Trehalose and N-Acetyl Cysteine Alleviate Inflammatory Cytokine Production and Oxidative Stress in LPS-Stimulated Human Peripheral Blood Mononuclear Cells.

BACKGROUND: Evidence has shown that inflammation and oxidative stress are implicated in the development of a great number of human diseases. Trehalose possesses various biological effects including antioxidant and anti-inflammatory activities. However, there is little data on the effects of trehalose on human cells including peripheral blood mononuclear cells (PBMCs). Here, we aimed to investigate whether trehalose could attenuate oxidative stress and inflammation induced by lipopolysaccharides (LPS) in PBMCs. METHODS: The enzyme-linked immunosorbent assay (ELISA) and RT-PCR were used to assess the levels of inflammatory cytokines. To investigate the phosphorylation of c-Jun N-terminal kinase (JNK) and NF-κB, western blot analysis was utilized. Oxidant-antioxidant markers were assessed using ELISA and colorimetric procedures. RESULTS: The results revealed that trehalose significantly mitigated the effect of LPS on the phosphorylation of JNK and NF-κB-P65 (p < .00). This mitigation was associated with significantly reduced levels of inflammatory cytokines IL-6, TNF-α, and IL-1ß and increased levels of anti-inflammatory cytokine IL-10 (P < .05). The antioxidant N-acetyl cysteine (NAC) also showed similar effects on JNK and NF-κB-P65 phosphorylation and inflammatory cytokines (p < .00). Furthermore, trehalose alleviated oxidative stress in LPS-stimulated PBMCs as it reversed the altered levels of malondialdehyde and total thiols (p ≤ .05) and restored the activity of antioxidant enzymes glutathione peroxidase and manganese superoxide dismutase (p < .001). CONCLUSION: The results of this study indicated that trehalose prevented inflammation and oxidative stress in the LPS-stimulated PBMCs, providing evidence for the benefits of trehalose as a potential therapeutic agent in inflammatory conditions. ABBREVIATIONS: LPS: Lipopolysaccharide; NAC: N-Acetyl cysteine; ROS: Reactive oxygen species; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; SOD: Superoxide dismutase; GPx: Glutathione peroxidase; MDA: Malondialdehyde; MAPK: Mitogen-activated protein kinases; JNK: c-Jun N-terminal kinase; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells.

Circulating mRNA and plasma levels of osteoprotegerin and receptor activator of NF-κB ligand in nonalcoholic fatty liver disease.

Pathogenesis of the beginning and progression of nonalcoholic fatty liver disease (NAFLD) has not been clarified exactly. The osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis seems to play an imperative function in the onset and progression of this disease. The goal of the present study was to investigate the peripheral blood mononuclear cell (PBMC) expression and plasma levels of RANKL and OPG cytokines in NAFLD patients and compare them with healthy group. Plasma levels of OPG and RANKL were determined with ELISA kits in 57 men with NAFLD and 25 healthy men as controls. Biochemical and anthropometric parameters tests were also evaluated in the study groups. RANKL and OPG mRNA contents were evaluated by quantitative RT-PCR. OPG contents were markedly decreased in NAFLD patients as compared with healthy patients [1.43 (1.05-5.45)] versus [2.94 (1.76-4.73)] ng/mL; P = 0.007). The levels of RANKL were significantly reduced in NAFLD patients [74.00 (56.26-203.52) ng/mL] than in healthy patients [119.37 (83.71-150.13) ng/mL]; (P = 0.03). Also, OPG and RANKL gene expression were significantly decreased in NAFLD patients in comparison with the control group (P < 0.05). Moreover, receiver operating characteristic curve indicated that OPG may have a good capability to discriminate between NAFLD patients and normal individuals. A positive correlation was observed between OPG and RANKL in plasma sample (r = 0.495) (P = 0.000). Decreased plasma levels and gene expression of RANKL and OPG cytokines in NAFLD patients indicate that there is a relationship between these cytokines and the pathology of NAFLD disease. Confirmation of this association as well as the mechanism and role of these cytokines in NAFLD require further studies.

