Diacerein mitigates renal ischemia/reperfusion injury via inhibition of renal inflammation, dendritic cells maturation and apoptosis: the role of TLR4/NF-kB/NLRP3/IL-1beta signaling pathway / La diacereína mitiga la lesión por isquemia/reperfusión renal a través de la inhibición de la inflamación renal, la maduración de las células dendríticas y la apoptosis: el papel de la vía de señalización TLR4/NF-kB/NLRP3/IL-1beta

SUMMARY: One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/ reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1β), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R.

La isquemia renal es una de los motivos del daño renal agudo. Sin embargo, los enfoques protectores y terapéuticos para este problema son limitados. La diacereína es un fármaco antiinflamatorio caracterizado por numerosas actividades biológicas. Nuestro objetivo fue determinar el impacto de mejora de la diacereína en la condición de lesión por isquemia/ reperfusión renal (I/R), explorando los mecanismos subyacentes. Veinticuatro ratas macho se distribuyeron en cuatro grupos (n= 6): grupo simulado; grupo de diacereína (DIA); grupo I/R, en el que una pinza no aplastante ocluyó el pedículo renal izquierdo durante 45 min, y el riñón derecho fue nefrectomizado durante 5 min antes del proceso de reperfusión; Grupo I/R + diacereína, inyectado por vía intraperitoneal con 50 mg de diacereína/kg i.m. 30 min antes de la operación I/R. Se encontró que la isquemia/ reperfusión afecta la función renal e induce alteraciones histopatológicas. El análisis de citometría de flujo demostró una expresión elevada de células dendríticas innatas y maduras en tejidos renales I/R. Además, se observó una regulación positiva en la expresión de los genes inflamatorios (TLR4, Myd88 y NLRP3) y una sobreexpresión de las citoquinas proinflamatorias (IL-1β), marcadores apoptóticos (caspasa-3) y piroptóticos (caspasa-1) en animales con experiencia en I/R. Los deterioros antes mencionados fueron mitigados por el tratamiento previo a la diacereína I/R. La diacereína alivió la inflamación y la apoptosis inducidas por I/R. Por lo tanto, podría ser un agente protector prometedor contra I/R.

Clinical observation of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis in the early and mid-term stage / 中国药房

OBJECTIVE To investigate clinical efficacy and safety of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis （KOA） in the early and mid-term stage. METHODS Totally 100 KOA patients were randomly divided into control group and trial group， with 50 cases in each group. Control group received Diacerein capsules orally， 50 mg every time， bid. Trial group additionally received Jipei dilong ointment， once a day， on the basis of control group. Both groups had a treatment course of 4 weeks， and were followed up for 3 months after treatment. The clinical efficacy of 2 groups， visual analogue scale （VAS）， Western Ontario and McMaster University osteoarthritis index （WOMAC） score， Lysholm scores before and after treatment， at 3-month follow-up after treatment were all observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin 1β （IL-1β）， IL-6， superoxide dismutase （SOD）， malondialdehyde （MDA）， nitric oxide （NO）， cartilage oligomeric matrix protein （COMP）， matrix metalloproteinase-13 （MMP-13） and C-telopeptide of type Ⅱ collagen （CTX-Ⅱ） were detected in knee joint fluid. The incidence of adverse drug reactions was recorded. RESULTS After 4 weeks of treatment， total effective rate was 96.0% in trial group and 90.0% in control group， without statistical significance between 2 groups （P＞0.05）. At 3- 2019YFC1712500） month follow-up after treatment， total effective rate of trial group was 94.0%， and was higher than 62.0% of control group（P＜0.05）. After 4 weeks of treatment and at 3-month follow-up after treatment， VAS score， WOMAC score，the contents ofTNF-α， IL-1β， IL-6， MDA， NO， COMP， MMP-13 and CTX-Ⅱ in knee joint fluid of two groups were significantly lower than before； Lysholm score and SOD activity of knee joint fluid were significantly higher than before， and the trial group was significantly better than the control group during the same period （P＜0.05）. And there was no statistical significance in the incidence of adverse drug reactions between two groups（P＞0.05）. CONCLUSION For the treatment of KOA in early and mid- term stage， Jipei dilong ointment combined with diacerein relieve pain， improve knee function by inhibiting inflammatory reaction， reducing oxidative stress and inhibiting chondrocyte and matrix degradation， and have low incidence of adverse drug reactions.

