Pharmacological properties of mangiferin: bioavailability, mechanisms of action and clinical perspectives.

This review aims to provide an in-depth analysis of the pharmacological properties of mangiferin, focusing primarily on its bioavailability and mechanisms of action, and its potential therapeutic applications, especially in the context of chronic diseases. We conducted a comprehensive examination of in vitro and in vivo studies, as well as clinical trials involving mangiferin or plant extracts containing mangiferin. The primary source of mangiferin is Mangifera indica, but it's also found in other plant species from the families Anacardiaceae, Gentianaceae, and Iridaceae. Mangiferin has exhibited a myriad of therapeutic properties, presenting itself as a promising candidate for treating various chronic conditions including neurodegenerative disorders, cardiovascular diseases, renal and pulmonary diseases, diabetes, and obesity. Despite the promising results showcased in many in vitro studies and certain animal studies, the application of mangiferin has been limited due to its poor solubility, absorption, and overall bioavailability. Mangiferin offers significant therapeutic potential in treating a spectrum of chronic diseases, as evidenced by both in vitro and clinical trials. However, the challenges concerning its bioavailability necessitate further research, particularly in optimizing its delivery and absorption, to harness its full medicinal potential. This review serves as a comprehensive update on the health-promoting and therapeutic activities of mangiferin.

Major Targets Involved in Clinical Management of Migraine.

BACKGROUND: There has been a protracted effort to identify reliable targets for migraine. It is believed that each year, hundreds of millions of individuals worldwide suffer from migraines, making this widespread neurological ailment the second leading cause of years of disability worldwide. The rationale of this study is to identify the major targets involved in migraine attacks. METHODS: For this review, specialized databases were searched, such as PubMed, EMBASE, DynaMed Plus, and Science Direct databases that included the pathophysiological mechanisms of migraine, focusing on in vitro and in vivo studies in the clinical management of migraine. RESULTS: Calcitonin gene-related peptide, Pituitary adenylate cyclase-activating polypeptide (PACAP), NOD-like receptor Protein (NLRP3), Serotonin, and some other neuroinflammatory biomarkers are collectively responsible for the cerebral blood vessel dilation and involved in the nociceptive pain which leads to migraine attack. CONCLUSION: Migraine biomarkers such as CGRP, PACAP, NLRP3, Nitric oxide synthase, MMP9, and Serotonin could be targets for developing drugs. Present marketed medications temporarily reduce symptoms and pain and have serious cardiovascular side effects. It is suggested that herbal treatment may help prevent migraine attacks without adverse effects. Natural biomolecules that may give better treatment than the present marketed medication and full fledge research should be carried out with natural biomarkers by the Network Pharmacological approach.

Theoretical evaluation of Cleome species' bioactive compounds and therapeutic potential: A literature review.

The species of Cleome genus are taxonomically included in the family of Cleomaceae and in the order of Brassicales, representing flowering plants with a long history of use in traditional medicine. Phytochemical screening experiments revealed that Cleome species contain a wide range of beneficial bioactive compounds, including alkaloids, essential oils, fatty acids, flavonoids, terpenes, sterols, and anthocyanins, indicating a therapeutic potential. Furthermore, due to the presence of these phytocompounds, there are various plant species in this genus that have demonstrated a wide range of genotypic, chemo typic, and biological activity in several ecological settings around the world. The potential biological actions and pharmacological effects, such as analgesic, anti-inflammatory, antipyretic, anti-diabetic, antidepressant, antibacterial, anti-arthritic, anticancer, and hepatoprotective are closely related to the active substances contained in various parts of the plants. By centralizing medical data provided by the scientific literature, we offer in the present work a comprehensive perspective on a wide range of bioactive compounds identified from diverse Cleome species, emphasizing the correlation of natural active substances with potential pharmacological activities that can contribute to the improvement of therapeutic management for a range of pathologies. In addition, this review suggests future research perspectives to improve the use of phytochemicals contained in the species of Cleome genus, both in terms of increasing therapeutic efficacy and safety profiles, but also in terms of identifying a possible new pharmacological effect.

Computer Aided Drug Design Approach to Screen Phytoconstituents of Adhatoda vasica as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme.

