Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy： A study based on the PI3K/AKT/mTOR signaling pathway / 临床肝胆病杂志

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Quantitative Analyses of Sennosides A and B in Over-the-Counter Drugs Containing Rhubarb or Rhubarb and Senna Leaf / 医薬品情報学

Objective: Sennosides A and B, which are dianthrone glycosides contained in Rhubarb and Senna Leaf, exhibit laxative effect. Although a number of over-the-counter (OTC) drugs used as laxatives contain Rhubarb or Rhubarb and Senna Leaf, the total amounts of sennosides A and B are not mentioned in the package insert. To determine the total amounts of sennosides A and B in OTC drugs containing Rhubarb or Rhubarb and Senna Leaf, quantitative analyses of sennosides A and B were performed for 24 OTC drugs.Methods: Sennosides A and B were extracted from 24 OTC drugs and quantitatively analyzed by high-performance liquid chromatography. Statistical analyses were carried out by a one-way analysis of variance followed by Dunnett's test or Tukey's test.Results: The OTC drugs contained sennosides A and B in the range of 1.5-10 mg in the minimum daily dosage and in the range of 2.7-17 mg in the maximum daily dosage. In 11 of the OTC drugs (Products Nos. 1-5, 11, 12, and 15-18), the maximum daily dosage contained almost equal or higher amounts of sennosides A and B compared to that in a tablet of the prescription medicine Pursennid® 12 mg. Furthermore, the amounts of sennosides A and B in the maximum daily dosage were significantly higher in products Nos. 1 and 11 and lower in products Nos. 8-10, 14, and 20-24 compared to those of a tablet of Pursennid® 12 mg.Conclusion: Although some OTC drugs have the same Rhubarb content, the total amounts of sennosides A and B can vary. Thus,there is no correlation between the Rhubarb content and total amounts of sennosides A and B. This is because of the inconsistent quality of Rhubarb and/or the differences in the manufacturing methods of the OTC drugs containing Rhubarb. Because the total amounts of sennosides A and B cannot be estimated based on the Rhubarb content, a constipated patient should start taking an OTC drug containing Rhubarb at the minimum daily dosage. It is also recommended that the total amounts of sennosides A and B are mentioned in the package insert of OTC drugs containing Rhubarb or Rhubarb and Senna Leaf.

Chinese Medicine Plaster as A New Treatment for Surgical Site Infection in Patients with Cesarean Delivery: A Randomized, Double-Blind, Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial.@*METHODS@#This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments.@*RESULTS@#During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P<0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P<0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49 ± 2.68 days vs. 8.96 ± 2.35 days, P<0.01). The rate of postoperative C-reactive protein elevation (≽100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P<0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group.@*CONCLUSIONS@#CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626).

Therapeutic effect of retention enema with compound rhubarb decoction on a rat model of minimal hepatic encephalopathy based on bile acid metabolomics / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of rhubarb decoction （RD） retention enema on a rat model of minimal hepatic encephalopathy （MHE） and its mechanism of action based on bile acid （BA） metabolomics. MethodsA total of 55 male Sprague－Dawley rats were randomly divided into blank group （NC group with 10 rats）， hepatic encephalopathy group （HE group with 15 rats）， MHE group with 15 rats， and MHE+rhubarb decoction treatment group （MHEY group with 15 rats）. Intraperitoneal injection of carbon tetrachloride （CCl4） and thioacetamide （TAA） was performed to establish a rat model of MHE or HE， and the rats were sacrificed after 2 weeks of administration. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， total bilirubin （TBil）， and total bile acid （TBA） and the concentration of blood ammonia were measured； the colonic contents were collected to measure pH value； liver and brain tissue samples were collected， and HE staining was used to observe the histopathological changes of the liver； the bile was collected， and liquid chromatography－mass spectrometry was used to perform BA－targeted metabolomics analysis. Continuous data were expressed as mean±standard deviation； a one－way analysis of variance was used for comparison between multiple groups， and the least significant difference t－test was used for further comparison between two groups. ResultsCompared with the NC group， the HE group and the MHE group had a significant increase in searching platform latency （after modelling and after administration） and a significant reduction in the number of platform crossings （all P<0.05）； compared with the MHE group， the MHEY group had a significant reduction in searching platform latency （after administration） and a significant increase in the number of platform crossings， and the HE group had a significant increase in searching platform latency and a significant reduction in the number of platform crossings （all P<0.05）. Compared with the NC group， the HE group and the MHE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）； compared with the MHE group， the MHEY group had significant reductions in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）， and the HE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）. The MHE group had significantly lower TBA， primary BA， and secondary BA than the NC group （all P<0.05）； compared with the MHE group， the HE group had significantly lower TBA and primary BA （all P<0.05）， and the MHEY group had significantly higher TBA and primary BA （all P<0.05）. Compared with the NC group， the MHE group had significant reductions in GCDCA， GUDCA， GHDCA， TCDCA， TUDCA， GLCA， and TLCA （all P<0.05） and significant increases in γ－MCA， THCA， 7－KDCA， AlloLCA， and α－MCA （all P<0.05）， and compared with the MHE group， the MHEY group had significant increases in THDCA， TMCA， TCDCA， TUDCA， and TLCA （all P<0.05）. ConclusionRD retention enema can improve liver injury and cognitive function in a rat model of MHE induced by CCl4 and TAA by regulating the enterohepatic circulation of BA， possibly by increasing the synthesis of taurine－binding BA.