Study on postprandial bioequivalence of Diacerein capsules in healthy volunteers / 中国药房

OBJECTIVE To evaluate the postprandial bioequivalence of two kinds of Diacerein capsules in healthy volunteers with oral administration . METHODS A total of 24 adult healthy subjects were included and randomly divided into two groups ， with 12 subjects in each group . A randomized ，open，double-cycle cross -over trial design was adopted . Both groups took 50 mg of the test preparation （domestic Diacerein capsules ）or the reference preparation （Ambridine®）respectively at 30 min after eating the standard meal in the morning of the first day of each cycle of the trial . The cleaning period was one week . Blood samples were collected at different time points before and after taking the medicine and the protein was precipitated with methanol for sample pretreatment. The concentration of active metabolite rhein was determined by LC -MS/MS using emodin as internal standard . The pharmacokinetic parameters were calculated with DAS 3.2.9 software，and the bioequivalence of test and reference preparation were evaluated. RESULTS After the subjects took the test preparation and the reference preparation after meal ， the main pharmacokinetic parameters of rhein were as follows ：cmax were（3 517±1 121）and（3 225±755）ng/mL；AUC0－24h were （25 764±6 134）and（24 316±5 856）ng·h/mL；AUC0－∞ were（26 679±6 409）and（25 170±6 415）ng·h/mL；tmaxwere 3.50 （0.67，12.00）and 4.00（1.50，7.00）h；t1/2 were（4.26±1.12）and（4.19±1.05）h，respectively. The 90% confidence intervals of the geometric mean ratios of cmax，AUC0－24h and AUC 0－∞ were 100.8%-113.9%，103.1%-109.4% and 103.2%-109.9%，respectively. CONCLUSIONS The test preparation and reference preparation are bioequivalent in the postprandial state of healthy subjects .

Manejo no quirúrgico de la artrosis de rodilla: ¿Son efectivos los medicamentos orales complementarios? / Non-surgical management of knee osteoarthritis: are complementary oral medications effective?

La artrosis es una enfermedad progresiva de las articulaciones sinoviales que causa dolor, impotencia funcional, discapacidad, y degeneración progresiva de la articulación. En sus tratamientos, sobre todo en etapas tempranas, existen distintas intervenciones para evitar tanto su desarrollo y progresión como también para lograr un adecuado manejo de los síntomas, y hay tratamientos médicos orales no convencionales con evidencia controvertida. El objetivo de este trabajo es proporcionar una actualización, dirigida a especialistas en Ortopedia y Traumatología, respecto a la evidencia actual sobre las terapias complementarias orales en el tratamiento de la artrosis de rodilla. Se hace referencia a los métodos fármacológicos complementarios más usados y estudiados, mencionando el método de acción y las consecuencias estudiadas sobre la artrosis de rodilla. Se finaliza con una tabla de recomendaciones basada en evidencia actual.

Osteoarthritis (OA) is a progressive disease of the synovial joints that causes pain, functional impairment, disability, and progressive degeneration of the joint. Regarding its treatments, especially in early stages, there are different interventions to avoid its development and progression and also to achieve an adequate management of symptoms, and there are unconventional oral medical treatments with controversial evidence. The objective of the present paper is to provide an update, to specialists in Orthopedics and Traumatology, regarding the current evidence on complementary oral therapies in the treatment of knee osteoarthritis. References are made to the most widely used and studied complementary pharmacological methods, mentioning the method of action and the consequences studied on knee osteoarthritis. The article ends with a table of recommendations based on current evidence.

A comparative study of the efficacy of glucosamine sulfate and diacerein in the treatment of adult Kashin-Beck disease / 中华地方病学杂志

