Based on the interaction between supramolecules of traditional Chinese medicine and enterobacteria to explore the material basis of combination of Rhei Radix et Rhizoma - Coptidis Rhizoma / 药学学报

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Mechanism of Rhei Radix et Rhizoma-Coptidis Rhizoma Improving Liver Insulin Resistance in db/db Mice by Regulating AMPK/ULK1/Beclin1 Pathway / 中国实验方剂学杂志

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1）/key molecule of autophagy， benzyl chloride 1 （Beclin1） pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group， metformin group （0.26 g·kg-1）， and low-， middle-， and high-dose groups （2.25， 4.5， 9 g·kg-1） of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set， with 12 mice in each group. After eight weeks of continuous intragastric administration， the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed， and fasting blood glucose （FBG） was measured using a Roche blood glucose device. Fasting serum insulin （FINS） was measured using an enzyme-linked immunosorbent assay， and the insulin resistance index （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK， Beclin1， autophagy associated protein 5 （Atg5）， and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B （LC3B） and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR （Real-time PCR） was used to measure mRNA expression levels of AMPK， Beclin1， Atg5， ULK1， and p62. ResultCompared with the blank group， the model group exhibited a significant increase in body mass （P<0.01）. Additionally， the levels of FBG， FINS， and HOMA-IR significantly changed （P<0.01）. The structure of liver cells was disordered. The protein expression levels of AMPK， Beclin1， and Atg5 in liver tissue were significantly decreased （P<0.01）， while the expression level of p62 protein was significantly increased （P<0.01）. The expression levels of mRNA and proteins were consistent. Compared with the model group， the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased （P<0.05）. FBG， FINS， and HOMA-IR were significantly decreased （P<0.05，P<0.01）. After treatment， the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK， Beclin1， Atg5， LC3B， and ULK1 were increased （P<0.05，P<0.01）， while the protein expression of p62 was decreased （P<0.01）. The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance， regulate the AMPK autophagy signaling pathway， alleviate insulin resistance in db/db mice， and effectively prevent the occurrence and development of type 2 diabetes.

Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics / 中草药·英文版

OBJECTIVE@#Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (1H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored.@*METHODS@#Models of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by 1H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.@*RESULTS@#Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS.@*CONCLUSION@#For the first time, we studied the pharmacokinetics and metabolomics differences of RhRR-EuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma / 中国中药杂志

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.

Progress of Rhei Radix et Rhizoma and Its Combination in Treatment of Cerebral Hemorrhage： A Review / 中国实验方剂学杂志

Cerebral hemorrhage accounts for about 10%-15% of all strokes， and its pathogenesis is complex. Currently， the main clinical treatment is mainly medical symptomatic treatment， including the use of antihypertensive drugs， hypoglycemic drugs， and hemostatic drugs， and surgical treatment is required in some cases， but there is still a lack of effective treatment. In recent years， traditional Chinese medicine and proprietary Chinese medicine have been widely accepted for their stable efficacy， high safety， and low cost. Rhei Radix et Rhizoma is one of the most commonly used herbal medicines for the treatment of cerebral hemorrhage. This paper summarizes the relevant literature on the treatment of cerebral hemorrhage with Rhei Radix et Rhizoma and finds that its active ingredients are mainly anthraquinones， such as emodin， Rhei Radix et Rhizoma acid， and Rhei Radix et Rhizoma phenol. The herbal formulas are Da Chengqitang， Shengdi Dahuangtang， Liangxue Tongyufang， and Naoxueshu oral liquid. The effects involve protecting the blood-brain barrier， promoting hematoma absorption， reducing inflammation levels， decreasing lactic acid accumulation at the bleeding site， and increasing the expression of brain-derived neurotrophic factors. The pathways involved include aquaporin 4 （AQP4）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， Toll-like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB）， nuclear factor E2-related factor 2 （Nrf2）， and Wnt3a/β-linked protein pathway. This paper summarizes the progress of clinical studies and animal experiments on the treatment of cerebral hemorrhage with active ingredients of Rhei Radix et Rhizoma and herbal compounds containing Rhei Radix et Rhizoma， so as to provide a reference for the treatment protocol of cerebral hemorrhage.

