Possible therapeutic effect of carvacrol on asthmatic patients: A randomized,double blind,placebo‐controlled,Phase II clinical trial

The relaxant effects of carvacrol, a phenolic monoterpene, on tracheal smooth muscle and its preventive effect on asthmatic animals were reported. The effect of carvacrol in asthmatic patients was examined in the placebo group (Group P, n = 11) receiving placebo and treatment group (Group C, n = 12), which received carvacrol capsule (1.2 mg/kg/day) for 2 months in a double‐blind manner. Pulmonary function tests, respiratory symptoms, hematological indices, and high‐sensitivity C‐reactive protein (hs‐CRP) were measured before, 1 and 2 months after starting treatment. At the end of treatment period, Pulmonary function tests values in Group C were significantly increased (p < .05 to p < .001). Most respiratory symptoms were also significantly reduced in Group C at the end of 2‐month treatment (p < .05 to p < .001). Total and differential white blood cell (p < .05 to p < .001), as well as serum levels of hs‐CRP in Group C were also significantly reduced after 2‐month treatment with carvacrol (p < .001). Mean corpuscular hemoglobin concentration and hematocrit were changed in Group C (p < .05 and p < .01, respectively). However, in Group P, there was no significant changes in the evaluated parameters. Pulmonary function tests were increased but respiratory symptoms, inflammatory cells, and hs‐CRP were reduced in asthmatic patients who received carvacrol that indicates its therapeutic effect on asthma.     

The Effect of Zataria multiflora and its Constituent,Carvacrol, on Tracheal Responsiveness and Lung Pathology in Guinea Pig Model of COPD

The effects of Zataria multiflora (Z. multiflora) and its constituent, carvacrol, in guinea pigs model of chronic obstructive pulmonary disease (COPD) were examined. Animals were divided into control, COPD, COPD + drinking water containing three concentrations of extract of Z. multiflora (0.4, 0.8 and 1.6 mg/ml), COPD + drinking water containing three concentrations of carvacrol (60, 120 and 240 µg/ml) and COPD + dexamethasone (50 µg/ml). COPD was induced by exposing animals to cigarette smoke for 3 months. Emphysema as a pathological change of the lung and tracheal responsiveness were measured (n = 5 for control and COPD groups and n = 6 for another groups). Tracheal responsiveness (p < 0.05) and emphysema were significantly increased (p < 0.001) in COPD compared to the control group. Tracheal responsiveness in COPD groups treated with two higher concentrations of the Z. multiflora and three concentrations of carvacrol, and emphysema in treated with highest concentration of Z. multiflora and carvacrol were significantly improved compared to COPD group. Studied parameters were also significantly improved in the treated group with dexamethasone compared to COPD animals (p < 0.05 to p < 0.01). The results indicated a preventive effect of Z. multiflora extract and its constituent, carvacrol, on tracheal responsiveness and pathological changes of the lung. Copyright © 2015 John Wiley & Sons, Ltd.     

Piperine Decreases Binding of Drugs to Human Plasma and Increases Uptake by Brain Microvascular Endothelial Cells

We previously reported that piperine, an active alkaloidal principal of black and long peppers, enhances drug bioavailability by inhibiting drug metabolism. Another mechanism influencing drug availability/uptake is its free fraction. Since piperine is highly lipophilic, we hypothesize that it could also interact with drugs through binding displacement and influence their bioavailability. Accordingly, using equilibrium dialysis, we investigated whether piperine alters the binding of model drug ligands, that is flunitrazepam, diazepam, warfarin, salicylic acid, propranolol, lidocaine, and disopyramide to human plasma (n = 4). Since alterations in binding influence drug disposition, we also studied the effects of piperine on the uptake of plasma bound ³H‐propranolol and ¹⁴C‐warfarin by cultured bovine brain microvascular endothelial cells (BMECs). Piperine (1–1000 μM) increased the free fraction (fu) of both albumin and alpha‐acid glycoprotein bound drugs in a concentration‐dependent manner (p < 0.01). Moreover, piperine (10 μM) increased the uptake of ³H‐propranolol and ¹⁴C‐warfarin by BMECs (p < 0.01). In conclusion, our findings provide the first evidence that piperine displaces plasma bound drugs from both albumin and alpha‐acid glycoprotein and facilitates drug uptake across biological membranes (e.g. BMEC). Moreover, it is feasible that piperine may similarly facilitate the transport of drugs into tissues, in vivo, and alter both pharmacokinetics and pharmacodynamics of administered drugs. Copyright © 2017 John Wiley & Sons, Ltd.     