A novel coronavirus (COVID-19) was identified as one of the severe acute respiratory syndrome coronaviruses (SARS-CoV-2) and emerged as a pandemic in 2020. Thus, there is an urgent need to screen and develop an agent to suppress the proliferation of viral particles of SARS-CoV-2, and several drugs have entered clinical trial phases to assess their therapeutic potential. The objective of the present study is to screen phytochemicals against the main viral protease using molecular docking studies. The phytochemicals vasicine, vasicinone, vasicinolone, vasicol, vasicolinone, adhatodine, adhavasicinone, aniflorine, anisotine, vasnetine, and orientin from Adhatoda vasica were selected, and the compounds were docked with various viral protein targets, including specific SARS-CoV-2 main protease (PDBID:6Y84), using AutoDock, Schrodinger, Biovia discovery studio, and virtual screening tools. Adhatodine and vasnetine showed a better binding affinity of -9.60 KJ/mol and -8.78 KJ/mol, respectively. In molecular docking simulations for 10 ns, these compounds illustrated strong hydrogen-bonding interactions with the protein active site and induced a potential conformational change in the ligand-binding site. The results were compared with the antiviral drugs nirmatrelvir and ritonavir. These results suggest that these phytochemicals can be studied as potential inhibitors against SARS-CoV-2 protease and may have an antiviral effect on coronavirus. However, further in vitro and in vivo efficacy activity needs to be investigated for these phytochemicals.

Development and characterization of a nano-drug delivery system containing vasaka phospholipid complex to improve bioavailability using quality by design approach.

BACKGROUND AND PURPOSE: Vasicine is a potential bronchodilator and can be used for the effective management of asthma and bronchitis. It has low absorption in the gastrointestinal tract due to its poor solubility thereby low bioavailability. The objective of this research was to develop a novel drug delivery system of vasaka extract to improve its bioavailability by enhancing the solubility and absorption of vasicine. EXPERIMENTAL APPROACH: Vasaka-loaded phytosomes were developed and optimized by thin-layer hydration technique using systematic quality by design approach. Box-Behnken design (32 factorial design) using Design-Expert software was employed to optimize phytosome wherein phosphatidylcholine concentration (X1), stirring temperature (X2), and stirring time (X3) were selected as independent variables. Yield (%), particle size (nm), and entrapment efficiency (%) were evaluated as responses. The optimized phytosome was characterized by studying the surface morphology such as FE-SEM and TEM analysis, thermal characteristics by thermal gravimetric analysis and spectral and diffraction studies by FTIR and XRD analysis and studying the dissolution behaviour of phytosome by in vitro release study. FINDINGS/RESULTS: The percentage yield, particle size, and entrapment efficiency values of the phytosomes were found in the range of 30.03-97.03%, 231.0-701.4 nm, and 20.02-95.88% w/w, respectively. The optimized phytosome showed the zeta potential of -23.2 mV exhibited good stability and SEM and TEM analysis revealed the spherical shape and smooth particles with the uniform particle size distribution of phytosomes. The comparative in vitro drug release study of vasaka extract and phytosome revealed the sustained release characteristics of phytosome which reached 68.80% at 8 h compared to vasaka extract reached a maximum of 45.08% at 4 h. CONCLUSION AND IMPLICATION: The results highlighted the importance of optimization of formulation development using quality by design strategy to achieve consistent quality of pharmaceutical products.

Pharmacological inhibition of guanosine triphosphate cyclohydrolase1 elevates tyrosine phosphorylation of caveolin1 and cellular senescence.

The role of 2,4-diamino-6-hydroxypyrimidine (DAHP), on cellular-senescence remains unclear as differential effects of DAHP have been reported in cardiovascular and cerebrovascular systems. We investigated the effect of pharmacologically-induced guanosine-triphosphate-cyclohydrolase1 (GTPCH1)-inhibition, through DAHP, on cellular-senescence in experimentally-induced diabetic and non-diabetic Wistar rats. Cellular-senescence was evaluated through senescence-associated events, namely, cell-cycle-arrest of peripheral blood mononuclear cells (PBMNCs); myocardial DNA fragmentation, total antioxidant capacity (TAC), telomerase-activity, nicotinamide adenine dinucleotide (NAD+)-content and tyrosine14-phosphorylation of caveolin1 (pY14) in similarly-aged, pubertal Wistar rats with streptozotocin (STZ) and/or DAHP. Oxidative stress (OS) indices such as myocardial biopterin concentrations (tetrahydrobiopterin-BH4 and dihydrobiopterin-BH2) and plasma total nitrite and nitrate (NOx) were determined. DAHP, per se, exhibited distinct senescence; in addition, in STZ+DAHP (the cardiomyopathy model), there was a marked accumulation of cells in G0G1 phase, as evidenced through flow-cytometry analysis, as-well-as fragmented DNA, than the respective controls suggesting the DAHP-mediated onset of senescence in circulating cells and the myocardium, with or without STZ. Concentrations of BH4 and BH2, and NOx were impaired in STZ and/or DAHP, indicating elevated OS in the treatment groups. In the independent treatment groups or the combination treatment, typical senescence indicators including myocardial telomerase-activity, NAD+-content and TAC were significantly reduced, while there was a marked elevation in the concentrations of pY14 as compared to the respective controls, reinforcing the occurrence of senescence in PBMNCs and the myocardium. We postulate that DAHP promotes early onset of cellular-senescence, potentially through OS-mediated cellular events in diabetic or non-diabetic models.

