Ameliorative effect of chitosan nanoparticles in capacitation media on post-thawing in vitro fertilizing ability of bovine spermatozoa.

This study aimed to investigate the effect of supplementation of chitosan nanoparticles (CSNPs) on the capacitation of bovine spermatozoa during the in vitro fertilization process. Hyperactivated motility (HAM) and acrosome reaction (AR) of sperm cells as well as in vitro fertilization and cleavage rates are the main parameters used to estimate the effect of CSNPs on bovine spermatozoa's fertilizing ability. In this study, three different concentrations of CSNPs (10, 20 and 100 µg/mL) were prepared and characterized. Motile spermatozoa were separated from frozen-thawed semen by a swim-up technique and capacitated in Sperm-TALP medium supplemented with heparin only without CSNPs treatment (positive control), heparin + 10 µg/mL CSNPs, heparin + 20 µg/mL CSNPs, heparin + 100 µg/mL CSNPs and the last one served as a negative control tube which supplemented with 10 µg/mL CSNPs without adding heparin. Sperm cells were incubated for 90 min at 39°C in a 5% CO2 incubator and evaluated every 30 min at intervals. Cumulus oophorus complex (COCs) were matured in a 5% CO2 incubator at 39°C and inseminated in vitro with frozen-thawed bull sperm of the above concentrations. The inseminated oocytes were incubated at 39°C in a 5% CO2 incubator for 24 h and then examined for evidence of fertilization. The results of this investigation showed that HAM and AR were best affected by CSNPs at a concentration of 20 µg/mL during an incubation time of 60 min. As time went on, the overall proportion of spermatozoa with progressive motility (PM) decreased across all groups, and a substantially lower value was found at the dose mentioned above. Additionally, the impact of sperm treated with CSNPs on fertilization rate was assessed. The outcomes demonstrated that in comparison to the other concentrations (10 and 100 µg/mL), the positive control and the negative control, the proportion of fertilized oocytes was significantly higher in the CSNPs concentration (20 µg/mL). In conclusion, it could be inferred from this investigation that CSNPs support sperm functions during IVF and can be used for biomedical interventions in bovine spermatozoa. Additionally, a high IVF rate was achieved by using sperm treated with CSNPs as CSNPs enhance sperm capacitation and acrosome reaction.

Photodynamic Activity of Chlorophyllin and Polyethylenimine on Pseudomonas aeruginosa Planktonic, Biofilm and Persister Cells.

Antimicrobial photodynamic inactivation is considered a promising antimicrobial approach that may not develop resistance in the near future. Here, we investigate the influence of the photosensitizer chlorophyllin (CHL) and the cationic permeabilizer polyethylenimine (PEI), exposed to a red light-emitting diode, on the human pathogen Pseudomonas aeruginosa free-living planktonic cells, the sessile biofilm and persister cells. The broth microdilution checkerboard method was used to test antimicrobial susceptibility. As a substrate for biofilms, the Calgary biofilm device was used, and the quantification of the biofilm biomass was carried out using a crystal violet assay. Serine hydroxamate was used for the induction of persisters. Our findings reveal that PEI ameliorates the antimicrobial activity of CHL against P. aeruginosa planktonic and biofilm states, and the concentration required to eradicate the bacteria in the biofilm is more than fourfold that is required to eradicate planktonic cells. Interestingly, the persister cells are more susceptible to CHL/PEI (31.25/100 µg mL-1) than the growing cells by 1.7 ± 0.12 and 0.4 ± 0.1 log10 reduction, respectively, after 15 min of illumination. These data demonstrate that CHL excited with red light together with PEI is promising for the eradication of P. aeruginosa, and the susceptibility of P. aeruginosa to CHL/PEI is influenced by the concentrations and the exposure time.

Thymus satureioides Coss. combats oral ulcer via inhibition of inflammation, proteolysis, and apoptosis.