Effect of garlic intake on inflammatory mediators: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Garlic is a species in the onion genus, Allium. Data have shown that garlic has anti-inflammatory activity; however, the findings are inconclusive and inconsistent. We aimed to evaluate the impact of garlic intake on inflammatory mediators through systematic review and meta-analysis of existing data. METHODS: Electronic databases were completely investigated using databases of ISI Web of Science, Medline, Scopus, Cochrane Library and EMBASE until October 2019. A random effects model and the generic reverse variance procedure were used for quantitative data production. Sensitivity analyses and prespecified subgroup were done to evaluate potential heterogeneity. Random effect meta-regression was conducted to investigate the effects of possible confounders on the assessed effect size. RESULTS: Ten trials with one observational study, including 530 participants, met the eligibility criteria. The findings showed reduction in the tumour necrosis factor alpha (TNF-α) (-0.31 pg/mL, 95% CI -1.07 to 0.46) and C reactive protein (CRP) levels (-0.20 mg/L, 95% CI -1.4 to 1.05) following supplementation with garlic, although it had no marked impact on the interleukin 6 (IL-6) level (0.37 pg/mL, 95% CI -0.58 to 1.33). In the subgroup analysis, we found that garlic supplementation significantly decreased TNF-α, highly sensitive CRP and IL-6 levels in subgroups of >8, >6 and ≥4 weeks of intervention duration, respectively, and dose of garlic consumption between 2 and 2.4 g/day. CONCLUSION: These findings suggested that current evidence may support garlic as an adjunct to pharmacological management of metabolic diseases. PROSPERO REGISTRATION NUMBER: CRD42018108816.

The effects of rosmarinic acid on oxidative stress parameters and inflammatory cytokines in lipopolysaccharide-induced peripheral blood mononuclear cells.

Rosmarinic acid (RA) is a potential herbal medicine and has received considerable attention due to its strong antioxidant properties. The aim of this study is to investigate the impact of RA on inflammation and oxidative stress induced by lipopolysaccharide (LPS) in peripheral blood mononuclear cells (PBMCs). PBMCs were pre-treated with various contents of RA (20, 40, 80 µM) for 24 h, then, stimulated with LPS (10 ng/ml) for more 6 h. ELISA and Real-time PCR were done to detect the levels of IL-6, TNF-α, COX-2, IL-1ß and IL-10. Western blot was done to investigate the phosphorylated amounts of P65-NF-κB and JNK. Inflammatory cytokines and oxidant-antioxidant parameters were determined by colorimetric and ELISA methods. The results indicated that LPS augmented the protein levels of IL-6, TNF-α, and IL-1ß cytokines as well as the mRNA levels of IL-6, TNF-α, IL-1ß, COX-2, and IL-10 cytokines in in PBMCs. However, pretreatment with RA could reduce the impact of LPS on inflammatory markers. In addition, RA inhibited P65-NF-κB and JNK phosphorylation. LPS also caused a decrease in antioxidant enzymes, total thiol, and total antioxidant capacity as well as an increment in malondialdehyde and nitric oxide metabolite contents that RA abrogated them. Collectively, our finding demonstrated that RA ameliorates LPS-induced inflammation in PBMCs. RA reduces oxidative stress by preventing lipid peroxidation and nitric oxide production as well as restarting the activity of the GPx and SOD enzymes. Furthermore, our findings indicated that RA was able to protect PBMCs from inflammation via inhibiting the NF-κB and JNK MAPK pathways. This evidence shows a promising therapeutic role for RA in inflammatory status.

Protective effect of Nasturtium officinale R. Br and quercetin against cyclophosphamide-induced hepatotoxicity in rats.