Astragalus membranaceus prevents daunorubicin‐induced apoptosis of cultured neonatal cardiomyocytes: role of free radical effect of Astragalus membranaceus on daunorubicin cardiotoxicity

Anthracyclines are antitumor antibiotics with significant activity against solid and hematologic malignancies. One problem preventing more widespread use has been the development of cardiotoxicity. To determine whether antioxidant agents can reduce the cardiotoxicity of anthracyclines, a herb Astragalus membranaceus was introduced, which has been widely used for the treatment of cardiovascular diseases in China and was confirmed to be an effective antioxidant agent recently. Pre‐treatment with Astragalus membranaceus significantly attenuated the daunorubicin‐induced increases of reactive oxygen species (p < 0.001), apoptosis (p < 0.05) and the secretions of LDH (p < 0.01) in cultured neonatal cardiomyocytes. Astragalus membranaceus also raised the EC₅₀ of daunorubicin 1.24‐fold. Compared with Astragalus membranaceus, N‐acetyl‐l ‐cysteine had similar effects on daunorubicin‐induced cell injury, however, superoxide dismutase reduced reactive oxygen species without attenuating apoptosis. The subcellular distribution of DNR was similar to the distribution of MitoTracker Red 580 in mitochondria, which was mainly in the cytoplasm around the nuclear membrane in cultured neonatal cardiomyocytes. In conclusion, the results suggested that Astragalus membranaceus is potentially protective against daunorubicin cardiotoxicity by decreasing free radical release and apoptosis in cultured neonatal cardiomyocytes. The main subcellular distribution of daunorubicin may be in the mitochondria. Copyright © 2009 John Wiley & Sons, Ltd.     

Complementary Usage of Rhodiola crenulata (L.) in Chronic Obstructive Pulmonary Disease Patients: The Effects on Cytokines and T Cells

Although chronic obstructive pulmonary disease (COPD) is an inflammatory disease predominantly involving T cells, no study of Rhodiola as an immunomodulator in COPD patients has been reported. In this study, COPD patients took Rhodiola crenulata 500 mg (n = 38) or placebo (starch/phosphate buffered saline) (n = 19) daily for 12 weeks and were compared with untreated, age‐matched, and sex‐matched non‐COPD control subjects. Our results showed that serum levels of IL‐2, IL‐10, and IFN‐γ in COPD patients before treatment are significantly higher than levels in non‐COPD controls (p < 0.05). A significant decrease in IFN‐γ was seen in the Rhodiola treatment group (p < 0.05) but not in the placebo group (p > 0.05). The results suggested that Rhodiola treatment had beneficial antiinflammation effects, lower COPD assessment test score and decreased high‐sensitivity C‐reactive protein, on COPD patients (p < 0.05). The effects of Rhodiola treatment on COPD patients were shown to decrease the IFN‐γ concentration and CD8⁺ count but increase the expressions of CD4⁺CD25⁺FOXP3⁺ and CD4⁺CD25⁺CD45⁺FOXP3⁺ in the blood significantly (p < 0.05). This is the first trial using Rhodiola as a complementary therapy for COPD patients. T cells play an important role in the pathogenesis of COPD through the increased expression of CD8⁺ T cells and IFN‐γ and may be a viable target for potential therapy. Copyright © 2014 John Wiley & Sons, Ltd.     

