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Protective effect of dried safflower petal aqueous extract and its main constituent, carthamus yellow, against lipopolysaccharide-induced inflammation in RAW264.7 macrophages
Journal of The Science of Food and Agriculture
Abstract
Safflower, whose botanic name is Carthamus tinctorius L., is a member of the family Compositae or Asteraceae. Carthamus yellow (CY) is the main constituent of safflower and is composed of safflomin A and safflomin B. Dried safflower petals are used in folk medicine and have been shown to invigorate blood circulation, break up blood stasis, and promote menstruation. In addition, dried safflower petals contain yellow dyes that are used to color food and cosmetics. In this study, we investigated the effects of dried safflower petals aqueous extracts (SFA) and CY on lipopolysaccharide (LPS)-induced inflammation using RAW264.7 macrophages.
Our data showed that treatment with SFA (1-1000 microg mL(-1)) and CY (1-2000 microg mL(-1)) does not cause cytotoxicity in cells. SFA and CY inhibited LPS-stimulated nitric oxide (NO), prostaglandin E(2) (PGE(2)), and interleukin 1β (IL-1β) release, through attenuation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. Further, SFA and CY suppressed the LPS-induced phosphorylation of nuclear factor-κB, which was associated with the inhibition of IκB-α degradation.
These results suggest that SFA and CY provide an anti-inflammatory response through inhibiting the production of NO and PGE(2) by the downregulation of iNOS and COX-2 gene expression. Thus safflower petals have the potential to provide a therapeutic approach to inflammation-associated disorders.
... SFA (250, 500, and 1000 µg/mL) reduced the cytokine production after 24 h in a concentration dependent manner, as wells as caused much more strongly effect than CY (250, 500, 1000, and 2000 µg/mL). [41] Pomegranate peel polyphenols (PPPs) and their main components punicalagin (PC) and ellagic acid (EA) also decreased cytokine release in the LPSactivated RAW264.7 cells. Macrophages were firstly pretreated with different concentrations of PPPs (100 μg/mL), PC (50 μg/mL), EA (50 μg/mL) for 1 h, and then stimulated with LPS (1 μg/mL) for 20 min or 24 h. ...
... ↓ TNF-α production [40] Ternstroemiagymnanthera stem bark aqueous extract ↓ TNF-α production [41] (Continued) ...
... The results indicated that both the extract and its main constituent after 2 h treatment notably inhibited NF-κB expression in a concentration-dependent manner, and at the same time significantly increased the expression of IκB-α, which prevents the NF-κB activation and translocation to the nucleus. [41] In the next study, RAW264.7 cells were firstly pre-treated with PeTP (.5, 1, and 2 mg/mL) for 1 h and then stimulated with LPS for another hour. Western blot analysis presented that the phosphorylation and degradation of IκB-α were inhibited by the extract in a concentrationdependent manner. ...
Macrophages play important roles in acute and chronic inflammation. Upon their activation, they secrete a variety of mediators, including cytokines, which are involved in the inflammatory response. Polyphenols are a wide group of compounds with many health-promoting properties. They are characterized by antioxidant, anti-cancer and anti-inflammatory activity. Numerous studies conducted on single phenols shed light on plant extracts rich in these compounds. The aim of this descriptive review is to demonstrate the anti-inflammatory role of phenol-rich natural extracts by modulating the NF-κB signaling pathway in macrophage cells. Additionally, this article focuses on the influence of phenolic extracts on the inhibition of pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α. The cited studies prove that plant extracts possess anti-inflammatory activity, and due to the wide role of inflammation in various diseases, from cardiovascular diseases to cancer, they can be used as therapeutic agents. What’s more, increasing awareness in the area of proper nutrition and consumption of food rich in polyphenols may have a protective effect on human health.
... 3 It was determined that KhD-6 contained biologically active substances such as, gallic acid Retention factor (Rf)=0.27, costunoloids Rf=0.71, saflomin A Rf=0.21, E-guggulsterone Rf=0.5, apigenin Rf=0.46, and as a polyphenolic compound-flavonoids and essential oil. 4 The other studies have shown that these biologically active substances had an effects of reducing inflammatory cytokines, inhibiting microglial activity, apoptosis, and protecting nerves. [5][6][7][8] The neuroinflammation induces vascular permeability, leukocytes infiltration, activation of glial cells, and release of inflammatory mediators. 9 During migraine progression the neuroinflammation is related to the activation of glia in the hypothalamus. ...
... 17 During the migraine pathogenesis the levels of IL-1â, IL-6 and TNF-á were significantly higher. 6 Evidences are showing that IL-1â contributes to migraine pathogenesis, for example in internal jugular blood the level of IL-1â was increased during continuous and occasional migraine. 18 Fig 2B. ...
Background
Migraine is a highly prevalent neurovascular disorder with complicated treatment due to multifactorial pathophysiology. During the recent years, the prevalence of migraine in Mongolia is increasing and has reached 26.5% by 2019 which indicates an increase of 5.2% over the past 10 years. The industry of traditional medicine in Mongolia has a long history of development, hence, it is evident that various herbal medicines such as but not limited to Khurtsiin deed-6 (KhD-6) can be considered as generally safe and effective against several diseases including migraine. KhD-6’s single component has shown excellent analgesic, anti-inflammatory and neuroprotective effect, while the whole compound effectiveness and molecular mechanism had not been assessed for the treatment of migraine.
Objectives
To study the effects of Khurtsiin deed-6 compound on inflammation and neuronal cell damage in migraine model in rats.
Methods
A total of 36 rats were randomly divided into the following six groups including control group, Nitroglycerin-induced (NTG-induced) migraine model group, KhD-6 groups of 50 mg/kg, 100 mg/kg and 150 mg/kg doses, and Ibuprofen (IBU) 85 mg/kg treated group. Corresponding treatments were administered intragastrically for 10 days to animals of experimental groups. Then NTG-induced migraine model group, three KhD-6 groups and IBU group were subcutaneously injected with Nitroglycerin (10mg/kg) 1 hour after the last treatment. Experimental animals were observed for two hours after Nitroglycerin injection to confirm the model establishment. After four hours, all rats were anesthetized and blood was collected from three rats from each group in order to detect levels of Nitric oxide (NO), calcitonin gene-related peptide (CGRP) and endothelin (ET) by ELISA method. The remaining three animals of each experimental group were perfused under anesthesia for the removal of their brains and isolation of the trigeminal nucleus caudalis (TNC). A polymerase chain reaction (PCR) method was used to analyze OX42, COX2, RAGE, GFAP, BDNF, BAX, and Bcl expressions.
Results
NTG-induced rat migraine model presents increased NO and CGRP levels in serum as well as c-Fos expression in the brain trigeminal nucleus area, which indicates that the migraine model was successfully generated. NO and CGRP levels in serum were suppressed in KhD-6 and IBU treated groups. The c-Fos expression decreased significantly in the TNC not only in Khurtsiin-6 compound, but also in IBU treated groups. Furthermore, KhD-6 compound inhibits neuro-inflammatory pathways by reducing COX2 expression, OX42 and GFAP activation. It inhibits neuronal cell death through suppressing RAGE, BAX, Bcl expression and increasing BDNF expression.
Conclusion
KhD-6 offers analgesic and neuroprotective effects in the NTG-induced migraine rat model by inhibiting the activation of glial cells and the secretion of neuroinflammatory factors in the TNC region.
... 3 It was determined that KhD-6 contained biologically active substances such as, gallic acid Retention factor (Rf)=0.27, costunoloids Rf=0.71, saflomin A Rf=0.21, E-guggulsterone Rf=0.5, apigenin Rf=0.46, and as a polyphenolic compound-flavonoids and essential oil. 4 The other studies have shown that these biologically active substances had an effects of reducing inflammatory cytokines, inhibiting microglial activity, apoptosis, and protecting nerves. [5][6][7][8] The neuroinflammation induces vascular permeability, leukocytes infiltration, activation of glial cells, and release of inflammatory mediators. 9 During migraine progression the neuroinflammation is related to the activation of glia in the hypothalamus. ...
... 17 During the migraine pathogenesis the levels of IL-1â, IL-6 and TNF-á were significantly higher. 6 Evidences are showing that IL-1â contributes to migraine pathogenesis, for example in internal jugular blood the level of IL-1â was increased during continuous and occasional migraine. 18 Fig 2B. ...
Objectives: To investigate the anti-inflammatory activity of Khurtsiin deed-6 in migraine and neurodegeneration rat models. Methods: This study uses nitroglycerin induced migraine was model and alcohol exposed neurodegeneration model in Wistar rats to evaluate anti-inflammatory effect of Khurtsiin deed-6 at the 3 different doses of 50, 100and 150 mg/kg, orally. After anesthesia, the brains were removed, then trigeminal nucleus caudal is and hippocampus region isolated from fresh brain. And followed by protein and RNA extraction. Interleukin-1β expression was analyzed by real time polymerase chain reaction. Results: Nitroglycerin induced rat migraine model had increased Interleukin-1β expression in brain TNC area (p<0.001). It has been decreased dramatically after treatment of Khurtsiin deed-6 by doses of 50mg/kg, 100mg/kg and 150mg/kg treatment in brain trigeminal nucleus caudal is region (p<0.01) comparing ibuprofen treated group. Moreover alcohol exposed neurodegeneration rat model had observed increased Interleukin-1β expression in brain Hp area (p<0.001). But Khurtsiin deed-6 doses of 50mg/kg, 100mg/kg and 150mg/kg treatment reduced neuroinflammatory cytokines IL1β expression in hippocampus region (p<0.01, p<0.001) of alcoholic rat models comparing pyridoxamine administrated animals. Conclusion: The present finding indicates that Khurtsiin deed-6shows anti-inflammatory activity decreasing the level of Interleukin -1β cytokine in nitroglycerin induced migraine and alcohol exposed neurodegeneration rat models
... Moreover, quinochalcone C-glycosides have been described in safflower, the most representative are the water soluble compounds hydroxy safflor yellow A (HSYA), safflor yellow A (SYA), and hydroxy safflor yellow B [4][5][6]. The bioactive properties of HSYA, used in Chinese medicine for treatment of cerebrovascular and cardiovascular disease, have been previously studied [7][8][9][10]. Anti-inflammatory properties [8] and neuroprotective effects have been reported [10]. ...
... The bioactive properties of HSYA, used in Chinese medicine for treatment of cerebrovascular and cardiovascular disease, have been previously studied [7][8][9][10]. Anti-inflammatory properties [8] and neuroprotective effects have been reported [10]. Among molecular mechanisms, antioxidant activity has been described [7,11]. ...
(1) Carthamus Tinctorius L. (safflower) is extensively used in traditional herbal medicine. (2) The aim of this study was to investigate the bioactive properties of polyphenol extracts from flowers of Carthamus Tinctorius (CT) cultivated in Italy. We also evaluated the properties of two bioactive water-soluble flavonoid compounds, hydroxy safflor yellow A (HSYA) and safflor yellow A (SYA), contained in Carthamus Tinctorius petals. (3) The total polyphenol content was 3.5 ± 0.2 g gallic acid equivalent (GAE)/100 g, flavonoids content was 330 ± 23 mg catechin equivalent (CE)/100 g in the flowers. The extract showed a high antioxidant activity evaluated by oxygen radical absorbance capacity (ORAC) and 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assays. In addition, flower extract, SYA, and HSYA were able to reduce the susceptibility of low-density lipoprotein to copper-induced lipid peroxidation. In order to investigate the bioactive properties of flower extract, SYA, and HSYA we also studied their modulatory effect of oxidative stress on human dermal fibroblasts (HuDe) oxidized by tert-butyl hydroperoxide (t-BOOH). The CT extract at concentrations ranging from 0.01–20 μg GAE/mL of polyphenols, exerted a protective effect against t-BOOH triggered oxidative stress. At higher concentration the extract exerted a pro-oxidant effect. Similar results have been obtained using HSYA and SYA. (4) These results demonstrate a biphasic effect exerted by HSYA, SYA, and flower extracts on oxidative stress.
... Meanwhile, flavonoids also play an important role in plant biotic and abiotic stresses, such as protection against light and temperature, as well as defense against insect infestation and pathogens [6][7][8]. In plants, flavonoids contribute to various pharmacological applications [9][10][11]. Recently, more than 10,000 flavonoid compounds were discovered and divided into nine subgroups: flavonols, anthocyanidins, flavanones, dihydro flavonols (DHFs), flavan-3,4-diols, flavones, flavan-3-ols, proanthocyanidins (PAs), and isoflavonoids [12,13]. ...
Flavonol synthase gene (FLS) is a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily and plays an important role in plant flavonoids biosynthetic pathways. Safflower (Carthamus tinctorius L.), a key source of traditional Chinese medicine, is widely cultivated in China. Although the flavonoid biosynthetic pathway has been studied in several model species, it still remains to be explored in safflower. In this study, we aimed to elucidate the role of CtFLS1 gene in flavonoid biosynthesis and drought stress responses. The bioinformatics analysis on the CtFLS1 gene showed that it contains two FLS-specific motifs (PxxxIRxxxEQP and SxxTxLVP), suggesting its independent evolution. Further, the expression level of CtFLS1 in safflower showed a positive correlation with the accumulation level of total flavonoid content in four different flowering stages. In addition, CtFLS1-overexpression (OE) Arabidopsis plants significantly induced the expression levels of key genes involved in flavonol pathway. On the contrary, the expression of anthocyanin pathway-related genes and MYB transcription factors showed down-regulation. Furthermore, CtFLS1-OE plants promoted seed germination, as well as resistance to osmotic pressure and drought, and reduced sensitivity to ABA compared to mutant and wild-type plants. Moreover, CtFLS1 and CtANS1 were both subcellularly located at the cell membrane and nucleus; the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assay showed that they interacted with each other at the cell membrane. Altogether, these findings suggest the positive role of CtFLS1 in alleviating drought stress by stimulating flavonols and anthocyanin accumulation in safflower.
... In addition, quinochalcone C-glycosides have also been reported in safflower with the most predominant been the water soluble components of hydroxy safflor yellow A, safflor yellow A, and hydroxy safflor yellow B [22]. Bioactive properties of hydroxy safflor yellow A have been utilized in Chinese medicine for the treatment of cerebrovascular and cardiovascular disease [46], [47]. ...
