Nutraceutically-enhanced oral delivery of vitamin D3 via Bio-SNEDDS: Demonstrating in vivo superiority over pediatric formulations.

BACKGROUND: Vitamin D3 (VD3) deficiency among children in Saudi Arabia remains a pressing concern due to its poor bioavailability and the limitations of current pediatric formulations. To address this challenge, we developed a groundbreaking pediatric self-nanoemulsifying drug delivery system (Bio-SNEDDS) for VD3, fortified with black seed oil and moringa seed oil for dual therapeutic benefits. Through meticulous formulation optimization using ternary phase diagrams and comprehensive testing, our Bio-SNEDDS demonstrated exceptional performance. METHODS: Bio-SNEDDS were manufactured by incorporating Black seed oil and moringa seed oil as bioactive nutraceutical excipients along with various cosurfactant and surfactants. Bio-SNEDDS were systematically optimized through ternary phase diagrams, visual tests, droplet size analysis, drug solubilization studies, dispersion assessments, and pharmacokinetic testing in rats compared to Vi-De 3®. RESULTS: Pseudoternary phase diagrams identified oil blends producing large nanoemulsion regions optimal for SNEDDS formation. The optimized F1 Bio-SNEDDS showed a mean droplet diameter of 33.7 nm, solubilized 154.46 mg/g VD3 with no metabolite formation, and maintained >88% VD3 in solution during 24 h dispersion testing. Notably, in vivo pharmacokinetic evaluation at a high VD3 dose demonstrated an approximately two-fold greater relative bioavailability over Vi-De 3®, validating the superb oral delivery performance of Bio-SNEDDS even under challenging high-dose conditions. CONCLUSIONS: The Bio-SNEDDS provides an effective VD3 delivery strategy with established in vivo superiority over marketed products, along with offering additional health benefits from the natural oils.

Herb-drug interaction: Effect of sinapic acid on the pharmacokinetics of dasatinib in rats.

Dasatinib (DAS) is a narrow therapeutic index drug and novel oral multitarget inhibitor of tyrosine kinase and approved for the first-line therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome (Ph + ) acute lymphoblastic leukemia (ALL). DAS, a known potent substrate of cytochrome (CYP) 3A, P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) and is subject to auto-induction. The dietary supplementation of sinapic acid (SA) or concomitant use of SA containing herbs/foods may alter the pharmacokinetics as well as pharmacodynamics of DAS, that may probably lead to potential interactions. Protein expression in rat hepatic and intestinal tissues, as well as the in vivo pharmacokinetics of DAS and the roles of CYP3 A2 and drug transporters Pgp-MDR1 and BCPR/ABCG2, suggested a likely interaction mechanism. The single dose of DAS (25 mg/kg) was given orally to rats with or without SA pretreatment (20 mg/kg p.o. per day for 7 days, n = 6). The plasma concentration of DAS was estimated by using Ultra-High-Performance Liquid Chromatography Mass spectrometry (UHPLC-MS/MS). The in vivo pharmacokinetics and protein expression study demonstrate that SA pretreatment has potential to alter the DAS pharmacokinetics. The increase in Cmax, AUC and AUMC proposes increase in bioavailability and rate of absorption via modulation of CYP3 A2, PgP-MDR1 and BCPR/ABCG2 protein expression. Thus, the concomitant use of SA alone or with DAS may cause serious life-threatening drug interactions.

Phytomediated selenium nanoparticles and light regimes elicited in vitro callus cultures for biomass accumulation and secondary metabolite production in Caralluma tuberculata.

Introduction: Caralluma tuberculata holds significant importance as a medicinal plant due to its abundance of bioactive metabolites, which offer a wide range of therapeutic potentials. However, the sustainable production of this plant is challenged by overexploitation, changes in natural conditions, slow growth rate, and inadequate biosynthesis of bioactive compounds in wild populations. Therefore, the current study was conducted to establish an in vitro based elicitation strategy (nano elicitors and light regimes) for the enhancement of biomass and production of secondary metabolites. Methods: Garlic clove extract was employed as a stabilizing, reducing, or capping agent in the green formulation of Selenium nanoparticles (SeNPs) and various physicochemical characterization analyses such as UV visible spectroscopy, scanning electron microscopy (SEM), energy dispersive X-Ray (EDX) Spectroscopy, fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) were performed. Furthermore, the effects of phytosynthesized SeNPs at various concentrations (0, 50, 100, 200, and 400 µg/L on callus proliferation and biosynthesis of medicinal metabolites under different light regimes were investigated. Results and discussion: Cultures grown on Murashige and Skoog (MS) media containing SeNPs (100 µg/L), in a dark environment for two weeks, and then transferred into normal light, accumulated maximum fresh weight (4,750 mg/L FW), phenolic contents (TPC: 3.91 mg/g DW), flavonoid content (TFC: 2.04 mg/g DW) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) antioxidant activity (85%). Maximum superoxide dismutase (SOD: 4.36 U/mg) and peroxide dismutase activity (POD: 3.85 U/mg) were determined in those cultures exposed to SeNPs (100 µg/L) under complete dark conditions. While the callus cultures proliferate on media augmented with SeNPs (200 µg/L) and kept under dark conditions for two weeks and then shifted to normal light conditions exhibited the highest catalase (CAT: 3.25 U/mg) and ascorbate peroxidase (APx: 1.93 U/mg) activities. Furthermore, LC-ESI-MS/MS analysis confirmed the effects of SeNPs and light conditions that elicited the antidiabetic metabolites (cumarins, gallic acid, caffeic acid, ferulic acid, catechin, querctin and rutin). This protocol can be scaled up for the industrial production of plant biomass and pharmacologically potent metabolites using in vitro callus cultures of C. tuberculata.