Effects of Curcumin on Serum Vitamin E Concentrations in Individuals with Metabolic Syndrome

Vitamin E is an important lipid‐soluble antioxidant. The aim of the present study was to investigate the effect of curcumin on serum vitamin E levels in subjects with metabolic syndrome (MetS). A total of 120 subjects aged 18–65 years old with MetS were recruited in this study according to the International Diabetic Federation Criteria. Included subjects were randomized into three groups: subjects receiving lecithinized curcumin (1 g/day equivalent to 200‐mg pure curcumin per day) for a period of 6 weeks )n = 40), patients receiving unformulated curcumin (1 g/day) for a period of 6 weeks )n = 40) and a control group receiving placebo for the same period (n = 40). Vitamin E was determined in all patients before and after the intervention using high‐performance liquid chromatography method. Results showed that curcumin has no improving effect on serum levels of vitamin E (p > 0.05). There were significant differences between pre‐trial and post‐trial levels of vitamin E/low‐density lipoprotein cholesterol ratio (p < 0.05), vitamin E/high‐density lipoprotein cholesterol ratio (p < 0.05), vitamin E/total cholesterol ratio (p < 0.01) and vitamin E/triglyceride ratio (p < 0.05) between the three groups of the study. Results of the present study did not suggest any improving effect of curcumin supplementation on serum vitamin E concentrations in subjects with MetS. Copyright © 2017 John Wiley & Sons, Ltd.     

Effects of saffron (Crocus sativus L.) supplementation on inflammatory biomarkers: A systematic review and meta‐analysis

The effect of saffron supplementation on subclinical inflammation remains inconclusive. We performed a systematic review and meta‐analysis to summarize available findings on the effect of saffron supplementation on inflammatory biomarkers (C‐reactive protein [CRP], tumor necrosis factor‐α [TNF‐α], and interleukin‐6 [IL‐6]) in adults. We searched PubMed/Medline, Scopus, Web of Science, and Google Scholar databases up to November 2019 using relevant keywords to identify eligible trials. All randomized controlled trials (RCTs) that examined the effect of oral saffron supplementation on plasma concentrations of CRP, TNF‐α, and IL‐6 were included. For each outcome, mean differences and SDs were pooled using a random‐effects model. Overall, eight RCTs were included in this meta‐analysis. The pooled results showed that saffron supplementation did not result in significant changes in serum CRP (weighted mean difference [WMD]: ?0.43 mg/L; 95% confidence interval [CI]: ?1.04 to 0.17; p = .16), serum TNF‐α (WMD: ?1.29 pg/mL; 95% CI: ?4.13 to 1.55; p = .37), and IL‐6 concentrations (WMD: 0.11 pg/mL; 95% CI: ?0.79 to 1.00; p = .81). Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin. Similarly, saffron was found to decrease TNF‐α in studies that recruited non‐diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day. We also found a significant non‐linear effect of saffron dosage on serum CRP concentrations (p_{non‐linearity} = .03). The overall results indicated that saffron supplementation did not affect inflammatory cytokines. Further high‐quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers.     

Curcuminoid Treatment for Knee Osteoarthritis: A Randomized Double‐Blind Placebo‐Controlled Trial

Treatment of osteoarthritis (OA) is challenging owing to the inefficacy and long‐term adverse events of currently available medications including non‐steroidal anti‐inflammatory drugs. Curcuminoids are polyphenolic phytochemicals with established anti‐inflammatory properties and protective effects on chondrocytes. The aim of this study is to investigate the clinical efficacy of curcuminoids in patients suffering from knee OA. A pilot randomized double‐blind placebo‐control parallel‐group clinical trial was conducted among patients with mild‐to‐moderate knee OA. Patients were assigned to curcuminoids (1500 mg/day in 3 divided doses; n = 19) or matched placebo (n = 21) for 6 weeks. Efficacy measures were changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS) and Lequesne's pain functional index (LPFI) scores during the study. There was no significant difference in age, gender, body mass index, and VAS, WOMAC and LPFI scores between the study groups at baseline (p > 0.05). Treatment with curcuminoids was associated with significantly greater reductions in WOMAC (p = 0.001), VAS (p < 0.001) and LPFI (p = 0.013) scores compared with placebo. With respect to WOMAC subscales, there were significant improvements in the pain and physical function scores (p < 0.001) but not stiffness score (p > 0.05). There was no considerable adverse effect in both groups. To conclude, curcuminoids represent an effective and safe alternative treatment for OA. Copyright © 2014 John Wiley & Sons, Ltd.     

