Terpenes in the management of chronic kidney disease.

Chronic kidney disease (CKD) is a chronic and progressive systemic condition that characterizes irreversible alterations in the kidneys' function and structure over an extended period, spanning months to years. CKD is the one of the major causes of mortality worldwide. However, very limited treatment options are available in the market for management of the CKD. Diabetes and hypertension are the key risk factors for the progression of CKD. It is majorly characterised by glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Plants are considered safe and effective in treating various chronic conditions. A diverse group of phytoconstituents, including polyphenols, flavonoids, alkaloids, tannins, saponins, and terpenes, have found significant benefits in managing chronic ailments. Terpenes constitute a diverse group of plant compounds with various therapeutic benefits. Evidence-based pharmacological studies underscore the crucial role played by terpenes in preventing and managing CKD. These substances demonstrate the capacity to hinder detrimental pathways, such as oxidative stress, inflammation and fibrosis, thereby demonstrating benefit in renal dysfunction. This review offers a comprehensive overview of the roles and positive attributes of commonly occurring terpenes in managing the causes and risk factors of CKD and the associated conditions.

Eutectic solutions for healing: a comprehensive review on therapeutic deep eutectic solvents (TheDES).

OBJECTIVE: TheDES are formed by mixing a Hydrogen Bond Donor (HBD) and a Hydrogen Bond Acceptor (HBA) in appropriate molar ratios. These solvents have been shown to enhance drug solubility, permeability, and delivery. The main objective of the present article is to review these advantages of TheDES. SIGNIFICANCE: TheDES show unique properties, such as low toxicity, biodegradability, improved bioavailability and enhanced drug delivery of poorly soluble active pharmaceutical ingredients. They are also biocompatible in nature which makes them a promising candidate for various therapeutic applications, including drug formulations, drug delivery and other biomedical uses. The development and utilization of TheDES shows significant advancement in pharmaceutical research, providing new opportunities for improving drug delivery. METHODS: The current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to demonstrate the effectiveness of TheDES in enhancing drug solubility, permeability, and delivery. All chosen articles were selected considering their significance, quality, and approach to addressing issues. RESULT: As a result, various TheDES were identified that can be formulated in different ways: one component can act as a vehicle for an API, either HBD or HBA can be an API, both HBD and HBA can be APIs, or the individual components of DES are not therapeutically active but the resulting DES possesses therapeutic activity. Additionally, TheDES were also recognized to enhance drug delivery and solubility for different APIs, including NSAIDs, anesthetic drugs, antifungals, and others.

Nanotechnology-based fungal detection and treatment: current status and future perspective.

Fungal infections impose a significant impact on global health and encompass major expenditures in medical treatments. Human mycoses, a fungal co-infection associated with SARS-CoV-2, is caused by opportunistic fungal pathogens and is often overlooked or misdiagnosed. Recently, there is increasing threat about spread of antimicrobial resistance in fungus, mostly in hospitals and other healthcare facilities. The diagnosis and treatment of fungal infections are associated with several issues, including tedious and non-selective detection methods, the growth of drug-resistant bacteria, severe side effects, and ineffective drug delivery. Thus, a rapid and sensitive diagnostic method and a high-efficacy and low-toxicity therapeutic approach are needed. Nanomedicine has emerged as a viable option for overcoming these limitations. Due to the unique physicochemical and optical properties of nanomaterials and newer biosensing techniques, nanodiagnostics play an important role in the accurate and prompt differentiation and detection of fungal diseases. Additionally, nano-based drug delivery techniques can increase drug permeability, reduce adverse effects, and extend systemic circulation time and drug half-life. This review paper is aimed at highlighting recent, promising, and unique trends in nanotechnology to design and develop diagnostics and treatment methods for fungal diseases.

Dysbiosis and Alzheimer's disease: role of probiotics, prebiotics and synbiotics.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia and the accumulation of amyloid beta in the brain. Recently, microbial dysbiosis has been identified as one of the major factors involved in the onset and progression of AD. Imbalance in gut microbiota is known to affect central nervous system (CNS) functions through the gut-brain axis and involves inflammatory, immune, neuroendocrine and metabolic pathways. An altered gut microbiome is known to affect the gut and BBB permeability, resulting in imbalance in levels of neurotransmitters and neuroactive peptides/factors. Restoration of levels of beneficial microorganisms in the gut has demonstrated promising effects in AD in pre-clinical and clinical studies. The current review enlists the important beneficial microbial species present in the gut, the effect of their metabolites on CNS, mechanisms involved in dysbiosis related to AD and the beneficial effects of probiotics on AD. It also highlights challenges involved in large-scale manufacturing and quality control of probiotic formulations.