Oral ulcer is a frequent condition that commonly affects the tongue and in which 75% of the patients experience pain, and 25% report taste changes. The available therapies are not sufficiently effective for rapid and complete healing of tongue ulcers. We previously annotated the metabolites of Thymus satureioides (TS) aerial parts and reported their antioxidant, dermacosmeceutical and hepatoprotective properties. In this study, we performed in silico analysis, by applying network pharmacology and molecular docking, followed by experimental validation of the effect of local application of T. satureioides (TS) gel at two different concentrations on the healing of acetic-acid-induced tongue ulcer in rats. Salvianolic acid A, phloretic acid caffeate, rosmarinic acid, apigenin, and luteolin were the top bioactive ingredients of TS extract. Network pharmacology showed that the most relevant targets of these active constituents were TLR4, COX-2, MMP-9, TNF-α, and Caspase-3. Molecular docking showed that rosmarinic acid and salvianolic acid had a relatively strong binding affinity, compared to the other compounds, toward all the target proteins. Experimental validation in tongue ulcer model in rats and immunohistochemistry experiments showed that application of a gel containing TS extract (5 and 10%) was effective in healing the tongue ulcer via downregulation of COX-2, TNF-α, MMP-9, and Caspase-3. This study suggests that T. satureioides extract could act as a topical treatment for tongue ulcers by combating inflammation, apoptosis, and proteolysis. The possible treatment potential of some constituents including rosmarinic acid and salvianolic acid in oral ulcerations awaits further investigations to confirm their potency.

Thymus satureioides Coss.: Mineral Composition, Nutritional Value, Phytochemical Profiling, and Dermatological Properties.

Zaitra, Thymus satureioides, is an aromatic plant with a long history of use in traditional medicine. In this study, we assessed the mineral composition, nutritional value, phytocontents, and dermatological properties of the aerial parts of T. satureioides. The plant contained high contents of calcium and iron, moderate levels of magnesium, manganese, and zinc, and low contents of total nitrogen, total phosphorus, total potassium, and copper. It is rich in several amino acids, including asparagine, 4-hydroxyproline, isoleucine, and leucine, and the essential amino acids account for 60.8%. The extract contains considerable amounts of polyphenols and flavonoids (TPC = 118.17 mg GAE/g extract and TFC = 32.32 mg quercetin/g extract). It also comprises 46 secondary metabolites, identified through LC-MS/MS analysis, belonging to phenolic acids, chalcones, and flavonoids. The extract elicited pronounced antioxidant activities, inhibited the growth of P. aeruginosa (MIC = 50 mg/mL), and reduced biofilm formation by up to 35.13% using the » sub-MIC of 12.5 mg/mL. Moreover, bacterial extracellular proteins and exopolysaccharides were diminished by 46.15% and 69.04%, respectively. Likewise, the swimming of the bacterium was impaired (56.94% decrease) in the presence of the extract. In silico, skin permeability and sensitization effects revealed that out of the 46 identified compounds, 33 were predicted to be exempt from any skin sensitivity risk (Human Sensitizer Score ≤ 0.5), while extensive skin permeabilities were observed (Log Kp = -3.35--11.98 cm/s). This study provides scientific evidence about the pronounced activities of T. satureioides, supports its traditional uses, and promotes its utilization in the development of new drugs, food supplements, and dermatological agents.

Cupressus arizonica Greene: Phytochemical Profile and Cosmeceutical and Dermatological Properties of Its Leaf Extracts.

For many decades, natural resources have traditionally been employed in skin care. Here, we explored the phytochemical profile of the aqueous and ethanolic leaf extracts of Cupressus arizonica Greene and assessed their antioxidant, antiaging and antibacterial activities in vitro. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis led to the tentative identification of 67 compounds consisting mainly of phenolic and fatty acids, diterpene acids, proanthocyanidins and flavonoid and biflavonoid glycosides. The aqueous extract demonstrated substantial in vitro antioxidant potential at FRAP and DPPH assays and inhibited the four target enzymes (collagenase, elastase, tyrosinase, and hyaluronidase) engaged in skin remodeling and aging with IC50 values close to those of the standard drugs. Moreover, the aqueous extract at 25 mg/mL suppressed biofilm formation by Pseudomonas aeruginosa, a bacterial pathogen causing common skin manifestations, and decreased its swarming and swimming motilities. In conclusion, C. arizonica leaves can be considered a promising candidate for potential application in skin aging.

