Diabetic kidney disease (DKD) is the primary cause of mortality among diabetic patients. With the increasing prevalence of diabetes, it has become a major concern around the world. The therapeutic effect of clinical use of drugs is far from expected, and therapy choices to slow the progression of DKD remain restricted. Therefore, research on new drugs and treatments for DKD has been a hot topic in the medical field. It has been found that rhein has the potential to target the pathogenesis of DKD and has a wide range of pharmacological effects on DKD, such as anti-nephritis, decreasing blood glucose, controlling blood lipids and renal protection. In recent years, the medical value of rhein in the treatment of diabetes, DKD and renal disease has gradually attracted worldwide attention, especially its potential in the treatment of DKD. Currently, DKD can only be treated with medications from a single symptom and are accompanied by adverse effects, while rhein improves DKD with a multi-pathway and multi-target approach. Therefore, this paper reviews the therapeutic effects of rhein on DKD, and proposes solutions to the limitations of rhein itself, in order to provide valuable references for the clinical application of rhein in DKD and the development of new drugs.
Humans ; Diabetic Nephropathies/drug therapy* ; Kidney/pathology* ; Anthraquinones/therapeutic use* ; Diabetes Mellitus

Animals ; Anthraquinones ; isolation & purification ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Kidney Failure, Chronic ; drug therapy ; Phytotherapy ; Rheum ; chemistry

Animals ; Anthraquinones ; therapeutic use ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Drug Therapy, Combination ; Liver Cirrhosis, Experimental ; chemically induced ; drug therapy ; Male ; Pyrazines ; therapeutic use ; Rats ; Rats, Wistar

OBJECTIVETo verify the pharmacological hypothesis of prescriptions by studying the targeted distribution of major components in stewed rhubarb in the rat model with acute pancreatitis (AP).

METHODNormal SD rats (control group, n = 5) and the AP model induced with intraperitoneal cerulein (model group, n = 5) were taken as the experimental objects. Rats of the two groups were orally administered with stewed rhubarb granules (20 g x kg(-1)). Their heart, liver, spleen, lung, kidney and pancreas were collected two hours after the administration. Such constituents as emodin, chrysophanol, physcion, rhein and aloe-emodin and their concentrations in each tissue homogenate were detected by high performance liquid chromatography-mass-mass.

RESULTAloe-emodin and physcion in stewed rhubarb whose concentrations in liver and kidney of normal rats were higher than that in pancreatic tissues, while the distribution spectrums and concentrations of the remaining components in pancreatic tissues had no significant difference with that of other organs. The concentrations of emodin, aloe-emodin, rhein and chrysophanol in stewed rhubarb in pancreatic tissues of the AP model group were higher than that in other tissues and organs, while their concentrations in pancreatic, renal and splenic tissues were notably higher than that in the normal group.

CONCLUSIONIn the conditions of AP, effective components in stewed rhubarb show a targeted distribution feature in pancreas, which provides experimental basis for the pharmacological hypothesis of prescriptions.

Acute Disease ; Animals ; Anthraquinones ; pharmacokinetics ; pharmacology ; therapeutic use ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; therapeutic use ; Male ; Organ Specificity ; Pancreatitis ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry

OBJECTIVETo observe the therapeutic efficacy of Qianggu Granule (QGG), Diacerein Capsule (DC), and QGG + DC in treating knee osteoarthritis (KOA, belonging to Gan-Shen insufficiency induced vein stasis syndrome), and to explore the clinical advantages of QGG + DC.

METHODSNinety patients in line with the diagnosis standard were randomly assigned to three groups, i. e., the QGG group (30 case, treated by QGG), the Western medicine treatment group (30 case, treated by DC), and the combination therapy group (30 case, treated by QGG +DC). Then the patients' symptoms and signs were scored. Meanwhile, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumor necrosis factor alpha (TNF-alpha), comprehensive efficacy, and adverse reactions, etc. were assessed.

RESULTSThe ache could be obviously alleviated, the patients' joint function could be improved, and their quality of daily activities could be elevated in all the 3 groups. There was statistical difference in the symptoms and signs scores, CRP, ESR, and TNF-alpha before and after treatment (P < 0.05). Better effects were obtained in the combination therapy group (P < 0.05). As for the comprehensive efficacy, it was better in the QGG + DC group than in the QGG group and the DC group, showing statistical difference (P < 0.01).

