Ligusticum chuanxiong Hort: A review of chemistry and pharmacology

Context: Ligusticum chuanxiong Hort (LC; Umbelliferae) is an effective medical plant, which has been extensively applied for many years to treat various diseases with other Chinese herbal medicines. Although a considerable amount of scientific research was reported on LC in the last decade, it is currently scattered across various publications. The present review comprises the chemical and pharmacological research on LC in the last decade.

Objective: The objective of this review is to bring together most of the scientific research available on LC and evaluate its effects and mechanisms.

Methods: The information for 82 cases included in this review was compiled using major databases such as Medline, Elsevier, Springer, Pubmed, and Scholar.

Results: The compounds contained in LC can be divided into five kinds, essential oil (EO), alkaloids, phenolic acids, phthalide lactones, and other constituents. A great deal of pharmacological research has been done, which mainly focuses on cardiovascular and cerebrovascular effects, antioxidation, neuroprotection, antifibrosis, antinociception, antiinflammation, and antineoplastic activity.

Conclusion: A large number of pharmacological and chemical studies during the last 10 years have demonstrated the vast medicinal potential of LC. It is still very clear that LC is a plant with widespread use now and also with extraordinary potential for the future. The documents strongly support the view that LC has beneficial therapeutic properties and indicates its potential as an effective adaptogenic herbal remedy.     

The pharmacology,toxicology and potential applications of arecoline: a review

Context: Arecoline is an effective constituent of Areca catechu L. (Arecaceae) with various pharmacological effects. However, investigations also revealed that long use of arecoline could arouse some oral diseases.

Objective: The present review gathers the fragmented information available in the literature (before 1 October 2015) regarding pharmacology and toxicology of arecoline. We also discussed the potential developments and applications of arecoline in the future.

Methods: All the available information regarding the arecoline is compiled from scientific databases, including Science Direct, PubMed, Web of Science, Scopus, etc.

Results: Previous research demonstrated that arecoline is one of the major effective constituents in A. catechu. Additionally, arecoline has a wide spectrum of pharmacological activities including effects on nervous, cardiovascular, digestive and endocrine systems and anti-parasitic effects. What’s more, arecoline is reported to be the primary toxic constituent of A. catechu, and the main toxic effects include oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC) and genotoxicity.

Conclusion: Arecoline has great potential to be a therapeutic drug for various ailments. However, further investigations are needed in the future to reduce or eliminate its toxicities before developing into new drug.     

Polydatin: A review of pharmacology and pharmacokinetics

Abstract

Context: Polydatin, also named piceid (3,4′,5-trihydroxystilbene-3-β-d-glucoside, PD), is a monocrystalline compound isolated from Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae), but is also detected in grape, peanut, hop cones, red wines, hop pellets, cocoa-containing products, chocolate products and many daily diets. There are numerous investigations reported of PD in the past 22 years, but they are usually scattered across various publications, which may block further research and clinical use of PD.

Objective: The article summarizes and evaluates the published scientific information of PD pharmacological effects and pharmacokinetics since 1990.

Materials and methods: The information from 98 cases included in this review was compiled using major databases such as MEDLINE, Elsevier, Springer, PubMed, Scholar and CNKI.

Results: Numerous pharmacological investigations of PD mainly focus on cardiovascular effects, neuroprotection, anti-inflammatory and immunoregulatory effects, anti-oxidation, anti-tumor, liver and lung protection, etc.

Conclusion: A great number of pharmacological and pharmacokinetic investigations in the past 22 years have demonstrated that PD has favorable therapeutic properties, indicating its potential as an effective material. However, further research is needed to explore its molecular mechanisms of action and definitive target proteins.     

Recent advances in cyclodextrin delivery techniques

Introduction: Active pharmaceutical ingredients (APIs) are evolving from low-molecular-weight drugs to peptide-, protein-, gene-, oligonucleotide- and cell-based drugs. Therefore, advanced pharmaceutical technologies are required to achieve manifestation of the drug efficacy, side effect reduction and the adequate dosage form design.

Areas covered: In this review, the authors highlight the recent advances in drug delivery techniques utilizing cyclodextrins (CyDs), and cyclic oligosaccharides consisting of α-1,4-linked α-D-glucopyranose units, for various drugs described above. Especially, drug delivery system consisting of combination systems of CyDs and functional materials such as dendrimer, liposome and PEG are introduced. Furthermore, the utilities of CyDs as APIs have been also described.