Rosmarinic acid attenuates hepatic steatosis by modulating ER stress and autophagy in oleic acid-induced HepG2 cells.

Non-alcoholic fatty acid disease (NAFLD) has become an emerging entity of liver disorders worldwide. Oxidative stress and deranged autophagy-induced endoplasmic reticulum (ER) stress has recently been recognized as one of the prime factors involved in the pathological mechanism underlying NAFLD and progressive non-alcoholic steato-hepatitis (NASH). Epidemiological and experimental data reveal the potency of dietary polyphenols in averting NAFLD. In this line, to analyse and address the underlying pathogenic mechanisms, in the present study, oleic acid-induced HepG2 cells were treated with rosmarinic acid (RA), a dietary polyphenol with well-established cytoprotective properties. Treatment with rosmarinic acid (20 µg) was found to potently counter the elevated levels of total cholesterol (TC) and triglycerides (TG). Additionally, exposure of oleic acid-induced HepG2 cells to rosmarinic acid showed reduced levels of ROS and increased activity of enzymic and non-enzymic antioxidants. The steatotic HepG2 cells presented a pronounced increase in the expression of key ER stress markers such as p-PERK, p-IRE-1, ATF-6, p-eIF-α and CHOP, which was considerably reduced upon treatment with rosmarinic acid. Moreover, exposure to rosmarinic acid altered the deranged autophagic mechanism in oleic acid-induced HepG2 cells, which was observed via the protein expression of Beclin 1, LC31, ATG5 and ATG7. This study demonstrates that rosmarinic acid abrogates NAFLD via diminishing ER stress by nullifying oxidative stress and restoring deranged autophagy and can be used as a potent adjunct in the treatment of NAFLD, thus illustrating the valuable application of polyphenols in combating NAFLD.

Inhibition of New Delhi Metallo-ß-Lactamase 1 (NDM-1) Producing Escherichia coli IR-6 by Selected Plant Extracts and Their Synergistic Actions with Antibiotics.

Improper use of antibiotics has led to a great concern in the development of pathogenic microbial resistance. New Delhi metallo-ß-lactamase 1 (NDM-1) producing bacteria are resistant to most of the ß-lactam antibiotics, and so far, no new compounds have been clinically tested against these bacteria. In this study, ethanol extracts from the leaves of 240 medicinal plant species were screened for antibacterial activity against an NDM-1 Escherichia coli strain. The extracts that showed antibacterial activity were then tested for minimum inhibitory concentrations (MICs) and zones of inhibition. The extract from Combretum albidum G. Don, Hibiscus acetosella Welw. ex Hiern, Hibiscus cannabinus L., Hibiscus furcatus Willd., Punica granatum L., and Tamarindus indica L. showed bactericidal activity between 5 and 15 mg/ml and the MIC was between 2.56 and 5.12 mg/ml. All six plant extracts inhibited activity of the NDM-1 enzyme in vitro, and the IC50 value ranged between 0.50 and 1.2 ng/µl. Disruption of bacterial cell wall integrity by the plant extracts was clearly visible with scanning electron microscopy. Increases in membrane permeability caused 79.4-89.7% bacterial cell deaths as investigated by fluorescence-activated cell sorting. All the plant extracts showed synergistic effects when combined with colistin [fractional inhibitory concentration (ΣFIC) = 0.125-0.375], meropenem (ΣFIC = 0.09-0.313), and tetracycline (ΣFIC = 0.125-0.313). Thus, the plant extracts can be fractionated for the identification of active compounds, which could be used as new antibacterial compounds for the development of drugs against NDM-1 E. coli in addition to their use in combination therapy.

