Antioxidant Activity and Cardioprotective Effect of Potentilla reptans L. via Ischemic Preconditioning (IPC)

Background and objectives:  Potentilla reptans L. from Rosaceae family is used as traditional medicine in Iran and other countries. Previous investigations on Potentilla species have reported strong antioxidant activity and cardioprotective effect. In this study, antioxidant activity of aerial parts and root of Potentilla reptans, and the cardio protective role of its root on preconditioning ischemia reperfusion injury have been investigated. Methods: Antioxidant activity of aerial parts and root of this plant were measured by DPPH and FRAP methods and its total phenolics content was estimated by Folin-Ciocalteu assay. Catechin was isolated from ethyl acetate fraction by Paper chromatography. Cardioprotective role of P. reptans root were evaluated by thirty five rats in five groups.The hearts were subjected to 30 minutes of ischemia and 100 minutes of reperfusion. The ischemic preconditioning (IPC) protocol was applied before the main ischemia. The myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining. The hemodynamic parameters, arrhythmia scoring and coronary flow were measured during reperfusion. Results: Potentilla reptans root showed stronger antioxidant activity and total phenolics content compared to the aerial parts. Total extract of root significantly decreased the infarct size and increased coronary flow in a concentration-dependent manner. Conclusion: Our results showed that the protective effects of Potentilla reptans root appeared by its phenolic compounds and reactive oxygen species (ROS) inhibition mechanism

The Effect of Curcumin on the Gut-Brain Axis: Therapeutic Implications

: The gut-brain axis describes the bidirectional communication between the gut, the enteric nervous system, and the central nervous system. The gut-brain axis has attracted increasing attention owing to its regulatory effect on dysbiosis and a wide range of related diseases. Several types of nutrients, such as curcumin, have been proposed as regulators of the dysbiotic state, and preclinical experiments have suggested that curcumin is not only beneficial but also safe. This review focuses on the interplay between curcumin and the gut microbiota. Moreover, it provides a comprehensive review of the crosstalk between the gut-brain axis and disease, whilst also discussing curcumin-mediated gut-brain axis-dependent and -independent signaling about modulation of gut microbiota dysbiosis. This will help to define the utility of curcumin as a novel therapeutic agent to regulate intestinal microflora dysbiosis

Impact of phytochemicals on PPAR receptors : implications for disease treatments

Peroxisome proliferator-activated receptors (PPARs) are members of the ligand-dependent nuclear receptor family. PPARs have attracted wide attention as pharmacologic mediators to manage multiple diseases and their underlying signaling targets. They mediate a broad range of specific biological activities and multiple organ toxicity, including cellular differentiation, metabolic syndrome, cancer, atherosclerosis, neurodegeneration, cardiovascular diseases, and inflammation related to their up/downstream signaling pathways. Consequently, several types of selective PPAR ligands, such as fibrates and thiazolidinediones (TZDs), have been approved as their pharmacological agonists. Despite these advances, the use of PPAR agonists is known to cause adverse effects in various systems. Conversely, some naturally occurring PPAR agonists, including polyunsaturated fatty acids and natural endogenous PPAR agonists curcumin and resveratrol, have been introduced as safe agonists as a result of their clinical evidence or preclinical experiments. This review focuses on research on plant-derived active ingredients (natural phytochemicals) as potential safe and promising PPAR agonists. Moreover, it provides a comprehensive review and critique of the role of phytochemicals in PPARs-related diseases and provides an understanding of phytochemical-mediated PPAR-dependent and -independent cascades. The findings of this research will help to define the functions of phytochemicals as potent PPAR pharmacological agonists in underlying disease mechanisms and their related complications

Hydro-alcoholic extract of Matricaria recutita exhibited dual anti-spasmodic effect via modulation of Ca2+ channels, NO and PKA2-kinase pathway in rabbit jejunum

Objective: Several studies have shown the antispasmodic activity of Matricariarecutita without detailing the underlying mechanism(s). The present study was designed to determine whether the antispasmodic mechanisms of M. recutita extract mediated via histaminergic/cholinergic receptors, Ca2+channels, activation of PKA2 and NO release in isolated rabbit jejunum. Methods and Materials: The concentration- dependent (3 × 10-3–1.3 × 10-2 mg/ml) antispasmodic effect of the hydro-alcoholic extract of M. recutita flowers was studied in isolated rabbit jejunum. The isolated jejunum preparations were divided into seven groups, including the pharmacological probes that modulate cholinergic, histaminergic, and nitrergic receptors, as well as PKA2. Results: M. recutita inhibited spontaneous smooth muscle contractility of the jejunum in a concentration-dependent manner (3 × 10-3–1.3 × 10-2 mg/ml) and reduced both K+- and Ca2+-induced contractions, which is similar to the effect of verapamil. The antispasmodic effect of M. recutita wasinhibited by H89 (a PKA2 inhibitor). The myorelaxant effect of M. recutita increased in the presence of ACh/His and H89. Conclusion: M. recutita evoked antispasmodic and spasmolytic effects mediated through different signaling pathways. Our results have shown this dual inhibitory effect is mediated by blocking Ca2+ channels, activating His and ACh receptors, releasing NO, and activating PKA2

Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles

Glycogen synthase kinase-3 beta (GSK-3ß) regulates glycogen metabolism and many different cellulars, including apoptosis, signaling, and neural. It is a crucial therapeutic receptor in heart disease, type 2 diabetes, and Alzheimer’s. In this study, using computational methods, flavonoid compounds were investigated for potential inhibitors against GSK-3ß. Virtual screening was utilized to investigate flavonoid compounds obtained from the PubChem database. Structure of human heart mitochondria of GSK-3ß receptor constructed by homology modeling. Best binding poses were discovered via in silico molecular docking simulation. We surveyed noncovalent interactions among amino acid residues involved in the active site of the modeled Protein and compounds via molecular docking and molecular dynamics (MD). Moreover, ADMET characteristics of best docking conformers have been investigated. The obtained results revealed that compound 1 containing chromenone moiety with binding energy H-bond -11.4 kcal/mol inhibited effectively binding pocket of the GSK-3ß receptor. Moreover, MD simulation analysis (RMSD and radius of gyration indicated complex of the compound and GSK-3b receptor remained stable throughout 100 ns MD simulation, and also analysis of ADMET profiles revealed that selected compounds had good drug-likeness and pharmacokinetic properties. Hence, it was suggested that compounds with chromenone scaffold could potentially inhibit GSK3ß. Structural modification of the chromenone derivatives may result in the discovery of promising candidates for identifying novel drugs as GSK-3ß inhibitors

Intraperitoneal Rupture of Infected Cyst in a Patient with Polycystic Kidney Disease after Kidney Transplant: A Case Report

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder characterized by progressive renal cysts formation and extra-renal manifestations. Infection within the cysts and abscess formation are rare but life threatening if left untreated. We present a rare case of peritonitis presentation due to intraperitoneal rupture of an infected cyst in a woman with polycystic kidney disease. Case description: A 42-year-old woman presented with constant progressing abdominal pain and vomiting. She complained of abdominal distention, bloating, and a change in bowel habits from two days ago. On physical examination, bilateral enlarged masses of flanks, generalized tenderness, and distention of the abdomen were found. The patient received conventional therapy. After appropriate fluid and electrolyte management and rescue care, appropriate antibiotics were prescribed, and laparotomy was performed. The rupture of an infected cyst of the right polycystic kidney into the peritoneal cavity was the cause of peritonitis in this patient. She successfully underwent a right radical nephrectomy (32×21cm, and 3,300 gr). The postoperative period was uneventful and the patient was discharged from the hospital after a week. Conclusion: Antibiotic therapy is the first step in the treatment of renal cyst infection. When primary antibiotic therapy fails, drainage of the infected cyst is recommended. In medically fit patients for surgery and patients who present with complications of the infected cyst, radical surgery and nephrectomy is the procedure of choice. The best outcome is achieved after nephrectomy

Potentilla reptans L. preconditioning regulates H19 and MIAT long noncoding RNAs in H9C2 myoblasts Ischemia/Reperfusion model

Abstract The present study aimed to evaluate the effect of the ethyl acetate fraction of P. reptans root (PEF) preconditioning on expressions of lncRNAs H19 and MIAT in H9C2 myoblasts I/R injury. H9C2 cells were treated with different concentrations ranging from (10–400 µg/ml) of PEF for 24 h, followed by simulation of I/R condition. For I/R experiments, H9C2 cells were subjected with the oxygen and glucose deprivation for 2 h. H9C2 cell viability was significantly enhanced by PEF preconditioning under I/R condition in a concentration-dependent manner up to 200 µg/ml as a EC50. The PEF significantly diminished the expression of lncRNA MIAT and rate of apoptosis against the I/R group. In addition, PEF pretreated before stimulation I/R condition increased H19 expression compared to the normal PEF group with no statistically significant differences between groups. Hence, the results suggest that PEF can protect cardiomyocytes during hypoxia-induced myocardial cell injury by targeting specific involved genes

The effect of curcumin on the gut-brain axis: therapeutic implications

The gut-brain axis describes the bidirectional communication between the gut, the enteric nervous system, and the central nervous system. The gut-brain axis has attracted increasing attention owing to its regulatory effect on dysbiosis and a wide range of related diseases. Several types of nutrients, such as curcumin, have been proposed as regulators of the dysbiotic state, and preclinical experiments have suggested that curcumin is not only beneficial but also safe. This review focuses on the interplay between curcumin and the gut microbiota. Moreover, it provides a comprehensive review of the crosstalk between the gut-brain axis and disease, whilst also discussing curcumin-mediated gut-brain axis-dependent and -independent signaling about modulation of gut microbiota dysbiosis. This will help to define the utility of curcumin as a novel therapeutic agent to regulate intestinal microflora dysbiosis. </p