Effects of Lamiaceae family plants and their bioactive ingredients on coronavirus-induced lung inflammation.

Coronaviruses (CoVs) are a family of viruses that cause infection in respiratory and intestinal systems. Different types of CoVs, those responsible for the SARS-CoV and the new global pandemic of coronavirus disease 2019 in people, have been found. Some plants were used as food additives: spices and dietary and/or medicinal purposes in folk medicine. We aimed to provide evidence about possible effects of two Lamiaceae family plants on control or treatment of CoVs-induced inflammation. The keywords including coronaviruses, Thymus vulgaris, Zataria multiflora, thymol, carvacrol, antivirus, and anti-inflammatory and antioxidant effects were searched in various databases such as PubMed, Web of Sciences (ISI), and Google Scholar until September 2022. The medicinal herbs and their main ingredients, thymol and carvacrol, showed antiviral properties and reduced inflammatory mediators, including IL-1ß; IL-6, and TNF-α, at both gene and protein levels but increased the levels of IFN-γ in the serum as anti-inflammatory cytokine. These medicinal herbs and their constituents also reduce oxidative stress and enhance antioxidant capacity. The results of molecular docking analyses also indicated that polyphenol components such as thymol, carvone, and carvacrol could inhibit the entry of the viruses into the host cells in molecular docking analyses. The antiviral, anti-inflammatory, and antioxidant effects of these plants may be due to actions of their phenolic compounds that modulate immune response and may be useful in the control and treatment of CoV-induced lung disorder.

Effects of Herbs and Derived Natural Products on Lipopolysaccharide-Induced Toxicity: A Literature Review.

Introduction: Oxidative stress (OS) during inflammation can increase inflammatory responses and damage tissue. Lipopolysaccharide (LPS) can induce oxidative stress and inflammation in several organs. Natural products have several biological activities including anti-inflammatory, antioxidant, and immunoregulatory properties. The aims of the study are to study the possible therapeutic effects of natural products on LPS inducing toxicity on the nervous system, lung, liver, and immune system. Methods: The in vitro and in vivo research articles that were published in the last 5 years were included in the current study. The keywords included "lipopolysaccharide," "toxicity," "natural products," and "plant extract" were searched in different databases such as Scopus, PubMed, and Google Scholar until October 2021. Results: The results of most studies indicated that some medicinal herbs and their potent natural products can help to prevent, treat, and manage LPS-induced toxicity. Medicinal herbs and plant-derived natural products showed promising effects on managing and treating oxidative stress, inflammation, and immunomodulation by several mechanisms. Conclusion: However, these findings provide information about natural products for the prevention and treatment of LPS-induced toxicity, but the scientific validation of natural products requires more evidence on animal models to replace modern commercial medicine.

The effects of Crocus sativus L. (Saffron) and its ingredients on dietary intakes in cardiovascular disease in Iranian population: A systematic review and meta-analysis.

Cardiovascular disease (CVD) is one of the most common causes of mortality around the world. The aim of this study is to summarize and conclude the clinical evidence regarding the use of Crocus sativus (C. sativus) and its ingredients on cardiovascular risk factors. A systematic search was conducted with PubMed, Web of Science (ISI), and Scopus in the English language from 2015 until September 2021. A fixed-effect or random-effects model were applied to pool standard mean difference (SMD) and its 95 % confidence intervals (CI). Randomized controlled studies that assessed the clinical effects of C. sativus and its ingredients on dietary intake (Energy, Carbohydrate, Protein, and total Fat) in human subjects were included. Seven studies comprising 421 participants were included in the meta-analysis. Pooling of results showed significant effect of saffron on total fat (-0.14; 95% CI: -0.49 to 0.20; I2 = 57.3%) and significant effect of crocin on Energy (0.94; 95% CI: -0.77 to 2.65; I2 = 95.9%), Carbohydrate (0.44; 95% CI: -0.74 to 1.62; I2 = 92.6%), and Protein (-0.04; 95% CI: -0.26 to 0.34; I2 = 0.0%). Present meta-analysis suggests that treatment with crocins is more effective than saffron in energy, carbohydrate, and protein, while saffron is more effective than crocins in fat. However, further studies are needed to confirm these findings.

Comparing the Effects of Pulsatile and Continuous Flushing on Time and Type of Peripheral Intravenous Catheters Patency: A Randomized Clinical Trial.