Expert opinion: To achieve the controlled release and/or targeting of low-molecular-weight drugs in systemic administration, the construction of novel CyDs and CyD the supramolecular system should be a useful approach because of the stable complexation of drugs with CyDs. In addition, the combination systems of CyDs and various carriers have the potential as advanced drug delivery systems for proteins and nucleic acids. Furthermore, CyDs have great potential as APIs for various diseases with few side effects, although the detailed mechanism, especially cellular uptake of CyDs, should be clarified.     

Therapeutic potential of naringin: an overview

Context: Naringin is a natural flavanone glycoside that is found in the Chinese herbal medicines and citrus fruits. Studies have demonstrated that naringin possesses numerous biological and pharmacological properties, but few reviews of these studies have been performed.

Objective: The present review gathers the fragmented information available in the literature describing the extraction of naringin, its pharmacology and its controlled release formulations. Current research progress and the therapeutic potential of naringin are also discussed.

Methods: A literature survey for relevant information regarding the biological and pharmacological properties of naringin was conducted using Pubmed, Sciencedirect, MEDLINE, Springerlink and Google Scholar electronic databases from the year 2007–2015.

Results: Naringin modulates signalling pathways and interacts with signalling molecules and thus has a wide range of pharmacological activities, including anti-inflammatory, anti-cancer activities, as well as effects on bone regeneration, metabolic syndrome, oxidative stress, genetic damage and central nervous system (CNS) diseases. Information was gathered that showed the extraction of naringin can be improved using several modifications. There has been some progress in the development of controlled release formulations of naringin.

Conclusion: Naringin is a promising candidate for further in vivo studies and clinical use. More detailed studies regarding its mechanism of action are required.     

SHIP2 and its involvement in various diseases

Importance of the field: Inositol polyphosphate 5-phosphatase (SHIP2) is an important negative regulator of intracellular phosphatidylinositol phosphate, a key second messenger of various intracellular signaling pathways. The functional upregulation of SHIP2 results in signaling blockade, leading to related disorders.

Areas covered in this review: We first summarize the role of SHIP2 in the regulation of insulin signaling and type 2 diabetes, including remarkable advances in pharmacological approaches. In addition, this review highlights new findings regarding the involvement of SHIP2 in a number of diseases, including cancer, neurodegenerative diseases, and atherosclerosis.

What the reader will gain: Recently identified small-molecule inhibitors of SHIP2 phosphatase activity emphasize the potential therapeutic value of SHIP2. In addition, currently available evidence demonstrates the importance of the scaffolding-type protein function of SHIP2. Understanding this interesting function will help clarify the complicated involvement of SHIP2 in various disorders.

Take home message: Recent studies have demonstrated that SHIP2 is a promising therapeutic target for not only type 2 diabetes, but also cancer, neurodegenerative diseases, and atherosclerosis. Targeting SHIP2 through specific small-molecule inhibitors will have beneficial effects on these diseases.     

Designing drugs with multi-target activity: the next step in the treatment of neurodegenerative disorders

Introduction: Neurodegenerative diseases have had devastating effects on patients' quality of life. These complex diseases have several pathways that are affected to initiate cell death. Current therapies, designed to address only a single target, fall short in mitigating or preventing disease progression, and disease-modifying drugs are desperately needed. Over the past several years, a new paradigm has emerged which has as a goal the targeting of multiple disease etiological pathways. Such “multi-targeted designed drugs” (MTDD) have shown great promise in preclinical studies as neuroprotective agents, as well as being able to afford symptomatic relief to blunt the day-to-day burden of these illnesses.

Areas covered: In this review, the authors evaluate the use of chemical scaffolds that led themselves exquisitely to the development of MTDDs in central nervous system disorders. Some of the examples discussed have also transitioned into the clinic, which underscores the importance of pursuing drug discovery programs within the multifunctional arena.

Expert opinion: Currently, very little can be done to slow the progress of neurodegeneration. The multifaceted profile of neurodegeneration necessitates a change in paradigm toward the design of compounds that address several drug targets simultaneously. With successful compounds in clinical trials as well as compounds moving into the clinic, support is growing and the feasibility of this approach is now becoming recognized. This review shows that several small molecule scaffolds can be successfully utilized to design MTDD compounds with good CNS pharmacokinetics.     

Galanin receptors as a potential target for neurological disease

Introduction: Galanin is a 29/30 amino acid long neuropeptide that is widely expressed in the brains of many mammals. Galanin exerts its biological activities through three different G protein-coupled receptors, GalR1, GalR2 and GalR3. The widespread distribution of galanin and its receptors in the CNS and the various physiological and pharmacological effects of galanin make the galanin receptors attractive drug targets.

