Antitussive, Expectorant and Antipyretic Effect of the Ethanolic Extract of the Leaves of Momordica charantia L.

The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.

Research Progress on Anti-Inflammatory Effects and Related Mechanisms of Astragalin.

Chronic inflammation is a significant contributor to the development of cancer, cardiovascular disease, diabetes, obesity, autoimmune disease, inflammatory bowel disease, and other illnesses. In the academic field, there is a constant demand for effective methods to alleviate inflammation. Astragalin (AST), a type of flavonoid glycoside that is the primary component in several widely used traditional Chinese anti-inflammatory medications in clinical practice, has garnered attention from numerous experts and scholars. This article focuses on the anti-inflammatory effects of AST and conducts research on relevant literature from 2003 to 2023. The findings indicate that AST demonstrates promising anti-inflammatory potential in various models of inflammatory diseases. Specifically, AST is believed to possess inhibitory effects on inflammation-related factors and protein levels in various in vitro cell models, such as macrophages, microglia, and epithelial cells. In vivo studies have shown that AST effectively alleviates neuroinflammation and brain damage while also exhibiting potential for treating moderate diseases such as depression and stroke; it also demonstrates significant anti-inflammatory effects on both large and small intestinal epithelial cells. Animal experiments have further demonstrated that AST exerts therapeutic effects on colitis mice. Molecular biology studies have revealed that AST regulates complex signaling networks, including NF-κB, MAPK, JAK/STAT pathways, etc. In conclusion, this review will provide insights and references for the development of AST as an anti-inflammatory agent as well as for related drug development.

Astragalin ameliorates renal injury in diabetic mice by modulating mitochondrial quality control via AMPK-dependent PGC1α pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus, and oxidative stress and mitochondrial dysfunction play an important role in this process. It has been shown that aldose reductase (ALR2) catalyzes NADPH-dependent reduction of glucose to sorbitol, resulting in oxidative stress and mitochondrial dysfunction in diabetic patients. Astragalin (AG), a flavonoid extracted from Thesium chinense Turcz., shows an inhibitory activity on ALR2. In this study, we investigated the therapeutic effects of AG against renal injury in streptozocin (STZ)-induced diabetic mouse model. Diabetic mice were orally administered AG (5, 10 mg·kg-1·d-1) for 4 weeks. We showed that AG treatment greatly improved the proteinuria and ameliorated renal pathological damage without affecting the elevated blood glucose in diabetic mice. Furthermore, AG treatment significantly suppressed highly activated ALR2, and reduced oxidative stress in the kidney of diabetic mice and in high glucose and lipids-stimulated HK2 cells in vitro. We demonstrated that AG treatment modulated mitochondrial quality control and ameliorated apoptosis, boosting mitochondrial biogenesis, maintaining mitochondrial dynamic homeostasis, and improving energy metabolism disorder in vivo and in vitro. In high glucose and lipids-stimulated HK2 cells, we found that AG (20 µM) restored the phosphorylation level of AMPK, and upregulated the expression and transcriptional activity of PGC1α, whereas treatment with H2O2, blockade of AMPK with Compound C or knockdown of AMPKα with siRNA abolished the protective effect of AG on mitochondrial function, suggesting that antioxidant effects and activation of AMPK-dependent PGC1α pathway might be the molecular mechanisms underlying the protective effects of AG on mitochondrial quality control. We conclude that AG could be a promising drug candidate for the treatment of diabetic renal injury through activating AMPK.

Isolation of Pro-Osteogenic Compounds from Euptelea polyandra That Reciprocally Regulate Osteoblast and Osteoclast Differentiation.

