Anhydrosafflor yellow B

Optimization of green extraction process with natural deep eutectic solvent and comparative in vivo pharmacokinetics of bioactive compounds from Astragalus-Safflower pair.[Pubmed:37062134]

Phytomedicine. 2023 Jun;114:154814.

INTRODUCTION: Natural deep eutectic solvents (NaDESs) are promising not only in componential extraction, but also in drug delivery system due to their green and safe features. In this work, NaDESs were applied to extract bioactive components from Astragalus-Safflower pair, a classic traditional Chinese medicine combination. Furthermore, ready-to-use crude extracts were administrated to SD rats. METHODS: Total 9 NaDESs composed of food grade ingredients were screened for the extraction of representative 9 components (hydroxysafflor yellow A, Anhydrosafflor yellow B, eleutheroside B, calycosin-7-O-glucoside, kaempferol-3-O-rutinoside, ononin, calycosin, astraganoside, and carthamin) from Astragalus-Safflower pair. Afterwards, genetic artificial neural network (GNN) was adopted for optimizing the ultrasound-assisted extraction process. After SD rats were orally administrated with the ready-to-use crude extracts extracted under the optimized conditions, the in vivo pharmacokinetic characteristics of 5 components were evaluated comprehensively from weight, gender, solvent and modeling surgery, under a well-established UPLC-MS/MS method. RESULTS: Betaine-Lactic acid (Bet-Lac) was eventually determined as the optimal extraction solvent for subsequent experiments. The optimal ultrasound assisted extraction process was as follows: 90 min of extraction time, 65 degrees C of temperature, 80% of Bet-Lac content and 50 mg/ml of solid-liquid ratio. Bet-Lac enhanced to varying degrees the bioavailability of analytes in normal and cerebral ischemia/reperfusion injured (CI/RI) rats in contrast with corresponding rats administrated with water extract groups (p < 0.05). Besides, the bioavailability of active components in CI/RI rat plasma was significantly lower than that in normal rats (p < 0.05), indicating pathological damage of CI/R had a significant impact on pharmacokinetic profile of compounds in rats. However, gender and body weight had no significant effects on the pharmacokinetic profile of bioactive components. CONCLUSIONS: NaDESs exhibited higher extraction efficiency than conventional solvents. And GNN is reliable to optimize the ultrasound assisted extraction process. This study supported the potential of non-toxic NaDESs as solvents for extraction process and drug delivery systems at the same time.

Composition of major quinochalcone hydroxysafflor yellow A and anhydrosafflor yellow B is associated with colour of safflower (Carthamus tinctorius) during colour-transition but not with overall antioxidant capacity: A study on 144 cultivars.[Pubmed:36461404]

Food Res Int. 2022 Dec;162(Pt B):112098.

Yellow pigments in the water-extract of safflower (Carthamus tinctorius L.) belong to quinochalcone flavonoid family and are widely used as food colourants. The aim of the study was to characterize the main quinochalcone compounds in safflower water-extract during blooming period when floret changed colour. Mass-spectrometry results showed that hydroxysafflor yellow A (HSYA) and Anhydrosafflor yellow B (AHSYB) were the most abundant. Based on 370 florets samples collected from 144 cultivars, the contents of HSYA and AHSYB were determined, which showed that only AHSYB content had relatively strong positive association with colour indexes. The ratio of HSYA/AHSYB and visual colour exhibited certain patterns: yellow = 2, orange = 3-4, red = more dispersed, mostly falling 5-6. Most of the florets had HSYA increased first and decreased, while AHSYB decreased all the time when floret changed colour as yellow --> orange --> red. Regardless of the composition of HSYA/AHSYB in florets, the antioxidant capacities of safflower petal water-extracts were the same.