Introduction: Peripheral intravenous catheters (PICs) patency techniques such as flushing are being developed. According to some studies, flushing can be used continuously or in pulsatile forms. This study aimed to compare the effects of pulsatile flushing (PF) and continuous flushing (CF) on time and type of PICs patency. Methods: In this double-blind randomized clinical trial, 71 patients were randomly assigned into two groups of PF (n=35) and CF (n=36). The PF protocol was performed as successive injections of 1 mL normal saline (N/S) per second (sec) with a delay of less than 1 sec until the completion of 5 mL of solution. However, CF protocol was performed by injecting 5 mL N/S within 5 sec without any delay before and after each medicine administration. Data related to the time and type of PICs patency were collected using a patency checklist every 12 hours (h) up to 96 h. The statistical analysis was done by R statistical software (Version 3.5.1). Results: The results showed that the number of PICs remaining open was not significantly different between PF and CF groups during 96 h. The highest number of PICs excluded from the study was related to the time of 96 h as a result of partial patency in the two groups. Conclusion: There was no difference between CF and PF regarding the time and type of PICs patency. Thus, both techniques can be used to maintain the catheter patency.

Effects of Medicinal Plants and Flavonoids on Parkinson's Disease: A Review on Basic and Clinical Evidences.

Parkinson's disease (PD) is a neurodegenerative disorder which is characterized by typical symptoms including gradual progressive muscle rigidity, tremor and loss of motor skills. Although there is no definitive cure for PD, the extract of some medicinal plants and their ingredients have been suggested to relieve its symptoms and to prevent disability in patients. This review is focused on therapeutic effects of some medicinal plants and their ingredients on PD. The findings presented in this review were collected from experimental and clinical studies in databases including PubMed, Web of Science and Google Scholar until the end of May 2019. The keywords "neurotoxicity " or "Parkinson's disease" or "neuroprotective" and "Medicinal plants" and "Flavonoids" were searched. Based on the results of animal and clinical studies, the extract of medicinal plants and their components which are discussed in this review have neuro-protective effects against PD. These protective properties mainly are mediated through inhibition of dopamine metabolizing enzymes, reduction oxidant markers, increase of antioxidant agents and suppression of neuro-inflammation.

Possible therapeutic effects of Crocus sativus stigma and its petal flavonoid, kaempferol, on respiratory disorders.

CONTEXT: Crocus sativus L. (Iridaceae), or saffron, has been used as food additives and spices. In the traditional medicine of Iran, C. sativus has been used for the treatment of liver disorders, coughs, and as an anti-inflammatory agent for eyes. OBJECTIVE: The current study reviewed the possible therapeutic effects of C. sativus stigma and its petal flavonoid (kaempferol) on respiratory disorders with several mechanisms such as anti-inflammatory, and smooth muscle relaxant effects. MATERIALS AND METHODS: This review article searched databases including PubMed, Google Scholar, and ScienceDirect, up to November 2019. The keywords including; 'Crocus sativus', 'saffron', 'kaempferol', 'airway inflammation', and 'smooth muscle relaxant' were searched. RESULTS: C. sativus reduced nitric oxide (NO), inducible nitric oxide synthase (iNOS) levels and inflammatory cytokines in the lung tissue. Saffron and kaempferol reduced white blood cells (WBCs) and the percentage of neutrophils and eosinophils in bronchoalveolar lavage fluid. Moreover, saffron reduced tracheal responsiveness to methacholine and ovalbumin on tracheal smooth muscles. In addition, kaempferol reduced the total leukocyte and eosinophil counts similar to the effect of dexamethasone and also showed relaxant effects on smooth muscle. DISCUSSION AND CONCLUSION: Crocus sativus and its petal flavonoid, kaempferol, showed relatively potent therapeutic effects on respiratory disorders by relaxation of tracheal smooth muscles via stimulatory or blocking effects on ß-adrenoceptor and muscarinic receptors, respectively. Saffron and kaempferol also decreased production of NO, inflammatory cytokines and chemokines in respiratory systems.

The Possible Therapeutic Effects of Some Medicinal Plants for Chronic Cough in Children.

