Review of Rhubarbs: Chemistry and Pharmacology

Rhubarb is a perennial herb belonging to the genus Rheum L. (Polygonaceae). Rhei Radix et Rhizoma (rhubarb roots and rhizomes) is one of the most popular Chinese materia medica and has been widely used for strong laxative function. About 200 compounds with six different types of skeletons (anthraquinone, anthrone, stilbene, flavonoids, acylglucoside, and pyrone) have so far been isolated from eighteen species of the genus Rheum L. These constituents showed extensive pharmacological activities including cathartic, diuretic, anticancer, hepatoprotective, anti-inflammatory, and analgesic effects, as well as toxicological effects. Chemical fingerprint, LC-MS, and other analytical techniques have been used for the quality control of rhubarb. This comprehensive review summarizes the researches into the isolation, pharmacological activities, and phytochemical analysis reported since investigations began in the late 1940s. In addition, pharmacokinetic studies and clinical application of rhubarb are also discussed in present paper.

Integrated gut microbiota,plasma metabolomics and network pharmacology to reveal the anti-ischemic stroke effect of cooked rhubarb

Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum Maxim.ex Balf.)with millet wine.It is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe constipation.This study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in rats.We used integrated analysis of gut microbiota,metabolomics,and network pharmacology.Methods:The compounds in CR were identified using LC-MS/MS.The impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE staining.Changes in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also determined.Gut microbiota composition was analyzed through 16S rRNA gene sequencing.Serum metabolites were examined using untargeted metabolomics and Spearman correlation analysis.The pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut microbiota.Results:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction area.CR also ameliorates brain and intestinal barrier damage caused by stroke.It also decreased inflammation and oxidative stress in IS rats.Furthermore,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier repair.Notably,CR primarily influences the primary bile acid biosynthesis pathway.The pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential targets.CR relies on gut microbiota for its anti-inflammatory effects to improve IS.Conclusion:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid metabolism.It emerges as a potential therapeutic agent for IS.

Technical Points of Green Prevention and Control Technology of Major Diseases and Pests in Lixian Rhubarb(Rheum palmatum L.)

Based on different types of diseases,pests and weeds in the whole growth period of rhubarb(sowing period-harvesting period),the corresponding green prevention and control technology is proposed,aiming to further reduce the application amount of pesticides and fertilizers in the production of medicinal sources of Lixian rhubarb during the"14 th Five-Year Plan"period.The results will provide a theoretical basis for increasing the promotion and application of agricultural prevention and control(including disease-resistant varieties,ecological regulation),physical prevention and control,biological prevention and control measures,thus ensuring effective protection of the ecological environment,green,healthy and sustainable development of traditional Chinese medicine agriculture in Longnan,and source quality of authentic medicinal materials.

Effect of Rhubarb Decoction on the Isolated Intestinal Movement of Ophicephalus argus

[Objective] The aim of this study was to investigate effects of rhubarb decoction with different concentrations on the isolated intestinal movement performance of Ophicephalus argus,and to discuss its pharmacological mechanism.[Method] With RM6240C biological signal collection and processing system,tension values of the isolated intestine before and after the treatment by rhubarb decoction with different concentrations were recorded by the isolated organ method.[Result] Rhubarb decoction with concentration of 0.062 and 0.125 g/ml showed obvious enhancement on the isolated intestinal contraction of Ophicephalus argus,while rhubarb decoction with concentration of 0.250 and 0.500 g/ml showed inhibition on the isolated intestinal contraction of Ophicephalus argus.There was an extremely significant difference in rhubarb decoction with concentration of lower than 0.500 g/ml and more than 0.500 g/ml.With the increase of rhubarb concentration,the intestinal movement of Ophicephalus argus enhanced,but the contraction frequency did not change obviously.[Conclusion] Rhubarb decoction has remarkable effects on the contraction of smooth muscle in the isolated intestines of Ophicephalus argus.