Areas covered: This review provides an overview of the role of galanin and its receptors in the CNS, the involvement of the galaninergic system in various neurological diseases and the development of new galanin receptor-specific ligands.

Expert opinion: Recent advances and novel approaches in migrating the directions of subtype-selective ligand development and chemical modifications of the peptide backbone highlight the importance of the galanin neurochemical system as a potential target for drug development.     

Changing anticoagulant paradigms for atrial fibrillation: dabigatran,apixaban and rivaroxaban

Introduction: Vitamin K antagonists (VKAs) are the main therapeutic agents used to prevent embolic events in patients with atrial fibrillation (AF). Despite their proven efficacy, VKAs are underused and have several limitations. In recent years, there has been great interest in the development of new oral anticoagulants with a more efficient pharmacological profile, first tested in venous thromboembolism prevention and later in AF.

Areas covered: The authors review the pharmacological differences between dabigatran, rivaroxaban and apixaban, and potential subgroups of patients in whom these new drugs would constitute a possible alternative to VKA therapy. Pharmacodynamic and pharmacokinetic data from each compound are analyzed in respect to their potential use in AF. This article provides an exhaustive review of the current status of this topic and the controversies still regarding each drug.

Expert opinion: Apixaban and rivaroxaban are under evaluation for thromboembolic prevention in AF; dabigatran was recently approved for this indication. Therefore, it is important to know the characteristics of these drugs as a potential alternative to VKAs.     

Cellular delivery of siRNA and antisense oligonucleotides via receptor-mediated endocytosis

Introduction: There is great potential for antisense and siRNA oligonucleotides to become mainstream therapeutic entities thanks to their high specificity and wide therapeutic target space compared with small molecules. Despite this potential, the pharmacological targets within the cells are less accessible to oligonucleotides that are hydrophilic and often charged. Oligonucleotides access their intracellular targets mainly by means of endocytosis, but only a fraction of them reach their targets, as delivery requires functional synergy of cellular uptake and intracellular trafficking.

Areas covered: This review provides an update on the progress of receptor-targeted delivery of oligonucleotides over the last 15 years and summarizes various targeting moieties for oligonucleotide delivery and coupling strategies. To inspire new strategies that can lead to oligonucleotides in the clinic, this review highlights how oligonucleotides successfully reach their intracellular targets by means of receptor-mediated endocytosis.

Expert opinion: Understanding the mechanisms of oligonucleotide internalization has led to greater cellular uptake and superior endosomal release through the rational design of receptor-targeted delivery systems. Further improvements will again depend on a better understanding of the intracellular trafficking of oligonucleotides.     

Innovations in bioadhesive vaginal drug delivery system

Introduction: Vagina, due to its anatomical position and physiological characteristics is increasingly being explored as a site for drug delivery in recent years. This route coupled with bioadhesion phenomena has born fruitful results in delivering drugs both locally as well as systemically.

Areas covered: Bioadhesive vaginal drug delivery system has been used for the treatment of local diseases affecting the vagina like candidiasis, STD, vaginal dryness, and so on. Also, research has demonstrated that drugs can be successfully delivered to systemic circulation via vaginal mucosa for treatment of various diseases like migraine and osteoporosis. Besides, this vaginal route has also been used for uterine targeting of drugs. This review focuses on these recent innovations that have been patented in the area of bioadhesive vaginal drug delivery systems. The review also highlights certain physicochemical characteristics of bioadhesive polymers that affect drug delivery through this route.

Expert opinion: An in-depth study of this review will give an insight into the potential areas that can be explored while designing a bioadhesive vaginal drug delivery system. Also, the in vitro and in vivo experimental results discussed in the review will help stimulate research in development and optimization of newer formulations.     

Traditional uses,medicinal properties,and phytopharmacology of Ficus racemosa: A review

Ficus racemosa Linn. (Moraceae) is a popular medicinal plant in India, which has long been used in Ayurveda, the ancient system of Indian medicine, for various diseases/disorders including diabetes, liver disorders, diarrhea, inflammatory conditions, hemorrhoids, respiratory, and urinary diseases. F. racemosa is pharmacologically studied for various activities including antidiabetic, antipyretic, anti-inflammatory, antitussive, hepatoprotective, and antimicrobial activities. A wide range of phytochemical constituents have been identified and isolated from various parts of F. racemosa. In this review, a comprehensive account of its traditional uses, phytochemical constituents, and pharmacological effects is presented in view of the many recent findings of importance on this plant.     

