Efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis: A systematic review and meta-analysis.

OBJECTIVE: To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)- 6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events. CONCLUSION: TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation.

A hybrid platform featuring nanomagnetic ligand fishing for discovering COX-2 selective inhibitors from aerial part of Saussurea laniceps Hand.-Mazz.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea laniceps Hand.-Mazz. (Compositae) is a representative "snow lotus" herb well known in Chinese folk medicine to treat inflammation-related diseases such as arthritis. S. laniceps (SL) shows anti-inflammatory and analgesic potencies and contains various constituents potentially with cyclooxygenase-2 (COX-2) selective inhibition. The herb is a valuable source of natural alternatives to synthetic COX-2 selective nonsteroidal anti-inflammatory drugs, a common medication for rheumatoid arthritis (RA) and osteoarthritis (OA) reported with serious cardiovascular side effects. AIM OF THE STUDY: Based on an innovative drug screening platform, this study aimed to discover safe, effective COX-2 selective inhibitors from SL. MATERIALS AND METHODS: An enzyme-anchored nanomagnetic fishing assay was developed to separate COX-2 ligands from SL. Cell and animal models of cardiomyocytes, lipopolysaccharide-stimulated macrophages, rat adjuvant-induced arthritis, and anterior cruciate ligament transection-induced OA rats, were adopted to screen the single/combined ligands regarding toxicity and bioactivity levels. Molecular docking was employed to unravel binding mechanisms of the ligands towards COX-1 and COX-2. RESULTS: Four COX-2 selective compounds were separated from SL using optimized COX-2-functionalized magnetic nanoparticles. All the four ligands were proved with evidently lower cardiotoxicity both in vitro and in vivo than celecoxib, a known COX-2 selective inhibitor. Two ligands, scopoletin and syringin, exhibited potent anti-arthritic activities in rat models of RA and OA by alleviating clinical statuses, immune responses, and joint pathological features; their optimum combination ratio was discovered with stronger remedial effects on rat OA than single administrations. The COX-1/2 binding modes of the two phytochemicals contributed to explain their cardiac safety and therapeutic performances. CONCLUSIONS: The screened chemicals are promising to be developed as COX-2 selective inhibitors as part of treating RA and OA. The hybrid strategy for discovering therapeutic agents from SL is shown here to be efficient; it should be equally valuable for finding other active chemicals in other natural sources.

Expanding Patch Testing Beyond the Baseline Series: Usefulness of Customized Antimicrobials, Vehicles, and Cosmetics Series.

BACKGROUND: Testing cosmetics and their ingredients is essential to avoid missing relevant allergens and to monitor fluctuating incidence of hypersensitivity. OBJECTIVE: The aim of this study was to review the usefulness of patch testing with a customized antimicrobials, vehicles, and cosmetics (AVC) series over 15 years at a single Canadian site. METHODS: Between January 1, 2005, and December 31, 2019, patients suspected of having cosmetics allergy were patch tested with a 40-allergen AVC series in addition to the North American Contact Dermatitis Group standard screening series. We reviewed the patch test results of 2868 patients. RESULTS: We consecutively patch tested with the baseline series 6103 patients, of which 2868 (47%) were also tested with the AVC series. Of 53 different allergens that were tested at some point, 26 remained in the series throughout the 15-year span. The most common positive allergens were thimerosal (4.52%), polyvidone-iodine (2.25%), propolis (2.06%), sodium metabisulfite (1.94%), dodecyl gallate (1.53%), carmine (1.10%), lauryl glucoside (1.01%), sandalwood oil (0.7%), and tert-butylhydroquinone (0.7%). CONCLUSIONS: Although the expansion of the North American Contact Dermatitis Group standard screening series has decreased the yield from the AVC series from 21.1% to 13.9%, it still remains a useful adjunct for patients suspected of having cosmetics or disinfectants allergy.

Salidroside as a potential neuroprotective agent for ischemic stroke: a review of sources, pharmacokinetics, mechanism and safety.