Preliminary literature review on Baghdad's aging population and the authors' experiences have demonstrated that the challenges associated with aging process have not been given much attention. Anti-aging plants which have been associated with health promoting properties have been utilized as interventions to curb the aging process. This has been achieved as they contain active ingredients which have been scientifically proven to have medicinal and antiaging properties through various laboratory species as previously reported. This study sought to identify these phytochemicals both quantitatively and qualitatively using different techniques. Three plants, Apium graveolens, Carthamus tinctorious and Punica granatum were obtained at a local market in Baghdad and extracted with water. The resultant mixture was purified by a whatman paper and the solvent dried using a spray dryer. The resultant residue was kept for further analysis. Qualitative method of screening different phytochemicals among them tannins, carbohydrates, glycosides, phenols, resins, flavonoids, saponins, alkaloids, proteins, coumarins, terpenes and steroids was done. The methanolic extracts were further screened using GC-MS and their mass spectrum compared with compounds from the database library. Separation and identification of the three extracts was also done using High Performance Liquid Chromatography and mineral analysis of selenium, zinc and calcium were conducted using Atomic Absorption Spectroscopy. GC-MS results revealed that Safflower had the highest number of major compounds while celery plant had the least. In safflower Triisobutyl (3-phenylpropoxy) silane was the highest in concentration at 16.73% while in celery plant the highest active component was 1H-Indole at a concentration of 16.37%. In pomegranate plant, the highest active component was 6-Octadecenoic acid, methyl ester with a concentration of 20.24%. HPLC analysis did not reveal the six standards used in this study for safflower and pomegranate plants however, in celery plant resverastrol, b-sistine and rutin were identified at concentrations of 4.93%, 16.09% and 5.22 % respectively. Qualitative phytochemical screening showed that safflower and pomegranate exhibited similar trend in all the phytochemicals and also there presence was more compared to celery plant. Selenium ion was not detected although zinc was found but in minute concentrations. Calcium ion was also detected in high concentrations although it was significantly lower in pomegranate plant at 35.4%. In conclusion, GC-MS profiling of the phytochemicals among the three plants revealed varying components with different concentrations. This was also reflected on the qualitative determinations although pomegranate and safflower exhibited similar occurrence of the phytochemicals.
... This constituent inhibited inflammation in TNF-α-induced rat chondrocytes by regulating the NF-κB/SIRT1/AMPK pathways and endoplasmic reticulum stress [61]. Another study found that aqueous extracts from the petals of C. tinctorius and its main constituent safflower yellow prevented NO production and PGE2 in LPS-stimulated RAW264.7 cells by downregulating iNOS and COX-2 expressions [62]. Polyacetylene glucosides isolated from florets of C. tinctorius significantly inhibited NO production in LPS-stimulated RAW264.7 cells [27]. ...
This study aimed to elucidate the anti-inflammatory activity of C. tinctorius leaves by measuring inflammatory parameters such as nitric oxide (NO) production and mRNA expression of iNOS, interleukin-6 (IL-6), and IL-1β in lipopolysaccharide (LPS)-induced HaCaT cells. Further, the effect of C. tinctorius ethanol extract on the MAPKs/NF-κB signaling pathway was examined in HaCaT cells. The phytochemical profile of the ethanol extract of C. tinctorius leaves was determined using UPLC-QTOF-MS/MS. The results indicated that the ethanol extract of C. tinctorius effectively attenuated LPS-induced secretion of NO, IL-6, and IL-1β in HaCaT cells. Further, LPS-stimulated mRNA and protein expressions of iNOS were decreased by pre-treatment with C. tinctorius ethanol extract at the transcriptional level in HaCaT cells. Moreover, the ethanol extract of C. tinctorius suppressed NF-κB signaling in LPS-induced HaCaT cells. This suppression was mediated by MAPKs/NF-κB signaling, inhibiting the phosphorylation of p38 and p65 in HaCaT cells. However, there is no significant effect on the phosphorylation of JNK by the ethanol extract. The QTOF-MS/MS analysis revealed the identification of 27 components in the ethanol extract of C. tinctorius leaves. The data demonstrate that the ethanol extract of C. tinctorius leaves protects the LPS-induced HaCaT cells by inhibiting the expression of iNOS, IL-6, and IL-1β and suppressing the phosphorylation of the p38, p65, p-JNK via inactivation of MAPKs/NF-κB signaling pathway. These results demonstrate that C. tinctorius leaves may serve as a potential candidate to prevent inflammation-related diseases.
... Petal aqueous extract and safflower A from C. tinctorius demonstrated antiinflammatory potential by showing inhibition of NO and PGE2 production in RAW264.7 cells through downregulation of iNOS and COX2 expressions (Wang et al. 2010). Hydroalcohol extract of safflower and kaempferol derivative obtained from it had also shown anti-inflammatory potential in animal model of carrageenan and xylene induced ear edema model (Wang et al. 2014). ...
Carthamus tinctorius L., also known as safflower, is a highly exploited medicinal plant from Asteraceae family. It has been used in agriculture for its oil, food, and fodder and in textile industries as natural dyes. It has also been used in different traditional medicinal systems for the treatment of various diseases in countries around the world. Scientific researches explored its anticoagulant, antihypertensive, cardioprotective, antioxidant, neuroprotective, anti-melanogenic, immune-stimulatory, antitumor, anti-arthritic, anti-inflammatory, anti-obesity, and antidiabetic activities. The presence of various phytoconstituents such as flavonoids, phenyltethanoids glycosides, coumarins, fatty acids, steroids, alkaloids, alkane diols, riboflavin, and safflower polysaccharides are believed to be responsible for its diverse medicinal significances. Hence, this plant not only serves as a source of lead molecule for drug development but it can also be used to develop nutraceuticals and functional foods as well. Furthermore, as a good source of natural yellow and red pigments, it can provide suitable natural alternative to the synthetic coloring agents. KeywordsCarthamus tinctorius L.SafflowerTraditional medicineHydroxysafflower ASafflower yellow
... SFA and CY inhibited LPSstimulated nitric oxide (NO), prostaglandin E 2 (PGE 2 ), and interleukin 1β (IL-1β) release, through attenuation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. Furthermore, SFA and CY suppressed the LPS-induced phosphorylation of nuclear factor-κB, which was associated with the inhibition of IκB-α degradation [172]. ...
The chemical groups isolated from Carthamus tinctorius were included oils, proteins, minerals, phenolics, flavonoids, alkaloids, lignans, carboxylic acids, steroids, polysaccharides, quinochalcone C-glycosides and quinone-containing chalcones. It exerted many pharmacological activities including central nervous, cardiac, vascular, anticoagulant, reproductive, gastrointestinal, antioxidant, hypolipidemic, metabolic and many other pharmacological effects. This paper will highlight the chemical constituents and pharmacological effects of Carthamus tinctorius.
... In addition, quinochalcone C-glycosides have also been reported in safflower with the most predominant been the water soluble components of hydroxy safflor yellow A, safflor yellow A, and hydroxy safflor yellow B [22]. Bioactive properties of hydroxy safflor yellow A have been utilized in Chinese medicine for the treatment of cerebrovascular and cardiovascular disease [46], [47]. ...
Preliminary literature review on Baghdad's aging population and the authors' experiences have demonstrated that the challenges associated with aging process have not been given much attention. Anti-aging plants which have been associated with health promoting properties have been utilized as interventions to curb the aging process. This has been achieved as they contain active ingredients which have been scientifically proven to have medicinal and antiaging properties through various laboratory species as previously reported. This study sought to identify these phytochemicals both quantitatively and qualitatively using different techniques. Three plants, Apium graveolens, Carthamus tinctorious and Punica granatum were obtained at a local market in Baghdad and extracted with water. The resultant mixture was purified by a whatman paper and the solvent dried using a spray dryer. The resultant residue was kept for further analysis. Qualitative method of screening different phytochemicals among them tannins, carbohydrates, glycosides, phenols, resins, flavonoids, saponins, alkaloids, proteins, coumarins, terpenes and steroids was done. The methanolic extracts were further screened using GC-MS and their mass spectrum compared with compounds from the database library. Separation and identification of the three extracts was also done using High Performance Liquid Chromatography and mineral analysis of selenium, zinc and calcium were conducted using Atomic Absorption Spectroscopy. GC-MS results revealed that Safflower had the highest number of major compounds while celery plant had the least. In safflower Triisobutyl (3-phenylpropoxy) silane was the highest in concentration at 16.73% while in celery plant the highest active component was 1H-Indole at a concentration of 16.37%. In pomegranate plant, the highest active component was 6-Octadecenoic acid, methyl ester with a concentration of 20.24%. HPLC analysis did not reveal the six standards used in this study for safflower and pomegranate plants however, in celery plant resverastrol, b-sistine and rutin were identified at concentrations of 4.93%, 16.09% and 5.22 % respectively. Qualitative phytochemical screening showed that safflower and pomegranate exhibited similar trend in all the phytochemicals and also there presence was more compared to celery plant. Selenium ion was not detected although zinc was found but in minute concentrations. Calcium ion was also detected in high concentrations although it was significantly lower in pomegranate plant at 35.4%. In conclusion, GC-MS profiling of the phytochemicals among the three plants revealed varying components with different concentrations. This was also reflected on the qualitative determinations although pomegranate and safflower exhibited similar occurrence of the phytochemicals.
... They could also upregulate SOD activity and inhibit malondialdehyde (MDA) and ROS accumulation [54][55][56]. In particular, the flavonoids in Carthami Flos have a good regulatory effect on oxidative stress response [57] and could inhibit NO production and inflammatory response by decreasing the protein expression of iNOS and COX-2 genes [58]. Cornus Officinalis Sieb. ...
Pulmonary hypertension (PH) is a chronic and progressive disease caused by obstructions and functional changes of small pulmonary arteries. Current treatment options of PH are costly with patients needing long-term taking medicine. The traditional Chinese medicine (TCM) compound “Shufeiya Recipe” was used to intervene in monocrotaline- (MCT-) induced pulmonary hypertension in rats. The rats were randomly divided into the control group, model group, positive drug (Sildenafil) group, and Shufeiya Recipe low-, moderate-, and high-dose groups. The improvement effect of the Shufeiya Recipe on the mean pulmonary artery pressure (mPAP) was assessed in PH rats, and pathological staining was used to observe the pathological changes of lung tissue. The impact of the Shufeiya Recipe on oxidative stress damage in rats with pulmonary hypertension and the regulation of SIRT3/FOXO3a and its downstream signaling pathways were determined. The results showed that Shufeiya Recipe could significantly downregulate mPAP and improve lung histopathological changes; downregulate serum levels of reactive oxygen species (ROS); upregulate the concentrations of COX-1 and COX-2 and the activity of Mn-SOD; inhibit oxidative response damage; promote the protein expression of SIRT3, FOXO3a, p-PI3K, p-AKT, and p-eNOS; increase the level of expression of NO, sGC, cGMP, and PKG; and downregulate the level of protein expression of Ras, p-MEK1/2, p-ERK1/2 and c-fos. These results indicate that Shufeiya Recipe can improve MCT-induced pulmonary hypertension in rats by regulating SIRT3/FOXO3a and its downstream PI3K/AKT/eNOS and Ras/ERK signaling pathways.
... Pharmacological experiments have demonstrated that Rhus chinensis Mill. possess wide-reaching biological functions including dilating coronary artery, improving myocardial ischemia, modulating immune system, anticoagulation and antithrombosis, antioxidation, anti-aging, antihypoxia, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc [6][7][8][9][10][11]. Due to the traditional use of Rhus chinensis Mill. in the prevention of liver cirrhosis [12], this study was therefore performed to study the effect of Rhus chinensis Mill. ...
Purpose: To study the effect of Rhus chinensis Mill. extract (RCME) on diethylnitrosamine (DEN)-induced liver cirrhosis in rats. Methods: RCME was obtained by extracting the dried Rhus chinensis Mill. in water. Liver cirrhosis rat model was prepared by injecting with DEN once a week for 8 weeks. After 8th-week of RCME treatment, biochemical index and oxidative stress were determined in DEN-induced liver cirrhosis in rats. Results: Compared with model group, plasma concentrations of alanine transaminase (ALT, 125.3 ± 4.1 U/L) and aspartate aminotransferase (AST, 152.4 ± 3.5 U/L) decreased significantly (p < 0.01) in the 8th week. Rhus chinensis Mill. extract (RCME) significantly decreased malondialdehyde (MDA, 0.18 ± 0.02 umol/L) and superoxide dismutase (SOD, 0.76 ± 0.05 U/mg protein) in DEN-induced liver cirrhosis in rats (p < 0.01) when compared with model group. Conclusion: RCME protects against diethylnitrosamine-induced liver cirrhosis in rats. However, further investigations are required to ascertain the plant extract’s suitability for the clinical management of liver cirrhosis.
... Although the results were comparable, SFA inhibited PGE 2 production much more strongly. Similarly, while both SFA and CY markedly suppressed COX-2 and iNOS expression in a concentration-dependent manner, SFA appeared to be more effective (38). ...
Recent decades have seen a rise in chronic inflammatory diseases such as diabetes, cardiovascular diseases, asthma, rheumatoid arthritis, neurodegenerative diseases. Importantly, such chronic inflammatory diseases also increase the risk of cancer development and there is a pressing need to identify new anti-inflammatory drugs. One promising source of new medication are natural polyphenolic compounds and polyphenol-rich preparations, extracts and foods, which have strong antioxidant properties. This paper reviews the anti-inflammatory role of polyphenolic-rich natural extracts, and their ability to modulate crucial pro-inflammatory mediators, such as cyclooxygenase-2, prostaglandin E2, inducible nitric oxide synthase, and nitric oxide, in macrophage cells. Our research confirms that natural compounds have health potential, and could be used in the treatment or prevention of inflammatory diseases.
... ml were 41.50, 35.38, 43.38, 24.84, and 39.20% lower than the model group (p < .05).Abbreviations: LPS, lipopolysaccharide; NO, nitric oxide; PEE, Phyllanthus emblica ethanol extract.TNF-α, IL-6, and IL-1β cytokines are important indicators of cellular inflammatory response, of which TNF-α causes severe inflammatory injury to cells and can induce synergistic effects with IL-1β and IL-6. These proinflammatory cytokines accelerate the arachidonic acid metabolism and cause excessive inflammation(Harun, Vidyadaran, Lim, Cole, & Ramasamy, 2015;Wang et al., 2011). In our study, as shown inTable 3,all PEE groups caused a decrease in IL-1β release by LPS-stimulated macrophages compared with the model group, demonstrating remarkable ...
Phyllanthus emblica (P. emblica) is a traditionally edible fruit that is good for treatment of biliary diseases, bronchitis, etc. It has obvious anti‐inflammatory activity, but few studies focus on its anti‐inflammatory active substance basis. The purpose of this study was to explore the material basis of anti‐inflammatory activity of P. emblica, purify, and identify anti‐inflammatory active monomers. Fisetin and gallic acid, which were identified after separation from ethanol extract components of P. emblica, exhibited the best anti‐inflammatory effects, markedly inhibiting nitric oxide and proinflammatory cytokine levels in LPS‐stimulated macrophages. In particular, fisetin with significant anti‐inflammatory activity was firstly identified from P. emblica. For the first time, our research systematically revealed the material basis of the anti‐inflammatory effects of P. emblica from the perspective of the composition of the bioactive substances and provided scientific research methods and ideas for researching bioactive monomers in other plant extracts.