Plant Growth Hormones and Micro-Tuberization in Breaking the Seed Dormancy of Bunium persicum (Boiss.) Fedts.

Bunium persicum is a valuable medicinal plant with limited production but high market demand. It thrives predominantly in high-altitude regions. The main challenges hindering its widespread cultivation are seed dormancy and a lengthy seed-to-seed cycle, making its large-scale cultivation difficult. Six genotypes of Bunium persicum were collected from different altitudes to evaluate its germination behavior and seed dormancy. The study was conducted during 2020-23 and comprised three experiments (viz., seed germination under an open field, controlled conditions, and micro-tuberization). Under open field conditions, germination percent was genotype dependent, and the highest germination percentage, root length, and shoot length were recorded in Shalimar Kalazeera-1. Germination behavior assessment of the Bunium persicum revealed that treatment T9 (GA3 (25 ppm) + TDZ (9 µM/L)) is effective in breaking the dormancy of Bunium persicum as well as in obtaining a higher germination percent for early development of the tubers. Similarly, with regard to the effect of temperature and moisture conditions, stratification under moist chilling conditions showed effectiveness in breaking seed dormancy as the germination percentage in stratified seeds was at par with the most efficient growth hormone. With regard to the in vitro micro-propagation, direct regeneration showed multiple shoot primordia at the base of the tubers without intervening callus phase from the MS medium supplemented with BA (22.2 µM) and NAA (13.95 µM) 4 weeks after sub-culturing. Similarly, medium supplemented with JA (8.0 mg/L) and BA (22.2 µM) produced well-organized somatic embryos with shiny surfaces, which appeared at the swelled basal portion of apical stems. Further, the combination of JA (6.0 mg/L) and BA (22.2 M) was effective in developing the micro-tubers and also enhanced the weight and length of Bunium persicum micro-tubers.

Probing the Phytochemical Composition and Antioxidant Activity of Moringa oleifera under Ideal Germination Conditions.

Moringa oleifera is a rich source of polyphenols whose contents and profile may vary according to environmental conditions, harvest season, and plant tissue. The present study aimed to characterize the profile of phenolic compounds in different tissues of M. oleifera grown under different temperatures (25, 30, and 35 °C), using HPLC/MS, as well as their constituent phytochemicals and in vitro antioxidant activities. The in vitro antioxidant activity of the extracts was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis-3-ethylenebenzothiozoline-6-sulfonicacid (ABTS), and ferric-reducing antioxidant power (FRAP) methods. The polyphenolic compounds were mainly found in the leaves at 30 °C. UPLC/QTOF-MS allowed for the identification of 34 polyphenolic components in seedlings, primarily consisting of glucosides, phenols, flavonoids, and methoxy flavones. At 30 °C, the specific activities of antioxidative enzymes were the highest in leaves, followed by seedlings and then seeds. The leaf and seed extracts also exhibited a greater accumulation of proline, glycine betaine, and antioxidants, such as ascorbic acid, and carotenoids, as measured by the inhibition of ROS production. We found that changes in the expression levels of the validated candidate genes Cu/Zn-SOD, APX, GPP, and TPS lead to significant differences in the germination rate and biochemical changes. These findings demonstrate that M. oleifera plants have high concentrations of phytochemicals and antioxidants, making them an excellent choice for further research to determine their use as health-promoting dietary supplements.

Nitric Oxide and Strigolactone Alleviate Mercury-Induced Oxidative Stress in Lens culinaris L. by Modulating Glyoxalase and Antioxidant Defense System.