Objective:To observe and compare the therapeutic effects of glucosamine sulfate (GS) and diacerein (DCN) on adult Kashin-Beck disease (KBD).Methods:A clinical randomized controlled trial was conducted in the historical severe KBD areas Fanrong Township, Fulu Town, Long'anqiao Town, Lianghe Town, Shaowen Township of Heilongjiang Province, and 240 patients were selected according to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), then divided into GS and DCN groups (gender, age, and KBD condition balanced) via the random number table method, with 120 patients in each group. Followed up once a month to investigate the patient's medication and clinical symptoms, and distributed drugs for the next stage. Fasting blood samples and urine samples were collected before, during, and at the end of treatment (0, 90, and 180 days). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-1β level and urine pyridinol (PYD) level. Visual analog scale (VAS) scores, evaluation of affected joints, self-evaluated efficacy, and evaluation of adverse reactions were carried out through questionnaires. Joint dysfunction scores and medications efficacy determination were performed according to the "Judgment of Kaschin-Beck Disease Treatment Effect" (WS/T 79-2011).Results:Expression of cytokines related to cartilage metabolism: after 180 days of treatment, serum IL-1β levels, urine PYD levels in GS group and urine PYD levels in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.332, - 5.420, - 5.204, P < 0.05). VAS scores: after 90 days of treatment, the pain, stiffness scores of patients in GS group and the pain, stiffness, and function scores in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.612, - 2.359, - 3.637, - 2.881, - 2.238, P < 0.05); after 180 days of treatment, the pain, stiffness and function scores of patients in GS and DCN groups were significantly lower than those of the same group at 0 day of treatment ( Z = - 6.738, - 9.530, - 7.781, - 5.428, - 3.761, - 3.587, P < 0.01). Evaluation of affected joints: after 90 and 180 days of treatment, except for pain of weather changes in DCN group, the scores of symptomatic joints in the two groups were lower than those at 0 day of treatment ( P < 0.05). Efficacy self-evaluation: after 180 days of treatment, the self-evaluated efficacy ratio of DCN group was higher than that of GS group and the same group after 90 days of treatment (χ 2 = 4.165, 4.022, P < 0.05). Evaluation of adverse reactions: after 90 and 180 days of treatment, the main adverse reactions of patients in GS and DCN groups were gastrointestinal symptoms. Joint dysfunction scores: after 90 days of treatment, the sum of the effective rate and the markedly effective rate of GS group was higher than that of DCN group (χ 2 = 4.993 , P < 0.05); while after the 180 days of treatment, there was no significant difference between the two groups (χ 2 = 0.417 , P > 0.05). Conclusions:Both GS and DCN have a certain therapeutic effect on adult KBD and can improve clinical symptoms. The GS takes effect quickly, and long-term use can protect cartilage from inflammatory factors to a certain extent.

Design and characterization of intra-oral fast dissolving tablets containing diacerein-solid dispersion

Diacerein (Diacetylrhein, DCN) is anthraquinone derivatives used in the curing of osteoarthritis, but its usage isrestricted due to its very poor solubility and wettability which result in bioavailability variation. The objective ofthis work was to design fast dissolving tablets (FDTs) of DCN solid dispersion. Solid dispersions (SDs) and physicalmixtures (PMs) were prepared with PEG4000, Polyvinylpyrolidone K25 (PVPK25), and Sorbitol. SD formationincreased the dissolution rate of DCN compared to PM; this demonstrates that the improvement of dissolution ratewith SD can be due to physical change in drug crystal which was confirmed by thermal analysis. SD with Sorbitol wasselected for the preparations of FDTs. Seven formulations were prepared by direct compression method using differentconcentrations of crospovidone (CP) as superdisintegrant and camphor as subliming agent. Pre- and post-compressionevaluation were carried for powder blend and the prepared FDTs, respectively. F7 (composed of 120 mg CP, 45 mgcamphor, 200 mg SD containing 50 mg DCN, 7.5 mg aspartame, 2.5 mg menthol, 2.5 mg Magnesium stearate, and22.5 mg lactose) showed the shortest disintegration time and the highest dissolution rate and it was selected for furtherinvestigation. Kinetic studies of the in vitro release results showed that F7 followed first-order kinetics. Stabilitystudies conducted for formula F7 showed good stability upon storage at 30oC/75% RH and 40oC/75% RH for 12 weeks.

The effect of food intake on the pk of rhein released from diacerein

Diacerein is a symptomatic slow-acting drug used for treating osteoarthritis. This drug is completely metabolized into the active metabolite rhein before reaching the systemic circulation. This study evaluated the effects of food on the pharmacokinetics of rhein released from diacerein in healthy Chinese subjects. This was a single-center, randomized, single-dose, open-label, two-period, cross-over study. Twenty-four healthy subjects were randomly selected to receive a single oral dose of 50 mg diacerein capsule in either fasted or fed state on two separate visits. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters were calculated using WinNonlin software. In the fasted and fed states, the main pharmacokinetic parameters of diacerein capsule were as follows: Cmax were (4471 ± 936), (3225 ± 755) ng/mL, t1/2 were (4.22 ± 0.42), (4.19 ± 1.05) h, tmax were (2.61 ± 1.25), (3.81 ± 1.29) h, AUC0-24 h were (24223 ± 4895), (24316 ± 5856) h·ng/mL, and AUC0-∞ were (24743 ± 5046), (25170 ± 6415) h·ng/mL. The absorption rate of diacerein capsule was obviously delayed by food intake but the absorption degree remained unaffected.

