Daidzin and its de-glycosylated constituent daidzein as a potential therapeutic for cardiovascular diseases: A review from bench to bed.

Continuing research is being conducted on novel preventive and therapeutic drugs for cardiovascular diseases (CVDs). Daidzein has shown potential beneficial effects regarding various CVDs and risk factors. However, data in this regard are inconsistent, and there is an urge to accumulate. Therefore, we reviewed the effects of daidzein and daidzin on CVDs. We conducted a search through Scopus, PubMed, Google Scholar, and Web of Science from inception up to October 2023 to find studies with the primary intention of assessing the impacts of daidzein and daidzin on cardiovascular disease in various in vitro, animal, and clinical settings. In vitro and animal studies showed that daidzein and daidzin are effective in terms of reducing inflammation, oxidative stress, hyperlipidemia, myocardial infarction, thromboembolism, hypertension, and aneurysms. However, clinical studies only confirmed a relatively small portion of the previous findings of the in vitro and animal investigations, including anti-hyperlipidemic effects. In conclusion, in vitro and animal studies have reported potential therapeutic effects for daidzein and daidzin regarding CVDs. However, most of the clinical studies were unable to exhibit the same results. Hence, further clinical studies are required to determine the outcomes of administering daidzein and its derivatives for an extended period and in various doses.

Caffeic acid and its derivative caffeic acid phenethyl ester as potential therapeutic compounds for cardiovascular diseases: A systematic review.

Cardiovascular diseases (CVDs) contribute to major public health issues. Some studies have found that caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) may effectively prevent or treat CVDs. However, there is a major need to sum up our current understanding of the possible beneficial or detrimental effects of CA and CAPE on CVDs and related mechanisms. Therefore, this study aimed to summarize the data on this topic. A methodical search was carried out on key databases, including Pubmed, Google Scholar, Scopus, and Web of Science, from the beginning to June 2024. Studies were then assessed for eligibility based on inclusion and exclusion criteria. Treatment with CA and CAPE significantly and positively affected cardiovascular health in various aspects, including atherosclerotic diseases, myocardial infarction, hypertension, cardiac arrhythmias, and hypercoagulation state. Several mechanisms were proposed to mediate these effects, including transcription factors and signaling pathways associated with antioxidant, cytostatic, and anti-inflammatory processes. CA and CAPE were found to have several beneficial effects via multiple mechanisms during the prevention and treatment of various CVDs. However, these promising effects were only reported through in vitro and animal studies, which reinforces the need for further evaluation of these effects via human clinical investigations.

Intra-peritoneal lavage of Zingiber officinale rhizome and its active constituent gingerol impede inflammation, angiogenesis, and fibrosis following post-operative peritoneal adhesion in male rats.

Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol compounds on surgical-induced peritoneal adhesion, and their strategies that disrupted the PA formation pathways to suppress their incidence. First, liquid chromatography-mass spectrometry (LC-MS) was established to separate and identify several chemical groups of ginger rhizome extract. In the next steps, male Wistar albino rats were randomly selected and divided into various groups, namely sham, control, ginger extract (0.6, 1.8, 5 %w/v), and gingerol (0.05, 0.1, 0.3, and 1 %w/v). Finally, we investigated the macroscopic parameters such as wound healing, body weight as well as spleen height and weight. In addition, visual peritoneal adhesion assessment was performed via Nair et al and Adhesion Scoring Scheme. Moreover, the microscopic parameters and biological assessment was performed via and immunoassays. The present findings revealed significant improvement in wound healing and reduction of the adhesion range, as Nair et al. and Adhesion Scoring Scheme scoring, in both the ginger and gingerol groups compared to the PA group (P < 0.05). Whereas, gingerol (0.3 % w/v) was able to increase the body weight in rats (P < 0.0001) at end stage of experiment. Also, inflammation, angiogenesis, and fibrosis were significantly decreased due to the downregulation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1, vascular endothelial growth factor (VEGF), respectively, in the ginger and gingerol groups compared to the PA group (P < 0.05). In contrast, the levels of IL-10 were increased in the ginger and gingerol groups compared to the control group (P < 0.01). Our results proved that ginger rhizome and gingerol, as novel therapeutic compounds, could be used to prevent PA for their beneficial anti-inflammatory as well as anti-fibrosis properties in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger and gingerol.