Combination of Mangifera indica L. Extract Supplementation Plus Methotrexate in Rheumatoid Arthritis Patients: A Pilot Study

The purpose of the present study was to evaluate the possible therapeutic effects and the safety of Mangifera indica extract (Vimang tablets, 300 mg) combined with methotrexate (MTX) on reducing disease activity in rheumatoid arthritis (RA). Twenty patients with active RA underwent a year of treatment with MTX (12.5 mg/week) associated to non‐steroidal anti‐inflammatory drugs (NSAIDs) and/or prednisone (5–10 mg/day) were randomly allocated to the experimental group (n = 10), that received the extract supplementation (900 mg/day) or preceding usual treatment (n = 10) during 180 days. RA activity was evaluated using the tender and swollen joint counts, erythrocyte sedimentation rate, disease activity score‐28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment's efficacy was demonstrated with ACR criteria. Only the patients of MTX‐Vimang group revealed statistically significant improvement in DAS 28 parameters with respect baseline data but no differences were observed between groups. ACR improvements amounted 80% only in MTX‐Vimang group at the 90 days (p < 0.001). In MTX‐Vimang group, 100% of patients decreased NSAIDs administration (p < 0.01) and 70% of those eradicated gastrointestinal side effects (p < 0.01) ensuing of the preceding treatment. Other adverse effects were not reported. Copyright © 2013 John Wiley & Sons, Ltd.     

Pharmacokinetic interaction of single dose of piperine with steady‐state carbamazepine in epilepsy patients

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability‐enhancer. The present study aimed at evaluating the effect of piperine on the steady‐state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t‐test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC_0‐12hr (p < 0.001), average C_ss (p < 0.001), t_1\2el (p < 0.05) and a decrease in K_el (p < 0.05), in both the dose groups, whereas changes in K_a and t_1\2a were not significant. Cmax (p < 0.01) and t_max (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption. Copyright © 2009 John Wiley & Sons, Ltd.     

Efficacy of artichoke leaf extract in non‐alcoholic fatty liver disease: A pilot double‐blind randomized controlled trial

Non‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and is potentially treatable, though there are few therapeutic agents available. Artichoke leaf extract (ALE) has shown potential as a hepatoprotective agent. This study sought to determine if ALE had therapeutic utility in patients with established NAFLD. In this randomized double‐blind placebo‐controlled parallel‐group trial, 100 subjects with ultrasound‐diagnosed NAFLD were randomized to either ALE 600 mg daily or placebo for a 2‐month period. NAFLD response was assessed by liver ultrasound and serological markers including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and AST to platelet ratio index (APRI) score. Ninety patients completed the study (49 ALE and 41 placebo) with no side effects reported. ALE treatment compared with placebo: Doppler sonography showed increased hepatic vein flow (p < .001), reduced portal vein diameter (p < .001) and liver size (p < .001), reduction in serum ALT (p < .001) and AST (p < .001) levels, improvement in AST/ALT ratio and APRI scores (p < .01), and reduction in total bilirubin. ALE supplementation reduced total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, non‐high‐density lipoprotein cholesterol, and triglyceride concentrations (p = .01). This study has shown beneficial effects of ALE supplementation on both ultrasound liver parameters and liver serum parameters (ALT, AST, APRI ratio, and total bilirubin) in patients with NAFLD.     

Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: A randomized controlled trial

Recent reports indicated that curcumin had beneficial effects in animal models of liver injury and cirrhosis. Current study aimed to investigate the effects of curcumin supplementation in patients with liver cirrhosis. In this randomized double‐blind placebo‐controlled trial, 70 patients with liver cirrhosis aged 20–70 years were randomly divided into two groups to receive 1,000 mg/day curcumin (n = 35) or placebo (n = 35) for 3 months. Model for end‐stage liver disease (MELD) (i), MELD, MELD‐Na, and Child–Pugh scores were used to assess the severity of cirrhosis. Sixty patients (29 in the curcumin group and 31 in the placebo group) completed the study. MELD(i) (15.55 ± 3.78 to 12.41 ± 3.07), MELD (15.31 ± 3.07 to 12.03 ± 2.79), MELD‐Na (15.97 ± 4.02 to 13.55 ± 3.51), and Child–Pugh (7.17 ± 1.54 to 6.72 ± 1.31) scores decreased significantly in the curcumin group after 3‐month intervention (p < .001, p < .001, p = .001, and p = .051, respectively), whereas they increased significantly in the placebo group (p < .001, p < .001, p < .001, p = .001, respectively). Significant differences were only observed between the two groups in MELD(i), MELD, MELD‐Na, and Child–Pugh scores after 3‐month intervention (p < .001 for all of them). In this pilot study, beneficial effects of curcumin supplementation were observed in decreasing disease activity scores and severity of cirrhosis in patients with cirrhosis.     