Design, synthesis and α-amylase inhibitory activity of novel chromone derivatives.

Quercetin is one of the naturally occurring polyphenol flavonoid predominantly known for antidiabetic activity. In the present study, by considering the structural requirements, twenty two novel chromone derivatives (5-26) as α-amylase inhibitor were designed and subsequently in silico evaluated for drug likeness behavior. Designed compounds were synthesized, characterized by spectral analysis and finally evaluated for the inhibition of α-amylase activity by in vitro assay. Tested compounds exhibited significant to weak activity with IC50 range of 12-125µM. Among the tested compounds, analogues 5, 8, 12, 13, 15, 17 and 22 exhibited significant human α-amylase inhibitory activity with IC50 values <25µM, which can be further explored as anti-hyperglycemic agents. Putative binding mode of the significant and least active α-amylase inhibitors with the target enzyme was also explored by the docking studies.

A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and ß-amyloid plaques in a triple transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative disorder typified by progressive deterioration of memory and the appearance of ß-amyloid peptide (Aß)-rich senile plaques. Recently we have identified a novel function of a patented formulation of modified Huanglian-Jie-Tu-Tang (HLJDT-M), a Chinese herbal medicine, in treating AD in in vitro studies (US patent No. 9,375,457). HLJDT-M is a formulation composed of Rhizoma Coptitis, Cortex Phellodendri and Fructus Gardeniae without Radix Scutellariae. Here, we assessed the efficacy of HLJDT-M on a triple transgenic mouse model of AD (3XTg-AD). Oral administration of HLJDT-M ameliorated the cognitive dysfunction of 3XTg-AD mice and lessened the plaque burden. In addition, biochemical assays revealed a significant decrease in levels of detergent-soluble and acid-soluble Aß via decreasing the levels of full length amyloid-ß precursor protein (FL-APP) and C-terminal fragments of APP (CTFs) in brain lysates of HLJDT-M-treated mice. HLJDT-M treatment also significantly reduced the levels of FL-APP and CTFs in N2a/SweAPP cells. In contrast, treatment using the classical formula HLJDT did not reduce the memory impairment of 3XTg-AD mice and, rather, increased the Aß/Fl-APP/CTFs in both animal and cell culture studies. Altogether, our study indicates that HLJDT-M is a promising herbal formulation to prevent and/or cure AD.

Rosmarinic Acid Mediates Mitochondrial Biogenesis in Insulin Resistant Skeletal Muscle Through Activation of AMPK.

Rosmarinic acid (RA), a polyphenol, is known to improve hepatic insulin sensitivity in experimental type 2 diabetes. However, its effect on skeletal muscle insulin resistance is meagerly understood. The present study was aimed to investigate the up- and downstream mediators of the molecular targets of RA in attenuating insulin resistance in the skeletal muscle both in vivo and in vitro. We found that supplementation of RA increased the expression of key genes involved in the mitochondrial biogenesis like PGC-1α, SIRT-1, and TFAM via activation of AMPK in the skeletal muscle of insulin resistant rats as well as in L6 myotubes. Further, RA treatment increased the glucose uptake and decreased the phosphorylation of serine IRS-1 while increasing the translocation of GLUT 4. Together, our findings evidenced that RA treatment significantly inhibit insulin resistance in skeletal muscle cells by enhancing mitochondrial biogenesis. J. Cell. Biochem. 118: 1839-1848, 2017. © 2017 Wiley Periodicals, Inc.

Novel hybrids of drug with bioactive heterocycles for enhancing biological activity.

A novel series of aceclofenac hybridised with 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles were designed using molecular hybridization approach and synthesised 6a-j. The structural integrity was confirmed by analytical methods. The hybrid molecules were subjected to in vitro cytotoxic studies against four human cancer cell lines PA-1, OAW-42, T47-D and MCF-7 by MTT assay method. The results indicate that the hybrid molecules bearing halogen on phenyl ring in 6th position of triazolo-thiadiazole exhibited significant cytotoxic activity. The test compounds were also screened for antifungal activity against two strains.

Comparative inhibitory potential of selected dietary bioactive polyphenols, phytosterols on CYP3A4 and CYP2D6 with fluorometric high-throughput screening.