Salidroside (Sal) is a bioactive extract principally from traditional herbal medicine such as Rhodiola rosea L., which has been commonly used for hundreds of years in Asia countries. The excellent neuroprotective capacity of Sal has been illuminated in recent studies. This work focused on the source, pharmacokinetics, safety and anti-ischemic stroke (IS) effect of Sal, especially emphasizing its mechanism of action and BBB permeability. Extensive databases, including Pubmed, Web of science (WOS), Google Scholar and China National Knowledge Infrastructure (CNKI), were applied to obtain relevant online literatures. Sal exerts powerful therapeutic effects on IS in experimental models either in vitro or in vivo due to its neuroprotection, with significantly diminishing infarct size, preventing cerebral edema and improving neurological function. Also, the findings suggest the underlying mechanisms involve anti-oxidation, anti-inflammation and anti-apoptosis by regulating multiple signaling pathways and key molecules, such as NF-κB, TNF-α and PI3K/Akt pathway. In pharmacokinetics, although showing a rapid absorption and elimination, bioavailability of Sal is elevated under some non-physiological conditions. The component and its metabolite (tyrosol) are capable of distributing to brain tissue and the later keeps a higher level of concentration. Moreover, Sal scarcely has obvious toxicity or side effects in a variety of animal experiments and clinical trials, but combination of drugs and perinatal use of medicine should be taken more attentions. Finally, as an active ingredient, not only is Sal isolated from diverse plants with limited yield, but also large batches of the products can be harvested by biological and chemical synthesis. With higher efficacy and better safety profiles, Sal could sever as a promising neuroprotectant for preventing and treating IS. Nevertheless, further investigations are still required to explore the pharmacodynamic and pharmacokinetic properties of Sal in the treatment of IS.

Polydatin for treating atherosclerotic diseases: A functional and mechanistic overview.

With the advancement of science and technology, the living standards of human beings have continuously improved, but the incidence and mortality from atherosclerosis worldwide have also increased by year. Although interventional surgery and the continuous development of new drugs have significant therapeutic effects, their side effects cannot be ignored. Polydatin, an active ingredient isolated from the natural medicine Polygonum cuspidatum, has been shown to have a prominent role in the treatment of cardiovascular diseases. Polydatin treats atherosclerosis mainly from three aspects: anti-inflammatory, regulating lipid metabolism and anti-oxidative stress. This article will review the pharmacological mechanism of polydatin in anti-atherosclerosis, the biological characteristics of Polygonum cuspidatum, the toxicology and pharmacokinetics of polydatin and will provide ideas for further research.

Post-transcriptional regulation activity through alternative splicing involved in the effects of Aloe vera on the Wnt/ß-catenin and Notch pathways in colorectal cancer cells.

Aloe vera (L.) Burm.f. is widely used as laxative drugs, cosmetics, and functional food due to a variety of therapeutic effects. However, several studies indicated a colonic carcinogenic activity of Aloe vera. But the underline mechanism has not been well clarified. This study aimed to explore the potential mechanism at the post-transcriptional level. Identification of Differential Expressed Alternative Splicing (DEAS) genes and events and the corresponding functional enrichment analyses were conducted on RKO cells after treated with Aloe vera aqueous extract and its two active components, aloin and aloesin. And RT-qPCR was conducted for validation. Results indicated that they induced 2200, 2342 and 2133 DEAS events, respectively. The GO enrichment and the COG classification results of DEAS genes showed that they were associated with transcription, as well as functions like signal transduction mechanisms. Moreover, DEAS genes related to the two colorectal cancerous pathways, Wnt and Notch pathways, were annotated. In conclusion, aloe extract, aloin and aloesin significantly regulated the DEAS profile of RKO cells. The colonic carcinogenicity of Aloe vera may due to its post-transcriptional regulatory activity through Alternative Splicing (AS) on genes, especially on Wnt-related and Notch-related key genes.

Benefits and Safety of Tripterygium Glycosides and Total Glucosides of Paeony for Rheumatoid Arthritis: An Overview of Systematic Reviews.

OBJECTIVE: To summarize the evidence from systematic reviews (SRs) on the benefits and safety of Tripterygium glycosides (TG) and total glucosides of paeony (TGP), commonly used to treat rheumatoid arthritis (RA) in China, for patients with RA. METHODS: SRs of randomized controlled trials (RCTs) on TG or TGP in treating RA were included, by searching 8 databases from their inception until December 2017. Two authors extracted data independently. We assessed the quality of SRs using AMSTAR and graded the quality of evidence according to the GRADE approach. RESULTS: Eleven SRs containing an average of 7.6 RCTs, involving a total of 7,012 participants were included in this overview. On the basis of included SRs, TG and TGP could improve the following indexes for RA patients: American College of Rheumatology (ACR) 20 response rate, ACR50 response rate and ACR70 response rate, swollen joint count, tender joint count, erythrocyte sedimentation rate and C-reactive protein. Moreover, TGP could reduce incidence of hepatotoxicity. The most common adverse effects of TG were gastrointestinal discomfort and gonad toxicity, while for TGP was mild to moderate diarrhea. The overall quality of evidence for these findings ranged from "low" to "moderate". CONCLUSIONS: TG and TGP might be 2 potentially effective complementary and alternative drugs for patients with RA. Nevertheless, due to gonad toxicity, TG should only be considered in elderly patients or patients without reproductive needs. More evidence from high quality RCTs and SRs is warranted to support the use of TG and TGP for RA patients.