Increasing cardiac troponin-I level as a cardiac injury index correlates with in-hospital mortality and biofactors in severe hospitalised COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 raised in 2019 (COVID-19) affects the lung tissue and other organs, specifically the heart. METHODS: The current study evaluated 120 hospitalised patients with severe COVID-19 between March 2021 and February 2022. Patients' demographics, vital signs, electrocardiogram abnormalities, clinical laboratory tests, including troponin I (TPI), mortality, and discharge type, were recorded. RESULTS: Among the 120 hospitalised patients with severe COVID-19, 54 (45.0%) patients were male, with an average age of 63.2 ± 1.4. Many patients have chronic comorbidities, including hypertension (51.6%), diabetes mellitus (34.1%), and ischemic heart disease (17.5%). The in-hospital and six months after the discharge mortality were 45.8% and 21.5%, respectively. Cardiac injury was observed in 14 (11.7%) patients with a mean TPI level of 8.386 ± 17.89 µg/L, and patients with cardiac injury had higher mortality than those without cardiac injury (P < 0.001). Furthermore, the cardiac injury was meaningfully correlated with age (ρ = 0.182, P = 0.019), history of ischemic heart disease (ρ = 0.176, P = 0.05), hospitalisation result and mortality (ρ = 0.261, P = 0.004), inpatient in ICU (ρ = 0.219, P = 0.016), and serum levels of urea (ρ = 0.244, P = 0.008) and creatinine (ρ = 0.197, P = 0.033). Additionally, the discharge results were significantly correlated with oxygen saturation with (ρ = -0.23, P = 0.02) and without (ρ = -0.3, P = 0.001) oxygen therapy, D-dimer (ρ = 0.328, P = 0.019), LDH (ρ = 0.308, P = 0.003), urea (ρ = 0.2, P = 0.03), and creatinine (ρ = 0.17, P = 0.06) levels. CONCLUSION: Elevated TPI levels are associated with increased mortality in severe COVID-19 patients. Therefore, TPI may be a beneficial biofactor for early diagnosis of cardiac injury and preventing a high mortality rate.

A mechanistic overview of sulforaphane and its derivatives application in diabetes and its complications.

Sulforaphane (SFN) is a type of phytochemical found in many cruciferous vegetables that has been shown to positively benefit the control of Type 2 Diabetes Mellitus (T2DM). The search was done from 2000 until December 2022 using PubMed, Scopus, Web of Sciences, and Google Scholar databases. We included all in vitro, in vivo, and clinical trials. Sulforaphane has been demonstrated to activate the PI3K/AKT and AMP-activated protein kinase pathways and the glucose transporter type 4 to increase insulin production and reduce insulin resistance. Interestingly, SFN possesses protective effects against diabetes complications, such as diabetic-induced hepatic damage, vascular inflammation and endothelial dysfunction, nephropathy, and neuropathy via nuclear factor erythroid 2-related factor 2 activation that leads to the translation of several anti-oxidant enzymes and regulation glycolysis, pentose phosphate pathway, fatty acid metabolism, glutamine metabolism, and glutathione metabolism. Furthermore, multiple clinical trial studies emphasized the ameliorating effects of SFN on T2DM patients. This review provides sufficient evidence for further research and development of sulforaphane as a hypoglycemic drug.

Peritoneal lavage with Glycyrrhiza glabra is effective in preventing peritoneal adhesion in a rat model.