Dermato-cosmeceutical properties of Pseudobombax ellipticum (Kunth) Dugand: Chemical profiling, in vitro and in silico studies.

Plant extracts and their individual components have been used to manage skin aging for several decades. Recently, the discovery of new natural bioactive agents, that not only enhance the skin health but also offer protection against various deleterious factors, such as free radicals, ultraviolet radiation, and microbial infections, has been a potential target by many researchers. The aim of the current work was to investigate the phytochemical profile of an ethanol bark extract from Pseudobombax ellipticum, and to evaluate its antioxidant, antiaging and antibacterial activities in vitro. Molecular docking and molecular dynamics studies were adopted to estimate and confirm the binding affinity of several compounds and explain their binding pattern at the binding sites of four target enzymes associated with skin aging, namely collagenase, elastase, tyrosinase, and hyaluronidase. HPLC-MS/MS analysis led to the tentative identification of 35 compounds comprising phenolic acids, and their glycosides, procyanidins and flavonoid glycosides. The extract demonstrated a promising in vitro antioxidant activity in the DPPH and FRAP assays (IC50 56.45 and 15.34 µg/mL, respectively), and was able to inhibit the aforementioned key enzymes with comparable results to the reference drugs. In addition, the extract (6.25 mg/mL) inhibited the biofilm production of Pseudomonas aeruginosa and diminished the swimming and swarming motilities. The docked compounds revealed appreciable binding energy with the tested enzymes and were stable throughout the molecular dynamic simulations. In view of this data, P. ellipticum bark can be regarded as a good candidate for prospective application in derma-cosmeceutical preparations.

Trends in utilization, outcomes, and readmissions after transcatheter mitral valve replacement.

BACKGROUND: There is a paucity of real-world data regarding the temporal trends and outcomes of trans-septal transcatheter mitral valve replacement (TS-TMVR) in the United States (US). METHODS: We queried the Nationwide Readmissions Database (October 2015 to December 2018) for patients undergoing TS-TMVR procedures. We reported the temporal trends in the utilization, in-hospital outcomes and 30-day readmissions after TS-TMVR. The main study outcome was in-hospital mortality. RESULTS: There was an increase in the number of TS-TMVR procedures over time (48 in 2015 vs. 978 in 2018, Ptrend < 0.001), with a notable increase in the proportion of women (Ptrend  = 0.04) and the prevalence of diabetes (Ptrend  = 0.03). There was an increase in the number of centers performing TS-TMVR (21 in 2015 vs. 164 in 2018, Ptrend < 0.001). The overall in-hospital mortality was 7.2% with no change over time (6.3% in 2015 vs. to 5.2% in 2018, Ptrend  = 0.67). There was no change in the frequency of in-hospital complications after TS-TMVR; however, the median length of stay has decreased over time. The overall 30-day readmission rate was 17.8%, with no change during the study years. The most frequent cause for 30-day readmission after TS-TMVR was acute heart failure followed by bleeding and infection-related complications. Prior coagulopathy and small-sized hospitals were independently associated with higher in-hospital mortality and 30-day readmissions. CONCLUSION: This nationwide observational analysis of real-world data showed an increase in the number of TS-TMVR procedures over time, which is now performed at a greater number of centers. There was no change in the rate of in-hospital mortality, complications or 30-day readmissions; but a significant reduction in the length of hospital stay over time was noted. As the number of TS-TMVR continue to expand, these data provide a perspective on the early experience with this procedure.

