Showing papers in "Dose-response in 2022"
TL;DR: It can be concluded that the newly synthesized gallium nanoparticles EA-GaNPs have an efficient antitumor activity that was manifested by reduction of the viability on the human breast cancer cell line (MCF-7) in vitro and in vivo.
Abstract: Cancer is a mortality contributor worldwide, and breast cancer is the most common among women. Despite the numerous breast cancer therapeutic strategies, they either have limitations or sometimes are resisted by cancer, so new approaches are needed to tackle those restrictions. Nanotechnology offers exciting leaps in the diagnosis and treatment of cancer, especially breast cancer. The main objective of this study was to investigate the effect of the newly synthesized gallium nanoparticles coated by Ellagic acid (EA-GaNPs) on the induced mammary gland carcinogenesis in female rats and their antibacterial activities comparison with standard antibiotics (Ketoconazole (100 μg/ml) and Gentamycin (4 μg/ml)) by disc diffusion method using eight different microbial species. The antitumor efficacy of EA-GaNPs was conducted both in vitro and in in vivo. The result of antimicrobial activity of EA-Ga NPs (1 mg/1 mL) revealed moderate toxicity behavior against Gram-positive {Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) and Gram-negative pathogenic bacteria {Escherichia coli, Proteus vulgarfs) also, antifungal activity was detected against {Aspergillus terreus). In vitro study showed that EA-GaNPs inhibited human breast cancer cell line (MCF-7) proliferation with IC50 of 2.86 μg/ml. Although in vivo; the administration of EA-GaNPs to DMBA-treated rats ameliorated the hyperplastic state of mammary gland carcinogenesis induced by DMBA. Additionally, EA-GaNPs administration significantly modulated the activities of ALT and AST, as well as the levels of urea and creatinine in serum. Also, EA-GaNPs administration improved the antioxidant state by increasing Superoxide dismutase activity and GSH content, and decreasing malondialdehyde content in the mammary tissue, besides enhancing the apoptotic activity through elevating the levels of caspase-3 and decreasing the protein intensities of protein kinase B & phosphatidyl inositide 3-kinases. Furthermore, a significant decrease in serum Total iron-binding capacity accompanied by a significant increase in the level of calcium was noted. So, it can be concluded that the newly synthesized nanoparticles EA-GaNPs have an efficient antitumor activity that was manifested by reduction of the viability on the human breast cancer cell line (MCF-7) in vitro. Also, in vivo against the chemically induced mammary gland carcinogenesis in a female rat model. Histopathological findings were in harmony with biochemical and molecular results showing the effectiveness of EA-GaNPs against mammary carcinogenesis. Therefore, EA-GaNPs could be a promising, potent anti-cancer compound.
10 citations
TL;DR: The current study validated the preventive and curative potential of Mp.Cr against urolithiasis and justified its traditional use in kidney stone disease.
Abstract: Background: Mentha piperita L. (peppermint) is one of the most widely consumed medicinal herbs that has gained attention from food and pharmaceutical industries due to its distinct aroma and taste. Purpose: Present study was aimed to rationalize the traditional use of peppermint in urolithiasis and to explore its possible underlying mechanism. Research Design: The aqueous methanolic crude extract of Mentha piperita (Mp.Cr) was assessed for phytochemical constituents and antioxidant activity. In vitro crystallization assays were performed to determine the inhibitory effects of Mp.Cr against crystal nucleation, aggregation and growth. In vivo urolithiasis model was developed in rats by the administration of ammonium chloride and ethylene glycol in drinking water. The antiurolithic effects of Mp.Cr were evaluated by analyzing kidney homogenate, biochemical and histological parameters. Results: HPLC analysis showed the presence of epicatechin, quercetin, gallic acid, syringic acid, kaempferol, caffeic acid and coumaric acid. The maximum quantity of quercetin equivalent flavonoid and gallic acid equivalent phenolic content was found to be 63.73 ± .24 mg QE/g and 43.76 ± .6 mg GAE/g of Mp.Cr, respectively. Mp.Cr significantly normalized urinary and serum biochemistry, similar to the standard cystone treatment. Conclusions: The current study validated the preventive and curative potential of Mp.Cr against urolithiasis and justified its traditional use in kidney stone disease.
9 citations
TL;DR: The preliminary study showed that baricitinib was effective and safe in treating progressing vitiligo and could promote tyrosinase activity, melanin content and TYR, TRP1 gene expression of MC-Ds in vitro.
Abstract: Objective To evaluate the clinical efficacy and safety of baricitinib, a Janus kinase (JAK) inhibitor, in treating patient with progressing vitiligo, and to further explore the regulation of baricitinib on melanocytes (MCs) in vitro. Methods Four patients with progressing vitiligo were treated with oral baricitinib for a total of 12 weeks. MCs were cultured in vitro and irradiated by high-dose ultraviolet B (UVB, 150mJ/cm2) to make an MC damaged model (MC-Ds). Baricitinib was added at a final concentration of 25 μM. Dopamine staining and NaOH method were used to measure the tyrosinase activity and melanin level, respectively, real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1). Results Significant re-pigmentation was observed in the week 12 without obvious side effects. Depigmentation occurred in 2 patients at the 3-month follow-up. Laboratory research found that higher doses of UVB irradiation (150mJ/cm2) could decrease melanin content of MCs, baricitinib (25 μM) could significantly promote tyrosinase activity, melanin content, and TYR, TRP-1 gene expression of MC-Ds. Conclusion Our preliminary study showed that baricitinib was effective and safe in treating progressing vitiligo. Baricitinib could promote tyrosinase activity, melanin content and TYR, TRP1 gene expression of MC-Ds in vitro.
