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.

Inhaled paraquat-induced lung injury in rat, improved by the extract of Zataria multiflora boiss and PPARγ agonist, pioglitazone.

The effects of a PPAR-γ agonist, pioglitazone and Zataria multiflora (Z. multiflora) on inhaled paraquat (PQ)-induced lung oxidative stress, inflammation, pathological changes and tracheal responsiveness were examined. The study was carried out in control rats exposed to normal aerosol of saline, PQl and PQh groups exposed to aerosols of 27 and 54 mg/m3 PQ, groups exposed to high PQ concentration (PQh) and treated with 200 and 800 mg/kg/day Z. multiflora, 5 and 10 mg/kg/day pioglitazone, low doses of Z. multiflora + pioglitazone, and 0.03 mg/kg/day dexamethasone. Increased tracheal responsiveness, transforming growth factor beta (TGF-ß) and lung pathological changes due to PQh were significantly improved by high doses of Z. multiflora and pioglitazone, dexamethasone and extract + pioglitazone, (p < 0.05 to p < 0.001). In group treated with low doses of the extract + pioglitazone, the improvements of most measured variables were significantly higher than the low dose of two agents alone (p < 0.05 to p < 0.001). Z. multiflora improved lung injury induced by inhaled PQ similar to dexamethasone and pioglitazone which could be mediated by PPAR-γ receptor.

The effects of Crocus sativus extract on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes and tracheal responsiveness in rats.

Paraquat is a green liquid toxin that is used in agriculture and can induce multi-organ including lung injury. Various pharmacological effects of Crocus sativus (C. sativus) were indicated in previous studies. In this research, the effects of C. sativus extract and pioglitazone on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes, and tracheal responsiveness were studied in rats. Eight groups of rats (n = 7 in each) including control (Ctrl), untreated paraquat aerosol exposed group (54 mg/m3, 8 times in alternate days), paraquat treated groups with dexamethasone (0.03 mg/kg/day, Dexa) as positive control, two doses of C. sativus extract (20 and 80 mg/kg/day, CS-20 and CS-80), pioglitazone (5 and 10 mg/kg/day, Pio-5 and Pio-10), and the combination of CS-20 + Pio-5 were studied. Total and differential WBC, levels of oxidant and antioxidant biomarkers in the BALF, lung tissue cytokine levels, tracheal responsiveness (TR), and pathological changes were measured. The levels of IFN-γ, IL-10, SOD, CAT, thiol, and EC50 were reduced, but MDA level, total and differential WBC count in the BALF and lung pathological changes were increased in the paraquat group (all, p < 0.001). The levels of IFN-γ, IL-10, SOD, CAT, thiol and EC50 were increased but BALF MDA level, lung pathological changes, total and differential WBC counts were reduced in all treated groups. The effects of C. sativus high dose and combination groups on measured parameters were equal or even higher than dexamethasone (p < 0.05 to p < 0.001). The effects of the combination of CS-20 + Pio-5 on most variables were significantly higher than CS-20 and Pio-5 alone (p < 0.05 to p < 0.001). C. sativus treatment improved inhaled paraquat-induced lung injury similar to dexamethasone and showed a synergistic effect with pioglitazone, suggesting possible PPAR-γ receptor-mediated effects of the plant.

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 Antioxidant, Anti-Inflammatory and Immunomodulatory Effects of Camel Milk.

Camel milk (CM) has been found to have several health benefits, including antiviral, antibacterial, anti-tumor, anti-fungal, antioxidant, hypoglycaemic and anti-cancer activities. In addition, CM can counter signs of aging and may be a useful naturopathic treatment for autoimmune diseases. The composition of CM varies with geographic origin, feeding conditions, seasonal and physiological changes, genetics and camel health status. In the present review, we collate the diverse scientific literature studying antioxidant, anti-inflammatory and immunomodulatory effects of CM and its bioactive compounds. The databases Scopus, PubMed, and Web of Science were searched until the end of September 2021 using the keywords: camel milk, antioxidant, anti-inflammatory, immunomodulatory. The anti-inflammatory mechanism of CM in various inflammatory disorders was consistently reported to be through modulating inflammatory cells and mediators. The common anti-inflammatory bioactive components of CM seem to be lactoferrin. The antioxidant effects of α-lactalbumin, ß-caseins and vitamin C of CM work by reducing or inhibiting the production of reactive oxygen species (ROS), hydroxyl radicals, nitric oxide (NO), superoxide anions and peroxyl radicals, likely alleviating oxidative stress. Higher levels of protective proteins such as lysozyme, IgG and secretory IgA compared to cow's milk, and insulin-like protein activity of CM on ß cells appear to be responsible for the immunomodulatory properties of CM. The evidence indicates that CM and its bioactive components has the potential to be a therapeutic value for diseases that are caused by inflammation, oxidative stress and/or immune-dysregulation.

