Therapeutic effects of medicinal plants and their constituents on lung cancer, in vitro, in vivo and clinical evidence.

The most common type of cancer in the world is lung cancer. Traditional treatments have an important role in cancer therapy. In the present review, the most recent findings on the effects of medicinal plants and their constituents or natural products (NP) in treating lung cancer are discussed. Empirical studies until the end of March 2022 were searched using the appropriate keywords through the databases PubMed, Science Direct and Scopus. The extracts and essential oils tested were all shown to effect lung cancer by several mechanisms including decreased tumour weight and volume, cell viability and modulation of cytokine. Some plant constituents increased expression of apoptotic proteins, the proportion of cells in the G2/M phase and subG0/G1 phase, and Cyt c levels. Also, natural products (NP) activate apoptotic pathways in lung cancer cell including p-JNK, Akt/mTOR, PI3/ AKT\ and Bax, Bcl2, but suppressed AXL phosphorylation. Plant-derived substances altered the cell morphology, reduced cell migration and metastasis, oxidative marker production, p-eIF2α and GRP78, IgG, IgM levels and reduced leukocyte counts, LDH, GGT, 5'NT and carcinoembryonic antigen (CEA). Therefore, medicinal plant extracts and their constituents could have promising therapeutic value for lung cancer, especially if used in combination with ordinary anti-cancer drugs.

The effect of Zataria multiflora hydroalcoholic extract on memory and lung changes induced by rats that inhaled paraquat.

Objectives: The effects of hydroalcoholic extract of Zataria multiflora (Z. multiflora) on memory changes, as well as lung injury due to inhaled paraqut (PQ) in rat, were examined.Method: Control group of rat with saline aerosol administration, PQ groups with PQ aerosol (27 and 54 mg/m3) administration, PQ groups treated with two doses of the extract (200 and 800 mg/kg/day) and dexamethasone (0.03 mg/kg/day) were studied. Shuttle box and Morris Water Maze (MWM) tests were carried out as well as oxidant, anti-oxidant markers, total and differential white blood cell (WBC) counts and cytokine levels in broncho-alveolar lavage (BALF).Results: Inhaled PQ significantly increased the escape latency and travelled distance in MWM test, but the time spent in the target quadrant on the probe day was significantly reduced (p < 0.05 to p < 0.001). The latency to enter the dark room at 3, 24, and 48 h after an electrical shock was reduced due to PQ (p < 0.05 to p < 0.001). Exposure to PQ significantly increased total WBC, neutrophil, eosinophil, lymphocyte, and monocyte counts, IL-10, interferon gama (INF-γ), nitrite (NO2), and malondialdehyde (MDA) levels, but catalase (CAT), superoxide dismutase (SOD), and thiol levels were decreased (p < 0.05 to p < 0.00). Z. multiflora and dexamethasone treatment significantly improved all behavioral as well as lung changes induced by inhaled PQ (p < 0.05 to p < 0.01).Conclusion: Z. multiflora treatment improved learning and memory impairment as well as lung inflammation and oxidative stress induced by inhaled PQ.

The effects of Nigella sativa on respiratory, allergic and immunologic disorders, evidence from experimental and clinical studies, a comprehensive and updated review.

Nigella sativa (N. sativa) seed had been used traditionally due to several pharmacological effects. The updated experimental and clinical effects of N. sativa and its constituents on respiratory, allergic and immunologic disorders are provided in this comprehensive review article. Various databases including PubMed, Science Direct and Scopus were used. The preventive effects of N. sativa on pulmonary diseases were mainly due to its constituents such as thymoquinone, thymol, carvacrol and alpha-hederin. Extracts and constituents of N. sativa showed the relaxant effect, with possible mechanisms indicating its bronchodilatory effect in obstructive pulmonary diseases. In experimental animal models of different respiratory diseases, the preventive effect of various extracts and constituents of N. sativa was demonstrated by mechanisms such as antioxidant, immunomodulatory and antiinflammatory effects. Bronchodilatory and preventive effects of the plant and its components on asthma, COPD and lung disorders due to exposure to noxious agents as well as on allergic and immunologic disorders were also shown in the clinical studies. Various extracts and constituents of N. sativa showed pharmacological and therapeutic effects on respiratory, allergic and immunologic disorders indicating possible remedy effect of that the plant and its effective substances in treating respiratory, allergic and immunologic diseases.