... Safflower (Carthamus tinctorius L., Honghua in Chinese) is an annual plant belonging to the Compositae or Asteraceae family [1][2][3], which is used in Chinese folk medicine, owing to its potent bioactive properties, for the treatment of dysmenorrhea, menopause, chest pain, and abdominal pain [4,5]. It promotes blood circulation, which removes blood stasis and dredges the meridian, and can therefore be used in clinics for treating various cardiovascular and cerebrovascular diseases, including ...
An evaluation of the ultrasonic extraction process and the antioxidant activities of hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) from safflower are presented herein. Using response surface methodology (RSM), based on a four-factor-three-level Box–Behnken design (BBD), the extraction parameters, namely, temperature, extraction time, solvent-to-material ratio, and extraction power, were optimized for maximizing the yields of HSYA and AHSYB. The maximum yield was obtained at a temperature of 66 °C with an extraction time of 36 min, solvent-to-material ratio of 16 mL/g, and the extraction power of 150 W, which was adjusted according to the actual conditions. The HSYA and AHSYB contents were determined using high performance liquid chromatography (HPLC). The yield and the comprehensive evaluation value of HSYA and AHSYB were calculated. The antioxidant activities of the extracts were determined using a ferric reducing antioxidant power (FRAP) kit and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. The results suggested that the safflower extracts possessed obvious ferric reducing and DPPH radical scavenging activities. The antioxidant activity increased with increasing concentration. The results suggested that optimizing the conditions of ultrasonic extraction using RSM can significantly increase the yields of HSYA and AHSYB from safflower. The safflower extracts showed better antioxidant activity. This study can encourage future research on cardiovascular and cerebrovascular diseases.
... Some studies aiming at identifying HSYA in the brain tissues of rats suggested that HSYA, which increased the activities of superoxide dismutase and catalase, can be potentially used as a neuroprotective agent for traumatic brain injury [25]. Carthamus yellow, which is composed of safflomin A and safflomin B, provided an anti-inflammatory response by inhibiting the production of NO through downregulating iNOS gene expression in LPS-induced macrophages [26]. HSYA also exerted a protective effect against LPS-induced neurotoxicity in dopaminergic neurons through a mechanism that may be associated with the inhibition of IL-1β, TNF-α, and NO [27]. ...
Objective:
Safflower has antioxidant and anti-inflammatory activities. The two forms of preparations for safflower which are widely used in China are injection and decoction. The first step of the process for preparing an injection involves extracting safflower with water, which actually yields a decoction. This study is intended to investigate how the preparation process influences the anti-inflammatory activity of safflower in vitro.
Methods:
Five samples, including a decoction (sample 1) and an injection (sample 5) of safflower, were prepared according to the national standard WS3-B-3825-98-2012 and were analyzed by the oxygen radical absorbance capacity (ORAC) method and the 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) method for comparison. Sample 1 and sample 5 were further tested by the Griess assay and ELISA for their effects on nitric oxide (NO) production and interleukin- (IL-) 1β content in lipopolysaccharide- (LPS-) activated RAW264.7 cells. The protein and mRNA levels of inducible nitric oxide synthase (iNOS) and IL-1β were measured by Western blotting and real-time quantitative PCR.
Results:
Sample 5 showed a significantly higher ORAC value and a lower half inhibitory concentration (IC50) for DPPH scavenging activity as compared to the other four samples (p < 0.05). LPS significantly upregulated the mRNA and protein expressions of iNOS and IL-1β as compared to the solvent control (p < 0.01). As compared to sample 1, sample 5 significantly decreased NO production, iNOS protein expression, and the contents of IL-1β mRNA and IL-1β protein at both 100 μg/ml and 200 μg/ml (all: p < 0.05) and significantly downregulated iNOS mRNA expression at 100 μg/ml (p < 0.05).
Conclusions:
Results of this study demonstrate that the safflower injection prepared according to the national standard has a significant effect of suppressing protein and mRNA expressions of iNOS and IL-1β as compared to its traditional decoction.
... At least 21 compounds have been found in XBJ, including amino acids, phenolic acids, flavonoid glycoside, terpene glycoside, and phthalide (10). Radix Salviae Miltiorrhiae (11)(12)(13)(14)(15), Rhizoma Chuanxiong (16,17), Flos Carthami (18,19), and Angelica Sinensis (20)(21)(22) are known to exert an antiinflammatory effect. The quality of XBJ has been strictly controlled according to the standard set by the China Ministry of Public Health. ...
Background:
To evaluate the efficacy and safety of Xuebijing injection (XBJ) treatment for acute organophosphorus pesticide poisoning.
Methods:
Using the PubMed, Cochrane, Embase, Sinomed, Wanfang, CNKI, and Weipu (VIP) databases from the beginning of the datasets until December 2017, all of the relevant randomized controlled trials were identified. Relative risks (RR), weighted mean difference (WMD), along with 95% confidence interval (95% CI) were used to analyze the main outcomes. Statistical analysis was performed using the RevMan software version 5.3. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook.
Results:
Twenty-six randomized controlled trials with 1,880 participants were collected in total. Compared with just conventional therapy alone, XBJ combined with conventional therapy significantly reduced the 7-day mortality rate (RR: 0.33; 95% CI: 0.22-0.49), CRP in the 50 mL group (WMD: -11.60; 95% CI: -14.38 to -8.83), CRP in the 100 mL group (WMD: -1.73; 95% CI: -2.91 to -0.55), AChE in the 50 mL group (WMD: -4.58;95% CI: -5.87 to -3.28), AChE in the 100 mL group (WMD: -1.73; 95% CI: -2.07 to -1.39), hospital stays in the 50 mL group (WMD: -4.26; 95% CI: -4.89 to -3.64), TNF-α in the 50 mL group (WMD: -2.66; 95% CI: -4.99 to -0.32), NF-κB in the 50 mL group (WMD: -13.07; 95% CI: -14.67 to -11.47), and CK-MB in the 50 mL group (WMD: -32.28; 95% CI: -40.62 to -23.93). However, there was no statistical difference of TNF-α in the 100 mL group (WMD: -2.17; 95% CI: -4.66 to 0.32).
Conclusions:
XBJ has a significant clinical efficacy for the treatment of patients with acute organophosphorus pesticide poisoning. The most effective dose is 50 mL, while the most effective frequency is twice a day. However, more studies are needed to confirm the extract efficacy of XBJ.
... HSYA suppressed the expression of TLR-4, Myd88, ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells. HSYA treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) [166]. The effects of dried safflower petals aqueous extracts (SFA) and Carthamus yellow (CY) were investigated on lipopolysaccharide (LPS)-induced inflammation using RAW264.7 macrophages. ...
The pharmacological studies showed that many medicinal plant possessed antiinflammatory activity. Biochemical and molecular investigations revealed that the anti-inflammatory activities of medicinal plants and plant-derived compounds were related to their interactions with several key enzymes, signaling cascades involving cytokines and regulatory transcription factors, and to their antioxidant effects. The current review highlighted the medicinal plants possessed antiinflammatory effects with special focus on their mode of action.
... SFA and CY inhibited LPSstimulated nitric oxide (NO), prostaglandin E 2 (PGE 2 ), and interleukin 1β (IL-1β) release, through attenuation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. Furthermore, SFA and CY suppressed the LPS-induced phosphorylation of nuclear factor-κB, which was associated with the inhibition of IκB-α degradation [172]. ...
The chemical groups isolated from Carthamus tinctorius were included oils, proteins, minerals, phenolics, flavonoids, alkaloids, lignans, carboxylic acids, steroids, polysaccharides, quinochalcone C-glycosides and quinone-containing chalcones. It exerted many pharmacological activities including central nervous, cardiac, vascular, anticoagulant, reproductive, gastrointestinal, antioxidant, hypolipidemic, metabolic and many other pharmacological effects. This paper will highlight the chemical constituents and pharmacological effects of Carthamus tinctorius.
... 2 Safflower petals are also used as a food additive and a natural pigment. 3 The main active ingredient of safflower is Carthamus yellow, which is composed of safflomin A and safflomin B. 4 However, the safety of safflower use has been challenged because it is often the target of artificial coloration and adulteration. The color of safflower is usually associated with the content of the active pharmaceutical ingredient, which makes it an important attribute for determining the quality of safflowers. ...
Objective: Rapid discrimination of three classes of safflowers, dyed safflower, adulterated safflower, and pure safflower using computer vision and image processing algorithms.
Methods: A low cost computer vision system (CVS) was designed to measure the color of safflowers in the RGB (red, green, blue), L?a?b?, and HSV (hue, saturation, vale) color spaces. The color moments in these three color spaces were extracted from the acquired images as color features of safflower. In addition, five kinds of pigments that are commonly used to dye safflowers were identified by high-performance liquid chromatography as a reference. Pattern recognition methods were investigated for rapid discrimination, including an unsupervised principal component analysis (PCA) algorithm and a supervised partial least squares discriminant analysis (PLS-DA) algorithm.
Results: The mean error (e?) between color values measured with the colorimeter and calculated with the CVS was 2.4%, with a high correlation coefficient (r) of 0.9905. This result indicated that the established CVS was reliable for color estimation of safflowers. The PLS-DA model, which had a total accuracy of 91.89%, outperformed the PCA model in classifying pure, adulterated, and dyed safflowers.
Conclusion: The color objectification is a promising tool for rapid identification of dyed and adulterated safflowers.
... In addition, the degree of liver cirrhosis observed in humans is similar to that observed in diethylnitrosamine (DEN)-induced rats [4,5]. Pharmacological experiments have demonstrated that Radix Bupleuri possesses wide-reaching biological activities, including coronary artery dilation, immune system modulation, anti-inflammatory properties and analgesia [6][7][8][9][10][11]. Due to the traditional use of Radix Bupleuri in the prevention of liver cirrhosis [12], this study was performed to investigate the protective effect of Radix Bupleuri extract (RBE) against liver cirrhosis in rats. ...
Purpose: To explore the effect of Radix Bupleuri extract (RBE) on diethylnitrosamine (DEN)-induced liver cirrhosis in rats. Methods: Rats were injected with DEN once a week for 8 weeks to induce liver cirrhosis. Some DENinduced rats were also treated with RBE, which was obtained by extracting dried Radix Bupleuri in water, for 8 weeks. Afterwards, biochemical indices and oxidative stress markers were assessed. Results: RBE significantly decreased serum concentrations of both alanine transaminase (137.3 ± 4.4 U/L, p < 0.01) and aspartate aminotransaminase (152.1 ± 3.4 U/L, p < 0.01) in DEN-induced rats at week 8. In addition, RBE significantly decreased malondialdehyde (0.13 ± 0.02 umol/L, p < 0.01) and superoxide dismutase (0.73 ± 0.04 U/mg protein, p < 0.01) levels in DEN-induced rats (p < 0.01). Conclusion: RBE exhibits a protective effect against DEN-induced liver cirrhosis in rats. Thus, it may have the potential to be used to treat liver cirrhosis in clinical settings. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.
... Salvia miltiorrhiza Bge is a herb that possesses wide-reaching biological activities, including coronary artery dilation, improvement of myocardial ischemia, and modulation of the immune system, as well as antithrombotic, antioxidation, anti-aging, antihypoxic, antifatigue, anti-inflammatory, anti-hepatic fibrosis, antitumor, and analgesia effects [7][8][9][10][11][12]. As S. miltiorrhiza is used in traditional Chinese medicine to prevent liver cirrhosis [13], the current study was conducted to evaluate the anti-cirrhosis effects of the herb in rats. ...
Purpose: To explore the effects of Salvia miltiorrhiza Bge.extract(SMBE) on diethylnitrosamine(DEN)- induced liver cirrhosis in rats. Methods: SMBE was obtained by extracting dried Salvia miltiorrhiza Bge. in water. Liver cirrhosis was induced in Wistar rats by injecting diethylnitrosamine in abdominal cavity once a week for 8 weeks. Concurrently, rats received either daily oral SMBE (SMBE group) or saline (control group). Clinical biochemical assessments, oxidative stress tests (malondialdehyde [MDA], superoxide dismutase [SOD]) were performed at 4 and 8 weeks after beginning DEN. Results: Compared to the control group, both plasma alanine transaminase (ALT, 245.6 ± 8.5 U/L) and aspartate aminotransferase (AST, 205.7 ± 5.1 U/L) were significantly lower in SMBE group after 8 weeks (p < 0.01 for both ALT and AST). SMBE group exhibited significantly lower MDA (0.41 ± 0.04 µmol/L) levels and higher SOD(0.53 ± 0.05 U/mg protein) activity than control at 8 weeks after commencing DEN (p < 0.01 for both MDA and SOD). Conclusion: SMBE has significant ameliorative effect on DEN-induced liver cirrhosis in rats. Antioxidant and anti-apoptotic effects of SMBE appear to be involved in these beneficial effects. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria.
... All of these compounds have been classified within the quino chalcone family of flavonoids. Previous studies also demonstrated that safflower yellow, including these compounds, provides the main biological functions of safflower, such as asodilative activity to reduce blood pressure and heart rate, anti-inflammatory, neuroprotective, and anti-hepatic fibrosis activities (Li et al. 2009;Wang et al. 2011;Li et al. 2012). Several studies have proven SY's pharmacological effects, including expansion of coronary arteries, myocardial protection, antioxidation, and cerebral protection (Yang et al. 2009;Chen et al. 2006). ...
Alzheimer’s disease (AD), the most common cause of dementia worldwide, is mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. Safflower yellow (SY) is a novel water extract of natural safflower and has been suggested to ameliorate memory deficits in several animal models of dementia. In this study, we aimed to investigate the effect and mechanism of SY on deficits of learning and memory and hyperphosphorylation of tau in APP/PS1 double transgenic mice. APP/PS1 mice were administered with SY (10, 30, 100 mg/kg) by oral gavage for three months at the age of six months. The ability of learning and memory was investigated using the step-down test and Morris water maze test, and protein level in the brain was evaluated using western blot. Here, we found that SY treatment can improve spatial learning and memory ability, and reduce tau hyperphosphorylation at Ser199, Thr205, Ser396, Ser404 sites in APP/PS1 mice. In addition, the activity the of cyclin-dependent kinase 5 (CDK-5) and glycogen synthase kinase 3β (GSK-3β), major kinases involved in tau phosphorylation, was siginificantly decreased in APP/PS1 mice by SY treatment. These results support SY can serve as a promising multitarget neuronal therapeutic agent for the treatment of AD.
... The results showed that, through the upregulation of the expression of bFGF and collagen type I protein, CY enhances the tensile strength of the tendon and alleviates the tendon adhesion and inflammatory reaction in the injured area, and promotes the repair of the injured tendon . By downregulating the expression of iNOS and COX-2 gene, CY inhibits the production of NO and PGE2, as well as provides an anti-inflammatory response (Wang et al., 2011). In addition, a recent study has demonstrated the inhibitory activities of CY on tyrosinase and melanin formation, which indicates that CY may be developed into an effective skin-whitening agent in the future . ...
