Integration of pharmacodynamics and metabolomics to reveal rhubarb anthraquinone protection against nonalcoholic fatty liver disease rat model.

OBJECTIVES: The objective of the present study was to investigate the effect of Rhubarb anthraquinone (RA) on a high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) rat model, and explore potential biomarker and metabolic pathways by using the metabolomics method. MATERIALS AND METHODS: We established HFD rats as the NAFLD model. Forty Sprague-Dawley rats were randomly divided into a control group, model group, RA low-dose group, RA medium-dose group, and RA high-dose group, and evaluated the protective effect of RA on NAFLD by detecting biochemical indicators of serum and pathological changes of liver tissue. Investigating potential biomarkers and metabolic pathways connected with RA's protective effects against NAFLD by UHPLC-Q-TOF-MS untargeted metabolomics. RESULTS: The results showed that RA significantly reversed the increase of TG, TC, ALT, AST, and ALP (P < .05), the decrease of HDL-C (P < .05), and alleviated pathological conditions in NAFLD rats. Based on potential biomarker analysis, RA affected metabolic pathways such as fatty acids biosynthesis, bile acids biosynthesis, and pentose phosphate pathway, delaying the progression of NAFLD. CONCLUSION: RA improved blood lipid levels, liver function, and pathological conditions of NAFLD rats. Meanwhile, affected the metabolic pathways and regulated the synthesis of fatty acids and bile acids in NAFLD rats.

Effect of Pulicaria mauritanica on Glucose Metabolism and Glycogen Content in Streptozotocin-Induced Diabetic Rats.

AIMS: The study aimed to assess the antihyperglycemic activity of Pulicaria mauritanica. BACKGROUND: Pulicaria mauritanica is a medicinal and aromatic plant used for the treatment of many diseases such as inflammation, diabetes, and intestinal disorders. OBJECTIVE: The main goals of this present paper were to confirm the antihyperglycemic capacity of aqueous extract from Pulicaria mauritanica in normoglycemic and diabetic rats over a period of time (7 days of treatment). METHODS: The effect of the aqueous extract of Pulicaria mauritanica from aerial parts (AEPM) on glucose and lipid metabolism was tested using an acute test (single dose during 6 hours) and subchronic assay (repeated oral administration for seven days) at a dose of 60 mg/kg and the serum glucose levels were measured in normoglycemic and streptozotocin(STZ)-induced diabetic rats. In addition, the glycogen content in the liver, extensor digitorum longus (EDL), and soleus was evaluated. The antioxidant activity, phytochemical screening, and quantification of some secondary metabolites of this extract were also performed. RESULTS: AEPM at a dose of 60 mg/kg reduced the plasma glucose concentrations significantly in STZ-induced diabetic rats after a single oral administration (p<0.05). This lowering effect became more significant during the repeated oral administration in hyperglycemic rats (p<0.0001). Also, the findings showed that this plant exhibited a significant increase in liver and skeletal soleus muscle glycogen content in diabetic rats. AEPM revealed a remarkable antioxidant activity in addition to the presence of polyphenol compounds such as flavonoids, tannins, saponins, sterols, glucides, terpenoids, quinones, anthraquinones, and mucilage. CONCLUSION: The study shows that AEPM exhibits antihyperglycemic activity in diabetic rats, and it increases liver and muscle glycogen content.

Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

BACKGROUND: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE: We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS: We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS: Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. CONCLUSIONS: GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.

Natural anthraquinones as novel photosentizers for antiparasitic photodynamic inactivation.