8 citations
TL;DR: It is concluded from the current study that extracts of colchicum, nux-vomica, and aloe-vera showed more potent effect and thus can be used as alternative options for the management of inflammatory and arthritic ailments.
Abstract: Background: Colchicum autumnale, Strychnous nux-vomica and Aloe barbadensis are the medicinal plants clinically utilized for the management of rhuematic disorders. Purpose: The present work was focused to evaluate the in-vitro anti-arthritic and anti-inflammatory activities of Colchicum (Colchicum autumnale), Nux-vomica (Strychnous nux-vomica), and Aloe-vera (Aloe barbadensis). Research Design: Primarily, the aqueous-ethanolic extracts of these medicinal plants were phytochemically screened followed by Fourier Transform Infrared (FTIR) analysis. Anti-arthritic activity by protein denaturation method and anti-inflammatory activity by human red blood cell (HRBC) membrane stabilization method at the concentration of 125, 250, and 500 µg/mL along with standard were performed. Results: Phytochemical screening revealed that alkaloids, saponins, terpenoids, phenols, and anthraquinones were found in all the extracts, and organic acids, amine group, aromatic or aliphatic compounds, esters and halogens, and phenolics were identified by FTIR. Protein denaturation method revealed that colchicum, nux-vomica, and aloe-vera showed maximum 98.5%, 99.6%, and 72.3% of inhibition at 500 µg/mL compared with that of standard drug, that is, Diclofenac sodium. Membrane stabilization method showed that colchicum, nux-vomica, and aloe-vera showed maximum 40.20%, 35.67%, and 40.1% protection at 500 µg/mL when compared with standard drug. Conclusion: It is concluded from the current study that extracts of colchicum, nux-vomica, and aloe-vera showed more potent effect and thus can be used as alternative options for the management of inflammatory and arthritic ailments.
8 citations
TL;DR: In this article , a self-dissolving microneedle system for local and systemic delivery of acyclovir using a topical lyophilized wafer was developed.
Abstract: Acyclovir is an antiviral drug that is frequently prescribed for the herpes virus. However, the drug requires frequent dosing due to limited bioavailability (10–26.7%). The rationale of the present study was to develop a self-dissolving microneedle system for local and systemic delivery of acyclovir using a topical lyophilized wafer on microneedle-treated skin to provide the drug at the site of infection. The microneedles prepared with hydroxypropyl methylcellulose (HPMC) (8% w/w) or HPMC (8% w/w)-polyvinyl pyrrolidone (PVP) (30% w/w) penetrated excised rat skin, showing sufficient mechanical strength and rapid polymer dissolution. The topical wafer was prepared with acyclovir (40% w/w; equivalent to 200 mg of drug), gelatin (10% w/w), mannitol (5% w/w), and sodium chloride (5% w/w). The uniform distribution of acyclovir within the wafer in an amorphous form was confirmed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). No polymer–drug interaction was evident in the lyophilized wafer as per Fourier transform infrared spectroscopy (FTIR) analysis. The wafer showed a sufficiently porous structure for rapid hydration as per scanning electron microscopy (SEM) analysis. During ex-vivo analysis, the skin was pre-treated with a self-dissolving microneedle array for 5 minutes, and the wafer was placed on this microporated-skin. Topical wafer provided ∼7–11 times higher skin concentration than the ID99 reported with a lower lag-time. Based on in-vivo testing, ∼2.58 µg/ml of Cmax was achieved in rabbit plasma during 24 hours’ study. Our findings suggest that the self-dissolving microneedle-assisted topical wafer, proposed for the first time, would be efficacious against the infection residing in the skin layer and for systemic therapy.
7 citations
TL;DR: These studies demonstrate the capacity of these agents to enhance EPC proliferation and angiogenesis functional applications, having a focus on repairing endothelial tissue damage due to acute injury (e.g., stroke), as well as damage from chronic conditions and normal aging processes.
Abstract: Hormetic-biphasic dose response relationships are reported herein for human endothelial progenitor cells involving estradiol, nicotine, the anti-diabetic agent pioglitazone, resveratrol, and progesterone. In general, these studies demonstrate the capacity of these agents to enhance EPC proliferation and angiogenesis functional applications, having a focus on repairing endothelial tissue damage due to acute injury (e.g., stroke), as well as damage from chronic conditions (e.g., atherosclerosis) and normal aging processes.
7 citations
TL;DR: The EMG amplitudes of most leg muscles tested were significantly greater during WBV exposure than in the no-WBV condition, and the dynamic semi-squat 4 mm whole-body vibration training is recommended for middle-aged and older women to improve lower limb muscle strength and function.
Abstract: Purpose The present study was designed to investigate the electromyographic (EMG) response in leg muscles to whole-body vibration while using different body positions and vibration amplitudes. Methods: An experimental study with repeated measures design involved a group of community-dwelling middle-aged and older women (n = 15; mean age=60.8 ± 4.18 years). Muscle activity of the gluteus maximus (GM), rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL), biceps femoris (BF), and gastrocnemius (GS) was measured by surface electromyography, which participants were performing three different body positions during three WBV amplitudes. The body positions included static semi-squat, static semi-squat with elastic band loading, and dynamic semi-squat. Vibration stimuli tested were 0 mm, 2 mm, and 4 mm amplitude and 30 Hz frequencies. And the maximum accelerations produced by vibration stimuli with amplitudes of 2 mm and 4 mm are approximately 1.83 g and 3.17 g. Results: Significantly greater muscle activity was recorded in VL, BF, and GS. When WBV was applied to training, compared with the same training without WBV (P < .05). There were significant main effects of body positions on EMGrms for the GM, RF, and VM (P < .05). Compared to static semi-squat, static semi-squat with elastic band significantly increased the EMGrms of GM, and dynamic semi-squat significantly increased the EMGrms of GM, RF and VM (P < .05). And there were significant main effects of amplitudes on EMGrms for the GM, RF, and VM (P < .05). The EMGrms of the VL, BF, and GS at 4 mm were significantly higher than 0 mm, and the EMGrms of the VL and BF at 4 mm were significantly higher than 2 mm. There was no significant body interaction between body positions and amplitudes (P > .05). Conclusions: The EMG amplitudes of most leg muscles tested were significantly greater during WBV exposure than in the no-WBV condition. The dynamic semi-squat 4 mm whole-body vibration training is recommended for middle-aged and older women to improve lower limb muscle strength and function.