Azaepothilone B and its derivatives: a patent review

Introduction: Azaepothilone B, also known as ixabepilone, is a semi synthetic second generation epothilone B analogue. Azaepothilone B, its derivatives, and analogues, are used for treating advance metastatic breast cancer. It has been used as a chemotherapeutic medication for cancer.

Areas covered: This review highlights the patents on different routes for synthesis of azaepothilone B, its derivatives and analogues. The review will also provide the reported pharmacological activity and its polymorphs in the treatment of several cancers, such as breast cancer (metastatic or locally advanced), non-Hodgkin’s lymphoma, and pancreatic cancer. In addition, it considers other proliferative diseases such as viral infections, degenerative diseases of the musculoskeletal system, kidney disease, and immune response related diseases. Different databases such as Espacenet, ISI Web of Knowledge, Patbase, and Thomson Innovation have been searched extensively to review the patents. The analysis has been done to indicate the patenting trend across years and the comparison of active assignees.

Expert opinion: Azaepothilone B, along with its derivatives and analogues, can damage cancer cells in very low concentrations and retain its activity when tumor cells are insensitive to paclitaxel. Hence, it is highly potent agent. Azaepothilone B alone, in combination with other chemotherapeutics, or in the form of formulations, led to applications in various types of cancer. Also, antiproliferative activity of azaepothilone B has great potential for the treatment of proliferative diseases, such as skin diseases and infections. Recent progress in synthesizing azaepothilone B has encouraged researchers to develop new methods for the synthesis of azaepothilone B, its derivatives, and analogues, to obtain maximum yield in minimum steps.     

Lipid and polymeric carrier-mediated nucleic acid delivery

Importance of the field: Nucleic acids such as plasmid DNA, antisense oligonucleotide, and RNA interference (RNAi) molecules, have a great potential to be used as therapeutics for the treatment of various genetic and acquired diseases. To design a successful nucleic acid delivery system, the pharmacological effect of nucleic acids, the physiological condition of the subjects or sites, and the physicochemical properties of nucleic acid and carriers have to be thoroughly examined.

Areas covered in this review: The commonly used lipids, polymers and corresponding delivery systems are reviewed in terms of their characteristics, applications, advantages and limitations.

What the reader will gain: This article aims to provide an overview of biological barriers and strategies to overcome these barriers by properly designing effective synthetic carriers for nucleic acid delivery.

Take home message: A thorough understanding of biological barriers and the structure–activity relationship of lipid and polymeric carriers is the key for effective nucleic acid therapy.     

The genus Hymenocrater: a comprehensive review

Context: The genus Hymenocrater Fisch. et Mey. (Lamiaceae) contains over 21 species in the world. Some species have been used in folk medicine around the world. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of various species of Hymenocrater.

Objective: This review brings together most of the available scientific research regarding the genus Hymenocrater. Through this review, the authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of Hymenocrater species.

Methods: This review has been compiled using references from major databases such as Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, Google Scholar, Scopus, PubMed, Springer Link and books, without limiting the dates of publication. General web searches were also carried out using Google and Yahoo search engines by applying some related search terms (e.g., Hymenocrater spp., phytochemical, pharmacological, extract, essential oil and traditional uses). The articles related to agriculture, ecology, and synthetic works and those using languages other than English or Persian have been excluded.

Results: The genus Hymenocrater contains essential oil. Flavonoids, phenolic acids and terpenoids are important constituents of this genus. The pharmacological studies confirmed that the species of the genus Hymenocrater showed antimicrobial, antiparasitic, antioxidant, anticancer and antidiabetic activities.

Conclusion: This review discusses the current knowledge of Hymenocrater species that review therapeutic potential, especially their effects on the cancer cells and gaps offering opportunities for future research.     

New substituted benzimidazole derivatives: a patent review (2013 – 2014)

Introduction: The benzimidazole nucleus is found in a variety of naturally occurring compounds and is of significant importance in medicinal chemistry. Owing to its conspicuous pharmacological properties, benzimidazoles have become an important pharmacophore and sub-structure in drug design and have been screened for a wide range of biological activities.

Areas covered: Areas covered in this paper include a review of the biological effects, mechanisms and synthesis of benzimidazole derivatives in the past 2 years based on patents. The patent databases Scifinder and esp@cenet were used to locate patent applications that were published between 2013 to present. Information from articles published is also included.

Expert opinion: Benzimidazole derivatives are remarkably effective compounds to many diseases and may have the potential to be the first effective therapy against Ebola virus. Therefore, it is of great importance to develop specific design software and sustainable industrial synthetic routes for the development of effective and clinically relevant benzimidazole compounds.     