Preventive effects of a standardized flavonoid extract of safflower in rotenone-induced Parkinson's disease rat model.[Pubmed:35940347]

Neuropharmacology. 2022 Oct 1;217:109209.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that occurs after Alzheimer's disease. Rotenone is a neurotoxin commonly used in creating PD models. Safflower (Carthamus tinctorius L.) contains some flavonoids that are effective against neurodegenerative diseases, and it has long been used in the treatment of cerebrovascular diseases in China. In this study, we investigated the preventive effect of safflower standardized flavonoid extract (SAFE) on a rotenone-induced PD rat model. The results showed that SAFE (17.5, 35, or 70 mg kg(-1).day(-1)) treatment modified the progressive loss in body weight, alleviated behavioral deficits, and promoted survival, especially in the middle-dose SAFE (35 mg kg(-1).day(-1)) group. SAFE treatment significantly modifies the progressive decrease in the level of DA and its metabolites, DOPAC and HVA, 5-HT and its metabolite 5-HIAA in the St, and levels of TH-positive DA-ergic neurons in the SNpc. SAFE also inhibited the decrease in TH and DA levels and increase in Ach content in the St. SAFE (35 mg kg(-1).day(-1)) group treatment modifying the rotenone-induced downregulation of JAK2, STAT3, and a7-nAChR, and also modifying the increase in ACh in the hippocampus. SAFE preventive treatment can also partially inhibit changes in the ECS parameters associated with PD. The marker components of SAFE such as Kaempferol 3-O-rutinoside or Anhydrosafflor yellow B can bind with TH, JAK2, STAT3, and a7-nAChR based on molecular docking analyses. Current studies have shown that SAFE is a potential candidate for the prevention of PD.

Pharmacological Activities of Safflower Yellow and Its Clinical Applications.[Pubmed:35795285]

Evid Based Complement Alternat Med. 2022 Jun 27;2022:2108557.

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.

Hydroxysafflor yellow A and anhydrosafflor yellow B alleviate ferroptosis and parthanatos in PC12 cells injured by OGD/R.[Pubmed:34923102]

Free Radic Biol Med. 2022 Feb 1;179:1-10.

Ferroptosis and parthanatos are two types of programmed cell death associated with cerebral ischemia. There is a sizeable interest in seeking chemical components for the regulation of ferroptosis and parthanatos. Hydroxysafflor yellow A (HSYA) and Anhydrosafflor yellow B (AHSYB) mitigated cell death caused by oxidative stress due to antioxidant capacity, yet the mechanism is still uncertain. Thus, we investigated whether HSYA and AHSYB prevent death through these two pathways with the aim to elucidate their potential protective mechanisms of cerebral ischemia. In this study, oxidative stress model was established by treating PC12 cells with oxygen glucose deprivation and reperfusion (OGD/R). Cellular functions and signaling pathways were analyzed in PC12 cells using cell counting kit-8 (CCK-8), flow cytometry, ELISA, iron assay kit, transmission electron microscopy (TEM), immunofluorescence, and western blot analysis. And the research proved HSYA and AHSYB protected cells from oxidative stress. The phenomenon is associated with ferroptosis and parthanatos. HSYA and AHSYB upregulated cystine/glutamate antiporter system x(c)(-) (system x(c)(-)) and glutathione peroxidase 4 (GPX4), returned the levels of GSH/GSSG ratio, reactive oxygen species (ROS) and iron ion, as well as alleviated lipid peroxidation. By reason of reducing ROS, HSYA and AHSYB restrained poly(ADP-ribose) polymerase-1 (PARP-1) overactivation, reduced the production of excess poly(ADP-ribose) (PAR) polymer and apoptosis inducing factor (AIF) nuclear translocation. The results suggested that HSYA and AHSYB limited ferroptosis and parthanatos to alleviate oxidative stress in PC12 cells. These findings may have implications for improving understanding of how drugs reduce oxidative stress and develop new strategies for treating degenerative diseases such as cerebral ischemia.

Hydroxysafflor Yellow A and Anhydrosafflor Yellow B Protect Against Cerebral Ischemia/Reperfusion Injury by Attenuating Oxidative Stress and Apoptosis via the Silent Information Regulator 1 Signaling Pathway.[Pubmed:34658877]

Front Pharmacol. 2021 Sep 30;12:739864.

