Role of Bioactive Compounds, Novel Drug Delivery Systems, and Polyherbal Formulations in the Management of Rheumatoid Arthritis.

Rheumatoid Arthritis (RA) is an autoimmune disorder that generally causes joint synovial inflammation as well as gradual cartilage and degenerative changes, resulting in progressive immobility. Cartilage destruction induces synovial inflammation, including synovial cell hyperplasia, increased synovial fluid, and synovial pane development. This phenomenon causes articular cartilage damage and joint alkalosis. Traditional medicinal system exerts their effect through several cellular mechanisms, including inhibition of inflammatory mediators, oxidative stress suppression, cartilage degradation inhibition, increasing antioxidants and decreasing rheumatic biomarkers. The medicinal plants have yielded a variety of active constituents from various chemical categories, including alkaloids, triterpenoids, steroids, glycosides, volatile oils, flavonoids, lignans, coumarins, terpenes, sesquiterpene lactones, anthocyanins, and anthraquinones. This review sheds light on the utilization of medicinal plants in the treatment of RA. It explains various phytoconstituents present in medicinal plants and their mechanism of action against RA. It also briefs about the uses of polyherbal formulations (PHF), which are currently in the market and the toxicity associated with the use of medicinal plants and PHF, along with the limitations and research gaps in the field of PHF. This review paper is an attempt to understand various mechanistic approaches employed by several medicinal plants, their possible drug delivery systems and synergistic effects for curing RA with minimum side effects.

Plasma Modification Techniques for Natural Polymer-Based Drug Delivery Systems.

Natural polymers have attracted significant attention in drug delivery applications due to their biocompatibility, biodegradability, and versatility. However, their surface properties often limit their use as drug delivery vehicles, as they may exhibit poor wettability, weak adhesion, and inadequate drug loading and release. Plasma treatment is a promising surface modification technique that can overcome these limitations by introducing various functional groups onto the natural polymer surface, thus enhancing its physicochemical and biological properties. This review provides a critical overview of recent advances in the plasma modification of natural polymer-based drug delivery systems, with a focus on controllable plasma treatment techniques. The review covers the fundamental principles of plasma generation, process control, and characterization of plasma-treated natural polymer surfaces. It discusses the various applications of plasma-modified natural polymer-based drug delivery systems, including improved biocompatibility, controlled drug release, and targeted drug delivery. The challenges and emerging trends in the field of plasma modification of natural polymer-based drug delivery systems are also highlighted. The review concludes with a discussion of the potential of controllable plasma treatment as a versatile and effective tool for the surface functionalization of natural polymer-based drug delivery systems.

Exploring the Multitarget Potential of Iridoids: Advances and Applications.

Iridoids are secondary plant metabolites that are multitarget compounds active against various diseases. Iridoids are structurally classified into iridoid glycosides and non-glycosidic iridoids according to the presence or absence of intramolecular glycosidic bonds; additionally, iridoid glycosides can be further subdivided into carbocyclic iridoids and secoiridoids. These monoterpenoids belong to the cyclopentan[c]-pyran system, which has a wide range of biological activities, including antiviral, anticancer, antiplasmodial, neuroprotective, anti-thrombolytic, antitrypanosomal, antidiabetic, hepatoprotective, anti-oxidant, antihyperlipidemic and anti-inflammatory properties. The basic chemical structure of iridoids in plants (the iridoid ring scaffold) is biosynthesized in plants by the enzyme iridoid synthase using 8-oxogeranial as a substrate. With advances in phytochemical research, many iridoid compounds with novel structure and outstanding activity have been identified in recent years. Biologically active iridoid derivatives have been found in a variety of plant families, including Plantaginaceae, Rubiaceae, Verbenaceae, and Scrophulariaceae. Iridoids have the potential of modulating many biological events in various diseases. This review highlights the multitarget potential of iridoids and includes a compilation of recent publications on the pharmacology of iridoids. Several in vitro and in vivo models used, along with the results, are also included in the paper. This paper's systematic summary was created by searching for relevant iridoid material on websites such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, and others. The compilation will provide the researchers with a thorough understanding of iridoid and its congeners, which will further help in designing a large number of potential compounds with a strong impact on curing various diseases.

Neuroprotective potential of ferulic acid against cyclophosphamide-induced neuroinflammation and behavioral changes.

In the present study, ferulic acid (FRA) has been explored for possible neuroprotective effects against cyclophosphamide (CP)-induced neurotoxicity in the Swiss Albino mice. Animals were divided into five groups and treated with FRA for fourteen days and a single dose of CP was administered on the seventh day. Animals were subjected to neurobehavioral tests such as the forced swim test and Morris Water Maze test. On day fifteenth, the brain was removed and used for biochemical analysis. The outcome of the study showed that CP administration induced significant neurotoxicity in the form of depression, anxiety, and cognitive dysfunction. Cyclophosphamide administration also reduced the activity of antioxidant enzymes, reduced the level of neurotransmitters (i.e., dopamine, 5-HT, and BDNF), anti-inflammatory cytokines (IL-10), and increased lipid peroxidation and proinflammatory cytokines (IL-1ß, IL-6, and TNF-α). Additionally, CP administration increased the level of acetylcholine esterase. Treatment with FRA significantly reversed these behavioral, and biochemical markers towards normal and mitigated CP-induced neurotoxic manifestation. PRACTICAL APPLICATIONS: Ferulic acid has a variety of pharmacological activities viz. anti-inflammatory, antioxidant, antimicrobial activity, anti-cancer, and anti-diabetic effects. The results of the present study showed that FRA mitigates the neurotoxicity (i.e., alteration of neurotransmitters, inflammation, and oxidative stress) induced by CP in mice. Treatment with FRA knowingly overturned the behavioral and biochemical markers in the direction of the moderated CP-influenced neurotoxic demonstration. Thus, FRA can be useful in the prevention of anticancer drugs induced neurotoxicity. Contrariwise, supplementary in-depth studies are obligatory to bring FRA from bench to bedside that it be used as an adjuvant among chemotherapeutically treated patients.