SOD-like Activities of Fifteen Constituents from Rhubarb

It is important to search for the ingredients with SOD—like activity present in Chinese traditional drugs.Four classes of constituents including fifteen compounds isolated from Chinese rhubarb were studied for their SOD-like activity by determining the percentage of scavenging effect of the superoxide radical anion (O2),(S％),The results showed that the SOD-like activities of four tanninoid compounds were stronger among which(—)-epi- catechin has the strongest SOD-like activity at lower concentrations:the activity of five stil- bene compounds is weaker:while chrysophanol-8-glucoside and desoxyrhaponticin have no SOD-like activity and,on the contrary.may promote the production of O_2^-

径向基函数神经网络和近红外光谱法鉴别大黄的应用

测定了41个大黄(Rhubarb)样品的近红外光谱数据,结合径向基函数神经网络模型,对正品与非正品大黄加以鉴别。为了提高神经网络的训练速度,在利用径向基函数神经网络建立模型之前,通过小波变换压缩了光谱变量,分析了建立模型的参数。结果表明,该法对大黄样品的识别正确率达97.56%,可用于大黄中药生产的质量控制。

X-ray Comparative Analysis of Rhubarb in Different Production Areas of Qinghai

[Objective] The aim of this study was to provide a basis for distinguishing quality of rhubarb in different production areas. [Method ] X-ray diffraction patterns of rhubarbs in different production areas of Qinghai were obtained by X-ray diffraction analysis, and then its similarity analysis was also investigated. [ Result] The content of chemical components in rhubarbs from different production areas had differences, but its diffraction patterns and diffraction peaks had certain fingerprint characteristics. [ Conclusion] X-ray diffraction method is a fast and effective method for identifying rhubarb and other Chinese herbal medicines in different production areas.

中药治疗榄香烯所致静脉炎58例

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Effects of rhubarb on isolated gastric muscle strips of guinea pigs

AIM:To study the effects of rhubarb (dried root of Rheum officinale Baill.) on contractile activity of isolated gastric muscle strips of guinea pigs and its possible mechanism. METHODS: A total of 48 guinea pigs were killed to remove the whole stomach. Then, the stomach was opened and the mucosal layer was removed. Parallel to the circular fibers, muscle strips were cut from the body. Each isolated gastric muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution, constantly warmed by water jacket at 37℃ and bubbled continuously with a mixed gas of 950 mL/L O2 and 50 mL/L CO2. After being incubated for 1 h with 1 g tension, rhubarb of varied concentrations (1%, 2%, 7%, 20% and 70%) was added cumulatively into the tissue chamber at intervals of 2 min. Atropine (10-6 mol/L) or isoptin (5x10-8 mol/L) or hexamethonium (10-5 mol/L) was given 2 min before the administration of rhubarb. The isometrical response was measured with an ink-writing recorder. RESULTS: Rhubarb dose dependently increased the resting tension of gastric body circular muscle (CM) (r = 0.726, P<0.05). Atropine (r= 0.829, A:0.05), isoptin (r= 0.764, A;0.05) and hexamethonium (r = 0.797, P<0.05) did not affect its action in a dose-related manner. Atropine apparently reduced the increasing action of 1%, 3%, 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Isoptin inhibited the effect of 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Hexamethonium reduced the increasing action of 1%, 10%, 30% and 100% rhubarb on the resting tension of gastric body CM. Rhubarb increased the contractile frequency of CM of body. While atropine, isoptin and hexamethonium did not inhibit the contractile frequency of gastric body CM in comparison with rhubarb at the same concentration, rhubarb at the highest concentration (100%) decreased the mean contractile amplitude of gastric body CM. Atropine, isoptin and hexamethonium did not affect the mean contractile amplitude of gastric body CM compared to rhubarb at the same concentration. CONCLUSION: Rhubarb has exciting actions on isolated gastric smooth muscle strips of guinea pig. The exciting action of rhubarb is partly mediated via cholinergic M receptor, cholinergic N receptor and L-type calcium channel.