CONCLUSIONSThe comprehensive therapeutic efficacy of applying QGG + DC in treating KOA (belonging to Gan-Shen insufficiency induced vein stasis syndrome) was superior to using QGG or DC alone. Besides, no obvious adverse reaction occurred.

Adult ; Anthraquinones ; therapeutic use ; Blood Sedimentation ; C-Reactive Protein ; analysis ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; Phytotherapy ; Tumor Necrosis Factor-alpha ; analysis

PURPOSE: Low grade inflammation is a well-known characteristic in obese subjects. We investigated body weight changes and inflammatory markers after 12-week intervention trial. MATERIALS AND METHODS: Twenty-six obese subjects were enrolled and 19 (13 men and 6 women) completed the study. Sibutramine is an FDA-approved drug for body weight control; therefore, we chose this drug as the standard treatment medication in this study. Patients were randomly allocated to receive an anti-inflammatory agent (Diacerein treatment group; n = 12) or placebo (n = 7) for 12 weeks. Anthropometry, body proportion by dual-energy X-ray absorptiometry, and metabolic parameters at the beginning and end of study were measured and compared. RESULTS: The treatment group had a tendency towards more reduction in anthropometry as compared to the placebo group, in body weight reduction (- 7.0 kg vs. - 4.6 kg), body mass index (- 2.51 kg/m2 vs. - 1.59 kg/m2), and waist circumference (- 7.3 cm vs. - 4.4 cm). These reductions were not statistically significant. Changes in levels of high-sensitivity C-reactive protein and adiponectin in the treatment group were more favorable than in the placebo group. CONCLUSION: This small pilot study showed no statistical difference for changes in anthropometry, and inflammatory markers between the two groups. Therefore, we could not find any additional effects of Diacerein on weight loss and inflammatory variables in this study.
Absorptiometry, Photon ; Adiponectin/blood ; Adult ; Anthraquinones/*therapeutic use ; Anti-Inflammatory Agents/*therapeutic use ; Appetite Depressants/therapeutic use ; C-Reactive Protein/analysis ; Cyclobutanes/*therapeutic use ; Double-Blind Method ; Female ; Humans ; Inflammation ; Lipoproteins, LDL/blood ; Male ; Obesity/*drug therapy/immunology ; Pilot Projects ; Tumor Necrosis Factor-alpha/blood ; Waist Circumference/drug effects/immunology ; Weight Loss/drug effects/*immunology

AIMTo evaluate the effects of maxillary sinus floor elevation by a tissue-engineered bone complex of beta-tricalcium phosphate (beta-TCP) and autologous osteoblasts in dogs.

METHODOLOGYAutologous osteoblasts from adult Beagle dogs were cultured in vitro. They were further combined with beta-TCP to construct the tissue-engineered bone complex. 12 cases of maxillary sinus floor elevation surgery were made bilaterally in 6 animals and randomly repaired with the following 3 groups of materials: Group A (osteoblasts/beta-TCP); Group B (beta-TCP); Group C (autogenous bone) (n=4 per group). A polychrome sequential fluorescent labeling was performed post-operatively and the animals were sacrificed 24 weeks after operation for histological observation.

RESULTSOur results showed that autologous osteoblasts were successfully expanded and the osteoblastic phenol-types were confirmed by ALP and Alizarin red staining. The cells could attach and proliferate well on the surface of the beta-TCP scaffold. The fluorescent and histological observation showed that the tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than beta-TCP along or even autologous bone. It had also maximally maintained the elevated sinus height than both control groups.

CONCLUSIONPorous beta-TCP has served as a good scaffold for autologous osteoblasts seeding. The tissue-engineered bone complex with beta-TCP and autologous osteoblasts might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation.

Alkaline Phosphatase ; analysis ; Alveolar Ridge Augmentation ; methods ; Animals ; Anthraquinones ; Biocompatible Materials ; therapeutic use ; Biomarkers ; analysis ; Bone Substitutes ; therapeutic use ; Bone Transplantation ; pathology ; Calcification, Physiologic ; physiology ; Calcium Phosphates ; therapeutic use ; Cell Adhesion ; physiology ; Cell Proliferation ; Dogs ; Fluorescent Dyes ; Guided Tissue Regeneration, Periodontal ; methods ; Maxilla ; surgery ; Maxillary Sinus ; surgery ; Models, Animal ; Osteoblasts ; transplantation ; Osteogenesis ; physiology ; Random Allocation ; Tissue Engineering ; methods ; Tissue Scaffolds ; Transplantation, Autologous

OBJECTIVETo evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA).