Experimental and clinical studies on the effects of Portulaca oleracea L. and its constituents on respiratory, allergic, and immunologic disorders, a review.

Various pharmacological effects for Portulaca oleracea were shown in previous studies. Therefore, the effects of P. oleracea and its derivatives on respiratory, allergic, and immunologic diseases according to update experimental and clinical studies are provided in this review article. PubMed/Medline, Scopus, and Google Scholar were searched using appropriate keywords until the end of December 2020. The effects of P. oleracea and its constituents such as quercetin and kaempferol on an animal model of asthma were shown. Portulaca oleracea and its constituents also showed therapeutic effects on chronic obstructive pulmonary disease and chronic bronchitis in both experimental and clinical studies. The possible bronchodilatory effect of P. oleracea and its ingredients was also reported. Portulaca oleracea and its constituents showed the preventive effect on lung cancer and a clinical study showed the effect of P. oleracea on patients with lung adenocarcinoma. In addition, a various constituents of P. oleracea including, quercetin and kaempferol showed therapeutic effects on lung infections. This review indicates the therapeutic effect of P. oleracea and its constituents on various lung and allergic disorders but more clinical studies are required to establish the clinical efficacy of this plant and its constituents on lung and allergic disorders.

Correlation of Serum Adipolin with Epicardial Fat Thickness and Severity of Coronary Artery Diseases in Acute Myocardial Infarction and Stable Angina Pectoris Patients.

OBJECTIVE: Adipolin/C1q/TNF-related protein-12 is a family of CTRPs highly expressed in adipose tissue with glucose-lowering and anti-inflammatory effects. Various risk factors have been suggested in the incidence of cardiovascular diseases, such as a decrease in anti-inflammatory or an increase in inflammatory factors. The purpose of the present study was to investigate the correlation of adipolin with anthropometric, angiographic, echocardiographic, and biochemical parameters. SUBJECT AND METHODS: A total of 90 patients who were candidates for angiography were included in the study and divided into 3 groups: 30 patients with acute myocardial infarction (AMI), 30 patients with stable angina pectoris (SAP), and 30 subjects as a control group with a history of chest pain but normal angiography. Anthropometric, angiographic, echocardiographic, and biochemical parameters were measured in all subjects. RESULTS: Serum adipolin levels were significantly decreased in patients with AMI compared with the SAP and control groups (p < 0.001 for both). In addition, there was a negative association between serum levels of adipolin and epicardial fat thickness (EFT) and Gensini score in CAD patients. The results of multivariate linear regression analysis revealed that EFT values were independently associated with serum adipolin levels. CONCLUSION: The current study showed an independent association of adipolin with EFT for the first time in patients with AMI. Decreased adipolin levels in patients with AMI may be involved in the process of atherosclerosis, which requires further study.

Rosuvastatin suppresses cytokine production and lung inflammation in asthmatic, hyperlipidemic and asthmatic-hyperlipidemic rat models.

BACKGROUND: Given the role that T lymphocytes play on the pathogenesis of allergic asthma, drugs targeting Th2 and Th17 cells may be a hopeful therapeutic strategy. This study aimed to evaluate the effect of rosuvastatin treatment on cytokine production and lung inflammation in allergic asthma. METHODS: The animals were assigned into control (C), asthmatic (A), hyperlipidemic (H), asthmatic-hyperlipidemic (AH), rosuvastatin (40 mg/kg/day intraperitoneally, for 3 weeks)-treated asthmatic (AR), rosuvastatin-treated hyperlipidemic (HR) and rosuvastatin-treated asthmatic-hyperlipidemic (AHR) groups (n = 6 in each group). The levels of IL-4, IFN-γ and IL-17, total and differential WBC counts in bronchoalveolar lavage fluid (BALF), Th1/Th2 balance, and pathological changes were evaluated. RESULTS: The BALF level of IL-4 in A, H and AH groups, and IL-17A in A and AH groups were significantly higher than that in C group (p < 0.05 to p < 0.001). IFN-γ level and Th1/Th2 balance (IFN­Î³/IL-4 ratio) in A and AH groups were significantly decreased (p < 0.05 to p < 0.01). Inflammatory cells infiltration, muscle hypertrophy and emphysema were also observed in A and AH groups. The BALF levels of IL-4 in AR, HR and AHR groups, IFN-γ level in HR group, and IL-17A level in AR and AHR groups showed a significant improvement compared to that of A, H and AH groups (p < 0.05 to p < 0.001). Rosuvastatin treatment increased Th1/Th2 balance in all treated groups (p < 0.05 to p < 0.01), decreased total WBC counts, neutrophilia, eosinophilia and lung inflammation in AR and AHR groups, and improved muscle hypertrophy and emphysema in AHR group. CONCLUSIONS: Rosuvastatin treatment improved lung pathological changes by suppression of Th2 and Th17-mediated cytokines which was unrelated to its lipid-lowering activity. Therefore, rosuvastatin might be a candidate immunomodulatory drug for treatment of patients with allergic asthma.