Effect of Shaoyaotang on Inflammatory Cytokines and Intestinal Flora in Rats with Dampness-heat Diarrhea / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Shaoyaotang on diarrhea， inflammation， and intestinal flora in rats with dampness-heat diarrhea and explore the mechanism of therapeutic principle "treating incontinent syndrome with dredging method" of Shaoyaotang. MethodThe dampness-heat diarrhea model was induced by high temperature， high humidity， high sugar and fat diet， and pathogenic factors. The rats were divided into normal group， model group （normal saline）， Shaoyaotang group （5.62 g·kg-1）， Rhei Radix et Rhizoma （RRER）-free Shaoyaotang group （5.15 g·kg-1）， and RRER group （0.01 g·kg-1）. The rats were treated correspondingly for five days， twice a day in the morning and evening. The diarrhea index was used to evaluate the antidiarrheal effect of each group three hours after the administration in the evening. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-2， and IL-6 in the serum were detected by enzyme-linked immunosorbent assay （ELISA） three hours after the last administration. The structure of intestinal flora in feces was characterized by 16sDNA. ResultCompared with the model group， the Shaoyaotang group， the RRER-free Shaoyaotang group， and the RRER group showed reduced diarrhea index （P<0.01）， with the onset rates ranking as the Shaoyaotang group>the RRER-free Shaoyaotang group>the RRER group. Those three groups with drug intervention all showed decreased levels of inflammatory factors （P<0.01）， especially the Shaoyaotang group， and no significant difference was observed between the RRER group and the RRER-free Shaoyaotang group. The abundance of pathogenic bacteria and conditioned pathogens （e.g. Escherichia-Shigella， Prevotella， Enterorhabdus， and Bacteroides） was reduced and the proliferation of probiotics （such as Ruminococcus， Turicibacter， and Lachnospiraceae） was increased in the groups with drug intervention （P<0.01）. For the structure of intestinal flora， the RRER group and the Shaoyaotang group were close to the normal group， and the RRER-free Shaoyaotang group was different from the other three groups （P<0.01）. ConclusionShaoyaotang can improve the outcome of rats with dampness-heat diarrhea through anti-inflammation and regulation of intestinal flora disorders. RRER in the prescription plays a key role in reducing the abundance of harmful bacteria and promoting the proliferation of probiotics， which is the key of Shaoyaotang in promoting the re-balance of intestinal flora. It also confirms the scientificity of treating dampness-heat diarrhea with RRER following the therapeutic principle "treating incontinent syndrome with dredging method".

Flavor Characterization of Rhei Radix et Rhizoma Processed with Nine-time Repeating Steaming and Sun-drying Based on Intelligent Sensory Technology / 中国实验方剂学杂志

ObjectiveTo analyze the flavor substances and change rules of Rhei Radix et Rhizoma during the process of nine-time repeating steaming and sun-drying. MethodThe flavor response values of Rhei Radix et Rhizoma samples were obtained by using PEN3 electronic nose system. The data were processed and analyzed by principal component analysis （PCA）， linear discriminant analysis （LDA） and Loadings analysis. ResultRhei Radix et Rhizoma processed with nine-time repeating steaming and sun-drying could be effectively distinguished into two categories as the sixth sample was the turning point. The samples steamed and dried for one to five times could be grouped into one category， the other four samples were obviously distinguished from them. The main flavor components reached the maximum response in the sample processed with six-time repeating steaming and sun-drying， and its response value of inorganic sulfur compounds was about 2.7 times that of the sample processed with one-time repeating steaming and sun-drying. In addition， compared with the raw products， the flavors of Rhei Radix et Rhizoma processed with nine-time repeating steaming and sun-drying and wine stewing changed significantly， and the response value of inorganic sulfur compounds in sample processed with nine-time repeating steaming and sun-drying was about 2.2 times that of raw products. From the perspective of flavor analysis， the response values of inorganic sulfur compounds and nitrogen-oxygen compounds in sample processed with nine-time repeating steaming and sun-drying were higher than those of wine-stewed products， and the two were not completely equivalent. ConclusionElectronic nose technology preliminarily clarifies the dynamic change rules of the flavor of Rhei Radix et Rhizoma during the process of nine-time repeating steaming and sun-drying from the flavor characteristics， and clarifies the difference between products processed with nine-time repeating steaming and sun-drying and wine-stewed products from the odor characteristics， which lays a foundation for revealing the processing principle of Rhei Radix et Rhizoma processed with nine-time repeating steaming and sun-drying.

