Protective effect of Rheum ribes extract against lead-induced hepatotoxicity in male rats

Abstract The effects of Rheum ribes on lead acetate levels and hepatic biochemical factors due to lead acetate toxicity were investigated. Forty male Wistar rats were designated into four groups: Control; lead acetate (receiving in drinking water at 0.6 g/L, daily); hydroalcoholic extract groups (200 and 400 mg/kg doses, gavage, once daily). Treatments were conducted for 10 days. On the 11th day, blood samples were collected to measure lead acetate levels and biochemical factors. Liver tissue samples were examined for histopathological changes. Lead serum levels were increased in lead acetate-treated rats (p<0.001). Lead acetate treatment was associated with a significant increase in liver tissue damage (p<0.001), while R. ribes extract prevented liver tissue damage (p<0.05). The levels of alanine aminotransferase and aspartate aminotransferase were significantly lower in the groups lead acetate + extract (two doses) than in the lead acetate group (p<0.001 and P<0.01, respectively), but alkaline phosphatase level, prothrombin time, partial thromboplastin time and international normalized ratio were not different between the lead acetate + extract groups and the lead acetate group. The results showed the inhibitory role of R. ribes on lead-induced hepato-toxicity. The results make Rhubarb a good candidate to protect against the deleterious effect of chronic lead intoxication after complementary studies

The clinical efficacy of external application of mirabilite and rhubarb combined with intrathoracic chemotherapy in treating malignant pleural effusion: A prospective, randomized, controlled clinical trial.

BACKGROUND: Malignant pleural effusion (MPE) is one of the commonest causes of an exudative pleural effusion. Breathlessness, dyspnea and other symptoms often seriously distress and affect the quality of life. The external application of mirabilite and rhubarb (EAMR) combined with intrathoracic infusion of cisplatin, as an alternative treatment for MPE, is popular in China. The study aims to assess its effectiveness and safety combined with intrathoracic chemotherapy. METHODS: This study is a prospective, randomized controlled clinical trial. Patient visits were performed at baseline and days 14 and 28 after treatment. Clinical outcomes were measured after chest drain placement using the criterion of efficacy refer to WHO standard, and QLQ-C30 questionnaire. RESULTS: Database records of patients treated in our institution for MPE between October, 2016 and March, 2019. The study included 84 eligible patients. They were categorized with a randomization schedule into treatment group (N = 42) and control group (N = 42). There is statistical significance in the comparison of the total effective rate between these 2 groups (66.67% vs 54.76%, P < .05). Furthermore, there is statistical significance in the comparison of items of Physical (1.95 ±â€Š0.50 vs 2.19 ±â€Š0.58%, P < .05), Pain (1.98 ±â€Š0.42 vs 2.07 ±â€Š0.32, P < .05), and Global Health (1.23 ±â€Š0.64 vs 1.13 ±â€Š0.23%, P < .05) between these 2 groups. None of the patients had adverse reactions such as skin allergy and chest tightness. CONCLUSIONS: The total effective rate of treatment group using extra external application of mirabilite rhubarb powder is significantly higher than that of control group. The improvement of patients' clinical symptoms is greater in treatment group and no adverse reactions is found. Therefore, external application of mirabilite and rhubarb combined with intrathoracic infusion of cisplatin is an effective method for the treatment of MPE, which is worth popularizing.

Potential preventive and therapeutic effect of Chinese herb rhubarb (da huang) for intensive care unit/pediatric intensive care unit gastrointestinal failure patients: A protocol for systematic review.