BACKGROUND: Cutaneous leishmaniasis (CL) is a vector-borne disease caused by obligate protist parasites from the genus Leishmania. The potential toxicity as well as the increased resistance of standard treatments has encouraged the development of new therapeutical strategies. Photodynamic inactivation (PDI) combines the use of a photosensitizer and light to generate reactive oxygen species and kill cells, including microorganisms. Vegetal kingdom constitutes an important source of bioactive compounds that deserve to be investigated in the search of naturally occurring drugs with leishmanicidal activity. PURPOSE: The purpose of this study was to test the antiparasitic activity of PDI (ApPDI) of five natural anthraquinones (AQs) obtained from Heterophyllaea lycioides (Rusby) Sandwith (Rubiacae). To support our results, effect of AQ mediated-PDI on parasite´s morphology and AQ uptake were studied. Cytotoxicity on fibroblasts was also evaluated. STUDY DESIGN/METHODS: Two monomers, soranjidiol (Sor) and 5-chlorosoranjidiol (5-ClSor) plus three bi-anthraquinones (bi-AQs), bisoranjidiol (Bisor), 7-chlorobisoranjidiol (7-ClBisor) and Lycionine (Lyc) were selected for this study. Recombinant L. amazonensis promastigote strain expressing luciferase was subjected to AQs and LED treatment. Following irradiation with variable light parameters, cell viability was quantified by bioluminescence. Alteration on parasite's morphology was analyzed by scanning electron microscopy (SEM). In addition, we verified the AQ uptake in Leishmania cells by fluorescence and their toxicity on fibroblasts by using MTT assay. RESULTS: Bisor, Sor and 5-ClSor exhibited photodynamic effect on L. amazonensis. SEM showed that promastigotes treated with Bisor-mediated PDI exhibited a significant alteration in shape and size. Sor and 5-ClSor presented higher uptake levels than bi-AQs (Bisor, Lyc and 7-ClBisor). Finally, Sor and Bisor presented the lowest toxic activity against fibroblasts. CONCLUSION: Taking together, our results indicate that Sor presents the highest specificity towards Leishmania cells with no toxicity on fibroblasts.

In vitro study of the nephrotoxicity of total Dahuang (Radix Et Rhizoma Rhei Palmati) anthraquinones and emodin in monolayer human proximal tubular epithelial cells cultured in a transwell chamber.

OBJECTIVE: To examine changes in the morphology and physiological functions of human proximal tubular epithelial cells (HK-2 cells) caused by total Dahuang (Radix Et Rhizoma Rhei Palmati) anthraquinones (TDA) and emodin. METHODS: HK-2 cells were cultured on polycarbonate (PCF) membranes to form a complete monolayer of cells. A fluorescein isothiocyanate-dextran (FITC) permeability assay was conducted and secretion of γ-glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), N-acetyl-ß-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) was examined. The reabsorption of glucose and the excretion of para-aminohippuric acid (PAH) by HK-2 cells were also examined. The morphology of HK-2 cells was observed using optical microscopy and scanning electron microscopy. The cytoskeleton of HK-2 cells was observed under a fluorescence microscope. RESULTS: Compared with the results for the dimethyl sulfoxide group, treatment of cells with TDA and emodin showed statistically significant differences in the FITC leakage rate, the apical / basolateral ratio of LDH and GGT, and the secretion of GGT, LDH, NAG and KIM-1. At 64 µg/mL, TDA markedly inhibited blood glucose reabsorption and remarkably suppressed PAH excretion by HK-2 cells. Both TDA and emodin caused various degrees of damage to the morphology and cytoskeleton of HK-2 cells with the degree of damage correlating positively with the dosage of the tested substances. CONCLUSION: Both TDA and emodin caused damage to human renal proximal tubular epithelial cells at certain dosages. At the same dosage, TDA caused more severe damage than emodin to the HK-2 cells.

Toxicological studies of stem bark extract from Schefflera barteri Harms (Araliaceae).

BACKGROUND: The use of herbal medicines as complements or alternatives to orthodox medicines has been on the increase. There has been the erroneous belief that these medicines are free from adverse effects. Schefflera barteri is popularly used in the West region of Cameroon for the treatment of various diseases such as diarrhea, spasm, pneumonia and animals bite. Considering the ethnopharmacological relevance of this plant, this study was designed to investigate the possible toxic effects of the stem bark extract of S. barteri. METHODS: The extract was prepared by maceration of stem bark dry powder in methylene chloride/methanol mixture. Phytochemical analysis was performed by chemical reaction method. Oral acute toxicity study was carried out by administering single geometric increasing doses (2 to 16 g/kg body weight) of plant extract to Swiss albino mice. For sub-acute toxicity study, repeated doses (100, 200, 400 and 800 mg/kg bw) of plant extract were given to Wistar albino rats for 28 consecutive days by oral route. At the end of the treatment period, hematological and biochemical parameters were assessed, as well as histopathological studies. RESULTS: Phytochemical analysis of stem bark extract of S. barteri revealed the presence of anthocyanins, anthraquinons and saponins. Acute toxicity results showed that the LD50 was greater than 16000 mg/kg. Sub-acute treatment significantly (P < 0.05) increased the level of serum transaminase, proteins and HDL cholesterol. On the other hand, the extract significantly (P < 0.05) reduced the level of leucocytes as well as neutrophils, basophils and monocytes in female. No significant variation of serum creatinine, LDL cholesterol, serum triglycerides as well as liver, spleen, testicles and ovaries proteins was noted. Histopathological analysis of organs showed vascular congestion, inflammation of peri-portal and vacuolization of hepatocytes at the level of the liver. Leucocytes infiltration of peri-portal veins were noticed on lungs and liver cells as well as inflammatory peri-bronchial and basal membranes seminar tube merely joined on lungs and testis respectively. CONCLUSION: The results suggest that acute administration of the stem bark extract of S. barteri is associated with signs of toxicity, administration over a long duration provokes hepatotoxicity, testes and lungs toxicities.

[Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver].

OBJECTIVE: To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver. METHODS: One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis. RESULTS: Compared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT. CONCLUSIONS: Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee.

AIM: To evaluate clinical effectiveness of diacerein as an adjuvant to diclofenac sodium in treatment of Indian patients with symptomatic osteoarthritis (OA) knee. METHODS: This is a prospective, double-blind, placebo-controlled and intention-to-treat study. An initial washout period of 1 week, was followed by 3 months treatment period during which patients were randomly divided to receive either capsule diacerein 50 mg or matched placebo once daily for the first month and twice daily for the next 2 months with diclofenac sodium 75 mg sustained release tablet once daily given to both groups. Patients were observed for one more month, using paracetamol as rescue therapy. Treatment efficacy was assessed by a visual analogue scale (VAS) and the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, patient and physician global assessment of OA, daily paracetamol intake. RESULTS: Of 84 patients screened, 74 patients formed the intent-to-treat population (37 patients in each group). At baseline, both groups were comparable and at the third month functional index and pain intensity were better in the diacerein group (VAS 15.33 ± 5.07; WOMAC 15.9 ± 2.40) as compared to the placebo group (VAS 22.83 ± 6.90;WOMAC 36.8 ± 2.92; P < 0.05). When analyzed at the fourth month, improvement persisted in the iacerein group (VAS 14.83 ± 5.16; WOMAC 16 ± 2.5) as compared to placebo group (VAS 33 ± 7.72; WOMAC 48.26 ± 3.5; P < 0.05), demonstrating the carry-over effect of diacerein, which was confirmed by lesser paracetamol consumption in the diacerein group (5.967 ± 0.8087) as compared to the placebo group (12.433 ± 2.128; P < 0.05). CONCLUSION: Use of diacerein and diclofenac sodium together decreases pain and improves joint function significantly more than diclofenac alone in OA knee.

Exposure to sennoside-digoxin interaction and risk of digoxin toxicity: a population-based nested case-control study.

AIMS: Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity. METHODS AND RESULTS: This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94). CONCLUSION: The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.

Experimental study on the molecular mechanism of anthraquinone cathartics in inducing melanosis coli.

OBJECTIVE: To explore the significance of colonic epithelial cell apoptosis and tumor necrosis factor α (TNF-α) changing in pathogenesis of melanosis coli (MC) in guinea pig and the molecular mechanism of rhubarb (Rhu) in inducing the disease, by means of using different dosages of Rhu to induce the disease. METHODS: One hundred and forty-four male guinea pigs, clean grade, were randomized according to their body weight into 5 groups, the untreated normal group and the 4 Rhu groups treated, respectively, with different doses of Rhu, 3 g/kg·d for low dose (Rhu-l) group, 6 g/kg·d for moderate dose (Rhu-m) group, 12 g/kg·d for high dose (Rhu-h) group and 24 g/kg·d for super-high dose (Rhu-s) group via gastric infusion. All animals were sacrificed 60 days later, their viscera were taken for observing the pathologic and morphologic changes with HE, melanin and melatonin staining, and the apoptosis of colonic epithelial cells was detected with TUNEL stain and transmission electric microscopy. In addition, the levels of TNF-α in serum and colonic tissue were measured using ELISA and RT-PCR. RESULTS: The pathological changes of MC could be found by naked eye in all Rhu groups, especially apparent at caecum and proximal end of colon, but did not found in gallbladder, jejunum and ileum. In normal guinea pigs, the colonic membrane was pink in color with no apparent pigment deposition. Membranous color deepened in the Rhu groups depending on the dosage of Rhu used. MC scoring showed the highest scores revealed in the Rhu-s group (6.00±0.00), which was significantly different to those in the Rhu-l (3.86±0.69), Rhu-m (4.43±0.79) and Rhu-h groups (4.88±0.35, all P<0.05). Levels of cell apoptosis in colon and TNF-α in serum in all Rhu groups were higher than those in the normal group (P<0.01), but showed no significant difference among the Rhu groups (P>0.05). Moreover, a positive correlation was found in the degree of induced MC with apoptosis rate and TNF-α level. CONCLUSIONS: Rhu (anthraquinone purgatives) had apparent effect on inducing MC; its molecular mechanism is maybe to destroy intestinal mucosal barrier and advance proinflammatory factor TNF-α releasing, which leads to colonic epithelial cells apoptosis, and finally induce the change of MC due to the deposition of brown pigments, i.e. the macrophage phagocytized apoptotic body, on the colonic membrane.

