Effects of Vitamin D and E Supplementation on Prevention of Bronchopulmonary Dysplasia (BPD) in Premature Neonates: A Systematic Review and Meta-Analysis.

BACKGROUND: Bronchopulmonary Dysplasia (BPD) has a multifactorial etiology. Vitamin E and vitamin D play an important role in lung development and can potentially be beneficial in the prevention of BPD. OBJECTIVE: The study aimed to compare the risk of BPD occurrence in preterm neonates supplemented with vitamin D or E versus those who did not get supplementation. METHODS: The literature search was conducted for this systematic review by searching the PubMed, Scopus, and Web of Science databases up to December 2022. Randomized controlled trials involved administering vitamin D or E to preterm neonates and examining the occurrence of BPD. We excluded non-English articles, and articles with non-relevant and insufficient data. We used the Critical Appraisal Skills Programme (CASP) checklist to assess the quality of the included studies. We used Egger's test to evaluate the risk of bias among the included studies. Heterogeneity was also assessed through Q-test and I2. We applied the random effect model for analysis. A P-value less than 0.05 was considered as significant. All the statistical analysis in the current study was performed using STATA 14. The Relative Risk (RR) was calculated as the effect size with 95% Confidence Interval (CI). RESULTS: Three eligible studies seeking the role of vitamin D in the prevention of BPD were analysed. Meta-analysis revealed that receiving vitamin D supplementation can significantly reduce the risk of BPD in preterm infants (RR = 0.357, 95% CI: 0.189-0.675, I2 = 0.0%; p = 0.002). Similarly, for assessing the role of Vitamin E in the prevention of BPD, three eligible studies were analysed. Vitamin E supplementation was not found to play a significant role in the reduction of BPD (RR = 0.659, 95%CI = 0.243-1.786, I2 = 38.7%; p = 0.412). CONCLUSION: Vitamin D supplementation could be beneficial in preventing BPD in preterm infants. However, evidence is not enough regarding vitamin E's role in reducing the incidence of BPD in preterm infants.

Role of microRNAs and their putative mechanism in regulating potato (Solanum tuberosum L.) life cycle and response to various environmental stresses.

The exponentially increasing population and the demand for food is inextricably linked. This has shifted global attention to improving crop plant traits to meet global food demands. Potato (Solanum tuberosum L.) is a major non-grain food crop that is grown all over the world. Currently, some of the major global potato research work focuses on the significance of microRNAs (miRNAs) in potato. miRNAs are a type of non-coding RNAs that regulate the gene expression of their target mRNA genes by cleavage and/or their translational inhibition. This suggests an essential role of miRNAs in a multitude of plant biological processes, including maintenance of genome integrity, plant growth, development and maturation, and initiation of responses to various stress conditions. Therefore, engineering miRNAs to generate stress-resistant varieties of potato may result in high yield and improved nutritional qualities. In this review, we discuss the potato miRNAs specifically known to play an essential role in the various stages of the potato life cycle, conferring stress-resistant characteristics, and modifying gene expression. This review highlights the significance of the miRNA machinery in plants, especially potato, encouraging further research into engineering miRNAs to boost crop yields and tolerance towards stress.

Mitochondrial-targeted curcumin inhibits T-cell activation via Nrf2 and inhibits graft-versus-host-disease in a mouse model.

Anti-inflammatory and immune suppressive agents are required to moderate hyper-activation of lymphocytes under disease conditions or organ transplantation. However, selective disruption of mitochondrial redox has not been evaluated as a therapeutic strategy for suppression of T-cell-mediated pathologies. Using mitochondrial targeted curcumin (MitoC), we studied the effect of mitochondrial redox modulation on T-cell responses by flow cytometry, transmission electron microscopy, transcriptomics, and proteomics, and the role of Nrf2 was studied using Nrf2- /- mice. MitoC decreased mitochondrial TrxR activity, enhanced mitochondrial ROS (mROS) production, depleted mitochondrial glutathione, and suppressed activation-induced increase in mitochondrial biomass. This led to suppression of T-cell responses and metabolic reprogramming towards Treg differentiation. MitoC induced nuclear translocation and DNA binding of Nrf2, leading to upregulation of Nrf2-dependent genes and proteins. MitoC-mediated changes in mitochondrial redox and modulation of T-cell responses are abolished in Nrf2- /- mice. Restoration of mitochondrial thiols abrogated inhibition of T-cell responses. MitoC suppressed alloantigen-induced lymphoblast formation, inflammatory cytokines, morbidity, and mortality in acute graft-versus-host disease mice. Disruption of mitochondrial thiols but not mROS increase inculcates an Nrf2-dependent immune-suppressive disposition in T cells for the propitious treatment of graft-versus-host disease.