Plants contain a large number of small-molecule compounds that are useful for targeting human health and in drug discovery. Healthy bone metabolism depends on the balance between bone-forming osteoblast activity and bone-resorbing osteoclast activity. In an ongoing study searching for 22 plant extracts effective against osteoporosis, we found that the crude extract of Euptelea polyandra Sieb. et Zucc (E. polyandra) had osteogenic bioactivity. In this study, we isolated two compounds, isoquercitrin (1) and astragalin (2), responsible for osteogenic bioactivity in osteoblastic MC3T3-E1 cells from the leaf of E. polyandra using column chromatography and the spectroscopic technique. This is the first report to isolate astragalin from E. polyandra. Compounds (1) and (2) promoted osteoblast differentiation by increasing alkaline phosphatase (ALP) activity and alizarin red S stain-positive calcium deposition, while simultaneously suppressing tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation in RAW264.7 cells at non-cytotoxic concentrations. Isoquercitrin (1) and astragalin (2) increased the expression of osteoblastic differentiation genes, Osterix, ALP, and Osteoprotegerin in the MC3T3-E1 cells, while suppressing osteoclast differentiation genes, TRAP, Cathepsin K, and MMP 9 in the RAW264.7 cells. These compounds may be ideal targets for the treatment of osteoporosis due to their dual function of promoting bone formation and inhibiting bone resorption.

Total Flavonoids in Artemisia absinthium L. and Evaluation of Its Anticancer Activity.

To overcome the shortcomings of traditional extraction methods, such as long extraction time and low efficiency, and considering the low content and high complexity of total flavonoids in Artemisia absinthium L., in this experiment, we adopted ultrasound-assisted enzymatic hydrolysis to improve the yield of total flavonoids, and combined this with molecular docking and network pharmacology to predict its core constituent targets, so as to evaluate its antitumor activity. The content of total flavonoids in Artemisia absinthium L. reached 3.80 ± 0.13%, and the main components included Astragalin, Cynaroside, Ononin, Rutin, Kaempferol-3-O-rutinoside, Diosmetin, Isorhamnetin, and Luteolin. Cynaroside and Astragalin exert their cervical cancer inhibitory functions by regulating several signaling proteins (e.g., EGFR, STAT3, CCND1, IGFIR, ESR1). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the anticancer activity of both compounds was associated with the ErbB signaling pathway and FoxO signaling pathway. MTT results showed that total flavonoids of Artemisia absinthium L. and its active components (Cynaroside and Astragalin) significantly inhibited the growth of HeLa cells in a concentration-dependent manner with IC50 of 396.0 ± 54.2 µg/mL and 449.0 ± 54.8 µg/mL, respectively. Furthermore, its active components can mediate apoptosis by inducing the accumulation of ROS.

Hyperoside as a UV Photoprotective or Photostimulating Compound-Evaluation of the Effect of UV Radiation with Selected UV-Absorbing Organic Compounds on Skin Cells.

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.

Astragalin alleviates cognitive deficits and neuronal damage in SAMP8 mice through upregulating estrogen receptor expression.

Senile plaques composed of ß-amyloid protein (Aß) and neurofibrillary tangles (NFTs) composed of intracellular hyper-phosphorylated tau are major causes of cognitive impairment and neuronal damage in Alzheimer disease (AD). Astragalin (AST), a naturally-occurring flavonoid compound, was reported to have neuroprotective effects in the brain, but its effects in AD remain unknown. Herein, the learning and memory deficits were alleviated and neuronal damage in the hippocampus were inhibited after the senescence-accelerated mouse prone 8 (SAMP8) mouse were given AST (5 mg/kg or 10 mg/kg) daily by gavage for 2 months. Furthermore, AST reduced Aß1-40 and Aß1-42 deposition, decreased ß-carboxyl-terminal fragment (ß-CTF) protein level and tau hyper-phosphorylation, but increased α-CTF protein level and glycogen synthase kinase-3beta (GSK-3ß) phosphorylation in hippocampus of SAMP8 mice. Meanwhile, the effects of AST on AD were also explored in vitro by treating primary neurons with amyloid-ß1-42 oligomers (Aß1-42O). Consistently, AST also alleviated amyloid-ß1-42 oligomers (Aß1-42O)-induced neuronal damage, amyloid plaques, and tau phosphorylation in vitro model. Of note, estrogen receptor (ER)α and ERß expression in the hippocampus of SAMP8 mice and Aß1-42O-treated neurons was significantly decreased but their levels were increased by AST. Moreover, in vivo and in vitro experiments revealed that ER antagonist, Fulvestrant, reversed the effects caused by AST. Altogether, our investigation indicates that AST may ameliorate cognitive deficits and AD-type pathologies in SAMP8 mice and Aß1-42O-treated neurons through upregulating ERα and ERß expression. Our findings indicate the value of AST as a potential reagent for AD treatment.