Calcium and potassium channels are involved in curcumin relaxant effect on tracheal smooth muscles.

Context: Curcumin, the active component of Curcuma longa L. (Zingiberaceae), exhibits a wide variety of biological activities including vasodilation and anti-inflammation.Objective: The relaxant effect of curcumin in tracheal smooth muscle (TSM) was not examined so far, thus, this study was designed to assess the relaxant effect of curcumin on rat TSM and examine the underlying mechanism(s) responsible for this effect.Materials and methods: TSM was contracted by KCl (60 mM) or methacholine (10 µM), and cumulative concentrations of curcumin (12.5, 25, 50, and 100 mg/mL) or theophylline (0.2, 0.4, 0.6, and 0.8 mM, as positive control) were added to organ bath. The relaxant effect of curcumin was examined in non-incubated or incubated tissues with atropine (1 µM), chlorpheniramine (1 µM), indomethacin (1 µM), and papaverine (100 µM).Results: In non-incubated TSM, curcumin showed significant relaxant effects on KCl-induced contraction in a concentration-dependent manner (p < 0.001 for all concentrations). The relaxant effects of curcumin 12.5, 25, and 50 mg/mL were significantly lower in atropine-incubated tissue compared to non-incubated TSM (p < 0.05 to p < 0.001). A significant difference was observed in EC50 between atropine-incubated (48.10 ± 2.55) and non-incubated (41.65 ± 1.81) tissues (p < 0.05). Theophylline showed a significant relaxant effect on both KCl and methacholine-induced contraction in a concentration-dependent manner (p < 0.001 for all cases).Conclusions: The results indicated a relatively potent relaxant effect of curcumin on TSM, which was less marked than the effect of theophylline. Calcium channel blocking and/or potassium channel opening properties of curcumin may be responsible for TSM relaxation.

Aminoguanidine affects systemic and lung inflammation induced by lipopolysaccharide in rats.

BACKGROUND: Nitric oxide is a mediator of potential importance in numerous physiological and inflammatory processes in the lung. Aminoguanidine (AG) has been shown to have anti-inflammation and radical scavenging properties. This study aimed to investigate the effects of AG, an iNOS inhibitor, on lipopolysaccharide (LPS)-induced systemic and lung inflammation in rats. METHODS: Male Wistar rats were divided into control, LPS (1 mg/kg/day i.p.), and LPS groups treated with AG 50, 100 or 150 mg/kg/day i.p. for five weeks. Total nitrite concentration, total and differential white blood cells (WBC) count, oxidative stress markers, and the levels of IL-4, IFN-γ, TGF-ß1, and PGE2 were assessed in the serum or bronchoalveolar lavage fluid (BALF). RESULTS: Administration of LPS decreased IL-4 level (p < 0.01) in BALF, total thiol content, superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.001) in BALF and serum, and increased total nitrite, malondialdehyde (MDA), IFN-γ, TGF-ß1 and PGE2 (p < 0.001) concentrations in BALF. Pre-treatment with AG increased BALF level of IL-4 and total thiol as well as SOD and CAT activities (p < 0.05 to p < 0.001), but decreased BALF levels of total nitrite, MDA, IFN-γ, TGF-ß1, and PGE2 (p < 0.01 to p < 0.001). AG treatment decreased total WBC count, lymphocytes and macrophages in BALF (p < 0.01 to p < 0.001) and improved lung pathological changes including interstitial inflammation and lymphoid infiltration (p < 0.05 to p < 0.001). CONCLUSIONS: AG treatment reduced oxidant markers, inflammatory cytokines and lung pathological changes but increased antioxidants and anti-inflammatory cytokines. Therefore, AG may play a significant protective role against inflammation and oxidative stress that cause lung injury.