Efficacy and safety of total glucosides of paeony combined with methotrexate and leflunomide for active rheumatoid arthritis: a meta-analysis.

Purpose: Total glucosides of paeony (TGP) have been confirmed to reduce hepatotoxicity caused by methotrexate (MTX) and leflunomide (LEF) in rheumatoid arthritis (RA). Nevertheless, high-quality evidence-based meta-analysis data on the issue are unavailable. This study aimed to evaluate the efficacy and safety of this combination treatment for RA. Materials and methods: PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials, Chinese Biomedical Literature database, China National Knowledge Internet, Wan Fang, and VIP were searched up to February 2019. Randomized controlled trials (RCTs) on the efficacy and safety of TGP combined MTX and LEF for RA were included. Results: Eight RCTs were included in the final meta-analysis. Pooled results showed better therapeutic effects against RA in the TGP-treated group (RR =1.10, 95% CI: 1.04 -1.16). The TGP+MTX+LEF group showed a reduced erythrocyte sedimentation rate (MD = -2.80 mm/h, 95% CI: -5.08 - -0.52), C-reactive protein level (MD = -4.17 mg/L, 95% CI: -7.84 - -0.51), and rheumatoid factor (MD = -12.09 IU/mL, 95% CI: -14.05 - -10.14). Besides, the combination treatment tended to benefit lipid profiles (total cholesterol: 95% CI: -1.27-0.06; triglycerides: 95% CI: -0.49 - -0.08; high-density lipoprotein cholesterol: 95% CI: 0.15-0.83; and low-density lipoprotein cholesterol: 95% CI: -0.54 - -0.02). Adverse events, hepatotoxicity in particular, significantly decreased (RR =0.55, 95% CI: 0.38-0.80) in the TGP group. Conclusion: Compared to MTX and LEF therapy, TGP combination treatment may be a more effective and safer strategy. It is advisable to apply TGP as an adjuvant given its hepatoprotective and possible lipid-regulating effect. However, further large-scale and high-quality clinical trials are warranted, and the efficacy of TGP in terms of its effect on lipid profiles should be further confirmed.

Total glucosides of paeony for the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Psoriasis is a common chronic relapsing immune-mediated inflammatory disease, the prevalence of which has increased in recent years. At present, there are many treatment methods available for the condition, but the curative effect is unsatisfactory. HYPOTHESIS/PURPOSE: This study aimed to evaluate the efficacy, adverse reactions, and recurrence rates of using paeoniflorin capsules for psoriasis treatment. STUDY DESIGN: systematic review and meta-analysis. METHODS: Randomized controlled trials comparing total glycosides of paeony (TGP) with other treatments for patients with psoriasis were retrieved by searching EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials electronic databases. Cochrane bias risk tool was used to evaluate the quality of randomized controlled trial (RCT) methodology. The primary outcome measure is the effective number. Secondary outcomes included psoriasis area and severity index (PASI), adverse reactions, recurrence, and inflammatory biomarkers. RESULTS: In all, 30 RCTs with 2,802 participants were included in this meta-analysis. The studies were generally of low methodological quality. Although there was no statistically significant difference between the use of TGP capsule alone and other monotherapies in the treatment of psoriasis (RR: 0.93; 95% CI: 0.76-1.15; p = 0.50), the addition of TGP to other therapies had an advantage over monotherapy with regard to the effective number (RR: 1.31; 95% CI: 1.26-1.37; p < 0.00001), PASI (RR: -3.40; 95% CI: -4.22,-2.57; p < 0.00001), adverse reactions, recurrence rate (RR: 0.42; 95% CI: 0.24-0.74; p = 0.002), and inflammatory inhibition (RR:-12.54; 95% CI: -18.50, -6.59; p < 0.0001). CONCLUSIONS: TGP can be used to treat psoriasis with reduced adverse reactions and recurrence rates. However, the mechanism of TGP in psoriasis treatment requires to be evaluated further in high-quality, large-sample, and rigorous clinical studies.