Carthamus tinctorius L. is a multifunctional cash crop. Its flowers and seeds are extensively used in traditional herbal medicine in China, Korea, Japan, and other Asian countries, for treating various ailments such as gynecological, cardiovascular, and cerebrovascular diseases as well as blood stasis and osteoporosis. More than 100 compounds have been isolated and identified from C. tinctorius. Flavonoids and alkaloids, especially the quinochalcone c-glycoside hydroxysafflor yellow A, N-(p-Coumaroyl)serotonin, and N-feruloylserotonin, are responsible for most of the pharmacological activities of C. tinctorius. In this paper, comprehensive and up-to-date information on the phytochemistry and pharmacology of C. tinctorius is presented. This information will be helpful for further explorations of the therapeutic potential of C. tinctorius and may provide future research opportunities.
... Dried safflower petal aqueous extract (SFA) and its main constituent cathamus yellow (CY), which is composed of safflomin A and safflomin B, were shown to protect against lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. SFA and CY inhibited LPS-stimulated nitric oxide (NO), prostaglandin E 2 (PGE 2 ), and interleukin 1β (il-1β) release through attenuation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression (Wang et al., 2011). Moreover, methanol extract of Carthamus tinctorius (MEC) also was demonstrated to have antiinflammatory action involving in hemeoxygenase-1(HO-1) induction. ...
Carthamus tinctorius L. (safflower) is a widely used traditional Chinese medicine, which has been used to treat dysmenorrhea, amenorrhea, postpartum abdominal pain and mass, trauma and pain of joints in China for many years. This article summarizes the up-to-date and comprehensive information on safflower covering the aspects of the botanical identity, chemical constituents, pharmacological studies, TCM applications and dietary usage, clinical evidences, quality evaluation and assurance, and safety evaluation and toxicity issue. Carthamus tinctorius L. is an annual or biennial herbal plant in the family of Compositae, and its tubular flowers have been used as the medicinal material. In terms of chemical constituents, quinochalcones and flavonoids are considered as the characteristic and active constituents of safflower. In accordance with the traditional application and clinical practice of safflower, modern pharmacological studies have also demonstrated that safflower possesses a wide range of medicinal functions, such as dilating coronary artery, improving myocardial ischemia, modulating immune system, anticoagulation and antithrombosis, antioxidation, antiaging, antihypoxia, antifatigue, anti-inflammation, antihepatic fibrosis, antitumor, analgesia, etc. What is more, quality control and toxicity issues are also presented to have a better understanding of safflower.
... Modern pharmacological experiments have demonstrated that safflower with its active compounds possesses wide-reaching biological activities, including dilating coronary artery, improving myocardial ischemia, modulating immune system, anticoagulation and antithrombosis, antioxidation, anti-aging, antihypoxia, antifatigue, antiinflammation, antihepatic fibrosis, antitumor, analgesia, etc [2][3][4][5][6][7]. Due to its traditional use of CTL in the prevention of cardiovascular disease [8], this study was therefore performed on models of thrombosis in rats and compared to the standard antiplatelet agent, aspirin [9]. ...
Purpose: To explore the effects of Carthamus tinctorius L. (CTL) extracts on thrombosis in rats. Methods: CTL extract was obtained in hot water (60 degrees C), dried in a hot air oven and then freeze-dried. The rats were divided into 6 groups: normal group, control group, reference group (aspirin 5 mg/kg) as well as groups that received 20, 40 and 80 mg/kg doses of CTL, respectively. For each group, treatment was given orally once daily for 14 days. Common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, as well as plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1 alpha(6-keto-PGF1 alpha) were measured in rats. Results: Compared with the control group, all doses of CTL extracts significantly and dose-dependently prolonged thrombosis occlusion time, reduced the weight of thrombus and increased inhibition rate (p < 0.01). Plasma TXB2 concentration of all CTL extracts groups decreased dose-dependently (p < 0.05) while that of 6-keto-PGF1 alpha was increased (p < 0.05). There was association between 6-keto-PGF1 alpha/TXB2 and arterial or venous thrombus weight for all treatments, and also with occlusion time for CTL treatment but not for aspirin. Conclusion: CTL has a significant effect on thrombosis in rats. However, further studies are required to determine its clinical potentials.
... Modern pharmacological experiments have demonstrated that Carthamus tinctorius L with its active compounds possesse wide-reaching biological activities, including dilated coronary artery, improved myocardial ischemia, modulated immune system, anticoagulation and antithrombosis, anti-oxidation, anti-aging, antihypoxia, anti-fatigue, anti-inflammation, antihepatic fibrosis, antitumor, analgesia, etc [6][7][8][9][10][11]. Due to its traditional use of Carthamus tinctorius L in the prevention of liver cirrhosis [12], this study was performed on models of liver cirrhosis in rats. ...
Purpose: To explore the effects of Carthamus tinctorius L. extract (CTLE) on diethylnitrosamine (DEN)- induced liver cirrhosis in rats. Methods: CTLE was obtained by extracting the dried Carthamus tinctorius L. in water. Liver cirrhosis was induced by injecting the rats with DEN once a week for 8 weeks. Following this treatment, clinical biochemical assessments, as well as oxidative stress test and histopathological examination were performed. Results: Compared with the control group, plasma concentrations of alanine transaminase (ALT) and aspartate aminotransferase (AST) both decreased significantly (p < 0.01) after 8 weeks. The degree of liver fibrosis, cirrhosis and necrosis decreased in CTLE-treated rats. CTLE significantly inhibited malondialdehyde (MDA) and superoxide dismutases (SOD) in DEN-induced rat liver (p < 0.01) compared with control group. Conclusion: CTLE has significant inhibitory effect on diethylnitrosamine-induced liver cirrhosis in rats, which can be developed for future clinical applications.
Background
Safflower thrives in dry environments but faces difficulties with flowering in wet and rainy summers. Flavonoids play a role in flower development and can potentially alleviate these challenges. Furthermore, the FLOWERING LOCUS T (FT) family of phosphatidylethanolamine-binding protein (PEBP) genes play a crucial role in the photoperiodic flowering pathway. However, their direct impact on flowering and flavonoid biosynthesis under different light duration is elusive.
Results
Utilizing the genome sequencing of Safflower (Jihong NO.1), the current study identifies three specific genes (CtFT1, CtFT2, and CtFT3) that exhibit upregulation in response to long-day conditions. The overexpression of CtFT2, displayed an early, whereas CtFT1 and CtFT3 late flowering phenotype in Arabidopsis thaliana. Interestingly, the transient overexpression of CtFT1 in safflower leaves caused early flowering, while overexpressing CtFT2 and CtFT3 led to late flowering. Additionally, overexpressing CtFT3 in Arabidopsis and CtFT1, CtFT2, and CtFT3 in safflower leaves, significantly increased flavonoid synthesis.
Conclusions
These findings showed that overexpression of CtFT genes could affect the flowering time and significantly increase the flavonoid content of safflower. The function of CtFT gene is different in safflower and Arabidopsis. This study provides valuable insights into the role of CtFT genes in flower formation and flavonoid synthesis in safflower, which may help in improving safflower breeding quality and its adaptability to diverse environmental conditions.
Qiangxin Lishui Prescription (QLP) has been clinically applied for treating heart failure with remarkable curative effects. A multi‐component pharmacokinetic research is very necessary for determining active substances in it. This study aims to profile the traits and differences in the pharmacokinetics of salvianolic acid B, astragaloside IV, calycosin‐7‐O‐ β ‐D‐glucoside and kaempferol in QLP between normal and chronic heart failure (CHF) rats by microdialysis combined with ultra‐high‐performance liquid chromatography‐tandem mass spectrometry (UHPLC‐MS/MS). Sensitive, selective, and online microdialysis combined with the UHPLC‐MS/MS method was successfully established and applied to study the pharmacokinetics of QLP. The pathological condition of CHF could lead to the enhancement of systematic exposure and reduction of the metabolic rate of four bioactive components for better bioavailability and therapeutic efficacy. The pharmacokinetic results will provide data support for the clinical application of QLP.
Ethnopharmacological relevance:
Kheaw-Hom (KH) remedy, a Thai traditional medicine (TTM) on the National List of Essential Medicines, has long been clinically used to treat fever and inflammation in children. However, no in vitro or in vivo anti-inflammatory or bioactive compound studies are published in the literature.
Aims of the study:
To explore the in vitro and in vivo anti-inflammatory activities of KH remedy and its bioactive compound and analyze relationships between flavor and ethnopharmacological activities of plant components in KH remedy according to TTM theory.
Materials and methods:
Ethyl p-methoxycinnamate (EPMC), a bioactive compound of KH remedy was analyzed using high performance liquid chromatography (HPLC). In vitro anti-inflammatory activities of ethanolic extract (KHE), aqueous extract (KHA), acid-hydrolysis of KHA (KHA-h), acid-hydrolysis of KH powder (KHP-h), and EPMC were investigated using lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-alpha (TNF-α) production in murine macrophage RAW 264.7 cells. In vivo anti-inflammatory activities of KH powder (KHP) and KHE were determined using carrageenan-induced paw edema and ethyl phenylpropiolate (EPP)-induced ear edema in rats and PGE2 production in tissue samples was examined.
Results:
KHP-h showed the highest EPMC content (21.33 ± 1.08 mg/g of extract) and inhibited PGE2, NO, and TNF-α production with IC50 values of 11.92 ± 0.21, 30.61 ± 3.12, and 56.71 ± 2.91 μg/mL, respectively, followed by KHE and KHA-h while KHA did not. EPMC, a bioactive compound of KH remedy showed high anti-inflammatory activities through three pathways. KHP oral administration (100 mg/kg) significantly minimized rat paw inflammation at 1, 2, and 3 h while KHE (100 mg/kg) noticeably reduced at 2 and 3 h. KHP (100, 200, and 400 mg/kg) and KHE (100 mg/kg) significantly inhibited PGE2 production. KHP (1% w/v) notably reduced rat ear edema at 30, 60, and 120 min whereas KHE at all concentrations decreased swelling at 120 min. KHP and KHE at all doses significantly inhibited PGE2 production. Cool flavor was the main KH remedy flavor. Spicy plant components and some fragrant components showed high anti-inflammatory activity.
Conclusions:
Results from the in vivo study strongly paralleled the in vitro study. These findings support the rational use of KH remedy according to TTM theory for fever treatment and inflammation in children.
GuHong injection is composed of safflower and N-acetyl-L-glutamine. It is widely used in clinical for cerebrovascular diseases, such as ischemic stroke and related diseases. The objective of this review is to comprehensively summarize the most recent information related to GuHong in the treatment of stroke, including chemical composition, clinical studies, potential pharmacological mechanisms and pharmacokinetics. Additionally, it examines possible scientific gaps in current study and aims to provide a reliable reference for future GuHong studies. The systematic review reveals that the chemical composition of safflower in GuHong is more than 300 chemical components in five categories. GuHong injection is primarily used in clinical applications for acute ischemic stroke and related diseases. Pharmacological investigations have indicated that GuHong acts in the early and recovery stages of ischemic stroke by anti-inflammatory, anti-oxidative stress, anti-coagulation, neuroprotective and anti-apoptotic mechanisms simultaneously. Pharmacokinetic studies found that the main exposed substances in rat plasma after GuHong administration are hydroxysafflor yellow A and N-acetyl-L-glutamine, and N-acetyl-L-glutamine could exert its pharmacological effect across the blood-brain barrier. As a combination of Chinese herb and chemical drug, GuHong injection has great value in drug research and clinical treatment, especially for ischemic stroke disease. This article represents a comprehensive and systematic review of existing studies on GuHong injection, including chemical composition, pharmacological mechanism, and pharmacokinetics, which provides reference significance for the clinical treatment of ischemic stroke with GuHong, as well as provides guidance for further study.
The present study was carried out to determine variations in flower and dye yield and chemical contents of safflower genotypes with different flower colors in 2017–2018. The flower and dyestuff yields of the genotype ranged between 6.6–12.0 kg da⁻¹ and 218.1–421.7 g da⁻¹, respectively. The TPC and high antioxidant capacity values were listed according to flower color as yellow > orange > red > white. Gallic, rosmarinic and chlorogenic acid were higher in orange-flowered genotypes, kaempferol in red-flowered and catechin in yellow and orange-flowered. The oil content ranged between 4.32–6.12%. In flowers, linoleic acid ranged between 32.77–48.27%, α-linolenic acid 1.85–3.38% and γ-linolenic acid 14.76–18.50%. According to the Headspace Solid Phase Microextraction (HS-SPME) technique; the main scent molecules of flowers were β-caryophyllene, α-pinene, 1-tetradecene, β-cedrene, α-cedrene and β-myrcene. The C* value of flowers was positively correlated with the total phenolic content and dyestuff content in both years, and genotypes with high C value showed high antioxidant activity. Askon-42 can be recommended for high flower yield, dyestuff content and yield among genotypes, and US-10 genotype for the total phenolic content and antioxidant activity. For further research, it will guide the use of different colored safflower flower extracts, which are natural dye sources, in natural cosmetic products.
Water deficit affects safflower development, but its effects can be mitigated by potassium fertilization. We use morphological, nutritional and production components to evaluate the effect of potassium fertilization in safflower response to water deficiency and subsequent rehydration. The experimental design used was completely randomized in a 3 × 3 factorial scheme, consisting of doses (0, 80, 160 kg ha−1) of potassium chloride (KCl) and water tensions in the soil, – 10 kPa (without water deficiency), – 50 kPa (moderate water deficiency) and – 70 kPa (severe water deficiency), with four repetitions. Plant height, number of leaves, number of branches, number of capitula and stem diameter were evaluated at 30 days after the imposition of water regimes and at 20 days after rehydration. The nutritional status of leaves and grains was evaluated after rehydration and at harvest, respectively, through the levels of nitrogen (N), phosphorus (P), potassium (K), calcium (Ca) and magnesium (Mg). Potassium fertilization positively influenced morphology, nutrition and safflower production, and the effects were accentuated with the application of 160 kg ha−1 of KCl without water deficiency and under moderate water deficiency. Under severe water deficiency, there was no recovery of safflower. Therefore, the dose of 160 kg ha−1 of KCl is adequate to mitigate the effects of only moderate water deficiency in safflower.
Ethnopharmacological relevance
Alzheimer's disease (AD) is a multicausal neurodegenerative disease clinically characterized by generalized dementia. The pathogenic process of AD not only is progressive and complex but also involves multiple factors and mechanisms, including β-amyloid (Aβ) aggregation, tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. As the first-line treatment for AD, cholinesterase inhibitors can, to a certain extent, relieve AD symptoms and delay AD progression. Nonetheless, the current treatment strategies for AD are far from meeting clinical expectations, and more options for AD treatment should be applied in clinical practice.
