Curcuminoids as cell signaling pathway modulators: A potential strategy for cancer prevention.

Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidences reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoids, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/ß-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoids also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoids against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKß, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology-based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.

Antifungal Activity of Plant Secondary Metabolites on Candida albicans: An Updated Review.

Fungal infections have been increasing continuously worldwide, especially in immunocompromised individuals. Fungi, regarded as eukaryotic pathogens, have many similarities to the host cells, which inhibit anti-fungal drug development progress. Various fungal model systems have been studied, and it was concluded that Candida spp. is the most common disease-causing fungus. Candida species are well known to cause infections not only in our mouth, skin, and vagina, but they are also a frequent cause of life-threatening hospital bloodstream infections. The morphological and developmental pathways of Candida have been studied extensively, providing insight into the fungus development. Candida albicans is known to be the most pathogenic species responsible for a variety of infections in humans. Conventional anti-fungal drugs, mainly azoles drugs available in the market, have been used for years developing resistance in C. albicans. Hence, the production of new anti-fungal drugs, which require detailed molecular knowledge of fungal pathogenesis, needs to be encouraged. Therefore, this review targets the new approach of "Green Medicines" or the phytochemicals and their secondary metabolites as a source of novel anti-fungal agents to overcome the drug resistance of C. albicans, their mechanism of action, and their combined effects with the available anti-fungal drugs.

Ion homeostasis for salinity tolerance in plants: a molecular approach.

Soil salinity is one of the major environmental stresses faced by the plants. Sodium chloride is the most important salt responsible for inducing salt stress by disrupting the osmotic potential. Due to various innate mechanisms, plants adapt to the sodic niche around them. Genes and transcription factors regulating ion transport and exclusion such as salt overly sensitive (SOS), Na+ /H+ exchangers (NHXs), high sodium affinity transporter (HKT) and plasma membrane protein (PMP) are activated during salinity stress and help in alleviating cells of ion toxicity. For salt tolerance in plants signal transduction and gene expression is regulated via transcription factors such as NAM (no apical meristem), ATAF (Arabidopsis transcription activation factor), CUC (cup-shaped cotyledon), Apetala 2/ethylene responsive factor (AP2/ERF), W-box binding factor (WRKY) and basic leucine zipper domain (bZIP). Cross-talk between all these transcription factors and genes aid in developing the tolerance mechanisms adopted by plants against salt stress. These genes and transcription factors regulate the movement of ions out of the cells by opening various membrane ion channels. Mutants or knockouts of all these genes are known to be less salt-tolerant compared to wild-types. Using novel molecular techniques such as analysis of genome, transcriptome, ionome and metabolome of a plant, can help in expanding the understanding of salt tolerance mechanism in plants. In this review, we discuss the genes responsible for imparting salt tolerance under salinity stress through transport dynamics of ion balance and need to integrate high-throughput molecular biology techniques to delineate the issue.

Preclinical Evidence for the Pharmacological Actions of Glycyrrhizic Acid: A Comprehensive Review.

Glycyrrhiza glabra L. (Family: Fabaceae) is one of the important traditional medicinal plant used extensively in folk medicine. It is known for its ethnopharmacological value in curing a wide variety of ailments. Glycyrrhizin, an active compound of G. glabra, possesses anti-inflammatory activity due to which it is mostly used in traditional herbal medicine for the treatment and management of chronic diseases. The present review is focused extensively on the pharmacology, pharmacokinetics, toxicology, and potential effects of Glycyrrhizic Acid (GA). A thorough literature survey was conducted to identify various studies that reported on the GA on PubMed, Science Direct and Google Scholar.

Crocus sativus L. Extract Containing Polyphenols Modulates Oxidative Stress and Inflammatory Response against Anti-Tuberculosis Drugs-Induced Liver Injury.

The purpose of this study is to analyze the polyphenolic rich extract of Crocus sativus L. petals (CSP) in modulating liver oxidative stress and inflammatory response status against rifampicin isoniazid (INH-RIF) drug-induced liver injury. The INH-RIF was administered for 14 days with varying doses in Wistar rats, while silymarin was administered as standard dose. We report the defensive impacts of CSP against INH-RIF induced liver oxidative stress and proinflammatory cytokine. The CSP treatment at both doses significantly controlled all modulating biochemical hepatic injury indicators and resulted in the attenuation of arbitral INH-RIF damage. The components present in CSP identified by LC-ESI-Q-TOF-MS were found to be flavonoids and fatty acids. It can be inferred that CSP possesses a hepatoprotective capacity against INH-RIF-mediated hepatic injury, which may prove to be a medically beneficial natural product for the management of drug-induced liver injury.

Zingerone (4-(4-hydroxy-3-methylphenyl)butan-2-one) ameliorates renal function via controlling oxidative burst and inflammation in experimental diabetic nephropathy.

Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals. The treatment with zingerone markedly abrogated ROS levels, inhibited the NF-кB activation and considerably reduced level of other downstream inflammatory molecules (TNF-α, IL-6, IL-1ß), furthermore, zingerone treatment improved renal functioning by significantly decreasing the levels of kidney toxicity markers KIM-1, BUN, creatinine, and LDH and suppressed TGF-ß. Collectively, these findings indicate that zingerone treatment improved renal function by anti-hyperglycaemic, anti-oxidant, and anti-inflammatory effects, suggesting the efficacy of zingerone in the treatment of DN.

Neuroprotective Strategies for Neurological Disorders by Natural Products: An update.

Nature has bestowed mankind with surplus resources (natural products) on land and water. Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. These natural products have been experimentally documented to possess various biological properties such as antioxidant, anti-inflammatory and anti-apoptotic activities. In vitro and in vivo studies have further established the usefulness of natural products in various preclinical models of neurodegenerative disorders. Natural products include phytoconstituents, like polyphenolic antioxidants, found in herbs, fruits, nuts, vegetables and also in marine and freshwater flora. These phytoconstituents may potentially suppress neurodegeneration and improve memory as well as cognitive functions of the brain. Also, they are known to play a pivotal role in the prevention and cure of different neurodegenerative diseases, such as Alzheimer's disease, epilepsy, Parkinson's disease and other neuronal disorders. The large-scale neuro-pharmacological activities of natural products have been documented due to the result of either the inhibition of inflammatory processes, or the up-regulation of various cell survival proteins or a combination of both. Due to the scarcity of human studies on neuroprotective effects of natural products, this review focuses on the various established activities of natural products in in vitro and in vivo preclinical models, and their potential neuro-therapeutic applications using the available knowledge in the literature.

Role of Proteomics in Crop Stress Tolerance.

Plants often experience various biotic and abiotic stresses during their life cycle. The abiotic stresses include mainly drought, salt, temperature (low/high), flooding and nutritional deficiency/excess which hamper crop growth and yield to a great extent. In view of a projection 50% of the crop loss is attributable to abiotic stresses. However, abiotic stresses cause a myriad of changes in physiological, molecular and biochemical processes operating in plants. It is now widely reported that several proteins respond to these stresses at pre- and post-transcriptional and translational levels. By knowing the role of these stress inducible proteins, it would be easy to comprehensively expound the processes of stress tolerance in plants. The proteomics study offers a new approach to discover proteins and pathways associated with crop physiological and stress responses. Thus, studying the plants at proteomic levels could help understand the pathways involved in stress tolerance. Furthermore, improving the understanding of the identified key metabolic proteins involved in tolerance can be implemented into biotechnological applications, regarding recombinant/transgenic formation. Additionally, the investigation of identified metabolic processes ultimately supports the development of antistress strategies. In this review, we discussed the role of proteomics in crop stress tolerance. We also discussed different abiotic stresses and their effects on plants, particularly with reference to stress-induced expression of proteins, and how proteomics could act as vital biotechnological tools for improving stress tolerance in plants.

Jasmonates: Multifunctional Roles in Stress Tolerance.

Jasmonates (JAs) [Jasmonic acid (JA) and methyl jasmonates (MeJAs)] are known to take part in various physiological processes. Exogenous application of JAs so far tested on different plants under abiotic stresses particularly salinity, drought, and temperature (low/high) conditions have proved effective in improving plant stress tolerance. However, its extent of effectiveness entirely depends on the type of plant species tested or its concentration. The effects of introgression or silencing of different JA- and Me-JA-related genes have been summarized in this review, which have shown a substantial role in improving crop yield and quality in different plants under stress or non-stress conditions. Regulation of JAs synthesis is impaired in stressed as well as unstressed plant cells/tissues, which is believed to be associated with a variety of metabolic events including signal transduction. Although, mitogen activated protein kinases (MAPKs) are important components of JA signaling and biosynthesis pathways, nitric oxide, ROS, calcium, ABA, ethylene, and salicylic acid are also important mediators of plant growth and development during JA signal transduction and synthesis. The exploration of other signaling molecules can be beneficial to examine the details of underlying molecular mechanisms of JA signal transduction. Much work is to be done in near future to find the proper answers of the questions like action of JA related metabolites, and identification of universal JA receptors etc. Complete signaling pathways involving MAPKs, CDPK, TGA, SIPK, WIPK, and WRKY transcription factors are yet to be investigated to understand the complete mechanism of action of JAs.

Plant cytochrome P450s: nomenclature and involvement in natural product biosynthesis.