Developmental activities have escalated mercury (Hg) content in the environment and caused food security problems. The present investigation describes mercury-incited stress in Lens culinaris (lentil) and its mitigation by supplementation of sodium nitroprusside (SNP) and strigolactone (GR24). Lentil exposure to Hg decreased root and shoot length, relative water content and biochemical variables. Exogenous application of SNP and GR24 alone or in combination enhanced all of the aforementioned growth parameters. Hg treatment increased electrolyte leakage and malondialdehyde content, but this significantly decreased with combined application (Hg + SNP + GR24). SNP and GR24 boosted mineral uptake and reduced Hg accumulation, thus minimizing the adverse impacts of Hg. An increase in mineral accretion was recorded in lentil roots and shoots in the presence of SNP and GR24, which might support the growth of lentil plants under Hg stress. Hg accumulation was decreased in lentil roots and shoots by supplementation of SNP and GR24. The methylglyoxal level was reduced in lentil plants with increase in glyoxalase enzymes. Antioxidant and glyoxylase enzyme activities were increased by the presence of SNP and GR24. Therefore, synergistic application of nitric oxide and strigolactone protected lentil plants against Hg-incited oxidative pressure by boosting antioxidant defense and the glyoxalase system, which assisted in biochemical processes regulation.

Anti-cancer activity of guggulsterone by modulating apoptotic markers: a systematic review and meta-analysis.

Background: Guggulsterone (pregna-4,17-diene-3,16-dione; C21H28O2) is an effective phytosterol isolated from the gum resin of the tree Commiphora wightii (Family Burseraceae) and is responsible for many of the properties of guggul. This plant is widely used as traditional medicine in Ayurveda and Unani system of medicine. It exhibits several pharmacological activities, such as anti-inflammatory, analgesic, antibacterial, anti-septic and anticancer. In this article, the activities of Guggulsterone against cancerous cells were determined and summarized. Methods: Using 7 databases (PubMed, PMC, Google Scholar, Science Direct, Scopus, Cochrane and Ctri.gov), the literature search was conducted since conception until June 2021. Extensive literature search yielded 55,280 studies from all the databases. A total of 40 articles were included in the systematic review and of them, 23 articles were included in the meta-analysis.The cancerous cell lines used in the studies were for pancreatic cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, cholangiocarcinoma, oesophageal adenocarcinoma, prostrate cancer, colon cancer, breast cancer, gut derived adenocarcinoma, gastric cancer, colorectal cancer, bladder cancer, glioblastoma, histiocytic leukemia, acute myeloid leukemia and non-small cell lung cancer. The reliability of the selected studies was assessed using ToxRTool. Results: Based on this review, guggulsterone significantly affected pancreatic cancer (MiaPaCa-2, Panc-1, PC-Sw, CD18/HPAF, Capan1, PC-3), hepatocellular carcinoma (Hep3B, HepG2, PLC/PRF/5R), head and neck squamous cell carcinoma (SCC4, UM-22b, 1483), cholangiocarcinoma (HuCC-T1, RBE, Sk-ChA-1, Mz-ChA-1) and oesophageal adenocarcinoma (CP-18821, OE19), prostrate cancer (PC-3), colon cancer (HT-29), breast cancer (MCF7/DOX), gut derived adenocarcinoma (Bic-1), gastric cancer (SGC-7901), colorectal cancer (HCT116), bladder cancer (T24, TSGH8301), glioblastoma (A172, U87MG, T98G), histiocytic leukemia (U937), acute myeloid leukemia (HL60, U937) and non-small cell lung cancer (A549, H1975) by inducing apoptotic pathways, inhibiting cell proliferation, and regulating the expression of genes involved in apoptosis. Guggulsterone is known to have therapeutic and preventive effects on various categories of cancers. It can inhibit the progression of tumors and can even reduce their size by inducing apoptosis, exerting anti-angiogenic effects, and modulating various signaling cascades. In vitro studies reveal that Guggulsterone inhibits and suppresses the proliferation of an extensive range of cancer cells by decreasing intrinsic mitochondrial apoptosis, regulating NF-kB/STAT3/ß-Catenin/PI3K/Akt/CHOP pathway, modulating the expression of associated genes/proteins, and inhibiting angiogenesis. Furthermore, Guggulsterone reduces the production of inflammatory markers, such as CDX2 and COX-2. The other mechanism of the Guggulsterone activity is the reversal of P-glycoprotein-mediated multidrug resistance. Twenty three studies were selected for meta-analysis following the PRISMA statements. Fixed effect model was used for reporting the odds ratio. The primary endpoint was percentage apoptosis. 11 of 23 studies reported the apoptotic effect at t = 24 h and pooled odds ratio was 3.984 (CI 3.263 to 4.865, p < 0.001). 12 studies used Guggulsterone for t > 24 h and the odds ratio was 11.171 (CI 9.148 to 13.643, 95% CI, p < 0.001). The sub-group analysis based on cancer type, Guggulsterone dose, and treatment effects. Significant alterations in the level of apoptotic markers were reported by Guggulsterone treatment. Conclusion: This study suggested that Guggulsterone has apoptotic effects against various cancer types. Further investigation of its pharmacological activity and mechanism of action should be conducted. In vivo experiments and clinical trials are required to confirm the anticancer activity.