Analysis of chloroplast genomes and development of specific DNA barcodes for identifying the original species of Rhei Radix et Rhizoma / 药学学报

Rhei Radix et Rhizoma is one of the most used medicinal materials in China. Its original species are Rheum palmatum, Rh. tanguticum, and Rh. officinale. Rhei Radix et Rhizoma derived from different original species are significantly different in their active ingredients and pharmacological effects. To develop an accurate, rapid, and specific identification method, we obtained the chloroplast genomes of the three original species by Illumina Novaseq sequencing. We designed specific DNA barcodes from the hypervariable regions, which can accurately identify the three original species. The experimental results showed that the total length of the chloroplast genomes of Rh. tanguticum, Rh. officinale and Rh. palmatum were 161 039 bp, 161 093 bp, and 161 136 bp, respectively. All the three genomes were represented as typical quadripartite structures. A total of 131 genes, including 86 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes were identified from each chloroplast genome. Five pairs of primers based on the hypervariable regions were designed to efficiently amplify 42 samples. Results confirmed that five hypervariable regions, rps16-trnQ, psaA-ycf3, psbE-petL, ndhF-rpl32, and trnT-trnL, can be used as specific DNA barcodes for the identification of Rh. tanguticum, Rh. officinale, and Rh. palmatum. These results provided genetic information for further species identification of Rhei Radix et Rhizoma, and improve the safety of this clinical medication as well as standardize the market for Rhei Radix et Rhizoma.

Effect of auricular combined with rhubarb powder acupoint application on improving the quality of bowel preparation in colonoscopy patients / 国际中医中药杂志

Objective:To explore the effect of auricular point pressing pill combined with rhubarb acupoint application on intestinal preparation and prevention of adverse events in colonoscopy.Methods:A total of 220 patients who met the inclusion criteria from May 2019 to February 2020 were randomly divided into 4 groups, 55 in each group. The control group was only given compound polyethylene glycol electrolyte powder. The auricular plaster group was combined with auricular point pressing pill on the basis of the control group. The acupoint sticking group was combined with rhubarb acupoint application on the basis of the control group. The combination group was combined with auricular point pressing pill and rhubarb acupoint application on the basis of the control group. The quality of bowel preparation was evaluated by Boston Bowel Preparation Scale(BBPS), and the adverse events such as perianal discomfort, defecation discomfort, abdominal pain and abdominal distension were observed.Results:After treatment, there was significant difference in BBPS score among the four groups ( F=3.038, P=0.030). The BBPS score in the acupoint sticking group (7.45 ± 1.20 vs. 6.78 ± 1.32) and combination group (7.26 ± 1.11 vs. 6.78 ± 1.32) were significantly higher than those in the control group( P<0.05). After treatment, there were significant differences in abdominal pain and abdominal distension scores among the four groups ( F=2.947, 5.879, P=0.034, 0.001). The scores of perianal discomfort (0.07 ± 0.38 vs. 0.44 ± 1.07), defecation discomfort (0.40 ± 0.81 vs. 0.87 ± 1.32) and abdominal pain (0.93 ± 1.32 vs. 1.69 ± 1.61) in the combination group were significantly lower than those in the control group ( P<0.05), and the abdominal distension score (1.05 ± 1.00 vs. 1.64 ± 0.95) in the acupoint sticking was significantly lower than that of the control group ( P<0.05). Conclusion:Auricular combined with rhubarb powder acupoint application can improve the quality of bowel preparation and reduce intestinal adverse reactions. It can be used with polyethylene glycol electrolyte powder for the intestinal preparation process.