Cyclophosphamide (CPA) is used in the management of autoimmune conditions and malignant illnesses. However, its therapeutic use is limited because of its severe side effects, especially hepatotoxicity attributed to oxidative stress. Nasturtium officinale R. Br (watercress or WC) has pharmacological properties, such as anti-inflammation, and antioxidant activities. Therefore, the present study was design to assess effects of WC or its active ingredient, quercetin (QE), against CPA-induced hepatotoxicity. For this study, 49 male Wistar rats (200-250 g) were randomly selected and categorized into seven equal groups. The animals were pre- and post-treated with both hydroalcoholic extract of WC (500 mg/kg) and quercetin (75 mg/kg) for 10 consecutive days, and intraperitoneal administration of CPA (200 mg/kg) was performed on only day 10, one hour before the last dose of WC or quercetin. On day 11, all the animals were sacrificed, and their blood and liver were gathered for evaluation of the liver enzyme, hepatic oxidative stress markers, antioxidant enzymes activity, and hematoxylin and eosin staining. CPA significantly increased malondialdehyde (MDA), protein carbonyl (PCO) and nitric oxide (NO) levels and liver biomarkers. Otherwise, hepatic catalase (CAT), reduced glutathione (GSH), total thiol content (tSH), and ferric reducing antioxidant power (FRAP) were considerably lower than the control group. Results showed that WC has the ability to reduce the changes (MDA, PCO, FRAP, CAT, ALT and AST) and QE (MDA, PCO, AST) induced by CPA (p < 0.05). Histopathological finding confirmed the indicated results. These findings propose that WC and QE have protective effect against the CPA-induced hepatotoxicity by decreasing oxidative stress.

Novel osteoprotective nanocochleate formulation: A dual combination therapy-codelivery system against glucocorticoid induced osteoporosis.

Phosphatidylserine nanocochleates (Nanocochs) are novel delivery systems that may play a prominent osteoprotective role with their cargo, vitamin D3 (Vit-D3), against osteoporosis. Therefore, this study was conducted to characterize a Nanococh containing vitamin D3 (Nanococh-D3) and investigate its potential role in improving GIO in a rat model. Roll-shaped Nanococh-D3 particles were obtained in a size range of 320 nm with a sustained release performance. Oral Nanococh-D3 significantly increased the bioavailability of Vit-D3, enhanced bone mechanical strength, and improved osteogenic biomarkers including B-ALP, osteocalcin, Ca, and OPG in GIO rats. This formulation markedly suppressed gene expression of RANK and RANKL in treated rats. Histomorphometric analysis showed significant repairs in bone tissues and TRAP staining indicated a significant decrease in osteoclasts using Nanococh-D3 in osteoporotic rats. Nanococh alone similar to Nanococh-D3 acted better than AL as a standard anti-osteoporotic drug in the improvement of bone strength. In conclusion, our results established the potential role of Nanococh-D3 against osteoporosis in rats.

The hydroalcoholic extract of watercress attenuates protein oxidation, oxidative stress, and liver damage after bile duct ligation in rats.

Cholestatic liver disease is recognized by extreme collagen formation and deposition, which is mediated by free radicals. The aim of the current study was to investigate the probable hepatoprotective effects of hydroalcoholic extract of watercress (WC) against oxidative stress and liver injury in bile duct ligation (BDL)- induced cholestatic rats. A total of 32 male Wistar rats were divided into four groups; sham control (SC), BDL, SC + hydroalcoholic extract of WC and BDL + hydroalcoholic extract of WC. WC-treated rats received daily WC 500 mg/kg/day for 10 days. Biochemical tests, hepatic oxidative stress markers, and antioxidant enzymes activity were estimated. Further, liver hydroxyproline content was assayed and histological analysis was made. The BDL model markedly elevated the protein carbonyl (PCO) and hydroxyproline contents and decreased the glutathione peroxidase (GPx) activity. Hydroalcoholic extract of WC significantly decreased the surge in liver PCO and hydroxyproline levels and increased the reduced GPx enzyme activity contents in the hepatic tissue. As determined by hematoxylin and eosin staining, BDL considerably induced hepatocyte necrosis. Moreover, these changes were significantly attenuated by the hydroalcoholic extract of WC treatment. Our data indicate that the hydroalcoholic extract of WC extract attenuated liver damage in BDL rats by decreasing the hydroxyproline content and histopathological indexes. Also, it reduced oxidative stress by preventing the hepatic protein oxidation and enhancing the activity of the GPx enzyme via antioxidative effect and free-radical scavenging. Our findings suggest that hydroalcoholic extract of WC could be a beneficial new curative agent for cholestatic liver damage.

Redox imbalance and IL-17 responses in memory CD4+ T cells from patients with psoriasis.