Simultaneous determination of 10 rhubarb anthraquinones and rhaponticin in Compound gentian and sodium bicarbonate tablets by UPLC / 中国药房

OBJECTIVE To establish a method for the simultaneous determination of 10 rhubarb anthraquinones in Compound gentian sodium bicarbonate tablets and the content of rhaponticin，which are the characteristic components of artifacts，and to use the method to evaluate the quality of compound preparation containing Rheum officinale. METHODS The ultra-performance liquid chromatography （UPLC） method was adopted to determine the contents of 10 rhubarb anthraquinones （aloe-emodin-8-O-glucoside， rheinic acid-8-O-β-D-glucoside，emodin-8-O-glucoside，chrysophanol-8-O-β-D-glucoside，emodin monomethyl ether-8-O-β-D-glucoside， aloe-emodin，rheinic acid，emodin，chrysophanol，emodin monomethyl ether） and rhaponticin in 40 batches of Compound gentian sodium bicarbonate tablets from 8 manufacturers. The determination was performed on the Agilent Eclipse Plus C18 column with a mobile phase consisted of acetonitrile-0.1% phosphoric acid solution （gradient elution） at a flow rate of 0.3 mL/min； the column temperature was set at 30 ℃ ，and the injection volume was 5 μL. Combining principal component analysis and cluster analysis to synthesize the results of content determination，the quality of samples from different manufacturers was evaluated. RESULTS All of above 11 components showed favorable linear relationships with peak areas in their respective mass concentration ranges （r≥0.999 3），with RSDs of precision，repeatability and stability 296261547@qq.com less than 3% （n＝6）； average sample recoveries ranged 96.82%-98.92% （RSD≤1.74%，n＝6）； their contents were 0971-8247794。E-mail：304436784@qq.com 0.011 7-0.252 0，0-0.323 3，0.131 3-1.236 6，0.081 1-1.056 2，0.015 2-0.189 8，0.001 8-0.152 3，0-0.255 2，0.001 9-0.223 4，0.054 3-0.303 0，0.022 7-0.172 2，0-2.835 9 mg/g，respectively. The cumulative variance contribution of the first three principal components was 95.533%； the 40 batches of samples can be clustered into 4 categories：samples from enterprises a and d were in a category of their own，samples from enterprises f，b，g and e were in a category，and samples from enterprises c and h were in a category. There were large differences in the content of rhubarb anthraquinone in the samples from 8 manufacturers，and rhaponticin was only detected in the sample from one enterprise. CONCLUSIONS Established UPLC method is stable and reliable； it can be used for the content determination of 10 rhubarb anthraquinones and rhaponticin in Compound gentian sodium bicarbonate tablets.

The renal protective effect of Mongolian medicine rhubarb-3 decoction on rats with chronic renal failure based on TGF-(i/Smad signaling pathway / 中国药理学通报