Analysis on Quality Transfer Law of Rhei Radix et Rhizoma Steamed with Rice-wine During Processing Based on Correlation Between External Appearance Color and Internal Component / 中国实验方剂学杂志

Objective:The correlation between the appearance color of cooked rhubarb samples and the components characterized by high performance liquid chromatography （HPLC） fingerprint was studied to reveal the quality transfer law in the steaming process of processed products with rice-wine. Method:The visual analyzer was used to analyze the change of the appearance color of cooked rhubarb sample powder at different processing time， the common components and their relative peak areas of processed products with rice-wine were identified by HPLC fingerprint， as well as multivariate statistics and Pearson correlation analysis were used to cluster， discriminate and analyze the appearance color and the component variables in HPLC fingerprint. Result:During the processing of cooked rhubarb， the <italic>a</italic>^* （red-green value） of sample powder had no obvious change， but the <italic>L</italic>^* （lightness value）， <italic>b</italic>^*<italic> </italic>（yellow-blue value） and <italic>E</italic>^*<italic>ab </italic>（total chromaticity value） showed a decreasing trend， and the appearance color changed from bright to dark， from yellow to brown. A total of 46 chromatographic peaks in the fingerprint were identified at 254 nm and 280 nm， and 18 of them were identified by comparison with reference standards. The change trend of <italic>L</italic>^*，<italic> b</italic>^*<italic> </italic>and <italic>E</italic>^*<italic>ab </italic>were positively correlated with the contents of tannins （catechin， epicatechin and ethyl gallate）， stilbene glycoside （<italic>trans</italic>-3，5，4′-trihydroxystyryl-4′-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucoside）， phenylbutanone glycoside of 4′-hydroxyphenyl-2-butanone-4′-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-［2ʺ-<italic>O</italic>-gallic-6ʺ-<italic>O</italic>-（4ʺ-hydroxy）-cinnamoyl）-glucoside， conjugated anthraquinones （aloe emodin-8-<italic>O</italic>-glucoside， rhein-8-<italic>O</italic>-glucoside， emodin-8-<italic>O</italic>-glucoside） and <italic>ω</italic>-hydroxyemodin （<italic>P</italic><0.05， <italic>P</italic><0.01）， and negatively correlated with the contents of free anthraquinones （emodin， aloe emodin and physcion）. Compared with 254 nm， the similarities of chromatographic peaks at 280 nm was more obvious， and the number of detected common peaks was more， which could reflect more subtle differences in chemical composition. Conclusion:Tannins， stilbene glycosides and phenylbutanone glycosides are strongly correlated with <italic>L</italic>^*， while anthraquinones are strongly correlated with <italic>b</italic>^*， the decrease of <italic>E</italic>^*<italic>ab</italic> is mainly related to the increase of free anthraquinone content and the decrease of catechins， <italic>ω</italic>-hydroxyemodin， stilbene glycosides， conjugated anthraquinone and phenylbutanone glycosides. The change of appearance color index of process samples can reflect the change trend of the contents of medicinal components in cooked rhubarb to some extent.

Resource Value Discovery and Utilization of Wastes in Industrialization of Rhei Radix et Rhizoma / 中国实验方剂学杂志

The recycling of traditional Chinese medicine （TCM） wastes is an important research topic to be solved urgently in the industrialization of TCM resources. Rhei Radix et Rhizoma is a bulk Chinese herb mainly derived from Rheum palmatum，R. tanguticum，and R. officinale. At present，these three medicinal plants have been cultivated on a large scale and widely used in the fields of medicine，health care，food，cosmetics，and veterinary medicine，with an annual demand of more than 5 500 tons（1 ton=1 000 kg）. However，a large number of wastes such as non-medicinal parts and residues produced in the production and deep processing are discarded because there is no effective way of utilization，resulting in serious waste of resources and environmental pollution. The non-medicinal parts contain not only the chemical components and pharmacological effects similar to those of roots and rhizomes but also a variety of amino acids，mineral elements，and conventional nutrients. They have a long history of use，and the content of some resource components is higher than that in roots and rhizomes. In particular，their stems and leaves exhibit great potential to be consumed as food and medicine due to high safety. Besides，the content of anthraquinones in Rhei Radix et Rhizoma residue is high and it possesses good antibacterial activity. It can be seen that the waste from the industrialization of Rhei Radix et Rhizoma has high utilization value. Hence，based on the relevant literature and investigation on the application of producing areas in China and abroad，the paper summarized the utilization status of their medicinal and non-medicinal parts，the waste production in the industrialization，as well as the active substances and utilization ways and put forward the multi-level and multi-path utilization strategy of Rhei Radix et Rhizoma wastes，in order to provide reference for the rational development and application of Rhei Radix et Rhizoma resources and promote the effective utilization and green development of the corresponding wastes.