Therapeutic effect of combined drug therapy on knee joint of Kaschin-Beck disease / 中华地方病学杂志

Objective To investigate the effect of knee joint injection of sodium hyaluronate combined with oral administration of diacerein and/or glucosamine sulfate on knee joint of Kaschin-Beck disease.Methods The method of prospective study was used,80 patients with Kaschin-Beck disease admitted to the General Internal Medicine,Guang'an People's Hospital from January 2015 to December 2017 were selected as subjects.They were divided into 4 groups according to the difference of their medication methods,20 cases per group.Group A was treated with intra-articular injection of sodium hyaluronate,Group B was treated with intra-articular injection of sodium hyaluronate + oral diacerein,Group C was treated with intra-articular injection of sodium hyaluronate + oral glucosamine sulfate,Group D was treated with intra-articular injection of sodium hyaluronate + oral diacerein and glucosamine sulfate,and the overall therapeutic effects of the 4 groups were compared.Results The knee joint scores of Group D at 7,14,90,and 180 days after treatment were (6.25 ± 2.01),(4.22 ± 1.15),(2.21 ± 1.01),and (1.15 ± 0.15) scores,respectively,they were significantly lower than those of Group A [(12.11 ± 3.02),(11.91 ± 2.98),(11.85 ± 2.85),(11.05 ± 2.52) scores],Group B [(9.11 ± 2.85),(8.32 ± 2.45),(7.55 ± 2.32),(6.15 ± 2.01) scores] and Group C [(9.12 ± 2.84),(8.23 ± 2.32),(7.43 ± 2.29),(6.11 ± 2.00) scores],the differences were statistically significant (P ＜ 0.05).The total effective rates of the 4 groups were 60％ (12/20),65％ (13/20),70％ (14/20),and 90％ (18/20),respectively,Group D was significantly higher than those of other 3 groups (x2 =18.250,18.250,16.000,P ＜ 0.05).The scores of 20 m walking pain and joint tenderness in Group D after treatment and follow-up period were lower than those of other 3 groups (P ＜ 0.05).Conclusions In the clinical practice of Kaschin-Beck disease,intra-articular injection of sodium hyaluronate combined with oral diacerein and glucosamine sulfate can improve the knee joint function of patients,alleviate pain and enhance the overall therapeutic effect.The combined therapy has great clinical value.

Study on Preparation and Related Properties of Diacerein-loaded PLGA Microspheres for Intra-articular Injection / 中国药房

OBJECTIVE:To prepare Diacerein (DCR)-loaded (poly lactic-co-glycolic acid) PLGA microspheres for intra-articular injection and investigate its related properties. METHODS:PLGA was used as microspheres material,and the microsphere was prepared by emulsification solvent evaporation method. The contents of DCR-PLGA microspheres were determined by HPLC,and drug-loading amount and entrapment efficiency were also calculated. Using entrapment efficiency as evaluation index,the preparation technology was optimized by orthogonal test. The morphology and particle size of microspheres were observed by optical microscope and SEM. Accumulative release rate was investigated by using in vitro release test. RESULTS:The linear range of DCR was 2.1-105.0 μg/mL(r＝0.999 9). RSDs of precision,stability,reproducibility and recovery tests were all lower than 2.0%. The optimal technology was PLGA concentration of 200 mg/mL,volume ratio of oil-water 1∶50,polyvinyl alcohol concentration of 1%. The prepared DCR-PLGA microspheres were spherical,average particle size was(11.2±4.7)μm, drug-loading amount was(4.25 ± 0.26)% and encapsulation rate was(92.30 ± 1.93)%,respectively. The drug release rate of DCR-PLGA microspheres within 360 h was about(73.08 ± 5.33)%. CONCLUSIONS:DCR-PLGA microspheres are prepared successfully with good morphology,suitable particle size and obvious sustained release effect,which are suitable for intra-articular injection.