6 citations
TL;DR: This paper represents the first assessment of agent-induced hormetic dose responses in induced pluripotent stem cells and their derived cells, and compares with hormetic responses in multiple adult and embryonic stem cells.
Abstract: This paper represents the first assessment of agent-induced hormetic dose responses in induced pluripotent stem cells and their derived cells. The hormetic dose responses were induced by a broad range of chemicals, including pharmaceuticals (eg, metformin), dietary supplements/extracts from medicinal plants (eg, curcumin), and endogenous agents (eg, melatonin). The paper assesses the mechanistic foundations of these induced hormetic dose responses, their therapeutic implications and comparison with hormetic responses in multiple adult and embryonic stem cells.
6 citations
TL;DR: In this paper, the authors examined the antioxidant capacity and in vitro response of phytochemical constituents of Withania somnifera (Ashwagandha) on standard parameters of healthy volunteer semen.
Abstract: Background: Phytomedicine is becoming more acceptable as an alternative medicinal approach in the modern era. Objectives: The current study examined the antioxidant capacity and in vitro response of phytochemical constituents of Withania somnifera (Ashwagandha) on standard parameters of healthy volunteer semen. Methods: The phytochemicals and their pharmacological response in a hydroethanolic (30:70 v/v) extract of W. somnifera roots were determined using standard protocols. Results: The constituents included flavonoids, phenolic acids, alkaloids, and terpenoids were reported. High-performance liquid chromatography and Fourier-transform infrared spectroscopy determined a diverse array of biologically active chemical constituents in the extract. The extract of W. somnifera exhibits substantial antioxidant properties, including total antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl inhibition, H2O2 scavenging, and Fe3+ reducing potential (P < .05). The analysis of essential natural minerals explored adequate levels determined using atomic absorption spectrophotometer. Cytotoxic studies revealed significant thrombolytic, RBC membrane stabilization, and DNA damage protection activity (P < .05) while remaining non-mutagenic against Salmonella typhi TA98 and TA100. The best protective response of W. somnifera extract on human semen parameters (n = 30), such as total motility, progressive motility, and viability, demonstrated a significant (P < .05) improvement, particularly at the dose of 25 μg/mL and 50 μg/mL. Conclusion: The study concludes that W. somnifera possesses favorable in vitro characteristics that could aid in the preservation of sperm during intrauterine insemination and in vitro fertilization.
5 citations
TL;DR: The newly conjugated Q-SBA-15 system improved the apoptotic fate through caspase-mediated apoptosis via PI3K/AKT/mTOR signaling pathway and hence, it can be potentially employed as an anticancer agent for lung cancer.
Abstract: Lung cancer is considered as one of the most serious disease worldwide. The progress of drug carriers based on nonmaterial, which selectively hold chemotherapeutic agents to cancer cells, has become a major focus in biomedical research. This study aimed to evaluate the growth inhibition and apoptosis induction of the human lung cancer cells (A-549) by Q-loaded SBA-15 conjugate system. Mesoporous silica nanoparticles (SBA-15) as host materials for transporting therapeutics medicaments were fabricated for targeted drug delivery toward lung cancer. With the objective of increasing bioavailability and aqueous solubility of flavonoids, SBA-15 was successfully loaded with the quercetin (Q)—a major flavonoid and characterized with the help of Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The biological investigation on A549 cell line confirmed that the efficacy of Q-SBA-15 is much higher than only Q. Moreover, the apoptotic pathway of synthesized Q-SBA-15 NPs examined that the Q-SBA-15–mediated apoptosis via PI3K/AKT/mTOR signaling pathway. Thus, the newly conjugated Q-SBA-15 system improved the apoptotic fate through caspase-mediated apoptosis via PI3K/AKT/mTOR signaling pathway and hence, it can be potentially employed as an anticancer agent for lung cancer.
5 citations
TL;DR: In this paper , the authors used Moringa oleifera leaves with different concentrations as reducing as well capping agent for the synthesis of silver nanoparticles (AgNPs) using bio-reduction method.
Abstract: Background In the field of nanotechnology, the metallic nanoparticles are of remarkable interest because of their unique electronic, magnetic, chemical, and mechanical properties. Purpose: In the present work, silver nanoparticles (AgNPs) were synthesized using bio-reduction method. Research Design: Silver nitrate was used as metallic precursor and the extract of Moringa oleifera leaves with different concentrations was used as reducing as well capping agent. The extract exhibited strong potential in rapid reduction of silver ions for the synthesis of silver nanoparticles. The synthesized silver nanoparticles were characterized by UV-visible spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) techniques. Results: The absorption SPR peaks appeared in the range of 415 to 439 nm. SEM analysis exhibited that particles were spherical in shape with size distribution range from 10 nm to 25 nm. The synthesized silver nanoparticles were pure crystalline in nature as confirmed by the XRD spectra with average crystallite size 7 nm. In vitro antibacterial activity of the prepared silver nanoparticles colloidal samples as well the extract was studied using different concentrations of AgNPs (C1 = 100 μg/ml, C2 = 50 μg/ml, C3 = 25 μg/ml) by well diffusion method against Gram negative Escherichia coli. The antibacterial performance was assessed by measuring the zone of inhibition (ZOI). Conclusions The results suggested that AgNPs prepared by green approach can be considered as an alternative antibacterial agent.