Environmental sustainable: Biogenic copper oxide nanoparticles as nano-pesticides for investigating bioactivities against phytopathogens.

Endocrine-disrupting chemicals (EDCs) are of interest in human physiopathology and have been extensively studied for their effects on the endocrine system. Research also focuses on the environmental impact of EDCs, including pesticides and engineered nanoparticles, and their toxicity to organisms. Green nanofabrication has surfaced as an environmentally conscious and sustainable approach to manufacture antimicrobial agents that can effectively manage phytopathogens. In this study, we examined the current understanding of the pathogenic activities of Azadirachta indica aqueous formulated green synthesized copper oxide nanoparticles (CuONPs) against phytopathogens. The CuONPs were analyzed and studied using a range of analytical and microscopic techniques, such as UV-visible spectrophotometer, Transmission electron microscope (TEM), Scanning electron microscope (SEM), X-ray diffraction (XRD) and Fourier transformed infrared spectroscopy (FTIR). The XRD spectral results revealed that the particles had a high crystal size, with an average size ranging from 40 to 100 nm. TEM and SEM images were utilized to verify the size and shape of the CuONPs, revealing that they varied between 20 and 80 nm. The existence of potential functional molecules involved in the reduction of the nanoparticles was confirmed by FTIR spectra and UV analysis. Biogenically synthesized CuONPs revealed significantly enhanced antimicrobial activities at 100 mg/L concentration in vitro by the biological method. The synthesized CuONPs at 500 µg/ml had a strong antioxidant activity which was examined through the free radicle scavenging method. Overall results of the green synthesized CuONPs have demonstrated significant synergetic effects in biological activities which can play a crucial impact in plant pathology against numerous phytopathogens.

Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism.

Dasatinib (DAS), a narrow-therapeutic index drug, Bcr-Abl, and Src family kinases multitarget inhibitor have been approved for chronic myelogenous leukemia (CML) and Ph-positive acute lymphocytic leukemia (Ph+ ALL). Apigenin (APG) has a long history of human usage in food, herbs, health supplements, and traditional medicine, and it poses low risk of damage. The concomitant use of APG containing herbs/foods and traditional medicine may alter the pharmacokinetics of DAS, that probably lead to possible herb-drug interactions. The pharmacokinetic interaction of APG pretreatment with DAS in rat plasma following single and co-oral dosing was successfully deliberated using the UPLC-MS/MS method. The in vivo pharmacokinetics and protein expression of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 demonstrate that APG pretreatment has potential to drastically changed the DAS pharmacokinetics where escalation in the Cmax, AUC(0-t), AUMC(0-inf_obs), T1/2, Tmax, and MRT and reduction in Kel, Vd, and Cl significantly in rats pretreated with APG 40 mg/kg, thus escalating systemic bioavailability and increasing the rate of absorption via modulation of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 protein expression. Therefore, the concomitant consumption of APG containing food or traditional herb with DAS may cause serious life-threatening drug interactions and more systematic clinical study on herb-drug interactions is required, as well as adequate regulation in herbal safety and efficacy.

The Development and Optimization of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for the Intravenous Delivery of Propofol.