Corneal pharmacokinetics of the 2% diacerein eye drops between multiple administration and single administration / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration. · METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total). The concentrations of the metabolites of diacerein in the cornea were measured by high performance liquid chromatography after given eye drop 5, 15, 30, 60, 120, and 180min. The pharmacokinetic parameters were calculated by pharmacokinetic software (DAS2.1.1). ·RESULTS: The metabolites of diacerein, rhein, was detected in the cornea at each time point. The concentration of the metabolite of diacerein in the cornea was 318.678±40.88,210.02±25.66,188.83±31.74,112.24± 11.70,90.28±22.01 and 57.67±13.71μ g/g after given eye drop 5, 15, 30, 60, 120, and 180min in the multiple administration group. The concentration in the single administration group was 145.17 ± 19.29, 97.95 ± 10.49, 71.18±18.70,39.11±2.44,18.10±2.34 and 9.08±2.04μ g/g respectively. The concentration of rhein in the cornea was the highest at 5min after the administration in the two groups. The concentration of the multiple administration group was higher than that in the single administration group at 5, 15, 30, 60, 120, and 180min (P<0.01). The half-life of the drug was 0.89 ± 0.31h in the single administration group. · CONCLUSION: Compared with the single administration, the conjunctival sac multiple administration has the advantages of high drug concentration and long duration. Therefor the conjunctival sac multiple administration is a more effective method to treat acute infectious corneal diseases.

Diacerein, its beneficial impact on chondrocytes and notable new clinical applications

Diacerein (DCN) was obtained by diacetylation of an anthraquinone derivative rhein and was approved by FDA in 2008, in the treatment of osteoarthritis due to its inhibitory effect on proinflammatory cytokines, including IL-6 and IL-1ß. It was synthesized in 1980s and marketed as a tablet in some European Union and Asian countries from 1994. Along with its great potential in the treatment of osteoarthritis, its other applications are also being explored day by day, such as in the treatment of psoriasis, epidermolysis bullosa, breast cancer, type 2 diabetes and periodontitis. The main aim of this review is to explore mechanism of action, various applications and side effects associated with DCN. This has been reviewed that apart from the risk of diarrhea on long-term administration of DCN, various clinical studies has also shown its modest benefits in treatment of various pathological conditions. Hence, DCN is emerging as a new and potentially safe derivative with maximum therapeutic efficacies and minimum side effects which can results in improving the living status of patients suffering from various inflammatory diseases

Effect of diacerein as an add-on to metformin in patients with type 2 diabetes mellitus and inadequate glycemic control

ABSTRACT Objective To evaluate the effect of diacerein as an add-on to metformin in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control. Materials and methods A randomized, double-blind, placebo-controlled clinical trial was carried out on 12 patients with T2DM and inadequate glycemic control [glycated hemoglobin A1c (A1C) ≥ 7%] with metformin as monotherapy (≥ 1500 mg per day) for at least the previous 90 days. Fasting and postprandial glucose were measured before and after the pharmacological intervention. A1C, lipid profile, creatinine and uric acid were also evaluated. After randomization, all patients continued with their dose of metformin. Six subjects received placebo and the other six volunteers took diacerein. Data were tested using the Wilcoxon signed-rank, Mann-Whitney U and chi-square tests. The Institutional Ethics Committee approved the study protocol. Results After 90 days of diacerein as an add-on to metformin, there was a significant decrease in fasting glucose (196 ± 79 vs. 149 ± 70 mg/dL, p < 0.05), postprandial glucose (262 ± 99 vs. 187 ± 70 mg/dlL, p < 0.05) and A1C (8.4 ± 2.0 vs. 6.7 ± 1.7 %, p < 0.05). Conclusions Diacerein as an add-on to metformin in patients with T2DM improved their glycemic control.