Protective effects of curcumin against ischemia-reperfusion injury in the liver.

Liver ischemia/reperfusion (I/R) injury is a major complication of hepatic surgery and transplantation. It is one of the leading causes of morbidity and mortality because of post-surgery hepatic dysfunction. Several studies have suggested different mechanisms are involved in the pathogenesis of I/R injury in the liver that includes oxidative stress, inflammation, mitochondria dysfunction, liver Kupffer cells (KCs) activation, vascular cell adhesion molecule overexpression, and facilitation of polymorphonuclear neutrophil injury. Curcumin is a natural product extracted from Curcuma longa that is known to suppress these pathways and as a result reduces liver ischemia-reperfusion injury. This paper gives an overview of the protective effects of curcumin against I/R injury in the liver and discusses the studies that have linked biological functions of curcumin with liver I/R injury improvement.

Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum leaves and its effect on lung pathological changes in an ovalbumin-induced rat model of asthma.

BACKGROUND: Ocimum species (Lamiaceae) has been traditionally used for treatment of upper respiratory tract infections, bronchitis, coughs, sore throat, and wound healing. The Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum (O. basilicum) leaves was examined in ovalbumin sensitized animals. METHODS: Wistar rats were divided to six groups; non-sensitized, sensitized to ovalbumin, sensitized and treated with dexamethasone (1.25 µg/mL), and O. basilicum extract (0.75, 1.50 and 3.00 mg/mL) in drinking water for 21 days. The levels of interleukin 4 (IL-4), interferon gamma (IFN-γ), IFN-γ/IL-4 ratio, immunoglobulin E (IgE), phospholipase A2 (PLA2) and total protein (TP) in BALF, and lung pathological changes were examined. RESULTS: A significant increase in IL-4, IgE, PLA2 and TP levels, all lung pathological indices as well as significant decrease in IFN-γ/IL-4 ratio was seen in the asthmatic compared to the control rats (P < 0.05 to P < 0.001). Treatment with O. basilicum extract resulted in decreased IL-4, IgE, PLA2 and TP levels, but increased IFN-γ/IL-4 ratio compared to untreated sensitized rats (P < 0.01 to P < 0.001). The plant significantly improved the pathological changes of sensitized rats (P < 0.05 to P < 0.01). The improvement effects of higher concentrations of the O. basilicum extract were significantly more than those of dexamethasone (P < 0.05 to P < 0.001). CONCLUSION: The improvement effects of O. basilicum on pathological changes, immunological and inflammatory markers in sensitized rats comparable or even more potent than dexamethasone suggests the therapeutic potential of the plant in asthma.

Comparative Antitussive Effects of Medicinal Plants and Their Constituents.

CONTEXT: The cough is a protective reflex, with 2 types, one being more sensitive to mechanical stimulation and the other to chemical stimulation, such as sulfur dioxide, ammonia, citric acid, and capsaicin. Some evidence is available that suppressant therapy is most effective when used for the short-term reduction of coughing. Today, use of herbal drugs is increasing all over the world for various ailments, including to provide antitussive activity. OBJECTIVE: The study intended to review the antitussive effects of various extracts, some fractions, and some constituents of the studied medicinal plants. DESIGN: Various databases, including the Medline, Science Direct, Scopus, and Google Scholar, were searched for studies published between 1978 and 2015, using the keywords antitussive and cough and the names of various medicinal plants and their constituents. SETTING: The study took place in the districts related to Mashhad University of Medical Sciences (Mashhad, Iran). OUTCOME MEASURES: The antitussive effects of medicinal plants and their constituents were normalized to 50 mg/kg and 1 mg/mL against various cough stimulants and compared. RESULTS: The most potent antitussive effect was observed for Nigella sativa and Linum usitatissimum on coughs induced by sulfur dioxide. Artemisia absinthium showed a higher antitussive effect on cough induced by ammonia compared with the other studied medicinal plants. The antitussive effects of Cuminum cyminum and Glycyrrhiza glabra were more potent on cough induced by citric acid than other medicinal plants. CONCLUSIONS: These results suggest the therapeutic potential of the studied medicinal plants as antitussive therapies. However, only a few clinical studies have examined the antitussive effects of medicinal plants, and more clinical studies are needed. The underlying mechanisms of the antitussive effects of medicinal plants should be also examined in further studies.