PURPOSE: Propofol is a relatively short-acting potent anesthetic lipophilic drug used during short surgical procedures. Despite the success of propofol intravenous emulsions, drawbacks to such formulations include inherent emulsion instability, the lack of a safe vehicle to prevent sepsis, and concern regarding hyperlipidemia-related side effects. The aim of the current investigation was to develop a novel, lipid-based self-nanoemulsifying drug delivery system (SNEDDS) for propofol with improved stability and anesthetic activity for human use. METHODS: A series of SNEDDS formulations were developed using naturally obtained medium-chain/long-chain mono-, di-, and triglycerides, glyceryl monocaprylate, and water-soluble cosolvents with hydrogenated castor oil constructing ternary phase diagrams for propofol. The developed SNEDDS formulations were characterized using visual observation, particle size analysis, zeta potential, transmission electron microscopy, equilibrium solubility, in vitro dynamic dispersion and stability, and in vivo sleeping disorder studies in rats. The in vivo bioavailability of the SNEDDSs in rats was also studied to compare the representative formulations with the marketed product Diprivan®. RESULTS: Medium-chain triglycerides (M810) with mono-diglycerides (CMCM) as an oil blend and hydrogenated castor oil (KHS15) as a surfactant were selected as key ingredients in ternary phase diagram studies. The nanoemulsifying regions were identified from the studies and a number of SNEDDSs were formulated. Results from the characterization studies demonstrated the formation of efficient nanosized particles (28-45 nm globule size, 0.10-0.20 PDI) in the optimized SNEDDS with a drug loading of 50 mg/g, which is almost 500-fold higher than free propofol. TEM analysis showed the formation of spherical and homogeneous nanoparticles of less than 50 nm. The dissolution rate of the representative SNEDDS was faster than raw propofol and able to maintain 99% propofol in aqueous solution for around 24 h. The optimized liquid SNEDDS formulation was found to be thermodynamically stable. The intravenous administration of the SNEDDS in male Wistar rats induced a sleeping time of 73-88 min. The mean plasma concentrations after the IV administration of propofol nano-formulations PF2-SNEDDS and PF8-SNEDDS were 1348.07 ± 27.31 and 1138.66 ± 44.97 µg/mL, as compared to 891.44 ± 26.05 µg/mL (p = 0.05) observed after the IV administration of raw propofol. CONCLUSION: Propofol-loaded SNEDDS formulations could be a potential pharmaceutical product with improved stability, bioavailability, and anesthetic activity.

Nutritional Profiling, Phytochemical Composition and Antidiabetic Potential of Taraxacum officinale, an Underutilized Herb.

Taraxacum officinale (T. officinale), a wild vegetable with a number of health claims, has been mostly ignored and unexplored. The study aims to compare the nutritional, phytochemical as well as antidiabetic potential of fresh as well as shade-dried leaves of T. officinale, in order to recommend its best form as a dietary antidiabetic product. The results revealed that as compared to fresh leaves, the shade-dried leaves, in addition to possessing higher levels of carbohydrates, crude protein, crude fat, crude fiber, etc., also contain appreciable amounts of total phenols (5833.12 ± 4.222 mg/100), total flavonoids (188.84 ± 0.019 mg/100 g), ascorbic acid (34.70 ± 0.026 mg/100 g), ß-carotene (3.88 ± 1.473 mg/100 g) and total chlorophyll (239.51 ± 0.015 mg/100 g) antioxidants. The study revealed the presence of medicinally important antidiabetic flavonoid quercetin present in T. officinale leaves. Among the three solvent systems used, the aqueous extract of shade-dried T. officinale leaves comparatively demonstrated potent antidiabetic activity under in vitro conditions in a dose-dependent manner via targeting α-amylase and α-glucosidase, the two potent enzymes of carbohydrate metabolism. Therefore, in addition to being a nutritious herb, the shade-dried leaves of T. officinale have great potential to suppress post-prandial glucose rise and can be better exploited through clinical trials to be used as a dietary intervention for better management of diabetes.

Brassinosteroid Supplementation Alleviates Chromium Toxicity in Soybean (Glycine max L.) via Reducing Its Translocation.

Chromium (Cr) phytotoxicity severely inhibits plant growth and development which makes it a prerequisite to developing techniques that prevent Cr accumulation in food chains. However, little is explored related to the protective role of brassinosteroids (BRs) against Cr-induced stress in soybean plants. Herein, the morpho-physiological, biochemical, and molecular responses of soybean cultivars with/without foliar application of BRs under Cr toxicity were intensely investigated. Our outcomes deliberated that BRs application noticeably reduced Cr-induced phytotoxicity by lowering Cr uptake (37.7/43.63%), accumulation (63.92/81.73%), and translocation (26.23/38.14%) in XD-18/HD-19, plant tissues, respectively; besides, improved seed germination ratio, photosynthetic attributes, plant growth, and biomass, as well as prevented nutrient uptake inhibition under Cr stress, especially in HD-19 cultivar. Furthermore, BRs stimulated antioxidative defense systems, both enzymatic and non-enzymatic, the compartmentalization of ion chelation, diminished extra production of reactive oxygen species (ROS), and electrolyte leakage in response to Cr-induced toxicity, specifically in HD-19. In addition, BRs improved Cr stress tolerance in soybean seedlings by regulating the expression of stress-related genes involved in Cr accumulation, and translocation. Inclusively, by considering the above-mentioned biomarkers, foliar spray of BRs might be considered an effective inhibitor of Cr-induced damages in soybean cultivars, even in Cr polluted soil.