Cytochrome P450 (CYP450) inhibition by the bioactive molecules of dietary supplements or herbal products leading to greater potential for toxicity of co-administered drugs. The present study was aimed to compare the inhibitory potential of selected common dietary bioactive molecules (Gallic acid, Ellagic acid, ß-Sitosterol, Stigmasterol, Quercetin and Rutin) on CYP3A4 and CYP2D6 to assess safety through its inhibitory potency and to predict interaction potential with co-administered drugs. CYP450-CO complex assay was carried out for all the selected dietary bioactive molecules in isolated rat microsomes. CYP450 concentration of the rat liver microsome was found to be 0.474 nmol/mg protein, quercetin in DMSO has shown maximum inhibition on CYP450 (51.02 ± 1.24 %) but less when compared with positive control (79.02 ± 1.61 %). In high throughput fluorometric assay, IC50 value of quercetin (49.08 ± 1.02-54.36 ± 0.85 µg/ml) and gallic acid (78.46 ± 1.32-83.84 ± 1.06 µg/ml) was lower than other bioactive compounds on CYP3A4 and CYP2D6 respectively but it was higher than positive controls (06.28 ± 1.76-07.74 ± 1.32 µg/ml). In comparison of in vitro inhibitory potential on CYP3A4 and CYP2D6, consumption of food or herbal or dietary supplements containing quercetin and gallic acid without any limitation should be carefully considered when narrow therapeutic drugs are administered together.

Quantitative analysis of heavy metals in medicinal plants collected from environmentally diverse locations in India for use in a novel phytopharmaceutical product.

It is important to monitor the quality of the phytopharmaceutical product as its therapeutic potential depends on standardized delivery of active ingredients present in the botanical source. Minimal presence of toxic impurities like heavy metals (HMs) is warranted to ensure product safety and prevent hazardous health impacts. In the present study, conducted as part of the development of a novel phytopharmaceutical product, the chemical profile of 13 heavy metals (Fe, Cu, Mn, Zn, Ni, Co, Mo, V, Cr, As, Pb, Hg, and Cd) was studied in the whole plant, fruit, and rhizome of Bacopa monnieri, Hippophae rhamnoides, and Dioscorea bulbifera, respectively, from environmentally diverse regions in India. Most samples had HM profiles within permissible limits as established by regulatory authorities, with the exception of Cd and Hg in low-altitude regions. This study indicates geographical regions in India suitable for procuring raw materials to develop and manufacture phytopharmaceutical products.

Design, synthesis and QSAR studies on a series of 2, 5-disubstituted- 1,3,4-oxadiazole derivatives of diclofenac and naproxen for analgesic and anti-inflammatory activity.

A series of twenty molecules belonging to 2,5-disubstituted-1,3,4-oxadiazole derivatives of Diclofenac and Naproxen were designed, synthesized and their structures were confirmed by spectroscopy. The target compounds were evaluated for anti-inflammatory and analgesic activity. The result indicates that the compounds 12, 4, 6, 7 and 15 were found to have good analgesic and anti-inflammatory activities, while the compounds 12 and 14 were found to have good analgesic and the compound 22 were found to have good anti-inflammatory activities. HQSAR and Topomer QSAR studies were performed to get insights in the structures contributing for biological activity. The compounds bearing mono-substitution such as Cl, OCH3 and NO2 in the phenyl ring were found to have maximum analgesic and anti-inflammatory activities.

Assessment of montelukast, doxofylline, and tiotropium with budesonide for the treatment of asthma: which is the best among the second-line treatment? A randomized trial.

PURPOSE: Data comparing various second-line treatments for asthma with subjective and objective assessment are lacking. This study aimed to compare the efficacy and safety of montelukast, doxofylline, and tiotropium with a low-dose budesonide in patients with mild to moderate persistent asthma. METHODS: Patients, all of whom were concurrently using inhaled budesonide (400 µg), were treated for 6 months with formoterol (12 µg), montelukast (10 mg), doxofylline (400 mg), or tiotropium (18 µg). Outcomes included forced expiratory volume in 1 second (FEV1), Saint George Respiratory Questionnaire (SGRQ) scores, asthma symptom scores (daytime and nighttime), and assessment of tolerability and rescue medication use. FINDINGS: A total of 297 patients completed the study. In all 4 groups, significant improvements were observed in all the outcome measures, with formoterol treatment having greater and earlier improvements than the other 3 second-line controller medications with budesonide. Among the second-line treatments, monteradlukast improved the FEV1 from day 45 (P < 0.01), SGRQ scores from day 30 (P < 0.0001), daytime scores from day 30 (P < 0.05), nighttime scores from day 30 (P < 0.0001), and rescue medication use from day 15 (P < .0001) at a faster rate than doxofylline or tiotropium with budesonide. No patients discontinued the treatment because of adverse reactions. IMPLICATIONS: Among the tested second-line treatment regimens, the budesonide/montelukast combination was found to be superior to either the budesonide/doxofylline or budesonide/tiotropium combination in all the outcome measures without adversely affecting the tolerability of the patients. Further clinical studies with blinding techniques are likely to be useful.

