PMID: 

Life Sci. 2019 Sep 1 ;232:116662. Epub 2019 Jul 16. PMID: 31323271

Abstract Title: 

Astragaloside IV protects against hyperglycemia-induced vascular endothelial dysfunction by inhibiting oxidative stress and Calpain-1 activation.

Abstract: 

AIMS: Vascular endothelial cells act as a selective barrier between circulating blood and vessel wall and play an important role in the occurrence and development of cardiovascular diseases. Astragaloside IV (As-IV) has a protective effect on vascular endothelial cells, but its underlying mechanism remains unclear. This study is aimed at investigating the effect of As-IV on endothelial dysfunction (ED).METHODS: Male Sprague-Dawley (SD) were injected intraperitoneally with 65 mg/kg streptozotocin (STZ) to induce diabetes and then administered orally with As-IV (40, 80 mg/kg) for 8 weeks. Vascular function was evaluated by vascular reactivity in vivo and in vitro. The expression of calpain-1 and eNOS in the aorta of diabetic rats was examined by western blot. NO production was measured using nitrate reductase method. Oxidative stress was determined by measuring SOD, GSH-px and ROS.RESULTS: Our results showed that As-IV administration significantly improved diabetes associated ED in vivo, and both NAC (an antioxidant) and MDL-28170 (calpain-1 inhibitor) significantly attenuated hyperglycemia-induced ED in vitro. Meanwhile, pretreatment with the inhibitor l-NAME nearly abolished vasodilation to ACh in all groups of rats. Furthermore, As-IV increased NO production and the expression of eNOS in the thoracic aorta of diabetic rats. In addition, the levels of ROS were significantly increased, and the activity of SOD and GSH-px were decreased in diabetic rats, while As-IV administration reversed this change in a concentration-dependent manner.CONCLUSION: These results suggest that As-IV improves endothelial dysfunction in thoracic aortas from diabetic rats by reducing oxidative stress and calpain-1.

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PMID: 

Int Immunopharmacol. 2019 Oct ;75:105651. Epub 2019 Aug 8. PMID: 31401385

Abstract Title: 

Astragaloside IV ameliorates motor deficits and dopaminergic neuron degeneration via inhibiting neuroinflammation and oxidative stress in a Parkinson's disease mouse model.

Abstract: 

Oxidative stress and neuroinflammation are the key and early events during the pathological process of Parkinson's disease (PD). Thus, therapeutic intervention to regulate oxidative stress and neuroinflammation would be an effective strategy to alleviate the progression of PD. Astragaloside IV, the main active component isolated from Astragalus membranaceus, has been shown to possess anti-inflammatory and anti-oxidant properties in neurodegeneration diseases, however, the molecular mechanisms of Astragaloside IV in the pathology of PD are still unclear. In this study, we explored the mechanisms of Astragaloside IV of PD on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model and lipopolysaccharide (LPS)-induced BV2 microglia cells. Our results showed Astragaloside IV significantly alleviated behavioral impairments and dopaminergic neuron degeneration induced by MPTP. Also, Astragaloside IV inhibited microglia activation and reduced the oxidative stress of MPTP mouse model. In addition, Astragaloside IV significantly inhibited NFκB mediated NLRP3 inflammasome activation and activated Nrf2 both in vivo and in vitro. Furthermore, Astragaloside IV lessened reactive oxygen species (ROS) generation in LPS-induced BV2 microglia cells remarkably. These findings demonstrate that Astragaloside IV protects dopaminergic neuron from neuroinflammation and oxidative stress which are largely dependent upon activation of the Nrf2 pathways and suppression of NFκB/NLRP3 inflammasome signaling pathway. Therefore, Astragaloside IV is a promising neuroprotective agent that should be further developed for neurodegeneration diseases.

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PMID: 

J Ethnopharmacol. 2019 Oct 19:112319. Epub 2019 Oct 19. PMID: 31639488

Abstract Title: 

