(−)-Epigallocatechin gallate (EGCG) has become a popular disease-preventive supplement worldwide because it may aid in slowing down the onset of age-related diseases such as cancer, diabetes and ...tissue degeneration. As largely demonstrated in cell culture studies, EGCG possesses antioxidant properties and exhibits favorable effects on gene expression, signal transduction and other cell functions. However, only limited effects have been observed in experimental animals and human epidemiological studies. The inconsistency between the biological activity of EGCG in cell cultures and in vivo can be attributed to its low stability, which not only decreases its bioavailability but also leads to the formation of degradation products and prooxidant molecules with possible side-effects. Understanding EGCG degradation kinetics in solution and in vivo is crucial for its successful clinical application. Ambient conditions (pH, temperature, oxygen) can either enhance or decrease the stability of EGCG, thus influencing its biological activity. Usage of stabilizers and/or encapsulation of EGCG into particulate systems such as nanoparticles or microparticles can significantly increase its stability. In this review, the effects of ambient conditions, stabilizers and encapsulation systems on EGCG stability, activity and degradation rate are illustrated.
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Arctigenin (AR) and its glycoside, arctiin, are two major active ingredients of Arctium lappa L (A lappa), a popular medicinal herb and health supplement frequently used in Asia. In the past several ...decades, bioactive components from A lappa have attracted the attention of researchers due to their promising therapeutic effects. In the current article, we aimed to provide an overview of the pharmacology of AR and arctiin, focusing on their anti-inflammatory effects, pharmacokinetics properties and clinical efficacies. Compared to acrtiin, AR was reported as the most potent bioactive component of A lappa in the majority of studies. AR exhibits potent anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS) via modulation of several cytokines. Due to its potent anti-inflammatory effects, AR may serve as a potential therapeutic compound against both acute inflammation and various chronic diseases. However, pharmacokinetic studies demonstrated the extensive glucuronidation and hydrolysis of AR in liver, intestine and plasma, which might hinder its in vivo and clinical efficacy after oral administration. Based on the reviewed pharmacological and pharmacokinetic characteristics of AR, further pharmacokinetic and pharmacodynamic studies of AR via alternative administration routes are suggested to promote its ability to serve as a therapeutic agent as well as an ideal bioactive marker for A lappa.
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Andrographis paniculata has long been part of the traditional herbal medicine system in Asia and in Scandinavia. Andrographolide was isolated as a major bioactive constituent of A. ...paniculata in 1951, and since 1984, andrographolide and its analogs have been scrutinized with modern drug discovery approach for anti-inflammatory properties. With this accumulated wealth of pre-clinical data, it is imperative to review and consolidate different sources of information, to decipher the major anti-inflammatory mechanisms of action in inflammatory diseases, and to provide direction for future studies. Andrographolide and its analogs have been shown to provide anti-inflammatory benefits in a variety of inflammatory disease models. Among the diverse signaling pathways investigated, inhibition of NF-κB activity is the prevailing anti-inflammatory mechanism elicited by andrographolide. There is also increasing evidence supporting endogenous antioxidant defense enhancement by andrographolide through Nrf2 activation. However, the exact pathway leading to NF-κB and Nrf2 activation by andrographolide has yet to be elucidated. Validation and consensus on the major mechanistic actions of andrographolide in different inflammatory conditions are required before translating current findings into clinical settings. There are a few clinical trials conducted using andrographolide in fixed combination formulation which have shown anti-inflammatory benefits and good safety profile. A concerted effort is definitely needed to identify potent andrographolide lead compounds with improved pharmacokinetics and toxicological properties. Taken together, andrographolide and its analogs have great potential to be the next new class of anti-inflammatory agents, and more andrographolide molecules are likely moving towards clinical study stage in the near future.
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5-aminosalicylic acid (5-ASA) is the most widely used drug for the treatment of ulcerative colitis. The benefits of targeted delivery of 5-ASA to the large intestine are well known, ...resulting in reduced systemic absorption and increased local concentrations at the disease site. In the present study, a 5-ASA colon delivery system based on the time-dependent strategy, exploiting the relatively consistent small intestinal transit time (SITT), was manufactured and evaluated in vitro as well as in vivo. The system was obtained by successive spray-coating of an immediate-release tablet core with low-viscosity HPMC and Eudragit® L. The enteric film was effective in preventing release during the acidic stage of the in vitro test, while the HPMC coating brought about reproducible lag phases prior to release in phosphate buffer medium. A γ-scintigraphy investigation pointed out that, following administration to fasted and fed volunteers, disintegration of the units never occurred prior to colon arrival. In all cases, a lag time preceded the appearance of the drug and its N-acetyl metabolite in the bloodstream, which was found to correlate with the time of disintegration in a linear mode. The plasma levels of the drug and metabolite as well as their cumulative urinary recovery were relatively low with respect to those reported when 5-ASA is delivered to the small bowel.