INTRODUCTION: The Chinese herb da huang (DH) (Rhubarb) is commonly used for GIF intensive care unit (ICU)/pediatric intensive care unit (PICU) gastrointestinal failure (GIF) patients in China. However, the potential preventive and therapeutic effect of DH in these patients has not yet been studied systematically. OBJECTIVES: The aim of this study was to evaluate the preventive and therapeutic effects of DH in treating ICU/PICU GIF patients with the most recent evidence. METHODS: We systematically searched 7 databases from inception to March 30, 2018. RevMan 5.3 software was used to perform a meta-analysis. GRADE methodology was applied to evaluate the quality of evidence for each outcome. The review protocol was registered on PROSPERO (CRD42018092710) in advance. RESULTS: Seven studies comprising 788 pediatric or adult participants were included in this analysis. Three indicators, including GIF occurrence rates (gastrointestinal mucosal hemorrhage, enteroplegia), multiple organ dysfunction syndrome (MODS)-related items (occurrence rates of MODS, mortality rates of MODS) and duration in the ICU was analyzed. The GIF occurrence rate meta-analysis result was (RR 0.47, CI 95% 0.37-0.60; P = .95); MODS related items indicator result was (RR 0.44, CI 95% 0.33-0.59; P = .41); ICU duration ICU result was (RR -2.87, CI 95% -3.53--2.21; P = .40). The safety of Chinese herb DH (Rhubarb) remains unclear. CONCLUSION: Current evidence suggests that the Chinese herb rhubarb (DH) powder combined with Western medicine was inferior to Western medicine alone in terms of preventive and therapeutic effects in ICU/PICU patients in terms of decreasing GIF occurrence rates (gastrointestinal mucosal hemorrhage and enteroplegia), occurrence rates of MODS, mortality from MODS, and shortened duration time in the ICU/PICU. However, larger sample sizes and rigorously-designed studies are necessary to conclusively determine the association between DH powder and outcomes in ICU/PICU GIF patients.

Extraction, structural characterization, and immunoregulatory effect of a polysaccharide fraction from Radix Aconiti Lateralis Preparata (Fuzi).

A water-soluble polysaccharide fraction named FZPS-1 was obtained from Radix Aconiti Lateralis Preparata (Fuzi in Chinese). Physicochemical and instrumental analyses indicated that the purified FZPS-1 with an average molecular weight of 6.29 × 106 Da was composed of D-arabinose and d-glucose with a molar ratio of 7.5:92.5. It would contain the main chain fragments of →4)-α-D-Glc-(1 â†’ 4)-α-D-Glc-(1→, with the side chain of terminal α-L-Ara-(1 â†’ linked at C6 of D-Glc skeleton. FZPS-1 exhibited significant antioxidative activity and immunomodulatory activity, wherein it promotes macrophage phagocytosis and increases the secretion of macrophage-derived biological factors in RAW 264.7 cells, and a cyclophosphamide-induced immunosuppressed model in a dose-dependent manner. Oral administration of FZPS-1 ameliorated chronic diarrhea in rhubarb-induced spleen deficiency rats and was related to its immunomodulatory activity. Therefore, the obtained FZPS-1 could be potentially utilized as a natural immunomodulatory agent in functional food supplements or drugs.

Network pharmacology oriented study reveals inflammatory state-dependent dietary supplement hepatotoxicity responses in normal and diseased rats.

Rhubarb, a well-used herbal and dietary supplement, has been widely used as a laxative in many countries. The dietary supplement rhubarb may reveal differential hepatotoxicity responses in normal and diseased subjects; however, its underlying mechanism is unclear. By using a network pharmacology approach, we found that the components contained in rhubarb had associations with a liver disease-related protein network that could be enriched into two subnetworks: a pro-inflammatory protein network associated with liver inflammation and an anti-inflammatory protein network related to liver fibrosis. In addition, macrophages were found to have an association with these subnetworks. Herein, the differential toxicity responses of rhubarb in normal and diseased rats were illustrated by in vivo pharmacology experiments. Rhubarb induced liver injury in normal rats with dose-dependent increases in the pro-inflammatory response; in contrast, it failed to induce hepatotoxic effects in a liver fibrosis rat model and was accompanied by an increase in anti-inflammatory protein expression. Further study showed elevation of high mobility group box-1 (HMGB1) in the sera and liver tissues and remarkable pro-inflammatory activation of Kupffer cells in liver tissue; these phenomena were associated with the hepatotoxic effect of rhubarb and could be blocked by inhibiting either HMGB1 or Kupffer cells through glycyrrhizin or GdCl3, respectively. Interestingly, we also observed attenuated pro-inflammatory activation of Kupffer cells in a liver fibrosis rat model together with a non-hepatotoxic response to rhubarb. These results suggest that the divergent immune states in normal and diseased subjects may contribute to the differential toxicity responses to rhubarb.