Hydroxysafflor yellow A (HSYA) and Anhydrosafflor yellow B (AHSYB) are the main water-soluble compounds in Carthamus tinctorius L. However, studies on the effect of AHSYB on cerebral ischemia/reperfusion (I/R) injury and the therapeutic effect of HSYA by regulating silent information regulator 1 (SIRT1) pathway remain obscure. In this study, we investigated whether the neuroprotective effects of HSYA and AHSYB on oxygen-glucose deprivation/reoxygenation in primary-cultured hippocampal neuronal cells and the middle cerebral artery occlusion and reperfusion model in rats are associated with the regulation of the SIRT1 pathway. In vitro, HSYA and AHSYB increased cell viability, depressed oxidation properties, and reduced neuronal cell apoptosis. In vivo results showed that HSYA and AHSYB effectively reduced infarct volume, improved neurological function, suppressed apoptosis, and decreased the oxidative stress reaction. Besides, RT-PCR and Western blot analysis showed that HSYA and AHSYB increased the mRNA and protein expressions of the main factors in the SIRT1 pathway, including SIRT1, forkhead box O (FOXO) 1, and peroxisome proliferator-activated receptor coactivator 1alpha (PGC1alpha), decreased the expression of Bax, and increased the expression of Bcl-2. The results from immunohistochemistry also showed that the expressions of SIRT1, FOXO1, and PGC1alpha were increased after treatment with HSYA and AHSYB. Furthermore, the neuroprotective effects of HSYA and AHSYB were abolished by EX527 (SIRT1-specific inhibitor). These results indicated that HSYA and AHSYB should be developed into potential drugs for treating cerebral I/R injury via the SIRT1 pathway. Although HSYA and AHSYB have different chemical structures, both of them exert similar neuroprotective properties against I/R injury in vitro and in vivo, which means that AHSYB is also a non-negligible component in safflower.

Optimized separation of anhydrosafflor yellow B from safflower by high-speed counter-current chromatography and evaluation of its cardio-protective effect.[Pubmed:34606545]

Food Funct. 2021 Oct 4;12(19):9360-9371.

Anhydrosafflor yellow B (AHSYB) is a major active water-soluble pigment in Safflower, but it has not received enough attention yet. In this study, high-speed counter-current chromatography (HSCCC) was used to prepare AHSYB from safflower. The parameters of the separation process were optimized by response surface methodology for the first time. The entropy weight method (EWM) was applied to calculate the information entropy and the weight of five indexes, and then figure out a comprehensive index of the HSCCC separation effect. Under the optimized separation conditions, a HSCCC apparatus speed of 850 rpm, a flow rate of 2 mL min(-1) for the mobile phase and a separation temperature of 40 degrees C for AHSYB were achieved with a purity of 98%. Furthermore, AHSYB was found to have cardio-protective effects by inhibiting apoptosis via the mitochondrial-mediated pathway in oxygen-glucose deprivation/reoxygenation-induced H9c2 cells. This research provides good method guides for the rapid and efficient separation of active compounds from food-grade Chinese herb medicines.

An integrative strategy for discovery of functional compound combination from Traditional Chinese Medicine: Danhong Injection as a model.[Pubmed:33714107]

Biomed Pharmacother. 2021 Jun;138:111451.

Traditional Chinese Medicine formulas, which are usually considered exerting their holistic clinical benefits via multi-component, multi-target manner, are unique resources for the discovery of multi-component drug combinations. In order to screen and optimize the functional compound combination (FCC) from TCM, we established a novel four-step 'GCIC' strategy, including 'Global profiling', 'Chemical structural classification', 'Intra-group screening' and 'Component-knockout optimization'. Following this strategy, an FCC consisted of four components from Danhong Injection (DHI) was identified, containing ferulic acid, cryptotanshinone, quercetin and Anhydrosafflor yellow B. The holistic neuroprotective effects of the FCC were further investigated, indicating that the combination can both activate the antioxidative and anti-inflammatory responses in PC12 cells to protect them from oxidative stress. Major signaling pathways as Nrf2/ARE and Nrf2/AMPK/GSK3beta were involved in the protective process of FCC. The 'GCIC' strategy established in this study might provide an alternation to traditional strategies in discovering the bioactive components from herbal medicines, especially compounded TCM formulas.

Greener extraction process and enhanced in vivo bioavailability of bioactive components from Carthamus tinctorius L. by natural deep eutectic solvents.[Pubmed:33524695]

Food Chem. 2021 Jun 30;348:129090.

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%.

Traditional Chinese medicine network pharmacology study on exploring the mechanism of Xuebijing Injection in the treatment of coronavirus disease 2019.[Pubmed:33357725]

Chin J Nat Med. 2020 Dec;18(12):941-951.