Immunoregulatory actions of polysaccharides from Chinese herbal medicine

Importance of the field: Polysaccharides, one of main classes of bioactive substances from Chinese herbal medicine (CHM), have been indicated to have wide pharmacological activities, especially broad immunomodulatory and antitumour effects. However, their immunoregulatory mechanisms are still not fully understood yet.

Areas covered in this review: Polysaccharides from CHM (CHMPS) are reviewed with focus on their immunoregulatory function, describing their immunoregulatory actions on immune organs, immune cells and immune molecules, and discussing their effects on cell surface receptors and cell signaling pathways.

What the reader will gain: A better understanding of the immunoregulatory effects of CHMPS and their structure–function relationship.

Take home message: CHMPS can active or regulate the immune system including innate and adaptive responses, and have profound effects on different diseases. Through examining the molecular mechanisms of the immunomodulating effects of CHMPS, it can be shown that CHMPS have the potential to be an adjuvant in cancer therapies.     

Advances in quantitative structure–activity relationship models of anti-Alzheimer’s agents

Introduction: Alzheimer’s disease (AD) is one of the lethal diseases, mainly affecting older people. The unclear root cause and involvement of various enzymes in the pathological conditions confirm the complexity of the disease. Quantitative structure–activity relationship (QSAR) techniques are of great significance in the design of drugs against AD.

Areas covered: In the present review, the authors provide a basic background about AD and QSAR techniques. Furthermore, they review the various QSAR studies reported against various targets of AD. The information provided for each QSAR study includes chemical scaffold and target enzyme under study, applied QSAR technique and outcomes of the respective study.

Expert opinion: In silico techniques like QSAR hold great potential in designing leads against a complex disease like AD. In combination with other in silico techniques, QSAR can provide more useful and rational insight to facilitate the discovery of novel compounds. Only few QSAR studies on imaging agents have been reported; hence, more QSAR studies are recommended to explore the biomarker or imaging agents for improving diagnosis. Again, for proper symptomatic treatment, multi-target drugs acting on more than one target are required. Hence, more multi-target QSAR studies are recommended in future to achieve this goal.     

Diuretics in clinical practice. Part I: mechanisms of action,pharmacological effects and clinical indications of diuretic compounds

Importance of the field: Diuretics are among the most important drugs of our therapeutic armamentarium and have been broadly used for >?50 years, providing important help towards the treatment of several diseases. Although all diuretics act primarily by impairing sodium reabsorption in the renal tubules, they differ in their mechanism and site of action and, therefore, in their specific pharmacological properties and clinical indications. Loop diuretics are mainly used for oedematous disorders (i.e., cardiac failure, nephrotic syndrome) and for blood pressure and volume control in renal disease; thiazides and related agents are among the most prescribed drugs for hypertension treatment; aldosterone-blockers are traditionally used for primary or secondary aldosteronism; and other diuretic classes have more specific indications.

Areas covered in this review: This article discusses the mechanisms of action, pharmacological effects and clinical indications of the various diuretic classes used in everyday clinical practice, with emphasis on recent knowledge suggesting beneficial effects of certain diuretics on clinical conditions distinct from the traditional indications of these drugs (i.e., heart protection for aldosterone blockers).

What the reader will gain: Reader will gain insights into the effective use of diuretic agents for various medical conditions, representing their established or emerging therapeutic indications.

Take home message: Knowledge of the pharmacologic properties and mechanisms of action of diuretic agents is a prerequisite for the successful choice and effective clinical use of these compounds.     

Thymus hormones as prospective anti-inflammatory agents

Importance of the field: Inflammatory diseases are characterized by severe immune imbalances, leading to excessive or inappropriate release of mediators, which, in turn, result in massive damage to organs and systems. Effective means to control inappropriate immune reactions are often life-critical needs. Available data on the role of thymus-derived hormones in inflammation show their great potential.

Areas covered in this review: The review aims to systematize information for the last two decades on immune system regulation by thymic peptide hormones, with a primary focus on the role of these hormones in the systemic inflammatory response and inflammatory diseases. Anti-inflammatory potential of three thymic hormones – thymulin, thymosin-alpha, and thymopoietin – is discussed, reviewing recently published clinical and experimental studies.

What the reader will gain: Our analysis revealed the regulation of inflammatory processes via thymic hormones that could be prospective for therapeutic application. This regulation may be mediated through thymic hormone effects on peripheral immune cell activities and bidirectional coupling between thymic hormones and the hypothalamic–pituitary–adrenal axis.

Take-home message: In view of the role of thymic hormones in immune and neuroendocrine systems, they could be suitable as therapeutic agents for inflammation.