BACKGROUND: Intraperitoneal adhesion formation is a significant problem following surgeries, resulting in substantial clinical and economic consequences. Glycyrrhiza glabra has several pharmacological properties consisting of anti-inflammatory, anti-microbial, anti-oxidant, anti-cancer, and immunomodulatory activities. AIM: Therefore, we aimed to investigate the impacts of G. glabra on the development of post-operative abdominal adhesion in a rat model. METHODS: Male Wistar rats weighing 200-250 g were divided into six groups (n = 8): Group 1: normal group (non-surgical), and the surgical groups including Group 2: control group received the vehicle, Group 3: G. glabra 0.5% w/v, Group 4: G. glabra 1% w/v, Group 5: G. glabra 2% w/v, and Group 6: dexamethasone, 0.4% w/v. The intra-abdominal adhesion was performed utilizing soft sterilized sandpaper on one side of the cecum, and the peritoneum was slightly washed with 2 ml of the extract or vehicle. In addition, macroscopic examination of adhesion scoring and the levels of inflammatory mediators [interferon (IFN)-γ, prostaglandin E2 (PGE2)], fibrosis markers [interleukin (IL)-4, transforming growth factor (TGF)-ꞵ], and oxidative factors [malondialdehyde (MDA), nitric oxide metabolites (NO), and reduced glutathione (GSH)] were evaluated. In vitro toxicities were also done on mouse fibroblast L929 and NIH/3T3 cell lines. RESULTS: We found higher levels of adhesion (P < 0.001), IFN-γ(P < 0.001), PGE2(P < 0.001), IL-4(P < 0.001), TGF-ß(P < 0.001), MDA(P < 0.001), and NO(P < 0.001), and lower levels of GSH(P < 0.001) in the control group. In contrast, G. glabra concentration dependent and dexamethasone alleviated the levels of adhesion (P < 0.05), inflammatory mediators (P < 0.001-0.05), fibrosis (P < 0.001-0.05), and oxidative (P < 0.001-0.05) factors, while propagating the anti-oxidant marker (P < 0.001-0.05) in comparison to the control group. Results also showed that the extract did not significantly reduce cell viability up to 300 µg/ml (P > 0.05). CONCLUSION: G. glabra could concentration-dependently mitigate peritoneal adhesion formation through its anti-inflammatory, anti-fibrosis, and anti-oxidant properties. However, further clinical investigations are required to approve that G. glabra may be a promising candidate against post-surgical adhesive complications.

Protective Effect of Portulaca oleracea on Streptozotocin-Induced Type I Diabetes-Associated Reproductive System Dysfunction and Inflammation.

BACKGROUND: Type-one diabetes (T1D), a chronic autoimmune disease with marked inflammatory responses, is associated with infertility complications and implications. Based on the anti-diabetic, antioxidant, and anti-hyperlipidemic potential of Portulaca oleracea (PO), this study aimed to evaluate the protective effect of this plant extract on streptozotocin-induced type-I-diabetes-associated reproductive system dysfunction and inflammation. METHODS: Male rats were randomly divided into four experimental groups: control, diabetic, and treatment/s (PO extract at 100 or 300 mg/kg/daily). Then food and water consumption, body, testis and epididymis weights, histopathological evaluation, seminiferous tubules diameter, sperm count and motility, glucose levels, sex hormones, and inflammatory and oxidative stress markers were evaluated. RESULTS: Our results showed that streptozotocin-induced diabetes significantly increased food and water consumption; increased glucose, MDA, TGF-ß1, and TNF-α levels; and decreased the seminiferous tubules diameter, sperm count and motility, levels of LH, testosterone, total thiol, VEGF, and SOD activity. Interestingly, PO extract (phytochemically characterized by using liquid chromatography-mass spectrometry to detect bioactive molecules) significantly ameliorated these parameters and histopathological indexes' damage in rats. CONCLUSION: Even if more preclinical assessments are needed to better characterize the mechanism/s of action, the results of this study will pave the way for the rational use of PO on diabetic-associated clinical complications and implications.

Evaluation of the Therapeutic Effects of the Hydroethanolic Extract of Portulaca oleracea on Surgical-Induced Peritoneal Adhesion.