DISPEL: database for ascertaining the best medicinal plants to cure human diseases.

Medicinal plants are anticipated to be one of the most valuable resources for the remedial usage in the treatment of various ailments. The data on key medicinal plants and their therapeutic efficacy against various ailments are quite scattered and not available on a single platform. Moreover, currently there is no means/mechanism of finding the best medicinal plant(s) from numerous plants known to cure any disease. DISPEL (Diseases Plants Eliminate) is a compendium of medicinal plants available across the world that are used to cure infectious as well as non-infectious diseases in humans. The association of a medicinal plant with a disease it cures is hereby referred to as 'medicinal plant-disease cured' linkage. The DISPEL database hosts ∼60 000 'medicinal plant-disease cured' linkages encompassing ∼5500 medicinal plants and ∼1000 diseases. This platform provides interactive and detailed visualization of medicinal plants, diseases and their relations using comprehensible network graph representation. The user has the freedom to search the database by specifying the name of disease(s) as well as the scientific/common name(s) of plant. Each 'medicinal plant-disease cured' relation is scored based on the availability of any medicine/product derived from that medicinal plant, information about active compound(s), knowledge regarding the part of plant that is effective and number of distinct articles/books/websites confirming the effectiveness of the medicinal plant. The user can find the best plant(s) that can be used to cure any desired disease(s). The DISPEL database is the first step towards generating the 'most-effective' combination of plants to cure a disease since it delineates as well as ranks all the therapeutic medicinal plants for that disease. The combination of best medicinal plants can then be used to conduct clinical trials and thus pave the way for their use in clinics for treatment of diseases. Database URL https://compbio.iitr.ac.in/dispel.

Culinary spices and herbs in managing early and long-COVID-19 complications: A comprehensive review.

Human race is preparing for the upsurge and aftermath of COVID-19 pandemic complicated by novel variants, new waves, variable mortality rate, and post-COVID complications. Despite use of repurposed drugs, symptomatic treatments and licensing of multiple vaccines, the daily number of cases and rate of transmission are significant. Culinary spices and herbs have been historically used in pandemic and non-pandemic times to reduce respiratory viral burden. Specific food items and culinary spices can boost the levels of protective immunity and also offer therapeutic benefits against impervious bugs via well-known as well as less-known but scientifically testable mechanisms. Here, we analyzed the phytochemicals profile of Ayurvedic herbs and inferred from the clinical trials/observational studies to provide a focused and succinct perspective on the relevance of "food-based" traditional decoction to moderate COVID-19 disease and long-COVID via modulation of immunity and reinstatement of homeostasis. We also underscore the druggable targets in pathogenesis of COVID-19 which are relevant to the ongoing clinical trials using spices and herbs. This information will provide a strong scientific rationale for standardization of the traditional herbs-based therapies and adopting the use of herbs, spices, and their formulations for reducing SARS-CoV-2 transmission, long-COVID symptoms, and COVID-19 disease progression.

Herb-Induced Liver Injury by Ayurvedic Medicine With Severe Lactic Acidosis: A Case Report.

Lactate is the basic blood parameter in the arsenal of an intensivist when managing a critically ill patient. A 62-year-old male presented with nausea and vomiting. He had been using an Ayurvedic medication, Insulin Management Expert (IME-9), for his type 2 diabetes mellitus and was found to have severe lactic acidosis that was resistant to initial fluid resuscitation and Ayurvedic medicine-induced liver injury. He required admission to critical care for organ support and ultimately recovered. Because current literature on the adverse effects of this Ayurvedic medication, particularly hepatotoxicity, is limited, causality was determined using the adverse drug association tool Roussel Uclaf Causality Assessment Method (RUCAM), which determined this as a probable cause with a strong score of seven. As a result, our case adds a vital gear to the wheel of current research literature.