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.

The Influence of Compatibility of Rhubarb and Radix Scutellariae on the Pharmacokinetics of Anthraquinones and Flavonoids in Rat Plasma.

BACKGROUND AND OBJECTIVES: Rhubarb-Radix scutellariae is a classic herb pair, which is commonly used to clear away heat and toxin in clinic. The aim of this study was to investigate the influence of compatibility of Rhubarb and Radix scutellariae on the pharmacokinetic behaviors of anthraquinones and flavonoids in rat plasma. METHODS: Eighteen rats were randomly divided into three groups, and were orally administered Rhubarb and/or Radix scutellariae extracts. A sensitive and rapid UPLC-MS/MS method was developed and validated to determine the concentrations of baicalin, baicalein, wogonside, wogonin, rhein, and emodin in rat plasma. The concentrations of phase II conjugates of flavonoid aglycones and anthraquinone aglycones were also determined after hydrolyzing the plasma with sulfatase. RESULTS: Compared with administration of Radix scutellariae alone, co-administration of Rhubarb significantly decreased the first maximum plasma concentration (C max1) of baicalin, wogonside, and the phase II conjugates of baicalein, wogonin to 46.40, 61.27, 41.49, and 20.50%, respectively. The area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) was significantly decreased from 82.60 ± 20.22 to 51.91 ± 7.46 µM·h for rhein and 276.83 ± 98.02 to 175.42 ± 86.82 µM·h for the phase II conjugates of wogonin after compatibility. The time to reach the first maximum plasma concentration (T max1) of anthraquinones was shortened and the second peak of anthraquinones disappeared after compatibility. CONCLUSIONS: Compatibility of Rhubarb and Radix scutellariae can significantly affect the pharmacokinetic behaviors of characteristic constituents of the two herbs. The cause of these pharmacokinetic differences was further discussed combined with the in vivo ADME (absorption, disposition, metabolism, and excretion) processes of anthraquinones and flavonoids.

The Effects of Rheum palmatum L. on the Pharmacokinetic of Major Diterpene Alkaloids of Aconitum carmichaelii Debx. in Rats.

BACKGROUND AND OBJECTIVES: Aconitum carmichaelii Debx. (Fuzi) is usually compatible with Rheum palmatum L. (Dahuang) in clinic. The study is conducted to investigate the influence of Dahuang on the pharmacokinetics of Fuzi. METHODS: Twelve rats were randomly divided into two groups. Fuzi group was orally administered a single dose of 38.4 mg/kg total alkaloids from Fuzi, and Fuzi-Dahuang group was given 38.4 mg/kg total alkaloids from Fuzi and 76.8 mg/kg Dahuang anthraquinones at the same time. The plasma concentrations of aconitine (AC), mesaconitine (MC), and hypaconitine (HC), benzoylaconine (BAC), benzoylmesaconine (BMC), benzoylhypaconine (BHC), and aconine (ACN) were determined by ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry method. The pharmacokinetic parameters were calculated including maximum plasma concentration (C max), area under the plasma concentration-time curve in all time-points (AUClast), apparent volume of distribution (V z/F), apparent plasma clearance (CL/F), elimination half-life (T 1/2), and time to achieve maximum concentration (T max). RESULTS: AUClast of diester diterpene alkaloids (DDAs) were 58.20, 169.78, 278.48 ng·h/mL for AC, MC, and HC in Fuzi-Dahuang group which were remarkably lower than that in Fuzi group (71.62, 183.13, 410.59 ng·h/mL for AC, MC, HC). CL/F was significantly increased from 173.88 to 218.85 mL/h for AC, 433.22 to 800.21 mL/h for MC, 1150.61 to 1307.30 mL/h for HC after combination. However, with the significantly increased C max, AUClast of monoester diterpene alkaloids (MDAs) and amine diterpenoid alkaloids (ADAs) were 152.42, 1238.95, 287.96, 123.33 ng·h/mL for BAC, BHC, BMC, ACN in Fuzi-Dahuang group which were remarkably higher than that in Fuzi group (54.47, 1105.48, 200.75, 86.48 ng·h/mL for BAC, BHC, BMC, ACN). At the same time, CL/F was significantly decreased from 1030.15 to 607.09, 3594.06 to 1437.54, 1441.23 to 1310.14, and 391.30 to 239.50 mL/h for each one after combination. CONCLUSIONS: Fuzi diterpene alkaloids pharmacokinetics was greatly influenced by Dahuang which may account for the compatibility mechanism of effect-enhancing and toxicity-reducing.