Aim To study the protective effect of Mon¬golian medicine rhubarb-3 decoction on renal function of CRF model rats and explore its mechanism.Meth¬ods SD rats were randomly divided into normal group and model group.The model group was established by adenine gavage.After successful modeling, they were randomly divided into model, positive, rhubarb-3 de¬coction low, medium and high dose groups, which were administered at intervals for 12 weeks.The bio¬chemical detection of CSF, BUN and Scr was per¬formed.The pathological changes of renal tissues were observed by HE and Masson staining.The expression of PCNA and a-SMA in renal tissues was detected by immunohistochemistry.The mRNA expressions of CK18, Vimentin, TGF-pi and FN in kidney tissues were detected by RT-PCR.The expressions of a-SMA, E-cadherin, PCNA, Smad2, Smad3 protein in kidney tissue were detected by Western blot.TGF-pi induced abnormal proliferation of I IMC and interstitial transfor¬ mation of HK-2, and at the same time, it was treated with serum containing rhubarb-3 decoction.The prolif¬eration of HMC was detected by CCK-8.Interstitial transformation of HK-2 was detected by RT-PCR.Re- suits Compared with the model group, BUN and Scr in CRF rats decreased, and the expression of fibrosis- related proteins and genes in renal tissue decreased af¬ter rhubarb-3 decoction treatment.The serum contai¬ning rhubarb-3 decoction significantly inhibited HMC proliferation and HK-2 interstitial transformation.Con¬clusions Rhubarb-3 Decoction can improve renal function in CRF model rats, and its mechanism may be related to inhibiting HMC proliferation and HK-2 inter¬stitial transformation and probably regulating TGF-f}/ Smad signaling pathway.

Molecular mechanism of rhubarb in treatment of acute pancreatitis based on network pharmacology and molecular docking / 中国药理学通报

Aim To analyze the molecular mechanism of rhubarb in the treatment of aeute pancreatitis ( AP) by network pharmacology and molecular docking.Methods TCMSP,TCMID and Swiss target predic¬tion databases were used to screen the active compo¬nents and targets of rhubarb,and genecards and OMIM databases were used to screen the targets of AP.Then the active ingredient drug target network of rhubarb and theactive ingredient disease target network of rhubarb for AP were constructed by using Cytoscape software.PPI network was constructed in string database, and go and KEGG enrichment analysis was performed in metascape database and R language.Finally,molecular docking was used to verify the possibility of binding the core active components to the core target.Results A total of 192 active components and 1 882 AP targets were obtained.The first three active components of rhubarb in the treatment of AP were beta sitosterol, aloe emodin and eupatin.The core target of rhubarb in the treatment of AP was hsp90aal.Go enrichment analysis focused on reaction to toxic substances, while KEGG enrichment analysis was significantly enriched in p53 signaling pathway closely related to AP.Molecular docking showed good binding and stable conformation.Conclusions Rhubarb can affect the expression of AP related genes and proteins through p53 signaling pathway, thereby inhibiting cell apoptosis and allevia¬ting the inflammatory injury of AP.

Establishment of fingerprint and content determination of 3 differential components in Rheum palmatum before and after steaming with wine derived from different producing areas / 中国药房

OBJECTIVE To establish H PLC fingerprint of Rheum palmatum before and after steaming with wine ，and to determine the contents of 3 differential components. METHODS HPLC method was used to establish the fingerprints of 15 batches of R. palmatum （before wine-steaming ）and prepared rhubarb （after wine-steaming ）and the similarity evaluation was conducted. The chemical pattern recognition analysis was carried out by principal component analysis ，cluster analysis ，partial least squares- discriminant analysis and orthogonal partial least squares-discriminant analysis. The contents of gallic acid ，resveratrol-4′-O- glucoside and resveratrol- 4′-O-（6″-galloyl）-glucoside in 30 batches of samples were determined. RESULTS In the fingerprint study，48 common peaks were demarcated for R. palmatum and 47 for prepared rhubarb as well as 17 common peaks were identified by reference substance. Cluster analysis and principal component analysis showed that R. palmatum derived from Qinghai before and after steaming with wine could be distinguished from those from Sichuan and Gansu. The results of content determination showed that the contents of 3 differential components in R. palmatum derived from Qinghai before and after steaming with wine were higher than those from other two production areas ；the contents of gallic acid in prepared rhubarb derived from those production areas were higher than R. palmatum ；the contents of resveratrol- 4′-O-glucoside and resveratrol- 4′-O- （6″-galloyl）-glucoside in R. palmatum derived from those production areas were higher than prepared rhubarb. CONCLUSIONS Fingerprint and content determination method established in this study can quickly ，scientifically and accurately evaluate the quality of R. palmatum from different producing areas before and after wine steaming ，which provide a basis for the processing specification and quality control of R. palmatum .