Cytochrome P450s constitute the largest family of enzymatic proteins in plants acting on various endogenous and xenobiotic molecules. They are monooxygenases that insert one oxygen atom into inert hydrophobic molecules to make them more reactive and hydro-soluble. Besides for physiological functions, the extremely versatile cytochrome P450 biocatalysts are highly demanded in the fields of biotechnology, medicine, and phytoremediation. The nature of reactions catalyzed by P450s is irreversible, which makes these enzymes attractions in the evolution of plant metabolic pathways. P450s are prime targets in metabolic engineering approaches for improving plant defense against insects and pathogens and for production of secondary metabolites such as the anti-neoplastic drugs taxol or indole alkaloids. The emerging examples of P450 involvement in natural product synthesis in traditional medicinal plant species are becoming increasingly interesting, as they provide new alternatives to modern medicines. In view of the divergent roles of P450s, we review their classification and nomenclature, functions and evolution, role in biosynthesis of secondary metabolites, and use as tools in pharmacology.

Achieving crop stress tolerance and improvement--an overview of genomic techniques.

The inexorable exposure of plants to the combinations of abiotic stresses has affected the worldwide food supply. The crop improvement against these abiotic stresses has been captivating approach to increase the yield and enhance the stress tolerance. By using traditional and modern breeding methods, the characters that confer tolerance to these stresses were accomplished. No doubt genetic engineering and molecular breeding have helped in comprehending the intricate nature of stress response. Understanding of abiotic stress-involved cellular pathways provides vital information on such responses. On the other hand, genomic research for crop improvement has raised new assessments in breeding new varieties against abiotic stresses. Interpretation of responses of the crop plants under stress is of great significance by studying the main role of crops in food and biofuel production. This review presents genomic-based approaches revealing the complex networks controlling the mechanisms of abiotic stress tolerance, and the possible modes of assimilating information attained by genomic-based approaches due to the advancement in isolation and functional analysis of genes controlling the yield and abiotic stress tolerance are discussed.

A Review on Pharmacological Properties of Zingerone (4-(4-Hydroxy-3-methoxyphenyl)-2-butanone).

Humans have been using natural products for medicinal use for ages. Natural products of therapeutic importance are compounds derived from plants, animals, or any microorganism. Ginger is also one of the most commonly used condiments and a natural drug in vogue. It is a traditional medicine, having some active ingredients used for the treatment of numerous diseases. During recent research on ginger, various ingredients like zingerone, shogaol, and paradol have been obtained from it. Zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone) is a nontoxic and inexpensive compound with varied pharmacological activities. It is the least pungent component of Zingiber officinale. Zingerone is absent in fresh ginger but cooking or heating transforms gingerol to zingerone. Zingerone closely related to vanillin from vanilla and eugenol from clove. Zingerone has potent anti-inflammatory, antidiabetic, antilipolytic, antidiarrhoeic, antispasmodic, and so forth properties. Besides, it displays the property of enhancing growth and immune stimulation. It behaves as appetite stimulant, anxiolytic, antithrombotic, radiation protective, and antimicrobial. Also, it inhibits the reactive nitrogen species which are important in causing Alzheimer's disease and many other disorders. This review is written to shed light on the various pharmacological properties of zingerone and its role in alleviating numerous human and animal diseases.

Modulation of plant growth and metabolism in cadmium-enriched environments.

Cadmium (Cd) is a water soluble metal pollutant that is not essential to plant growth.It has attracted attention from soil scientists and plant nutritionists in recent years because of its toxicity and mobility in the soil-plant continuum. Even low levels of Cd (0.1-1 J.!M) cause adverse effects on plant growth and metabolism. Cadmium is known to trigger the synthesis of reactive oxygen species, hinder utilization, uptake and transport of essential nutrients and water, and modify photosynthetic machinery,thereby resulting in plant tissue death. Although the effects of Cd are dose- as well as plant species-dependent, some plants show Cd tolerance through a wide range of cellular responses. Such tolerance results from synthesis of osmolytes,generation of enzymatic and non-enzymatic antioxidants and metal-detoxifying peptides, changes in gene expression, and metal ion homeostasis and compartmentalization of ligand-metal complexes. Cd toxicity in plants produces effects on chlorophyllbio synthesis, reduces photosynthesis, and upsets plant water relations and hormonal and/or nutritional balances. All of these effects on plants and on plant metabolism ultimately reduce growth and productivity.In this review, we describe the extent to which Cd affects underlying metabolic processes in plants and how such altered processes affect plant growth. We review the sources of Cd contamination, its uptake, transportation and bioavailability and accumulation in plants, and its antagonistic and synergistic effects with other metals and compounds. We further address the effects of Cd on plant genetics and metabolism,and how plants respond to mitigate the adverse effects of Cd exposure, as well as strategies(e.g., plant breeding) that can reduce the impact of Cd contamination on plants.