The effects of medicinal plants on muscarinic receptors in various types of smooth muscle.

Pharmacological agents that can affect muscarinic receptors are commonly used to treat or manage various diseases. Medicinal plants have been used from ancient time to treat cardiovascular, gastrointestinal, respiratory, and urogenital disorders, which may related to their muscarinic receptors effects. Several pharmacological studies revealed the inhibitory or stimulatory effect of some herbal plants on muscarinic receptors. Medline, PubMed, Science Direct, Scopus, and Google Scholar as online database were searched from the beginning of 1983 to March 2018 using following keywords: muscarinic receptor, medicinal plant, herbal medicine, and smooth muscle, animal, human, in vivo, and in vitro. The original studies in English language were included. Based on the results of the reviewed articles, more than 70 medicinal plants extracts or constituents affected muscarinic receptors (stimulatory or inhibitory) of smooth muscles in cardiovascular, gastrointestinal, respiratory, and urogenital systems. Among them, there are some tropical plant and herbs that have been traditionally used as food additive. The therapeutic properties of these plants may be regarded in treatment of cardiovascular (hypertension and tachycardia); gastrointestinal (diarrhea, colitis, and constipation); and urological (overactive bladder, abortion, and preterm labor) diseases. However, more clinical trials are needed to use some of these medicinal plants in clinical target therapy.

Effect of α-Hederin on IL-2 and IL-17 mRNA and miRNA-133a Levels in Lungs of Ovalbumin-Sensitized Male Rats.

α-hederin, a saponin that is a major constituent of English Ivy (Hedera helix) is effective in the treatment of asthma. In the present study, the effect of α-hederin on lung tissue pathology and the levels of the inflammatory mediators; IL-2 mRNA, IL-17 mRNA, and MicroRNAs (miRNA)-133a was evaluated in a rat ovalbumin (OVA)-sensitized model of asthma. Rats were divided randomly into control (C), OVA-sensitized (S), OVA-sensitized pretreated with the antioxidant, thymoquinone (3 mg/kg, S + TQ) or OVA-sensitized pretreated with α-hederin (0.02 mg/kg, S + AH) groups. Levels of IL-2 and IL-17 mRNA were higher in the OVA-sensitized group than controls while the level of miRNA-133a gene expression was lower. IL-2 mRNA and miRNA-133a gene expression in the S + TQ group was higher than in the control and OVA-sensitized groups while the level of IL-17 mRNA in the S + TQ group was lower than in the OVA-sensitized group. Pretreatment with α-hederin decreased IL-17 mRNA levels and increased miRNA-133a gene expression compared with OVA-sensitized animals. All pathological changes in pretreated groups were lower than the OVA-sensitized group. These results showed a beneficial effect of α-hederin in OVA-sensitized rats, suggesting that α-hederin affects the IL-2 and IL-17 secretion pathways, altering miRNA-133a expression.

The Protective Effect of α-Hederin, the Active Constituent of Nigella sativa, on Lung Inflammation and Blood Cytokines in Ovalbumin Sensitized Guinea Pigs.

In the present study, the preventive effect of two different concentrations of α-hederin, the active constituent of Nigella sativa, on lung inflammation and blood cytokines in ovalbumin sensitized guinea pigs was examined. Forty eight male adult guinea pigs were divided into control (C), sensitized (S) and sensitized pretreated groups; with thymoquinone (S+TQ), low dose (S+LAH) and high dose of α-hederin (S+HAH) and inhaled fluticasone propionate (S+FP). The lung histopathology and blood levels of IL-4, IFN-γ and IL-17 were assessed. Compared to sensitized animals, all pathological changes improved significantly in pretreated groups (p < 0.001 to p < 0.05). These improvements in α-hederin pretreated groups were similar to S+TQ and S+FP groups except cellular infiltration in S+LAH and S+HAH groups which was lower than S+TQ group (p < 0.05). The blood IL-4 and IL-17 levels in S+HAH groups showed a significant decrease compared to S group (p < 0.05) which were similar to S+TQ and S+FP groups. The level of IFN-γ in S+LAH and S+HAH groups increased significantly compared to S group (p < 0.05) which was higher than S+FP group (p < 0.05). Blood IL-4 in S+HAH group was significantly lower than S+LAH group (p < 0.05). In conclusion, α-hederin could attenuate the lung inflammation and improve the changes of cytokines like thymoquinone and fluticasone in used dosages.