Organ specific differences in alteration of aquaporin expression in rats treated with sennoside A, senna anthraquinones and rhubarb anthraquinones / 中国药理学与毒理学杂志

OBJECTIVE Senna and rhubarb are classified as stimulative laxatives, and known to have similar effec?tive constituents, the anthraquinones. Being protected by theβ-glucoside bond, the anthraquinones can reach the intes?tines where they are degraded into complex metabolites by enzymes secreted from the intestinal microbiome. It is these complex metabolites that produce the laxative effects. Then the similarities and differences of action between the anthra?quinones require further elucidation. METHODS Here, we studied metabolites of senna anthraquinones (SAQ), rhubarb anthraquinones (RAQ) and their chemical marker, sennoside A (SA), in a rat diarrhea model. In the in vitro biotransfor?mation experiments, SAQ, RAQ and SA were incubated with rat fecal flora solution and the metabolites produced were analyzed using HPLC. In the in vivo studies, the same compounds were investigated for purgation induction, with mea?surement of histopathology and multiple aquaporins (Aqps) gene expression in six organs. RESULTS SAQ and RAQ had similar principal constituents but could be degraded into different metabolites. A similar profile of Aqps down-regula?tion for all compounds was seen in the colon, suggesting a similar mechanism of action for purgation. However, in the kidneys and livers of the diarrhea-rats, down-regulation of Aqps was found in the RAQ-rats whereas up-regulation of Aqps was seen in the SAQ-rats. Furthermore, the RAQ-rats showed lower aquaporin 2 (Aqp2) protein expression in the kidneys, whilst the SA-rats and SAQ-rats had higher Aqp2 protein expression in the kidneys. This may have implications for side effects of SAQ or RAQ in patients with chronic kidney or liver diseases. CONCLUSION SAQ and RAQ showed similar laxative actions with a similar mechanism, they could display different actions in rat kidneys and livers. We suggest that the clinical usage of senna or rhubarb products should be clarified for patients having chronic kidney or liver diseases.

Regulative effect of Rhubarb dispensing granule on autophagy and gastrointestinal motility of Cajal interstitial cells in rats with chronic transit constipation / 国际中医中药杂志

Objective:To study the regulative effect of Rhubarb dispensing granule on autophagy and gastrointestinal motility of Cajal interstitial cells in rats with chronic transit constipation (STC).Methods:A total of 75 rats were randomly divided into control group, model group, low, medium and high dose groups with 15 rats in each group. Except for the control group, the STC rat models were established by intragastric administration of compound diphenoxylate suspension. Rats in low, medium and high dose groups were given Rhubarb dispensing granule of 1, 2 and 4 g/kg by gavage respectively, while rats in control group and model group were given normal saline with the same volume by gavage, once a day for 14 consecutive days. Fecal moisture content and intestinal propulsion rate were measured. The serum levels of substance P (SP), vasoactive intestinal peptide (VIP), NO and NOS were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The c-kit level in colon tissue was detected by immunohistochemistry. The mRNA and protein levels of c-kit and Beclin1 in colon tissue were detected by PCR and Western blot.Results:Compared with the model group, the fecal moisture content, the carbon pushing distance and the intestinal pushing rate of the low, medium and high dose groups were significantly increased ( P<0.05), the serum SP level was increased ( P<0.05), the serum VIP, NO and NOS levels of the low, medium and high dose groups were decreased ( P<0.05), and the average expression score of c-kit in colon tissue of the low, medium and high dose groups was significantly increased ( P<0.05). The levels of c-kit mRNA (2.33 ± 0.35, 3.04 ± 0.17, 3.83 ± 0.23 vs. 0.61 ± 0.07) and protein (0.42 ± 0.06, 0.60 ± 0.07, 0.79 ± 0.08 vs. 0.22 ± 0.04)in colon tissue of rats in low, medium and high dose groups were increased ( P<0.05), and Beclin1 mRNA (4.17 ± 0.37, 3.35 ± 0.44, 1.05 ± 0.28 vs. 6.04 ± 0.31) and protein (0.76 ± 0.11, 0.57 ± 0.08, 0.43 ± 0.05 vs. 0.91 ± 0.06) were decreased ( P<0.05). Conclusion:Rhubarb dispensing granule could significantly increase the fecal moisture, intestinal motility rate, serum SP level and colonic tissue c-kit level, decrease serum VIP, NO, NOS level and colonic tissue Beclin1 level in rats with chronic transit constipation, and then inhibit autophagy of Cajal interstitial cells and regulate gastrointestinal motility in rats with chronic transit constipation.