The use of plants or their isolated bioactive components for the prevention and treatment of various disorders has been developed. Here, we aim to identify effective medicinal plants for relief of cough and respiratory symptoms in children. The data of this review article were obtained from published articles in scientific databases, including PubMed, Google Scholar, and Scopus, until December 2019. The keywords, including "Zataria multiflora Boiss." OR "Portulaca oleracea L." OR "Ferula assa-foetida L." OR "Nigella sativa L." AND "respiratory symptoms" OR "airway inflammation" OR "smooth muscle relaxant effects," were searched individually or combined. The mentioned medicinal plants decreased total white blood cell (WBC), neutrophils, and eosinophils counts of blood and lung lavage in animal model-induced respiratory disorders. These plants also have protective effects on serum immunoglobulin, antibody titer, eosinophil count, and proinflammatory cytokines. Evidence from the studies indicated that the abovementioned medicinal plants have smooth muscle relaxant properties (bronchodilator effects) via stimulation of ß-adrenoceptor or inhibition of muscarinic receptors (in vitro) and also improved the pulmonary function test in clinical settings. These medicinal plants are safe and easy to use. Based on the anti-inflammatory, anti-antispasmodic, and immunomodulatory effects, the clinical benefit may be assumed, therefore considering a place for these medicinal plants in relieve of chronic cough and symptoms of children's allergy, asthma, and common cold.

Anti-Asthmatic Effects of Portulaca Oleracea and its Constituents, a Review.

OBJECTIVES: The medicinal plants are believed to enhance the natural resistance of the body to infections. Some of the main constituents of the plant and derived materials such as, proteins, lectins and polysaccharides have anti-inflammatory effects. Portulaca oleracea (P. oleracea) were used traditionally for dietary, food additive, spice and various medicinal purposes. This review article is focus on the anti-asthmatic effects of P. oleracea and its constituents. METHODS: Various databases, such as the PubMed, Scopus, and Google Scholar, were searched the keywords including "Portulaca oleracea", "Quercetin", "Anti-inflammatory", "Antioxidant", "Cytokines", "Smooth muscle ", and " Relaxant effects " until the end of Jul 2018. RESULTS: P. oleracea extracts and its constituents increased IFN-γ, IL-2, IFNγ/IL-4 and IL- 10/IL-4 ratio, but decreased secretion of TNF-α, IL-4 and chemokines in both in vitro and in vivo studies. P. oleracea extracts and quercetin also significantly decreased production of NO, stimulated ß-adrenoceptor and/or blocking muscarinic receptors in tracheal smooth muscles. Conclusion: P. oleracea extracts and quercetin showed relatively potent anti-asthmatic effects due to decreased production of NO, inflammatory cytokines and chemokines, reduced oxidant while enhanced antioxidant markers, and also showed potent relaxant effects on tracheal smooth muscles via stimulatory on ß-adrenoceptor or/and blocking muscarinic receptors.

T helper cells subtypes and their cytokine gene expression affected by carvacrol in sensitized mice administered during sensitization period.

Th1, Th2, Th17, and Treg cells and their cytokine gene expressions in splenocytes of control mice, ovalbumin sensitized (S), and S treated with dexamethasone and carvacrol during a sensitization period were examined. Th2 and Th17 population as well as the gene expression of IL-4, IL-17, and TGF-ß were increased, but Th1, Th1/Th2 ratio, the gene expression of IFN-γ and FOXP3 as well as the IFN-γ/IL-4 ratio were decreased in S compared with control group ( P < 0.001 for all cases). Carvacrol treatment caused significant reduction of Th2 and Th17 population as well as gene expression of IL-4, IL-17, and TGF-ß but increase in Treg cells, Th1/Th2 ratio, gene expressions of FOXP3, IFN-γ, and IFN-γ/IL-4 ratio ( P < 0.05 to P < 0.001). The population of Th1, Th2, Th17 cells as well as the gene expression of IL-4, IL-17, and TGF-ß were significantly decreased, but only Treg was increased in the dexamethasone treatment group ( P < 0.05 to P < 0.001). Carvacrol treatment during the sensitization period showed a more specific effect on Th1/Th2 imbalance in sensitized mice than dexamethasone, which may indicate the therapeutic potentials of carvacrol in disorders associated with Th1/Th2 imbalance such as asthma.

The Effect of Zataria multiflora on Th1/Th2 and Th17/T Regulatory in a Mouse Model of Allergic Asthma.

