In Vivo and In Silico Assessment of the Cardioprotective Effect of Thymus linearis Extract against Ischemic Myocardial Injury.

Myocardial infarction is irreversible cardiac tissue necrosis due to the blockage of one of the arteries. It leads to an insufficient supply of oxygen and nutrients, creating muscular damage in the affected regions. In the present study, aqueous methanolic extract of Thymus linearis was prepared to evaluate its activity against ischemic stress due to free radical production. GC-MS analysis was performed to evaluate the phytochemicals present in the plant extract. A chemical database of 30 compounds was virtually screened against NF-κB, COX2, and MCL, where γ-cadinene, ß-bisabolene, and ß-caryophyllene were found to be the best interacting ligands. To systematically assess cardioprotective activity against ischemia, isoproterenol and doxorubicin were used to induce cardiotoxicity in rats. The prepared extract of T. linearis (100 mg/kg) was given daily to animals for 21 days before injecting isoproterenol (85 mg/kg of animal weight) subcutaneously in two doses on the 20th and 21st days. In the case of doxorubicin, cardiotoxicity was induced in rats by a single injection (15 mg/kg) on the seventh day, and the extract was given to animals for 10 consecutive days. Animals' blood samples were used to monitor cardiac, liver, and other marker enzymes, including LDH, CPK, and AST. Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were also assayed in blood plasma to determine the degree of oxidative stress. H&E staining was performed to evaluate cardioprotection by plant extract, showing significant preventive effects in reducing cardiac injury induced by isoproterenol and doxorubicin.

Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats.

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.

In Vitro Antioxidant Activities and the Therapeutic Potential of Some Newly Synthesized Chalcones Against 4-Acetaminophenol Induced Hepatotoxicity in Rats.

The lack of safety and efficacy of existing hepatoprotective agents urge the need to explore novel hepatoprotective agents. The research work was planned to study the therapeutic potential of some newly synthesized chalcones against 4-acetaminophenol induced hepatotoxicity in rats. Male albino rats (N = 30) were divided into 6 groups of 5 animals each i.e. group I; Toxic control (4-acetaminophenol), group II; normal control (Normal saline), group III; Positive control (silymarin; 50 mg/kg bw) and groups IV-VI (test groups) treated with 3 chalcone analogues i-e 3a, 3f & 3 g (100, 150, 150 mg/kg bw, respectively). All the study group animals were administered with 4-acetaminophenol to induce hepatotoxicity except normal control. Following hepatotoxicity induction, test group animals were administered with selected doses of test compounds and toxic group animals left untreated. Liver enzymes including ALT, AST, ALP and serum bilirubin were determined photometrically. Antioxidant activities of test compounds were also determined. Histopathological examination of liver biopsies was also carried out through H & E staining. The test chalcones (3a, 3f & 3 g) significantly decreased the levels of liver enzymes and serum bilirubin toward normal and the pattern of results in the test group animals were comparable to silymarin administered animals indicating the hepatoprotective potential of test compounds. Moreover, the test chalcones (3a, 3f & 3 g) antagonized the effect of 4-acetaminophenol and thus, raised the catalase (CAT) and superoxide dismutase (SOD) while decreased the malondialdehyde (MDA) in experimental animals. The test chalcones (3a, 3f & 3 g) on histological examination of liver showed improvement of tissue morphology. The study concluded that the tested compounds have antioxidant potential and may act as hepatoprotective agent. However, in-depth studies are required to validate their safety and to elucidate the exact mechanism of action.

Aspirin Repurposing in Folate-Decorated Nanoparticles: Another Way to Target Breast Cancer.