An In Silico Investigation to Explore Anti-Cancer Potential of Foeniculum vulgare Mill. Phytoconstituents for the Management of Human Breast Cancer.

Breast cancer is one of the most prevalent cancers in the world. Traditionally, medicinal plants have been used to cure various types of diseases and disorders. Based on a literature survey, the current study was undertaken to explore the anticancer potential of Foeniculum vulgare Mill. phytoconstituents against breast cancer target protein (PDB ID: 6CHZ) by the molecular docking technique. Molecular docking was done using Autodock/vina software. Toxicity was predicted by the Protox II server and drug likeness was predicted by Molinspiration. 100 ns MD simulation of the best protein-ligand complexes were done using the Amber 18 tool. The present molecular docking investigation has revealed that among the 40 selected phytoconstituents of F. vulgare, α-pinene and D-limonene showed best binding energy (-6 and -5.9 kcal/mol respectively) with the breast cancer target. α-Pinene and D-limonene followed all the parameters of toxicity, and 100 ns MD simulations of α-pinene and D-limonene complexes with 6CHZ were found to be stable. α-Pinene and D-limonene can be used as new therapeutic agents to cure breast cancer.

Defense interplay of the zinc-oxide nanoparticles and melatonin in alleviating the arsenic stress in soybean (Glycine max L.).

Present study showed the successful application of the modified hydrothermal method for synthesizing the zinc oxide nanoparticles (ZnO-NPs) efficiently. Well as-synthesized ZnO-NPs are analyzed for various techniques viz., X-ray diffraction (XRD), SEM micrographs, EDAX/Mapping pattern, Raman Spectroscopy Pattern, UV, Photoluminescence (PL) and X-ray photoemission spectroscopy (XPS) analysis. All these measurements showed that ZnO-NPs are highly pure with no internal defects, and can be potentially used in the plant applications. Hence, we further determined the effect of these nanoparticles and melatonin for the modulation of the As tolerance in soybean plants by examining the various growth attributes and metabolic parameters. Our results demonstrated that As-stress inhibited growth (∼34%), photosynthesis-related parameters (∼18-28%) and induced ROS accumulation; however, all these attributes are substantially reversed by the ZnO-NPs and melatonin treatments. Moreover, the As stress induced malondialdehyde (MDA; 71%) and hydrogen peroxide (H2O2; 82%) are partially reversed by the ZnO-NPs and melatonin in the As-stressed plants. This might have resulted due to the ZnO-NPs and melatonin induced activities of the antioxidants plant defense. Overall, the ZnO-NPs and melatonin supplementation separately and in combination positively regulated the As tolerance in soybean; however, the effect of their combined application on the As tolerance was more profound relative to the individual application. These results suggested the synergetic effect of the ZnO-NPs and melatonin on the As tolerance in soybean. However, the in-depth mechanism underlying the defense crosstalk between the ZnO-NPs and melatonin needs to be further explored.

Newly-synthesized iron-oxide nanoparticles showed synergetic effect with citric acid for alleviating arsenic phytotoxicity in soybean.

In the current investigation, we presented the success of the modified hydrothermal method for synthesizing the iron-oxide nanoparticles (Fe2O3-NPs) efficiently. These NPs were further characterized by using different techniques such as X-ray diffraction (XRD), scanning electron microscope (SEM) micrographs, energy-dispersive X-ray spectroscopy (EDAX)/Mapping pattern, Raman Spectroscopy Pattern, ultra violet (UV) and Photoluminescence (PL). All these analyses revealed highly pure nature of Fe2O3-NPs with no internal defects, and suggested its application for plant growth improvement. Therefore, we further investigated the separate as well as combined effects of the Fe2O3-NPs and citric acid (CA) in the alleviation of arsenic (As) toxicity in the soybean (Glycine max L.), by evaluating the different plant growth and metabolic attributes. Results of our study revealed that As-induced growth inhibition, reduction of photosynthesis, water use efficiency (WUE), and reactive oxygen species (ROS) accumulation whereas application of the Fe2O3-NPs and CA significantly reversed all these adverse effects in soybean plants. Moreover, the As-stress induced malondialdehyde (MDA) and hydrogen peroxide (H2O2) production were partially reversed by the Fe2O3-NPs and CA in the As-stressed plants by 16% and 10% (MDA) and 29% and 12% (H2O2). This might have resulted due to the Fe2O3-NPs and CA induced activities of the antioxidant defense in plants. Overall, the Fe2O3-NPs and CA supplementation separately and in combination positively regulated the As tolerance in soybean; however, the effect of the combined application on the As tolerance was more profound relative to the individual application. These results suggested the synergetic effect of the Fe2O3-NPs and CA on the As-tolerance in soybean. However, in-depth mechanism underlying the defense crosstalk between the Fe2O3-NPs and CA needs to be further explored.