OBJECTIVE: Peritoneal adhesion (PA) is an abnormal connective tissue that usually occurs between tissues adjacent to damaged organs during processes such as surgery. In this study, the anti-inflammatory and antioxidant effects of Portulaca oleracea (PO) were investigated against postoperative-induced peritoneal adhesion. METHODS: Thirty healthy male Wistar rats (220 ± 20 g, 6-8 weeks) were randomly divided into four groups: (1) normal, (2) control (induced peritoneal adhesion), and (3) and (4) PO extracts (induced peritoneal adhesion and received 100 or 300 mg/kg/day of PO extract for seven days). Finally, macroscopic and microscopic examinations were performed using different scoring systems and immunoassays in the peritoneal lavage fluid. RESULTS: We found that the levels of adhesion scores and interleukin- (IL-) 1ß, IL-6, IL-10, tumour necrosis factor- (TNF-) α, transforming growth factor- (TGF-) ß 1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were increased in the control group. However, PO extract (100 and 300 mg/kg) notably reduced inflammatory (IL-1ß, IL-6, and TNF-α), fibrosis (TGF-ß 1), angiogenesis (VEGF), and oxidative (MDA) factors, while increased anti-inflammatory cytokine IL-10, antioxidant factor glutathione (GSH), compared to the control group. CONCLUSION: Oral administration of PO improved postoperational-induced PA by alleviating the oxidative factors, fibrosis, inflammatory cytokines, angiogenesis biomarkers, and stimulating antioxidative factors. Hence, PO can be considered a potential herbal medicine to manage postoperative PA. However, further clinical studies are required to approve the effectiveness of PO.

Promising influences of Scutellaria baicalensis and its two active constituents, baicalin, and baicalein, against metabolic syndrome: A review.

Metabolic syndrome is known as a group of metabolic abnormalities with features including central obesity, insulin resistance, hypercholesterolemia, hypertriglyceridemia, and hypertension as well as low level of high-density lipoprotein (HDL)-cholesterol. Previous studies showed the ameliorating effects of Scutellaria baicalensis on metabolic syndrome parameters, including antidiabetic, anti-hyperlipidemic, anti-obesity, and antihypertensive. In this review, we deeply and mechanistically evaluated different studies on the effect of S. baicalensis and its two major bioactive constituents, baicalin, and baicalein, on the critical components of metabolic syndrome, including diabetes, hyperlipidemia, obesity, hypertension, and atherosclerosis. Scientific databases, including PubMed, Scopus, and Google Scholar were searched in the English language until the end of June 2020. Accordingly, S. baicalensis, and its two major bioactive constituents, baicalin and baicalein, represent promising effects on the control of metabolic syndrome and its related disorders such as obesity, hyperlipidemia, atherosclerosis, diabetes, and their following complications. In summary, our findings show that S. baicalensis and its active constituents, baicalin and baicalein, by activation and upregulation of AMPK and PPAR-γ as the main signaling in the hemostasis of glucose and lipid metabolisms may be favorable candidates for the prevention and treatment of the metabolic syndrome.

Colchicine effectively attenuates inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) in patients with non-ST-segment elevation myocardial infarction: a randomised, double-blind, placebo-controlled clinical trial.

Myocardial infarction without ST-segment elevation (NSTEMI) is considered an inflammatory disorder associated with a high mortality rate worldwide. High-sensitivity C-reactive protein (hs-CRP) is an important inflammatory marker for NSTEMI and related to cardiovascular events. Colchicine, as a potent anti-inflammatory drug, is frequently prescribed for the treatment of gout and pericarditis. The present study aimed to evaluate the effects of colchicine, as an anti-inflammatory drug, on hs-CRP levels in NSTEMI patients. We performed a randomised, double-blind, placebo-controlled trial involving 150 NSTEMI patients referred to Imam Reza and Ghaem Hospitals affiliated to Mashhad University of Medical Sciences. The patients were randomised to receive colchicine or placebo along with optimal medications for 30 days. The hs-CRP was measured at the admission and end of the study. Our results revealed that, in both colchicine and placebo groups, hs-CRP levels were significantly mitigated in NSTEMI patients compared to baseline (P < 0.001). However, the decreasing properties of colchicine on hs-CRP levels were remarkably stronger than placebo following the 30 days of treatment (P < 0.001). Nevertheless, neither colchicine nor placebo treatment could achieve hs-CRP levels lower than 2 mg/L. There were no significant differences between the effects of colchicine on the hs-CRP decrease in diabetic and non-diabetic, male and female, and normal and preserved LVEF NSTEMI patients. It can be concluded that colchicine may prevent the disease progression and succedent cardiovascular events in NSTEMI patients by attenuating the inflammation.