Astragaloside IV alleviates ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Apoptosis plays an important role in cerebral ischemia-reperfusion injury and triggers a series of pathological changes which may even be life-threatening. Astragaloside-IV (AS-IV), a natural compound extracted from Astragalus (Astragalus membranaceus (Fisch.) Bunge., Leguminosae, Huangqi in Chinese), showed neuroprotective effects in the study of cerebral ischemia-reperfusion injury. In this study we investigate the effects of AS-IV on apoptosis induced by transient cerebral ischemia and reperfusion in rats, as well as the associated regulatory factors.METHODS: AS-IV was administrated to male Sprague-Dawley (SD) rats after transient cerebral ischemia and reperfusion surgery (12.5, 25, and 50 mg/kg, once per day, continued for 7 days after surgey). After seven days of continuous administration, neurological function, cerebral infarction volume, and pathological changes of brain tissue were detected. Fas, FasL, Caspase-8, Bax, and Bcl-2 mRNA levels were determined by real-time PCR. Caspase-8, Bid, Cytochrome C (Cyto C), cleaved Caspase-3 proteins were determined by western blot and immunohistochemistry was used to quantify Cyto C.RESULTS: AS-IV significantly attenuated the neurological deficit in rats with ischemica-reperfusion injury, and reduced cerebral infarction and neuronal apoptosis. AS-IV inhibited the mRNA upregulation of Fas, FasL, Caspase-8, and Bax/Bcl-2. Furthermore, the protein level of apoptosis cytokines Caspase-8, Bid, cleaved Caspase-3 and Cyto C were also inhibited after ischemia reperfusion, suggesting that AS-IV might alleviate ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway.

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PMID: 

Exp Ther Med. 2019 Nov ;18(5):3741-3750. Epub 2019 Sep 25. PMID: 31641375

Abstract Title: 

Astragaloside IV regulates NF-κB-mediated cellular senescence and apoptosis of hepatic stellate cells to suppress PDGF-BB-induced activation.

Abstract: 

Activated hepatic stellate cells (HSCs) are the principal effectors during hepatic fibrosis, which is characterized by the accumulation of extracellular matrix. Therefore, present therapies and investigations into hepatic fibrosis mainly focus on the suppression of activated HSCs. Astragaloside IV (ASIV) is an effective constituent extracted from the plantand has exhibited anti-fibrotic properties in hepatic fibrosis. However, its protective mechanism against hepatic fibrosis is not fully understood. The present study aimed to investigate the mechanistic role of ASIV on rat HSC-T6 cells activated with platelet-derived growth factor (PDGF)-BB. HSC-T6 cells were activated using PDGF-BB and subsequently treated with ASIV (final concentrations of 20 and 40µg/ml) for 48 h. ASIV treatment decreased the expression of α1 type I collagen, α-smooth muscle actin and fibronectin on mRNA and protein levels, suggesting that ASIV suppresses PDGF-BB-induced HSC-T6 activation. Senescence-associated β-galactosidase activity, p21, high-mobility group AT-hook 1and p53, common biomarkers of senescence, were upregulated by ASIV treatment. In addition, the expression of telomerase reverse transcriptase was reduced. ASIV promoted apoptosis of PDGF-BB-activated HSC-T6 cells. The NF-κB signaling pathway, which controls cellular senescence and apoptosis, was demonstrated to be stimulated by ASIV by increasing p65, p52, p50 and inhibitor of NF-κB kinase α expression levels, and by suppressing the expression of NF-κB inhibitor α. Taken together, these results demonstrated that ASIV promoted cellular senescence and apoptosis by activating the NF-κB pathway to suppress PDGF-BB-induced HSC-T6 activation; with potential implications for the treatment of hepatic fibrosis.

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PMID: 

J Nutr Sci Vitaminol (Tokyo). 2019 ;65(Supplement):S109-S112. PMID: 31619607

Abstract Title: 

Novel Antioxidative Activity of Astaxanthin and Its Synergistic Effect with Vitamin E.

Abstract: 

Astaxanthin (Asx) is known to be a potent quencher of singlet oxygen and an efficient scavenger of superoxide anion. However, the scavenging activity of Asx toward the hydroxyl radical was currently unclear because the high lipophilicity of Asx prevents analysis of such activity in water. Liposomes containing Asx (Asx-lipo) were previously shown to be dispersed in water. Analysis of the hydroxyl radical scavenging activity of Asx-lipo demonstrated a dose-dependence in water, with the effect of Asx being more potent than the vitamin Eα-tocopherol (α-T). Furthermore, liposomes co-encapsulating Asx and vitamin E derivatives, namely tocotrienols (T3), showed a synergistic elimination effect on singlet oxygen and hydroxyl radical, although the antioxidative activity of liposomes co-encapsulating Asx and α-T was lower than the calculated additive value of each independent activity. A calculation of the most stable structure of Asx in the presence of α-T or T3, suggested that only T3 was able to hydrogen bond with Asx, and the Asx polyene chain partially interacting with the α-T3 triene chain, which could explain the synergistic effect between Asx and T3, but not Asx and α-T. This review introduces the hydroxyl radical scavenging activity of Asx, and its synergistic effect with T3.