Efficacy of a Proprietary Trigonella foenum‐graecum L. De‐Husked Seed Extract in Reducing Menopausal Symptoms in Otherwise Healthy Women: A Double‐Blind,Randomized, Placebo‐Controlled Study

Trigonella foenum‐graecum seed extract has demonstrated hormone modulatory activity, providing biological plausibility for relieving menopausal symptoms. The study aimed to assess efficacy of a standardized T. foenum‐graecum de‐husked seed extract in reducing menopausal symptoms in healthy aging women. The study was a double‐blind, randomized, placebo‐controlled trial that recruited 115 women aged 40 to 65 years of which 59 were allocated to active (n = 54 completed) and 56 to placebo (n = 50 completed). Active treatment was T. foenum‐graecum de‐husked seed extract, 600 mg per day for 12 weeks. Outcome measures included Menopause‐Specific Quality of Life (MENQOL) questionnaire, frequency of hot flushes and night sweats and serum estradiol levels. There was a significant reduction in menopausal symptoms in the active group compared with placebo as assessed by total MENQOL score (p < 0.001); reflected by significant improvements in the vasomotor (p < 0.001), psychosocial (p < 0.001), physical (p < 0.001) and sexual symptoms (p < 0.001) domains. Vasomotor outcomes correlated with hot flushes, the active group reporting significantly less daytime hot flushes and night sweats at 12 weeks (p < 0.001). The average estradiol levels were similar in both the active group and placebo group after treatment. This study demonstrated that this proprietary T. foenum‐graecum de‐husked seed extract may reduce menopausal symptoms in healthy women. Copyright © 2017 John Wiley & Sons, Ltd.     

Adjuvant Therapy with Bioavailability‐Boosted Curcuminoids Suppresses Systemic Inflammation and Improves Quality of Life in Patients with Solid Tumors: A Randomized Double‐Blind Placebo‐Controlled Trial

Curcuminoids are bioactive polyphenolics with potent antiinflammatory properties. Although several lines of in vitro and preclinical evidence suggest potent anticancer effects of curcuminoids, clinical findings have not been conclusive. The present randomized double‐blind placebo‐controlled trial aimed to evaluate the efficacy of curcuminoids as adjuvant therapy in cancer patients. Eighty subjects with solid tumors who were under standard chemotherapy regimens were randomly assigned to a bioavailability‐boosted curcuminoids preparation (180 mg/day; n = 40) or matched placebo (n = 40) for a period of 8 weeks. Efficacy measures were changes in the health‐related quality of life (QoL) score (evaluated using the University of Washington index) and serum levels of a panel of mediators implicated in systemic inflammation including interleukins 6 (IL‐6) and 8 (IL‐8), TNF‐α, transforming growth factor‐β (TGFβ), high‐sensitivity C‐reactive protein (hs‐CRP), calcitonin gene‐related peptide (CGRP), substance P and monocyte chemotactic protein‐1 (MCP‐1). Curcuminoid supplementation was associated with a significantly greater improvement in QoL compared with placebo (p < 0.001). Consistently, the magnitude of reductions in TNF‐α (p < 0.001), TGFβ (p < 0.001), IL‐6 (p = 0.061), substance P (p = 0.005), hs‐CRP (p < 0.001), CGRP (p < 0.001) and MCP‐1 (p < 0.001) were all significantly greater in the curcuminoids versus placebo group. In contrast, the extent of reduction in serum IL‐8 was significantly greater with placebo versus curcuminoids (p = 0.012). Quality of life variations were associated with changes in serum TGFβ levels in both correlation and regression analyses. Adjuvant therapy with a bioavailable curcuminoid preparation can significantly improve QoL and suppress systemic inflammation in patients with solid tumors who are under treatment with standard chemotherapy protocols. Copyright © 2014 John Wiley & Sons, Ltd.     