Identification of Potent Bioassay Guided Terpenoid and Glycoside Root Fractions of Astragalus candolleanus against Clinically Significant Bacterial Strains.

Antibiotic resistance represents one of the biggest challenges, and there is an urgent need for plant-based antimicrobial agents that enable managing this crisis effectively. In this work, we aimed to investigate the antibacterial activity of Astragalus candolleanus (A. candolleanus) hydromethanolic root extract against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Kocuria rhizophila) strains by the cup-plate method. The root was powdered and extracted with 70% methanol by cold maceration for 5 days. Preliminary phytochemical screening was performed with different solvents in the order of increasing polarity. Pure compounds were isolated by column chromatography and were characterized through liquid chromatography-mass spectrometry. Targeted predictions of the isolated compounds were also studied using Swiss Target prediction software and prediction of activity spectra for substances. The extract showed a broad zone of inhibition against pathogenic bacteria. Four pure compounds were isolated, of which a novel terpenoid compound has been identified as stemmadenine along with scillirosidin, cephalotaxine, and myxoxanthophyll. The structures of the isolated phytoconstituents were elucidated by spectral analysis. The four pure components isolated from the roots of A. candolleanus are suggested to be effective against tested pathogens. Overall results of drug design suggest that myxoxanthophyll is a promising bioactive compound endowed with antibacterial activity.

Current Strategies and Novel Drug Approaches for Alzheimer Disease.

Alzheimer's Disease (AD) is a chronic, devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured, but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc. are being used to manage the symptoms of Alzheimer's disease. The paper's objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Enormous literature survey was conducted and published articles of PubMed, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer's disease. Currently, several strategies are being investigated for the treatment of Alzheimer's disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

Antimicrobial Peptidomimetics for Recurrent Septicemia Infections: In Vitro Study for Immuno Compromised Disease Target.

The frequency of Bacillus subtilis infection such as pneumonia pan-opthalmitis, visceral abscess or musculoskeletal infection etc. complications following bacteremia, meningitis in children & the infection associated with majority of motor vehicle accidents associated with trauma & gun shoot injury. Antibiotics which appear especially useful in the treatment of Bacillus. infection are clindamycin and vancomycin to which vast majority of strains are susceptible in vitro. Our objective is to test the synthesized peptidomimetics with the efforts mainly directed towards the identification of antibacterial compounds against recurrent septicemia infection. Six peptidomimetics namely G-A-L-D (C60-soot Glu-ala-leu-Asp), D-P-F (C60-soot Asp-pro-Phe), I-R (C60-soot Ile-Arg), L-R (C60-soot leu-Arg), E-R (C60-soot Glu-Arg), D-E (C60-soot Asp-Glu), the column eluted compounds were tested for disc diffusion using gram positive Bacillus Subtilis strains at different concentrations predicted by pH and inhibitory concentrations. I-R (C60-soot Ile-Arg), & D-E (C60-soot Asp-Glu) was found to be very effective along with 5 compounds against Bacillus Subtilis strain tested. Maximum activity 100 µg/ml for synthesized peptidomimetics with the corresponding zonal inhibition diameter (11 mm; 11 mm; 14 mm; 11 mm; 11 mm; 14 mm) against Bacillus subtilis strain. This is the first evidence based report that proves I-R (C60-soot Ile-Arg) & D-E (C60-soot Asp-Glu) has shown antibacterial action against gram positive strains of Bacillus Subtilis against recurrent septicemia infection.

Adverse drug reaction monitoring during antimicrobial therapy for septicemia patients at a university hospital in New Delhi.

BACKGROUND/AIMS: Adverse drug reaction (ADR) is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product. The present study was conducted in order to monitor the frequency and severity of ADR during antimicrobial therapy of septicemia. METHODS: A prospective, observational, and noncomparative study was conducted over a period of 6 months on patients of septicemia admitted at a university hospital. Naranjo algorithm scale was used for causality assessment. Severity assessment was done by Hartwig severity scale. RESULTS: ADRs in selected hospitalized patients of septicemia was found to be in 26.5% of the study population. During the study period, 12 ADRs were confirmed occurring in 9, out of 34 admitted patients. Pediatric patients experienced maximum ADRs, 44.4%. Females experienced a significantly higher incidence of ADRs, 66.7%. According to Naranjo's probability scale, 8.3% of ADRs were found to be definite, 58.3% as probable, and 33.3% as possible. A higher proportion of these ADRs, 66.7% were preventable in nature. Severity assessment showed that more than half of ADRs were moderate. Teicoplanin was found to be the commonest antimicrobial agent associated with ADRs, followed by gemifloxacin and ofloxacin. CONCLUSION: The incidence and severity of ADRs observed in the present study was substantially high indicating the need of extra vigilant during the antimicrobial therapy of septicemia.