All stages of the inflammatory process involved in T cell-mediated chronic skin disorders like psoriasis are affected by redox imbalance. On the other hand, Th17 cells have a critical role in the pathogenesis of psoriasis. In this study, we evaluated redox status in memory CD4 + T cells and plasma of patients with psoriasis and its correlation with IL-17 response. To this end, memory T cells were isolated from 10 patients with psoriasis and 10 controls. Intracellular Glutathione (GSH), reactive oxygen species (ROS) and superoxide as well as IL-17 were measured using flow cytometry. Plasma total anti-oxidant capacity (TAC) was quantified by ferric reducing ability of plasma (FRAP) assay. The expression of catalase (CAT), superoxide dismutase 1(SOD1), superoxide dismutase 2 (SOD2), nuclear factor, erythroid 2 like 2 (NFE2L2) and cytochrome b-245 beta chain (CYBB) genes were analysed using real-time PCR. Our results showed an increased intracellular ROS production in memory CD4 + T cells of patients compared to controls, (P = 0.04). Furthermore, a significant decrease in expression of catalase gene was found in patients, (P = 0.02). However, no significant differences were observed for intracellular GSH, IL-17 and TAC levels between patients and controls. Also, no correlation was seen between the intracellular IL-17 level and intracellular ROS, GSH and catalase gene expression levels. Collectively, we found an increased ROS production in stimulated memory T cells of patients that could be due to reduced expression of catalase gene. However, it seems that these redox abnormalities have no relationship with IL-17 response in memory T cells.

Melatonin and metformin co-loaded nanoliposomes efficiently attenuate liver damage induced by bile duct ligation in rats.

In the current study, the therapeutic effectiveness of the metformin (Met) and melatonin (Mel) co-loaded liposomes was investigated on cholestasis induced by bile duct ligation (BDL) in male rats. Histopathological analysis, biochemical analysis, and oxidative stress markers were assayed to determine the therapeutic effect of Met and Mel co-loaded liposomes on cholestasis. Histopathological analysis revealed that the simultaneous administration of Met and Mel, whether in the free (C-Mel-Met) or liposomal (C-Lipo-Mel-Met) forms, reduced inflammation as well as proliferation of bile ducts; however, results were more prominent in the liposomal form of Mel and Met. Additionaly, serum levels of aspartate aminotransferase (AST) were significantly (p < 0.001) higher in (C-Mel-Met) treated rats compared with (BDL) rats; however, (C-Lipo-Mel-Met) treated rats exhibited significant (p < 0.05) lower AST rates in comparison to (BDL) rats. Moreover, a significant (p < 0.0001) drop in bilirubin levels was detected in (C-Lipo-Mel-Met) treated rats in comparison to (BDL) rats; it is noteworthy mentioning that bilirubin levels in (C-Lipo-Mel-Met) treated rats were insignificant in comparison to sham-control (SC) rats. Furthermore, rats concomitantly administered Met and Mel, exhibited significant downregulation in the expression levels of inflammatory cytokine genes such as TNF-α and IL-1 gene expression, where the downregulation was more prominent in the liposomal from. Our findings demonestrate that the concomitant administration of metformin and melatonin in the liposomal form had more therapeutic effect on liver injury than their free forms through improving histological changes, reducing biochemical markers and favoring oxidant- antioxidant balance.

A comprehensive review of ethnomedicinal approaches, phytochemical analysis, and pharmacological potential of Vitex trifolia L.

Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense potential in preventing and treating chronic diseases. Vitex trifolia L. (V. trifolia), a shrub with a rich history in traditional medicine, particularly in Eastern Asia, has garnered attention for its diverse therapeutic applications. This comprehensive review aims to bridge traditional knowledge and contemporary insights by investigating ethnopharmacology, phytochemistry, and pharmacological effects of V. trifolia. The keyword "V. trifolia" and its synonyms were searched within the main scientific databases including PubMed, Web of Science, ScienceDirect, Google Scholar, and Baidu Scholar (from 1974 to 2022, last search: 21.10.2023). Phytochemical analyses reveal a spectrum of secondary metabolites in V. trifolia, including terpenoids, flavonoids, lignans, phytosterols, anthraquinones, and fatty acids. Notably, terpenoids and flavonoids emerge as the main bioactive metabolites. Pharmacological studies validate its therapeutic potential, demonstrating significant antioxidant, anti-inflammatory, hepatoprotective, anticancer, anti-amnesic, antimicrobial, antiviral, anti-malaria, antispasmodic activities, and reported insecticidal effects. Despite existing literature exploring pharmacological attributes and secondary metabolites of related species, a conspicuous gap exists, specifically focusing on the pharmacological activities and novel methods of purification of pure metabolites from V. trifolia. This review aimed to fill this gap by delving into traditional medicinal applications, exploring secondary metabolites comprehensively, and providing an in-depth analysis of pharmacological effects of pure metabolites. Combining traditional uses with contemporary pharmacological insights, this article sought to serve as a crucial reference for future research and practical application of V. trifolia. This approach contributes substantially to understanding the plant, fostering scientific inquiry, and facilitating its broader application in healthcare.

Antioxidant and hepatoprotective activities of Juniperus excelsa M. Bieb against bile duct ligation-induced cholestasis.

Background and purpose: Cholestasis is caused by a malfunction of the biliary liver system. Oxidative stress plays an essential role in the progression of cholestasis. This study aimed to investigate the antioxidant and hepatoprotective effects of ethanolic extract of Juniperus excelsa M. Bieb (JE) fruits on hepatic impairment induced by bile duct ligation (BDL) in rats. Experimental approach: Forty male Wistar rats were randomly divided into 4 groups; sham control + vehicle (SC), BDL + vehicle (BDL), BDL + JE extract (BDL + JE), and SC + extract (SC + JE). One day after surgery, the animals were treated with vehicle or ethanolic extract of JE (500 mg/kg/day) for 7 days. Finally, the blood was taken for biochemical and oxidative stress analysis. Furthermore, the liver tissue of rats was removed for histological examination. Findings/Results: Treatment with the extract of JE decreased the ALP level, whereas it enhanced total protein content compared to the BDL group. Also, JE increased the activity of SOD and GPx, as well as FRAP content compared to the BDL group; while it did not significantly affect the levels of MDA and inflammation markers. However, JE could not improve BDL-induced histopathological alterations in hepatic tissue. Conclusion and implication: This study demonstrated that JE may be useful as an adjuvant therapy by attenuating ALP activity, increasing serum total protein and FRAP content, as well as improving the antioxidant enzymes activity of SOD and GPx. However, further research is warranted to explore the other underlying mechanisms of action.

Effect of metformin on the long non-coding RNA expression levels in type 2 diabetes: an in vitro and clinical trial study.

BACKGROUND: It has been suggested that the anti-hyperglycemic effect of metformin could be associated with its impact on long non-coding RNA (lncRNA) expression levels. Accordingly, in the current study, we evaluated the effect of metformin on the expression of H19, MEG3, MALAT1, and GAS5 in in vitro and in vivo situations. METHODS: The effect of hyperglycemia and metformin treatment on the lncRNAs expression level was evaluated in HepG2 cells. A total of 179 age- and sex-matched subjects, including 88 newly diagnosed patients with type 2 diabetes (T2D) and 91 healthy volunteers, were included in the case-control phase of the study. Moreover, 40 newly diagnosed patients participated in the study's open-labeled non-controlled clinical trial phase. The expression levels of lncRNA in HepG2 cells and whole blood samples were determined using QRT-PCR. RESULTS: In vitro results showed that hyperglycemia induced H19 and MALAT1 and decreased GAS5 expression levels. Moreover, metformin decreased H19 and increased GAS5 expression in high glucose-treated cells. Case-control study findings revealed that the circulating levels of H19, MALAT1, and MEG3 were significantly elevated in T2D patients compared to the control subjects. Finally, results showed that the level of circulating H19 levels decreased while GAS5 increased in T2D patients after taking metformin for 2 months. CONCLUSION: The results of the current study provided evidence that metformin could exert its effect in the treatment of T2D by altering the expression levels of H19 and GAS5.

Renoprotective effects of zinc sulfate against transient liver ischemia/reperfusion injury in rats.