Neurite Outgrowth-Promoting Compounds from the Petals of Paeonia lactiflora in PC12 Cells.

Isorhamnetin-3-O-glucoside and astragalin, flavonol glucosides, were isolated from the petals of Paeonia lactiflora as neurite outgrowth-promoting compounds. Isoquercitrin, formed by demethylating the B ring of isorhamnetin-3-O-glucoside or by adding a hydroxyl group to the B ring of astragalin, was evaluated for neurite outgrowth-promoting activity and was compared with the activities of isorhamnetin-3-O-glucoside and astragalin. The activities of isorhamnetin, kaempferol, and quercetin, aglycones corresponding to isorhamnetin-3-O-glucoside, astragalin, and isoquercitrin, respectively, were also evaluated. Isorhamnetin-3-O-glucoside and astragalin showed much stronger neurite outgrowth-promoting activities than the activities of the other tested flavonoids. They exhibited relatively weak anti-oxidant activities and moderate AChE inhibitory activities compared to the activities of the other tested flavonoids. Isorhamnetin-3-O-glucoside and astragalin promoted morphological neurite outgrowth and the expression of neurofilaments induced by NGF in PC12 cells. Isorhamnetin-3-O-glucoside and astragalin might be candidate compounds as neural differentiation agents in peripheral nerves and functional food ingredients preventing cognitive decline.

Astragalin mediates the pharmacological effects of Lysimachia candida Lindl on adipogenesis via downregulating PPARG and FKBP51 signaling cascade.

Metabolic disturbances in different tissue cells and obesity are caused by excessive calorie intake, and medicinal plants are potential sources of phytochemicals for combating these health problems. This study investigated the role of methanolic extract of the folklore medicinal plant Lysimachia candida (LCM) and its phytochemical, astragalin, in managing obesity in vivo and in vitro. Administration of LCM (200 mg/kg/body weight) daily for 140 days significantly decreased both the body weight gain (15.66%) and blood triglyceride and free fatty acid levels in high-fat-diet-fed male Wistar rats but caused no substantial change in leptin and adiponectin levels. The protein expression of adipogenic transcription factors in visceral adipose tissue was significantly reduced. Further, the 3T3-L1 cell-based assay revealed that the butanol fraction of LCM and its isolated compound, astragalin, exhibited antiadipogenic activity through downregulating adipogenic transcription factors and regulatory proteins. Molecular docking studies were performed to depict the possible binding patterns of astragalin to adipogenesis proteins. Overall, we show the potential antiobesity effects of L. candida and its bioactive compound, astragalin, and suggest clinical studies with LCM and astragalin.

Astragalin Inhibits Cigarette Smoke-Induced Pulmonary Thrombosis and Alveolar Inflammation and Disrupts PAR Activation and Oxidative Stress-Responsive MAPK-Signaling.

Epidemiological evidence shows that smoking causes a thrombophilic milieu that may play a role in the pathophysiology of chronic obstructive pulmonary disease (COPD) as well as pulmonary thromboembolism. The increased nicotine level induces a prothrombotic status and abnormal blood coagulation in smokers. Since several anticoagulants increase bleeding risk, alternative therapies need to be identified to protect against thrombosis without affecting hemostasis. Astragalin is a flavonoid present in persimmon leaves and green tea seeds and exhibits diverse activities of antioxidant and anti-inflammation. The current study investigated that astragalin attenuated smoking-induced pulmonary thrombosis and alveolar inflammation. In addition, it was explored that molecular links between thrombosis and inflammation entailed protease-activated receptor (PAR) activation and oxidative stress-responsive mitogen-activated protein kinase (MAPK)-signaling. BALB/c mice were orally administrated with 10-20 mg/kg astragalin and exposed to cigarette smoke for 8 weeks. For the in vitro study, 10 U/mL thrombin was added to alveolar epithelial A549 cells in the presence of 1-20 µM astragalin. The cigarette smoking-induced the expression of PAR-1 and PAR-2 in lung tissues, which was attenuated by the administration of ≥10 mg/kg astragalin. The oral supplementation of ≥10 mg/kg astragalin to cigarette smoke-challenged mice attenuated the protein induction of urokinase plasminogen activator, plasminogen activator inhibitor-1and tissue factor, and instead enhanced the induction of tissue plasminogen activator in lung tissues. The astragalin treatment alleviated cigarette smoke-induced lung emphysema and pulmonary thrombosis. Astragalin caused lymphocytosis and neutrophilia in bronchoalveolar lavage fluid due to cigarette smoke but curtailed infiltration of neutrophils and macrophages in airways. Furthermore, this compound retarded thrombin-induced activation of PAR proteins and expression of inflammatory mediators in alveolar cells. Treating astragalin interrupted PAR proteins-activated reactive oxygen species production and MAPK signaling leading to alveolar inflammation. Accordingly, astragalin may interrupt the smoking-induced oxidative stress-MAPK signaling-inflammation axis via disconnection between alveolar PAR activation and pulmonary thromboembolism.