Liquiritinapioside - A mineralocorticoid-like substance from liquorice.

Surface plasmon resonance (SPR) analysis of the main components of liquorice was performed and a novel strong mineralocorticoid receptor (MR) agonist, namely liquiritinapioside (LA), whose the binding constant was 1.093 × 10-5 M, was reported. As a supplement, LA has been further demonstrated to have a strong MR binding capacity through competitive binding experiments (the enrichment factor of LA was 10.22%). This study also validated the activity of LA on H9c2 cells. The expression of collagen I and the results of Masson staining were used to determine the ability of this substance to cause H9c2 cell fibrosis. Moreover, western blotting was used to verify the mechanism of compound-induced myocardial fibrosis. Overall, the attained results showed that LA could induce the activation of the TGF-ß1/p38 MAPK signalling pathway through the MR to induce H9c2 cell fibrosis.

Influence of Sodium Glucose Cotransporter 2 Inhibition on Physiological Adaptation to Endurance Exercise Training.

CONTEXT: The combination of two beneficial antidiabetes interventions, regular exercise and pharmaceuticals, is intuitively appealing. However, metformin, the most commonly prescribed diabetes medication, attenuates the favorable physiological adaptations to exercise; in turn, exercise may impede the action of metformin. OBJECTIVE: We sought to determine the influence of an alternative diabetes treatment, sodium glucose cotransporter 2 (SGLT2) inhibition, on the response to endurance exercise training. DESIGN, PARTICIPANTS, AND INTERVENTION: In a randomized, double-blind, repeated measures parallel design, 30 sedentary overweight and obese men and women were assigned to 12 weeks of supervised endurance exercise training, with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: ≤10 mg/day). OUTCOME MEASUREMENTS AND RESULTS: Endurance exercise training favorably modified body mass, body composition (dual-energy x-ray absorptiometry), peak oxygen uptake (graded exercise with indirect calorimetry), responses to standardized submaximal exercise (indirect calorimetry, heart rate, and blood lactate), and skeletal muscle (vastus lateralis) citrate synthase activity (main effects of exercise training, all P < 0.05); SGLT2 inhibition did not influence any of these physiological adaptations (exercise training × treatment interaction, all P > 0.05). However, after endurance exercise training, fasting blood glucose was greater with SGLT2 inhibition, and increased insulin sensitivity (oral glucose tolerance test/Matsuda index) was abrogated with SGLT2 inhibition (exercise training × treatment interaction, P < 0.01). CONCLUSION: The efficacy of combining two beneficial antidiabetes interventions, regular endurance exercise and SGLT2 inhibition, was not supported. SGLT2 inhibition blunted endurance exercise training-induced improvements in insulin sensitivity, independent of effects on aerobic fitness or body composition.

Corilagin, a promising medicinal herbal agent.

Corilagin, a gallotannin, is one of the major active components of many ethnopharmacological plants. It was isolated from Caesalpinia coriaria (Jacq.) Willd. (dividivi) by Schmidt in 1951 for the first time. In the past few decades, corilagin was reported to exhibit anti-tumor, anti-inflammatory and hepatoprotective activities, etc. However, little attention was paid to its pharmacological properties due to the complicated and inefficient extract method. In recent years, with the development of extraction technology corilagin was much easier to obtain than before. Thus, people return to pay attention to its anti-tumor, hepatoprotective, and anti-inflammatory activities, particularly as an anti-tumor agent candidate. Our research team had focused on the distribution, preparation and anti-tumor activity of corilagin since 2005. We found corilagin showed good anti-tumor activity on hepatocellular carcinoma and ovarian cancer. What's more, corilagin showed a low level of toxicity toward normal cells and tissues. Due to the extensive attention that corilagin has received, we present a systematic review of the pharmacological effects of corilagin. In this review, we summarized all the pharmacological effects of corilagin with a focus on the molecular mechanism of anti-tumor activity and show you how corilagin affected the signaling pathways of tumor cells as well as its physicochemical properties, distribution and preparation methods.

Efficacy and safety of total glucosides of paeony combined with acitretin in the treatment of moderate-to-severe plaque psoriasis: a double-blind, randomised, placebo-controlled trial.