The neuroprotective effect of rhubarb on MCAO model rats / 中国药理学通报

Aim To study the neuroprotective effect of rhubarb extract on MCAO model rats and explore its mechanism of action. Methods Forty-five SPF male Sprague-Dawley rats were randomly divided into sham group, MCAO group, and MCAO + rhubarb group. MCAO model was prepared by silk plug method, and rhubarb extract was administered at a concentration of 200 mg · kg

Study on antipyretic effect of rhubarb on rats and its antipyretic ingredients / 中国中药杂志

A combination of LC-MS technology and activity evaluation was used to identify the antipyretic ingredients in rhubarb. The rat model of fever was established with dried yeast and then was administered ethanol extract and different polar fractions of rhubarb. Next, the anal temperature of these rats was measured and recorded at 0.5, 1, 2, 3, 4 and 5 h after administration, and the inhibition rate of each part on the rise of body temperature was calculated. The inhibition rate is higher and the antipyretic effect is better. The chemical composition of the effective fraction was analyzed with UPLC-ESI-Orbitrap-MS/MS technology. Compared with the model group, the increase of body temperature of ethanol extract group all reduced at each measurement time especially after 3 h, and the inhibition rate were 38.7%(P<0.05), 78.2%(P<0.01) and 72.4%(P<0.01) at 3 h, 4 h, and 5 h after administration, respectively. Both n-butanol and water fraction showed some antipyretic activity in the early stage, with the inhibition rate of 28.1%(P<0.01) and 24.9%(P<0.05) at 1 h after administration, respectively, while other fractions were not active. Thirty-three and twelve compounds were identified from n-butanol and water fraction by LC-MS/MS analysis, respectively, including ten tannins, fifteen anthraquinone glycosides, four anthrone glycosides, one phenolic glycoside, one naphthaline derivative, one anthraquinone and one sucrose. These results revealed that rhubarb had antipyretic activity on rats, and tannin and anthraquinone glycosides were the main active ingredients inside.

Design and evaluation of rhubarb total free anthraquinones oral colon-specific drug delivery granules to improve the purgative effect

Rhubarb is commonly used as a cathartic in Asian countries. However, researchers have devotedextensive concerns to the quality control and safety of rhubarb and traditional Chinese preparations composed of rhubarb due to the instable purgative effect and potential nephrotoxicity of anthraquinones. In this study, we aimed to prepare rhubarb total free anthraquinones (RTFA) oral colon-specific drug delivery granules (RTFA-OCDD-GN) to delivery anthraquinones to colon to produce purgative effect. RTFA-OCDD-GN were prepared using chitosan and Eudragit S100 through a double-layer coating process and the formulation was optimized. Continuous release studies were performed in a simulated gastric fluid (pH 1.2), followed by a small-intestinal fluid (pH 6.8) and a colonic fluid (pH 7.4, containing rat cecal contents). The purgative effect test was performed in rats. The dissolution profile of RTFA-OCDD-GN showed that the accumulative dissolution rate of RTFA was about 83.0% in the simulated colonic fluid containing rat cecal contents and only about 9.0% in the simulated gastrointestinal fluids. And the RTFA-OCDD-GN could produce the comparative purgative activity as rhubarb, suggesting it could deliver the free AQs to the colon. The RTFA-OCDD-GN was a useful media to enhance the purgative activity of free anthraquinones after administered orally.

Analysis on Bidirectional Regulation of Purging and Astringency About Raw and Steamed Products of Rhei Radix et Rhizoma and Their Active Components / 中国实验方剂学杂志

Objective:To elucidate the characteristics of bidirectional regulation of raw and steamed products of Rhei Radix et Rhizoma and their active components, in order to provide scientific basis for clinical rational use of this decoction pieces. Method:Mice were randomly divided into the blank group(distilled water, 10 mL·kg-1), raw rhubarb group(1.62 g·kg-1), steamed rhubarb group(0.972 g·kg-1), raw rhubarb anthraquinone group(0.22 g·kg-1), steamed rhubarb anthraquinone group(0.19 g·kg-1), raw rhubarb tannin group(0.17 g·kg-1) and steamed rhubarb tannin group(0.027 g·kg-1). Each group was divided into 3 batches of 10 mice. Mice in each group were given the corresponding dose by continuous gavage for 7 days, the diarrhea index(EI) of mice in each group was recorded every day. The serum levels of motilin(MTL), vasoactive intestinal peptide(VIP) and epinephrine(EPI) were measured on day 1,3,7. Result:Compared with the blank group, EI of the rhubarb group increased significantly on the 3rd day(Pth day of administration(Prd day(Pth day(Pst day of administration, on the 3rd day of administration, the MTL level in the steamed rhubarb anthraquinone group increased significantly(PPPth day of administration, the MTL levels of the raw and steamed rhubarb tannin groups increased to the level in the blank group, the VIP level of the raw rhubarb anthraquinone group increased significantly(PPConclusion:The combined anthraquinone and hydrolyzable tannin in rhubarb can promote gastrointestinal motility and diarrhea. The effect of astringent intestines is caused by the monomer tannin produced by digestion and decomposition of condensed tannin, which may be one of the mechanisms of bidirectional regulation of rhubarb decoction pieces.