Astragalin attenuates oxidative stress and acute inflammatory responses in carrageenan-induced paw edema in mice.

Astragalin is a flavonoid existed in several edible and medicinal plants and was recorded to have multiple biological and pharmacological significances. This work aimed to assess the possible protective effect of astragalin administration against oxidative tension, acute inflammation and histopathological deformations in a mouse paw edema model induced following intra sub-plantar injection of carrageenan. Thirty-six male Swiss mice were divided into four groups: control, carrageenan, astragalin (75 mg/kg) + carrageenan, and indomethacin (10 mg/kg) + carrageenan. Astragalin administration for five consecutive days to carrageenan injected mice showed a significant reduction in the development of paw in a time dependent effect, inhibited lipoperoxidation by-product, malondialdehyde and increased superoxide dismutase and catalase activities. Astragalin was found also to suppress the inflammatory signaling in the inflamed tissue as exhibited by the decreased myeloperoxidase activity along with the decreased protein and transcriptional level of pro-inflammatory cytokines including tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6. Moreover, inducible nitric oxide synthase and cyclooxygenase-2 expressions and their products (nitric oxide and prostaglandin E2) were downregulated. Additionally, astragalin decreased monocyte chemoattractant protein-1 and nuclear factor kappa B expression in the inflamed paw tissue. The recorded findings provide evidences for the potential application of astragalin as a plant-derived remedy for the treatment of acute inflammation due to its promising antioxidant and anti-inflammatory activities along with its ameliorative impact against the histopathological changes in the paw tissue.

Evaluation Procoagulant Activity and Mechanism of Astragalin.

Astragalin, isolated from flowers of Rosa chinensis Jacq., is a kind of flavonoid, with anti-inflammatory, antioxidant, antiviral, analgesic, antibacterial, antiallergic, and antihepatotoxic effects. However, no studieson the procoagulant effect of astragalin have been reported. This study aimed to investigate the procoagulant activity of astragalin and its mechanism. Its procoagulant effect was investigated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) in vitro, and a rat model established by heparin sodium was used to evaluate the mechanism for the procoagulant effect in vivo. The results showed that astragalin had good procoagulant effects compared with the control group in vitro. Compared with the model group in vivo, astragalin could shorten the coagulation time and significantly increase the number of platelets. Meanwhile, astragalin could significantly reduce the effectual time of PT and APTT and increase the content of FIB. The contents of 6-keto-PGF1α and eNOS significantly decreased. Astragalin could increase whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and packedcell volume (PCV). All of the above revealed that astragalin had good procoagulant effects by promoting the intrinsic and extrinsic coagulation system.

Modulating heterologous pathways and optimizing fermentation conditions for biosynthesis of kaempferol and astragalin from naringenin in Escherichia coli.