Clopidogrel-herb Interactions: A Pharmacokinetic and Pharmacodynamic Assessment in a Rat Model.

BACKGROUND: Herbs usually contain a mixture of biologically active constituents, which can interact with numerous prescribed drugs and alter their safety profiles. OBJECTIVES: The current investigation was aimed to evaluate the effect of commonly used herbal products including black seed (Nigella sativa), garden cress (Lepidium sativum), and fenugreek (Trigonella foenum-graecum) on the pharmacokinetics and pharmacodynamics of clopidogrel using a Wistar rat model. METHODS: A GC-MS analysis revealed the presence of several phytoconstitutents (polyphenols) in the extracts of black seed, garden cress, and fenugreek. These polyphenols have the potential to interfere with clopidogrel effect. Plasma concentrations of clopidogrel were measured at different time points in the absence and presence of the concurrent use of tested herbal products and the pharmacokinetic parameters were calculated. Bleeding time was measured in various groups as a measure of the antiplatelet effect of clopidogrel. RESULTS: Area under the plasma concentration-time curves (AUC0-∞) of clopidogrel were 35.53 ±0.89 µg/ml*h (p<0.05), 26.01 ±0.90 µg/ml*h (p>0.05) and 32.80 ±2.51 µg/ml*h (p<0.05) in the black seed, garden cress and fenugreek group, respectively, compared with that of the control group (27.02 ±0.42 µg/ml*h). Treatment with black seed also caused an increase in clopidogrel Cmax by 31.52% (p<0.05) and with fenugreek by 21.42% (p<0.05); Cmax, did not changed with garden cress treatment (6.48 ±0.15 µg/ml versus 6.12 ±0.21 µg/ml, p>0.05). The pharmacodynamic evaluation of the antiplatelet effect of clopidogrel in the presence of herbal products treatment showed a significant prolongation in the bleeding time from a control baseline by ~22-26%, and by added ~8-12% in reference to clopidogrel therapeutic effect (p<0.05). CONCLUSION: The concurrent use of black seed, fenugreek, or garden cress can alter the pharmacokinetics and pharmacodynamics of clopidogrel to varying degrees due to the presence of various bioactive polyphenols. This is probably due to changes in drug disposition and its antiplatelet action. Further confirmation can determine the clinical relevance of these observations and identify the exact constituents responsible for such activities.

Antagonistic, Anti-oxidant, Anti-inflammatory and Anti-diabetic Probiotic Potential of Lactobacillus agilis Isolated From the Rhizosphere of the Medicinal Plants.

Potential probiotic bacteria can be used as a biotherapeutic agent and a sustainable alternative to antibiotics, as an anti-oxidative, anti-inflammatory, and anti-diabetic agent without causing any serious side effects. Mostly human-friendly Lactic acid bacteria (LAB) have been isolated from the animal-human origin to be used as biotherapeutic agents or to produce useful metabolites (nutraceutical). However, less information is known about the role of medicinal plants associated LAB as biotherapeutic agents. The isolation of 115 human-friendly Lactobacillus strains was done from the rhizosphere of the medicinal plants Ocimum tenuiflorum, Azadirachta indica, Ficus carica. The obtained bacteria were then tested for their safe status before being using it for a beneficial purpose. Out of 115 strains, 29 (25%) were negative for blood hemolytic activities. Among these 29 isolates, three isolates did not show a breakdown of gelatin and were recognized as safe. Antibiotic resistance assay showed resistance of two of them against antibiotics discs of Streptomycin (10 µg), Ciprofloxacin (20 µg), Vancomycin (30 µg), Metronidazole (10 µg), Ampicillin (5 µg), Chloramphenicol (30 µg), Kanamycin (30 µg), Erythromycin (15 µg), Penicillin (10 µg) and Tetracycline (30 µg). The bacterial isolate (T-2) was found safe that was identified as Lactobacillus agilis by sequence analysis of 16 s rRNA gene and processed in vitro as an anti-bacterial, anti-oxidant, anti-diabetic, and anti-inflammatory agent. Free radical scavenging activities and inhibition of α-amylase activities for Lactobacillus agilis were found relative to standard drug values as 68% and 73% and 51.3% and 65.3%, respectively. The in-vitro anti-inflammatory assay showed 61.6% (Lactobacillus agilis) while showed 69% (aspirin) activity for denaturation albumin protein. The results suggested that Lactobacillus agilis can be used as a potential probiotic strain as well as can be used to produce nutraceuticals.