Vanillin attenuates thioacetamide-induced renal assault by direct and indirect mediation of the TGFß, ERK and Smad signalling pathways in rats.

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin-6 (IL-6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta-1 (TGF-ß1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule-1 (KIM-1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α-smooth muscle actin (α-SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α-SMA renal expression and TNFα, IL-6, TGF-ß1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM-1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF-ß type I receptors (ALK5) biding site.

Acute and chronic metabolic effects of carvedilol in high-fructose, high-fat diet-fed mice: implication of ß-arrestin2 pathway.

We aimed to investigate the acute and chronic effects of carvedilol on insulin resistance in high-fructose, high-fat diet (HFrHFD) - fed mice and the implication of the ß-arrestin2 pathway. The acute effect of carvedilol (10 mg/kg, i.p.) on glucose tolerance and hepatic lipid signaling in normal and insulin resistant mice was investigated. Then, the chronic effect of carvedilol on insulin resistance and dyslipidemia in HFrHFD-fed mice was examined. Changes in ß-arrestin2 and its downstream signals in liver, skeletal muscle, and adipose tissue were measured. This involved measuring phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) levels and protein kinase B (AKT) activity. Carvedilol acutely reduced fasting blood glucose levels in both normal and insulin resistant mice without significantly affecting the glucose tolerance. These acute effects were associated with increased hepatic PIP2 but decreased hepatic DAG levels. Chronic administration of carvedilol significantly ameliorated insulin resistance and dyslipidemia in HFrHFD-fed mice. These chronic effects were associated with increased ß-arrestin2, PIP2, and AKT activity levels but decreased DAG levels in the classical insulin target tissues. In conclusion, carvedilol acutely maintains glucose homeostasis and chronically ameliorates insulin resistance and dyslipidemia in HFrHFD-fed mice. The insulin sensitizing effects of carvedilol are highly correlated with the upregulation of ß-arrestin2 pathway.

Anti-Inflammatory, Antipyretic, and Analgesic Properties of Potamogeton perfoliatus Extract: In Vitro and In Vivo Study.

Natural antioxidants, especially those of plant origins, have shown a plethora of biological activities with substantial economic value, as they can be extracted from agro-wastes and/or under exploited plant species. The perennial hydrophyte, Potamogeton perfoliatus, has been used traditionally to treat several health disorders; however, little is known about its biological and its medicinal effects. Here, we used an integrated in vitro and in vivo framework to examine the potential effect of P. perfoliatus on oxidative stress, nociception, inflammatory models, and brewer's yeast-induced pyrexia in mice. Our results suggested a consistent in vitro inhibition of three enzymes, namely 5-lipoxygenase, cyclooxygenases 1 and 2 (COX-1 and COX-2), as well as a potent antioxidant effect. These results were confirmed in vivo where the studied extract attenuated carrageenan-induced paw edema, carrageenan-induced leukocyte migration into the peritoneal cavity by 25, 44 and 64% at 200, 400 and 600 mg/kg, p.o., respectively. Moreover, the extract decreased acetic acid-induced vascular permeability by 45% at 600 mg/kg, p.o., and chemical hyperalgesia in mice by 86% by 400 mg/kg, p.o., in acetic acid-induced writhing assay. The extract (400 mg/kg) showed a longer response latency at the 3 h time point (2.5 fold of the control) similar to the nalbuphine, the standard opioid analgesic. Additionally, pronounced antipyretic effects were observed at 600 mg/kg, comparable to paracetamol. Using LC-MS/MS, we identified 15 secondary metabolites that most likely contributed to the obtained biological activities. Altogether, our findings indicate that P. perfoliatus has anti-inflammatory, antioxidant, analgesic and antipyretic effects, thus supporting its traditional use and promoting its valorization as a potential candidate in treating oxidative stress-associated diseases.

The influence of coconut oil on the growth, immune, and antioxidative responses and the intestinal digestive enzymes and histomorphometry features of Nile tilapia (Oreochromis niloticus).