METHODSA total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated.

RESULTSTotally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians' overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P > 0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P < 0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P < 0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P < 0. 001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events.

CONCLUSIONSDiacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.

Adult ; Aged ; Anthraquinones ; administration & dosage ; adverse effects ; therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; adverse effects ; therapeutic use ; Diclofenac ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; physiopathology ; Safety

OBJECTIVEThe aim of the present study is to investigate the effect of rhein treatment on the first-phase insulin secretory function in db/db mice.

METHODTwenty 4-week-old male db/db mice were randomized to treatment with rhein (120 mg x kg(-1), n = 10) and placebo respectively (1% natrium cellulose solution, n = 10) by gavage for 8 weeks respectively. Ten age-matched non-diabetic male littermates db/m mice treated with placebo were studied as non-diabetic control. Body weight and fasting blood glucose level were measured before and after medication. The islets were isolated after 8 weeks' gavage. Islet perifusion system was set up, and all columns were perfused in parallel at a flow rate of 0.5 mL x min(-1) with KRB (2.8 mmol L(-1) glucose) at 37 degrees C. After 60-min static incubation with KRB (2.8 mmol x L(-1) glucose), the islets were stimulated in the continuous presence of a high concentration of 16.7 mmol x L(-1) glucose. Samples were collected every 20-second until 2-min, every 1-min until 5-min, thereafter every 5-min until 30-min. Samples were immediately stocked at -80 degrees C until further analysis.

RESULTCompared with the db/db control group, the fasting glucose concentration was significantly decreased in the rhein treatment group. The first-phase insulin secretory function was impaired significantly in db/db mice, while the first-phase insulin secretory peak was obvious in the rhein treatment mice.

CONCLUSIONRhein treatment significantly improved glucose tolerance, restored the first-phase insulin secretion and protected the islets function.

Animals ; Anthraquinones ; therapeutic use ; Blood Glucose ; analysis ; Body Weight ; drug effects ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; In Situ Nick-End Labeling ; Insulin ; secretion ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVETo investigate the effect of rhein on the development of hepatic fibrosis.

METHODSThe animal models were made with carbon tetrachloride (CCl(4)) mixed with vegetable oil (3/2, v/v), which was injected subcutaneously twice a week for 6 weeks, and with 5% ethanol for free drinking water. At the same time, Rhein was administrated at the dose of 25 mg/kg or 100 mg/kg once a day for 6 weeks. The changes of both biochemical markers, such as the levels of alanine aminotransferase (ALT), hyaluronic acid (HA), procollagen type III (PCIII) in serum and SOD, malondialdehyde (MDA) in liver, and related histopathological parametres were determined.

RESULTSCompared with the model group, there were three kinds of changes in the larger quantity of rhein treated group. (1) The levels of ALT, HA, PCIII in serum and MDA in liver homogenate were decreased significantly (from 150 U/L +/- 16 U/L to 78 U/L +/- 18 U/L, 321 microg/L +/- 97 microg/L to 217 microg/L +/- 75 microg/L, 31 microg/L +/- 14 microg/L to 16 microg/L +/- 6 microg/L and 3.67 nmol/mg +/- 0.68 nmol/mg to 1.88 nmol/mg +/- 0.34 nmol/mg, respectively, t > or 2.977, P<0.01). However the level of SOD in liver was increased (from 62.45 NU/mg +/- 8.74 NU/mg to 91.26 NU/mg +/- 14.04 NU/mg, t=4.453, P<0.01). (2) The expressions of transforming growth factor beta 1 (TGF-beta 1) and alpha-smooth muscle actin (alpha-SMA) in liver were markedly reduced (P<0.05 and P<0.01). (3) The collagen staining positive area was decreased and the grade of fibrosis was reduced significantly in liver (P<0.05 and P<0.01).

CONCLUSIONRhein can protect hepatocyte from injury and prevent the progress of hepatic fibrosis in rats, which may associate with that rhein plays a role in antioxidation, anti-inflammation, inhibiting the expression of TGF-beta1 and suppressing the activation of hepatic stellate cells (HSCs).

Animals ; Anthraquinones ; pharmacology ; therapeutic use ; Anti-Inflammatory Agents ; pharmacology ; Antioxidants ; pharmacology ; Collagen ; analysis ; Liver ; drug effects ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; antagonists & inhibitors ; Transforming Growth Factor beta1