The Effects of Pre‐Exercise Ginger Supplementation on Muscle Damage and Delayed Onset Muscle Soreness

Ginger possesses analgesic and pharmacological properties mimicking non‐steroidal antiinflammatory drugs. We aimed to determine if ginger supplementation is efficacious for attenuating muscle damage and delayed onset muscle soreness (DOMS) following high‐intensity resistance exercise. Following a 5‐day supplementation period of placebo or 4 g ginger (randomized groups), 20 non‐weight trained participants performed a high‐intensity elbow flexor eccentric exercise protocol to induce muscle damage. Markers associated with muscle damage and DOMS were repeatedly measured before supplementation and for 4 days following the exercise protocol. Repeated measures analysis of variance revealed one repetition maximum lift decreased significantly 24 h post‐exercise in both groups (p < 0.005), improved 48 h post‐exercise only in the ginger group (p = 0.002), and improved at 72 (p = 0.021) and 96 h (p = 0.044) only in the placebo group. Blood creatine kinase significantly increased for both groups (p = 0.015) but continued to increase only in the ginger group 72 (p = 0.006) and 96 h (p = 0.027) post‐exercise. Visual analog scale of pain was significantly elevated following eccentric exercise (p < 0.001) and was not influenced by ginger. In conclusion, 4 g of ginger supplementation may be used to accelerate recovery of muscle strength following intense exercise but does not influence indicators of muscle damage or DOMS. Copyright © 2015 John Wiley & Sons, Ltd.     

Cinnamaldehyde,Carvacrol and Organic Acids Affect Gene Expression of Selected Oxidative Stress and Inflammation Markers in IPEC‐J2 Cells Exposed to Salmonella typhimurium

Essential oils and organic acids are used as feed additives to improve health status and reduce colonization with pathogens. Although bactericidal in vitro, concentrations achieved in the animal gut are probably not lethal to pathogens. The aim of this study was to investigate the effects of cinnamaldehyde, carvacrol and cinnamic, lactic and propionic acids on the ability of Salmonella typhimurium ATCC 14028 (ST) to invade intestinal epithelial cells (IPEC‐J2) and on the expression levels of immune related genes in the cells. The minimum inhibitory concentration (MIC) and non‐inhibitory concentration (NIC) were determined and influence on the invasion capacity of ST was investigated. The structure of fimbriae and flagella was analysed by electron microscopy, and expression levels of HSP70, IkBa, IL‐8 and IL‐10 in the IPEC‐J2 cells were carried out by q‐PCR. Cinnamaldehyde, carvacrol and cinnamic and propionic acids inhibited ST invasion but not cell viability, bacterial viability and motility or the development of flagella. Propionic acid and cinnamaldehyde in combination with cinnamic acid caused structural impairment of fimbriae. Cinnamaldehyde up‐regulated expression of HSP70 irrespective of the presence of organic acids or ST; exposure to carvacrol induced HSP70 only in the presence of propionic acid and ST. © 2016 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.     

Effects of Supplementation with Heracleum persicum Fruit Extract on Serum Lipids in Patients Undergoing Coronary Angiography: A Pilot Trial

Heracleum persicum Desf. Ex Fischer (Apiaceae) is a native medicinal plant in the Iranian traditional medicine and also a safe and common dietary spice. The present pilot study aimed to investigate the impact of supplementation with H. persicum fruits on serum lipid concentrations in a group of patients with minimal coronary artery disease. Subjects who were diagnosed with <50% luminal narrowing in any of the major coronary arteries in coronary angiography were recruited for this trial and were randomized to receive either H. persicum hydroalcoholic fruit extract (n = 15; 300 mg/day) or placebo (n = 12) for a period of 6 months. Serum concentrations of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and triglycerides were measured at baseline and at the end of study. No significant difference in concentrations of total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol was observed between H. persicum extract and placebo groups (p > 0.05). However, serum triglycerides levels were reduced after H. persicum extract supplementation in a borderline significant manner (p = 0.063). Short‐term supplementation with H. persicum fruit extract might be used as an adjunctive treatment for patients with hypertriglyceridemia. Copyright © 2014 John Wiley & Sons, Ltd.     