Aim of the review
The aim of this review was to investigate published reports of C. tinctorius L. and its active constituents in AD treatment through a literature review.
Materials and methods
Information was retrieved from scientific databases including Web of Science, ScienceDirect, Scopus, Google Scholar, Chemical Abstracts Services and books, PubMed, dissertations and technical reports. Keywords used for the search engines were “Honghua” or “Carthamus tinctorius L.” or “safflower” in conjunction with “(native weeds OR alien invasive)”AND “Chinese herbal medicine”.
Results
A total of 47 literatures about C. tinctorius L. and its active constituents in AD treatment through signaling pathways, immune cells, and disease-related mediators and systematically elucidates potential mechanisms from the point of anti-Aβ aggregation, suppressing tau protein hyperphosphorylation, increasing cholinergic neurotransmitters levels, inhibiting oxidative stress, anti-neuroinflammation, ameliorating synaptic plasticity, and anti-apoptosis.
Conclusions
Chinese herbal medicine (CHM) is a treasure endowed by nature to mankind. Emerging studies have confirmed that CHM and its active constituents play a positive role in AD treatment. Carthamus tinctorius L., the most commonly used CHM, can be used with medicine and food, with the effect of activating blood circulation and eliminating blood stasis. In the paper, we have concluded that the existing therapeutic mechanisms of C. tinctorius L. and summarized the potential mechanisms of C. tinctorius L. and its active constituents in AD treatment through a literature review.
Background:
Safflower is an annual herb used in traditional Chinese herbal medicine. It consists of the dried flowers of the Compositae plant safflower. It is found in the central inland areas of Asia and is widely cultivated throughout the country. Its resistance to cold weather and droughts and its tolerance and adaptability to salts and alkalis are strong. Safflower has the effect of activating blood circulation, dispersing blood stasis, and relieving pain. A natural pigment named safflower yellow (SY) can be extracted from safflower petals. Chemically, SY is a water-soluble flavonoid and the main active ingredient of safflower. The main chemical constituents, pharmacological properties, and clinical applications of SY are reviewed in this paper, thereby providing a reference for the use of safflower in preventing and treating human diseases.
Methods:
The literature published in recent years was reviewed, and the main chemical components of SY were identified based on chemical formula and structure. The pharmacological properties of hydroxysafflor yellow A (HSYA), SYA, SYB, and anhydrosafflor yellow B (AHSYB) were reviewed.
Results:
The main chemical constituents of SY included HSYA, SYA, SYB, and AHSYB. These ingredients have a wide range of pharmacological activities. SY has protective effects on the heart, kidneys, liver, nerves, lungs, and brain. Moreover, its effects include, but are not limited to, improving cardiovascular and cerebrovascular diseases, abirritation, regulating lipids, and treating cancer and diabetic complications. HSYA is widely recognised as an effective ingredient to treat cardiovascular and cerebrovascular diseases.
Conclusion:
SY has a wide range of pharmacological activities, among which improving cardiovascular and cerebrovascular diseases are the most significant.
Natural deep eutectic solvents (NaDESs) are promising green alternatives to conventional solvents widely applied in the extraction of natural products due to their physical and chemical superiorities. In present study, 22 NaDESs consisted from food grade ingredients were screened in ultrasonic assisted extraction (UAE) of bioactive compounds from safflower. The oral bioavailabilities of hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (ASYB) in the extracts were then investigated in SD rats with the help of HPLC-MS technique. The results revealed that L-proline-acetamide (L-Pro-Am) was an effective solvent with the yields of HSYA and ASYB at 32.83 and 8.80 mg/g. Pharmacokinetic studies revealed that the blood level of HSYA and ASYB were significantly higher after oral administration of L-Pro-Am extract than that of aqueous extract. Especially, the relative bioavailabilities (to aqueous extract) of HSYA and ASYB were calculated 183.5% and 429.8%.
Safflower (Carthamus tinctorius L.) has long been grown as a crop due to its commercial utility as oil, animal feed, and pharmacologically significant secondary metabolites. The integration of omics approaches, including genomics, transcriptomics, metabolomics, and proteomics datasets, has provided more comprehensive knowledge of the chemical composition of crop plants for multiple applications. Knowledge of a metabolome of plant is crucial to optimize the evolution of crop traits, improve crop yields and quality, and ensure nutritional and health factors that provide the opportunity to produce functional food or feedstuffs. Safflower contains numerous chemical components that possess many pharmacological activities including central nervous, cardiac, vascular, anticoagulant, reproductive, gastrointestinal, antioxidant, hypolipidemic, and metabolic activities, providing many other human health benefits. In addition to classical metabolite studies, this review focuses on several metabolite-based working techniques and updates to provide a summary of the current medical applications of safflower.
Metabolic syndrome, such as diabetes mellitus, obesity, atherosclerosis, and high blood pressure (HBP), are closely linked pathophysiologically. However, current monotherapies for metabolic syndrome fail to target the multifactorial pathology via multiple mechanisms, as well as resolving the dysfunctionality of the cells and organs of the body. We aimed to provide a comprehensive and up-to-date review of the pharmacological advances, therapeutic potential, and phytochemistry of Salvia miltiorrhiza, Carthamus tinctorius, and Danhong injection (DHI). We discussed the molecular mechanisms of the bioactive constituents relating to diabetes mellitus and metabolic disease for further research and drug development. Interestingly, Salvia miltiorrhiza, Carthamus tinctorius, and DHI have anti-inflammatory, anti-glycemic, anti-thrombotic, and anti-cancer properties; and they mainly act by targeting the dysfunctional vasculatures including the inflammatory components of the disease to provide vascular repair as well as resolving oxidative stress. The major bioactive chemical constituents of these plants include polyphenolic acids, diterpene compounds, carthamin, and hydroxysafflor yellow A. Treatment of diabetes mellitus and its associated cardiovascular complication requires a comprehensive approach involving the use of appropriate traditional Chinese medicine formula. Danshen, Honghua, and DHI target the multiple risk factors regulating the physiologic function of the body and restore normalcy, apart from the traditional advice on exercise and diet control as treatment options in a metabolic syndrome patient.
The compatibility of Salviae Miltiorrhizae Radix et Rhizoma (SMRR) and Carthamii Flos (CF) is a common pair-herb used in the modern traditional Chinese medicine prescriptions. As a function of promoting blood circulation and removing blood stasis, both SMRR and CF have been clinically used for hundreds of years and enduring popularity until today. At present, there have been many listed Chinese medicine prescriptions which were compatible with SMRR and CF. In this paper, we reviewed the research status of the formulae preparations, pair-herb compatibility, and component compatibility of SMRR and CF. We clarified the research advances in the chemistry, pharmacology, effective material base, and pharmacokinetics before and after the compatibility of SMRR and CF. Further, we indicated the scientificity and necessity of its compatibility and provided the references for the further research and modern formulation development of SMRR and CF.
Background:
Safflower polysaccharide (SPS) is one of the most important active components of safflower (Carthamus tinctorius L.), which has been confirmed to have the immune-regulatory function and antitumor effect. This study aimed to explore the effects of safflower polysaccharide (SPS) on tongue squamous cell carcinoma (TSCC).
Methods:
HN-6 cells were treated with 5 μg/mL cisplatin and various concentrations of SPS (0, 0.02, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28 mg/mL), and cell proliferation was measured. After treatment with 5 μg/mL cisplatin and 0.64 mg/mL SPS, the induction of apoptosis and the protein and mRNA expression of Bax, Bcl-2, COX-2, and cleaved caspase-3 in HN-6 cells were quantified. In addition, HN-6 cells were implanted into mice to establish an in vivo tumor xenograft model. Animals were randomly assigned to three groups: SPS treatment, cisplatin treatment, and the model group (no treatment). The body weight, tumor volume, and tumor weight were measured, and the expression of the above molecules was determined.
Results:
SPS treatment (0.02-0.64 mg/mL) for 24-72 h inhibited HN-6 cell proliferation. In addition, 0.64 mg/mL SFP markedly induced apoptosis in HN-6 cells and arrested the cell cycle at the G0/G1 phase. Compared with the control group, the expression of Bcl-2 and COX-2 was markedly reduced by SPS treatment, whereas the expression of Bax and cleaved caspase-3 was increased. Moreover, SPS significantly inhibited the growth of the tumor xenograft, with similar changes in the expression of Bcl-2, COX-2, Bax, and cleaved caspase-3 in the tumor xenograft to the in vitro analysis.
Conclusions:
Our results indicated that SPS may inhibit TSCC development through regulation of Bcl-2, COX-2, Bax, and cleaved caspase-3 expression.
Background
Gastrointestinal (GI) symptoms are common in the general population. This investigation studied the effects of Carthami flos (CF), a natural product, on GI motility.
Methods
We checked the intestinal transit rates (ITRs) or gastric emptying in normal and in GI-motility-dysfunction (GMD) mice in vivo. The GMD mice were made by acetic acid or streptozotocin.
Results
Both ITRs and gastric emptying were increased by CF (0.0025–0.25 g/kg) dose dependently. Also, in the GMD mice models, acetic-acid-induced peritoneal irritation, and streptozotocin-induced diabetic mice, the ITRs were decreased compared to normal mice, and these decreases were inhibited by CF.
Conclusion
These results suggest that CF is one of the good candidates for the development of a prokinetic agent that may regulate GI-motility functions.
Carthamin yellow (CY), which is a flavonoid compound isolated from safflower, has various pharmacological effects including promoting blood circulation to remove blood stasis and alleviating pain. CY is a herb used in Chinese traditional medicines. Intervertebral disc degeneration (IDD) is a common spinal disorder and degeneration of nucleus pulposus (NP) cells and inflammation are significant parts of the pathological cascade. The curative effect of CY on NP cells in association with degeneration and inflammation remains to be elucidated. In the present study, rat NP cells were isolated, cultured and used to detect the suppressive effects of CY on lipopolysaccharide (LPS)-induced genetic expression variation and the expression of matrix degradation enzymes, including matrix metallopeptidase-3, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4 and ADAMTS-5. A protective effect of CY on NP cells was observed against LPS-induced matrix degradation and inflammation. Western blotting results demonstrated that pretreatment with CY significantly suppressed the LPS-induced activation of the mitogen activated protein kinase (MAPK) pathway. The results of the present study suggested that CY exerted anti-degenerative and anti-inflammatory effects on NP cells via inhibition of MAPK pathway activation. Therefore, CY may be a potential therapeutic drug for the treatment of IDD in the future.
The present work aimed at investigating the pattern recognition receptor (PRR) and immunostimulatory mechanism of a purified Dendrobium huoshanense polysaccharide (DHP). We found that DHP could bind to the surface of macrophages and stimulate macrophages to secrete NO, TNF-α and IL-1β. To unravel the mechanism for the binding of DHP to macrophages, flow cytometry, confocal laser-scanning microscopy, affinity electrophoresis, SDS-PAGE and western blotting were employed to verify the type of PRR responsible for the recognition of DHP by RAW264.7 macrophages and peritoneal macrophages of C3H/HeN and C3H/HeJ macrophages. Results showed that toll-like receptor 4 (TLR4) was an essential receptor for macrophages to directly bind DHP. Further, the phosphorylation of ERK, JNK, Akt and p38 were observed to be time-dependently promoted by DHP, as well as the nuclear translocation of NF-κB p65. These results suggest that DHP activates macrophages via its direct binding to TLR4 to trigger TLR4 signaling pathways.
A sensitive ultrafast liquid chromatography coupled with triple quadrupole mass spectrometric (UFLC-MS/MS) method for the quantification of anhydrosafflor yellow B (AHSYB), a major active water-soluble pigment from Carthamus tinctorius, in rat plasma has been developed and validated. Sample preparation was achieved by protein precipitation of plasma with four volumes of methanol. Rutin was used as the internal standard (IS). The analytes were separated using a C18 column with an 8min gradient elution, followed by mass spectrometric detection using negative electrospray ionization (ESI(-)) in multiple reaction monitoring (MRM) mode. The method was linear in the concentration range of 25-10,000ng/mL for AHSYB. Intra-day and inter-day precision variation was less than 6.5%. The relative error of accuracy was within ±9.4%. The mean recovery of AHSYB was higher than 70.9%. The established method was successfully applied to the pharmacokinetic study after intravenous (2.5mg/kg) and oral (30mg/kg) dosing of AHSYB in normal rats. And the pharmacokinetic properties of AHSYB in rats with acute blood stasis and the differences between normal and acute blood stasis syndrome rats were also investigated. The results showed that the compound was poorly absorbed (∼0.3%) and the AUC0-t, AUC0-∞ and F were all significantly lower (P<0.05) in acute blood stasis syndrome rats, suggesting that disease condition may alter the body metabolism by enhancing metabolite enzyme activity.
In the course of screening for immunomodulators, we found a significant blastogenic activity specific for splenic B cells in the extracts of safflower (Carthamus tinctorius L.). Active fractions termed SF1 and SF2 were purified from dried petals of safflower by boiling water extraction, ethanol precipitation and Sepharose CL-2B column chromatography. The elution profiles of the gel filtration indicated that the molecular weight of SF1 and SF2 was estimated to be more than 100 kD. Major components of SF1 and SF2 seem to be polysaccharides, and structural analysis of alditol acetate derivatives by GC-MS revealed some differences between SF1 and SF2 in the sugar component. Biological activities of SF1 and SF2 on B cells and macrophages were examined in comparison with lipopolysaccharides (LPS). SF1 and SF2 induced both the proliferation and the IgM production of B cells to the equivalent level as those induced by LPS. In macrophages, SF1 and SF2 effectively stimulated the production of NO. However, SF1 stimulated the production of IL-1, IL-6, and TNF as much as LPS, while SF2 induced them only weakly or not at all. Thus, these results suggest that SF1 and SF2 activate B cells and macrophages in different mechanisms.
Previous reports have shown that safflower-seed extract and its major antioxidant constituents, serotonin hydroxycinnamic amides, attenuated atherosclerotic lesion formation in apoE-deficient mice, as well as inflammation and aortic stiffness in human subjects. In the present report, we examined a still unknown cell-based mechanism of serotonin derivatives against the development of atherosclerosis, focusing our attention on their action against the increase of adhesion molecules and the release of chemotactic factors on human aortic endothelial cells, phenomena that represent the key events in the early stages of atherosclerogenesis. Serotonin derivatives N-(p-coumaroyl)serotonin and N-feruloylserotonin exerted an inhibitory effect on short-term high glucose-induced up-regulation of mRNA and protein of adhesion and migration factors, and the consequent adhesion and migration of monocytes to endothelial cells; they inhibited the activation of transcription factors such as NF-kappaB, and the overproduction of the mitochondrial superoxide by acting as scavengers of the superoxide radical. In addition, serotonin derivative concentration inside the cells and inside the mitochondria was increased in a time-dependent manner. These results identify a mechanism of action of serotonin derivatives against endothelial damage at a cellular level, and underline their benefits against the disorders and complications related to reactive oxygen species.
