Peroxisome proliferator-activated receptors: Key regulators of tumor progression and growth.

One of the main causes of death on the globe is cancer. Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors, including PPARα, PPARδ and PPARγ, which are important in regulating cancer cell proliferation, survival, apoptosis, and tumor growth. Activation of PPARs by endogenous or synthetic compounds regulates tumor progression in various tissues. Although each PPAR isotype suppresses or promotes tumor development depending on the specific tissues or ligands, the mechanism is still unclear. PPARs are receiving interest as possible therapeutic targets for a number of disorders. Numerous clinical studies are being conducted on PPARs as possible therapeutic targets for cancer. Therefore, this review will focus on the existing and future uses of PPARs agonists and antagonists in treating malignancies. PubMed, Science Direct, and Scopus databases were searched regarding the effect of PPARs on various types of cancers until the end of May 2023. The results of the review articles showed the therapeutic influence of PPARs on a wide range of cancer on in vitro, in vivo and clinical studies. However, further experimental and clinical studies are needed to be conducted on the influence of PPARs on various cancers.

Effects of Crocus sativus and its constituent, safranal, and pioglitazone, on systemic inflammation and oxidative stress induced by paraquat aerosol in rats.

Objectives: The effects of Crocus sativus, safranal, and pioglitazone on aerosolized paraquat (PQ)-induced systemic changes were examined. Materials and Methods: Control (Ctrl) and PQ groups of rats were exposed to saline or PQ (27 and 54 mg/m3, PQ-L and PQ-H) aerosols eight times on alternate days. Nine PQ-H groups were treated with dexamethasone (0.03 mg/kg/day, Dexa), two doses of C. sativus extract (20 and 80 mg/kg/day, CS-L and CS-H), safranal (0.8 and 3.2 mg/kg/day, Saf-L and Saf-H), pioglitazone (5 and 10 mg/kg/day, Pio-L and Pio-H), and the combination of low dose of the pioglitazone and extract or safranal (Pio + CS and Pio + Saf) after the end of PQ exposure. Results: Interferon-gamma (INF-γ), interleukin 10 (IL-10), superoxide dismutase (SOD), catalase (CAT), and thiol serum levels were reduced, but tumor necrosis factor (TNF-α), malondialdehyde (MDA), and total and differential WBC were increased in both PQ groups (P<0.05 to P<0.001). All measured variables were improved in all treated groups (P<0.05 to P<0.001). The effects of high dose of C. sativus and safranal on measured parameters were higher than dexamethasone (P<0.05 to P<0.001). The effects of Pio + CS and Pio + Saf treatment on most variables were significantly higher than three agents alone (P<0.05 to P<0.001). Conclusion: C. sativus and safranal improved inhaled PQ-induced systemic inflammation and oxidative stress similar to those of dexamethasone and showed synergic effects with pioglitazone suggesting the possible PPARγ receptor-mediated effects of the plant and its constituent.

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.

Paraquat-induced systemic inflammation and oxidative stress in rats improved by Curcuma longa ethanolic extract, curcumin and a PPAR agonist.

The effect of Curcuma longa (Cl) ethanolic extract, nano-curcumin (Cu) and a PPARγ activator, pioglitazone on inhaled paraquat (PQ)-induced systemic inflammation and oxidative stress was examined in the present study. Control rats were exposed to normal saline and PQ groups to 27 and 54 mg/m3 (PQ-L and PQ-H) aerosols. Nine other PQ-H groups were treated with Curcuma longa (Cl, 150 and 600 mg/kg/day), nano-curcumin (Cu, 2 and 8 mg/kg/day), pioglitazone (Pio, 5 and 10 mg/kg), low dose of Pio + Cl and Cu and dexamethasone (0.03 mg/kg/day) for 16 days after PQ exposure period (n = 8). Total and differential WBC counts, malondialdehyde (MDA) and TNF-α levels were increased but thiol, catalase (CAT), superoxide dismutase (SOD), IL-10 and IFN-γ levels were decreased in the blood in the both PQ groups (p < 0.05 to p < 0.001). Treatment with Dexa and both doses of Cl, Cu, and Pio improved all measured variables compared to the PQ-H group (p < 0.05 to p < 0.001). The improvements of most variables in the treated group with low dose of Pio + Cl and Cu were higher than the effects of three agents alone. Systemic inflammation and oxidative stress induced by inhaled PQ were improved by Cl, Cu and Pio. In addition, a synergic effect between Pio with those of Cl and Cu was shown, suggesting PPARγ mediated effects of the plant and its derivative Cu.