Chemical composition of Gastrocotyle hispida (Forssk.) bunge and Heliotropium crispum Desf. and evaluation of their multiple in vitro biological potentials.

Medicinal plants largely serve as a source of bioactive compounds in traditional medicines to cure various diseases. The present study was aimed at chemical composition, antioxidant, antimicrobial, cytotoxic and antihemolytic potential of five different extracts of G. hispida and H. crispum (Boraginaceae). G. hispida methanolic extract displayed highest number (eleven) of polyphenolic compounds by using high performance liquid chromatography (HPLC). Functional groups were identified by Fourier-transformed infrared spectroscopy (FTIR) and elements (Si, Fe, Ba, Mg, Ti, Ca, Mg and Cr) were observed by using laser-induced breakdown spectroscopy (LIBS) which were also highly expressed in G. hispida as compared to H. crispum. Antioxidant activity was determined via six assays and antibacterial activity was observed in decreasing order of methanol > ethanol > chloroform > ethyl acetate > n-Hexane in both species. Cytotoxic potential was investigated against brine shrimps and then liver (HepG2) and skin (HT144) cancer cell lines which was detected highest in the G. hispida ethanolic extract (50.76 % and 72.95 %). However, H. crispum chloroform extract revealed highest (31.869 µg/mL) antihemolytic activity and its methanolic extract indicated highest (13.5 %) alpha-amylase inhibitory potential. Altogether, results suggested that both species could be used effectively in food and drug industries owing to the presence of vital bioactive compounds and elements. In future, we recommend to isolate active compounds and to perform in vivo biological assays to further validate their potential biological applications.

Herbal immune-boosters: Substantial warriors of pandemic Covid-19 battle.

Current scenario depicts that world has been clenched by COVID-19 pandemic. Inevitably, public health and safety measures could be undertaken in order to dwindle the infection threat and mortality. Moreover, to overcome the global menace and drawing out world from moribund stage, there is an exigency for social distancing and quarantines. Since December, 2019, coronavirus, SARS-CoV-2 (COVID-19) have came into existence and up till now world is still in the state of shock.At this point of time, COVID-19 has entered perilous phase, creating havoc among individuals, and this has been directly implied due to enhanced globalisation and ability of the virus to acclimatize at all conditions. The unabated transmission is due to lack of drugs, vaccines and therapeutics against this viral outbreak. But research is still underway to formulate the vaccines or drugs by this means, as scientific communities are continuously working to unravel the pharmacologically active compounds that might offer a new insight for curbing infections and pandemics. Therefore, the topical COVID-19 situation highlights an immediate need for effective therapeutics against SARS-CoV-2. Towards this effort, the present review discusses the vital concepts related to COVID-19, in terms of its origin, transmission, clinical aspects and diagnosis. However, here, we have formulated the novel concept hitherto, ancient means of traditional medicines or herbal plants to beat this pandemic.

Development and optimization of sitagliptin and dapagliflozin loaded oral self-nanoemulsifying formulation against type 2 diabetes mellitus.

Control of hyperglycemia and prevention of glucose reabsorption (glucotoxicity) are important objectives in the management of type 2 diabetes. This study deals with an oral combined dosage form design for two anti-diabetic drugs, sitagliptin and dapagliflozin using self-nanoemulsifying drug delivery systems (SNEDDS). The SNEDDS were developed using naturally obtained bioactive medium-chain/long-chain triglycerides oil, mixed glycerides and nonionic surfactants, and droplet size was measured followed by the test for antioxidant activities. Equilibrium solubility and dynamic dispersion experiments were conducted to achieve the maximum drug loading. The in vitro digestion, in vivo bioavailability, and anti-diabetic effects were studied to compare the representative SNEDDS with marketed product Dapazin®. The representative SNEDDS containing black seed oil showed excellent self-emulsification performance with transparent appearance. Characterization of the SNEDDS showed nanodroplets of around 50-66.57 nm in size (confirmed by TEM analysis), in addition to the high drug loading capacity without causing any precipitation in the gastro-intestinal tract. The SNEDDS provided higher antioxidant activity compared to the pure drugs. The in vivo pharmacokinetic parameters of SNEDDS showed significant increase in C max (1.99 ± 0.21 µg mL-1), AUC (17.94 ± 1.25 µg mL-1), and oral absorption (2-fold) of dapagliflozin compared to the commercial product in the rat model. The anti-diabetic studies showed the significant inhibition of glucose level in treated diabetic mice by SNEDDS combined dose compared to the single drug therapy. The combined dose of sitagliptin-dapagliflozin using SNEDDS could be a potential oral pharmaceutical product for the improved treatment of type 2 diabetes mellitus.