Metabolic analysis of the effect of rheum on a taurocholate-induced acute pancreatitis rat model

ABSTRACT The effects of rheum on serum parameters in a taurocholate-induced acute pancreatitis (AP) rat model were investigated using pathological and biochemical tests, and a proton nuclear magnetic resonance (1H NMR)-based metabonomic strategy. Healthy rats and rats with AP were either treated with rheum (7.5% at a dose of 1.5 g/kg) or left untreated. Serum samples were collected from the AP and rheum-treated groups at 6, 12, and 24 h after treatment. The effect of rheum on pathological changes in the pancreatic was investigated to validate the AP model. We obtained 1H NMR spectra and analyzed the results using the partial least squares discriminant method. The results of the pathological and metabolic analyses revealed an amelioration of multiple metabolic abnormalities and an increase in the aerobic respiration ratio after treatment, compared with the AP groups. These results were attributed to improvements in energy supply and the elimination of metabolic products. The study also promoted NMR-based metabonomic analysis as a feasible method of assessing traditional Chinese drugs.

Glutinous rice amylopectin can adjust the plasma gut-regulated peptide levels in rhubarb-induced spleen deficiency rats.

The pharmacological effects of glutinous rice (GR) and GR amylopectin (GRA) on the gastrointestine were investigated in rhubarb-induced spleen deficiency rats by determining the levels of gastrointestinal hormones such as the peptides serum gastrin, amylase motilin, and somatostatin. GR and GRA were given by gavage at various doses of GR (7.5, 15, and 30 g per kg body weight) and GRA (3.8, 7.6, and 15 g per kg body weight) every day for 4 weeks, respectively. The results indicated that the final body weight of rats in the highest-dose GR (GRH) group and all the GRA groups significantly (P < 0.05) increased (7.2-12.1%) compared with the model control (MC) group. All the GR and GRA treated groups had significantly (P < 0.05) higher gastrin contents (32.8-51.2%), motilin levels (13.8-39.2%), and amylase contents (22.5-39.4%) and the GRH and highest-dose GRA (GRAH) groups had significantly (P < 0.05) lower somatostatin contents compared with the MC group. Meanwhile, the somatostatin contents were negatively correlated with the motilin levels (r = -0.964, P < 0.01) and amylase contents (r = -0.981, P < 0.01). The GRAH treatment group had the highest final body weight, gastrin contents, motilin levels, and amylase contents and the lowest somatostatin contents, which demonstrated that GRA might play the most important role in the spleen-regulating activities of GR.

[Advance in studies on effect of Glycyrrhizae Radix et Rhizoma in relieving purgative activity of Rhei Radix et Rhizoma].

Rhei Radix et Rhizoma, as a commonly used traditional Chinese medicine, has been widely applied in clinic. Its major purgative constituent is anthraquinones, which are believed to be a toxic ingredient. Glycyrrhizae Radix et Rhizoma has been reputed as the best alexipharmic to moderate medicine natures. In this paper, the effect of Glycyrrhizae Radix et Rhizoma in relieving purgative activity of Rhei Radix et Rhizoma was studied in two aspects--the boiling process and intestinal metabolism; Studies on combined administration of Glycyrrhizae Radix et Rhizoma and Rhei Radix et Rhizoma in recent years were summarized according to chemical constituent, intestinal flora, I/II phase metabolism and drug transport. However, the material basis and mechanism for their compatibility remain unclear, further studies will be made in the future.