Although acitretin has been widely used for the treatment of psoriasis, additional safer and more effective approaches, including traditional Chinese medicine, are needed. To investigate the efficacy and safety of total glucosides of paeony (TGP) combined with acitretin in the treatment of moderate-to-severe plaque psoriasis. A randomised, double-blind, placebo-controlled, multi-centre clinical study was conducted. In total, 108 patients with moderate-to-severe plaque psoriasis were randomly assigned to treatment with "TGP plus acitretin" (group A) or "placebo plus acitretin" (group B) for 12 weeks. After 12 weeks of therapy, the percentage of patients achieving a 50% reduction in Psoriasis Area and Severity Index was 90% in group A and 70.5% in group B (p<0.05). The rate of serum alanine aminotransferase elevation was 6.25% in group A and 20.4% in group B (p<0.05). TGP is conducive to enhancing anti-psoriatic efficacy and reducing liver damage due to acitretin. TGP combined with acitretin is a safe and effective treatment approach for moderate-to-severe plaque psoriasis.

Allergenic Ingredients in Facial Wet Wipes.

BACKGROUND: Allergic contact dermatitis commonly occurs on the face. Facial cleansing wipes may be an underrecognized source of allergens. OBJECTIVE: The aim of this study was to determine the frequency of potentially allergenic ingredients in facial wet wipes. METHODS: Ingredient lists from name brand and generic facial wipes from 4 large retailers were analyzed. RESULTS: In the 178 facial wipes examined, a total of 485 ingredients were identified (average, 16.7 ingredients per wipe). Excluding botanicals, the top 15 potentially allergenic ingredients were glycerin (64.0%), fragrance (63.5%), phenoxyethanol (53.9%), citric acid (51.1%), disodium EDTA (44.4%), sorbic acid derivatives (39.3%), tocopherol derivatives (38.8%), polyethylene glycol derivatives (32.6%), glyceryl stearate (31.5%), sodium citrate (29.8%), glucosides (27.5%), cetearyl alcohol (25.8%), propylene glycol (25.3%), sodium benzoate (24.2%), and ceteareth-20 (23.6%)/parabens (23.6%). Of note, methylisothiazolinone (2.2%) and methylchloroisothiazolinone (1.1%) were uncommon. The top potential allergens of botanical origin included Aloe barbadensis (41.0%), chamomile extracts (27.0%), tea extracts (21.3%), Cucumis sativus (20.2%), and Hamamelis virginiana (10.7%). CONCLUSIONS: Many potential allergens are present in facial wet wipes, including fragrances, preservatives, botanicals, glucosides, and propylene glycol.

Clinical study of total glucosides of paeony for the treatment of diabetic kidney disease in patients with diabetes mellitus.

BACKGROUND AND AIM: Total glucosides of paeony (TGP), an active compound extracted from dried roots of Paeonia lactiflora Pall, have anti-inflammatory effects. This study investigated the efficacy and safety of TGP for treating diabetic kidney disease (DKD) in type 2 diabetes mellitus patients. METHODS: An open-label, prospective, randomized, parallel-group, single-site study involving 76 patients with DKD. Patients were randomized into two groups: losartan group (n = 38), treated with losartan 100 mg/day for 6 months and TGP group (n = 38), treated with TGP 1800 mg/day and losartan 100 mg/day for 6 months. Serum hs-CRP, MCP-1, and TNF-α were determined before and after treatment. Urinary albumin excretion rate (UAER), fasting blood glucose, serum creatinine, and lipid profiles were examined. RESULTS: At the end-point, UAER decreased in the TGP group compared with baseline. UAER in the losartan group decreased to a level lower than before treatment. The rate of decline in the losartan group was significantly lower than the TGP group. There were no significant differences in serum creatinine and albumin levels between TGP and losartan groups at the end-point. Serum hs-CRP, MCP-1, and TNF-α levels were significantly lower in both groups after treatment. After treatment, serum hs-CRP, MCP-1, and TNF-α in the TGP group decreased more than the losartan group. Positive correlations were observed between UAER and hs-CRP, MCP-1, and TNF-α. No statistically significant difference in side effects was observed between groups. CONCLUSION: Our study showed that TGP treatment could reduce the albuminuria and inflammatory markers in type 2 diabetes mellitus patients with DKD.