A Brief Review of Plant Cell Transfection, Gene Transcript Expression, and Genotypic Integration for Enhancing Compound Production.

Plants possess a plethora of important secondary metabolites, which are unique sources of natural pigments, pharmaceutical compounds, food additives, natural pesticides, and other industrial components. The commercial significance of such metabolites/compounds has directed the research toward their production and exploration of methods for enhancement of production. Biotechnological tools are critical in selecting, integrating, multiplying, improving, and analyzing medicinal plants for secondary metabolite production. Out of many techniques that are being explored to enhance secondary metabolite production, "plant cell transfection" is the latest tool to achieve maximum output from the plant source. It is based upon the introduction of foreign DNA into the plant cell relying on physical treatment such as electroporation, cell squeezing, sonoporation, optical transfection nanoparticles, magnetofection, and chemical treatment or biological treatment that depends upon carrier. One of the promising tools that have been exploited is CRISPR-Cas9. Overall, the abovementioned tools focus on the stable transfection of desired gene transcripts. Since the integration and continuous expression of transfected gene of particular trait represents stable transfection of host cell genome, resulting from transfer of required trait to daughter cells ultimately leading to enhanced production of secondary metabolites of interest. This chapter will review a set of biotechnological tools that are candidates for achieving the enhanced bioactive compound production indicated here to be used for drug discovery.

Therapeutic Potential of Quercetin and its Derivatives in Epilepsy: Evidence from Preclinical Studies.

Quercetin is a polyphenolic bioactive compound highly enriched in dietary fruits, vegetables, nuts, and berries. Quercetin and its derivatives like rutin and hyperoside are known for their beneficial effects in various neurological conditions including epilepsy. The clinical studies of quercetin and its derivatives in relation to epilepsy are limited. This review provides the evidence of most recent knowledge of anticonvulsant properties of quercetin and its derivatives on preclinical studies. Additionally, the studies demonstrating antiseizure potential of various plants extracts enriched with quercetin and its derivatives has been included in this review. Herein, we have also discussed neuroprotective effect of these bioactive compound and presented underlying mechanisms responsible for anticonvulsant properties in brief. Finally, limitations of quercetin and its derivatives as antiseizure compounds as well as possible strategies to enhance efficacy have also been discussed.

Transcriptome Analysis of Podoscypha petalodes Strain GGF6 Reveals the Diversity of Proteins Involved in Lignocellulose Degradation and Ligninolytic Function.

The present study reports transcriptomic profiling of a Basidiomycota fungus, Podoscypha petalodes strain GGF6 belonging to the family Podoscyphaceae, isolated from the North-Western Himalayan ranges in Himachal Pradesh, India. Podoscypha petalodes strain GGF6 possesses significant biotechnological potential as it has been reported for endocellulase, laccase, and other lignocellulolytic enzymes under submerged fermentation conditions. The present study attempts to enhance our knowledge of its lignocellulolytic potential as no previous omics-based analysis is available for this white-rot fungus. The transcriptomic analysis of P. petalodes GGF6 reveals the presence of 280 CAZy proteins. Furthermore, bioprospecting transcriptome signatures in the fungi revealed a diverse array of proteins associated with cellulose, hemicellulose, pectin, and lignin degradation. Interestingly, two copper-dependent lytic polysaccharide monooxygenases (AA14) and one pyrroloquinolinequinone-dependent oxidoreductase (AA12) were also identified, which are known to help in the lignocellulosic plant biomass degradation. Overall, this transcriptome profiling-based study provides deeper molecular-level insights into this Basidiomycota fungi, P. petalodes, for its potential application in diverse biotechnological applications, not only in the biofuel industry but also in the environmental biodegradation of recalcitrant molecules. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01037-6.

Asiatic acid attenuates aluminium chloride-induced behavioral changes, neuronal loss and astrocyte activation in rats.