The trials of finding non-conventional and alternative aquafeed ingredients are increasing. In this sense, this study evaluated the influence of coconut oil on the growth, feed utilization, immune, and antioxidative responses of Nile tilapia. Five test diets were formulated by mixing coconut oil with the other ingredients at 0, 1, 2, 3, and 4% of the total ration and presented for tilapia for 60 successive days. The final weight, SGR, weight gain (WG), and feed intake were superior in fish delivered 2% of coconut oil (P < 0.05). Concurrently, fish that received 2% coconut oil had lower FCR and higher PER than fish of the control and 4% groups (P < 0.05). Higher lipase activity was observed in fish of 2% and 3% levels than the remaining groups (P < 0.05). Besides, the amylase and protease activities of fish in 1%, 2%, and 3% groups were higher than the 0% level (P < 0.05). The total blood cholesterol, RBCs, and PCV showed higher values in Nile tilapia fed 2% and 3% coconut oil (P < 0.05). The lysozyme and phagocytic activities were higher in fish fed 2% and 3% levels than the control (P < 0.05), while the phagocytic index in 2% and 3% levels was higher than 0% and 4% levels. Furthermore, SOD and CAT were higher in fish fed 1%, 2%, and 3% than fish fed 0% and 4% levels while GSH was higher in fish of 1%, 2%, and 3% than fish fed 0% level (P < 0.05). However, the MDA level was markedly lower in fish fed 25, 3%, and 4% coconut oil than the 0% level (P < 0.05). The intestine's histological structure in all groups appeared normal, forming of intestinal villi projecting from the intestinal wall. Also, the structure of the hepatopancreas had a normal architecture in all groups. To sum up, the inclusion of coconut oil at 2 to 3% is recommended as a replacer for fish oil in Nile tilapia diets.

The concurrent exposure to aluminium and fructose induces liver injury in rats: Protection by monoammonium glycyrrhizinate.

Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it unavoidable. It is implicated in the aetiology of different neurodegenerative diseases and can induce liver injury. In addition, insulin resistance (IR) plays an essential role in the pathogenesis and the progression of liver disorders. The increased consumption of fructose contained in soft drinks and western pattern diet results in IR that along with the wide distribution of aluminium make the concurrent exposure conceivable and increase the risk of liver injury. Therefore, the present study explores the hepatotoxic effects of aluminium and fructose administered concurrently and evaluates the possible protection by monoammonium glycyrrhizinate (MAG). Liver injury was induced by the administration of aluminium chloride (34 mg/kg/d) plus 10% (w/v) fructose in drinking water. Male rats were treated with either MAG (40 mg/kg/d) or silymarin (SIL, 100 mg/kg/d). The concurrent administration of aluminium and fructose (FRUAL) induced liver injury manifested as a significant elevation of serum liver enzymes activities, bilirubin level, and prothrombin time, as well as reduction of albumin level. On the other hand, the administration of MAG improved the FRUAL-induced aberrations of liver function tests and hepatic cytoarchitecture. We assume that the MAG-induced suppression of oxidative stress, toll-like receptor 4 pathway activation, inflammation, and apoptosis might play a crucial role in the hepatoprotective effect of MAG in this model. Intriguingly, the hepatoprotective effect MAG against FRUAL-induced liver injury surpasses that of the gold standard SIL, suggesting MAG as a better alternative to SIL.

Carvedilol protects against hepatic ischemia/reperfusion injury in high-fructose/high-fat diet-fed mice: Role of G protein-coupled receptor kinase 2 and 5.