Research progress in original species identification in industry chain of Rhei Radix et Rhizoma / 中国中药杂志

Rhei Radix et Rhizoma is a kind of commonly used Chinese medicinal materials. Due to the overharvesting, the wild resource is endangering. Large market demand caused severely adulterant of commercial Rhei Radix et Rhizoma medicinal materials and decoction pieces. This manuscript reviewed the advances of the original species authentication in the industrial chain of Rhei Radix et Rhizoma during the latest decade, including characteristics and microscopic features, phytochemical analysis on anthraquinones, and molecular authentication based on DNA barcoding. Accordingly, an original species authentication route for the industrial chain of Rhei Radix et Rhizoma was summarized:(1)the identification of seeds and seedlings by DNA barcoding;(2) the selection of high variable sites based on the chloroplast genome;(3)biomonitoring of the Rhei Radix et Rhizoma medicinal materials and decoction pieces by two-dimensional DNA barcode;(4)traceability of Chinese patent medicines by third-generation sequencing. In conclusion, the combination of molecular identification and traditional identification methods provides a new idea for the identification of the original species of Rhei Radix et Rhizoma in the industrial chain and a essential guidance for the research of drug safety and efficacy of Rhei Radix et Rhizoma.

Botanical origin identification of Rhei Radix et Rhizoma based on color digitalization / 中国中药杂志

The color characteristic information of Rhei Radix et Rhizoma powder was obtained by spectrophotometer, the feasibility of rapid identification of Rhei Radix et Rhizoma origin based on chromaticity value was studied by statistical analysis. The results of rank correlation analysis showed that a~*(P<0.01), b~*(P<0.01) had significantly correlation with the origin of medicinal herbs, which could be used as two important parameters to distinguish the origin of Rhei Radix et Rhizoma, the larger the a~* value, the more red the powder color,and the greater the b~* value, the more yellow the powder color. Meanwhile, through Fisher discriminant analysis, the linear discriminant functions of different genus Rhei Radix et Rhizoma were established, which was Rheum tanguticum=40.666a~*+0.019b~*-213.303, Rh. palmatum=34.121a~*+0.061b~*-151.770, Rh. officinale=28.071a~*+0.113b~*-104.604 3, the coincidence rate of cross-validation was over 95%, among them, the discriminant rate of Rh. tanguticum and Rh. officinale reached 100%;In addition, using the percentile method to analyze the 90% reference value range of three different origin of Rhei Radix et Rhizoma, as a result, Rh. tanguticum a~*(10.236 5-10.604 7), b~*(32.294 8-34.841 7); Rh. palmatum a~*(8.602 7-8.770 0), b~*(27.534 8-28.968 6), and Rh. officinale a~*(6.825 7-7.464 3),b~*(21.001 6-27.716 4). According to this study, rank correlation analysis and Fisher discriminant analysis are feasible to distinguish the base of Rhei Radix et Rhizoma in a certain range, and provide some theoretical basis for the identification of Rhei Radix et Rhizoma. It also provides a new method and idea for the identification of other multi-base Chinese medicine.

Research progress of effect of Rhei Radix et Rhizoma and its anthraquinone in treatment of autoimmune diseases / 中国中药杂志

Rhei Radix et Rhizoma was first recorded in Shennong Ben Cao Jing, with a wide range of pharmacological activities. Autoimmune disease is a kind of disease that damages the tissue structure and function of immune cells and their components due to the impairment of immune tolerance function, including atherosclerosis, multiple sclerosis, gout, rheumatoid arthritis, autoimmune thyroiditis, ulcerative colitis, type 1 diabetes and IgA nephropathy. In recent years, clinical and experimental studies show that Rhei Radix et Rhizoma has potential therapeutic effects on autoimmune diseases. Under the guidance of the theory of traditional Chinese medicine, this paper reviews therapeutic and intervening effects of Rhei Radix et Rhizoma and its main active ingredient anthraquinone on autoimmune diseases. It also puts forward new study directions in view of the existing problems in studies of rhubarb and its anthraquinone, with the aim to provide reference for clinical treatment and scientific studies of effect of Rhei Radix et Rhizomaon autoimmune diseases.