Asthma is a chronic inflammatory disease with no definite treatment and more research is needed to overcome this condition. The aim of this study was to investigate the effect of the extract of Zataria multiflora (Z. multiflora) as a medicinal plant on cytokine genes expression in an experimental mouse model of asthma. Adult mice were randomly divided into the following groups: control (C), untreated asthma (A), asthmatic groups treated with dexamethasone (D) and Z. multiflora extract (200, 400, and 800 µg/mL; Z1, Z2, and Z3, respectively), (for groups C, A, and D n = 5 and for groups Z1, Z2, and Z3 n = 6). For induction of the mouse model of asthma, animals were sensitized with intraperitoneal injection and inhalation of ovalbumin (OVA). The number of T helper (Th) subtype cells (using flow cytometry) and the levels of IFN-γ, FOXP3, IL-4, TGF-ß, IL-17 gene expression (by real time PCR) were assessed in mice splenocytes. The observed changes in spleen cells of group A compared to group C were increased number of Th2 and Th17 cells, enhancement of gene expression of IL-4, IL-17, and TGF-ß (p < 0.001 for all cases), reduction of Th1 cells and Th1/Th2 ratio (p < 0.001 for both cases) and decrease in gene expression of IFN-γ, FOXP3 and IFN-γ/IL-4 ratio (p < 0.01 for IFN-γ and p < 0.001 for other cases). The observed changes in spleen cells of treated compared to untreated A group were enhancement of Treg cells and Th1/Th2 ratio (p < 0.001 for both cases), increase in IFN-γ (p < 0.05) and FOXP3 (p < 0.001) gene expression and IFN-γ/IL-4 ratio (p < 0.01) as well as reduction of Th2 and Th17 cells (p < 0.01 to p < 0.001), decrease gene expression of IL-4, IL-17, and TGF-ß (p < 0.05 to p < 0.001). The findings showed that the extract of Z. multiflora decreased pro-inflammatory cytokines in asthma (IL-4 and IL-17 and TGF-ß) but increased anti-inflammatory cytokines (IFN-γ) gene expression and the number of Treg (FOXP3) in splenocytes of asthmatic mice which may indicate the specific therapeutic effect of the plant extract in allergy, autoimmunity, and infectious diseases via potentiating Th1 and suppressing Th2 and Th17 cells.

Immunomodulatory effect of characterized extract of Zataria multiflora on Th1, Th2 and Th17 in normal and Th2 polarization state.

The effect of the extract of Zataria multiflora (Z. multiflora) on IFN-γ, FOXP3, IL-4, TGF-ß, and IL-17 gene expression was evaluated in cultured splenocytes obtained from control, nontreated asthma or sensitized mice (group S), Sensetized animals treated with dexamethasone or three concentrations of Z. multiflora extract (200, 400 and 800 µg/ml) (n = 6, for each group). IFN-γ and FOXP3 gene expressions were significantly decreased (P < 0.001 for both cases) but IL-4 (P < 0.001) and IL-17 (P < 0.05) were increased in group S compared to control group. Z. Multiflora extract 800 µg/ml, significantly upregulated IFN-γ gene expression (P < 0.01) and its 400 and 800 µg/ml concentrations increased FOXP3 gene expression (P < 0.05 and P < 0.001, respectively) compared to group S. Z. multiflora extract at all concentrations (200, 400 and 800 µg/ml) decreased TGF-ß gene expression and its lowest concentration significantly reduced IL-17 gene expression compared to group S (P < 0.001 for all cases). Only IL-4 and TGF-ß gene expression was significantly decreased following treatment with dexamethasone (P < 0.001 for both cases). The results indicated an increase in IFN-γ and FOXP3 but decrease in TGF-ß and IL-17 gene expression profile in sensitized splenocytes treated with the extract, which might be partially due to the presence of one of its constituent, carvacrol.

Effect of carvacrol on various cytokines genes expression in splenocytes of asthmatic mice.