Standardised pomegranate peel extract lavage prevents postoperative peritoneal adhesion by regulating TGF-ß and VEGF levels.

Peritoneal adhesion represents a severe complication following surgery. Punica granatum (pomegranate) possesses several anti-oxidative and anti-inflammatory properties. Pomegranate peel extract (PPEx) can alleviate the production of various inflammatory factors and cytokines. Thus, we sought to evaluate the anti-adhesion effects of pomegranate in rats. Thirty male Wistar rats (6-week-old, 220 ± 20 g) were divided into five groups (n = 6): normal group without any surgical procedures, control group, and experimental groups receiving 2 ml of 1%, 2%, and 4% w/v PPEx, respectively. Peritoneal adhesions were examined macroscopically. Furthermore, we evaluated inflammatory cytokines levels [interleukin 6 (IL-6), and tumour necrosis factor-α (TNF-α)], growth factors [transforming growth factor- ß1 (TGF-ß1), and vascular endothelial growth factor (VEGF)], and oxidative stress parameters [nitric oxide metabolites (NO), and malondialdehyde (MDA), and glutathione (GSH)] using biochemical methods. Our results showed that the adhesion score and IL-6, TNF-α, TGF-ß1, VEGF, NO, and MDA levels were increased in the control group. In contrast, the GSH level was diminished in the control group compared with the normal group (P < 0.001). PPEx (1 and 2% w/v) markedly reduced all measured parameters compared with the control group (P < 0.001-0.05). PPEx may reduce peritoneal adhesion by alleviating adhesion formation, IL-6, TNF-α, TGF-ß1, VEGF, NO, and MDA, and stimulating anti-oxidative factors. Therefore, PPEx may be considered an appropriate candidate for the treatment of postoperative peritoneal adhesion.

Evaluation of the Effects of Peritoneal Lavage with Rosmarinus officinalis Extract against the Prevention of Postsurgical-Induced Peritoneal Adhesion.

Postoperative adhesions are regarded as the major complication following abdominal surgery. Rosmarinus officinalis has shown antioxidative and anti-inflammatory effects. Therefore, we aimed to assess the influence of 70% v/v hydro-ethanolic extract of the aerial parts of R. officinalis against postoperative abdominal adhesions in a rat model. Forty-eight male Wistar rats (190 ± 20 g) were divided into six groups of eight: group 1 = normal group, without any surgical procedures, group 2 = control group, group 3 = vehicle group, and groups 3, 4, and 5 = experimental groups receiving 2 mL of 4, 2, or 1% w/v R. officinalis treatment. Adhesion levels were macroscopically examined. Additionally, the levels of inflammatory cytokines (interleukin-6, interleukin-1ß, and TNF-α), growth factors (transforming growth factor-ß1, and vascular endothelial growth factor), oxidative (NO, nitric oxide and MDA, malondialdehyde), and antioxidative (GSH, glutathione) factors were evaluated. Our results revealed that the adhesion score, interleukin-6, interleukin-1ß, TNF-α, transforming growth factor-ß1, vascular endothelial growth factor, NO, and MDA levels were significantly increased in the vehicle group, while the GSH level was diminished. R. officinalis treatment notably ameliorated the adhesion score following postoperative abdominal adhesions compared with the vehicle group. Our results also revealed that R. officinalis markedly reduced inflammatory cytokines, oxidative factors, fibrosis, and angiogenesis biomarkers, whereas it increased the antioxidative factor. Therefore, R. officinalis may be a potential candidate for the management of postoperative peritoneal adhesion.