Effects of rhubarb on the expression of glucocorticoids receptor and regulation of cellular immunity in burn-induced septic rats / 中华医学杂志(英文版)

Background:@#It is important to modulate the expression of glucocorticoids receptor (GR) in tress and maintain the immunity homeostasis in sepsis process. Rhubarb have been shown to have potential effects on anti-inflammatory and immune modulation. The present study was designed to investigate the effects of rhubarb on the expression of GR and cellular immunity in burn-induced septic rats.@*Methods:@#Sixty-six healthy male Sprague Dawley (SD) rats were randomized into sepsis group (n = 24), rhubarb group (n = 24), and control group (n = 18); each group were further randomized into 12, 24, and 72 h subgroups according to different time points. During onset of the sepsis model, the rats in the rhubarb group were infused with 50 mg/kg rhubarb powder dissolved into 1 mL saline through gastric tube, while sepsis and control groups were treated with saline. The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were analyzed by radiation ligands binding assay. The percentages of CD4+, CD8+,CD4+CD25+T cells, CD19+B cells as well as natural killer (NK) cells in the lymphocytes in peripheral blood were detected by flow cytometer. For assessing the differences among groups, one-way analysis of variance (ANOVA) with Scheffe multi-comparison techniques were employed. Comparisons between time-based measurements within each group were performed with ANOVA repeated measurement.@*Results:@#The binding activity of GR in liver cytosol and binding capacity of GR in peripheral blood leucocyte were significantly decreased in a time-dependent manner in sepsis group (t = 23.045, P < 0.01; t = 24.395, P < 0.05, respectively), which were increased in a time-dependent manner after rhubarb administration (t = 19.965, P < 0.05; t = 17.140, P < 0.05, respectively). Twelve hours after sepsis, the percentages of CD4+ T cells, CD4+/CD25+ T cell ratio, and CD19+ B cells in the peripheral blood were significantly increased in the sepsis group (t = -3.395, P < 0.01; t = 2.568, P < 0.05; t = 2.993, P < 0.05, vs. control mice, respectively). However, the percentage of NK cells in the peripheral blood were significantly decreased in the sepsis group (t = -2.022, P < 0.05, vs. control mice). Twelve hours after sepsis, the percentage of CD8+ T cells were significantly decreased in the peripheral blood in the sepsis group (t = -2.191, P < 0.05, vs. control mice) and were significantly increased in the rhubarb group (t = 2.953, P < 0.05, vs. sepsis mice). Seventy-two hours after sepsis, the ratio of CD4+/CD25+ T cell in peripheral blood were significantly increased in the sepsis group (t = 2.508, P < 0.05, vs. control mice) while were significantly decreased in the rhubarb group (t = 3.378, P < 0.05, vs. control mice). Furthermore, the percentages of CD19+ B cell in peripheral blood were significantly decreased at 72 h in the rhubarb group (t = 2.041, P < 0.05 vs. sepsis group).@*Conclusions:@#Rhubarb might play potential anti-inflammatory and immunomodulatory roles in the sepsis processes.

Protective effect of Rhubarb on newborn rats with bronchopulmonary dysplasia / 中华实用儿科临床杂志