Coumarin linked thiazole derivatives as potential α-glucosidase inhibitors to treat diabetes mellitus.

Diabetes is a leading cause of kidney failure, blindness, heart attacks and lower limb amputation. Prevalence of diabetes is rising globally. α-glucosidase is validated target for controlling hyperglycemia because of its role in catalysing hydrolysis of carbohydrates to glucose in GIT. In an attempt to find novel safe and effective α-glucosidase inhibitors, coumarin linked thiazole was identified as potential scaffold on the basis of its interactions with the active site of α-glucosidase studied in silico. A series of coumarin linked thiazole derivatives were synthesized and analyzed for α-glucosidase inhibitory potential in an in-vitro assay. The synthesized molecules showed potent inhibition of α-glucosidase with IC50 values ranging from 0.14 to 9.38 µM. The most potent compound 2-[(4-bromophenyl) amino)-N-(4- (2-oxo-2H-chromen-3-yl) thiazol-2-yl] acetamide was further docked with α-glucosidase and molecular dynamics studies were carried out for 100 ns which suggested the stability of protein and ligand in the protein active site over the simulation period and role of hydrophobic interactions slightly more than the electrostatic/polar interactions in ligand- receptor stability. In summary, our results demonstrate efficacy of coumarin-linked thiazole as potential leads for further optimization and development.

Challenges and Opportunities of Metal Chelation Therapy in Trace Metals Overload-Induced Alzheimer's Disease.

Essential trace metals like zinc (Zn), iron (Fe), and copper (Cu) play an important physiological role in the metabolomics and healthy functioning of body organs, including the brain. However, abnormal accumulation of trace metals in the brain and dyshomeostasis in the different regions of the brain have emerged as contributing factors in neuronal degeneration, Aß aggregation, and Tau formation. The link between these essential trace metal ions and the risk of AD has been widely studied, although the conclusions have been ambiguous. Despite the absence of evidence for any clinical benefit, therapeutic chelation is still hypothesized to be a therapeutic option for AD. Furthermore, the parameters like bioavailability, ability to cross the BBB, and chelation specificity must be taken into consideration while selecting a suitable chelation therapy. The data in this review summarizes that the primary intervention in AD is brain metal homeostasis along with brain metal scavenging. This review evaluates the impact of different trace metals (Cu, Zn, Fe) on normal brain functioning and their association with neurodegeneration in AD. Also, it investigates the therapeutic potential of metal chelators in the management of AD. An extensive literature search was carried out on the "Web of Science, PubMed, Science Direct, and Google Scholar" to investigate the effect of trace elements in neurological impairment and the role of metal chelators in AD. In addition, the current review highlights the advantages and limitations of chelation therapies and the difficulties involved in developing selective metal chelation therapy in AD patients.

ß-cyclodextrin and its derivatives: application in wastewater treatment.

Water is one of the basic necessities of life and having clean water is extremely important for human health. In recent years, ß-cyclodextrin (ß-CD)-based polymers and nanosystems have been extensively studied as adsorbents for the purpose of water purification. They present high efficiency and capability to remove inorganic, organic, and heavy metal impurities from wastewater as compared to conventional methods of water purification. ß-CDs are cyclic polysaccharides having specific dimension of hydrophobic cavities and hydrophilic functional groups. The hydrophobic cavities form inclusion complexes through host-guest interactions. The hydroxyl groups form sites of hydrogen bonding and electrostatic interaction with pollutants. Additionally, they are also the sites of modification to bring about different derivatisation and polymerization reactions in order to impart desirable properties for efficient adsorption material. This article comprises of various derivatives of ß-cyclodextrins: their nanoparticulate systems and their characterization and applications to remove different types of impurities from wastewater. The chemical reactions for their synthesis and mechanism of adsorption are highlighted.

The Wnt/ß-catenin pathway in breast cancer therapy: a pre-clinical perspective of its targeting for clinical translation.