Septic shock, caused by exaggerated host responses to various microbial products typified by lipopolysaccharide (LPS), remains the leading cause of death in trauma patients. Gaining insight into the nature of host interactions with LPS will certainly facilitate attempts to develop effective anti-sepsis drugs. Tremendous progress has been made during the past few years in understanding the mechanisms of pathogen-induced host responses. Toll-like receptor (TLR) 4 and 2 have been implicated as major receptors for signaling initiated by LPS and many other microbial products following their binding to CD14. In addition, many signaling intermediates involved in LPS-induced cell activation, particularly activation of the transcription factor NF-kappaB, have been identified and characterized. Further investigations with these molecules will certainly reward us with more effective therapeutic drugs to treat septic shock as well as many other inflammatory and infectious disorders.
Previous work has shown that hydroxysafflor yellow A (HSYA), extracted from Carthamus tinctorius L. markedly extended the coagulation time in mice and exhibited a significant antithrombotic effect in rats. The present study was conducted to demonstrate further its neuroprotective effects on cerebral ischemic injury in both in vivo and in vitro studies. In vivo, male Wistar-Kyoto (WKY) rats with middle cerebral artery occlusion (MCAO) were evaluated for neurological deficit scores followed by the treatment with a single dose of HSYA. Furthermore, the infarction area of the brain was assessed in the brain slices. In vitro, the effect of HSYA was tested in cultured fetal cortical cells exposed to glutamate and sodium cyanide (NaCN) to identify its neuroprotection against neurons damage. The results in vivo showed that sublingular vein injection of HSYA at doses of 3.0 mg/kg and 6.0 mg/kg exerted significant neuroprotective effects on rats with focal cerebral ischemic injury by significantly decreasing neurological deficit scores and reducing the infarct area compared with the saline group, HSYA at a dose of 6.0 mg/kg showed a similar potency as nimodipine at a dose of 0.2 mg/kg. Sublingular vein injection of HSYA at the dose of 1.5 mg/kg showed a neuroprotective effect, however, with no significant difference when compared with the saline group. Results in vitro showed that HSYA significantly inhibited neuron damage induced by exposure to glutamate and sodium cyanide (NaCN) in cultured fetal cortical cells. Noticeably, the neuroprotective action of HSYA on glutamate-mediated neuron injury was much better than that of HSYA on NaCN-induced neuron damage. All these findings suggest that HSYA might act as a potential neuroprotective agent useful in the treatment in focal cerebral ischemia.
Abbreviations
HSYA:hydroxysafflor yellow A
TTC:2,3,5-triphenyltetrazolium chloride
MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide
DMEM:Dulbecco's modified Eagle medium
FCS:Fetal calf serum
MCAO:middle cerebral artery occlusion
ECA:external carotid artery
ICA:internal carotid artery
LDH:lactate dehydrogenase
NMDA:N-methyl-D-aspartate
The therapeutic effects of hydroxysafflor yellow A (HSYA), extracted from Carthamus tinctorius. L, on focal cerebral ischemic injury in rats and its related mechanisms have been investigated. Focal cerebral ischemia in rats were made by inserting a monofilament suture into internal carotid artery to block the origin of the middle cerebral artery and administrated by HSYA via sublingular vein injection in doses of 1.5, 3.0, 6.0 mg kg(-1) at 30 min after the onset of ischemia, in comparison with the potency of nimodipine at a dose of 0.2 mg kg(-1). Then, 24 h later, the evaluation for neurological deficit scores of the rats were recorded and postmortem infarct areas determined by quantitative image analysis. At the end of the experiment, blood samples were taken to determine plasma 6-Keto-PGF1alpha/TXB2 by radioimmunoassays and blood rheological parameters. The effects exerted by HSYA on thrombosis formation by artery vein by-pass method and ADP-induced platelet aggregation in vivo and in vitro were investigated, respectively. The results indicated that more than 30% of the area of ischemic cerebrum was observed in the ischemic model group. HSYA dose-dependently improved the neurological deficit scores and reduced the cerebral infarct area, and HSYA bore a similarity in potency of the therapeutic effects on focal cerebral ischemia to nimodipine. The inhibition rates of thrombosis formation by HSYA at the designated doses were 20.3%, 43.6% and 54.2%, respectively, compared with saline-treated group. Inhibitory activities of HSYA were observed on ADP-induced platelets aggregation in a dose-dependent manner, and the maximum inhibitory aggregation rate of HSYA was 41.8%. HSYA provided a suppressive effect on production of TXA2 without significant effect on plasma PGI2 concentrations. Blood rheological parameters were markedly improved by HSYA, such as whole blood viscosity (from 21.71 +/- 4.77 to 11.61 +/- 0.90 mPa.s), plasma viscosity (from 2.73 +/- 0.53 to 1.42 +/- 0.07 mPa.s), deformability (from 0.66 +/- 0.26 to 0.77 +/- 0.33) and aggregation of erythrocyte (from 3.24 +/- 0.41 to 2.57 +/- 0.30), but no significant effect of HSYA on homatocrit was found (from 51.38 +/- 4.68% to 49.91 +/- 2.32%). HSYA appears to be a good potential agent to treat focal cerebral ischemia, and the underlying mechanisms exerted by HSYA might be involved in its inhibitory effects on thrombosis formation and platelet aggregation as well as its beneficial action on regulation of PGI2/TXA2 and blood rheological changes in rats.
Imatinib exerts potent antileukemic effects in vitro and in vivo. Despite its well known antitumor activity, the potential of imatinib for the treatment of inflammatory diseases remains elusive so far. Our current report provides strong evidence that imatinib has potent antiinflammatory effects. It potently inhibits LPS- and Con A-induced TNF-α production by human myeloid cells in vitro (peripheral blood mononuclear cells, CD14-selected monocytes, and monocyte-derived macrophages). Of note, the production of the antiinflammatory cytokine IL-10 was not significantly regulated by imatinib. In line with this observation, phosphorylation of IκB and subsequent DNA binding of NF-κB, which is critically involved in TNF-α, but not IL-10 expression, was reduced by imatinib. Using several murine models of acute hepatitis, we could corroborate our in vitro findings, as imatinib prevented macrophage- and TNF-α-dependent inflammatory damage of the liver induced by injection of either Con A or d-galactosamine/LPS by inhibition of hepatic TNF-α production. Of note, d-galactosamine/TNF-induced hepatitis was not affected, showing that imatinib does not directly inhibit TNF-α-induced hepatocellular cell death. These findings suggest a potent antiinflammatory role of imatinib by modulation of TNF-α production in monocytes/macrophages. This observation might be of therapeutic value for the treatment of TNF-mediated diseases.
• cytokines
• monocytes/macrophages
• immunosuppression
Bacterial and viral products, such as bacterial lipopolysaccharide (LPS), cause inducible (i) NO synthase (NOS) synthesis, which in turn produces massive amounts of nitric oxide (NO). NO, by inactivating enzymes and leading to cell death, is toxic not only to invading viruses and bacteria, but also to host cells. Injection of LPS induces interleukin (IL)-1beta, IL-1alpha, and iNOS synthesis in the anterior pituitary and pineal glands, meninges, and choroid plexus, regions outside the blood-brain barrier. Thereafter, this induction occurs in the hypothalamic regions (such as the temperature-regulating centers), paraventricular nucleus (releasing and inhibiting hormone neurons), and the arcuate nucleus (a region containing these neurons and axons bound for the median eminence). Aging of the anterior pituitary and pineal with resultant decreased secretion of pituitary hormones and the pineal hormone melatonin, respectively, may be caused by NO. The induction of iNOS in the temperature-regulating centers by infections may cause the decreased febrile response in the aged by loss of thermosensitive neurons. NO may play a role in the progression of Alzheimer's disease and parkinsonism. LPS similarly activates cytokine and iNOS production in the cardiovascular system leading to coronary heart disease. Fat is a major source of NO stimulated by leptin. As fat stores increase, leptin and NO release increases in parallel in a circadian rhythm with maxima at night. NO could be responsible for increased coronary heart disease as obesity supervenes. Antioxidants, such as melatonin, vitamin C, and vitamin E, probably play important roles in reducing or eliminating the oxidant damage produced by NO.
In inflamed joints of rheumatoid arthritis, PGE(2) is highly expressed, and IL-10 and IL-6 are also abundant. PGE(2) is a well-known activator of the cAMP signaling pathway, and there is functional cross-talk between cAMP signaling and the Jak-STAT signaling pathway. In this study, we evaluated the modulating effect of PGE(2) on STAT signaling and its biological function induced by IL-10 and IL-6, and elucidated its mechanism in THP-1 cells. STAT phosphorylation was determined by Western blot, and gene expression was analyzed using real-time PCR. Pretreatment with PGE(2) significantly augmented IL-10-induced STAT3 and STAT1 phosphorylation, as well as suppressors of cytokine signaling 3 (SOCS3) and IL-1R antagonist gene expression. In contrast, PGE(2) suppressed IL-6-induced phosphorylation of STAT3 and STAT1. These PGE(2)-induced modulating effects were largely reversed by actinomycin D. Pretreatment with dibutyryl cAMP augmented IL-10-induced, but did not change IL-6-induced STAT3 phosphorylation. Misoprostol, an EP2/3/4 agonist, and butaprost, an EP2 agonist, augmented IL-10-induced STAT3 phosphorylation and SOCS3 gene expression, but sulprostone, an EP1/3 agonist, had no effect. H89, a protein kinase A inhibitor, and LY294002, a PI3K inhibitor, diminished PGE(2)-mediated augmentation of IL-10-induced STAT3 phosphorylation. In this study, we found that PGE(2) selectively regulates cytokine signaling via increased intracellular cAMP levels and de novo gene expression, and these modulating effects may be mediated through EP2 or EP4 receptors. PGE(2) may modulate immune responses by alteration of cytokine signaling in THP-1 cells.
Inducible nitric oxide synthase (iNOS, also named NOSII or NOS2) is a high-output Ca ++-independent NOS whose expression can be induced in a wide range of cells and tissues by cytokines and other agents (for a review see ...
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This review will discuss the recent literature on the molecular mechanism of NF-κB activation, with special focus on IκBα dynamism involved in iNOS- and chemokine-induction in glial cells. NF-κB, a heterotrimer composed of p50, p65 (Rel A) and IκBα, has been shown to be activated by elimination of the regulatory subunit IκBα from the heterotrimer. The elimination of IκBα (formation of active NF-κB, p50·p65) is due to phosplorylation of serines 32 and 36 of IκBα, followed by polyubiquitination and 26S proteasomal degradation of IκBα. Experiments using stable clones of rat C6 glioma cells transfected with dominant negative IκBα (serines 32 and 36 replaced by alanine) suggest that NF-κB activation (phosphorylation of IκBα) is involved in LPS/IFNγ- or IL-1β/IFNγ-induced iNOS expression. Furthermore, the time courses of phosphorylation, ubiquitination of IκBα and proteasome activity after IL-1β treatment also suggest that 26S proteasomal degradation of IκBα is more crucial for chemokine expression in glial cells.
The regulation of the transcription factor NF-κB activity occurs at several levels including controlled cytoplasmic-nuclear shuttling and modulation of its transcriptional activity. A critical component in NF-κB regulation is the IκB kinase (IKK) complex. This review is focused on recent progress as well as unanswered questions regarding the regulation and function of NF-κB and IKK.
Brazilin, the main constituent of Caesalpinia sappan L., is a natural red pigment that has been reported to possess anti-inflammatory properties. This study aimed to identify a novel anti-inflammatory mechanism of brazilin. We found that brazilin did not cause cytotoxicity below 300 μM, and activated heme oxygenase-1 (HO-1) protein synthesis in a concentration-dependent manner at 10–300 μM in RAW264.7 macrophages without affecting mRNA transcription of HO-1. Additionally, brazilin increased bilirubin production and HO-1 activity in RAW264.7 macrophages. In lipopolysaccharide (LPS)-stimulated macrophages, brazilin suppressed the release of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β and tumor necrosis factor-α (TNF-α), and reduced the expression of inducible nitric oxide synthase (iNOS). A specific inhibitor of HO-1, Zn(II) protoporphyrin IX, blocked the suppression of NO production, cytokines release and iNOS expression by brazilin. These results suggest that brazilin possesses anti-inflammatory actions in macrophages and works through a novel mechanism involving the action of HO-1.
In this paper, we propose a modified Polak–Ribière–Polyak (PRP) conjugate gradient method. An attractive property of the proposed
method is that the direction generated by the method is always a descent direction for the objective function. This property
is independent of the line search used. Moreover, if exact line search is used, the method reduces to the ordinary PRP method.
Under appropriate conditions, we show that the modified PRP method with Armijo-type line search is globally convergent. We
also present extensive preliminary numerical experiments to show the efficiency of the proposed method.
Hydroxysafflor yellow A (HSYA), is a component of the flower, Carthamus tinctorius L. In this study, we investigated its effect on Human Umbilical Vein Endothelial Cells (HUVECs) under hypoxia. We evaluated cell viability using the MTT kit. The cell cycle distribution was analyzed by PI staining flow cytometric analysis. PI AnnexinV-FITC detection and the TUNEL assay were performed to evaluate the apoptosis rate. Nitric oxide (NO) generation in cell supernatant was measured by the Griess assay. RT-PCR, Western blot and Immunocytochemistry analysis were used to evaluate the changes of Bcl-2, Bax, p53 and eNOS. Our data showed that HSYA inhibited cell apoptosis and cell cycle G1 arrest induced by hypoxia. HSYA treatment increased the Bcl-2/Bax ratio of protein and mRNA, reduced p53 protein expression in cell nucleus. In addition, HSYA enhanced the NO content of cell supernatant under hypoxia, accompanied with upregulating eNOS mRNA expression and protein level. Taken together, these results demonstrate that HSYA could protect HUVECs from hypoxia induced injuries by inhibiting cell apoptosis and cell cycle arrest. These findings have partly revealed the molecular mechanism of HSYA on treating of ischemic heart disease. We expected our experiments might provide some clues for further research.
Free radical scavenging activity of the extracts of petals (bud, early stage, full blooming and ending stage), leaf, stem, root and seeds of Mogami-benibana (safflower, Carthamus tinctorius Linne), the contents of the major active components of carthamin and polyphenols, and neuroprotective effect of the petal extracts and carthamin in the brain of mice and rats were examined. Water extracts of Mogami-benibana petals scavenged superoxide, hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and singlet oxygen. The scavenging activities of the extract of safflower petals with various colors showed the order of orange, yellow and white from high to low. This order is consistent with the contents of carthamin, which is a pigment of orange color and is found highest in orange petals and lowest in white petals. There was also a relationship between DPPH radical scavenging activity and carthamin content in the petal extracts of safflower. The neuroprotective effects were examined in cellular and animal models. Mogami-benibana petal extract inhibited glutamate-induced C6 glia cell death, significantly decreased the formation of malondialdehyde in mouse cerebrum, and inhibited the increase in thiobarbituric acid reactive substances and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebral cortex of rats subjected to an injection of FeCl(3) solution into the sensory motor cortex. Carthamin showed similar effects in inhibiting 8-OHdG by the petal extract in rats. These results suggest that the petal extract of Mogami-benibana has free radical scavenging activity and neuroprotective effect and carthamin is one of the major active components.