Aluminium (Al) is a potent neurotoxic metal known to cause neurodegeneration. Al exposure causes oxidative stress by accumulation of reactive oxygen species, followed by the activation of neuronal cell death in the brain. Asiatic acid (AA), the major bioactive compound of Centella asiatica (a medicinal plant), act as multifunctional drug as well as an antioxidant. Thus, the present study aimed to investigate the potential neuroprotective effect of AA against Al neurotoxicity. Rats were orally administered aluminium chloride (AlCl3; 100 mg/kg b. wt.) dissolved in distilled water for 8 weeks or AA (75 mg/kg b. wt.) in combination with AlCl3. The results showed that AlCl3-intoxication causes significant impairment of memory, enhances anxiety-like behavior, acetyl cholinesterase (AChE) activity, malondialdehydes (MDA) level, and concomitant decrease in the activities of superoxide dismutase (SOD) and catalase (CAT) in the cortex and hippocampus regions of rat brain. In addition, AlCl3-intoxication enhanced neuronal loss and reactive astrogliosis in both regions. However, co-administration of AA with AlCl3 significantly attenuated the behavioral alterations, restored SOD and CAT activities, while reduced AChE activity and MDA content. Further, the study demonstrated that AA attenuates neuronal loss and reactive astrogliosis in rat brain. In conclusion, the study suggests that AA protects rat brain from Al neurotoxicity by inhibiting oxidative stress, neuronal loss and reactive astrogliosis.

Evaluation of traditional ayurvedic Kadha for prevention and management of the novel Coronavirus (SARS-CoV-2) using in silico approach.

Since the emergence of novel Coronavirus (SARS-CoV-2) infection in Wuhan, China in December 2019, it has now spread to over 205 countries. The ever-growing list of globally spread corona virus-19 disease (COVID-19) patients has demonstrated the high transmission rate among the human population. Currently, there are no FDA approved drugs or vaccines to prevent and treat the infection of the SARS-CoV-2. Considering the current state of affairs, there is an urgent unmet medical need to identify novel and effective approaches for the prevention and treatment of COVID-19 by re-evaluating the knowledge of traditional medicines and repurposing of drugs. Here, we used molecular docking and molecular dynamics simulation approach to explore the beneficial roles of phytochemicals and active pharmacological agents present in the Indian herbs which are widely used in the preparation of Ayurvedic medicines in the form of Kadha to control various respiratory disorders such as cough, cold and flu. Our study has identified an array of phytochemicals present in these herbs which have significant docking scores and potential to inhibit different stages of SARS-CoV-2 infection as well as other Coronavirus target proteins. The phytochemicals present in these herbs possess significant anti-inflammatory property. Apart from this, based on their pharmaceutical characteristics, we have also performed in-silico drug-likeness and predicted pharmacokinetics of the selected phytochemicals found in the Kadha. Overall our study provides scientific justification in terms of binding of active ingredients present in different plants used in Kadha preparation with viral proteins and target proteins for prevention and treatment of the COVID-19.Communicated by Ramaswamy H. Sarma.

Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography-Tandem Mass Spectrometry-Based Bioanalytical Method.

Rottlerin is a key bioactive phytoconstituent present in the pericarp of Mallotus philippensis. It shows promising multifaceted pharmacological actions against cancer. However, there is hardly any report for the quantification of rottlerin in the biological matrix and on its pharmacokinetic behavior. Therefore, we aimed in the present study to assess selective in vitro ADME properties and in vivo pharmacokinetics of isolated and characterized rottlerin using a newly developed and validated liquid chromatography-tandem mass spectrometry-based highly sensitive bioanalytical method. The method was found to be simple (mobile phase and analytical column), sensitive (1.9 ng/mL), and rapid (run time of 2.5 min). All the validation parameters were within the acceptable criteria of the United States Food and Drug Administration's bioanalytical method validation guideline. The method was found to be very useful to assess lipophilicity, plasma stability, metabolic stability, plasma protein binding of rottlerin, as well as its oral and intravenous pharmacokinetics in mice. Rottlerin showed a number of drug-like pharmacokinetic properties (in vitro). Moreover, it displayed an excellent half-life (>2 h) and oral bioavailability (>35%) as compared to other members of natural phenolics. The present study is the first-time report of in vitro ADME properties and in vivo preclinical pharmacokinetics of rottlerin. The generated information is very much useful for its further development as a phytotherapeutics toward cancer therapy.