[Study of introduction apoptosis of hepatocarcinoma cell SMMC-7721 by anthraquinone extracted from rubiqmnone and molecular mechanism].

OBJECTIVE: To research the effect of anthraquinone extracted from rubiqmnone on growth inhibition, introduction apoptosis and expression of relative gene of bcl-2 of hepatocarcinoma cell SMMC 7721, and provide the effective target of gene therapy. METHOD: The growth inhibition effect was detected by MTF. Morpholgy, DNA agarose gel electrophoresis and flow cytometry were used to observe the cell apoptosis. The effect of anthraquinone on bcl-2mRNA expression was analyzed by RT-PCR. RESULT: Anthraquinone could inhibit the growth of hepatocarcinoma cell SMMC 7721. The typical apoptosis cells were found by inverted microscope and common microscope. DNA agarose gel electrophoresis showed a typical apoptosis strip. G1 period of cell cycle had apoptosis peak of abnormal diploid by PI simple stain, and cell cycle stopped at G1 period. The apoptosis fuction of anthraquinone introdution hepatocarcinoma cell was further certified by Annexin V-FITC/PI. Anthraquinone could decrease the expression of bcl-2mRNA by RT-PCR. CONCLUSION: Anthraquinone can significantly inhibit growth of hepatocarcinoma cell and induce apoptosis. The mocular mechanism may be related to down-regulating the expression of bcl-2 gene.

Microcalorimetric assay on the antimicrobial property of five hydroxyanthraquinone derivatives in rhubarb (Rheum palmatum L.) to Bifidobacterium adolescentis.

It was found that the intestinal bacteria balance would be deteriorated by rhubarb especially in long term treatment. Bifidobacteria is one of the most common species of probiotics in human intestine. The suppression of this particular probiotic, such as Bifidobacterium adolescentis, one of the dominant anaerobes in the intestines of humans, might lead to imbalance of intestinal flora and is considered to be potentially riskful for human health. Hence, the inhibitory effects of the five main components of hydroxyanthraquinones (HAQs) contained in rhubarb on B. adolescentis growth were investigated by microcalorimetry to discover the suppression potential of rhubarb and the structure-function relationship of such HAQs. The value of the maximum power- output (P(max)) and slope (k) of the thermogenic growth curves of B. adolescentis were found of decrease in the presence of the five HAQs, while the peak time (T(p)) of the thermogenic curves were found to be delayed. The sequence of antimicrobial activity of the five HAQs is rhein>emodin>aloe-emodin>chrysophanol>physicion. The functional groups carboxyl, hydroxyl and hydroxylmethyl on phenyl ring in HAQs could improve the antimicrobial activity. The influence of substituent groups on anti- B. adolescentis activity might be related with the polarity and the sequence was carboxyl>hydroxyl>hydroxylmethyl>methyl and methoxyl.

Assessment of the renal protection and hepatotoxicity of rhubarb extract in rats.

AIM OF THE STUDY: Rhubarb is well used to treat chronic renal failure (CRF) in China and Japan, but recent studies reported that the anthraquinone derivatives contained in rhubarb had nephrotoxicity. In this investigation an attempt was made to assess the value and toxic potential of rhubarb to treat CRF. MATERIALS AND METHODS: Histopathologic and biochemical tests combined with toxicokinetic analysis were performed to investigate the nephrotoxic potential and protective effect of rhubarb extract. RESULTS: In normal rat groups, no death was observed and no renal lesion was found after repetitive administration of rhubarb for 3 weeks. The survival rate, pathologic conditions and biochemical indexes of CRF rats treated with rhubarb at two dosages were all improved and significant amelioration was found in the low dosage group compared to the untreated CRF group. Rhein was the mainly absorbable anthraquinone derivative into systemic circulation after oral administration and the area under curve of rhein in CRF groups was lower than that in normal groups at same dosage. CONCLUSIONS: After 3 weeks of administration of rhubarb extract, there was evidence of protective effect to CRF rats, while incidences of hepatotoxicity with minimal to mild hyaline droplets were also observed in normal rats.

[Study on processed senna found in health teas].