Effects of diacerein on inflammatory cytokines and adipose metabolism as well asthe expression of chemerin in adipose tissue of type 2 diabetic rats / 西安交通大学学报(医学版)

Objective To study the effects of diacerein and its metabolite rhein on plasma inflammatory cytokine level and expression of perirenal adipose tissue chemerin in type 2 diabetes mellitus (T2DM) rats and its role in regulating glucose and lipid metabolism.Methods We randomly divided 56 SD male rats into 5 groups: normal control group (Group A), T2DM group (Group B), pioglitazone group (Group C), diacerein group (Group D), and pioglitazone+diacerein group (Group E).Group A was fed with ordinary feed whereas the other groups were fed with high-fat diet.At the end of week 8, rats in Groups B, C, D and E were injected intraperitoneally with 30mg/kg of STZ solution to create the model.Those in Group A were injected with the same volume of sterile sodium citrate solution.OGTT examination was taken to screen the model rats at the end of week 10.The successful mode was chosen according to OGTT result.Then Group C was treated with pioglitazone 10mg/(kg·d) orally, Group D with diacerein 50mg/(kg·d), Group E with pioglitazone 10mg/(kg·d)+diacerein 50mg/(kg·d), and Group A and B were given the same volume of normal saline.The intervention lasted 4 weeks.At the end of experiment weeks 10 and 14, FBG, FINS, TC, TG, LDL-C, IL-1β, IL-6, and TNF-α were detected in the fasting rats with free access to water.After blood sample was taken at the end of week 14, all rats were killed and theperirenal adipose tissue was isolated, the expression of chemerin in perirenal adipose tissue was detected by Western blotting.Results At the end of week 10, FBG, FINS, TG, TC, LDL-C, IL-1β, IL-6, and TNF-α were higher in Groups B, C, D and E than in Group A while HDL-C was lower (all P<0.01).At the end of week 14, TC, TG, and LDL-C were lower in Groups C, D and E than in Group B but higher than Group A while HDL-C was lower than in Group A (all P<0.05).Group E had greater changes in glucose and lipid metabolism and inflammatory cytokine level than Groups C and D (P<0.05).Western blotting results showed that the expression of chemerin in perirenal adipose tissue increased higher in Group B than in Groups A, C, D and E (P<0.05).The expression of chemerin were also higher in Groups C and D than in Groups A and E (P<0.05), but there was no significant difference between Groups A and E.Conclusion Diacerein can regulate the metabolism of glucose and lipid, improve insulin resistance by reducing the expression of chemerin and the level of inflammatory cytokines.

Effects of anti-inflammatory drugs of diacerein on glucose and lipid metabolism in type 2 diabetic rats / 医学研究生学报

Objective Recent studies have shown that inflammatory cytokines are involved in the occurrence and development of diabetes mellitus .The article aimed to investigate the effects of anti-inflammatory drug--diacerein on hepatic PPAR-γand GLUT-2 protein expression and its role in the regulation of glucose and lipid metabolism in rats with type 2 diabetes mellitus ( T2DM) . Methods 55 male SD rats were randomly divided into 4 groups:normal control group (n=10), T2DM group (n=15), pioglitazone intervention group(n=15), and diacerein treatment group(n=15) .Rats in normal control group were fed with normal diet , the other 3 groups were fed with high fat diet .At the end of 8th experi-ment week, rats in 3 groups fed with high fat diet were treated with intraperitoneal injection of 30mg/kg streptozotocin ( STZ) solution, while rats in normal control group were injected with the same volume of sterile sodium citrate solution .At the end of 10th week, OGTT modeling rats were screened .Rats in pioglitazone intervention group were treated with 10 mg/kg pioglitazone by intragastric administra-tion, rats in diacerein group was treated with 50mg/kg diacerein by intragastric administration , and rats in normal control group and T2DM group were given the same volume of normal saline .The intervention lasted 4 weeks.At the end of 8th, 10th and 14th week, the blood examination of glycolipid , FINS, IL-1βand liver function indexes was done on fasting rats .Fourteenth weeks later , after getting blood samples , all rats were sacrificed and liver tissues were isolated .Western blot was applied in the detection of PPAR γand immu-nohistochemistry was applied to detect GLUT-2 protein in livers. Results At the end of 8th week, the FBG level in pioglitazone in-tervention group increased compared with normal control group ( P0 .05) show-ing higher levels compared with T 2DM group ( P<0.01).At 14th weekend, the GLUT-2 expression levels in normal control group (0.209±0.023), pioglitazone intervention group (0.226±0.017) and diacerein treatment group (0.232±0.012) were higher than that of T2DM group (0.173±0.009,P<0.01);and the GLUT-2 expression levels in pioglitazone intervention group and diacerein treatment group were higher than that of normal control group (P<0.05).The expression level of liver PPAR-γwas in positive correlation with those of GLUT-2 protein, HDL-C, FINS, ISI ( r=0.815, 0.780, 0.747, P<0.01) and in negative correlation with those of FBG , HbA1c, TC, TG, AST, ALT, IL-1β(r=-0.465,-5.716,-0.615,-0.675,-0.617,-0.521,-4.827, P<0.05). Conclusion Diacerein can enhance liver PPAR-γand GLUT-2 expression levels and reduce the levels of IL-1β, HbA1c and blood lipid, thus im-prove insulin resistance in T 2DM rats.

