinese medicine from the same plant, through multivariate statistical analysis and semi-quantitative analysis to screen the difference in chemical ingredients between these two herbal medicines from same medicinal plant. A total of 33 peaks were detected within 25 min, and 28 of them were identified or tentatively characterized by comparing the retention time and mass spectrometry data. Based on the results, 12 characteristic components were screened out by multivariate statistical analysis, and their content change trends were compared by semi-quantitative analysis.