Breast cancer affects more than 1 million women per year worldwide. Through this study, we developed a nanoparticle-based drug delivery system to target breast cancer cells. Aspirin has been found to inhibit thromboembolic diseases with its tumor-preventing activity. As a consequence, it relieves disease symptoms and severity. Here, mesoporous silica nanoparticles (MNPs) have been used to deliver aspirin to the tumor location. MNP-based aspirin in folic acid (F)-conjugated polydopamine (MNP-Asp-PD-PG-F) vehicles are prepared for targeted breast cancer therapy. The vehicle hinges on MNP altered with polymer polyethylene glycol (PG), polydopamine (PD), and F. The delivery vehicle was studied for in vitro drug release, cytotoxicity, and breast cancer cell proliferation. F-conjugated drug delivery vehicles let MNPs achieve an elevated targeting efficacy, ideal for cancer therapy. It was also observed that compared to free aspirin, our drug delivery system (MNP-Asp-PD-PG-F) has a higher cytotoxic and antiproliferative effect on breast cancer cells. The drug delivery system can be proposed as a targeted breast cancer therapy that could be further focused on other targeted cancer therapies. Delivering aspirin by the PD-PG-F system on the tumor sites promises a therapeutic potential for breast cancer treatment.

A pH-sensitive, stimuli-responsive, superabsorbent, smart hydrogel from psyllium (Plantago ovata) for intelligent drug delivery.

Herein, we report a polysaccharide-based hydrogel isolated from psyllium husk (a well-known dietary fiber) and evaluated for its swelling properties in deionized water (DW) at different physiological pH values, i.e., 1.2, 6.8 and 7.4. Swelling of psyllium hydrogel (PSH) in DW under the influence of temperature and at different concentrations of NaCl and KCl solutions was also examined. A pH-dependent swelling pattern of PSH was observed following the order DW > pH 7.4 > pH 6.8 > pH 1.2. Stimuli-responsive swelling and deswelling (on-off switching) behavior of PSH was observed in DW and ethanol, DW and normal saline, at pH 7.4 and pH 1.2 environments, respectively. Similar swelling behavior and on-off switching attribute of PSH-containing tablets indicated the unaltered nature of PSH even after compression. Scanning electron micrographs of swollen and then freeze-dried PSH via transverse and longitudinal cross-sections revealed hollow channels with an average pore size of 6 ± 2 µm. Furthermore, PSH concentration-dependent sustained release of theophylline from tablet formulation was witnessed for >15 h following the non-Fickian diffusion mechanism. Subacute toxicity studies revealed the non-toxic nature of PSH. Therefore, dietary fiber-based material, i.e., PSH could be a valuable pharmaceutical excipient for intelligent and targeted drug delivery.

A stimuli-responsive, superporous and non-toxic smart hydrogel from seeds of mugwort (Artemisia vulgaris): stimuli responsive swelling/deswelling, intelligent drug delivery and enhanced aceclofenac bioavailability.

Artemisia vulgaris seeds extrude hydrogel (AVH), which shows extraordinary swelling in water, at pH 6.8, and 7.4, which follows second-order kinetics. AVH exhibits reversible swelling/deswelling in ethanol and normal saline as well at pH 7.4 and pH 1.2. Therefore, AVH shows stimuli-responsiveness in different physiological conditions, solvents, and electrolytes. The superporous nature of AVH in swollen/freeze-dried sculpture is exposed in their SEM micrographs. AVH-based aceclofenac tablet formulations offer sustained-release under simulated conditions of the gastrointestinal tract (GIT) in terms of pH and transit time. Pharmacokinetic studies also show the delay and prolonged plasma concentration with t max of 8 h, therefore, such formulations can be used to enhance the bioavailability of aceclofenac. The swelling behavior of the AVH tablet is also assessed using MRI. The in vivo fate of the AVH tablet is monitored by X-ray during the transit through the GIT. Acute toxicity studies of AVH indicate the absence of any toxicity which reveals the safety profile of AVH. Therefore, AVH can be used for oral, topical and ophthalmic drug delivery systems. These results establish the potential of AVH as a stimuli sensitive, pH-dependent, and sustained-release biomaterial for targeted drug delivery.

Terminal drought and seed priming improves drought tolerance in wheat.