INTRODUCTION: Despite various treatments available, there is still a high mortality rate in breast cancer patients. Thus, there exists an unmet need for new therapeutic interventions. Studies show that the Wnt/ß-catenin signaling pathway is involved in breast cancer metastasis because of its transcriptional control on epithelial to mesenchymal transition. AREAS COVERED: This comprehensive review explores the Wnt signaling pathway as a potential target for treating breast cancer and other breast cancer subtypes. We discuss the Wnt signaling pathway, its role in breast cancer metastasis, and its effect on breast cancer stem cells. Further, endogenous agents that cause Wnt pathway inactivation are outlined. Finally, various natural and chemical compounds modulating the Wnt pathway used in pre-clinical or clinical trials for breast cancer treatment are discussed. EXPERT OPINION: In vitro and in vivo studies indicate an immense potential of agents targeting the Wnt signaling pathway to prevent and manage breast cancer. Still, more clinical studies are required to support their use in humans. Apart from the agents already in clinical trials, several drug combinations discussed may be translated into clinical practice in a few years.

Design of experiment-based LC-MS/MS method development for simultaneous estimation of nateglinide and metformin hydrochloride in rat plasma.

This research aims to develop and validate a bioanalytical method for simultaneous estimation of an antidiabetic combination using LC-MS/MS in rat plasma. Nateglinide and metformin hydrochloride are commonly used combination for clinical management of Type 2 diabetes. Hence, simultaneous determination in plasma is essential for the rapid analysis of samples from the pharmacokinetic studies. Statistical optimization was carried out for liquid chromatography (LC) parameters and mass spectroscopic (MS) parameters by design of experiment (DoE) (Design Expert Version 11, Stat Ease Inc., USA) approach. A 33 full factorial design was used for optimization of LC parameters; %methanol, %formic acid, and flow rate were selected as independent variables, whereas peak area and tailing factor were considered as dependent variables for both drugs. Box-Behnken design was used to optimize MS parameters including drying gas flow rate, nebulizing gas flow rate, DL temperature, heat block temperature, and positive voltage as independent factors, and responses selected were [M + H]+ intensity of nateglinide and metformin hydrochloride. The [M + H]+ intensity of the optimized method for nateglinide and metformin hydrochloride were 2,462,838 and 11,873,826, respectively. The model was found significant for optimizing LC and MS parameters with p < 0.05 for both nateglinide and metformin hydrochloride. The optimized method was validated as per the ICH-M10 guideline, which was accurate, precise, and selective. The method was cost-effective and capable of quantitating concentrations in picogram levels for nateglinide and metformin hydrochloride simultaneously.

Therapeutic and Industrial Applications of Curdlan With Overview on Its Recent Patents.

Curdlan is an exopolysaccharide, which is composed of glucose linked with ß-(1,3)-glycosidic bond and is produced by bacteria, such as Alcaligenes spp., Agrobacterium spp., Paenibacillus spp., Rhizobium spp., Saccharomyces cerevisiae, Candida spp., and fungal sources like Aureobasidium pullulan, Poria cocos, etc. Curdlan has been utilized in the food and pharmaceutical industries for its prebiotic, viscosifying, and water-holding properties for decades. Recently, the usefulness of curdlan has been further explored by the pharmaceutical industry for its potential therapeutic applications. Curdlan has exhibited immunoregulatory and antitumor activity in preclinical settings. It was observed that curdlan can prevent the proliferation of malarial merozoites in vivo; therefore, it may be considered as a promising therapy for the treatment of end-stage malaria. In addition, curdlan has demonstrated potent antiviral effects against human immunodeficiency virus (HIV) and Aedes aegypti virus. It has been suggested that the virucidal properties of curdlans should be extended further for other deadly viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19). The prebiotic property of curdlan would confer beneficial effects on the host by promoting the growth of healthy microbiota in the gut and consequently help to reduce gastrointestinal disorders. Therefore, curdlan can be employed in the manufacture of prebiotics for the management of various gastrointestinal dysbiosis problems. Studies on the mechanism of action of curdlan-induced suppression in microbial and tumor cells at the cellular and molecular levels would not only enhance our understanding regarding the therapeutic effectiveness of curdlan but also help in the discovery of new drugs and dietary supplements. The primary focus of this review is to highlight the therapeutic interventions of curdlan as an anticancer, anti-malaria, antiviral, and antibacterial agent in humans. In addition, our review provides the latest information about the chemistry and biosynthesis of curdlan and its applications for making novel dairy products, functional foods, and nutraceuticals and also details about the recent patents of curdlan and its derivatives.