Gut microbial diversity in rat model induced by rhubarb.

Rhubarb is often used to establish chronic diarrhea and spleen (Pi)-deficiency syndrome animal models in China. In this study, we utilized the enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) method to detect changes in bacterial diversity in feces and the bowel mucosa associated with this model. Total microbial genomic DNA from the small bowel (duodenum, jejunum, and ileum), large bowel (proximal colon, distal colon, and rectum), cecum, and feces of normal and rhubarb-exposed rats were used as templates for the ERIC-PCR analysis. We found that the fecal microbial composition did not correspond to the bowel bacteria mix. More bacterial diversity was observed in the ileum of rhubarb-exposed rats (P<0.05). Furthermore, a 380 bp product was found to be increased in rhubarb-exposed rats both in faces and the bowel mucosa. The product was cloned and sequenced and showed high similarity with regions of the Bacteroides genome. AS a result of discriminant analysis with the SPSS software, the Canonical Discriminant Function Formulae for model rats was established.

[Understanding differences between Rheum palmatum and R. franzenbachii from perspective of chemistry, efficacy and toxicity].

Rheum franzenbachii (called Tudahuang in local) has some similarities with R. palmatum (rhubarb) collected by "China Pharmacopoeia" and is often used as a substitute of rhubarb. Can Tudahuang simply replace rhubarb in the application or whether is there difference between Tudahuang and rhubarb, and what is the difference it is important to verify the difference and understand its proper application in the field of clinical practice. In this paper, we discussed the differences of the two herbs from the views of chemistry, efficacy and toxicity based on the author's previous research work as well as literatures, by using the major role of the rhubarb "diarrhea" as the basic point. The analysis result showed that the role of diarrhea Tudahuang was much weaker than that of rhubarb. The reason lies in the difference between the contents of combined anthraquinones component. While acute toxicity in mice of Tudahuang is stronger than that of rhubarb. Thus, Tudahuang should not simply replace rhubarb in practice.

Distinguishing characteristics of urothelial carcinoma in kidney transplant recipients between China and Western countries.

OBJECTIVE: To identify significant distinctive characteristics of urothelial carcinoma (UC) in kidney transplant recipients between China and Western countries and investigate probable tumor screening and treatment factors contributing to these differences. METHODS: Renal transplant recipients from 1998 to 2011 in our institution diagnosed with UC were included in this study. Our data on tumor incidence, clinical characteristics, and outcomes were compared with literature reports. RESULTS: Among 2572 renal transplant recipients identified, 24 (0.93%) experienced UC, including 10 men and 14 women of overall mean age of 49.3 ± 11.6 years at transplantation and 53.5 ± 9.5 years at tumor detection. The Chinese traditional herbal intake mainly focused on 2 preparations: Aristolochic acid and rhubarb (the latter was mainly used in patients with chronic renal impairment) in 20 people. There were 21 (87.5%) cases of upper (UTUC) 5 cases of bilateral, and 13 cases of multifocal urinary tract urothelial carcinoma. Four subjects died owing to tumor progression at 4-63 months postoperatively. CONCLUSIONS: UC in renal transplant recipients shared notable characteristics in China with widespread herb intake: UTUC predominance; multifocal and bilateral organ involvement; high rates of recurrence, progression, and dissemination, in contrast with bladder tumor dominance in Western countries. As a consequence, we suggest that bilateral nephroureterectomy should be performed prophylactically in high-risk patients, especially those with a long history of Chinese herb intake. The relationship of rhubarb consumption to UC in renal transplant recipients should be noted and evaluated.

Acute kidney injury after ingestion of rhubarb: secondary oxalate nephropathy in a patient with type 1 diabetes.

