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Background Lignans are large group of polyphenols that are formed by the coupling of two coniferyl alcohol residues. Based on their origin, lignans are broadly grouped into plant lignans such as isolariciresinol, secoisolariciresinol diglucoside, lariciresinol, and matairesinol; and mammalian lignans such as enterodiol and enterolactone. Based on the oxidation level of the lignan skeleton, they are also categorized into numerous groups such as dibenzylfuran, dibenzylbutyrolactol, dihydroxybenzylbutane, arylnaphtalene and aryltetraline lactone derivatives. Depending on structural type and concentration, numerous dietary lignans have been shown to possess biological activities including protective effect against diseases such as hormone-dependent tumors and cardiovascular diseases. Also, they display antioxidant properties in tissues and organs including the liver and the brain, lignans are found in most fiber-rich seeds such as sesame and pumpkin, and grains including barley, wheat, oats and rye. Scope and approach This paper focus on the metabolism in humans, and recent studies on the antioxidant and possible prooxidant effects of lignans at three levels: in vitro, in vivo in animals and clinical studies. Key Findings and Conclusions: Most of the studies investigating the antioxidant effect of lignans were in vitro and animal models and only five clinical trials were found; one evaluating the effect of enterolactone on low-density lipoprotein (LDL) peroxidation and four investigating the effects of plant lignans including flaxseed lignan components, secoisolariciresinol and sesamin on lipid peroxidation. So, lignans seem to be a valuable source for identifying new molecules for preventing various diseases especially cardiovascular disorders. Since most of studies are preclinical, however, further clinical trials are required to achieve more conclusive results.

Summary Background & aims Type 2 diabetes mellitus (T2DM) is a metabolic disorder affecting a growing number of patients all over the world. T2DM complications are positively associated with HbA1c which is a long-term glycemic marker. Medicinal plants and their isolated phytochemicals have been extensively used as dietary supplements for the management of chronic disorders including T2DM. Current paper aims to review clinical trials evaluated the effect of phytochemicals for long-term management of T2DM considering the HbA1c level. Methods Electronic databases including PubMed, Scopus and Cochrane were searched using the keywords “phytochemical”, “extract”, “herb”, or “plant” and “HbA1c” or “glycosylated hemoglobin” in the title/abstract from the date of inception until May 2017. English and Persian language papers were included. References of the retrieved papers were also screened for relevant studies. Results Of 2435 studies, 39 relevant clinical trials were finally included in which phytochemicals including berberine, curcumin, catechin, silymarin, resveratrol, pycnogenol, isoflavones, lignans, isohumulone, saponins, corn bran hemicellulose and pinitol were examined. Berberine and silymarin had the strongest evidence regarding their effectiveness in long-term management of HbA1c; however, lack of enough toxicological studies suggests to stay on the safe side for the administration of these agents in diabetic patients. Conclusions Current data regarding the efficacy of other phytochemicals are still controversial due to small follow-up period, methodological problems and small sample size. Future well-designed clinical trials are necessary to confirm the safety and efficacy of phytochemicals for long-term glycemic control of diabetic patients.

Type 2 diabetes mellitus (T2DM) is a metabolic disorders characterized by insulin resistance and β-cell dysfunction with an increasing worldwide incidence. Several studies have revealed that long-term glucotoxicity results in β-cell failure and death through induction of endoplasmic reticulum (ER) stress. Owing to the chronic progression of T2DM and the low effectiveness of antidiabetic drugs in long-term use, medicinal plants and their secondary metabolites seem to be the promising alternatives. Here we have provided a comprehensive review regarding the role of phytochemicals to alleviate ER stress in T2DM. Ginsenoside compound K, baicalein, quercetin, isopulegol, kaempferol, liquiritigenin, aspalathin, and tyrosol have demonstrated remarkable improvement of T2DM via modulation of ER stress. Arctigenin and total glycosides of peony have been shown to be effective in the treatment of diabetic retinopathy through modulation of ER stress. The effectiveness of grape seed proanthocyanidins and wolfberry is also shown in the relief of diabetic neuropathy and retinopathy. Resveratrol is involved in the prevention of atherosclerosis via ER stress modulation. Taken together, the data described herein revealed the capability of herbal constituents to prevent different complications of T2DM via a decrease in ER stress which open new doors to the treatment of diabetes.