Cost-Effectiveness of Dapagliflozin as Add-On to Metformin for the Treatment of Type 2 Diabetes Mellitus in Greece.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that has been spread worldwide over the past three decades and associated with increased morbidity and mortality resulting in considerable socioeconomic implications for national healthcare systems. Effective management of disease is highly needed ensuring patients receive the best possible care within the available budget. The objective of this study was to evaluate the long-term cost-effectiveness of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, compared with a sulfonylurea (SU) or a dipeptidyl-peptidase-4 inhibitor (DPP-4i), when added to metformin, in T2DM patients inadequately controlled on metformin alone in Greece. METHODS: The published and validated Cardiff diabetes model, a lifetime micro-simulation model, was adapted to a Greek healthcare setting to determine the incidence of micro- and macro-vascular complications and diabetes-specific and all-cause mortality. Clinical, cost, and utility data were retrieved from literature and assigned to model parameters to calculate total quality-adjusted life-years (QALYs) and total costs as well as incremental cost-effectiveness ratios (ICERs). The analysis was conducted from the perspective of a third-party payer in Greece. Uncertainty surrounding important model parameters was explored with univariate and probabilistic sensitivity analyses (PSA). RESULTS: Over a patient's lifetime, dapagliflozin was associated with 0.48 and 0.04 incremental QALYs compared with SU and DPP-4i, respectively, at additional costs of €5142 and €756, respectively. The corresponding ICERs were €10,623 and €17,695 per QALY gained versus the treatment with SU and DPP-4i, respectively. Results were robust across various univariate and scenario analyses. At the defined willingness-to-pay threshold of €34,000 per QALY gained, PSA estimated that treatment with dapagliflozin had a 100 % and 79.7 % probability of being cost-effective relative to the SU and DPP-4i treatments. CONCLUSIONS: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment alternative for patients with T2DM whose metformin regimen does not provide sufficient glycemic control in a Greek healthcare setting.

Pharmacokinetics, Safety, and Tolerability of Amygdalin and Paeoniflorin After Single and Multiple Intravenous Infusions of Huoxue-Tongluo Lyophilized Powder for Injection in Healthy Chinese Volunteers.

PURPOSE: Huoxue-Tongluo lyophilized powder for injection (HTLPI), a traditional Chinese medicine preparation, is a compound of Persicae semen and Paeoniae Radix Rubra that is used mainly for treating blood-stasis obstruction syndrome in the acute stage of cerebral ischemic stroke. Amygdalin (AD) and paeoniflorin (PF) are 2 typical bioactive components in HTLPI and were selected as indicators for this pharmacokinetic study of HTLPI. The objective of this study was to investigate the safety profile, tolerability, and pharmacokinetic properties of AD and PF after single and multiple intravenous infusions of HTLPI in healthy Chinese volunteers. METHODS: Twenty-one healthy Chinese subjects were recruited for this open-label, single ascending-dose (3, 6, and 9 g) and multiple-dose (6 g, once daily) study. Safety profile was assessed by adverse events and physical examination throughout the study. Serial plasma and urine samples were analyzed by HPLC-MS/MS. Pharmacokinetic parameters of AD and PF were calculated using noncompartmental analysis. FINDINGS: In the single-dose phase of the study, the mean maximum plasma concentration and the mean area under the plasma concentration-time curve of AD and PF increased proportionally with each dose escalation. In the multiple-dose phase, the steady state was achieved by day 4 after multiple-dose administration of 6 g HTLPI. Mean pharmacokinetic parameters achieved on day 1 were similar to those on day 7. No significant accumulation was observed after repeat doses of 6 g HTLPI. Approximately 79.6% of the administered AD and 48.4% of the administered PF were excreted unchanged in urine within 24 hours. No serious adverse events were observed during the entire study. IMPLICATIONS: The pharmacokinetic properties of AD and PF were linear after a single intravenous infusion of HTLPI in the dose range of 3-9 g. No systemic accumulation was observed with repeat doses of HTLPI. Sex had no significant effect on the pharmacokinetic properties of AD and PF. Intravenous infusion of HTLPI was well tolerated in healthy Chinese subjects.

Dietary supplementation with purified citrus limonin glucoside does not alter ex vivo functions of circulating T lymphocytes or monocytes in overweight/obese human adults.