The effects of Hippophae rhamnoides in neuroprotection and behavioral alterations against iron-induced epilepsy.

Epilepsy is a neurological disorder in which malfunctioning of the electrical activity of the brain causes recurrent, unprovoked seizures. Epilepsy causes wide symptoms that include cognitive dysfunction, anxiety, behavioral alterations, and histological impairments. In this study, the effect of Hippophae rhamnoides (Sea buckthorn/Sbt) on electrophysiology, behavior, and histology in iron-induced epilepsy was analyzed. Rats were randomly divided into four groups (n = 8); Control group, Epileptic group, Sbt treated epileptic group, and Sbt treated group. To induce epilepsy, the intracortical iron injection was administered at a dose of 5 µl of 100 mM FeCl3. A significant increase in epileptiform activity, behavioral abnormalities, and histological impairments was observed in the iron-induced epileptic rats. Hippophae rhamnoides berry extract was administered orally at a dose of 1 ml/kg body wt. for one month. Sbt administration significantly reduced the epileptiform activity, improved behavioral abnormalities, and improved histological impairments in epileptic rats. In conclusion, this study demonstrates the antiepileptic effect of Sbt that probably has exerted by its neuroprotective and behavioral alteration potential against iron-induced epilepsy.

Regulatory safety pharmacology and toxicity assessments of a standardized stem extract of Cassia occidentalis Linn. in rodents.

Cassia occidentalis Linn (CO) is an annual/perennial plant having traditional uses in the treatments of ringworm, gastrointestinal ailments and piles, bone fracture, and wound healing. Previously, we confirmed the medicinal use of the stem extract (ethanolic) of CO (henceforth CSE) in fracture healing at 250 mg/kg dose in rats and described an osteogenic mode of action of four phytochemicals present in CSE. Here we studied CSE's preclinical safety and toxicity. CSE prepared as per regulations of Current Good Manufacturing Practice for human pharmaceuticals/phytopharmaceuticals and all studies were performed in rodents in a GLP-accredited facility. In acute dose toxicity as per New Drug and Clinical Trial Rules, 2019 (prior name schedule Y), in rats and mice and ten-day dose range-finding study in rats, CSE showed no mortality and no gross abnormality at 2500 mg/kg dose. Safety Pharmacology showed no adverse effect on central nervous system, cardiovascular system, and respiratory system at 2500 mg/kg dose. CSE was not mutagenic in the Ames test and did not cause clastogenicity assessed by in vivo bone marrow genotoxicity assay. By a sub chronic (90 days) repeated dose (as per OECD, 408 guideline) study in rats, the no-observed-adverse-effect-level was found to be 2500 mg/kg assessed by clinico-biochemistry and all organs histopathology. We conclude that CSE is safe up to 10X the dose required for its osteogenic effect.

Pre-clinical evaluation of an innovative oral nano-formulation of baicalein for modulation of radiation responses.

There is an unmet medical need for non-toxic and effective radiation countermeasures for prevention of radiation toxicity during planned exposures. We have earlier shown that intraperitoneal administration of baicalein (BCL) offers significant survival benefit in animal model. Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of baicalein has been reported in pre-clinical model systems and also in healthy human volunteers. However, clinical translation of baicalein is hindered owing to poor bioavailability due to lipophilicity. In view of this, we fabricated and characterized in-situ solid lipid nanoparticles of baicalein (SLNB) with effective drug entrapment and release kinetics. SLNB offered significant protection to murine splenic lymphocytes against 4 Gy ionizing radiation (IR) induced apoptosis. Oral administration of SLNB exhibited ~70% protection to mice against whole body irradiation (WBI 7.5 Gy) induced mortality. Oral relative bioavailability of BCL was enhanced by over ~300% after entrapment in the SLNB as compared to BCL. Oral dosing of SLNB resulted in transient increase in neutrophil abundance in peripheral blood. Interestingly, we observed that treatment of human lung cancer cells (A549) with radioprotective dose of SLNB exhibited radio-sensitization as evinced by decrease in survival and clonogenic potential. Contrary to antioxidant nature of baicalein in normal cells, SLNB treatment induced significant increase in cellular ROS levels in A549 cells probably due to higher uptake and inhibition of TrxR. Thus, a pharmaceutically acceptable SLNB exhibited improved bioavailability, better radioprotection to normal cells and sensitized cancer cells to radiation induced killing as compared to BCL suggesting its possible utility as an adjuvant during cancer radiotherapy.