Endometriosis is an estrogen-dependent disease with inflammatory lesions at extra-uterine sites, causing pelvic pain and fertility reduction. Conventional therapies primarily focus on reducing systemic levels of estrogens; however, they do not have desirable effectiveness and possess considerable side effects. Therefore, there is a growing interest in the use of herbal medicine for the treatment of endometriosis. In this paper, electronic databases including PubMed, Scopus, Cochrane library and Google Scholar were searched to obtain any studies evaluating any herbal products in the management of endometriosis. Data were collected from 1980 to 2018. Most of studies investigating the effect of herbal medicines in endometriosis were in vitro and animal and only three clinical trials were found; one on Pinus pinaster bark extract (Pycnogenol) and two on Chinese herbal formulas. The studies on phytochemicals had mostly focused on polyphenolic compounds (epigallocatechin-3-gallate, genistein) and sesquiterpenes (β-caryophyllene, parthenolide). Various molecular mechanisms of action have been involved in beneficial effects of herbal medicines and phytochemicals including anti-inflammatory (via reduction of proinflammatory cytokines such as interleukin -1, interleukin -6, interleukin -8, transforming growth factor-beta, tumor necrosis factor-α, nuclear factor-kappa B, growth factors, monocyte chemoattractant protein-1), antioxidant (through downregulation of hydrogen peroxide, malondialdehyde, reactive oxygen species and upregulation of superoxide dismutase), anti-proliferative and apoptotic (via enhancing Bcl-2-associated X protein/ B-cell lymphoma-2 and caspase3, 8 and 9 activity), anti-angiogenic (by downregulation of vascular endothelial growth factor receptors/ vascular endothelial growth factor), anti-invasive (via decreasing expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and matrix metalloproteinases), immunomodulatory, and estrogen modulating activities. So, medicinal plants seem to be a valuable source for identifying new drugs for treatment of endometriosis; however, since most of studies are preclinical, further clinical trials are required to achieve more conclusive results.

Ethnopharmacological relevance Tragopogon graminifolius (T. graminifolius) from Asteraceae family has been used as a remedy in Persian traditional medicine for the treatment of various disorders such as wound healing. Aim of the study The purpose of this study is to investigate the compounds of T. graminifolius, which are responsible for its wound healing activity. Materials and methods The experiment was performed in three phases; each phase consisted of fractionation of extracts followed by scratch assay. The results of the scratch assay were expressed using scratch closure index (SCI), representing the contraction of scratch. Results In phase I, Ethyl acetate fraction (E) showed the maximum SCI (61.7 ± 3.5) that was selected for more fractionation in the next phase. In phase II, 12 fractions were obtained and labeled as fractions E- A to L, respectively. Based on the SCI of fractions, EF (SCI=68.9 ± 0.6) was the most active fraction in phase II and selected for further fractionation in phase III. In phase III, 8 fractions were resulted by fractionation of EF and labeled as EF- 1–8. Fraction EF5 with the highest SCI (30.8 ± 3.0) was the most effective fraction and Luteolin was the main component. Luteolin significantly improved viability of fibroblast cells and increased cell population that was accompanied by decreased cell apoptosis. Luteolin-induced cell number increase in the S and G2M phases of the cell cycle, further confirms the proliferative effect of this compound. Conclusion The results showed that the total extract and fractions of T. graminifolius stimulate proliferation and migration of skin fibroblast cells and Luteolin is one of the active compounds responsible for these effects.