As a representative drug for the treatment of severe community-acquired pneumonia and sepsis, Xuebijing (XBJ) injection is also one of the recommended drugs for the prevention and treatment of coronavirus disease 2019 (COVID-19), but its treatment mechanism for COVID-19 is still unclear. Therefore, this study aims to explore the potential mechanism of XBJ injection in the treatment of COVID-19 employing network pharmacology and molecular docking methods. The corresponding target genes of 45 main active ingredients in XBJ injection and COVID-19 were obtained by using multiple database retrieval and literature mining. 102 overlapping targets of them were screened as the core targets for analysis. Then built the PPI network, TCM-compound-target-disease, and disease-target-pathway networks with the help of Cytoscape 3.6.1 software. After that, utilized DAVID to perform gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to predict the action mechanism of overlapping targets. Finally, by applying molecular docking technology, all compounds were docked with COVID-19 3 CL protease(3CLpro), spike protein (S protein), and angiotensin-converting enzyme II (ACE2). The results indicated that quercetin, luteolin, apigenin and other compounds in XBJ injection could affect TNF, MAPK1, IL6 and other overlapping targets. Meanwhile, Anhydrosafflor yellow B (AHSYB), salvianolic acid B (SAB), and rutin could combine with COVID-19 crucial proteins, and then played the role of anti-inflammatory, antiviral and immune response to treat COVID-19. This study revealed the multiple active components, multiple targets, and multiple pathways of XBJ injection in the treatment of COVID-19, which provided a new perspective for the study of the mechanism of traditional Chinese medicine (TCM) in the treatment of COVID-19.

Neuroprotective Effects of Safflower Flavonoid Extract in 6-Hydroxydopamine-Induced Model of Parkinson's Disease May Be Related to its Anti-Inflammatory Action.[Pubmed:33182332]

Molecules. 2020 Nov 9;25(21):5206.

Safflower (Carthamus tinctorius. L.), a Chinese materia medica, is widely used for the treatment of cardiovascular and cerebrovascular diseases, with flavonoids being the major active components. Multiple flavonoids in safflower bind to Parkinson's disease (PD)-related protein DJ-1. Safflower flavonoid extract (SAFE) improved behavioral indicators in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD; however, the underlying mechanisms remain unclear. We used a 6-OHDA-induced mouse model of PD and a primary neuron-astrocyte coculture system to determine the neuroprotective effects and mechanisms of SAFE. After three weeks of SAFE administration, behavioral indicators of PD mice were improved. SAFE regulated the levels of tyrosine hydroxylase (TH) and dopamine metabolism. It significantly inhibited the activation of astrocytes surrounding the substantia nigra and reduced Iba-1 protein level in the striatum of PD mice. SAFE reduced the plasma content of inflammatory factors and suppressed the activation of nod-like receptor protein 3 (NLRP3) inflammasome. In the coculture system, kaempferol 3-O-rutinoside and Anhydrosafflor yellow B significantly improved neuronal survival, suppressed neuronal apoptosis, and reduced IL-1beta and IL-10 levels in the medium. Thus, SAFE showed a significant anti-PD effect, which is mainly associated with flavonoid anti-inflammatory activities.

Assessment of Metabolic Profiles in Florets of Carthamus Species Using Ultra-Performance Liquid Chromatography-Mass Spectrometry.[Pubmed:33143321]

Metabolites. 2020 Oct 30;10(11):440.

The genus Carthamus is a diverse group of plants belonging to the family Compositae. Florets of Carthamus species exhibit various colors, including white, yellow, orange, and red, which are related to their metabolite compositions. We aimed to investigate the metabolites accumulated in florets of three wild (C. lanatus, C. palaestinus, and C. turkestanicus) and one cultivated (C. tinctorius) species of safflower at three developmental stages. Metabolites were extracted from freeze-dried florets using 70% methanol; qualification and quantification were carried out using liquid chromatography quadrupole time-of-flight mass spectrometry in positive and negative ion modes followed by extraction of the peaks. Fifty-six metabolites, including phenylpropanoids, chalcones, isoflavonoids, flavanones, flavonols, flavones, and other primary metabolites, were identified for the first time in safflower wild species. The orange florets contained high abundances of safflomin A, Anhydrosafflor yellow B, and baimaside, whereas white/cream and light-yellow pigmented florets had high abundances of 1,5-dicaffeoylquinic acid, luteolin 7-O-glucuronide, and apigenin 7-O-beta-D-glucuronide. The principal component analysis clearly distinguished the samples based on their pigment types, indicating that color is a dominant factor dictating the identity and amount of the metabolites. Pearson correlation data based on levels of metabolites showed that orange and yellow florets were significantly correlated to each other. White and cream pigmented species were also highly correlated. Comparison between three developmental stages of safflower wild species based on their metabolite profile showed inconsistent. The findings of this study broaden the current knowledge of safflower metabolism. The wide diversity of metabolites in safflower materials also helps in efforts to improve crop quality and agronomic traits.