Comprehensive and updated review on anti-oxidant effects of Nigella sativa and its constituent, thymoquinone, in various disorders.

Several pharmacological effects were described for Nigella sativa (N. sativa) seed and it has been used traditionally to treat various diseases. In this review article, the updated and comprehensive anti-oxidant effects of N. sativa and its main constituent, thymoquinone (TQ), on various disorders are described. The relevant articles were retrieved through PubMed, Science Direct, and Scopus up to December 31, 2023. Various extracts and essential oils of N. sativa showed anti-oxidant effects on cardiovascular, endocrine, gastrointestinal and liver, neurologic, respiratory, and urogenital diseases by decreasing and increasing various oxidant and anti-oxidant marketers, respectively. The main constituent of the plant, TQ, also showed similar anti-oxidant effects as the plant itself. The anti-oxidant effects of different extracts and essential oils of N. sativa were demonstrated in various studies which were perhaps due to the main constituent of the plant, TQ. The findings of this review article suggest the possible therapeutic effect of N. sativa and TQ in oxidative stress disorders.

Saffron (Crocus sativus) and its constituents in ovalbumin-induced asthma model: a preclinical systematic review and meta-analysis.

Background: Animal and human studies have demonstrated that the saffron and the active components of saffron, including crocin, crocetin, and safranal, possess anti-inflammatory, antioxidant, and immunomodulatory properties. In this meta-analysis, the preclinical evidence and potential mechanism of saffron were explored in an animal model of ovalbumin-induced asthma. Methods: Studies related to saffron and its constituents in an animal model of ovalbumin-induced asthma from the beginning to March 2024 were searched from Scopus, PubMed, and Web of Science databases. The methodological quality of the studies was evaluated using the 15-item CAMARADES checklist. Data analysis was performed using STATA software version 17. Results: Thirteen studies with 536 animals (268 animals in the intervention group and 268 animals in the ovalbumin-induced group) were analyzed. The meta-analysis findings demonstrated that saffron and its constituents played a significant role in reducing total WBC, eosinophil, lymphocyte, and monocyte counts. Moreover, saffron showed a significant decrease in the levels of IL-4, IL-5, IL-13, IgE, histamine, endothelin, nitric oxide, and nitrite. Moreover, saffron was found to elevate EC50 thresholds and lower maximum response rates in experimental animals. The analysis revealed a significant identification of modulation in endoplasmic reticulum (ER) stress markers and miRNAs pathways. Conclusion: Saffron and its components may impact ovalbumin-induced asthma model in animals through anti-inflammatory, antioxidant, and immunomodulatory pathways, as well as improving pulmonary function and modulating ER stress markers and miRNAs pathways. As a result, saffron should be considered for further clinical trials in individuals suffering from asthma.

An overview of pharmacological effects of Crocus sativous and its constituents.

Crocus sativus L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of C. sativus and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both in vitro and in vivo. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of C. sativus may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of C. sativus and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of C. sativus and its main constituents in different disorders.

Systemic and Lung Inflammation and Oxidative Stress Associated With Behavioral Changes Induced by Inhaled Paraquat Are Ameliorated by Carvacrol.