Role of Faith healers: A barrier or a support system to medical care- a cross sectional study.

BACKGROUND AND AIMS: Faith healing is a method of treating illnesses through the exercise of faith rather than medical methods. The current study was done with the objective to find out demographic variables of faith healers, various conditions for which the people approach them, various practices and processes used and to look for scope of integrated approach to healthcare with faith healers. SETTINGS AND DESIGN: RHTC village was a sub center village of PHC Morad. Hence, for the study, all the villages which comes under PHC Morad were selected. The design of the study was a cross-sectional study. METHODS AND MATERIAL: The study was a cross sectional study where faith healers were interviewed based on a semi structured questionnaire comprising of both close and open-ended questions. STATISTICAL ANALYSIS USED: Absolute numbers. RESULTS: Different reasons for which the persons usually came for ranged from supernatural possession, unemployment, family problems etc., and various different processes were used by these healers to solve the problems included giving charms and amulets, personal sacrifices like "baddha" (Nischay/praan) and many others. CONCLUSION: The study concludes that faith healers in many conditions and situations became the first point of contact as the faith of the community in these faith healers is deeply rooted.

Thermostable and alkalistable exopolygalacturonase of Bacillus pumilus dcsr1: Characteristics and applicability.

The bioactive form of thermostable and alkali stable pectinase of Bacillus pumilus dcsr1 is a homodimer of the molecular mass of 60 kDa with a pI of 4.6. The enzyme is optimally active at 50 °C and pH 10.5, and its Michaelis constant (Km), maximum rate of reaction (Vmax), activation energy (Ea), and temperature quotient (Q10) values (for citrus pectin) are 0.29 mg mL-1, 116 µmole mg-1 min-1, 74.73 KJmol-1 and 1.57, respectively. The enzyme has a shelf life of one and a half years at room temperature as well as 4 °C. The activity of the enzyme is stimulated by Mn2+ and Ca2+ and inhibited by Hg+, Cd2+, Co2+, Zn2+, Fe2+, Pb2+, EDTA and urea to a varied extent. The conformational studies of the enzyme revealed a high ß-sheet content in the bioactive dimer, and high α-helix in the inactive monomer. The Circular Dichroism (CD) spectra of the dimer in the presence of inhibitors suggested a marked decrease in ß-sheet, and a significant increase in α-helix, suggesting a key role of ß-sheets in the enzyme catalysis. Based on the end product analysis, the enzyme is an exopolygalacturonase with a unique ability of transglycosylation. When ramie fibers were treated with the enzyme, removal of gummy material (pectin) was visible, confirming its applicability in the degumming process.

Physico-chemical, antioxidant and anti-microbial properties of some Ethiopian mono-floral honeys.

Honey has been widely used to treat several human pathogens. However, all honeys may not have equal potencies against different human pathogens. The purpose of the current work was to investigate the physico-chemical and antimicrobial qualities of some mono-floral honeys from Ethiopia against some human pathogen bacteria and fungi. In the study, seven different botanical origin honeys were used of which some were from plants known for their medicinal properties. The samples were tested for their major physico-chemical properties (sugar profiles, total free acids, pH, color, electric conductivity and total soluble substances) and their medicinal values as total antioxidant capacity, total phenolic content and antimicrobial properties as minimum inhibitory concentration against some human pathogens, following standard protocols. Generally, the average values of the physico-chemical properties of the samples were within the acceptable ranges of world honey quality values. The average total antioxidant value of the samples was 320.3 ± 15.1 with range of 225.4 ± 12.8-465.7 ± 21.8 µM Fe(II)/100g. Relatively higher values 421.5 ± 23.4 and 465.7 ± 21.8µM Fe(II)/100g recorded for Croton macrostachyus and Vernonia amygalina honeys respectively. The average phenolic contents of the samples varied from 233.3 ± 24.0 to 693.3 ± 26.8 mgGAE/kg and relatively higher values recorded for C. macrostachys and V. amygdalina honeys. The significant proportion of the tested samples showed strong antimicrobial qualities inhibiting the growth of tested pathogens at concentration of 10.5%-28.6% of MIC (% v/v). Honeys from medicinal plants (C. macrostachys and V. amygdalina) relatively showed more antimicrobial properties which could be due to the presence of plant specific phytochemicals which require further investigations.