Curcuma longa and curcumin affect respiratory and allergic disorders, experimental and clinical evidence: A comprehensive and updated review.

Curcuma longa and its constituents, mainly curcumin, showed various of pharmacological effects in previous studies. This review article provides updated and comprehensive experimental and clinical evidence regarding the effects of C. longa and curcumin on respiratory, allergic, and immunologic disorders. Using appropriate keywords, databases including PubMed, Science Direct, and Scopus were searched until the end of October 2021. C. longa extracts and its constituent, curcumin, showed the relaxant effect on tracheal smooth muscle, which indicates their bronchodilatory effect in obstructive pulmonary diseases. The preventive effects of extracts of C. longa and curcumin were shown in experimental animal models of different respiratory diseases through antioxidant, immunomodulatory, and anti-inflammatory mechanisms. C. longa and curcumin also showed preventive effects on some lung disorders in the clinical studies. It was shown that the effects of C. longa on pulmonary diseases were mainly due to its constituent, curcumin. Pharmacological effects of C. longa extracts and curcumin on respiratory, allergic, and immunologic disorders indicate the possible therapeutic effect of the plant and curcumin on these diseases.

Relaxant Effect of Urginea maritima on Tracheal Smooth Muscle Mediated by the Effect on Beta-2 Adrenergic, Muscarinic Receptors and Calcium and Potassium Channels.

Urginea maritima (U. maritima) showed anti-inflammatory, antioxidant, antibacterial, diuretic, vasodilatation, and wound-healing effects on fungal infections, cardiac disorders, digestive disorders, rheumatoid disease, and respiratory disorders such as bronchitis, bronchial nosocomial infections, and severe cough. To examine the bronchodilatory effect of U. maritima, the relaxant effect of its extract on rat tracheal smooth muscle (TSM) and its possible mechanism was examined in this study. Male Wistar rats' TSM were divided into eight groups (n = 8 in each group). Four of these groups were TSM tissues, contracted with KCl (60 mM) incubated with atropine, glibenclamide, and indomethacin and nonincubated TSM, while the other four groups were TSM tissues contracted with methacholine (10 µM) for 5 min, incubated with propranolol, chlorpheniramine, and diltiazem and nonincubated TSM. Cumulative concentrations of U. maritima extract (12.5, 25, 50, 100, 20, and 400 µg/ml) were then added to organ bath every 5 min. Theophylline (0.2, 0.4, 0.6, and 0.8 mM) as positive control and saline (1 ml) as negative control were also examined in nonincubated tissues. A concentration-dependent relaxant effect of U. maritima on nonincubated TSM contracted with KCl (60 mM) or methacholine (10 µM) (p < 0.01 and p < 0.001) was observed. The relaxant effects of U. maritima extract in the incubated tissues with glibenclamide, propranolol, diltiazem, atropine, and chlorpheniramine were significantly lower than those in the nonincubated tissues (p < 0.05 to p < 0.001). EC50 values of U. maritima extract in the incubated TSM with glibenclamide, propranolol, diltiazem, and atropine were significantly higher than those in the nonincubated tissues (p < 0.05 for diltiazem-incubated tissues and p < 0.001 for other cases). U. maritima extract displayed considerable relaxant effect on TSM comparable to the effect of theophylline. Beta-2 adrenoceptor stimulation and muscarinic receptor inhibition as well as potassium opening and calcium channels blocking effects are the possible mechanisms for the relaxant effects of the plant.

Thymoquinone Ameliorates Lung Inflammation and Pathological Changes Observed in Lipopolysaccharide-Induced Lung Injury.

Anti-inflammatory, antioxidant, and immunomodulatory effects of thymoquinone (TQ) have been shown. The effects of TQ on lipopolysaccharide- (LPS-) induced inflammation and pathological changes in rats' lung were investigated in this study. Four groups of rats included (1) control (saline treated); (2) LPS (treated with 1 mg/kg/day i.p. for two weeks); and (3 and 4) 5 or 10 mg/kg TQ i.p. 30 min prior to LPS administration. Total and differential WBC counts in the blood and bronchoalveolar fluid (BALF), TGF-ß1, INF-γ, PGE2, and IL-4 levels in the BALF and pathological changes of the lung were evaluated. Total WBC count and eosinophil, neutrophil, and monocyte percentage were increased, but the lymphocyte percentage was reduced in the blood and BALF. The BALF levels of PGE2, TGF-ß1, and INF-γ were also increased, but IL-4 level was reduced due to LPS administration. LPS also induced pathological insults in the lung of rats (P < 0.05 to P < 0.001 for all changes in LPS-exposed animals). Treatment with TQ showed a significant improvement in all changes induced by LPS (P < 0.05 to P < 0.05). TQ showed a protective effect on LPS-induced lung inflammation and pathological changes in rats which suggested a therapeutic potential for TQ on lung injury.