Resveratrol is a natural dietary phenolic compound which is extensively present in many edible fruits, including grape, berries, pomegranates, and peanuts. Reseveratrol has a broad spectrum of biological activities including anti-aging, chemopreventive, anti-carcinogenic, anti-inflammatory and antioxidant effects and thus it is effective in related diseases. Particularly, the positive effects of resveratrol in neuropsychological diseases have been proven in in-vitro and in-vivo studies. Some clinical trials have reported that resveratrol possesses preventive and therapeutic effects in cognitive disorders. Therefore, the current systematic review and meta-analysis aimed to assess the effects of resveratrol on cognition and memory performance as well as mood state. Electronic databases including Scopus, PubMed, Science Direct, and Cochrane library were searched with the keywords "Memory", "Cognitive", "Cognition" or "Mood" with "Resveratrol" until June 2017. Only clinical studies were included in this review. We have provided the most reliable evidence to date counting results obtained from 226 individuals from four randomized clinical trials evaluating the mentioned specific effects of resveratrol. The results of this meta-analysis showed that resveratrol has no significant effect on memory and cognitive performance assessed by auditory verbal learning tests. Two parameters of Profile of Mood States (POMS) including vigor and fatigue, decreased significantly by resveratrol. However, decrease in other parameters of POMS including tense/anxiety, depression, anger, and confusion by resveratrol was not significant. The key findings from this meta-analysis are that resveratrol has no significant impact on factors related to memory and cognitive performance, including learning ability, delayed recall, retention, and recognition with all effect sizes non-significant and effectively at zero. However, it has the potential to enhance mood. Further randomized, controlled trials are needed to achieve more conclusive results.

Ethnopharmacological relevance Herb–drug interactions are of great concern in health practices. Curcumin is a natural polyphenol extracted from turmeric, a spice widely used all over the world. Curcumin is clinically used due to its acceptable safety profile and therapeutic efficacy. Aim of the study Current paper aims to highlight the effect of curcumin on concomitantly used drugs. Methods Electronic databases including PubMed, Scopus and Science Direct were searched with the keywords "curcumin" in the title/abstract and "drug interaction," "drug metabolism," "cytochrome," "P-glycoprotein" and "P450" in the whole text. Results Curcumin can induce pharmacokinetic alterations such as changes in Cmax and AUC when concomitantly used with pharmacological agents like cardiovascular drugs, antidepressants, anticoagulants, antibiotics, chemotherapeutic agents, and antihistamines. The underlying mechanisms of these interactions include inhibition of cytochrome (CYP) isoenzymes and P-glycoprotein. There is only one clinical trial which proved a significant alteration of conventional drugs in concomitant use with curcumin indicating the need for further human studies. Conclusions Although in vitro and in vivo studies do not provide enough evidence to judge the clinical drug interactions of curcumin, physicians must remain cautious and avoid drug combinations which may lead to curcumin-drug interactions.

Ethnopharmacological relevance The genus Tamarix L., with the common name of tamarisk, consists of more than 60 species of halophyte plants which are used for medicinal purposes such as infections, wounds, and liver and spleen disorders by local people mostly in Asian and African countries. Aim of the review In spite of the potential health benefits of Tamarix spp., the plant is not yet well-known in modern medicine; thus, the aim of the present review is to provide a critical appraisal of the current state of the art regarding the ethnomedicinal uses, phytochemistry, and pharmacological properties of Tamarix spp. Materials and methods Electronic databases (Medline, Cochrane library, Science Direct, and Scopus) were searched with the words “Tamarix” and “Tamarisk” to collect all available data regarding different Tamarix species from the inception until May 2019. Results Tamarix spp. is traditionally used for gastrointestinal disorders, wounds, diabetes, and dental problems. Phenolic acids, flavonoids, and tannins constitute the main phytochemicals of these plants. Preclinical pharmacological evaluations have demonstrated several biological activities for Tamarix spp. including antidiabetic, hepatoprotective, wound healing, and anti-inflammatory; however, no clinical evidence have yet been provided to support the health benefits of these plants. Conclusions Tamarix spp. are plants rich in polyphenolic compounds with valuable medicinal properties; though, there are several methodological problems such as lack of a mechanistic approach and taxonomic ambiguities in the current available data. High-quality preclinical studies, as well as well-designed clinical trials are necessary to confirm the safety and efficacy of these plants in humans.