Comparison of the Effects of Iguratimod Combined with Methotrexate and Diacerein Respectively on Relat-ed Indexes of Refractory Rheumatoid Arthritis / 中国药房

OBJECTIVE:To compare the effects of iguratimod combined with methotrexate and diacerein respectively on relat-ed indexes of refractory rheumatoid arthritis (RRA). METHODS:98 RRA patients were randomly divided into control group (48 cases)and observation group(50 cases). Control group received Iguratimod tablet 25 mg,twice a day+Methotrexate tablet with ini-tial dose of 10 mg,once a week,increased to 12.5 mg after 2 weeks,increased to 15 mg in the second courses,once a week. Ob-servation group received Iguratimod tablet(the same dosage and usage with control group)+Diacerein granule 50 mg,twice a day. 4-week was a course,they were treated for 6 courses. Morning stiffness time,the numbers of 28 joints tenderness and swelling,28 joint disease activity score (DAS28),erythrocyte sedimentation rate (ESR),rheumatoid factor (RF),IL-1,vascular endothelial growth factor (VEGF),tumor necrosis factor (TNF)-α,C-reaction protein (CRP),malondialdehyde (MDA),superoxide dis-mutase(SOD),total antioxidant capacity(TAOC),early peak flow(peak E),left ventricular late flow peak flow(peak A),E/A and left ventricular ejection fraction(LVEF)before and after treatment,and the incidence of adverse reactions in 2 groups were ob-served. RESULTS:Before treatment,morning stiffness time,the numbers of 28 joints tenderness and swelling,DAS28 score, ESR,RF,IL-1,TNF-α,CRP,VEGF,MDA,TAOC and peak A in 2 groups were significantly lower than before treatment,and observation group was significantly lower than control group;SOD,peak E,E/A and LVEF in 2 groups were significantly higher than before treatment,and observation group was significantly higher than control group,with statistical significances (P0.05). CONCLUSIONS:Iguratimod combined with diacerein is superior to iguratimod combined with methotrexate in improving cardiac function,oxidation-antioxidant imbalance play and reducing inflammatory reactions in the treatment of RRA,with similar safety.

Compliance and tolerability evaluation of diacerein versus s-adenosyl methionine in osteoarthritis patients

Background: Diacerein and S-adenosyl methionine (SAMe) are symptomatic slow-acting drugs in osteoarthritis (SYSADOA). Diacerein is a semisynthetic, anthraquinone derivative, an interleukin 1beta inhibitor with anti-inflammatory, anti-catabolic and pro-anabolic properties on cartilage and synovial membrane. SAMe is a dietary supplement used in the management of OA. The objective of this study is to find out compliance and tolerability evaluation of Diacerein versus S-adenosyl methionine inpatients suffering from Osteoarthritis. Materials and methods: This was a prospective, randomized, interventional study conducted in Orthopedic OPD and ward in Rajah Muthiah Medical College and Hospital for a period of one year. A total of 80 patients were enrolled in this study as per the inclusion criteria. 40 patients in each group were randomly assigned to receive either diacerein 50mg BD or SAMe 200 mg TDS for12 weeks. The NSAID diclofenac 50 mg BD was administered orally for a short course of one week to both the groups to relieve acute symptoms. Efficacy of both the drugs was assessed using Lysholm knee scoring scale. The tolerability profile was evaluated during each clinical visit on weeks 1, 4 and 12. Gayathri C.R., Vanitha Samuel, Senthilnathan A, Nirmala P. Compliance and tolerability evaluation of diacerein versus sadenosyl methionine in osteoarthritis patients. IAIM, 2017; 4(11): 6-13. Page 7 Results: Diacerein and SAMe which were symptomatic slow-acting drugs show a profound reduction in pain starting from 4th to 12th week of treatment. Lower GI side effects like diarrheawere observed in the diacerein group and insomnia was reported in the SAMe group. Though the overall adverse effects were more in the diacerein group, compliance was better with regard to drug intake Conclusion: Both diacerein and SAMe were found to be effective in reducing the pain in Osteoarthritis patients. Diacerein with a good compliance factor was less tolerable because of the incidence of diarrhea. SAMe though better tolerated has a compliance score of fair to good.