TL;DR: The case of a patient in Massachusetts with early-stage Alzheimer’s disease who was treated with low doses of ionizing radiation to the brain and his impaired conversation, reading, and sense of humor were restored, especially his virtuosic clarinet jazz-playing, suggesting CT scans may have value in treating Alzheimer's patients and restoring, at least temporarily, important aspects of normal life activities.
Abstract: We report the case of a patient in Massachusetts with early-stage Alzheimer’s disease who was treated with low doses of ionizing radiation to the brain. He requested this treatment after reading about a patient with severe Alzheimer’s in Michigan who improved remarkably after receiving 4 CT scans. After his first treatment in April 2016, mental clarity improved. His impaired conversation, reading, and sense of humor were restored, especially his virtuosic clarinet jazz-playing. However, executive function remained deficient. He requested a treatment every 2 weeks, but his neurologist denied this, fearing opposition to this treatment, a diagnostic procedure that used ionizing radiation. Limited recovery was observed after each CT scan, lasting from several weeks to months, depending on the endpoints/behavior and the periodicity. Despite the positive responses, the physician was reluctant to continue beyond 6 due to concerns about adverse effects and disapproval for prescribing them. The patient began hyperbaric oxygen therapy as an alternative. But after 43 treatments, no conclusive benefit was observed. The patient died in September 2020 at age 77. This experience suggests CT scans may have value in treating Alzheimer’s patients and restoring, at least temporarily, important aspects of normal life activities. Such observations need testing and validation.
TL;DR: In this paper , the results of physical factors like density, color, refractive index, and solubility of the EOs produced by both the methods showed insignificant variations, which can be linked to the difference in the volatile bioactives composition due to different isolation techniques.
Abstract: Present research work evaluates variation in volatile chemicals profile and biological activities of essential oil (EO) obtained from the leaves of eucalyptus (Eucalyptus camaldulensis Dehnh.) using hydro-distillation (HD) and supercritical fluid extraction (SFE). The yield (1.32%) of volatile oil by HD was higher than the yield (.52%) of the SFE method (P < .05). The results of physical factors like density, color, refractive index, and solubility of the EOs produced by both the methods showed insignificant variations. Gas chromatography - mass spectrometry (GC-MS) compositional analysis showed that eucalyptol (31.10% and 30.43%) and α-pinene (11.02% and 10.35%) were the main constituents detected in SFE and HD extracted Eucalyptus camaldulensis EO, respectively. Antioxidant activity-related parameters, such as reducing ability and DPPH free radical scavenging capability exhibited by EO obtained via SFE were noted to be better than hydro-distilled EO. Supercritical fluid extracted and hydro-distilled essential oils demonstrated a considerable but variable antimicrobial potential against selected bacterial and fungal strains. Interestingly, oil extracted by SFE showed relatively higher hemolytic activity and biofilm inhibition potential. The variation in biological activities of tested EOs can be linked to the difference in the volatile bioactives composition due to different isolation techniques. In conclusion, the EO obtained from Eucalyptus leaves by the SFE method can be explored as a potential antioxidant and antimicrobial agent in the functional food and nutra-pharmaceutical sector.
TL;DR: Puerarin exerts a radioprotective effect by decreasing DNA damage and apoptosis through miR-34a-targeted PLGF through which patients receiving radiotherapy are protected from radiation-induced vascular endothelial cell damage.
Abstract: The aim is to explore the protective effects of Puerarin on radiation-induced vascular endothelial cell damage and its underlying mechanism. The apoptosis and DNA damage of Human umbilical vascular endothelial cells (HUVECs) exposed to radiation alone or in combination with glucose in the exposed group were significantly elevated (P < .05) compared with those in the control group. The Puerarin-treated HUVECs showed significant reduction in the radiation-induced apoptosis and DNA damage (P < .05). Furthermore, X-ray irradiation significantly increased the expression of miR-34a, which was reversed by pre-treatment with Puerarin. Placental Growth Factor (PLGF) was a target gene of miR-34a. The expression of PLGF in the peripheral blood of patients receiving radiotherapy significantly increased with an increase in the cumulative dose of radiation (P < .05), after which it began to decrease at the fourth week (P < .05) and then remained at a low level until the end of radiotherapy. Puerarin exerts a radioprotective effect by decreasing DNA damage and apoptosis through miR-34a-targeted PLGF.
TL;DR: Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose.
Abstract: Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.
TL;DR: The results illustrated that resveratrol and taxifolin have potential to prevent the metabolism of carbohydrates via inhibition of α-amylase and α-glucosidase, and prolongs metabolic function of incretin by inhibiting the enzymatic activity of DPP-IV.