五虎散治疗急性腰扭伤74例

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Effect of rhubarb on contractile response of gallbladder smooth muscle strips isolated from guinea pigs

AIM: To investigate the effect of rhubarb on contractile response of isolated gallbladder muscle strips from guinea pigs and its mechanism.METHODS: Guinea pigs were killed to remove the whole gallbladder. Two or three smooth muscle strips (8 mm×3mm) were cut along the longitudinal direction. The mucosa on each strip was carefully removed. Each longitudinal muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution (37 ℃), bubbled continuously with 950 mL/L O2 and 50 mL/L CO2. The resting tension (g), mean contractile amplitude (mm),and contractile frequency (waves/min) were simultaneously recorded on recorders. After 2-h equilibration, rhubarb (10, 20, 70, 200, 700, 1 000 g/L) was added cumulatively to the tissue chamber in turns every 2 min to observe their effects on gallbladder.Antagonists were given 3 min before administration of rhubarb to investigate the possible mechanism.RESULTS: Rhubarb increased the resting tension (from 0 to 0.40±0.02, P＜0.001), and decreased the mean contractile amplitude (from 5.22±0.71 to 2.73±0.41,P＜0.001). It also increased the contractile frequency of the gallbladder muscle strips in guinea pigs (from 4.09±0.46to 6.08±0.35, P＜0.001). The stimulation of rhubarb on the resting tension decreased from 3.98±0.22 to 1.58±0.12by atropine (P＜0.001), from3.98±0.22 to 2.09±0.19 by verapamil (P＜0.001) and from 3.98±0.22 to 2.67±0.43by phentolamine (P＜0.005). But the effect was not inhibited by hexamethonium (P＞0.05). In addition, the action of mean amplitude and frequency was not inhibited by the above antagonists.CONCLUSION: Rhubarb can stimulate the motility of isolated gallbladder muscle strips from guinea pigs. The stimulation of rhubarb might be relevant with M receptor,Ca2+ channel and α receptor partly.

Protective effect of rhubarb on barrier of intestinal mucosa

AIM To investigate the mechanism of the rhubarb on gut barrier protection. METHODS The models of gut barrier damage caused by hemorrhagic shock and intraperitoneal endotoxin were used to study the protective effect of rhubarb on the barrier of intestinal mucosa. They were randomly divided into four groups: treatment (rhubarb) group; positive control group; negative control group; placebo treatment group. The concentration of plasma endotoxin, tissue superoxide dismutase and lipoperoxide were measured. The histological analysis was also used. The effect of rhubarb on gut protection was observed. RESULTS The rhubarb could decrease intestinal permeability, attenuate endotoxin absorption within the gut, (the content of endotoxin in serum: shock group 0 557EU/ml±0 069EU/ml vs rhubarb group 0 345EU/ml±0 055EU/ml), obviously decrease the consumption of tissue SOD and the formation of tissue LPO (the content of SOD in serum, intestine and liver: endotoxin group 122 92NU/ml±43 19NU/ml, 292 24NU/ml±88 76NU/ml, 272 70NU/ml±85 79NU/ml vs rhubarb group 312 23NU/ml±54 93NU/ml, 391 09NU/mg±98 16NU/mg, 542 86NU/mg±119 93NU/mg; The content of LPO in intestine and liver: endotoxin group 8 57μmol/L±2 58μmol/L, 86 97μmol/L±46 54μmol/L vs rhubarb group 3 05μmol/L±1 13μmol/L, 13 18μmol/L±19 64μmol/L). Gut histopathology revealed that rhubarb could promote proliferation of gut goblet cells, increase secretion of mucus and protect intestinal mucosa in hemorrhagic shock model. CONCLUSION The mechanism of the rhubarb on gut barrier protection might involve in decreasing intestinal permeability, scavenging oxygen free radicals, promoting proliferation of goblet cells within intestinal mucosa.