Plants retain the preceding abiotic stress memory that may aid in attainment of tolerance to subsequent stresses. This study was conducted to evaluate the influence of terminal drought memory (drought priming) and seed priming in improving drought tolerance in wheat (Triticum aestivum L.). During first growing season, wheat was planted in field under optimal (well-watered) and drought stress imposed at reproductive stage (BBCH growth stage 49) until maturity (BBCH growth stage 83). Seeds collected from both sources were subjected to hydropriming or osmopriming (with 1.5% CaCl2 solution); while, dry seed was taken as control. Treated and control seeds, from both sources, were sown in soil filled pots. After the completion of seedling emergence, pots were maintained at 50% water holding capacity (drought) or 100% water holding capacity (well-watered). Drought stress suppressed the plant growth (2-44%), perturbed water relations (1-18%) and reduced yield (192%); however, osmolytes accumulation (3-14%) and malondialdehyde contents (26-29%) were increased under drought. The crop raised from the seeds collected from terminal drought stressed plants had better growth (5-63%), improved osmolyte accumulation (13-45%), and lower lipid peroxidation (3%) than the progeny of well-watered crop. Seed priming significantly improved the crop performance under drought stress as compared to control. However, osmopriming was more effective than hydropriming in this regard as it improved leaf area (9-43%), tissue water status (2-47%), osmolytes accumulation (6-48%) and grain yield (14-79%). In conclusion, terminal drought induced modifications in seed composition and seed priming improved transgenerational drought tolerance through improvement in tissue water status and osmolytes accumulation, and decrease in lipid peroxidation.

Author Correction: Effect of Plant Density, Boron Nutrition and Growth Regulation on Seed Mass, Emergence and Offspring Growth Plasticity in Cotton.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Effect of Plant Density, Boron Nutrition and Growth Regulation on Seed Mass, Emergence and Offspring Growth Plasticity in Cotton.

Seed nutrients reserves have direct relationship with seed functional traits and influence offspring performance. Effects of plant density, foliage boron (B) nutrition and mepiquat chloride (MC) growth regulation on seed nutrients reserves, seed mass and production, and emergence and offspring growth traits of cotton were studied in two years field experiment. Seed nutrients reserves and seed mass were decreased at higher maternal plant density relative to lower plant density with concomitant decrease in emergence and offspring seedling growth. However, maternal foliage B nutrition and MC growth regulation enhanced seed nutrients reserves, seed mass, emergence and offspring seedling growth performance. There was a significant positive relationship between seed mass and seed nutrients reserves indicating that changes in nutrient availability/uptake in response to maternal ecological factors determine variation in seed functional traits. Nonetheless, seed mass was positively correlated with emergence percentage and negatively with emergence timing. Furthermore, variation in offspring seedling growth traits with seed mass indicated the significance of initial seed nutrients reserves for early seedling vigour and establishment. In conclusion, lower maternal plant density, B nutrition and MC growth regulation ensued in higher emergence and offspring seedling growth of cotton because of higher seed nutrient reserves and seed mass.

Seed priming and transgenerational drought memory improves tolerance against salt stress in bread wheat.

This study was conducted to evaluate the potential of seed priming following terminal drought on tolerance against salt stress in bread wheat. Drought was imposed in field sown wheat at reproductive stage (BBCH growth stage 49) and was maintained till physiological maturity (BBCH growth stage 83). Seeds of bread wheat, collected from crop raised under terminal drought and/or well-watered conditions, were subjected to hydropriming and osmopriming (with 1.5% CaCl2) and were sown in soil-filled pots. After stand establishment, salt stress treatments viz. 10 mM NaCl (control) and 100 mM NaCl were imposed. Seed from terminal drought stressed source had less fat (5%), and more fibers (11%), proteins (22%) and total soluble phenolics (514%) than well-watered seed source. Salt stress reduced the plant growth, perturbed water relations and decreased yield. However, an increase in osmolytes accumulation (4-18%), malondialdehyde (MDA) (27-35%) and tissue Na+ contents (149-332%) was observed under salt stress. The seeds collected from drought stressed crop had better tolerance against salt stress as indicated by better yield (28%), improved water relations (3-18%), osmolytes accumulation (21-33%), and less MDA (8%) and Na contents (35%) than progeny of well-watered crop. Seed priming, osmopriming in particular, further improved the tolerance against salt stress through improvement in leaf area, water relations, leaf proline, glycine betaine and grain yield while lowering MDA and Na+ contents. In conclusion, changed seed composition during terminal drought and seed priming improved the salt tolerance in wheat by modulating the water relations, osmolytes accumulation and lipid peroxidation.