Antiinflammatory and anti-cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies.

Inflammation is commonly characterized as a defensive and protective reaction of the body to various exogenous or endogenous stimuli, which aims to maintain the body health. Punica granatum (pomegranate) and its constituent ellagic acid (EA) are recently more taken into accounts since their promising pharmacological effects. Therefore, we aimed to obtain a comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms. In the procedure, scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched in the English language, until the end of January 2019. Pomegranate belonging to the Punicaceae has been used for medical purposes from ancient and in different cultures. Several studies have also supported that EA is the major active compound of pomegranate and possesses antimutagenic, antiinflammatory, antifibrosis, anticancer, and antiaging properties. It has been suggested that pomegranate and EA possess promising immunomodulatory effects in preclinical models as well as human studies through regulation of the T-cell function and suppressing humoral immunity. Hopefully, we wish that this review and information could be helpful for designing further experiments to investigate the potential protective effects of pomegranate and EA.

Evaluation of the anti-oxidant and anti-inflammatory effects of the methanolic extract of Ferula szowitsiana root on PHA-induced inflammation in human lymphocytes.

Inflammation is defined as a defensive response of the body against either the endogenous or exogenous triggers, while this process becomes chronic leading to various disorders such as asthma, cancers, and multiple sclerosis. Recently, pharmacological properties of different constituents of F. szowitsiana have been reported. In the present study, we aimed to evaluate the anti-oxidative and anti-inflammatory effects of the methanolic extract of F. szowitsiana root on human isolated lymphocytes. The effects of either F. szowitsiana (10, 40 and 160 µg/ml) or dexamethasone (0.1 mM) were evaluated on the levels of cell proliferation, reactive oxygen species (ROS), nitric oxide (NO) production, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities, and total glutathione content (GSH) as well as the secretion of inflammatory cytokines [interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α] in the presence or absence of phytohemagglutinin (PHA) stimulation (n = 8 for each group). PHA stimulation notably elevated ROS, NO, MDA, IL-6, and TNF-α levels as well as diminished GSH, CAT and SOD levels. In PHA-stimulated, the results also revealed that F. szowitsiana (10-160 µg/ml) significantly decreased MDA, ROS, NO, IL-6 and TNF-α levels as well as increased CAT, SOD and GSH levels. Collectively, F. szowitsiana is able to attenuate the overproduction of inflammatory and oxidative stress markers in the presence of PHA-stimulated T lymphocytes, while to propagate the anti-oxidative defense. Contextually, the plant has promising healing effects in the different inflammatory disorders associated with the interference of the acquired immune system such as multiple sclerosis and asthma.

Anti-Inflammatory and Anti-Oxidant Activity of Portulaca oleracea Extract on LPS-Induced Rat Lung Injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are classified as two lung complications arising from various conditions such as sepsis, trauma, and lung inflammation. Previous studies have shown that the extract of the leaves of Portulaca oleracea (PO) possesses anti-inflammatory and anti-oxidant activities. In the present study, the effects of PO (50⁻200 mg/kg) and dexamethasone (Dexa; 1.5 mg/kg) on lipopolysaccharide (LPS)-induced ALI were investigated. Subsequentially, the lung wet/dry ratio; white blood cells (WBC); levels of nitric oxide (NO); myeloperoxidase (MPO); malondialdehyde (MDA); thiol groups formation; super oxide dismutase (SOD) and catalase (CAT) activities; and levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-10, prostaglandin E2 (PGE2), and transforming growth factor (TGF)-ß in the broncho alveolar lavage fluid (BALF) were evaluated in order to demonstrate the anti-oxidant and anti-inflammatory activity of PO. Our results show that PO suppresses lung inflammation by the reduction of IL-ß, IL-6, TNF-α, PGE2, and TGF-ß, as well as by the increase of IL-10 levels. We also found that PO improves the level of WBC, MPO, and MDA, as well as thiol group formation and SOD and CAT activities, compared with the LPS group. The results of our investigation also show that PO significantly decreased the lung wet/dry ratio as an index of interstitial edema. Taken together, our findings reveal that PO extract dose-dependently displays anti-oxidant and anti-inflammatory activity against LPS-induced rat ALI, paving the way for rational use of PO as a protective agent against lung-related inflammatory disease.