Comparative effects of Curcuma longa and curcumin on paraquat-induced systemic and lung oxidative stress and inflammation in rats.

Objective: Comparative effect of Curcuma longa (C. longa) ethanolic extract and curcumin on paraquat (PQ)-induced systemic and lung oxidative stress and inflammation were evaluated in the present study. Materials and Methods: Control animals were exposed to normal saline and PQ group to 54 mg/m3 PQ aerosols (8 times, each time for 30 min). Treatment groups were exposed to PQ and treated with 150 and 600 mg/kg/day C. longa, or 30 and 120 mg/kg/day curcumin after PQ exposure period for 16 days. Total and differential white blood cells (WBC) and oxidative markers were measured both in bronchoalveolar lavage (BALF) and blood at the end of the study. Results: Total and differential WBC counts as well as malondialdehyde (MDA) level were significantly increased but total thiol content and the activities of catalase (CAT) and superoxide dismutase (SOD) were reduced in both the BALF and blood of the PQ group in comparison with the control group (p<0.05 to p<0.001). Both doses of C. longa and curcumin diminished MDA level, total and differential WBC counts in the blood and BALF but increased CAT and SOD activities in both of them compared to PQ group (p<0.05 to p<0.001). The effects of C. longa and curcumin high dose on most variables were markedly more than low dose (p<0.05 to p<0.001). Furthermore, the effects of curcumin on some variables were markedly more than C. longa (p<0.05 to p<0.001). Conclusion: Both C. longa and curcumin improved PQ-induced systemic and lung inflammation and oxidative stress, but the effect of curcumin was more prominent.

The effect of 3-year parental smoking on asthma status of their children.

OBJECTIVE: Whilst the prevalence and severity of asthma influenced by environmental factors, the effect of parental smoking on asthma status of their children was examined. PATIENTS AND METHODS: Ninety asthmatic children, 32 with smoker and 58 with non-smoker parents (baseline age, 8.5 ± 3.5 and 8.2 ± 3.3 respectively) were studies in two sessions 3 years apart by evaluating respiratory symptoms (RS) prevalence and severity, various drugs used, and pulmonary function tests (PFT) including forced vital capacity; forced volume in the first second, peak expiratory flow; and maximum expiratory low at 75, 50 and 25% of vital capacity (FVC, FEV1, PEF, MEF75, MEF50 and MEF25, respectively). RESULTS: The prevalence and severity of all RS were significantly increased in asthmatic children with smoking parents after 3 years except prevalence and severity of night wheeze and the prevalence of chest wheeze (p < 0.05 to p < 0.001), but the PFT values were non-significantly reduced. In asthmatic children with non-smoking parents, the prevalence and severity of RS were decreased after 3 years, which was significant for night and chest wheeze for prevalence and night cough and chest wheeze for severity (all, p < 0.05), and the PFT values were increased, which were statistically significant for FVC, FEV1, MEF50 and MEF25 (p < 0.05 to p < 0.01). Drugs used by the group with smoking parents were increased and were significantly higher than their reduction in the groups with non-smoking parents at the end of the study (p < 0.05 for fluticasone propionate 125/salmeterol and budesonide160/formoterol). CONCLUSION: Long-term parental smoking increased prevalence and severity of RS and drug used but decreased PFT values of their asthmatic children.

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.

Intraperitoneal Lavage with Crocus sativus Prevents Postoperative-Induced Peritoneal Adhesion in a Rat Model: Evidence from Animal and Cellular Studies.