Abstract: The aim of current study was to investigate the inhibitory activities of resveratrol and taxifolin against α-amylase, α-glucosidase, and DPP-IV enzymes via in vitro analysis which was further validated by in silico studies. The analysis of molecular docking was also done to determine the binding capabilities of resveratrol and taxifolin with α-amylase, α-glucosidase, and DPP-IV enzymes. Resveratrol and taxifolin having IC50 values, 47.93 ± 5.21 μ M and 45.86 ± 3.78 μ M , respectively, showed weaker effect than acarbose (4.6 ± 1.26 μ M ) on α-amylase but showed significant effect to inhibit α-glucosidase (32.23 ± .556 μ M and 31.26 ± .556 μ M , respectively). IC50 value of resveratrol and taxifolin (5.638 ± .0016 μ M and 6.691 ± .004 μ M ) in comparison to diprotin A (IC50: 7.21 ± .021 μ M ) showed that they have significant inhibitory effect on DPP-IV enzyme. Our results illustrated that resveratrol and taxifolin have potential to prevent the metabolism of carbohydrates via inhibition of α-amylase and α-glucosidase, and prolongs metabolic function of incretin by inhibiting the enzymatic activity of DPP-IV. The results of molecular docking have also revealed that resveratrol and taxifolin have significant affinity to bind with α-amylase, α-glucosidase, and DPP-IV in comparison with standard drugs such as acarbose, miglitol, and diprotin.
TL;DR: In this article, the anti-Parkinson's (PD) potential of B cernua (BCE) was evaluated for 40 days and the results showed significant improvement in motor functions and coordination in a dose-dependent manner.
Abstract: The aims and objectives of the study were to evaluate the antiParkinson’s (PD) potential of B cernua (BCE). B cernua (Poir.) Müll. Arg. (B cernua) is a member of the Phyllanthaceae family. HPLC revealed the presence of various phytochemicals. Study was conducted for 40 days. After PD induction by paraquat behavioural studies were carried out. Biochemical parameters such as DPPH, NO-scavenging, Ferrous reducing power, MDA, GSH, CAT, SOD, acetylcholinesterase (AChE), neurotransmitter estimation and TNF-α and IL-6 levels were determined. DPPH, NO-scavenging and Ferrous reducing power assays showed 78.02%, 48.05% and 71.45% inhibitions, respectively. There was significant improvement in motor functions and coordination in a dose-dependent manner (50 < 250 < 500 mg/kg) in PD rat model. Biochemical markers; SOD, CAT, GPx and GSH showed significant restoration (P < .001) while MDA showed significant decrease (P < .05). The AChE level was significantly reduced (P < .05) at 500 mg/kg while neurotransmitters were significantly improved (P < .001) in a dose-dependent fashion. The ELISA results showed significant (P < .001) down-regulation of IL-6 and TNF-α level. In conclusion, it is suggested that BCE has the potential to reduce the symptoms of PD.
TL;DR: In this article , the authors evaluated the antioxidant, inhibition activity of the ethanolic, methanolic, and aqueous extracts of P.K roots against α-amylase and α-glucosidase in vitro, after the phytochemical analysis.
Abstract: Picrorhiza kurroa (P.K) usually familiar as kutki is a well-known plant in the Ayurvedic system of medicine due to its reported activities including antidiabetic, antibacterial, antioxidant, antitumor, anti-inflammatory, and hepatoprotective. The current research was intended to evaluate the antioxidant, inhibition activity of the ethanolic, methanolic, and aqueous extracts of P.K roots against α-amylase and α-glucosidase in vitro, after the phytochemical analysis. For this purpose, P.K roots were extracted with ethanol (EthPk), methanol (MthPk), and distilled water (AqPk) and phytochemical study of the extracts were performed to recognize the total phenolic content (TPC) and total flavonoids content (TFC). Antioxidant capability of the extracts was assessed by FRAP, ABTS, and DPPH assay. α-amylase inhibitory and α-glucosidase inhibitory activities were also determined. Software SPSS-23 was used to statistically analyze with One Way ANOVA and results were stated as mean standard deviation. Result of the study showed that MthPk contained the maximum concentration of TPC and TFC than EthPk and AqEh. Antioxidants in terms of DPPH (lowest IC50 = .894 ± .57), FRAP (612.54 ± 11.73) and ABTS (406.42 ± 4.02) assay was also maximum in MthPk. MthPk was also showed maximum inhibition activity against α-amylase and α-glucosidase with lowest IC50 (.39 ± .41; .61 ± .24), respectively. The extracts α-amylase and α-glucosidase inhibitory activities order was as MthPk > EthPk> AqPk. Results clearly specified that the methanolic extract of Picrorhiza kurroa have the maximum antioxidant, α-amylase, and α-glucosidase inhibitory activities. A positive correlation of TPC, TFC with antioxidant, and α-amylase and α-glucosidase inhibition activities of the P.K roots were also shown. The plant has capability to diminish the oxidative stress and can be used to treat diabetes by inhibiting α-amylase and α-glucosidase actions.
TL;DR: In vitro assay showed that WS + IR potentiates proliferation-inhibition and cell death of the A-549 cell line and suppresses sphere formation, providing cure insights into the molecular mechanisms of lung CSCs intervention.
Abstract: Cancer stem cells (CSCs) are implicated in the genesis, development, and recurrence of lung cancer (LC) with great resistance to radiation and chemotherapy. The aim of this study is to assess the inhibitory potential of ethanol extract of Withania somnifera (WS); 500 mg/kg body-weight/day and 8 Gy of ionizing radiation (IR) could inhibit the stemness gene and confer the radiosensitizing effect of W. somnifera extract in the female rat LC model. Compared to IR or WS, the in vitro assay showed that WS + IR potentiates proliferation-inhibition and cell death of the A-549 cell line and suppresses sphere formation. The Hedgehog (Hh) signaling associated with the expression levels of lung CSC markers, octamer-binding transcription factor-4 (OCT4), SRY-box 2 (SOX2), CD133, ATP Binding Cassette Subfamily G Member 2 (ABCG2), and NANOG was upregulated with stimulated epithelial-to-mesenchymal transition (EMT) indicators α-smooth muscle actin (α-SMA), Drosophila embryonic protein (SNAIL-1), Vimentin, and E-cadherin in the LC rat model. The W. somnifera extract plus IR inhibits Hh activation factors, which has resulted in the suppression of CSC gene markers and EMT factors. W. somnifera extract may be a significant adjuvant in the course of radiotherapy, contributing to the termination of tumor progression, and thus providing cure insights into the molecular mechanisms of lung CSCs intervention.