Objectives: Liver ischemia/reperfusion damage frequently occurs in setting of hepatic resection and liver transplantation. It leads to disturbance in remote organs such as heart, lung and kidneys. This study explored the consequences of hepatic ischemia/reperfusion on the oxidative stress parameters, biochemical factors, and histopathological alterations in the kidney's rats, as well as evaluated the role of zinc sulfate on above-mentioned parameters. Materials and methods: Twenty-eight male Wistar rats were accidently assigned into four groups (n = 7). They were Sham, ischemia/reperfusion, zinc sulfate pretreatment, and zinc sulfate pretreatment + ischemia/reperfusion groups. Sham group: obtained normal saline (2 ml/day, seven consecutive days), intraperitoneally, zinc sulfate pretreatment group: obtained zinc sulfate (5 mg/kg, seven consecutive days, intraperitoneally). Ischemia/reperfusion group: obtained normal saline as mentioned previous, then rats experienced the partial ischemia (%70) for 45 min followed by 60 min reperfusion. Zinc sulfate pretreatment group: obtained zinc sulfate as mentioned previous, then rats experience the partial ischemia/reperfusion as presented earlier. At the end of investigation, blood was withdrawn, liver and renal tissues were removed. Then, biochemical and oxidative stress parameters, and histological changes were evaluated in the mentioned tissues. Results: The findings of this experiment indicated that zinc sulfate markedly reduced the serum levels of liver and kidney function tests in relative to ischemia/reperfusion group. Also, antioxidant enzymes activity, ferric reducing antioxidant power, and nitric oxide significantly increased, while malondialdehyde level declined in the renal tissue of zinc sulfate + ischemia/reperfusion group compared to ischemia/reperfusion rats. Furthermore, zinc sulfate alleviated the liver and kidneys histopathological alterations following ischemia/reperfusion. Conclusion: Zinc sulfate ameliorated liver and kidney function, and improved oxidant-antioxidant balance in favor of antioxidants. It is suggested that zinc sulfate may be beneficial effects on hepato-renal injury after ischemia/reperfusion.

In vitro and Molecular Docking Analysis of Quercetin as an Anti-inflammatory and Antioxidant.

INTRODUCTION: Quercetin (3,3',4',5,7-pentahydroxyflavone) is a dietary flavonoid with good antioxidant and anti-inflammatory properties. AIMS: The present study aims to determine these effects in peripheral blood mononuclear cells (PBMCs) evoked by lipopolysaccharides (LPS). METHODS: The mRNA expression and protein secretion of inflammatory mediators were evaluated by enzyme- linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR), respectively. Western blotting was utilized for assessing p65-NF-κB phosphorylation. Ransod kits evaluated the glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in the cell lysates. Ultimately, the molecular docking approach was performed to investigate the biological activity of Quercetin against NF-κB pathway proteins and antioxidant enzymes. RESULTS: The findings revealed that quercetin significantly attenuated the expression and secretion of inflammatory mediators and p65-NF-κB phosphorylation in LPS-induced PBMCs. Additionally, quercetin dose-dependently improved the activities of SOD and GPx enzymes and decreased LPS-mediated oxidative stress in PBMCs. Moreover, quercetin has a considerable binding affinity to IκKb, the core element of the NF-κB pathway and the antioxidant enzyme SOD. CONCLUSION: The data show that quercetin plays a vital role in ameliorating inflammation and oxidative stress caused by LPS in PBMCs.

The Alleviating Impacts of Quercetin on Inflammation and Oxidant-antioxidant Imbalance in Rats with Allergic Asthma.