Hydroxysafflor yellow A (HSYA) is a main active monomer purified from Carthamus tinctorius L. The research is to study the inhibitory effect of HSYA on the inflammatory signal transduction pathway related factors which were induced by permanent cerebral ischemia in rats. By using the successive administration at a 30 min interval of HSYA and the rats permanent focal cerebral ischemia model established by a intraluminal suture occlusion method. After cerebral artery occlusion 3, 6, 12 and 24 h, cortex was removed for the next experiments. Western blotting was used to detect the expression of p65 protein and the phospho-IkappaB-alpha (pIkappaB-alpha) in the cytoplasm and nucleus. Nuclear factor-kappaB (NF-kappaB) DNA binding activity was measured by Trans-AM transcription factor assay kits. mRNA expression of cytokines TNF-alpha, IL-1beta, IL-6 and IL-10 was measured by the RT-PCR method. The result showed that intravenous injection of HSYA (10 mg x kg(-1)) to rats after cerebral occlusion, the p65 translocation activity and the phosphorylation of IkappaB-alpha were significantly inhibited. At the same time, HSYA suppressed p65 binding activity and the transcriptional level of pro-inflammatory cytokines including TNF-alpha, IL-1beta and IL-6, and promoted the mRNA expression of anti-inflammatory cytokine IL-10. In conclusion, the anti-cerebral ischemic mechanism of HSYA may be due to its inhibition of NF-kappaB activity and the mRNA expression of cytokines in the inflammatory transduction pathway.
Previous data demonstrated that hydroxysafflor yellow A (HSYA), a yellow color pigments extracted from the safflower, was an effective agent against focal cerebral ischemia. In the present study we demonstrated that HSYA prevented the injury in cultured cerebral cortical neurons induced by oxygen-glucose deprivation and increased the cell viability, as shown by the inhibition of both LDH and NO efflux. Further, HSYA administered orally 3 d before middle cerebral artery occlusion has the capacity to reduce cerebral infarct size and edema after 2 h cerebral ischemia followed by 24 h reperfusion in rats, and to significantly improve neurological behavior scores. Mean while, treatment with HSYA significantly decreased both mRNA and protein levels of IL-1beta, TNF-alpha in ischemic brain tissue. These results suggested that the protection of HSYA results from, at least in part, suppression of inflammatory responses following focal ischemia reperfusion.
Hydroxysafflor yellow A (HSYA) is a component of the flower Carthamus tinctorius L. The present investigation determines whether HSYA can modify the effects of hypoxia on vascular endothelial cells (EC) and its mechanisms. Human EC line (EAhy926) viability was determined using the MTT assay. EC cycle phase distribution was done with PI staining and flow cytometric analysis, and EC apoptosis was done by AnnexinV-FITC detection and the TUNEL assay. The protein levels of VEGF, Bcl-2, Bax, and HIF-1 alpha were determined by ELISA or Western blot analysis, and the mRNA expression of these genes by RT-PCR analysis. HIF-1 alpha transcriptional activity was measured using a reporter gene assay. HSYA improved cell viability under hypoxia in a concentration-dependent manner by attenuating its cycle arrest and inhibiting its apoptosis. HSYA upregulated the bcl-2/bax ratio, which is downregulated under hypoxia, increased VEGF protein concentration and VEGF mRNA expression and enhanced HIF-1 alpha protein accumulation and its transcriptional activity. In conclusion, HSAY could enhance the survival of ECs under hypoxia, which may be correlated with its effect of upregulating the bcl-2/bax ratio and promoting HIF-1 alpha protein accumulation, which increases VEGF. These findings provide evidence for the mechanisms by which HSYA maintains EC survival under hypoxia.
Safflower yellow (SY) is a mixture of chalconoid compounds extracted from Carthamus tinctorius L. Ig SY 1-2 g.kg-1.d-1 lowered the blood pressure of spontaneously hypertensive rats (SHR), for about 1.86-3.86 kPa. Five weeks after administration of SY, the plasma renin activity and angiotensin II level diminished in the SHR experimental groups. These suggest that the decrease of blood pressure is mediated by the renin-angiotensin system.
Safflower yellow (SY) extracted from Carthamus tinctorius L contained chalconoid compounds, 75% of which was safflomin A. SY ip 50-450 mg.kg-1.d-1 x 6-8 d in mice decreased serum lysozyme concentration and phagocytosing functions of both peritoneal macrophages and peripheral leukocytes; diminished the production of plaque forming cells, specific rosette forming cells, and antibody; inhibited delayed type hypersensitivity reaction and the activation of T suppressor cells elicited by supraoptimal immunization. Experiments in vitro showed inhibitory effects on [3H]TdR incorporation during human peripheral T- and B-lymphocyte proliferation by SY 0.03-3.0, 0.1-2.0 mg.ml-1 respectively, murine mixed lymphocyte culture response and the production of interleukin-2 by SY 0.1-2.5 mg.ml-1. In conclusion, SY produced declines in both nonspecific and specific immune functions.
The mutagenic potential of traditional Chinese drugs was studied. After extraction with boiling water and frozen vacuum drying, preparations from 102 raw drugs were tested with the Ames test, and the micronucleus and chromosomal aberration assays in mice in vivo. Astragalus mongholicus Bunge (+S9), Sophora japonica L. (+/- S9) and Eucommia ulmoides Oliv. (+/- S9) were found to significantly induce His+ revertants in Salmonella typhimurium TA98 and/or TA100. Besides these 3, 10 other extracts were positive in the chromosomal aberration and micronucleus assays in mice. They are Datura metal L., Artemisia capillaris Thunb., Carthamus tinctorius L., Forsythia suspensa Thumb., Rehmannia glutinosa f. Hueichingensis (fermented), Paeonia suffruticosa Andr., Platycodon grandiflorum Jacq. DC., Cinnamomum mairei Levl., Notopterygium incisium Ting., and Sophora flavescens Ait. The relevance of these findings is discussed.
This paper describes the screening studies of 104 commercial crude drugs for mutagenicity by the rec-assay with Bacillus subtilis as well as the reversion assay with Ames strains TA98 and TA100 of Salmonella typhimurium. The rec-assays showed that 13 water extracts and 27 methanol extracts of the crude drugs were positive. The Ames assays with or without metabolic activation showed that 24 water extracts and 16 methanol extracts were mutagenic. In total, mutagenic activities were found in 45 samples among the 104 crude drugs tested.
The transcription factor NF-kappa B has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-kappa B is through interactions with an inhibitor protein called I kappa B. Recent evidence confirms the existence of multiple forms of I kappa B that appear to regulate NF-kappa B by distinct mechanisms. NF-kappa B can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-kappa B to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of I kappa B. Exciting new research has elaborated several important and unexpected findings that explain mechanisms involved in the activation of NF-kappa B. In the nucleus, NF-kappa B dimers bind to target DNA elements and activate transcription of genes encoding proteins involved with immune or inflammation responses and with cell growth control. Recent data provide evidence that NF-kappa B is constitutively active in several cell types, potentially playing unexpected roles in regulation of gene expression. In addition to advances in describing the mechanisms of NF-kappa B activation, excitement in NF-kappa B research has been generated by the first report of a crystal structure for one form of NF-kappa B, the first gene knockout studies for different forms of NF-kB and of I kappa B, and the implications for therapies of diseases thought to involve the inappropriate activation of NF-kappa B.
The in vitro cytotoxicology of triclosan, the active ingredient in some mouthrinses and dentifrices used in the prevention and treatment of gingivitis and plaque, was studied using the Smulow-Glickman (S-G) human gingival epithelial cell line. The 24 h midpoint cytotoxicity value was 0.05-0.06 mM triclosan as assessed with the neutral red (NR) assay. Triclosan is used in dentifrices in combination with either zinc citrate or sodium fluoride (NaF). The sequence of potencies of these test agents, as assessed with the NR assay, was triclosan>zinc citrate>NaF; combinations of triclosan + zinc citrate and triclosan + NaF were additive in their toxicities. Damage to the integrity of the plasma membrane, as assessed by the leakage of lactic acid dehydrogenase during a 3-h exposure, was initially evident with 0.1 mM triclosan. When exposed to triclosan for 3 d, a lag in the growth kinetics of the S-G cells was first observed at 0.01 mM triclosan. A reduction in attachment of S-G cells to dentin chips, previously exposed to triclosan for 1 h, was noted at 0.25 mM triclosan and greater. Triclosan-induced cell death was apparently by apoptosis, as noted by fluorescence microscopy and DNA agarose gel electrophoresis of extracted oligonucleosomal fragments.
In recent years, the use of carthami flos (the flowers of Carthamus tinctorius L.) as a coloring and flavoring agent has increased as a food additive in Iran. In order to evaluate its safety, the teratogenic effects of carthami flos on the central nervous system development in mice was investigated. Furthermore, its cytotoxic effect on the rat nervous cell culture was studied to complete safety evaluations. For teratogenic studies, after natural mating, pregnant mice were divided into test and control groups. The groups were treated with different dosage regimens of aqueous carthami flos extract during 0-8 days of gestation. Embryos were then isolated at the 13th gestation day and evaluated for macroscopic, microscopic and morphometric characteristics. The results showed that in higher doses (1.6 and 2 mg/kg/day) the embryos were absorbed, whereas with lower dose (1.2 mg/kg/day) changes in external, internal and longitudinal diameters, open neuropore, changes in cellular orientation and cellular degeneration were observed. The results obtained from cytotoxic assay also demonstrated a concentration-dependent cytotoxic effect of carthami flos extract. It is concluded that the use of carthami flos as a food additive should be reconsidered.
This review will discuss the recent literature on the molecular mechanism of NF-kappaB activation, with special focus on IkappaB alpha dynamism involved in iNOS- and chemokine-induction in glial cells. NF-kappaB, a heterotrimer composed of p50, p65 (Rel A) and IkappaB alpha, has been shown to be activated by elimination of the regulatory subunit IkappaB alpha from the heterotrimer. The elimination of IkappaB alpha (formation of active NF-kappaB, p50-p65) is due to phosplorylation of serines 32 and 36 of IkappaB alpha, followed by polyubiquitination and 26S proteasomal degradation of IkappaB alpha. Experiments using stable clones of rat C6 glioma cells transfected with dominant negative IkappaB alpha (serines 32 and 36 replaced by alanine) suggest that NF-kappaB activation (phosphorylation of IkappaB alpha) is involved in LPS/IFNgamma- or IL-1beta/IFNgamma-induced iNOS expression. Furthermore, the time courses of phosphorylation, ubiquitination of IkappaB alpha and proteasome activity after IL-1beta treatment also suggest that 26S proteasomal degradation of IkappaB alpha is more crucial for chemokine expression in glial cells.
To study the effect of safflower injection (SI) on hemorheology and fibrinolytic system in treating patients of chronic cor pulmonale during acute attack.
Sixty patients were divided into two groups, 30 in each group. Both groups were treated with conventional therapy including anti-inflammatory, relieving cough and reducing sputum, cardial, diuretic and continuous low-flow oxygen inhalation. For the SI group, additional two courses of SI injection was given intravenously for 10 days as one course with an interval of 5 days between courses. The clinical therapeutic effect in the two groups and effect of treatment on hemorheology and fibrinolytic function were observed.
The total effective rate in the SI group was 86.7% and that in the control group was 63.3%, the difference between the two groups was significant (P < 0.05). After treatment, in the SI group, the high- and low-shear whole blood viscosity, plasma viscosity, erythrocyte agglutination index, hematocrit and fibrinogen lowered obviously, as compared with before treatment (P < 0.01 or P < 0.05), and the improvement in hemorrheologic property was better than that in the control group significantly (P < 0.05). The blood activities of anti-thrombin III, plasminogen and tectotype profibrinolytic activating factor were all higher than those in the control group (P < 0.05, P < 0.01). And SI showed more potent effect in improving anti-coagulation and fibrinolytic function of patients than that of the control (P < 0.05).
SI is an effective drug for treatment of hypercoagulability status in acute stage of chronic cor pulmonale, and is worthy of clinical application.
Prostaglandins are potent lipid molecules that affect key aspects of immunity. The original view of prostaglandins was that they were simply immunoinhibitory. This review focuses on recent findings concerning prostaglandin E2 (PGE2) and the PGD2 metabolite 15-deoxy-Delta(12,14)-PGJ2, and their divergent roles in immune regulation. We will highlight how these two seminal prostaglandins regulate immunity and inflammation, and play an emerging role in cancer progression. Understanding the diverse activities of these prostaglandins is crucial for the development of new therapies aimed at immune modulation.
Nitric oxide (NO) plays an important regulatory/modulatory role in a variety of inflammatory conditions. NO is a small, short-lived molecule that is released from a variety of cells in response to homeostatic and pathologic stimuli. It may act as a vasodilator and a platelet inhibitor and may interfere with adhesion molecules to prevent neutrophil adhesion. NO release may also lead to the formation of highly reactive species such as peroxynitrite and stable nitrosothiols and may cause mitochondrial damage and nitration of protein tyrosine residues. In addition, NO inhibits cell proliferation via inhibition of polyamine synthesis and cell uptake and may well act as a 'brake' on the proliferative response following cytokine exposure. All three isoforms of nitric oxide synthases are found in the kidney during inflammation. The site of NO release impacts significantly on its net function and structural impact. NO plays a protective role in many forms of immune injury, such as nephrotoxic serum-induced glomerulonephritis, autoimmune tubular interstitital nephritis, and experimental allergic encephalomyelitis. NO overproduction in sepsis, after cytokine exposure, inducible NO synthase transcription, and local inflammation can autoinhibit endothelial NO synthase, leading to selective renal and mesenteric vasoconstriction.
The regulation of the transcription factor NF-kappaB activity occurs at several levels including controlled cytoplasmic-nuclear shuttling and modulation of its transcriptional activity. A critical component in NF-kappaB regulation is the IkappaB kinase (IKK) complex. This review is focused on recent progress as well as unanswered questions regarding the regulation and function of NF-kappaB and IKK.