Management of cognitive determinants in senile dementia of Alzheimer's type: therapeutic potential of a novel polyherbal drug product.

BACKGROUND AND OBJECTIVE: The enigmatic etiology of neurodegenerative diseases poses a challenge for the development of novel and efficient drugs. The objective of the present study was to evaluate the efficacy of a polyherbal (test) formulation on cognitive functions, inflammatory markers and oxidative stress in healthy elderly as well as senile dementia of Alzheimer's type (SDAT) patients. METHOD: A randomized double-blind placebo- and active-controlled clinical trial was performed in healthy elderly subjects and SDAT patients with an age range of 60-75 years. The polyherbal test formulation along with a placebo was given to healthy elderly subjects while the SDAT patients received either the test formulation containing extracts of Bacopa monnieri (whole plant), Hippophae rhamnoides (leaves and fruits) and Dioscorea bulbifera (bulbils) at a dose of 500 mg or donepezil drug (Aricept) at a dose of 10 mg, twice daily, for a period of 12 months. After every three months, cognitive functions were assessed by determining the mini mental state examination (MMSE) score, digital symbol substitution (DSS; subtest of the Wechsler Adult Intelligence Scale-Revised), immediate and delayed word recall (digital memory apparatus-Medicaid systems, Chandigarh, India), attention span (Attention Span Apparatus-Medicaid systems, Chandigarh, India), functional activity questionnaire (FAQ) and depression (geriatric depression scale) scores. Further inflammatory markers and level of oxidative stress were analyzed using standard biochemical tests. RESULTS: The trial was performed in 109 healthy subjects and 123 SDAT patients of whom 97 healthy subjects and 104 SDAT patients completed the study. Administration of the test formulation for a period of 12 months was effective in improving cognitive functions in the SDAT patients, when compared to the donepezil-treated group, as determined by the DSS (38.984 ± 3.016 vs 35.852 ± 4.906, P = 0.0001), word recall immediate (3.594 ± 1.003 vs 2.794 ± 0.593, P < 0.0001) and attention span (4.918 ± 1.239 vs 4.396 ± 0.913, P = 0.0208) scores. A significant improvement in the FAQ (11.873 ± 2.751 vs 9.801 ± 1.458, P < 0.0001) and depression (16.387 ± 2.116 vs 21.006 ± 2.778, P < 0.0001) scores was also observed, whereas no significant differences were observed in the MMSE and word recall delayed scores. The level of inflammation and oxidative stress was markedly reduced in the SDAT patients treated with the test formulation when compared to the donepezil-treated group indicating a likely mechanism of action of the test formulation (homocysteine 30.22 ± 3.87 vs 44.73 ± 7.11 nmol/L, P < 0.0001; C-reactive protein [CRP] 4.751 ± 1.149 vs 5.887 ± 1.049 mg/L, P < 0.0001; tumour necrosis factor alpha [TNF-α] 1139.45 ± 198.87 vs 1598.77 ± 298.52 pg/ml, P < 0.0001; superoxide dismutase [SOD] 1145.92 ± 228.75 vs 1296 ± 225.72 U/g Hb, P = 0.0013; glutathione peroxidase [GPx] 20.78 ± 3.14 vs 25.99 ± 4.11 U/g Hb, P < 0.0001; glutathione [GSH] 9.358 ± 2.139 vs 6.831 ± 1.139 U/g Hb, P < 0.0001; thiobarbituric acid reactive substances [TBARS] 131.62 ± 29.68 vs 176.40 ± 68.11 nmol/g Hb, P < 0.0001). Similarly, when healthy elderly subjects treated with the test formulation for 12 months were compared to the placebo group, a significant (P < 0.001) improvement in cognitive measures (MMSE, DSS, word recall delayed but not immediate, attention span, FAQ and depression scores) and a reduction in inflammation (reduction in homocysteine, CRP, IL-6 and TNF-α levels) and oxidative stress levels (reduction in SOD, GPx and TBARS and increase in GSH) was observed. This indicated a protective effect of the test formulation in managing cognitive decline associated with the ageing process. CONCLUSION: The results of this study demonstrate the therapeutic potential of this novel polyherbal formulation for the management and treatment of SDAT.