Postoperative peritoneal adhesions are considered the major complication following abdominal surgeries. The primary clinical complications of peritoneal adhesion are intestinal obstruction, infertility, pelvic pain, and postoperative mortality. In this study, regarding the anti-inflammatory and antioxidant activities of Crocus sativus, we aimed to evaluate the effects of Crocus sativus on the prevention of postsurgical-induced peritoneal adhesion. Male Wistar-Albino rats were used to investigate the preventive effects of C. sativus extract (0.5%, 0.25% and 0.125% w/v) against postsurgical-induced peritoneal adhesion compared to pirfenidone (PFD, 7.5% w/v). We also investigated the protective effects of PFD (100 µg/ml) and C. sativus extract (100, 200, and 400 µg/ml) in TGF-ß1-induced fibrotic macrophage polarization. The levels of cell proliferation and oxidative, antioxidative, inflammatory and anti-inflammatory, fibrosis, and angiogenesis biomarkers were evaluated both in vivo and in vitro models. C. sativus extract ameliorates postoperational-induced peritoneal adhesion development by attenuating oxidative stress [malondialdehyde (MDA)]; inflammatory mediators [interleukin- (IL-) 6, tumour necrosis factor- (TNF-) α, and prostaglandin E2 (PGE2)]; fibrosis [transforming growth factor- (TGF-) ß1, IL-4, and plasminogen activator inhibitor (PAI)]; and angiogenesis [vascular endothelial growth factor (VEGF)] markers, while propagating antioxidant [glutathione (GSH)], anti-inflammatory (IL-10), and fibrinolytic [tissue plasminogen activator (tPA)] markers and tPA/PAI ratio. In a cellular model, we revealed that the extract, without any toxicity, regulated the levels of cell proliferation and inflammatory (TNF-α), angiogenesis (VEGF), anti-inflammatory (IL-10), M1 [inducible nitric oxide synthase (iNOS)] and M2 [arginase-1 (Arg 1)] biomarkers, and iNOS/Arg-1 ratio towards antifibrotic M1 phenotype of macrophage, in a concentration-dependent manner. Taken together, the current study indicated that C. sativus reduces peritoneal adhesion formation by modulating the macrophage polarization from M2 towards M1 cells.

Systemic inflammation and oxidative stress induced by inhaled paraquat in rat improved by carvacrol, possible role of PPARγ receptors.

Control rats were exposed to saline aerosol, two groups were exposed to paraquat (PQ), 27 (PQ-L) and 54 (PQ-H) mg/m3 aerosols and six groups were treated with carvacrol, 20 (C-L) and 80 (C-H) mg/kg/day, pioglitazone, 5 (Pio-L) and 10 (Pio-H) mg/kg/day, C-L+Pio-L and dexamethasone, 0.03 mg/kg/day, for 16 days after the end of exposure to PQ-H. Different variables were measured after the end of treatment period. Total and differential white blood cells counts, nitrite, malondialdehyde, interleukin (IL)-10, and interferon-gamma levels were significant increased, but thiol, superoxide dismutase, catalase, IL-17, and tumor necrosis factor alpha were decreased in the blood due to both doses of PQ (p < 0.05-p < 0.001). Most measured parameters were significantly improved in treated groups with both doses of carvacrol, pioglitazone, the combination of C-L+Pio-L and dexamethasone compared to PQ-H group (p < 0.05-p < 0.001). Treatment with C-L+Pio-L showed significantly higher effects compared to each one alone (p < 0.05-p < 0.001). Systemic oxidative stress and inflammation due to inhaled PQ were improved by carvacrol and pioglitazone. Higher effects of C-L+Pio-L than each one alone suggests carvacrol modulating PPAR-γ receptors.

Zataria multiflora and Pioglitazone Affect Systemic Inflammation and Oxidative Stress Induced by Inhaled Paraquat in Rats.