EXPRESSION OF INTERCELLULAR ADHESION MOLECULE IN LUNG TISSUES OF EXPERIMENTAL ACUTE LUNG INJURY AND THE AFFECT OF RHUBARB ON IT

Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. Methods. Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM1 mRNA. Results. In the lung tissues, the ICAM1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P<001), demonstrating the expression of ICAM1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P<001, P<005); the corresponding pathologic changes of lung tissues and the biological markers of the lung injury were significantly decreased or ameliorated. Conclusions. The increase of the expression of ICAM1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM1 mRNA expression.

Effects of rhubarb extracts on hyperexcitability of hippocampal CA1 neurons after fluid percussion injury

Objective To investigate the effects of rhubarb extracts,i.e.rhein and emodin,on the neuronal hyperexcitability and synaptic transmission,and to further reveal the mechanism of the secondary brain damage.Methods The fluid percussion injury(FPI) rat model and extracellular recording method were used.The evoked field potentials by stimulating Schaffer collaterals were collected from the ipsilateral(impact side) and the contralateral hippocampal CA1 areas of rat in vitro.And the field potentials,including the field excitatory postsynaptic potential and the population spike,were analyzed.Results After the impact was performed on the rat parietal cortex,the evoked field potentials in the ipsilateral hippocampus CA1 area were enhanced obviously.Rhubarb extracts reduced the slope of the field excitatory postsynaptic potential and the number of the population spike significantly while rhein and emodin increased the latency of the population spike obviously.Conclusion Rhubarb extracts,i.e. rhein and emodin,can depress the neuronal hyperexcitability,which suggests that rhein and emodin play an important role in protecting the central nervous system from neuronal damage after traumatic brain injury.FPI produces hyperexcitability of hippocampal CA1 neurons,probably by enhancing excitatory synaptic transmission.

Organ specific differences in alteration of aquaporin expression in rats treated with sennoside A,senna anthraquinones and rhubarb anthraquinones

OBJECTIVE Senna and rhubarb are classified as stimulative laxatives,and known to have similar effective constituents,the anthraquinones.Being protected by theβ-glucoside bond,the anthraquinones can reach the intestines 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 anthraquinones 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 biotransformation 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 measurement 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-regulation 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.

Effects of rhubarb and the active ingredients of rhubarb on the cytoplasmic free calcium in INTMNC of rabbits

INTRODUCTIONThe recent studies have shown that rhubarb has notonly the effect of removing stasis by purgation,butalso intestinal barrier effects.In order tofurther clarify the intestinal barrier mechanism ofrhubarb,we studied the effects of rhubarbdecoction and the active ingredients of rhubarb onthe cytoplasmic free calcium in isolated intestinalmononuclear ceils (INT-MNC).

Rhubarb ameliorates cognitive dysfunction in a rat model of Alzheimer’s disease through regulation of the intestinal microbiome

Objective:To determine the mechanism whereby rhubarb(Rheum tanguticum MAXIM.Ex BALF.)may ameliorate cognitive dysfunction through regulation of the intestinal microbiome.Methods:We used a rat model of human microbiome-associated(HMA)-AD to characterize the therapeutic effect of rhubarb on cognitive dysfunction by assessing learning and spatial memory,tissue pathology,and neurotransmitter expression in brain tissue.Then,16S rRNA gene sequencing was used to analyze the intestinal microbial composition of the rats before and after rhubarb intervention,to determine whether changes in the intestinal microbiome might underpin the beneficial effect of rhubarb on cognitive dysfunction.Results:Morris water maze experiments showed that the learning and spatial memory of HMAAD rats were improved after rhubarb administration.Examination of brain sections showed that rhubarb had a protective effect on neurons in the brain tissue of HMA-AD rats.Brain tissue neurotransmitter analysis showed that rhubarb significantly reduces the 5-hydorxytryptamine concentration in the hippocampus of HMA-AD rats(P Z.0013).Furthermore,rhubarb affected the abundance of the Lachnospiraceae_NK4A136_group and Lactobacillus in the large intestine.Conclusion:This study suggests that rhubarb ameliorates cognitive dysfunction in rats with HMA-AD by regulating the abundance of beneficial bacteria,which likely affects the concentration of 5-hydorxytryptamine in the hippocampus.