Anticonvulsant Activity of Viola tricolor against Seizures Induced by Pentylenetetrazol and Maximal Electroshock in Mice.

BACKGROUND: Recently, there has been much more interest in the use of medicinal plants in search of novel therapies for human neurodegenerative diseases such as epilepsy. In the present study, we investigated the anticonvulsant effects of Viola tricolor (V. tricolor) on seizure models induced by pentylenetetrazol (PTZ) and maximal electroshock stimulation (MES). METHODS: Totally, 260 mice were divided into 26 groups (n=10). Thirty minutes after treatment with the hydroalcoholic extract of V. tricolor (VHE 100, 200, and 400 mg/kg) and its ethyl acetate (EAF 50, 100, and 200 mg/kg) and n-butanol (NBF 50, 100, and 200 mg/kg) fractions as well as diazepam (3 mg/kg), seizure was induced by PTZ (100 mg/kg) or by MES (50 Hz, 1 s and 50 mA). Analysis was performed via ANOVA with the Tukey-Kramer post-hoc test using GraphPad Prism 6.01 (La Jolla, CA). RESULTS: The VHE (400 mg/kg) significantly enhanced latency to the first generalized tonic-clonic seizures (GTCs) induced by PTZ in comparison to the control group (P<0.001). All 3 concentrations of the EAF (50, 100, and 200 mg/kg) significantly prolonged the latency of PTZ-induced seizures compared to the control group. Additionally, all the concentrations of the NBF (50, 100, and 200 mg/kg) made a significant increment in GTCs latency induced by PTZ in comparison to the control group. On the other hand, all the concentrations of the VHE, EAF, and NBF significantly reduced the incidence of hind-limb tonic extension (HLTE) induced by MES, when compared to the control group. CONCLUSION: The present study showed that V. tricolor and its ethyl acetate and n-butanol fractions possessed anticonvulsant effects as confirmed by the prolongation of latency to the first GTCs induced by PTZ and decrement in the incidence of HLTE induced by MES.

Evaluation of the Sleep-Prolonging Effect of Lagenaria vulgaris and Cucurbita pepo Extracts on Pentobarbital-Induced Sleep and Possible Mechanisms of Action.

Introduction: Sleeplessness is the most common sleep disorder. In this study, the hypnotic effect of macerated (HAME) and soxhlet (HASE) extract of Lagenaria vulgaris (fruit and seed) and Cucurbita pepo (fruit) were studied in mice. Methods: Extracts and fractions were administered intra-peritoneally (i.p.) in mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Moreover, the influence of flumazenil or naloxone on the hypnotic effects of the extract and its toxic effects were evaluated. Results: The HAME and HASE of C. pepo prolonged the pentobarbital-induced sleep duration at dose of 200 mg/kg. The HAME of L. vulgaris (fruit) at dose of 200 mg/kg increased the sleeping time. The HAME and HASE of L. vulgaris (seed) increased sleep duration at doses of 50 and 100 mg/kg. Besides, flumazenil (2 mg/kg) reversed the effects of both diazepam (P < 0.001 vs. diazepam group), 200 mg/kg of HAME of C. pepo and 50 mg/kg of HAME and HASE of L. vulgaris (seed). All fractions especially ethyl-acetate fraction (EAF) of L. vulgaris (seed) increased the sleep duration. Naloxone reversed the hypnotic effect of HAME and HASE of L. vulgaris (seed). The extracts showed no neurotoxic effects on PC12 and L929 cell lines. Conclusion: The results showed that L. vulgaris (seed and fruit) and C. pepo potentiated pentobarbital hypnosis without toxic influence. The hypnotic effects of L. vulgaris seed was greater than its fruit and C. pepo. The GABA and opioid receptors may play role in the sleep-induction of L. vulgaris seed.