A comparative study of two separate analytical techniques for the simultaneous determination of diclofenac sodium and diacerein from combined dosage form

ABSTRACT Diclofenac sodium (DS) and diacerein (DC) have emerged as a potential combination therapy for the treatment of knee osteoarthritis. Therefore a validated analytical method is essential for the simultaneous estimation of both from combined dosage form. A ratio derivative spectrophotometric and a chromatographic technique have been developed for the simultaneous determination of DS and DC. The quantification was done at 263.00 nm for DC and 304.50 nm for DS in the first method, whereas 257 nm for DC and at 274 nm for DS for LC-DAD analysis in chromatographic method using acetate buffer and methanol as the mobile phase at a flow-rate 0.50 mL/min. Both of these methods are found to be linear in the concentration range under study with r2 value 0.999 and 0.996 for DS and DC respectively in ratio derivative spectroscopy and 0.998 and 0.999 for DS and DC respectively in LC-DAD study. Both of these methods are found to be accurate and precise, though greater robustness and precision is observed with chromatographic analysis over the ratio derivative spectroscopy. Statistically there was no significant difference between proposed ratio derivative spectrophotometric and LC-DAD methods.

Protective effect of diacerein on MIA-induced injury in rat osteoarthritis chondrocytes / 重庆医学

Objective To investigate the protective effect of diacerein on monosodium iodoacetate (MIA) induced injury in rat osteoarthritis chondrocytes .Methods The experiment was divided into five groups ,including the normal group ,model group (4μM MIA) ,diacerein low ,middle and high doses groups (1 ,10 ,100μM) .The viability of chondrocytes was detected by MTT assay . The activity of cysteinyl aspartate specific proteinase‐3 (Caspase‐3) was measured by spectrophotography .The activation of nuclear factor kappa B (NF‐κB) signaling pathway and expression level of downstream target molecule cell Bax ,Bcl‐2 ,matrix metalloprotei‐nase‐9 (MMP‐9) and MMP‐13 were detected by Western blot .Results 1 ,10 ,100μM diacerein could increase the viability of MIA‐induced chondrocytes and reduce the activity of Caspase‐3(P<0 .05) .10 ,100μM diacerein could decrease the phosphorylation level of IκBαand NF‐κB p65 ,furthermore downregulated the level of Bax ,MMP‐9 and MMP‐13 protein ,and upregulated the level of Bcl‐2 protein (P<0 .05) .Conclusion Diacerein could inhibit cell apoptosis and degradation of extracellular matrix in MIA‐induced rat chondrocytes ,which might be related to the NF‐κB signal pathway .

Effect and mechanism of qiangguixishu pills in the treatment with knee osteoarthritis / 中国生化药物杂志

Objective To study the effect of qiangguixishu pills in the treatment with knee osteoarthritis and influence in miR of circulating and inflammatory factor index.Methods 50 patients with KOA from October 2014 to October 2015 were randomly divided into two groups,the observation group and the control group,with 25 cases in each group.The control group using Diacerein capsules for treatment,the observation group received the Qiangguixishu pills for treatment,compared the WOMAC score and clinical efficacy before and after treatment between two groups,and changes of miR and inflammatory factors circulating.Results There was no difference in WOMAC score between the two groups before treatment;pain,joint stiffness, daily activities and comprehensive scores were decreased after treatment in two groups(P<0.05),and it was lower in the observation group than in the control group(P<0.05);There was no significant difference at blood miR-146a,miR-140,miR-21,IL-6,IL-1beta,TNF-alpha contents between the two groups,miR-21 beta,IL-6,IL-1 beta,TNF-alpha were lower than that before treatment in the two groups after treatment(P<0.05),miR-140,miR-146a were higher than before treatment(P<0.05),and compared with the control group,the above indicators at the observation group were had significant difference(P<0.05).Conclusion There were the therapeutic effect in the treatment with KOA by Qiangguixishu pills and its mechanism maybe realized by regulating the miR and inflammatory factor.