Research progress on processing history evolution as well as effect on chemical compositions and traditional pharmacological effects of Rhei Radix et Rhizoma / 中国中药杂志

Rhei Radix et Rhizoma(RRR) is a commonly used traditional Chinese medicine, with extensive pharmacological effects and clinical applications. This paper summarized processing history evolution of RRR and its effect on chemical compositions and pharmacological effects, and provided feasible insights for further studies on the chemical compositions and pharmacological effects of RRR before and after processing. Relevant information demonstrated that RRR has a long history of processing and various methods. At pre-sent, Chinese Pharmacopoeia mainly records four processing methods: cleaning(raw RRR), wine processing(RRR stir-fried with wine), steaming processing(RRR wine steaming), fried charcoal(RRR charring). RRR has a good effect in clearing heat effect, hemostatic effect and blood promoting effect, and its main chemical components are anthraquinone/anthrones, stilbene, phenylbutanone, chromogens, flavonoids and tannin compounds. This paper reviewed the history evolution of RRR and its effect on chemical composition and pharmacological changes, and put forward further study ideas, with the aim to provide a basic reference for processing mechanism, effective material basis and clinical application of RRR.

Study on potential hepatotoxicity of rhein in Rhei Radix et Rhizoma based on liver metabolism / 中国中药杂志

The bilirubin metabolism mediated by the phase Ⅱ metabolizing enzyme UGT1A1 in the liver was evaluated to study the potential hepatotoxicity risk based on investigation on the inhibitory effect of rhein and its metabolites on the UGT1A1 enzyme in Rhei Radix et Rhizoma. Firstly, in vitro liver microsomes incubation was used to initiate the phase Ⅱ metabolic reaction to investigate the inhibitory effect of rheinon UGT1A1 enzyme. Secondly, the phase Ⅰ and phase Ⅱ metabolic reactions were initiated to investigate the hepatotoxicity risk of rhein metabolites. It was found that the rhein and its phase Ⅱ metabolites had no significant inhibitory effect on UGT1A1 enzyme, but its phase Ⅰ metabolites significantly reduced UGT1A1 enzyme activity. Based on the metabolites analysis, it is speculated that the rhein phase Ⅰ metabolite rheinhydroxylate and its tautomers have certain hepatotoxicity risks, while the toxicity risk induced by the prototype and phase Ⅱ metabolites of rheinglucoside, rheinglucuronic acid and rhein sulfate is small.

Study on safe storage moisture content of Rhei Radix et Rhizoma using moisture absorbing math model / 中草药

Objective: The moisture absorption of Rhei Radix et Rhizoma (RRR) with different initial moisture content was studied under the conditions of relative humidity of 20%-85% and temperature of 5, 15, 25 and 35 ℃, respectively, so as to provide reference for the control of safe storage moisture and reasonable storage of RRR. Methods: RRR was stored at temperature of 5, 15, 25 and 35 ℃ and humidity of 45%, 60% and 75%, respectively. The samples were taken at different time points to determine its safe water activity with powder color and mildew as indicators. The isotherm adsorption data of RRR at 5, 15, 25 and 35 ℃ and water activity of 0.2-0.8 were obtained by static weighing method and six isotherm adsorption models, GAB, Oswin, Smith, Halsey, Henderso and Peleg, were used for fitting and evaluation. Results: The absolute safe water activity and relative safe water activity of RRR were 0.5 and 0.6, respectively. The adsorption isotherms of RRR at 5, 15, 25 and 35 ℃ were "S" type, which belonged to type II isotherm. Oswin model was the best fitting model and the model expression was: Meq=A[Aw/(1-Aw)B. According to the model, the absolute safe water content of RRR with different initial moisture content at 5 ℃ was 9.00%, 9.59%, 8.00%, 6.71% and relative safe water content was 10.17%, 10.89%, 9.20% and 8.07%, respectively; The absolute safe water content of RRR with different initial moisture content at 15 ℃ was 8.24%, 8.83%, 7.24%, 5.86% and relative safe water content was 9.57%, 10.17%, 8.59% and 7.20%, respectively; The absolute safe water content of that at 25 ℃ was 7.17%, 7.75%, 5.73%, 4.70% and the relative safe water content was 8.72%, 9.26%, 7.26% and 6.25%, respectively; The absolute safe water content of that at 35 ℃ was 8.00%, 8.45%, 6.53%, 5.21% and the relative safe water content was 9.74%, 9.85%, 8.40%, 7.27%, respectively. Conclusion: Oswin model can be used to predict the equilibrium moisture content of RRR in storage, which can provide reference for the control of safe moisture and scientific maintenance of RRR.