Asthma is an inflammatory disease of the airways. We assessed the anti-inflammatory and antioxidative impacts of quercetin, a plant derivative, on inflammatory and oxidative indices in lung tissue and serum of rats with asthma.Asth ma was induced by ovalbumin. Rats were divided into 4 groups: control, asthma+vehicle (Receieved normal saline), asthma+dexamethasone, and asthma+quercetin. After asthma induction, quercetin (50 mg/kg) and dexamethasone (2.5 mg/kg) were injected intraperitoneally once daily for 1 week. On day 50, lung histopathology indices; inflammatory factors; tissue gene expression, including GATA Binding Protein 3 (Gata-3), Tbx21 (T-bet), Transforming growth factor-ß (TGF-ß), Il10 (IL-10), Il1b (IL-1ß), Il6 (IL-6), Acta2 (α-SMA), and Tnf (TNF-α); and oxidative stress indices (malondialdehyde [MDA], catalase [CAT], glutathione peroxidase [GPX], superoxide dismutase [SOD], and total antioxidant capacity [TAC]) in tissue and serum, were evaluated. The results showed that quercetin reduced Gata3, Tnf, Tgfb1, Il1b, and Acta2 gene expression and increased Tbx21 gene expression following asthma. Quercetin also improved oxidative stress by decreasing MDA levels and increasing TAC, CAT, SOD, and GPX levels in serum and lung tissue. Furthermore, quercetin decreased IL6 and TNFα levels and increased IL10 levels in lung tissue after asthma was treated with quercetin. Quercetin ameliorates oxidative stress and inflammation caused by asthma, especially at the tissue level. Therefore, quercetin can be considered a potent antiasthmatic agent.

Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo.

Breast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study aimed to examine the suppressive effect of A.m alone and combined with docetaxel (DTX) on the breast cancer growth in mice models and the possible underlying mechanisms. In the present study, the mice were inoculated subcutaneously with the injections of 4T1 cells. Then, A.m, DTX, and their combination were administered intraperitoneally. The expressions of ß-catenin (ß-cat), FZD7, MMP2, HIF1-α, and VEGF A (vascular endothelial growth factor A) were investigated using RT-PCR method. Also, plasma alkaline phosphatase (ALP), alanine aminotransferase (GPT or ALT), aspartate transaminase (GOT or AST), serum creatinine, and urea were examined, and histological analyses of the tissues were conducted. The results demonstrated that A.m (500 mg/kg) combined with DTX significantly decreased the expression of ß-cat, MMP2, and FZD7 as compared with the negative control group and monotherapies. Also, the mRNA levels of HIF1-α and VEGF A were suppressed significantly by DTX + A.m (500 mg/kg). Tumor weights and sizes were significantly lower and tumor inhibition rate was significantly higher in the DTX + A.m group. The A.m 500 mg/kg + DTX also suppressed the serum GPT level in tumor-bearing mice and decreased the serum urea level. Taken together, our findings suggest that DTX combined with A.m at an optimal dose of 500 mg/kg as the optimal dose can inhibit ß-cat, FZD7, MMP2, and breast cancer growth via interrupting HIF-1α/VEGF signaling and might be used as a promising antiangiogenic agent for breast cancer treatment.

Melatonin-Attenuated Oxidative Stress in High-Risk Pregnant Women Receiving Enoxaparin and Aspirin.

Objective: In pregnancy, reducing inflammation and oxidative stress is important. Administration of melatonin during pregnancy can improve reproductive performance by improving the placental antioxidant system and inflammatory response. This investigation was carried out to evaluate the beneficial impact of melatonin on the oxidative stress state among high-risk pregnant women receiving enoxaparin and aspirin. Methods: In this double-blind, placebo-controlled trial, 40 pregnant women, aged 15-45 years at 6 weeks of pregnancy, were randomly selected and divided into intervention and control groups. The control group received prophylaxis enoxaparin and aspirin once daily between 6 and 16 weeks of pregnancy. The intervention group was taken enoxaparin and aspirin for 9 weeks and melatonin once daily from the sixth week of pregnancy to delivery time. Blood samples were taken to measure some oxidative stress biomarkers including total antioxidant capacity (TAC), malondialdehyde (MDA), total thiol (T-SH), protein carbonyl (PCO), and nitric oxide (NO). The level of high-sensitivity C-reactive protein (hs-CRP) was also determined. Results: TAC and T-SH levels increased significantly in the intervention group in comparison with the control group. Melatonin administration compared to the control group led to a significantly decreased level of NO and an insignificant hs-CRP level. Conclusion: Melatonin supplementation in high-risk pregnancy had favorable effects on TAC, T-SH, NO, and hs-CRP levels, improved antioxidant activity, and reduced inflammation. More studies are needed in different pregnancy conditions along with the measurement of different biomarkers.