BACKGROUND: Oxalosis is a metabolic disorder characterized by deposition of oxalate crystals in various organs including the kidney. Whereas primary forms result from genetic defects in oxalate metabolism, secondary forms of oxalosis can result from excessive intestinal oxalate absorption or increased endogenous production, e.g. after intoxication with ethylene glycol. CASE PRESENTATION: Here, we describe a case of acute crystal-induced renal failure associated with excessive ingestion of rhubarb in a type 1 diabetic with previously normal excretory renal function. Renal biopsy revealed mild mesangial sclerosis, but prominent tubular deposition of oxalate crystals in the kidney. Oxalate serum levels were increased. CONCLUSION: Acute secondary oxalate nephropathy due to excessive dietary intake of oxalate may lead to acute renal failure in patients with preexisting renal disease like mild diabetic nephropathy. Attention should be payed to special food behaviors when reasons for acute renal failure are explored.

Rheum officinale (a traditional Chinese medicine) for chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a major public health issue worldwide. Standard therapies to delay CKD progression include dietary protein restriction and administration of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) to help control blood pressure and confer additional renoprotective effects. Despite such interventions, CKD incidence and mortality rates continue to increase. Rheum officinale (Da Huang) a medicinal herb used widely in China to treat CKD has been reported to offer a range of pharmacological properties that may delay disease progression. OBJECTIVES: To assess the benefits and harms of Rheum officinale for preventing the progression of CKD. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register and CENTRAL (Issue 4, 2011), MEDLINE, EMBASE, the Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), VIP (Chongqing VIP Chinese Science and Technology Periodical Database), and Wanfang Data. We also handsearched reference lists of articles. We applied no restrictions on language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that assessed the benefits and harms of Rheum officinale for preventing the progression of CKD regardless of dosage, type, maturity, mode of administration, duration of treatment, or storage time before use. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We expressed results for dichotomous outcomes (need for renal replacement therapy, all-cause mortality, quality of life) as risk ratios (RR) with 95% confidence intervals (CI). Continuous outcomes (glomerular filtration rate (GFR), serum creatinine (SCr), creatinine clearance (CrCl), blood urea nitrogen (BUN)) were expressed as mean differences (MD) with 95% CIs. MAIN RESULTS: We identified nine studies that enrolled 682 participants. None of the studies reported blinding or group allocation methods. Seven studies were judged to be at low risk of incomplete outcome reporting; three studies were judged to be a low risk of selective reporting (protocols were available and/or all outcomes relevant to the this review were reported); and two studies were judged free of other potential biases.Seven studies compared Rheum officinale with no treatment and two made comparisons with captopril, an angiotensin-converting enzyme inhibitor (ACEi). Compared with no treatment, Rheum officinale had a positive effect on SCr (MD -87.49 µmol/L, 95% CI -139.25 to -35.72) and BUN (MD -10.61 mmol/L, 95% CI -19.45 to -2.21). Compared with captopril, a statistically significant difference was not demonstrated in relation to Rheum officinale for any outcome (BUN, CrCl, or patients' capacity to undertake work). No data were available on all-cause mortality or cost of treatment. Only minor adverse events were reported in association with Rheum officinale. AUTHORS' CONCLUSIONS: Currently available evidence concerning the efficacy of Rheum officinale to improve SCr and BUN levels in patients with CKD is both scant and low quality. Although Rheum officinale does not appear to be associated with serious adverse events among patients with CKD, there is no current evidence to support any recommendation for its use.

Rhubarb use in patients treated with Kampo medicines--a risk for gastric cancer?

In vitro mutagenic effects have been reported for ingredients contained in rhubarb. Therefore, rhubarb (Rhei Rhizoma) as an anthranoid laxative could be associated with a risk of developing gastric cancer as well as colorectal cancer. We are not aware of any reports that have examined the relationship between the use of rhubarb and the development of gastric cancer. During the period between 1979 and 1999, we treated 14,616 patients using various Kampo medicines, which sometimes contained rhubarb. In the present study, we determined whether patients, diagnosed with gastric cancer during the period between 1979 and 1999, had been administered rhubarb before the development of gastric cancer. Among the 10 enrolled patients, only 2 patients had been administered rhubarb before the development of gastric carcinoma. The other 8 patients had never received rhubarb before the development of gastric carcinoma. Rhubarb use may have little connection with the development of gastric cancer in practice, even if some ingredients in rhubarb have shown carcinogenic activity in experimental studies.