Nanotechnology-based antiviral therapeutics.

The host immune system is highly compromised in case of viral infections and relapses are very common. The capacity of the virus to destroy the host cell by liberating its own DNA or RNA and replicating inside the host cell poses challenges in the development of antiviral therapeutics. In recent years, many new technologies have been explored for diagnosis, prevention, and treatment of viral infections. Nanotechnology has emerged as one of the most promising technologies on account of its ability to deal with viral diseases in an effective manner, addressing the limitations of traditional antiviral medicines. It has not only helped us to overcome problems related to solubility and toxicity of drugs, but also imparted unique properties to drugs, which in turn has increased their potency and selectivity toward viral cells against the host cells. The initial part of the paper focuses on some important proteins of influenza, Ebola, HIV, herpes, Zika, dengue, and corona virus and those of the host cells important for their entry and replication into the host cells. This is followed by different types of nanomaterials which have served as delivery vehicles for the antiviral drugs. It includes various lipid-based, polymer-based, lipid-polymer hybrid-based, carbon-based, inorganic metal-based, surface-modified, and stimuli-sensitive nanomaterials and their application in antiviral therapeutics. The authors also highlight newer promising treatment approaches like nanotraps, nanorobots, nanobubbles, nanofibers, nanodiamonds, nanovaccines, and mathematical modeling for the future. The paper has been updated with the recent developments in nanotechnology-based approaches in view of the ongoing pandemic of COVID-19.Graphical abstract.

Box-Behnken design directed optimization for sensitivity assessment of anti-platelet drugs.

Optimization of electrospray ionization (ESI) parameters is routinely carried out by one factor at a time (OFAT) or auto-tune software (ATS). Design of experiments (DOE) approach has been reported to be an excellent alternative to OFAT or ATS. Box-Behnken Design (BBD) was successfully used to optimize ESI parameters like nebulizing gas flow rate, desolvation line temperature, heat block temperature, and drying gas flow rate for [M + H]+ intensity of Clopidogrel bisulfate (CLP) and Ticlopidine (TLP). BBD model was found to be significant with p < .0001 for both CLP and TLP. The predicted and optimized (OL) ESI parameters were used for chromatographic analysis and were compared against three levels of ESI parameters, i.e. low level (LL), medium level (ML), and high level (HL). The OL ESI parameters were subjected to chromatographic analysis and its mean peak area was significantly higher than mean peak area for LL, ML, and HL ESI in case of CLP and TLP (p < .001). However, no significant difference was observed between the mean peak area for ML and OL of TLP. Thus, BBD can be considered with 29 trials to optimize four mass spectrometric parameters. The liquid chromatographic parameters percentage of methanol, percentage of formic acid and flow rate were also optimized using BBD. However, the optimized method did not significantly influence the peak response over the non-optimized method.

Preparation and characterization of standardized pomegranate extract-phospholipid complex as an effective drug delivery tool.

Punicalagins, a pair of anomeric ellagitannins, present in Punica granatum (Pomegranates) are known to possess excellent antioxidant activity in vitro, but poor oral bioavailability. The reasons cited for poor bioavailability are their large molecular size, poor lipophilicity, and degradation by colonic microflora into less active metabolites. The objective of the present research work was to complex the standardized pomegranate extract (SPE) with phospholipid to formulate standardized pomegranate extract-phospholipid complex (SPEPC), characterize it and check its permeability through an ex vivo everted gut sac experiment. SPEPC was prepared by mixing SPE (30% punicalagins) and soya phosphatidylcholine (PC) in 1:1 v/v mixture of methanol and dioxane and spray-drying the mixture. The complex was characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. It was evaluated for its octanol solubility, dissolution, and permeability by everted the gut sac technique. The characterization methods confirmed the formation of complex. Increased n-octanol solubility of the complex proved its increased lipophilicity. Dissolution studies revealed that the phospholipid covering may prevent the punicalagins to be released in gastro-intestinal tract, thus preventing their colonic microbial degradation. SPEPC showed better apparent permeability than SPE in an everted gut sac technique. Hence, it could be concluded that phospholipid complex of SPE may be of potential use in increasing the permeability and hence the bioavailability of punicalagins.