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PMID: 

J Clin Pharm Ther. 2019 Oct 10. Epub 2019 Oct 10. PMID: 31602695

Abstract Title: 

A placebo controlled randomized clinical trial of Crocus sativus L. (saffron) on depression and food craving among overweight women with mild to moderate depression.

Abstract: 

WHAT IS KNOWN AND OBJECTIVE: Crocus sativus L., commonly known as saffron, has known anti-depressive properties. However, its effects on food craving and body weight in depressed patients are unknown. Hence, we aimed to evaluate the effects of saffron capsules on food craving, body weight and depression among overweight women with mild and moderate depression compared to the placebo.METHODS: Seventy-three women with BMI ≥ 25 comorbid with mild-to-moderate depression were recruited in this 12-week double-blind, placebo-controlled randomized clinical trial. Participants were randomly assigned into one of the two groups receiving daily either 30 mg of Crocus sativus capsules (15 mg twice/day) or placebo capsules (twice/day). We performed body composition assessments, and beck depression inventory-II at the baseline, and then 2, 4, 8 and 12 weeks later. One month after the participants stopped taking the capsules, weight differences were measured and compared between groups.RESULTS AND DISCUSSION: Fifty-two patients finished the study. The demographic and clinical variables at baseline were the same in two groups. Mean depression scores in the saffron group significantly decreased compared to placebo (mean ± SD: -8.4 score ± 5.9 vs -3.9 ± 5.5; t[50] = 2; P = .007; 95% CI: 1.3-7.7). There was not a significant effect of saffron on food craving using repeated-measures ANOVA, F(1, 29) = 0.38, P = .54. Patients in the saffron group showed fewer side effects.WHAT IS NEW AND CONCLUSION: Saffron capsules were not effective in reducing food craving, but as a safe over-the-counter supplement, it may help reduce the symptoms of depression in patients who experience mild or moderate depression and are overweight.

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PMID: 

J Pharm Pharmacol. 2019 Oct 23. Epub 2019 Oct 23. PMID: 31645086

Abstract Title: 

Pharmacological properties and therapeutic potential of saffron (Crocus sativus L.) in osteosarcoma.

Abstract: 

OBJECTIVES: In this comprehensive study, we aimed to investigate pharmacological properties and therapeutic significance of saffron in osteosarcoma cancer cells.METHODS: Plant materials were obtained from Safranbolu district of Karabuk, Turkey. For the determination of anticancer properties, thiazolyl blue tetrazolium bromide (MTT) cell viability, colony formation, wound closure, DNA ladder assays and gene expression analysis by real-time PCR were performed. Also, cellular inflammation, total antioxidant and oxidants status were determined.KEY FINDINGS: Dichloromethane and hexane extracts of saffron were significantly inhibited cell proliferation and interfered with colony forming and migration capabilities of U2-OS osteosarcoma cancer cells. Also, both extracts induced the activation of tumour suppressor CDKN2B gene and altered cellular morphology resembling the induction of apoptosis. However, DNA fragmentation was not observed after extract treatments. Saffron was also found to have no significant effect on cellular inflammation. Unexpectedly, both dichloromethane and hexane extracts of saffron had no marked effect on cellular total antioxidant and oxidant status. Lastly, vanillic acid, resveratrol, caffeic acid and 4-hydroxybenzoic acid were found to be highly rich in our extracts.CONCLUSIONS: Findings of this study demonstrated significant antiproliferative and antitumorigenic properties of saffron in osteosarcoma.

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PMID: 

Exp Ther Med. 2019 Nov ;18(5):3775-3782. Epub 2019 Sep 19. PMID: 31616509

Abstract Title: 

Crocetin protects against fulminant hepatic failure induced by lipopolysaccharide/D-galactosamine by decreasing apoptosis, inflammation and oxidative stress in a rat model.

Abstract: 