Hepatic ischemia/reperfusion injury (H-IRI) is associated with irreversible liver damage. The current study aimed to investigate the protective effect of carvedilol against H-IRI in high-fructose high-fat diet (HFrHFD)-fed mice and the role of G protein-coupled receptor kinase 2 and 5 (GRK2 and GRK5). Mice were fed HFrHFD for 16 weeks; then mice were subjected to 30 min of ischemia followed by 1 h of reperfusion at the end of feeding period. Carvedilol (20 mg/kg, i.p.) was administered 30 min before ischemia. To explore the role of GRK2 and GRK5 in mediating carvedilol effects, paroxetine (GRK2 inhibitor, 10 mg/kg, i.p.) and amlexanox (GRK5 inhibitor, 25 mg/kg, i.p.) were administered 30 min before carvedilol administration. Liver function, histopathology and hepatic oxidative stress, as well as inflammatory and apoptotic markers were measured at the end of the experiment. In addition, adrenergic receptor downstream signals were measured in the liver. Results showed increased markers of liver injury (ALT and AST) in mice subjected to H-IRI. Moreover, liver injury was associated with slight collagen deposits as revealed by histopathology and elevated hepatic levels of oxidative stress, inflammatory and apoptotic markers. On the other hand, carvedilol protected mice against H-IRI and improved all associated pathological changes. Furthermore, pre-injection of either GRK2 or GRK5 inhibitor did not change carvedilol effects on serum ALT level and liver collagen deposits, while increased its antioxidant, anti-inflammatory and anti-apoptotic effects. In conclusion, carvedilol protects against H-IRI in HFrHFD-fed mice. GRK2 and GRK5 may not play a potential role in mediating this effect.

Glycyrrhizic acid and silymarin alleviate the neurotoxic effects of aluminum in rats challenged with fructose-induced insulin resistance: possible role of toll-like receptor 4 pathway.

Aluminum is implicated in the etiology of different neurodegenerative diseases, diabetes and cancer. The current study was conducted to evaluate the protective effects of glycyrrhizic acid (GAM) and silymarin (SLY) on AlCl3-induced neurotoxicity in insulin resistant rats. Insulin resistance (IR) was induced by fructose (10%) in drinking water for 18 weeks. Rats received AlCl3 (34 mg/kg/day) with or without fructose, GAM (40 mg/kg/day), or SLY (100 mg/kg/day). The administration of GAM or SLY suppressed AlCl3-induced memory deficit, oxidative stress, and neuroinflammation in brain tissue of IR rats. Both agents inhibited AlCl3-induced activation of TLR4 signaling pathway including the downstream activation of NF-κB. The results show that IR can partly exacerbate AlCl3-induced neurotoxicity, particularly memory deficit and neuroinflammation. In addition, GAM and SLY showed promising neuroprotective effect against AlCl3-induced brain damage in IR rats. The neuroprotection induced by these natural products might be mediated through their antioxidant and anti-inflammatory effects. The latter effect seems to be mediated via inhibition of TLR4 signaling pathway providing new insights on the mechanisms implicated in AlCl3-induced neurotoxicity and the neuroprotection afforded by GAM and SLY.

HPLC-ESI-MS/MS Profiling of Polyphenolics of a Leaf Extract from Alpinia zerumbet (Zingiberaceae) and Its Anti-Inflammatory, Anti-Nociceptive, and Antipyretic Activities In Vivo.

Reactive oxygen species (ROS) have been linked to several health conditions, among them inflammation. Natural antioxidants may attenuate this damage. Our study aimed to investigate the chemical composition of a methanol leaf extract from Alpinia zerumbet and its possible antioxidant, anti-inflammatory, anti-nociceptive, and antipyretic effects. Altogether, 37 compounds, representing benzoic and cinnamic acid derivatives and flavonoids (aglycones and glycosides), were characterized. The extract showed substantial in vitro antioxidant effects, and inhibited both cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) in vitro, with a higher selectivity towards COX-2. It also inhibited 5-lipoxygenase (LOX) activity in vitro with nearly double the potency of zileuton, a reference 5-lipoxygenase (LOX) inhibitor. The extract exhibited anti-inflammatory effects against carrageenan-induced rat hind paw edema, and suppressed leukocyte infiltration into the peritoneal cavity in carrageenan-treated mice. Furthermore, it possessed antipyretic effects against fever induced by subcutaneous injection of Brewer's yeast in mice. Additionally, the extract demonstrated both central and peripheral anti-nociceptive effects in mice, as manifested by a decrease in the count of writhing, induced with acetic acid and an increase in the latency time in the hot plate test. These findings suggest that the leaf extract from Alpinia zerumbet could be a candidate for the development of a drug to treat inflammation and ROS related disorders.