Anticancer activity of Moringa oleifera mediated silver nanoparticles on human cervical carcinoma cells by apoptosis induction.

Silver nanomaterial plays a crucial role in the growing field of nanotechnology as there is an increasing commercial demand for silver nanoparticles (AgNPs) owing to their wide biological applications. The present investigation aims at developing anti-cancerous colloidal silver using Moringa olifera stem bark extract. Electron and atomic force microscopic images were taken to analyze the surface morphology of the synthesized AgNPs. The effects of synthesized AgNPs were tested against human cervical carcinoma cells (HeLa) and cell morphology was further evaluated using 4,6-diamidino-2-phenylindole (DAPI) staining. The efficiency of green synthesized AgNPs was studied with the help of fluorescence activated cell sorting (FACS) and was shown to induce apoptosis through reactive oxygen species (ROS) generation in HeLa cells.

Assessment of various second-line medications in addition to inhaled corticosteroid in asthma patients: a randomized controlled trial.

Many patients with persistent asthma cannot achieve the treatment goal for asthma with a single controller medication. The aim of the present study was to assess lung function and rescue medication use in asthma patients receiving four different categories of drugs in combination with an inhaled corticosteroid. Patients recruited to the study were randomized into four groups to receive budesonide with either formoterol, doxofylline, montelukast or tiotropium for a period of 3 months. Lung function (i.e. forced expiratory volume in 1 s (FEV1 )) and rescue medication use were determined at baseline and on Day 15, 30, 45, 60 and 90 of treatment. A total of 297 patients completed the study. At baseline, no significant differences (P > 0.05) were observed in any of the outcome measures. Significant within-group improvement in FEV1 was observed in all groups. On Day 90, between-group differences showed that the improvement in FEV1 was significantly (P < 0.05) higher for patients receiving budesonide + formoterol, followed by budesonide + montelukast and budesonide + doxofylline, and least for those receiving budesonide + tiotropium. Similarly, within- and between-group comparisons showed significant (P < 0.05) reductions in rescue medication use in all groups. However, the magnitude of the decrease was greater in the budesonide + formoterol group, followed by the budesonide + montelukast, budesonide + doxofylline and budesonide + tiotropium groups. Based on our findings, among the second-line treatment regimens, budesonide with either montelukast or doxofylline was found to be better than budesonide + tiotropium in patients with mild-to-moderate persistent asthma. Further studies with a longer duration are likely to be useful.

Pulmonary function assessment in mild to moderate persistent asthma patients receiving montelukast, doxofylline, and tiotropium with budesonide: a randomized controlled study.

BACKGROUND: There is no comparative study among asthma patients receiving first-line versus various second-line treatment regimens for mild to moderate persistent asthma. OBJECTIVE: We assessed the pulmonary function in asthma patients receiving montelukast, doxofylline, and tiotropium with budesonide in a pilot group. METHODS: Patients were recruited as per the study criteria and randomly allocated to 4 groups to receive budesonide (400 µg) with formoterol (12 µg), doxofylline (400 mg), montelukast (10 mg), or tiotropium (18 µg) for a period of 3 months. Outcomes included forced expiratory volume in 1 second (FEV1) and rescue medication use. RESULTS: A total of 167 patients were recruited; among them, 123 patients completed the study. At baseline, no significant difference (P > 0.05) was observed in any of the outcome measures. Significant within-group improvement in FEV1 was observed in all the groups. At day 90, between-group difference revealed that improvement in FEV1 was significantly (P < 0.05) high for budesonide plus formoterol followed by budesonide plus doxofylline, budesonide plus montelukast, and, lastly, budesonide plus tiotropium. Similarly, within-group comparison revealed a significant (P < 0.05) reduction in rescue medication use in all the groups. The intensity in decrease was more in budesonide plus formoterol group followed by budesonide plus doxofylline, budesonide plus montelukast, and budesonide plus tiotropium groups. CONCLUSION: On the basis of our findings, among the second-line treatment regimens, budesonide plus doxofylline and budesonide plus montelukast was found to be better than budesonide plus tiotropium in patients with mild to moderate persistent asthma. Further studies with a larger sample size are likely to be useful.