TL;DR: In this article , the authors focused on the protection effects of G.s Maxim in hypoxia-induced oxidative stress and apoptosis and found that G.S Maxim significantly increased survival and reduced oxidative stress in hypoxic mice.
Abstract: Hypoxia occurs in physiological situations and several pathological situations, inducing oxidative stress. G straminea Maxim (G.s Maxim) is a traditional Tibetan medicine that exerts several biological effects. This study focused on the protective effects of G.s Maxim in hypoxia-induced oxidative stress and apoptosis. We found that G.s Maxim significantly increased survival and reduced oxidative stress in hypoxic mice. Various extraction parts of G.s Maxim showed antioxidant activity and significantly improved survival in hypoxia-injured PC12 cells. G.s Maxim reduced hypoxia-induced cell apoptosis and leakage of lactate dehydrogenase. Hypoxic cells had increased malondialdehyde levels but reduced superoxide dismutase activity and G.s Maxim reversed these effects. Moreover, G.s Maxim suppressed hypoxia-induced apoptosis by inducing protein expression of B cell leukemia/lymphoma-2 and reducing the expression of hypoxia-inducible factor-1α, Bcl-2-associated X, and nuclear factor-k-gene binding. These findings suggest that G.s Maxim attenuates hypoxia-induced injury associated with oxidative stress and apoptosis.
TL;DR: Research results from focus groups demonstrated that policy stakeholders are knowledgeable about issues surrounding the public and perceptions about LDR and implications for policy consistent with LDR literature.
Abstract: Concern over low-dose radiation (LDR) (exposure of less than 100 milligray (mGy)) is resulting in people refusing diagnostic procedures and medical treatment 1 and also inhibiting revision of the linear no-threshold (LNT) assumption that informs much of science policy. This article reviews representative surveys in Ontario and Saskatchewan and focus groups conducted with science and policy stakeholders in addressing how the public and policy stakeholders understand issues of exposure to LDR and how policy issues can be addressed. Research results from focus groups demonstrated that policy stakeholders are knowledgeable about issues surrounding the public and perceptions about LDR and implications for policy consistent with LDR literature. Participants understood that the challenge went beyond providing more education about LDR and issues of emotions and biases must be addressed. This research resulted in rich suggestions for public communication and engagement surrounding LDR and a process for addressing the issue of the LNT.
TL;DR: In this paper , the effect of blood flow restriction resistance training under different external loads on the muscle strength and vertical jumping performance in volleyball players was examined, and a twoway repeated-measures analysis of variance was used to examine differences among the three groups and between the 2 testing time (pre-test vs post-test).
Abstract: Purpose To examine the effect of blood flow restriction resistance training under different external loads on the muscle strength and vertical jumping performance in volleyball players. Methods 18 well-trained collegiate male volleyball players were randomly divided into 3 groups: high-load resistance training group (HL-RT, 70% 1RM, n = 6), low-load blood flow restriction resistance training group (LL-BFR-RT, 30% 1RM, 50% arterial occlusion, n = 6), and high-load blood flow restriction resistance training group (HL-BFR-RT, 70% 1RM, 50% arterial occlusion, n = 6). Participants performed leg half-squat exercise 3 times per week for 8 weeks. Measurements of Isokinetic peak torque of knee extension and flexion, 1RM leg half-squat, squat jump, and 3 footed take-off were obtained before and after training. A two-way repeated-measures analysis of variance was used to examine differences among the 3 groups and between the 2 testing time (pre-test vs post-test). Results (1) The HL-RT group was significantly greater in muscle strength than that in the LL-BFR-RT group (P < .05), but no improvement in vertical jumping performance (P >.05). (2) Improvement in muscle strength and vertical jumping performance was significantly greater in the HL-BFR-RT group than that in the LL-BFR-RT group (P <.05). (3) The HL-BFR-RT group had greater but not significant improvement in muscle strength and vertical jumping performance than that in the HL-RT group. Conclusions Although increases in muscle strength were observed between training groups, HL-BFR-RT increased not only muscle strength but vertical jumping performance to a greater extent compared to LL-BFR-RT and HL-RT.
TL;DR: Curc and Lip acid can be considered as promising natural therapies against liver injury, induced by NHPA, through their antioxidant and antifibrotic actions.
Abstract: Background and objectives N-(4-hydroxyphenyl) acetamide (NHPA) is the most commonly used analgesic and antipyretic agent worldwide; however, it remains the leading cause of drug-induced acute liver failure. This study explored the potential impact of curcumin (Curc) and/or α-lipoic acid (Lip acid) on liver damage induced by NHPA overdose. Materials and Methods Male Wistar rats were intoxicated with a single oral dose of NHPA (1000 mg/kg) and treated with Curc (200 mg/kg p. o.) and/or Lip acid (100 mg/kg i. p.). These treatments were given in 2 doses at 2 hours and 10 hours post-NHPA-administration. Animals were sacrificed 24 hours post-NHPA-administration. Results Treatment with Curc and/or Lip acid showed effective reduction of NHPA-induced liver injury, demonstrated by reducing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, as well as hepatic nitric oxide and malondialdehyde. Curc and/or Lip acid treatments counteracted these changes. They also ameliorated NHPA-induced centrilobular hepatocellular necrosis, evidenced by histopathological examination. Moreover, Curc and Lip acid reduced the expression of alpha-smooth muscle actin and collagen III, upregulated by NHPA intoxication in response to oxidative stress and inflammation. Discussion and Conclusion Curc and Lip acid can be considered as promising natural therapies against liver injury, induced by NHPA, through their antioxidant and antifibrotic actions.