Objective To investigate the effect of Rhubarb on bronchopulmonary dysplasia(BPD) and its potential mechanism.Methods Neonatal Sprague-Dawley rats (postnatal day 4) were exposed to 600 mL/L 02 to induce BPD.The experimental rats were randomly divided into 4 groups with 16 in each group:air + saline group,air +Rhubarb (600 mg/kg)group,and hyperoxia + saline group,and hyperoxia + Rhubarb group.The rats were sacrificed and lung tissues were obtained on day 14 and 21 after birth.Hematoxylin-easin staining was used to detect the pathomorphology of the lungs.Apoptosis of the lung tissue was detected by means of TdT-mediated dUTP nick-end labeling (TUNEL).The expression of Fas was detected by adopting Western blot.The activity of Caspase-8 and Caspase-3was detected by using spectrophotometer.Results The lung structure of rats was markedly abnormal (decreased,enlarged and simplified alveoli) after being exposed to hyperoxia at any time point.The apoptosis indexes (39.91 ± 1.91vs.10.11 ± 1.64,48.80 ± 4.51 vs.12.90 ± 3.18),the expression levels of Fas (0.47 ± 0.02 vs.0.21 ± 0.01,0.55 ±0.02 vs.0.22 ±0.01) and the activities of Caspase-8 (52.59 ± 1.23 vs.40.74 ± 1.08,60.20 ± 3.48 vs.40.39 ±2.47) and Caspsase 3 (57.17 ± 1.88 vs.42.00 ± 1.19,64.57 ± 2.79 vs.41.54 ± 1.27) were all increased in the hyperoxia + saline group compared with those in the air + saline group on day 14 and 21,and the differences were statistically significant(all P ＜ 0.001).However,compared with the hyperoxia + saline group,Rhubarb administration dramatically decreased pulmonary apoptosis index (26.49 ± 2.65 vs.22.97 ± 3.66),Fas protein level (0.27 ± 0.03 vs.0.31 ± 0.01) and the activity of Caspase-8 (32.70 ± 2.69 vs.30.66 ± 4.48) and Caspase-3 (44.94 ± 1.60 vs.44.59 ± 1.66),and the differences were statistically significant (all P ＜ 0.001).Meanwhile,lung damage after hyperoxia was significantly attenuated in the hyperoxia + Rhubarb group.Conclusion Rhubarb can reduce the hyperoxic lung injury of BPD by reducing the apoptosis of newborn rat lung tissue cells,and the mechanism may involve the apoptosis pathway of Fas.

Optimization of Yi medicine processing technology for honeyed wine rhubarb by Box-behnken design response surface methodology / 中草药

Objective: To optimize the processing technology of honeyed wine rhubarb by Box-behnken design response surface methodology. Methods: Taking the content measurement combined with the sensory score as the index, the factors of particle size, steaming time, storage temperature, and moisture content were investigated by single factor tests. On the basis of the results of single factor experiments, the free and total anthraquinones contents and the extract content in honeyed wine rhubarb were determined by HPLC method and hot-dip method, respectively. Three factors (steaming time, storage temperature, and the moisture content) were investigated further by response surface, the processing technology of honeyed wine rhubarb was optimized by response surface methodology. Results: The optimal parameters of processing technology were as follows: particle size was the powder through 100 mesh sieves, steaming time was 3.5 h, storage temperature was 33 ℃, and moisture content was 43%. Conclusion: The optimized processing technology is simple and feasible, which can provide a reference for the processing of honeyed wine rhubarb.

Quality evaluation of rhubarb pieces by hplc fingerprint, q-tof/ms qualitative and multi-component quantitative analysis / 中草药

Objective To establish a more comprehensive quality evaluation method for rhubarb pieces. Methods Fingerprints of 35 batches of rhubarb pieces were determined by HPLC, the control fingerprint was established, the common peaks were calibrated and the similarity was evaluated. Components of common peaks were identified by Q-TOF/MS and the content of 13 anthraquinones confirmed by reference substance was determined. Results There were 45 common peaks in the fingerprint of rhubarb pieces, including 17 anthraquinones (among them, eight bound anthraquinones of aloe-emodin-8-O-glucoside, rhein-8-O-glucoside, emodin-1-O-glucoside, chrysophanol-1-O-glucoside, chrysophanol-8-O-glucoside, aloe-emodin-3-hydroxymethyl-O-glucoside, emodin-8-O- glucoside, physcion-8-O-glucoside and five free anthraquinones of aloe-emodin, rhein, emodin, chrysophanol, physcion were confirmed by reference substance), two anthrones (sennoside B and sennoside A, confirmed by reference substances), 17 tannins (among them, gallic acid, catechin, epigallocatechin gallate, epicatechin and epicatechin gallate were confirmed by reference substance), two stilbenes [resveratrol 4′-O-glucoside and resveratrol 4′-O-β-D-(6″-O-galloyl)-glucoside, confirmed by reference substances], four butyrophenone [among them, 4-(4′-hydroxyphenyl)-2-butanone 4′-O-β-D-(2″-O-galloyl-6″-O-p-hydroxy-cinnamyl) glucoside, confirmed by reference substances], two chromones and one naphthalenes. The content of 13 anthraquinones in 35 batches of rhubarb pieces was quite different. Conclusion The established method can be used to evaluate the quality of rhubarb pieces.