Evaluation of the Antioxidant and Anticancer Activities of Hydroalcoholic Extracts of Thymus daenensis Celak and Stachys pilifera Benth.

Herein, the effects of hydroalcoholic extracts of Thymus daenensis Celak (TDC) and Stachys pilifera Benth (SPB) plants on HepG2 cell line were investigated by using different analyses. Cytotoxicity and apoptosis of extracts were investigated by MTT method, AnnV/PI apoptosis assay, and their antioxidant capacity was evaluated by total thiol and glutathione peroxidase (GPX) assay. The results revealed that the SBP extract was more cytotoxic compared with the TDC extract and increased over time (128.49 µg/mL vs 107.11 µg/mL IC50 values for 24 and 72 h, respectively). Although, AnnV/PI apoptosis assay showed apoptosis induction for both extracts, but the caspase-3 activity assay revealed that TDC extract significantly increased caspase-3 activity compared with the control and SPB extract. Increasing the activity of GPX by SPB extract revealed that it has high antioxidant capacity. In conclusion, the TDC and SPB with high antioxidant capacity have high cytotoxicity against HepG2 cancer cells and have high capability as a medicinal plant.

Stachys pilifera Benth: A Review of Its Botany, Phytochemistry, Therapeutic Potential, and Toxicology.

Background: Stachys L. (Lamiaceae) includes more than 300 annual or perennial species growing in temperate regions of Southern Africa, the Mediterranean, America, and Asia. Stachys pilifera Benth (S. pilifera), also known as Marzeh Kuhi, is an endemic species from Iran. It is found in the mountainous habitats of the Zagros area. It has various traditional uses, and the phytochemical ingredients and some biological activities of this species have been examined in previous studies. Methods: PubMed, Science Direct, Google Scholar, Scopus, and Science Web databases were used to gather the data. The purpose of this review is to consolidate the scattered knowledge reported in the literature about botany, traditional uses, phytochemistry, pharmacological properties, and safety of S. pilifera and suggest its potential medicinal properties. Key Findings. In traditional Iranian medicine, S. pilifera manages various illnesses, such as rheumatoid arthritis, common cold, infections, asthma, and tussive. More than 30 compounds have been identified in S. pilifera essential oil. The compounds found in S. pilifera are phenolic compounds, monoterpenes, sesquiterpenes, flavonoids, alkaloids, and terpenoids, which have various properties such as antioxidant, nephroprotective, anti-inflammatory, antimicrobial, hepatoprotective, and anticancer properties. Conclusions: The literature reveals that S. pilifera is an essential source of bioactive phytochemicals and illustrates the unknown area of this plant for new investigations. Moreover, we recommend that future research focus on toxicology and quality control studies for S. pilifera to fill the knowledge gap and provide theoretical support for the plant's possible functional and clinical uses.

The Promising Therapeutic and Preventive Properties of Anthocyanidins/Anthocyanins on Prostate Cancer.

As water-soluble flavonoid derivatives, anthocyanidins and anthocyanins are the plants pigments mostly rich in berries, pomegranate, grapes, and dark color fruits. Many bioactivity properties of these advantageous phytochemicals have been reported; among them, their significant abilities in the suppression of tumor cells are of the promising therapeutic features, which have recently attracted great attention. The prostate malignancy, is considered the 2nd fatal and the most distributed cancer type in men worldwide. The present study was designated to gather the preclinical and clinical studies evaluating potencies of anthocyanidins/anthocyanins for the treatment and prevention of this cancer type for the first time. In general, findings confirm that the anthocyanins (especifically cyanidin-3-O-glucoside) indicated higher activity against prostatic neoplasms compared to their correlated anthocyanidins (e.g., delphinidin); in which potent anti-inflammatory, apoptosis, and anti-proliferative activities were analyzed. Complementary anti-prostate cancer assessment of diverse naturally occurred anthocyanidins/anthocyanins and their synthetically optimized derivatives through preclinical experiments and eventually confirmed by clinical trials can promisingly lead to discover natural-based chemotherapeutic drug options.