Most of the anti-inflammatory drugs in clinical practice are becoming outdated owing to their potential side and adverse effects. These are found to be highly unsafe for long term use. Thus, since ...last few years, new anti-inflammatory agents are being developed and number of them are in advanced stages of clinical trials. Heterocyclic molecules have gained great attention of chemists due to their similarity to different biological precursors. In the current review, we have highlighted the recent developments (2015 onwards) in designing and synthesis of various heterocyclic anti-inflammatory molecules along with detailed SAR studies. The principal objective of this review is to provide a profound overview of the recently explored heterocyclic anti-inflammatory agents belonging to various classes such as pyrazole, pyrimidine, benzimidazole, indole, and other related heterocyclic compounds. In addition, an enlarged view on potential interactions of synthetic preparations with target inflammatory enzymes or cytokines has been provided. We have also enlisted lead compounds undergoing different clinical trials against inflammation. The elementary aim of this review is to provide restructured knowledge regarding heterocyclic molecules which will be valuable for the scientists working in the field of anti-inflammatory chemistry. The authors believe that lead compounds mentioned in the report will help to design and develop novel anti-inflammatory drug molecules targeting various factors involved in the progression of inflammation.
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•This review is focused on the recent developments in heterocyclic anti-inflammatory agents (2015 onwards).•Anti-inflammatory agents bearing different heterocyclic moieties are discussed.•The SAR of newly synthesized derivatives is explained for understanding designing strategies.•This review may help medicinal chemists to design and develop novel anti-inflammatory drug molecules.
•Organosulfur and other bioactive compounds of Allium spp. are thermally unstable.•Conventional processing tends to decrease nutritional value and bioactivity.•Innovative processing is useful to ...preserve target compounds from Allium genus.
The use of Allium species and their extracts has been known since immemorial times due to their health beneficial properties. It is known that functional properties of Allium genus come from the high content of bioactive compounds. The biological activity of Allium extracts will be conditioned by the type of Allium variety, agricultural conditions, and specific extraction process used since all these factors affect the content and the profile of bioactive compounds. Innovative extraction techniques in comparison to conventional processes could be considered as a promising tool to recover bioactive compounds from Allium spp. with antimicrobial and anti-inflammatory properties. Trying to fill the gap in the literature, this paper reviews the chemical composition, the effects of processing on the nutritional and bioactive composition of Allium species and their extracts. Moreover, the antimicrobial and anti-inflammatory effects, as well as the bioavailability of bioactive compounds of edible members from the Allium genus is discussed.
Background
Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary ...dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti‐inflammatory drugs (NSAIDs) are drugs that act by blocking prostaglandin production. They inhibit the action of cyclooxygenase (COX), an enzyme responsible for the formation of prostaglandins. The COX enzyme exists in two forms, COX‐1 and COX‐2. Traditional NSAIDs are considered 'non‐selective' because they inhibit both COX‐1 and COX‐2 enzymes. More selective NSAIDs that solely target COX‐2 enzymes (COX‐2‐specific inhibitors) were launched in 1999 with the aim of reducing side effects commonly reported in association with NSAIDs, such as indigestion, headaches and drowsiness.
Objectives
To determine the effectiveness and safety of NSAIDs in the treatment of primary dysmenorrhoea.
Search methods
We searched the following databases in January 2015: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, November 2014 issue), MEDLINE, EMBASE and Web of Science. We also searched clinical trials registers (ClinicalTrials.gov and ICTRP). We checked the s of major scientific meetings and the reference lists of relevant articles.
Selection criteria
All randomised controlled trial (RCT) comparisons of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary dysmenorrhoea.
Data collection and analysis
Two review authors independently selected the studies, assessed their risk of bias and extracted data, calculating odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes, with 95% confidence intervals (CIs). We used inverse variance methods to combine data. We assessed the overall quality of the evidence using GRADE methods.
Main results
We included 80 randomised controlled trials (5820 women). They compared 20 different NSAIDs (18 non‐selective and two COX‐2‐specific) versus placebo, paracetamol or each other.
NSAIDs versus placebo
Among women with primary dysmenorrhoea, NSAIDs were more effective for pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09; 35 RCTs, I2 = 53%, low quality evidence). This suggests that if 18% of women taking placebo achieve moderate or excellent pain relief, between 45% and 53% taking NSAIDs will do so.