The acute respiratory distress syndrome (ARDS) is a major cause of morbidity after injury. We hypothesized that alveolar macrophage (AMPhi) chemokine and cytokine release after hemorrhage and sepsis is regulated by NF-kappaB and MAPK. Adult male rats underwent soft tissue trauma and hemorrhagic shock (~90 min) followed by crystalloid resuscitation. Sepsis was induced by cecal ligation and puncture (CLP) 20 h after resuscitation. AMPhi were harvested, and TNF-alpha, IL-6, and macrophage inflammatory protein (MIP)-2 release and serum IL-6 and TNF-alpha levels were measured at 5 h after HCLP. Lung tissues were analyzed for activation of NF-kappaB, myeloperoxidase activity, and wet/dry weight ratio. In control animals, AMPhi were stimulated with LPS with or without inhibitors of NF-kappaB and MAPK. Serum TNF-alpha and IL-6 levels and spontaneous AMPhi TNF-alpha and MIP-2 release were elevated (P < 0.05) after HCLP, concomitantly with the development of lung edema and leukocyte activation. Activation of NF-kappaB increased in lungs from the hemorrhage and CLP group compared with shams. Inhibition of NF-kappaB or the upstream MAPK significantly decreased LPS-stimulated AMPhi activation. Because enhanced release of inflammatory mediators by AMPhi may contribute to ARDS after severe trauma, inhibition of intracellular signaling pathways represents a target to attenuate organ injury under those conditions.
Two active polysaccharide fractions (SF1 and SF2) purified from dried safflower petals (Carthamus tinctorius L.) stimulated the synthesis of various cytokines by peritoneal macrophages. In a number of cell types, SF1 and SF2 induced a rapid degradation of IkappaB alpha essential for the activation of the transcription factor NF-kappaB. Toll-like receptor 4 (TLR4), but not TLR2, was expressed in all cell lines that responded to SF1 and SF2. Enforced expression of TLR4 and MD-2 rendered responsiveness to SF1 and SF2. Moreover, these safflower polysaccharides failed to induce the production of TNF-alpha and NO by peritoneal macrophages prepared from C3H/HeJ mice that have a point mutation in the Tlr4 gene. Thus, these observations clearly indicate that safflower polysaccharides activate the NF-kappaB signaling pathway via TLR4.
The role of nitric oxide (NO) generated by the inducible isoform of nitric oxide synthase (iNOS) is very complex. Induction of iNOS expression and hence NO production has been described to have beneficial antiviral, antiparasital, microbicidal, immunomodulatory, and antitumoral effects. However, induced at the wrong place or at the wrong time, iNOS has detrimental consequences and seems to be involved in the pathophysiology of different human diseases. The pathways regulating iNOS expression seem to vary in different cells or different species. In general, activation of the transcription factors nuclear factor (NF)-kappaB and signal transducer and activator of transcription (STAT)-1alpha and thereby activation of the iNOS promoter seems to be an essential step in the regulation of iNOS expression in most cells. Also, post-transcriptional mechanisms are critically involved in the regulation of iNOS expression.
The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect on brain injury after focal cerebral ischemia reperfusion, and to determine the possible mechanism. Behavioral tests were used to evaluate the damage to central nervous system. The infarct volume of brain was assessed in brain slices stained with 2% solution of 2,3,5-triphenyl tetrazolium chloride (TTC). Adult male Wistar rats were subjected to 2h of middle cerebral artery occlusion and 24h of reperfusion. Spectrophotometric assay was used to determine the content of malondialdehyde (MDA), and the activity of total antioxidative capability (T-AOC) and superoxide dismutase (SOD). The results showed that treatment with HSYA (2, 4, 8 mg/kg, i.v.) significantly decreased neurological deficit scores and reduced the percentage of infarction in the ipsilateral hemisphere compared with the model group. At the same time, HSYA treatment significantly attenuated the elevation of MDA content, the decrease in SOD activity, and the T-AOC in the ipsilateral hemisphere and serum. All of these findings suggest that HSYA might provide neuroprotection against cerebral ischemia/reperfusion injury through its antioxidant action.
To investigate the protective effect of hydroxysafflor yellow A (HSYA), a soluble element extracted from Carthamus tinctorius L., on focal cerebral ischemia in rats.
Focal cerebral ischemia in male Wistar-Kyoto (WKY) rats were induced by permanent middle cerebral artery occlusion (MCAO). Three doses of 1.5, 3.0 and 6.0 mg x kg(-1) of HSYA were administrated to three groups of rats, separately, via sublingular vein injection 30 min after the onset of ischemia. 24 h after ischemia in rats, neurological deficit scores were evaluated and the infarction area of brain was assessed by quantitative image analysis. The in vitro neuroprotective effect of HSYA was tested in cultured fetal cortical neurons exposed to glutamate and sodium cyanide (NaCN).
HSYA at doses of 3.0 and 6.0 mg x kg(-1) exerted significant neuroprotective effects on rats with focal cerebral ischemic injury as expressed by neurological deficit scores and reduced the infarct area as compared with saline group, and the potency of HSYA at dose of 6.0 mg x kg(-1) was similar to that of 0.2 mg x kg(-1) of nimodipine. In vitro studies, HSYA significantly inhibited neurons damage induced by exposure to glutamate and NaCN in cultured fetal cortical cells.
HSYA has potential neuroprotective action against focal cerebral ischemia in rats and cultured rat fetal cortical neurons as well.
The effects of defatted safflower seed extract and its phenolic constituents, serotonin derivatives, on atherosclerosis were studied. Ethanol-ethyl acetate extract of safflower seeds (SSE) inhibited low-density lipoprotein (LDL) oxidation induced in vitro by an azo-containing free-radical initiator V70 or copper ions. Two serotonin derivatives [N-(p-coumaroyl)serotonin, CS; N-feruloylserotonin, FS] and their glucosides were identified as the major phenolic constituents of the extract. The study with chemically synthesized materials revealed that a majority of the antioxidative activity of SSE was attributable to the aglycones of these two serotonin derivatives. Orally administered CS and FS suppressed CuSO(4)-induced plasma oxidation ex vivo. Long-term (15 week) dietary supplementation of SSE (1.0 wt %/wt) and synthetic serotonin derivatives (0.2-0.4%) significantly reduced the atherosclerotic lesion area in the aortic sinus of apolipoprotein E-deficient mice (29.2-79.7% reduction). The plasma level of both lipid peroxides and anti-oxidized LDL autoantibody titers decreased concomitantly with the reduction of lesion formation. Serotonin derivatives were detected as both intact and conjugated metabolites in the plasma of C57BL/6J mice fed on 1.0% SSE diet. These findings demonstrate that serotonin derivatives of SSE are absorbed into circulation and attenuate atherosclerotic lesion development possibly because of the inhibition of oxidized LDL formation through their strong antioxidative activity.
To observe dynamically the expressions of intercellular adhesion molecule-1 (ICAM-1) and P-selectin (Ps) in the vascular endothelium in rats with pulmonary thromboembolism (PTE) and the effect of Safflower Injection (SI).
Rats were randomly divided into the normal group, the model group and the treatment group. PTE model was induced by intravenous injection of auto-blood clots, and SI was injected intravenously immediately after modelling with 2 ml/(kg d) for 5 days to the rats in the treatment group. Animals were sacrificed in batches at the 1st, 3rd, 24th, 72nd and 120th h after embolization to observe the pathological changes and detect the protein and mRNA expressions of ICAM-1 and Ps in pulmonary vascular endothelium by immunohistochemistry and in situ hybridization respectively.
Pathological observation showed obvious embolism in pulmonary arteries and inflammatory reaction after modelling, which was abated after SI treatment. ICAM-1 and Ps expressions were elevated at the 3rd and the 1st h after embolization respectively (both P < 0.01), which also were abated in the treatment group.
SI may alleviate pulmonary injury in PTE rats by down-regulating the expressions of ICAM-1 and Ps.
The present study was conducted to investigate whether safflor yellow B (SYB) had a protective effect on cerebral ischemic injury and to determine the possible mechanisms in vivo and in vitro. In vivo, Male Wistar-Kyoto (WKY) rats were used to make the model of middle cerebral artery occlusion (MCAO). The behavioral test was used to measure neurological deficit scores for evaluation of the ischemic damage of brain. The infarction area of brain was assessed in brain slices stained with 2% solution of 2,3,5-triphenyl tetrazolium chloride (TTC). Spectrophotometric assay was used to determine the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), contents of malondialdehyde (MDA) and adenosine triphosphate (ATP) of the brain. Furthermore, the respiratory control ratio (RCR = state 3/state 4) was assessed in the brain mitochondria. In vitro, the effect of SYB was tested in cultured fetal cortical cells exposed to glutamate to identify its neuroprotection against neurons damage. The results in vivo showed that SYB at doses of 3.0 and 6.0 mg kg(-1) markedly decreased the neurological deficit scores and the infarction area in MCAO rats. At the same time, SYB significantly improved mitochondrial energy metabolism, decreased MDA content, and increased SOD and GPx activities in ischemic brain. The results in vitro showed that SYB remarkably inhibited neuron damage induced by glutamate in cultured fetal cortical cells. These suggest that SYB might act as a potential neuroprotective agent against the cerebral ischemia-induced injury in rat brain through reducing lipid peroxides, scavenging free radicals, and improving the energy metabolism.
Macrophages play an important role in host-defense and inflammation. In response to an immune challenge, macrophages become activated and produce proinflammatory mediators that contribute to nonspecific immunity. The mediators released by activated macrophages include: superoxide anion; reactive nitrogen intermediates, such as nitric oxide and peroxynitrite; bioactive lipids; and cytokines. Although essential to the immune response, overproduction of certain macrophage-derived mediators during an immune challenge or inflammatory response can result in tissue injury and cellular death. The present report is focused on understanding some of the molecular mechanisms used by macrophages to produce reactive nitrogen intermediates in response to immunostimulatory agents such as heat shock protein 60 and bacterial lipopolysaccharide. The role of Toll-like receptors and transcription factors such as nuclear factor kappa B (NFkappaB) in the innate immune response is also described. A basic understanding of the underlying molecular mechanisms responsible for macrophage activation should serve as a foundation for novel drug development aimed at modulating macrophage activity.
Sanguis Draconis (SD) is a kind of dragon's blood resin that is obtained from Daemomorops draco (Palmae). It is used in traditional medicine and has shown anti-inflammatory activity in some diseases. In this study, we examined the effects of Sanguis Dranonis ethanol extract (SDEE) on LPS-induced inflammation using RAW 264.7 cells. Our data indicated that SDEE inhibits LPS-stimulated NO, PGE2, IL-1 beta and TNF-alpha release, and iNOS and COX-2 expression. Furthermore, SDEE suppressed the LPS-induced p65 expression of NF-kappa B, which was associated with the inhibition of I kappa B-alpha degradation. We also found that the expression of HO-1 was significantly increased in RAW 264.7 cells by SDEE. These results suggest among possibilities of anti-inflammation that SDEE inhibits the production of NO and PGE2 by the down-regulation of iNOS and COX-2 gene expression via the suppression of NF-kappaB (p65) activation. SDEE can induce HO-1 over-expression in macrophage cells, which indicates that it may possess antioxidant properties. This result means that SEDD its anti-inflammatory effects in macrophages may be through a novel mechanism that involves the action of HO-1. Thus, SD could provide a potential therapeutic approach for inflammation-associated disorders.
In order to select the component drug in promoting blood circulation and removing blood stasis of Chinese herbal medicinal formula for dairy cow mastitis.
25 healthy rabbits were allocated randomly into five equal groups. The rabbits in four experimental groups were administered with decoctions of giant knotweed rhizome (GKR, rhizoma polygoni cuspidati), safflower (SF, flos carthami), red sage root (RSR, radix salviae miltiorrhizae) and chuanxiong rhizome (CXR, rhizoma Chuanxiong) by gastrogavage, respectively, in control group, physiological saline, once a day for seven successive days. After the last administration, all rabbits were intravenously injected with 10% macromolecular dextran to induce blood stasis. The blood samples of all rabbits were collected before the first administration, at 2h after the last administration and 1h after injection of dextran, respectively for determination of hemorheologic parameters by MVIS-2035 hemorheology auto-analyzing system.
The results showed that all of four kinds of herbs presented different degree of activating blood flow and removing blood stasis.
Red sage root was the best especially in resisting blood stasis induced by dextran, and would be selected as main component drug of the prescription for dairy cow mastitis.
Flavonoids in the water extract of Carthamus tinctorius L. exhibit potent biological activities such as anti-coagulant, vasodilation, anti-oxidant, neuroprotection and immunosuppressant. A high-performance liquid chromatographic method was established to evaluate the quality of Carthamus tinctorius through a simultaneous quantitation of eight flavonoids, hydroxysafflor yellow A (2), 6-hydroxykaempferol 3,6-di-O-beta-glucoside-7-O-beta-glucuronide (3), 6-hydroxykaempferol 3,6,7-tri-O-beta-glucoside (4), 6-hydroxykaempferol 3-O-beta-rutinoside-6-O-beta-glucoside (6), 6-hydroxykaempferol 3,6-di-O-beta-glucoside (7), 6-hydroxyapigenin 6-O-glucoside-7-O-glucuronide (8), anhydrosafflor yellow B (9), and kaempferol 3-O-beta-rutinoside (10), together with two other compounds named guanosine (1) and syringin (5). Among them, compound 8 was identified as a new compound. The compounds were separated on an Alltech Alltima-C(18) column with gradient elution of acetonitrile and 0.01% trifluoroacetic acid. The detection wavelength was 280 nm. All the compounds showed good linearity (r(2) >or= 0.9989). The recoveries, measured at three concentration levels, varied from 94.9% to 105.2%. This method was also validated with respect to precision, repeatability and accuracy, and was successfully applied to quantify the 10 components in 46 batches of C. tinctorius samples from different areas. Significant variations were found in the contents of these compounds in these samples. Compared with the reported analytical methods of C. tinctorius, this simple and reliable method provided a new basis for overall assessment on quality of C. tinctorius and should be considered as a suitable quality control method.
Hydroxysafflor yellow A (HSYA), the major and most active antioxidant from Carthamus tinctorius L., has been clinically prescribed in China to treat patients with cerebral ischemia, but the detailed mechanism is not known. This study examines the effect of HSYA on mitochondrial permeability transition pores (mtPTP) in the rat brain. HSYA at 10-80 micromol.l(-1) inhibited Ca(2+)- and H(2)O(2)-induced swelling of mitochondria isolated from rat brains. The addition of Ca(2+) generated reactive oxygen species (ROS) in isolated mitochondria. HSYA (10-80 micromol.l(-1)) inhibited Ca(2+)-induced generation of ROS. At the same time, HSYA significantly improved mitochondrial energy metabolism, enhanced ATP levels and the respiratory control ratio. These results suggest that HSYA inhibits the opening of mtPTP by a free radical scavenging action in the brain, and this may contribute to the neuroprotective effect of HSYA.
Effects of safflower yellow pigment on the blood fat and liver function of rabbits
- Qi
Clinical application of safflower (Carthamus tinctorius)
- Wang
Clinical observation on dead sperm excess disease of 182 cases
- Qu
The treatment of thorax rheumatism of 800 cases with milkvetch-peach-safflower, etc. decoction
- Zheng
Effects of some herbs on microcirculation of blood of rat's mesentery
- Qi