Paraquat (PQ) is an herbicide toxin that induces injury in different organs. The anti-inflammatory and antioxidant effects of carvacrol were reported previously. The effects of carvacrol and pioglitazone (Pio) alone and their combination on inhaled PQ-induced systemic and lung oxidative stress and inflammation as well as behavioral changes were examined in rats. In this study, animals were exposed to saline (control [Ctrl]) or PQ (PQ groups) aerosols. PQ-exposed animals were treated with 0.03 mg/kg/day dexamethasone (Dexa), 20 and 80 mg/kg/day carvacrol (C-L and C-H), 5 mg/kg/day Pio, and Pio+C-L for 16 days. Inhaled PQ markedly enhanced total and differential white blood cell (WBC) counts, nitric oxide (NO), and malondialdehyde (MDA) levels but decreased catalase (CAT) and superoxide dismutase (SOD) activities and thiol levels both in the bronchoalveolar lavage fluid (BALF) and blood and increased interferon-gamma (INF-γ) and interleukin-10 (IL-10) levels in the BALF (p < 0.001 for all cases) except lymphocyte count in blood which was not significantly changed. The escape latency and traveled distance were increased in the PQ group. However, the time spent in the target quadrant in the Morris water maze (MWM) test and the duration of time latency in the dark room in the shuttle box test were reduced after receiving an electrical shock (p < 0.05-p < 0.001). Inhaled PQ-induced changes were significantly improved in carvacrol, Pio, Dexa, and especially in the combination of the Pio+C-L treated groups (p < 0.05-p < 0.001). Carvacrol and Pio improved PQ-induced changes similar to Dexa, but ameliorative effects produced by combination treatments of Pio+C-L were more prominent than Pio and C-L alone, suggesting a potentiating effect for the combination of the two agents.

Phytochemical Characteristics and Anti-Inflammatory, Immunoregulatory, and Antioxidant Effects of Portulaca oleracea L.: A Comprehensive Review.

Portulaca oleracea L. (P. oleracea) or purslane is a plant from the Portulacaceae family, which is used as food and traditional medicine for various diseases. This review article provides comprehensive information on the antioxidant, immunomodulatory, and anti-inflammatory properties of P. oleracea and its constituents. The literature survey of the different databases until the end of June 2023 was explored based on the keywords including the "P. oleracea, purslane, anti-inflammatory, immunomodulatory, and antioxidant properties." The plant contains flavonoids, alkaloids, terpenoids, fatty acids, vitamins, minerals, and some other compounds. The results indicated that P. oleracea and its constituents showed anti-inflammatory and immunomodulatory properties through reduction of inflammatory mediators including interferon gama (IFN-γ), interleukin (IL)-10, IL-4, tumor necrosis factor-alpha (TNF-α), and nitric oxide. Improvement in cytokines' serum levels (IFN-γ, IL-10, and IL-4) and increased IgG and IgM serum levels, as well as reduction of IgE, phospholipase A2, and total protein were demonstrated for P. oleracea. The plant and its constituents also improved oxidative stress by reduction of oxidant and increase of antioxidant markers. P. oleracea could be considered as an effective remedy for various inflammatory and immune diseases.

Crocetin regulates Th1/Th2 and Th17/Treg balances, nitric oxide production, and nuclear localization of NF-κB in Th2-provoked and normal situations in human-isolated lymphocytes.

Crocetin is a natural carotenoid dicarboxylic acid derived from Crocus sativus. It has been utilized as natural biomedicine with healing effects. The immunoregulatory and anti-inflammatory properties may cause the biological activities of crocetin. Nevertheless, it is not still clear how this compound acts and causes an immune-modulatory impact on human lymphocytes. The effects of three concentrations (5, 10, and 20 µM) of crocetin or dexamethasone (0.1 mM) were assessed on gene expression and secretion of cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) level, and nitric oxide (NO) production in phytohaemagglutinin (PHA)-stimulated and non-stimulated lymphocytes. By incubation with PHA, gene expression and cytokine concentration comprising interferon (IFN)-γ, interleukin (IL)-17A, IL-10, and IL-4 were increased, along with NF-κB concentration and NO production (all, p < 0.001). In comparison with the controls, an alteration occurred in the T-helper (Th)2/Th1 and Th17/Treg balance in the stimulated lymphocyte toward a Th2 and Th17 response. In stimulated cells, crocetin and dexamethasone decreased pro-inflammatory significantly and increased anti-inflammatory cytokines and related gene expression, respectively. Moreover, Th17/Treg and Th1/Th2 balance was changed toward Treg and Th1 significantly reducing NF-κB and NO levels (p < 0.05 to p < 0.001). Promoting effects were represented by crocetin on T-cell subsets to Treg and Th1. Hence, it can have therapeutic value for treating predominant diseases of Th2 or Th17 cells.