Overweight/obesity is associated with chronic inflammation and impairs both innate and adaptive immune responses. Limonoids found in citrus fruits decreased cell proliferation and inflammation in animal studies. We hypothesized that limonin glucoside (LG) supplementation in vivo will decrease the ex vivo proliferation of T cells and the production of inflammatory cytokines by monocytes and T cells. In a double-blind, randomized, cross-over study, 10 overweight/obese human subjects were served purified LG or placebo drinks for 56 days each to determine the effects of LG on immune cell functions. The percentage of CD14+CD36+ cells in whole blood was analyzed by flow cytometry. Peripheral blood mononuclear cells were isolated and activated with CD3 plus CD28 antibodies (T-lymphocyte activation) or lipopolysaccharide (monocyte activation). Interferon γ, tumor necrosis factor α, interleukin (IL) 2, IL-4, and IL-10 were measured in supernatants from activated T cells. Supernatants from activated monocytes were analyzed for the production of tumor necrosis factor α, IL-1ß, and IL-6. Peripheral blood mononuclear cells were prestained with PKH dye and activated with CD3 plus CD28 antibodies to determine the proliferative responses of CD4+ and CD8+ T lymphocytes by flow cytometry. No differences were observed for CD14+CD36+ monocyte populations, T-cell proliferation, or the production of T cell and monocyte cytokines between the 2 treatments. Thus, LG supplementation in vivo did not affect ex vivo functions of T cells and monocytes, whereas it decreased several circulating markers of hepatic inflammation as we previously reported.

Alp Rose stem cells, olive oil squalene and a natural alkyl polyglucoside emulsifier: Are they appropriate ingredients of skin moisturizers - in vivo efficacy on normal and sodium lauryl sulfate - irritated skin?.

Background/Aim: Since skin moisturization may be achieved by both actives and chosen carrier, plant stem cells, squalene and natural alkyl polyglucoside emulsifier may be potential components of contemporary cosmetic products. The aim of the study was in vivo evaluation of the skin irritation potential and the efficacy of Alpine Rose stem cells incorporated into li-posomes and olive oil squalene as ingredients of moisturizing creams, with respect to the novel emulsifier used for creams' stabilization. Methods: With the employment of noninvasive skin biophysical measurements, skin hydration (EC), transepi-dermal water loss (TEWL), erythema index (EI) and viscoelas-ticity were measured on 76 healthy volunteers. In the first phase, skin irritation after a 24-hour occlusion and the long-term efficacy of creams (a 21-day study) on healthy skin were evaluated. Phase II of the study focused on the cream efficacy assessment after a 6-day treatment of sodium lauryl sulfate-irritated skin. Results: After a 24-hour occlusion, there were no significant changes in the EI for any tested sample. In the second phase of the study, the EI was not significantly altered for the cream containing squalene, while the application of all active samples resulted in a significant reduction of TEWL. In both phases of the study an EC increase was recorded, espe-cially for the squalene-containing cream. Conclusion: Due to the lack of skin irritation and skin barrier impairment along with the marked hydration effect, it could be said that the in-vestigated actives incorporated into alkyl polyglucoside emulsi-fier-stabilized creams may be safely applied as ingredients for "tailor-made" cosmetic moisturizers intended for normal and dry skin care, whereas olive oil squalene could be used for the treatment of irritated or sensitive skin as well. [Projekat Ministarstva nauke Republike Srbije, br. TR34031]

[Study of screening pseudoallergenic substances of Shuanghuanglian injection].

In this study, chemistry, biology and pharmacology were combinated to screen pseudoallergenic substances of Shuang-huanglian injection (SHLI) so that to establish a scientific and systematic approach to screen pseudoallergenic substances of traditional Chinese medicine injections. The mouse pseudoallergic reaction models were used to screen the pseudoallergic reaction of SHLI's intermediate extract and the intermediate extract's component or ingredient. Among the three intermediates of Shuanghuanglian injection (extract of Scutellaria baicalensis, extract of Lonicera japonica, extract of Forsythia suspensa) , pseudoallergic action of Forsythia suspensa was the strongest, Forsythia suspesnsa's pseudoallergic reaction mainly associated with the composition with largerchemical polarity. Further it was found that forsythiaside A and arctiin which existed in the the composition with largerchemical polarity caused obvious pseudoallergic reactions. SHLI with removal forsythoside A with the technology of HPLC-MS displayed reduced pseudoallergic reaction and a significant improved safety. This study provided a scientific basis for SHLI process improvements and also offered idea and research foundation for screening pseudoallergenic substances injections in other TCM injections.