Response surface optimization of the water immersion extraction and macroporous resin purification processes of anhydrosafflor yellow B from Carthamus tinctorius L.[Pubmed:32860216]

J Food Sci. 2020 Oct;85(10):3191-3201.

In this study,based on a developed high performance liquid chromatographic quantitative method, the suitable extraction and purification conditions of Anhydrosafflor yellow B (AHSYB) from safflower were determined by response surface methodology. The optimal water immersion extraction parameters were as follows: liquid to solid ratio of 22:1; extraction temperature of 75 degrees C; extraction time of 35 min. Under these conditions, the maximum extraction yield of AHSYB reached 0.465%. The aqueous extract was further purified by HPD-300 macroporous resin. The optimum adsorption conditions were: pH 2.8; adsorption flow rate of 1.9 mL/min; solution concentration of 0.06 g/mL. The optimum desorption conditions were: ethanol concentrations of 74%; desorption flow rate of 1.6 mL/min; elution volume of 4.4 BV. Under these conditions, the maximum adsorption ratio and desorption ratio reached 1.095 and 0.906 mg/g, respectively. The content of AHSYB reached 6.83%, which was 2.91 times higher than that before purification. PRACTICAL APPLICATION: The suitable conditions for water immersion extraction and macroporous resin purification of AHSYB are first determined, which facilitates the further utilization of AHSYB as a food and drug.

Three Ingredients of Safflower Alleviate Acute Lung Injury and Inhibit NET Release Induced by Lipopolysaccharide.[Pubmed:32189992]

Mediators Inflamm. 2020 Feb 29;2020:2720369.

Xuebijing injection is a Chinese herb compound to treat sepsis in China, but it contains many different kinds of components, and each component may have different effects in treating sepsis. The present study was performed to investigate the effect of three ingredients of Xuebijing, safflor yellow A (SYA), hydroxysafflor yellow A (HSYA), and Anhydrosafflor yellow B (AHSYB), in lipopolysaccharide- (LPS-) induced acute lung injury (ALI). LPS (10 mg/kg) was injected intratracheally to induce acute lung injury in mice, which were then treated with SYA, HSYA, and AHSYB. The blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected to detect degree of lung injury, level of inflammation, and neutrophil extracellular traps (NETs). In vitro experiments were performed using HL-60 cells stimulated with phorbol myristate acetate (PMA). Lung injury induced by LPS was alleviated by SYA, HSYA, and AHSYB as demonstrated by the histopathologic test. The three components inhibit LPS-induced elevation of the levels of inflammatory factors and wet-to-dry weight ratio as well as the amount of protein and cells in the BALF. They also induced a remarkably less overlay of myeloperoxidase (MPO) and histone in the immunofluorescence assay and reduced level of MPO-DNA complex in plasma. The in vitro assay showed a similar trend that the three components inhibited PMA-induced NET release in neutrophil-like HL-60 cells. Western blot demonstrated that phosphorylation of c-rapidly accelerated fibrosarcoma (c-Raf), mitogen-activated protein kinase ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) in the lungs of LPS-challenged mice, and PMA-treated HL-60 cells were all significantly reduced by SYA, HSYA, and AHSYB. Therefore, our data demonstrated that three components of XBJ, including SYA, HSYA, and AHSYB, showed a protective effect against LPS-induced lung injury and NET release.

Simultaneous Optimization of the Ultrasonic Extraction Method and Determination of the Antioxidant Activities of Hydroxysafflor Yellow A and Anhydrosafflor Yellow B from Safflower Using a Response Surface Methodology.[Pubmed:32182800]

Molecules. 2020 Mar 9;25(5):1226.

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 degrees 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.