TL;DR: Results highlight the modulatory properties of MgO and MnO nanoparticles and merit further studies delineating the molecular mechanisms through which these nanoparticles induce antidiabetic effects.
Abstract: Magnesium oxide (MgO) and manganese oxide (MnO) have been reported to be effective against Diabetes Mellitus (DM). However, their nanoparticulate form has not been evaluated for antidiabetic effect. MgO and MnO nanoparticles (15–35 nm) were synthesized and subsequently characterized by ultraviolet-visible spectroscopy (UV-VIS), zeta sizer, and scanning electron microscopy. 6–7 weeks old rats weighing 200–220 mg were divided into 07 equal groups (n = 8), namely, negative control (NC), positive control (PC), standard control (Std-C), MgO high dose group (MgO-300) and low dose group (MgO-150), and MnO nanoparticle high dose (MnO-30) and low dose group (MnO-15). Diabetes was chemically induced (streptozotocin 60 mg/kg B.W) in all groups except the NC. Animals were given CMD and water was ad libitum. Nanoparticles were supplemented for 30 days after the successful induction of diabetes. Blood and tissue samples were collected after the 30th day of the trial. The mean serum glucose, insulin, and glucagon levels were improved maximally in the MgO-300 group followed by MgO-150 and MnO-30 groups. Whereas the MnO-15 group fails to show any substantial improvement in the levels of glucose, insulin, and glucagon as compared to the positive control group. Interesting the serum triiodothyronine, thyroxine, and thyroid-stimulating hormone levels were markedly improved in all the nanoparticle treatment groups and were found to be similar to the standard control group. These results highlight the modulatory properties of MgO and MnO nanoparticles and merit further studies delineating the molecular mechanisms through which these nanoparticles induce antidiabetic effects.
TL;DR: The study revealed that pre-existing iron deficiency is connected with increased lead intake and can negatively impact health in gestational females and has an impact on the heme-biosynthetic pathways.
Abstract: Lead may be passed on from a mother to their unborn fetus. If she has been exposed to lead for an extended period, the lead deposited in their bones can be stimulated to be released into the bloodstream during gestation. This study was planned to examine blood lead level at the prenatal stage and its response to markers of iron deficiency during gestation. We collected 396 samples during the second trimester of gestation from women age 19 to 45 years. Hematological markers including hemoglobin, hepcidin, total iron-binding capacity (TIBC), ferritin, and blood iron were analyzed. For the detection of blood lead, we used Atomic absorption spectroscopy. The mean blood lead level of the control group was 3.25 ± .407 μg/dL, and in the iron deficiency group, it was 7.96 ± .502 μg/dL. At the same time, the women with iron deficiency anemia showed 22.12 ± 1.02 μg/dL of mean blood lead. Pearson’s approach showed a non-significant negative correlation between blood lead and hepcidin, while hemoglobin, total iron-binding capacity, ferritin, and serum iron showed a significant (.01) negative correlation with blood lead. Blood lead has no direct effect on iron deficiency markers. In contrast, iron deficiency contributes to an increase in lead accumulation during pregnancy. Iron and lead both have an impact on the heme-biosynthetic pathways. The study revealed that pre-existing iron deficiency is connected with increased lead intake and can negatively impact health in gestational females.
TL;DR: Combination of diclofenac with andrographolide showed better pharmacologic effects after carrageenan injection and was more synergistic at low-dose combinations.
Abstract: Studies into drug combination at low doses are a promising approach to the management of pain and inflammation. The aim of this study was to evaluate the anti-edema and anti-hyperalgesic effects of a combination of diclofenac and andrographolide. Male Sprague-Dawley rats were first treated with diclofenac or andrographolide alone (3–100 mg/kg), as well as a combination of the 2 drugs. Carrageenan was then injected into the right hind paw of rats, and changes in paw volume and sensitivity to mechanical (von Frey) and thermal (Hargreaves test) stimuli measured. Results showed drug combination produced synergistic effects at reducing paw edema especially at lower doses, with a Loewe synergy score of 13.02 ± 8.75 in SynergyFinder and a combination index of .41 ± .18 after isobolographic analysis. Again synergy scores for decreasing response to 1.0 and 3.6 g force application of von Frey filaments after drug combination were 10.127 ± 5.68 and 8.554 ± 6.53, respectively, in SynergyFinder. Synergistic effects were also seen after drug combination in the Hargreaves test with a synergy score of 5.136 ± 16.38. In conclusion, combination of diclofenac with andrographolide showed better pharmacologic effects after carrageenan injection and was more synergistic at low-dose combinations.
TL;DR: In-vivo studies on rats infected with Candida albicans confirmed superiority of nanogels over 1% Lamisil for eradication of fungal infection and confirmed that TBH loaded in Pluronic F127 co-poly-(acrylic acid) nanogel provided greater targetibility and cure rates of poorly soluble TBH in animal model and hence Nanogels could be a potential carrier for effective topical delivery of TBH for skin fungal infections treatment.