Recurrent spontaneous coronary artery dissection with ST-segment elevation: once RCA involvement then left main/LAD-case report.

BACKGROUND: Spontaneous coronary artery dissection is a rare disease with a more prevalence in women, mostly in the postpartum state, which was first described by Peretti in 1931. CASE PRESENTATION: This report describes a previously healthy woman who had a spontaneous coronary artery dissection. This case is related to the early postpartum period with a successful outcome. In addition, the diagnostic and therapeutic approaches of this unique clinical entity are discussed and reviewed. CONCLUSIONS: Because these kinds of cases are so rare, reporting these cases and the management and treatment approaches can guide other clinicians worldwide, and maybe a guideline for choosing the best approach around different situations could be published.

Stem cell and exosome therapies for regenerating damaged myocardium in heart failure.

Finding novel treatments for cardiovascular diseases (CVDs) is a hot topic in medicine; cell-based therapies have reported promising news for controlling dangerous complications of heart disease such as myocardial infarction (MI) and heart failure (HF). Various progenitor/stem cells were tested in various in-vivo, in-vitro, and clinical studies for regeneration or repairing the injured tissue in the myocardial to accelerate the healing. Fetal, adult, embryonic, and induced pluripotent stem cells (iPSC) have revealed the proper potency for cardiac tissue repair. As an essential communicator among cells, exosomes with specific contacts (proteins, lncRNAs, and miRNAs) greatly promote cardiac rehabilitation. Interestingly, stem cell-derived exosomes have more efficiency than stem cell transplantation. Therefore, stem cells induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), cardiac stem cells (CDC), and skeletal myoblasts) and their-derived exosomes will probably be considered an alternative therapy for CVDs remedy. In addition, stem cell-derived exosomes have been used in the diagnosis/prognosis of heart diseases. In this review, we explained the advances of stem cells/exosome-based treatment, their beneficial effects, and underlying mechanisms, which will present new insights in the clinical field in the future.

Evaluation of Anti-Nociceptive, Anti-Inflammatory, and Anti-Fibrotic effects of noscapine against a rat model of Achilles tendinopathy.

During tendinopathy, prolonged inflammation results in fibrosis and the adherence of tendons to the adjacent tissues, causing discomfort and movement disorders. As a natural compound, noscapine has several anti-inflammatory and anti-fibrotic properties. Therefore, we aimed to investigate the effects of noscapine against a rat model of tendinopathy. We created a surgical rat model of Achilles tendon damage to emulate tendinopathy. Briefly, an incision was made on the Achilles tendon, and it was then sutured using an absorbable surgical thread. Immediately, the injured area was topically treated with the vehicle, noscapine (0.2, 0.6, and 1.8 mg/kg), or dexamethasone (0.1 mg/kg) as a positive control. During the 19-day follow-up period, animals were assessed for weight, behavior, pain, and motor coordination testing. On day 20th, the rats were sacrificed, and the tendon tissue was isolated for macroscopic scoring, microscopic (H&E, Masson's trichrome, Ki67, p53) analyses, and cytokine secretion levels. The levels of macroscopic parameters, including thermal hyperalgesia, mechanical and cold allodynia, deterioration of motor coordination, tendon adhesion score, and microscopic indices, namely histological adhesion, vascular prominence and angiogenesis, and Ki67 and p53 levels, as well as fibrotic and inflammatory biomarkers (IL-6, TNF-α, TGF-ß, VEGF) were significantly increased in the vehicle group compared to the sham group (P < 0.05-0.001 for all cases). In contrast, the administration of noscapine (0.2, 0.6, and 1.8 mg/kg) attenuated the pain, fibrosis, and inflammatory indices in a dose-dependent manner compared to the vehicle group (P < 0.05-0.001). Histological research indicated that noscapine 0.6 and 1.8 mg/kg had the most remarkable healing effects. Interestingly, two higher doses of noscapine had impacts similar to those of the positive control group in both clinical and paraclinical assessments. Taken together, our findings suggested that noscapine could be a promising medicine for treating tendinopathies.