Hyptis pectinata: Redox Protection and Orofacial Antinociception

Hyptis pectinata L. Poit, known as ‘sambacaitá’, is used in Brazil to treat inflammatory and painful disorders. In this study, the antioxidant and orofacial antinociceptive properties of the aqueous extract of H. pectinata leaves (AEPH) were assessed using in vitro and in vivo models. Thus, AEPH reduced the 2,2‐diphenyl‐1‐picrylhydrazyl radical up to 72.10% with an EC₅₀ of 14.56 µg/ml. It also inhibited 40.80% of the lipoperoxidation induced by 2′‐azobis (2‐amidinopropane) dihydrochloride in the thiobarbituric acid‐reactive substances assay. The orofacial antinociceptive activity was evaluated in mice pre‐treated with AEPH (100, 200 and 400 mg/kg, p.o.) and morphine (5 mg/kg, i.p.), which received afterwards formalin‐ (20 µl, 2% solution, s.c.), glutamate‐ (40 µl, 25 mM, s.c.) and capsaicin‐ (20 µl, 2.5 µg, s.c.) to induce orofacial nociception. AEPH at all doses reduced (p < 0.001) the nociceptive response in the first (43–62%) and second (47–80%) phases of the formalin test. Besides, the effect of AEPH (400 mg/kg) was not changed in the presence of naloxone (1.5 mg/kg, i.p.), an opioid antagonist. AEPH significantly inhibited mice face rubbing for capsaicin (23–69%, p < 0.05) and glutamate (48–77%, p < 0.001) at all doses. The findings suggested the AEPH has peripheral and central antinociceptive activities, which are not related to opioid receptors. Copyright © 2012 John Wiley & Sons, Ltd.     

Inhibition of Proinflammatory Biomarkers in THP1 Macrophages by Polyphenols Derived From Chamomile,Meadowsweet and Willow bark

Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0–100 μM) were incubated with THP1 macrophages, and interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐alpha (TNF‐α) were measured. At concentrations of 10 μM, both apigenin and quercetin reduced IL‐6 significantly ( p < 0.05). Apigenin at 10 μM and quercetin at 25 μM reduced TNF‐α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL‐6 and TNF‐α production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts. Copyright © 2012 John Wiley & Sons, Ltd.     

Efficacy of mulberry leaf tablets in patients with mild dyslipidemia

Mulberry leaf is well known for its several biological effects. The purpose of this study was to evaluate the hypolipidemic effect of mulberry leaf in non‐diabetic patients with mild dyslipidemia. A within‐subjects research design was conducted at the out‐patient clinic in Thailand. Twenty‐three patients who met the NCEP ATP III criteria guideline for dyslipidemia and failed a 4 week diet therapy were enrolled and assigned to receive three tablets of 280 mg mulberry leaf tablet three times a day before meals for a period of 12 weeks. Routine blood analyses including lipid parameters and liver function tests were performed every 4 weeks. At 4 and 8 weeks of mulberry leaf tablet therapy, triglyceride was significantly decreased by 10.2% (p < 0.05) and 12.5% (p < 0.05), respectively, from baseline. At the end of the study, total cholesterol, triglyceride and LDL were significantly decreased by 4.9% (p < 0.05), 14.1% (p < 0.05) and 5.6% (p < 0.05), respectively, from baseline, whereas HDL was significantly increased by 19.7% (p < 0.05). Even though some patients experienced side effects such as mild diarrhea (26%), dizziness (8.7%) or constipation and bloating (4.3%), mulberry leaf tablet therapy is still capable and safe in reducing cholesterol levels and enhancing HDL in patients with mild dyslipidemia. Copyright © 2010 John Wiley & Sons, Ltd.