article Objective: The aim of this meta-analysis was to investigate whether statin therapy is associated with blood pressure (BP)-lowering in patients with or without hypertension. Background: The beneficial effects of statins on the cardiovascular system may in part be related to effects beyond lipid-lowering. It has been suggested that statins may reduce BP; however the available data are still ambiguous and often conflicting. Methods: Data from Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for the years 1966-January 2012 were searched for studies that investigated the effect of statins on BP in normotensive or in hypertensive subjects. We included all randomized controlled clinical trials that investi- gated this effect. Changes in systolic and diastolic BP were the key outcomes of interest. Results: The final analysis included 18 trials and 5628 subjects (4692 normotensive and 936 hypertensive patients) randomized to receive either statins or placebo. The weighted mean difference of systolic (ΔSBP) and diastolic blood pressure (ΔDBP) in normotensive patients for the 11 statin trials included were 0.03 (95% CI: −0.95-1.02; p = 0.95) and −0.28 (95% CI: −0.80-0.24; p = 0.29), respectively. For hypertensive patients treated with statins (8 trials) the weighted mean difference of ΔSBP and ΔDBP were 1.45 (95% CI: −0.49-3.39; p = 0.14) and −1.32 (95% CI: −3.93-1.28; p = 0.32) respectively. Conclusions: Despite previous suggestions statin therapy in normotensive or hypertensive patients does not lead to significant reductions in systolic or diastolic BP.

Background Findings from clinical studies of the efficacy and tolerability of nicotine preparations in maintaining remission of ulcerative colitis (UC) have been inconsistent. Objectives This systematic review and meta-analysis aimed to assess the efficacy and tolerability of nicotine preparations in inducing remission in UC. Methods A literature search (1966August 2010) of Scopus (EMBASE), PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted for clinical trials that investigated the efficacy and/or tolerability (any adverse events [AEs] and withdrawals due to AEs) of any nicotine preparation for the induction of remission in UC. Results The electronic searches yielded 788 items. Of these, 3 placebo-controlled trials representing 233 patients with UC and 2 randomized controlled trials that compared nicotine to corticosteroids in 81 patients with UC were included in meta-analysis. The summary relative risks (RRs) (95% CI) in comparing nicotine to placebo were 1.40 (0.63–3.12) ( P = NS) for clinical remission, 1.95 (1.38–2.78) ( P P = NS) for withdrawal due to AEs. The summary RRs in comparing nicotine to corticosteroids (prednisolone/prednisone) were 0.74 (0.5–1.09) ( P = NS) for clinical remission in 2 trials and 2.28 (0.76–6.83) ( P = NS) for withdrawal due to AEs. Conclusion The findings from this meta-analysis do not support the efficacy or tolerability of nicotine preparations in inducing remission in UC.

Phosphodiesterase inhibitors (PDEIs) are a class of drugs that are widely used because of their various pharmacological properties including cardiotonic, vasodilator, smooth muscle relaxant, antidepressant, antithrombotic, bronchodilator, antiinflammatory and enhancer of cognitive function. In the recent years, interest in drugs of plant origin has been progressively increased. Some pharmacologically active substances that come from plants demonstrate PDEI activity. They mainly belong to alkaloids, flavonoids, and saponins. In this review, studies on herbal PDEI were reviewed and their possible therapeutic applications were discussed. Screening plants for PDE inhibitory activity may help to develop standardized phytotherapeutic products or find new sources for new lead structures with PDEI pharmacological activity. The studies discussed in this paper are mainly in vitro and for more reasonable and conclusive results, it is required to conduct in vivo and finally human and clinical tests.