Active Components and Mechanism of Rhei Radix et Rhizoma on Renal Fibrosis Based on Network Pharmacology / 中国实验方剂学杂志

Objective::To explore the active components, potential targets and signaling pathways of Rhei Radix et Rhizoma in the treatment of renal fibrosis based on the network pharmacology method, and then to verify the target genes in vitro. Method::Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) were retrieved to obtain the main active ingredients of Rhei Radix et Rhizoma. The potential anti-renal fibrosis targets of Rhei Radix et Rhizoma were predicted by similarity ensemble approach (SEA), Swiss Institute of Bioinformatics (SIB) and GeneCards Database. Target protein-protein interaction (PPI) network was constructed by using String Version 10.5 database. David 6.8 software was used for gene ontology (GO) enrichment analysis and the Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of the key targets. Cytoscape Version 3.6.0 software was used for visualized analysis of PPI network, active ingredient-key target network and the ingredient-target-signal pathway network. In combination with Malachards database, the signal pathways with high correlation with renal fibrosis were screened. Then, cell experiments were used for verification: HK-2 cells were selected to establish fibrosis model by transforming growth factor-β1 (TGF-β1) stimulation. The cells were treated with rhein for 48 hours. Western blot assay was used to detect the protein expression level of hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), and platelet-derived growth factor receptor-α (PDGFR-α). Protein expression levels of E-cadherin and α smooth muscle actin (α-SMA) were detected by immunofluorescence. Apoptosis was detected with flow cytometry. Result::Totally 17 active ingredients of Rhei Radix et Rhizoma and 424 targets of anti-renal fibrosis effect were screened out, including five key targets: protein kinase B(Akt)1, mitogen activated protein kinases 3(MAPK3), epidermal growth factor receptor(EGFR), interleukin(IL)-6 and VEGFA in turn. The biological process of GO enrichment mainly involved signal transduction, cell proliferation and apoptotic process. The results of KEGG pathway enrichment showed that phosphatidylinositol 3-kinase(PI3K)/Akt, HIF-1, VEGF, and forkhead transcription factor (FoxO) pathways were related to the anti-renal fibrosis mechanism of Rhei Radix et Rhizoma. Results of the in vitro experiment proved that rhein could inhibit the expression of E-cadherin, α-SMA, HIF-1α, VEGF and PDGFR-α. In addition, rhein inhibited apoptosis induced by TGF-β1 in HK-2 cells. Part of the prediction results of network pharmacology were verified. Conclusion::This study reflects the multi-component, multi-target and multi-pathway mechanism characteristics of Rhei Radix et Rhizoma. The mechanisms of its anti-renal fibrosis effects may be related to inhibiting HIF-1 α / VEGF /PDGFR-α signaling pathway, apoptosis and epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells.

Brain Material Basis and Relevant Mechanism of Acute Stroke Treated with Rhei Radix et Rhizoma Based on Homotherapy for Heteropathy Using Proteomics / 中国实验方剂学杂志