The effects of Zataria multiflora (Z. multiflora) and pioglitazone (a PPAR-γ agonist) alone and in combination, on systemic inflammation and oxidative stress induced by inhaled paraquat (PQ) as a herbicide, which induced inflammation in rats, were examined. Rats were exposed to (1) saline (control) and (2) 54 mg/m3 PQ aerosols (8 times, every other day, each time for 30 min) without treatment or treated with (3 and 4) two doses of Z. multiflora (200 and 800 mg/kg/day), (5 and 6) two doses of pioglitazone (5 and 10 mg/kg/day), (7) low doses of Z.multiflora + pioglitazone, (Pio-5+Z-200 mg/kg/day) or (8) dexamethasone (0.03 mg/kg/day) for 16 days, after the last PQ exposure. Different variables were measured at the end of the treatment period. Exposure to PQ significantly increased total and differential white blood cells (WBC) counts, serum levels of nitrite (NO2), malondialdehyde (MDA), interleukin- (IL) 17, and tumor necrosis factor alpha (TNF-α), but reduced thiol, superoxide dismutase (SOD), catalase (CAT), IL-10, and interferon-gamma (INF-γ) (p < 0.05 to p < 0.001). Most measured parameters were significantly improved in groups treated with either doses of the extract, pioglitazone, Pio-5+Z-200 mg/kg/day, or dexamethasone compared to the PQ group (p < 0.05 to p < 0.001). The combination of low doses of Pio-5+Z-200 mg/kg/day showed significantly higher effects compared to each one alone (p < 0.05 to p < 0.001). Systemic oxidative stress and inflammation due to inhaled PQ were improved by Z. multiflora and pioglitazone. Higher effects of Pio-5+Z-200 mg/kg/day compared to each one alone suggest modulation of PPAR-γ receptors by the plant extract, but further studies using PPAR-γ antagonists need to be done in this regard.

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.

Carvacrol and PPARγ agonist, pioglitazone, affects inhaled paraquat-induced lung injury in rats.

Exposed rats to normal saline and paraquat (PQ) aerosol as control and PQ group, rats exposed to PQ and treated with 20 and 80 mg/kg/day carvacrol, 5 and 10 mg/kg/day pioglitazone, low dose of pioglitazone + carvacrol and 0.03 mg/kg/day dexamethasone (Dexa) for 16 days after the end of PQ exposure were studied (n = 6 in each group). Lung pathological changes, tracheal responsiveness to methacholine and ovalbumin (OVA) as well as transforming growth factor beta (TGF-ß) and interleukin (IL)-6 level in the lung tissue homogenize as well as TGF-ß, IL-6, oxidant and antioxidant levels oxidant and antioxidants were increased in PQ group (p < 0.01 to p < 0.001). Lung pathological changes, tracheal responsiveness to methacholine and OVA as well as TGF-ß, IL-6 oxidant and antioxidant levels were improved in all treated groups except lung pathological changes in treated group with low dose of pioglitazone (p < 0.05 to p < 0.001). The effects of low dose of pioglitazone and carvacrol alone were significantly lower than in the combination group of low dose of pioglitazone + carvacrol (p < 0.05 to p < 0.001). Carvacrol treatment improved inhaled PQ-induced lug injury similar to the effects of dexamethasone. The synergic effect of carvacrol and pioglitazone suggests PPAR-γ receptor mediated effects of carvacrol on inhaled PQ-induced lung injury.

Immediate and late systemic and lung effects of inhaled paraquat in rats.

The immediate and the late effects of inhaled Paraquat (PQ) on systemic and lung inflammation and oxidative stress were investigated. Rats were exposed to saline (control group) and two doses of inhaled PQ (27 and 54 mg/m3) and studied variables were measured: 1) one day after the end of PQ exposure as "immediate condition", 2) 16 days after the end of PQ exposure as "late condition". Total and differential white blood cells (WBC) counts, lipid peroxidation and nitrite were increased but thiol, superoxide dismutase and catalase in the blood and BALF as well as methacholine EC50 was reduced in both conditions in the animals exposed to PQ compared to control groups (p < 0. 05 to p < 0.001). Most studied parameters in the immediate condition were significantly higher than the late condition (p < 0.05 to p < 0.001). Systemic and lung inflammation and oxidative stress due to inhaled PQ in both the immediate and the late conditions were shown. Although most measured parameters in the immediate condition were higher, all variables were significantly different with the control group even in late condition, indicating a long-term effect of inhaled PQ toxicity, which may help in a more effective treatment of PQ poising in the future.

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.