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by sudden and severe liver dysfunction. Apoptosis and inflammation are essential for the pathogenesis of FHF. Crocetin, the major component present in saffron, has been reported to possess anti-inflammatory and antioxidant functions; however, its role in FHF is poorly understood. The aim of this study was to explore the protective effects of crocetin against lipopolysac§§charide (LPS)/D-galactosamine (D-GalN)-induced FHF and the underlying mechanisms in a rat model. For thestudy, rats were assigned to the LPS/D-GalN group or to the crocetin pre-treatment+LPS/D- GalN group. Each group was then further divided according to the different LPS/D-GalN treatment times of 0, 6, 12 or 48 h. The results demonstrated that crocetin pre-treatment efficiently protected against LPS/D-GalN-induced FHF by improving liver tissue morphology, reducing total bilirubin generation and decreasing the activities of alanine transaminase and aspartate aminotransferase. Moreover, crocetin pre-treatment significantly decreased hepatocyte apoptosis, p53 mRNA expression and the expression of proteins in the caspase family and the Bcl-2 pro-apoptotic family following LPS/D-GalN treatment. Furthermore, crocetin also decreased the secretion of pro-inflammatory cytokines in the serum and in the liver via suppression of NF-κB activation, and also suppressed hepatic oxidative stress. In conclusion, crocetin protected against LPS/D-GalN-induced FHF and inhibited apoptosis, inflammation and oxidative stress. The underlying mechanisms may be related to the regulation of apoptotic proteins in the caspase family and the Bcl-2 family, as well as the modulation of NF-κB expression. Therefore, crocetin may be used as a novel therapy for preventing FHF.

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PMID: 

J Inflamm Res. 2019 ;12:269-283. Epub 2019 Oct 8. PMID: 31632125

Abstract Title: 

Investigating the effect ofL. petal hydroalcoholic extract on inflammatory and enzymatic indices resulting from alcohol use in kidney and liver of male rats.

Abstract: 

Background: Studies have shown that consumption of high levels of alcohol causes many negative effects on the liver and kidneys where antioxidant ingredients can be a proper solution to reducing the resulting damages. So, the present study investigated the effect of hydroalcoholic extract ofL. (saffron) petal with antioxidant properties on the changes in inflammatory and enzymatic indices resulting from alcohol use in the male rats' kidney and liver.Materials and methods: After preparing the extract, LDwas determined and high-performance liquid chromatography (HPLC) was employed to specify the type and the rate of the active ingredients of the extract. Then, 36 male Wistar rats were randomly assigned into six groups (n=6). The first group was only administered with normal saline and the second group only received ethyl alcohol 6 mL/kg/day·BW. The third and the fourth groups received ethyl alcohol 6 mL/kg/day·BW plus 167.5 and 335 mg/kg/day·BW saffron petal extract for 8 weeks. The fifth and the sixth groups received ethyl alcohol 6 mL/kg/day·BW for the first 8 weeks and were subsequently gavage fed on saffron extract for 167.5 and 335 mg/kg/day·BW, respectively, during the next 8 weeks. In the beginning and after the termination of the treatment, blood samples were collected from all rats.Results: The LDof the extract was about 670 mg/kg. The HPLC results indicated that the extract contains important antioxidant ingredients. At the end of the study, the serum concentration of the inflammatory indices, renal enzymes, and hepatic enzymes experienced a significant reduction in all of the intervened groups compared to the negative control group (minimum significant difference:

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PMID: 

Physiol Behav. 2019 Oct 12 ;212:112699. Epub 2019 Oct 12. PMID: 31614158

Abstract Title: 

Antidepressant activity of crocin-I is associated with amelioration of neuroinflammation and attenuates oxidative damage induced by corticosterone in mice.

Abstract: 

Depression is the leading cause of mental health-related disease globally, and it affects an estimated 300 million people worldwide. However, its physiological causes are not fully understood. Since available antidepressants fail to achieve complete disease remission, treating diversification of depression may be a useful contribution. Crocin, one of the main glycosylated carotenoids of saffron, has been found to have numerous pharmacological activities and has been reported to be associated with neuroprotective effects. However, the biological action of crocin-I, a major member of the crocin family, on depression-like behavior, neuroinflammation and oxidative damage in depressed animals remains unclear. The present study showed that crocin-I exerts significant antidepressant effects in a model of chronic corticosterone (CORT)-induced depression, as evidenced by the attenuation of depression-like behaviors in the open field test, forced swimming test and tail suspension test. The antidepressant activity of crocin-I was probably achieved through the suppression of neuroinflammation (IL-1β) and oxidative stress in the mouse hippocampus. Additionally, the oral administration of crocin-I at a dose of 40 mg/kg reduced the CORT-induced accumulation of nicotinamide in the liver of the mice to improve the synthesis of NAD, thereby stimulating the activity of SIRT3 deacetylase to elevate the activity of antioxidants such as superoxide dismutase 2 and glutathione reductase. Moreover, crocin-I reduced the levels of oxidative damage markers (reactive oxygen species and malonaldehyde) to rescue impaired mitochondrial function caused by CORT treatment, which was represented by electron transport chain and oxidative phosphorylation normality, and thus rescue ATP production to the level of that in wild-type mice. Our findings shed new light on the mechanism of action of crocin-I on depression-like behavior and oxidative stress in individuals stressed by perceived conditions.

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