Senna singueana: Antioxidant, Hepatoprotective, Antiapoptotic Properties and Phytochemical Profiling of a Methanol Bark Extract.

Natural products are considered as an important source for the discovery of new drugs to treat aging-related degenerative diseases and liver injury. The present study profiled the chemical constituents of a methanol extract from Senna singueana bark using HPLC-PDA-ESI-MS/MS and 36 secondary metabolites were identified. Proanthocyanidins dominated the extract. Monomers, dimers, trimers of (epi)catechin, (epi)gallocatechin, (epi)guibourtinidol, (ent)cassiaflavan, and (epi)afzelechin represented the major constituents. The extract demonstrated notable antioxidant activities in vitro: In DPPH (EC50 of 20.8 µg/mL), FRAP (18.16 mM FeSO4/mg extract) assays, and total phenolic content amounted 474 mg gallic acid equivalent (GAE)/g extract determined with the Folin-Ciocalteu method. Also, in an in vivo model, the extract increased the survival rate of Caenorhabditis elegans worms pretreated with the pro-oxidant juglone from 43 to 64%, decreased intracellular ROS inside the wild-type nematodes by 47.90%, and induced nuclear translocation of the transcription factor DAF-16 in the transgenic strain TJ356. Additionally, the extract showed a remarkable hepatoprotective activity against d-galactosamine (d-GalN) induced hepatic injury in rats. It significantly reduced elevated AST (aspartate aminotransferase), and total bilirubin. Moreover, the extract induced a strong cytoplasmic Bcl-2 expression indicating suppression of apoptosis. In conclusion, the bark extract of S. sengueana represents an interesting candidate for further research in antioxidants and liver protection.

HPLC-PDA-MS/MS Characterization of Bioactive Secondary Metabolites from Turraea fischeri Bark Extract and Its Antioxidant and Hepatoprotective Activities In Vivo.

Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans. Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN) treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST), total bilirubin, gamma-glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione (GSH) was observed in rats treated with the bark extract in addition to D-galactosamine when compared with rats treated with D-galactosamine alone. In conclusion, T. fischeri is apromising candidate for health-promoting and for pharmaceutical applications.

Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin-induced diabetic rats.

CONTEXT: Momordica charantia Linn (Cucurbitaceae) (MC) is used in folk medicine to treat various diseases including diabetes mellitus. OBJECTIVE: This study investigates the antidiabetic activities of Momordica charantia (bitter gourd) on streptozotocin-induced type 2 diabetes mellitus in rats. MATERIALS AND METHODS: Male Wister rats were randomly assigned to 4 groups. Group I, Normal control; Group II, STZ diabetic; Group III and IV, Momordica charantia fruit juice was orally administered to diabetic rats (10 mL/kg/day either as prophylaxis for 14 days before induction of diabetes then 21 days treatment, or as treatment given for 21 days after induction of diabetes). The effects of MC juice were studied both in vivo and in vitro by studying the glucose uptake of isolated rat diaphragm muscles in the presence and absence of insulin. Histopathological examination of pancreas was also performed. RESULTS: This study showed that MC caused a significant reduction of serum glucose (135.99 ± 6.27 and 149.79 ± 1.90 vs. 253.40* ± 8.18) for prophylaxis and treatment respectively, fructosamine (0.99 ± 0.01 and 1.01 ± 0.04 vs. 3.04 ± 0.07), total cholesterol, triglycerides levels, insulin resistance index (1.13 ± 0.08 and 1.19 ± 0.05 vs. 1.48 ± 1.47) and pancreatic malondialdehyde content (p < 0.05). While it induced a significant increase of serum insulin (3.41 ± 0.08 and 3.28 ± 0.08 vs. 2.39 ± 0.27), HDL-cholesterol, total antioxidant capacity levels, ß cell function percent, and pancreatic reduced glutathione (GSH) content (p < 0.05) and improved histopathological changes of the pancreas. It also increased glucose uptake by diaphragms of normal (12.17 ± 0.60 vs. 9.07 ± 0.66) and diabetic rats (8.37 ± 0.28 vs. 4.29 ± 0.51) in the absence and presence of insulin (p < 0.05). CONCLUSIONS: Momordica charantia presents excellent antidiabetic and antioxidant activities and thus has great potential as a new source for diabetes treatment whether it is used for prophylaxis or treatment.