5-ASA drugs are commonly used for management of inflammatory bowel disease (IBD) during pregnancy. The safety of drug therapy for IBD during pregnancy is an important clinical concern. The present meta-analysis was performed to explore the risk of adverse pregnancy outcomes in women with IBD following exposure to 5-ASA drugs (mesalazine, sulfasalazine, balsalazide, and olsalazine). Bibliographic databases were searched upto June 2007 for studies investigating pregnancy outcomes in women with IBD following exposure to any 5-ASA drugs. The outcomes of interest were congenital abnormalities, stillbirth, spontaneous abortion, preterm delivery, and low birth weight. The odds ratios (OR) and confidence interval (CI) for the individual studies were pooled and heterogeneity analysis was performed. Seven studies with a total of 2200 pregnant women with IBD were included; 642 received 5-ASA drugs (mesalazine, sulfasalazine or olsalazine) and 1158 received no medication. The OR was found 1.16 (95% CI: 0.76-1.77, P=0.57) for congenital abnormalities, 2.38 (95% CI: 0.65-8.72, P=0.32) for stillbirth, 1.14 (95% CI: 0.65-2.01, P=0.74) for spontaneous abortion, 1.35 (95% CI: 0.85-2.13, P=0.26) for preterm delivery, and 0.93 (95% CI: 0.46-1.85, P=0.96) for low birth weight. In conclusion, this meta-analysis suggest that there is no more than an 1.16-fold increase in congenital malformations, an 2.38-fold increase in stillbirth, an 1.14-fold increase in spontaneous abortion, an 1.35-fold increase in preterm delivery, and an 0.93-fold increase in low birth weight.

Organophosphorus (OP) compounds are cholinesterase-inhibiting chemicals used as pesticide. Exposures to OPs cause a significant number of poisonings and deaths each year. One of the reported adverse effects in human exposure to OPs is hyperglycemia. Animal studies have also shown altered glucose homeostasis following acute or chronic exposures to OPs. The objective of this paper is to provide a brief review of the mechanisms involved in the OP-induced glucose homeostasis alteration. To reach this objective, a search of the literature using Medline/Index Medicus, Scopus, and Chemical Abstract were performed, most of relevant citations were studied and summarized. To better understand the nature of glucose homeostasis, the principles of glucose production, metabolism, and its hormonal control have been discussed. Collection of theses studies support the conclusion that hyperglycemia is the outcome of acute or chronic exposure to OPs. OPs can influence body glucose homeostasis by several mechanisms including physiological stress, oxidative stress, inhibition of paraoxonase, nitrosative stress, pancreatitis, inhibition of cholinesterase, stimulation of adrenal gland, and disturbance in metabolism of liver tryptophan.

Serotonin reuptake inhibitors (SRIs) are extensively used in management of clinical depression. Reports vary about the risk of these drugs during pregnancy. To determine the risk of exposure to SRIs, we pooled data from multiple clinical studies that investigated obstetrical outcomes in women exposed to this group of drugs during pregnancy. Studies were identified by search of PUBMED, OVID, and SCOPUS databases and the data were derived from 1990 to 2005 (August). Types of outcome investigated were spontaneous abortion, major malformations, cardiovascular malformations, and minor malformations. The criteria for inclusion of studies in this meta-analysis were exposure of women to any therapeutic dosage of SRI (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) during pregnancy. Our results find that SRIs do not increase the risk of major, cardiovascular and minor malformations but do increase the risk of spontaneous abortion significantly.

Objective To find scientific reasons for adverse events reported in traditional Iranian medicine (TIM) following administration of aqueous extract of Portulaca oleracea L. seed including itching and tingling of whole body, tachycardia, anxiety, dyspnea and severe nausea. Methods Electronic databases including PubMed, Scopus, and Web of Science were searched up to April 2013 to find papers focused on phytochemistry and biological activities of this plant. Results Among chemical constituents present in Portulaca oleracea , catecholamines, adenosine and niacin can cause adverse events similar to those reported in TIM. Conclusion Because of the short duration of action of adenosine, catecholamines and niacin seems to be the major role in appearance of adverse events reported in TIM for Portula oleracea seed. Mechanisms with consideration of receptor types and pharmacokinetics of catecholamine and niacin are warranted to confirm this hypothesis.