Formulation, Development, and Evaluation of Herbal Effervescent Mouthwash Tablet Containing Azadirachta Indica (Neem) and Curcumin for the Maintenance of Oral Hygiene.

BACKGROUND: Dental caries originate due to the localized dissolution of the hard tissues of teeth, mainly caused by acids, developed by the presence of microorganisms in the biofilm (dental plaque) on the surface of teeth causing "cavities". Commercially available liquid mouthwashes containing synthetic active ingredients possess limitations like teeth staining, higher alcoholic content, taste disturbances, xerostomia, and stability issues. OBJECTIVE: To make the solid preparation for oral hygiene (US6428770B1) in the form of herbal effervescent mouthwash tablet (CN106619318A, US8728446B2) using Azadirachta indica and Curcumin having antimicrobial, antibacterial, antiplaque, and anti-inflammatory activity. METHODS: The optimization study of effervescent granules was performed by 33 factorial design. A total of 27 preliminary experimental batches were prepared by the fusion method, varying the amount of citric acid, tartaric acid, and sodium bicarbonate. A complex of curcumin was prepared with hydroxyl propyl ß-cyclodextrin and further examined by scanning electron microscopy. The prepared tablets were evaluated for pre and post-compression parameters. The in vitro antimicrobial study was performed by Agar well diffusion method against S. mutans. RESULTS: All the experimental batches of effervescent granules were evaluated for pH, effervescent time, and CO2 content. Six batches were further selected for final tablet preparation. The results of the pre-compression parameters revealed excellent flow properties and post-compression parameters; the results were also significant. The antimicrobial study revealed the F3 as a final best formulation. CONCLUSION: The developed herbal formulation (F3) has a good potential to maintain oral hygiene as compared to alcoholic mouthwash and further studies may be necessary to confirm the efficacy of the formulation since only a single bacterial strain was assayed.

A potent enzybiotic against methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus is one of the most dreadful infectious agents, responsible for high mortality and morbidity in both humans and animals. The increased prevalence of multidrug-resistant (MDR) Staphylococcus aureus strains has limited the number of available treatment options, which calls for the development of alternative and effective modalities against MDR S. aureus. Endolysins are bacteriophage-derived antibacterials, which attack essential conserved elements of peptidoglycan that are vital for bacterial survival, making them promising alternatives or complements to existing antibiotics for tackling such infections. For developing endolysin lysin-methicillin-resistant-5 (LysMR-5) as an effective antimicrobial agent, we evaluated its physical and chemical characteristics, and its intrinsic antibacterial activity against staphylococcal strains, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we cloned, expressed, and purified LysMR-5 from S. aureus phage MR-5. In silico analysis revealed that LysMR-5 harbors two catalytic and one cell wall-binding domain. Biochemical characterization and LC-MS analysis showed that both catalytic domains were active and had no dependence on divalent ions for their action, Zn2+ exerted a negative effect. The optimal lytic activity of the endolysin was at 37 °C/pH 7.0 and in the presence of ≥ 300 mM concentration of NaCl. Circular dichroism (CD) demonstrated a loss in secondary structure with an increase in temperature confirming the thermosensitive nature of endolysin. Antibacterial assays revealed that LysMR-5 was active against diverse clinical isolates of staphylococci. It showed high lytic efficacy against S. aureus ATCC 43300, as an endolysin concentration as low as 15 µg/ml was sufficient to achieve maximum lytic activity within 30 min and it was further confirmed by scanning electron microscopy. Our results indicate that rapid and strong bactericidal activity of LysMR-5 makes it a valuable candidate for eradicating multidrug-resistant S. aureus.