Sennoside A and B were detected in 21 commercial health tea products surveyed in 2000-2007, but there were 8 products in which the leaves could not be identified as senna because the leaves had become discolored. The results of assay of sennoside levels and TLC chromatograms suggested that processed senna had been used in these products. Next, with reference to tea and health tea manufacturing methods, pharmaceutical senna was roasted or wet-processed experimentally. The results indicated that the discolored leaves contained in commercial health tea were most likely derived from senna leaves. Moreover, sennosides in medicinal doses were detected in some processed senna samples, and were determined to have a cathartic action in mice. Based on morphological confirmation and the results of component analysis, including sennoside, the discolored leaves found in commercial health teas were therefore determined to be senna leaves. There may be possible health risks, including diarrhea.

Evaluation of symptomatic slow-acting drugs in osteoarthritis using the GRADE system.

BACKGROUND: Symptomatic slow-acting drugs (SYSADOA) have been largely studied over the last decade. The objective of this study is to prepare a document providing recommendations for the use of SYSADOA in osteoarthritis (OA). METHODS: The following interventions were taken into consideration: avocado/soybean unsaponifiables, chondroitin sulfate, diacereine, glucosamine sulfate, hyaluronic acid, oral calcitonin, risedronate, strontium ranelate. Recommendations were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The GRADE system is based on a sequential assessment of the quality of evidence, followed by assessment of the balance between benefits versus downsides and subsequent judgment about the strength of recommendations. RESULTS: Chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid have demonstrated pain reduction and physical function improvement with very low toxicity, with moderate to high quality evidence. Even if pre-clinical data and some preliminary in vivo studies have suggested that oral calcitonin and strontium ranelate could be of potential interest in OA, additional well-designed studies are needed. CONCLUSION: In the benefit/risk ratio, the use of chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid could be of potential interest for the symptomatic management of OA.

[Reversal effect of aloe emodin liposomes on cisplatin resistance line A549/DDP human lung adenocarcinoma cells].

OBJECTIVE: To determine the reversal effect of aloe emodin liposomes (AE-L) on cisplatin resistance human lung adenocarcinoma cell line A549/DDP. METHOD: The un-cytotoxic and cytotoxic concentration of AE-L, and un-cytotoxic concentration of E-L were determined by MTT. The sensitivity of cisplatin were determined by MTT assay in above 3 groups. The intracellular concentration of cisplatin was detected by inductively coupled plasma mass spectrometry (ICP-MS). RESULT: The maximum non-toxic concentration group of AE-L (2.0 mg x L(-1)) increased the sensitivity of cisplatin in A549/DDP, decreased IC50 of cisplatin in A549/DDP from 16.81 mg x L(-1) to 5.86 mg x L(-1), and the hyp-cytotoxic concentration (7.0 mg x L(-1) ) group's IC50 decreased to 4.34 mg x L(-1); AE-L groups significantly increased intracellular concentration of cisplatin in A549/DDP cells. CONCLUSION: The results showed that aloe emodin can reverse multidrug resistance (MDR) of A549/DDP cells and the mechanism might be associated with the increase of intracellular concentration of cisplatin.

Regionally differential effects of sennoside A on spontaneous contractions of colon in mice.

Sennosides, the most popular irritant laxatives, cause purgative actions in the intestine through biotransformation to rhein anthrone; however, the underlying mechanisms remain unclear. The purpose of this study was to define colonic motor actions of sennoside A with special reference to purgative action. Mice received a single oral dose of 30 mg/kg sennoside A, and the colon was removed about 6 hr later. Contractions of longitudinal and circular muscles were recorded using an isometric force transducer and a pressure transducer, respectively. In longitudinal muscle preparations, spontaneous contractions were augmented in distal colon compared to control. In circular muscle preparations, contractions were reduced in the proximal colon, but increased in the distal colon. Particularly in the proximal colon, the frequency of high-amplitude contraction was reduced. In the control group, non-adrenergic, non-cholinergic treatment decreased the amplitude of contractions in the proximal colon, but not in the distal colon. In the sennoside A group, non-adrenergic, non-cholinergic treatment only slightly depressed the amplitude of contractions in the proximal and distal colon. To confirm a causal relationship between luminal prostaglandin level and purgative action of sennoside A, the mice were treated with indomethacin. Significant changes induced by sennoside A were attenuated by indomethacin treatment. The present study indicates that spontaneous motility is inhibited by sennoside A in the proximal colon, but accelerated in the distal colon, and that effects are associated with luminal prostanoid level and only partially with cholinergic nerve mediation.