Abstract: Research aimed to develop and evaluate biodegradable, pH-responsive chemically cross-linked Pluronic F127 co-poly- (acrylic acid) nanogels for dermal delivery of Terbinafine HCL (TBH) to increase its permeability and as a new approach to treat skin fungal infections. TBH-loaded nanogels were successfully synthesized from acrylic acid (AA) and Pluronic F127 by free-radical copolymerization technique using N,N′-methylene bisacrylamide (MBA) as crosslinker and ammonium persulphate (APS) as initiator. Prepared nanogels exhibited 93.51% drug entrapment efficiency (DEE), 45 nm particle size, pH-dependent swelling and release behavior. Nanogels were characterized using different physicochemical techniques. The ex-vivo skin retention studies through rat skin showed about 42.34% drug retention from nanogels while 1% Lamisil cream (marketed product) showed about 26.56% drug retention. Moreover, skin irritation studies showed that nanogels were not irritating. Nanogels showed improved in-vitro antifungal activity against Candida albicans compared to commercial product. In-vivo studies on rats infected with Candida albicans confirmed superiority of nanogels over 1% Lamisil for eradication of fungal infection. This confirms that TBH loaded in Pluronic F127 co-poly-(acrylic acid) nanogels provided greater targetibility and cure rates of poorly soluble TBH in animal model and hence nanogels could be a potential carrier for effective topical delivery of TBH for skin fungal infection treatment.
TL;DR: In this paper , EGCG was used to reduce hypermethylation of ACTN4 in kidney podocyte cells by downregulating DNA methyltransferase 1 (DNMT1) and contributing to the upregulation of the NF-KB p65, p-NF-KBp65, IKB-α, VEGF, IL-8, α-SMA, and FN levels.
Abstract: Actinin alpha 4 (ACTN4) is expressed in the kidney podocytes. ACTN4 gene methylation in patients with diabetic nephropathy (DN) remains high. Underlying mechanism of epigallocatechin-3-gallate (EGCG) inducing ACTN4 demethylation, and its inhibitory effect on DN renal fibrosis remains unclear. Methods: Human podocyte cell line, HPC, was treated with high glucose to establish model of DN. The levels of cytokines, vascular endothelial growth factor (VEGF) and interleukin (IL)-8, and fibrosis markers, alpha smooth muscle actin (α-SMA) and fibronectin (FN), were determined using enzyme-linked immunosorbent assay. HPC cells were treated with EGCG, and cell viability was determined by MTT assay, ACTN4 gene methylation was analyzed by MSP. mRNA and protein expression levels were measured using RT-qPCR and Western blotting, respectively. Results: Actinin alpha 4 gene promoter was hypermethylated in the high glucose-treated groups. EGCG reversed the hypermethylated status of ACTN4, along with the upregulation of ACTN4 levels and downregulation of DNA methyltransferase 1 (DNMT1), NF-κB p65, p-NF-κB p65, IκB-α, VEGF, IL-8, α-SMA, and FN levels (P<.05). Conclusion: Epigallocatechin-3-gallate reduced hypermethylation of ACTN4 in HPC cells by downregulating DNMT1 expression and restoring ACTN4 expression, contributing to the upregulation of the NF-KB p65, p-NF-KB p65, IKB-α, VEGF, IL-8, α-SMA, and FN levels (P<.05).
TL;DR: It was revealed that most novel compounds were effective antibacterial, whereas compound UA3 has shared significant anti-quorum sensing potential against Chromobacterium pseudoviolaceum.
Abstract: Quorum sensing (QS) is a major controller of virulence and biofilm formation in pathogenic bacteria. The aim of the research was to screen novel synthetic compounds (18) from 2 series (Pyrazole and Diene dione) for quorum sensing and biofilm inhibitory potential against resistant pathogens isolated from patients with chronic sinusitis. Most of the compounds have documented zone of inhibition against Gram positive strains Staphylococcus aureus, Enterococcus faecalis and moderate activity against Gram negative Klebseilla pneumoniae and Proteus mirabilis in comparison with standard antibiotic. Compounds Q1 and Q7 have given the maximum zone of inhibition 18 and 20 mm with MICs 0.312 mg/mL and .156 mg/mL against S aureus and E faecalis, respectively. Some compounds were equally potent at inhibiting the formation of biofilm which later established by phase contrast microscopy. Regarding quorum sensing inhibition, the tested concentration of synthetic compound UA3 0.313 mg/mL inhibited violacein production without decreasing Chromobacterium pseudoviolaceum count which was significantly lower than determined MIC’s. It was depicted from the results that selected compounds exhibited low level of cytotoxicity toward human red blood cells. Hence, these findings revealed that most novel compounds were effective antibacterial, whereas compound UA3 has shared significant anti-quorum sensing potential against Chromobacterium pseudoviolaceum.
TL;DR: In this article , the volatiles chemical composition and biological attributes of coriander leaves essential oil obtained by two extraction techniques namely supercritical fluid extraction and hydro-distillation is appraised.
Abstract: The volatiles chemical composition and biological attributes of coriander (Coriandrum sativum L.) leaves essential oil obtained by two extraction techniques namely supercritical fluid extraction and hydro-distillation is appraised. The coriander essential oil yield (.12%) by hydro-distillation was slightly higher than that of supercritical fluid extraction (.09%). The physico-chemical variables of the essential oil obtained from both the techniques varied in significantly (P < .05). GC-MS analysis identified 23 different components in supercritical fluid extracted oil and 18 components in hydro-distilled essential oil having linalool as major component (51.32% and 61.78%, respectively) followed by phytol (12.71%). The oil recovered by supercritical fluid extraction exhibited greater DPPH radical scavenging activity as well as reducing power as compared to the essential oil obtained by hydro-distillation technique along with a stronger biofilm inhibition and least hemolysis. The results of antimicrobial activity revealed that super critical fluid extracted essential oil has potent antifungal and antibacterial activity against P. multocida and A alternata, whereas hydro-distilled essential oil displayed better antimicrobial potential against E coli and A niger. Overall, these results depict that supercritical fluid extraction is superior than hydro-distillation with regard to isolation of better-quality coriander essential oil for nutra-pharmaceutical developments.