However, NSAIDs were associated with more adverse effects (overall adverse effects: OR 1.29, 95% CI 1.11 to 1.51, 25 RCTs, I2 = 0%, low quality evidence; gastrointestinal adverse effects: OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs, I2 = 30%; neurological adverse effects: OR 2.74, 95% CI 1.66 to 4.53, seven RCTs, I2 = 0%, low quality evidence). The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so.
NSAIDs versus other NSAIDs
When NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain relief or safety. However, the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials.
Non‐selective NSAIDs versus COX‐2‐specific selectors
Only two of the included studies utilised COX‐2‐specific inhibitors (etoricoxib and celecoxib). There was no evidence that COX‐2‐specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs; however data were very scanty.
NSAIDs versus paracetamol
NSAIDs appeared to be more effective for pain relief than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, three RCTs, I2 = 0%, low quality evidence). There was no evidence of a difference with regard to adverse effects, though data were very scanty.
Most of the studies were commercially funded (59%); a further 31% failed to state their source of funding.
Authors' conclusions
NSAIDs appear to be a very effective treatment for dysmenorrhoea, though women using them need to be aware of the substantial risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea. We rated the quality of the evidence as low for most comparisons, mainly due to poor reporting of study methods.
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Population aging is an irreversible global trend with economic and socio-political consequences. One of the most invalidating outcomes of aging in the elderly is cognitive decline, ...leading to dementia and often related to neurodegenerative disorders. Among these latter, Alzheimer’s disease (AD) is the major cause of dementia, affecting more than 30 million of individuals worldwide. To date, the treatment of AD remains a challenge because of an incomplete understanding of the events that lead to the selective neurodegeneration typical of Alzheimer’s brains. There is an enormous global demand for new effective therapies and researchers are investigating new fields. One promising strategy is the use of nutraceuticals as integrative, complementary and preventive therapy. Curcumin is one example of natural product with anti-AD properties, with promising potential for prevention, treatment and diagnostic. The limitations in the use of curcumin as therapeutic are represented by its pharmacokinetics profile and the low bioavailability after oral administration. However, curcumin has been the focus of intense research for new drug development. Here we analyzed some new approaches that have been applied in the attempt to improve its use, particularly new formulations, changes in the way of administration, nanotechnology-based delivery systems and the hybridization strategy.
Copper-based compounds are promising entities for target-specific next-generation anticancer and NSAIDS therapeutics. In lieu of this, benzimidazole scaffold plays an important role, because of their ...wide variety of potential functionalizations and coordination modes. Herein, we report three copper complexes 1-3 with benzimidazole-derived scaffolds, a biocompatible molecule, and secondary ligands viz, 1-10-phenanthroline and 2,2'-bipyridyl. All the copper complexes have been designed, synthesized and adequately characterized using various spectroscopic techniques. In-vitro, human serum albumin (HSA) binding was also carried out using fluorescence technique and in-silico molecular modeling studies, which exhibited significant binding affinities of the complexes with HSA. Furthermore, copper complexes 1-3 were tested for biological studies, i.e., anticancer as well as NSAIDS. In vitro cytotoxicity results were carried out on cultured MCF-7 cell lines. To get the insight over the mechanism of action, GSH depletion and change in lipid peroxidation were tested and thus confirmed the role of ROS generation, responsible for the cytotoxicity of the complexes 1-3. Moreover, the copper complexes 1-3 were tested for potential to act as NSAIDS on albino rats and mice in animal studies in-vivo. Additionally, we also predicted the mechanism of action of the copper complexes 1-3 using molecular modeling studies with COX-2 inhibitor.
Nowadays the global tendency towards physical activity reduction and an augmented dietary intake of fats, sugars and calories is leading to a growing propagation of overweight, obesity and ...lifestyle-related diseases, such diabetes, hypertension, dyslipidemia and metabolic syndrome. In particular, obesity, characterized as a state of low-level inflammation, is a powerful determinant both in the development of insulin resistance and in the progression to type 2 diabetes. A few molecular targets offer hope for anti-obesity therapeutics. One of the keys to success could be the induction of uncoupling protein 1 (UCP1) in abdominal white adipose tissue (WAT) and the regulation of cytokine secretions from both abdominal adipose cells and macrophage cells infiltrated into adipose tissue. Anti-obesity effects of fucoxanthin, a characteristic carotenoid, exactly belonging to xanthophylls, have been reported. Nutrigenomic studies reveal that fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose levels through the regulation of cytokine secretions from WAT. The key structure of anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups. Fucoxanthin, which can be isolated from edible brown seaweeds, recently displayed its many physiological functions and biological properties. We reviewed recent studies and this article aims to explain essential background of fucoxanthin, focusing on its promising potential anti-obesity effects. In this respect, fucoxanthin can be developed into promising marine drugs and nutritional products, in order to become a helpful functional food.
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