OBJECTIVES: With regard to pharmacological effects of carvacrol on the respiratory system, its effect on cytokines genes expression in splenocytes of asthmatic mice was examined in this study. MATERIALS AND METHODS: Splenocytes were isolated from non-sensitized (control group), sensitized mice to ovalbumin (OVA) (group S), and S animals treated with dexamethasone, and three concentrations of carvacrol. IL-4, IFN-γ, TGF-ß, FOXP3, and IL-17 genes expression were carried out in cultured splenocytes using the real-time PCR method. RESULTS: Compared to the control group, IFN-γ and FOXP3 genes expression were significantly decreased (P<0.001 for both cases), but IL-4 and IL-17 genes expression were significantly increased in the S group (P<0.001 and P<0.05, respectively). IL-4 gene expression due to treatment of all concentrations of carvacrol, TGF-ß gene expression due to its two higher concentrations, and IL-17 gene expression due to its high concentration were significantly decreased compared to group S (P<0.01 to P<0.001). IFN-γ gene expression was significantly increased due to last carvacrol concentration (300 µg/ml, P<0.01), and FOXP3 due to its two last concentrations (150 and 300 µg/ml, P<0.05 and P<0.001, respectively) in treated S splenocytes. Dexamethasone treatment of sensitized splenocytes only showed significant inhibitory effect on IL-4 and TGF-ß genes expression (P<0.001 for both cases). CONCLUSION: These results showed the immunomodulatory effect of carvacrol indicating increased IFN-γ and FOXP3 but decreased IL-4, TGF-ß, and IL-17 genes expression, which was more selective than the effect of dexamethasone in sensitized mice splenocytes, which indicates its possible therapeutic value in allergy, autoimmunity, and infectious diseases.

The role of nitric oxide on the oxytocin induce analgesia in mice.

OBJECTIVES: Analgesic effects of oxytocin and it's the other physiological effects were well-known. The aim of present study was determination of nitric oxide role on analgesic effects of oxytocin in mice. MATERIALS AND METHODS: 216 male Albino mice were divided randomly into two experimental groups, tail flick and formalin test. Each experimental group consists of three main groups including: saline, L-arginine (50 mg/kg) and L-NAME (10 mg/kg) intraperitoneal (IP) injection. 15 min after injection in each of the following groups, the animals in each groups divided to the three subgroups including: saline (n=12), oxytocin (1 mg/kg) (n=12) and oxytocin (1 mg/kg) + atosiban (1 mg/kg) (n=12) was injected IP and then after 30 min of use the formalin test and tail flick were to evaluate the response to pain. RESULTS: Area under the curve (AUC) in the late phase of the formalin test, in sub-groups oxytocin + saline and L-NAME were significantly decreased compared with saline + saline group (P<0.05 to P< 0.001), and AUC in L-arginine + saline and atosiban + saline + oxytocin were significantly increased compared with oxytocin + saline group (P<0.05). Tail flick tests as well as a significant reduction in the AUC in oxytocin + L-arginine and atosiban + saline + oxytocin groups were compared with Oxytocin + Saline group (P<0.001). CONCLUSION: Oxytocin has analgesic effects in the acute and late phase of pain in the formalin test. Moreover, exogenous increasing of nitric oxide reduced the analgesic effect of oxytocin.

The effect of carvacrol on systemic inflammation in guinea pigs model of COPD induced by cigarette smoke exposure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a epidemic disease which is mainly due to cigarette smoking. The effect of carvacrol on systemic inflammation in guinea pig model of COPD was examined in the present study. METHODS: Guinea pigs of both sexes were divided into 6 groups, including: control, COPD, COPD+drinking water containing three concentrations of carvacrol and COPD+dexamethasone. Animals were exposed to cigarette smoke for 3 months in order to induce animal model of COPD. Weight changes, serum levels of IL-8 and malondialdehyde (MDA) as well as total and differential white blood cell (WBC) were measured (n=5 for control and COPD groups and n=6 for other groups). RESULTS: Serum levels of IL-8 and MDA, total WBC (p<0.01 for all cases) and eosinophil counts (p<0.05) were increased and weight changes were decreased (p<0.05) in COPD group compared to controls. Serum MDA level and total WBC in treated groups with two higher carvacrol concentrations, eosinophil, neutrophil and lymphocyte percentage in those treated with its high concentration as well as IL-8 level and weight change in treated groups with its all concentrations and in dexamethasone treated group were significantly improved compared to COPD group (p<0.05 to p<0.001). CONCLUSION: These results showed a preventive effect of the carvacrol on all measured parameter in COPD guinea pigs which was comparable to the effect of dexamethasone at used concentrations.