Study on efficacy-enhancing and toxicity-reducing of different rhubarb processed products combined with atorvastatin / 中草药

Objective: To explore the effect of different processed products of rhubarb combined with atorvastatin (ATS) on the efficacy-enhancing and toxicity-reducing. Methods: L02 cells were used to investigate the hepatoprotective effects of raw rhubarb, wine-fried rhubarb and wine-steamed rhubarb in clinical application combined with ATS, and the extracts of the processed products with the best liver protection were screened out. The effective lipid-lowering dose range of the extract of the processed product was determined by HepG2 cell experiments; Finally, based on the model of hyperlipidemia in SD rats, the lipid-lowering and hepatoprotective effects of the optimal extract and ATS were generally evaluated by measuring the blood lipid and transaminase levels and related oxidative stress parameters, detecting the histopathological section of the liver. Results: The alcohol extract of wine-fried rhubarb in the three processed artillery products significantly improved the survival rate of L02 cells, and had the best protection effect on L02 cells induced by ATS. At the same time, the wine-fried rhubarb ethanol extract also effectively reduced the content of TC and TG in HepG2 hepatic steatosis cells. The liver-protection ratio and lipid-lowering ratio (mass ratio) of ATS to wine-fried rhubarb ethanol extract were 1:6.7-1:9.0 and 1:35.8-1:71.6. The wine-fried rhubarb ethanol extract and ATS reduced the blood lipid level and lipid content in the liver of hyperlipidemia rats; The serum levels of ALT and AST were significantly decreased, the SOD activity in the liver was significantly enhanced, and the MDA content was significantly reduced; And high-dose wine-fried rhubarb ethanol extract and ATS combination group significantly inhibited inflammatory cell infiltration and bile duct hyperplasia. Conclusion: The combination of wine-fried rhubarb ethanol extract and ATS can significantly improve the liver function damage caused by ATS, enhance the effect of lipid-lowering therapy on hyperlipidemic rats, and play a role in reducing toxicity and increasing efficiency.

Compound Compatibility Law of Rhubarb and Aconite Decoction Based on CYP450 Enzymes / 中国药学杂志

OBJECTIVE: To study the law of compatibility and detoxification of rhubarb and aconite decoction based on the CYP450 enzyme-mediated metabolic interaction. METHODS: The activities of CYP1A2 and CYP3A4 enzymes were determined by incubating the "Cocktail" probe drugs in vitro. The total content of CYP450 enzyme in liver microsomes was determined by carbon monoxide differential method. And the expression of CYP1A2 and CYP3A4 mRNA was detected by RT-PCR method. RESULTS: Rhubarb group, aconite root combined with rhubarb group and rhubarb combined with asarum group showed significant induction effects on CYP1A2 enzyme activity. CYP1A2 enzyme activity was significantly inhibited in the aconite root combined with asarum group. CYP3A4 enzyme activity was significantly inhibited in the asarum group and the aconite root combined with asarum group. Rhubarb group, rhubarb combined with asarum group and rhubarb and aconite decoction had significant induction effects on CYP3A4 enzyme activity. Rhubarb group significantly induced the total content of CYP450 enzyme, asarum group and aconitum root combined with asarum group inhibited the total content of CYP450 enzyme, rhubarb and aconite decoction had slight induction effects on the total content of CYP450, but there was no significant difference. Rhubarb group, rhubarb combined with asarum group and rhubarb and aconite decoction group could up-regulate the mRNA expression of CYP1A2. In addition, rhubarb and aconite decoction and rhubarb group could up-regulate the mRNA expression of CYP3A4. And asarum group and aconite combined with asarum group could down-regulate the mRNA expression of CYP3A4. CONCLUSION: The drug combination weakened the strong induction of CYP1A2 and CYP3A4 enzymes by rhubarb alone, reflecting the holism concept of compound traditional Chinese medicine. The effects of rhubarb and aconite decoction on CYP3A4 enzyme activity are likely to be regulated by the mRNA levels of CYP3A4 enzyme. Whether there is correlation between the cold-heat compatibility based on the pharmacological theory and the induction or inhibition of CYP450 enzyme needs further study.