Experimental and clinical reports on anti-inflammatory, antioxidant, and immunomodulatory effects of Curcuma longa and curcumin, an updated and comprehensive review.

Curcuma longa (C. longa) or turmeric is a plant with a long history of use in traditional medicine, especially for treating inflammatory conditions C. longa and its main constituent, curcumin (CUR), showed various pharmacological effects such as antioxidant and anti-microbial properties. The updated knowledge of anti-inflammatory, antioxidant, and immunomodulatory effects of C. longa and CUR is provided in this review article. Pharmacological effects of C. longa, and CUR, including anti-inflammatory, antioxidant, and immunomodulatory properties, were searched using various databases and appropriate keywords until September 2020. Various studies showed anti-inflammatory effects of C. longa and CUR, including decreased white blood cell, neutrophil, and eosinophil numbers, and its protective effects on serum levels of inflammatory mediators such as phospholipase A2 and total protein in different inflammatory disorders. The antioxidant effects of C. longa and CUR were also reported in several studies. The plant extracts and CUR decreased malondialdehyde and nitric oxide levels but increased thiol, superoxide dismutase, and catalase levels in oxidative stress conditions. Treatment with C. longa and CUR also improved immunoglobulin E (Ig)E, pro-inflammatory cytokine interleukin 4 (IL)-4, transforming growth factor-beta, IL-17, interferon-gamma levels, and type 1/type 2 helper cells (Th1)/(Th2) ratio in conditions with disturbance in the immune system. Therefore C. longa and CUR showed anti-inflammatory, antioxidant, and immunomodulatory effects, indicating a potential therapeutic effect of the plant and its constituent, CUR, for treating of inflammatory, oxidative, and immune dysregulation disorders.

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 contribution of beta-2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels and cyclooxygenase pathway in the relaxant effect of Allium cepa L. on the tracheal smooth muscle.

ETHNOPHARMACOLOGICAL RELEVANCE: There are report regarding therapeutic effects for Allium cepa L. (A. cepa) in Iranian traditional medicine and the plant has showed anti-inflammatory, anti-allergic, anti-hyperglycemic, antioxidant, anti-cancer, anti-hypertension, anti-hypercholesterolemia and anti-asthmatic activities in previous studies. AIM OF THE STUDY: In this study, the contribution of ß2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels, and cyclooxygenase pathway in the relaxant effect of A. cepa extract on tracheal smooth muscle (TSM) was assessed. MATERIALS AND METHODS: TSM was contracted by KCl (60 mM) or methacholine (10 µM) for 5 min and cumulative concentrations of A. cepa extract (2, 4, 8, 16, 32 and 64 mg/ml) were added to organ bath every 5 min. Theophylline (0.2, 0.4, 0.6 and 0.8 mM) as positive control, and saline (1 ml) as negative control were also examined in non-incubated tissues. The relaxant effect of A. cepa extract was examined on non-incubated and incubated TSM with propranolol, chlorpheniramine, diltiazem, atropine, glibenclamide and indomethacin. RESULTS: A. cepa showed concentration-dependent relaxant effects on non-incubated TSM contracted by KCl (60 mM) or methacholine (10 µM), (P < 0.01 to p < 0.001). There was no significant difference in the relaxant effects of A. cepa between non-incubated and incubated tissues with glibenclamide, atropine, chlorpheniramine and indomethacin. The plant extract showed significant lower relaxant effects in incubated TSM with propranolol and diltiazem compared to non-incubated tissues. EC50 values of A. cepa extract in incubated TSM with propranolol and diltiazem were significantly lower than non-incubated tissues (p < 0.001 and p < 0.05, respectively). The relaxant effects of different concentrations of the extract of A. cepa were not significantly different with those of theophylline. The concentrations of A. cepa extract and theophylline were significant correlated with their relaxant effects (p < 0.05 to p < 0.001). In incubated TSM with propranolol and diltiazem, concentration ratio minus one (CR-1) values was positive (2.65 ±â€¯0.63 and 1.28 ±â€¯0.43 respectively). CONCLUSION: The A. cepa extract showed relatively potent relaxant effect on TSM which was comparable to the effect of theophylline. The results showed that ß2-adrenergic stimulatory and/or calcium channel blockade are the possible mechanisms for the relaxant effects of the plant.