Silymarin preconditioning protected insulin resistant rats from liver ischemia-reperfusion injury: role of endogenous H2S.

BACKGROUND: Hydrogen sulfide (H2S) can protect against hepatic ischemia-reperfusion injury (HIR). However, it is unknown whether it can protect against HIR in insulin resistance. This study investigated the protective effects of silymarin against HIR in a rat model of insulin resistance and the possible involvement of endogenous H2S. MATERIALS AND METHODS: Insulin resistance was first established using 10% fructose in drinking water for 10 weeks. HIR was conducted in fructose-fed rats treated with saline or silymarin (100 mg/kg), 15 min before HIR (30 min ischemia, followed by 1 h reperfusion). Insulin resistance and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), total nitrites (NO2(-)), and H2S were measured. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), hydroxyproline, H2S synthesizing activity, and mRNA expression of cystathionine ß-synthase (CBS) or cystathionine γ-lyase (CSE) were determined. Additionally, histopathological examination involved H&E, Sirius red, and caspase-3 immunostaining. RESULTS: Fructose-induced insulin resistance increased serum ALT, TNF-α, H2S and H2S synthesizing activity, and hepatic MDA, hydroxyproline, and CSE mRNA and decreased NO2(-) and GSH. These changes exacerbated the HIR injury in which endogenous H2S production was auxiliary increased. Silymarin preconditioning decreased ALT, AST, MDA, NO2(-), TNF-α, and TNF-α/IL-10 ratio, increased GSH, IL-10, improved hepatic architecture, and lowered caspase-3 immunostaining. Serum H2S, its hepatic synthesizing activity, and CSE and CBS mRNA expressions were all suppressed by silymarin pretreatment. CONCLUSIONS: The increases in endogenous H2S exacerbate HIR injury, whereas silymarin preconditioning protected against HIR in insulin resistant rats via powerful antioxidant, anti-inflammatory, and antiapoptotic effects along with suppressing H2S production.

Morphological and molecular description of immature stages of Ornithodoros savignyi (Acari: Argasidae).

This study was designed to provide more details about larva, first nymph, and second nymph of Ornithodoros savignyi using a combination of light microscopy (LM), scanning electron microscopy (SEM), and partial sequence of mitochondrial 16S ribosomal ribonucleic acid (rRNA). The main characteristics of larva are wrinkled integument with many grooves, gnathosoma without camerostome cheeks, hypostome with a pair of large teeth apically, and tarsus without humps. The comparisons between the first and the second nymphs are different shape and distribution of dorsal grooves; a few spots without mammilla on the dorsal surface of the second nymph; 27 and 63-65 pairs of setae on the dorsal surface of the first and second nymphs, respectively; small holes on mammillae that are more dense in the second nymph; basis capitulum with two pairs of small setae in the second nymph; and one pair of sate in the first nymph, hypostome with dental formula 2/2 in the first nymph, and 3/3 in the second nymph. The partial 16S rRNA sequence of the second nymph that was determined as O. savignyi (450 bp) was deposited in GenBank under the accession number KU163242.