Objective:To explore the material basis and mechanism of acute stroke treated with Rhei Radix et Rhizoma based on Homotherapy for Heteropathy using the analysis of proteomics and bioinformatics. Method:A total of 60 male Sprague-Dawley（SD）rats were randomly divided into ischemic stroke（IS） sham-operation group (Sham1), IS model group (IS), IS+ Rhei Radix et Rhizoma treatment group (DH1)，ICH sham-operation group (Sham2), intracerebral hemorrhage（ICH） model group (ICH), and ICH + Rhei Radix et Rhizoma treatment group (DH2), with 10 rats in each group. After cerebral perfusion, the brain tissues were quantified by proteomic analysis, and differentially expressed proteins (DEPs) were identified. Specimens of IS, Sham1, and DH1 groups were collected at 24 hours, while those of ICH, Sham2, and DH2 groups were collected at 48 hours. The common DEPs were analyzed by bioinformatics, and the relevant DEPs were verified by Western blot. Result:Rhei Radix et Rhizoma regulated 21 common DEPs associated with acute stroke (including 12 up-regulated and 9 down-regulated). According to Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis, amyotrophic lateral sclerosis (ALS) pathway was enriched, and three proteins [Neurofilament light polypeptide (Nefl), Neurofilament medium polypeptide (Nefm), Neurofilament heavy polypeptide (Nefh)] involved in this pathway. Energy metabolism, ion homeostasis, regulation of synaptophysin, cell cycle and neurogenesis were the common mechanisms of "Homotherapy for Heteropathy". After treatment with Rhei Radix et Rhizoma, the expression levels of GTP binding protein REM2 (Rem2), tyrosine 3-monooxygena (Th), Nefl and neuromodulin (Gap43) were significantly higher than those of the corresponding model group (P<0.05). The expression of Nefl was down-regulated, while the expressions of Rem2，Th and Gap43 were up-regulated, which was consistent with the results of proteomics. Conclusion:Rhei Radix et Rhizoma-homotherapy-differential protein expression profile is established is study. Energy metabolism, ion homeostasis, regulation of synaptophysin, cell cycle and neurogenesis are the common mechanisms.

Analysis of Water Adsorption and Thermodynamic Properties of Three Rhei Radix et Rhizoma Decoction Pieces / 中国实验方剂学杂志

Objective:To investigate the moisture adsorption and thermodynamic characteristics of raw products， wine-processed products and fried charcoal products of Rhei Radix et Rhizoma， in order to guide their drying and storage. Method:Static isotherm weighing method was used to determine the adsorption isotherm curves of three Rhei Radix et Rhizoma decoction pieces at 25， 35， 45 ℃， and the test data were fitted with 7 commonly used water adsorption models to determine the best model for studying the adsorption thermodynamic parameters of these decoction pieces. Result:The best adsorption models of these three decoction pieces were all GAB model. At 25， 35， 45 ℃， the absolute safe moisture content of fried charcoal products was 7.43%， 6.79% and 6.20%， of wine-processed products was 8.68%， 8.17% and 7.03%， of raw products was 9.88%， 9.36% and 7.77%， respectively. At 25， 35， 45 ℃， the relative safe moisture content of fried charcoal products was 9.46%， 8.63% and 8.21%， of wine-processed products was 11.49%， 11.03% and 9.74%， of raw products was 13.49%， 12.66% and 11.14%， respectively. The net equivalent heat of adsorption （Qst） and differential entropy （Sd） of these three kinds of decoction pieces all decreased with the increase of equilibrium moisture content， Qst and Sd were in accordance with the entropy-enthalpy complementary theory. The constant velocity temperatures of raw products， wine-processed products and fried charcoal products of Rhei Radix et Rhizoma were 386.66， 391.15， 394.34 K （unit conversion of 1 K=-272.15 ℃）， their Gibbs free energies were 0.372 2， 0.406 0， 0.372 2 kJ·mol-1， respectively. Their adsorption processes were an unspontaneous process driven by enthalpy. Conclusion:The orders of equilibrium moisture content， monomolecular layer moisture content， Qst and Sd of three Rhei Radix et Rhizoma decoction pieces are all raw products>wine-processed products>fried charcoal products. The moisture absorption capacity of the decoction pieces is ranked as raw products>wine-processed products>fried charcoal products. The frying and roasting process significantly affects the hygroscopicity and thermodynamic properties of the three decoction pieces， the reason for this difference may be that the high temperature of the stir-frying results in the decrease of the hygroscopic groups and the increase of the hydrophobic materials in raw products， and the change in the texture of the decoction pieces. The research on the water adsorption characteristics of three Rhei Radix et Rhizoma decoction pieces can provide reference for selecting their storage conditions and drying process.