Kaempferol and astragalin are used as standards to assess the quality of Ginkgo biloba extract and Radix astragali, respectively, and possess numerous biological properties. In this study, we constructed a recombinant strain with a highly efficient biosynthetic pathway of kaempferol by screening key enzyme genes, designing a synthetic fusion enzyme and increasing the gene copy number. By optimizing conversion and fed-batch fermentation conditions, maximal kaempferol production reached 1184.2 ± 16.5 mg/L, which represents the highest yield of kaempferol from naringenin reported to date. Based on this result, glycosyltransferase (AtUGT78D2) and an efficient UDP-glucose synthesis pathway were introduced into the recombinant strain to produce astragalin, resulting in maximal astragalin production at 1738.5 ± 24.8 mg/L without kaempferol accumulation. The efficient synthesis pathway described in this study for kaempferol and astragalin biosynthesis can be widely used for flavonoid biosynthesis in Escherichia coli.

Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells.

A flavonoid Astragalin (kaempferol-3-O-ß-d-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O-ß-d-isomaltotrioside, Ast-Gal) on murine bone marrow-derived dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through the upregulation of surface markers, such as cluster of differentiation (CD)80, CD86, and Major histocompatibility complex (MHC) II in a dose-dependent manner, while Ast had little effects. Additionally, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as interleukin (IL)-1ß, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4⁺ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4⁺ T cells into Th1 cells. The addition of neutralizing IL-12 monoclonal antibody (mAb) to cultures of Ast-Gal-treated DCs and CD4⁺ T cells significantly decreased interferon (IFN)-γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

Apoptotic Effect of Astragalin in Melanoma Skin Cancers via Activation of Caspases and Inhibition of Sry-related HMg-Box Gene 10.

Though Astragalin (kaempferol-3-glucoside) contained in Paeonia lactiflora and other plants was known to have anti-oxidant, antiinflammatory, and anti-tumor activity, the anti-tumor mechanism of Astragalin has never been reported in melanomas until now. Thus, in the present study, the underlying apoptotic mechanism of Astragalin isolated from Aceriphyllum rossii was elucidated in A375P and SK-MEL-2 melanoma cells. Astragalin exerted cytotoxicity in A375P and SK-MEL-2 cells in a concentration-dependent manner. Also, Astragalin significantly increased the number of TdT-mediated dUTP nick end labeling positive cells and sub-G1 population as a feature of apoptosis in A375P and SK-MEL-2 cells compared with untreated control. Consistently, western blotting revealed that Astragalin activated caspase 9/3 and Bax, cleaved poly (ADP-ribose) polymerase, and attenuated the expression of cyclin D1, Mcl-1, and Sry-related HMg-Box gene 10 (SOX10) in A375P and SK-MEL-2 cells. Of note, ectopic expression of SOX10 reduced the apoptotic ability of Astragalin to inhibit proliferation, cleave poly (ADP-ribose) polymerase, and caspase 3 in A375P and SK-MEL-2 melanoma cells. Overall, our findings provide evidence that Astragalin induces apoptosis in A375P and SK-MEL-2 melanoma cells via activation of caspase9/3 and inhibition of SOX10 signaling. Copyright © 2017 John Wiley & Sons, Ltd.

Role of the p-Coumaroyl Moiety in the Antioxidant and Cytoprotective Effects of Flavonoid Glycosides: Comparison of Astragalin and Tiliroside.

The aim of this study was to explore the role of p-coumaroyl in the antioxidant and cytoprotective effects of flavonoid glycosides. The antioxidant effects of astragalin and tiliroside were compared using ferric ion reducing antioxidant power, DPPH• scavenging, ABTS•⁺ scavenging, •O2- scavenging, and Fe2+-chelating assays. The results of these assays revealed that astragalin and tiliroside both exhibited dose-dependent activities; however, tiliroside exhibited lower IC50 values than astragalin. In the Fe2+-chelating assay, tiliroside gave a larger shoulder-peak at 510 nm than astragalin, and was also found to be darker in color. Both of these compounds were subsequently evaluated in a Fenton-induced mesenchymal stem cell (MSC) damaged assay, where tiliroside performed more effectively as a cytoprotective agent than astragalin. Tiliroside bearing a 6''-O-p-coumaroyl moiety exhibits higher antioxidant and cytoprotective effects than astragalin. The 6''-O-p-coumaroyl moiety of tiliroside not only enhances the possibility of electron-transfer and hydrogen-atom-transfer-based multi-pathways, but also enhances the likelihood of Fe-chelating. The p-coumaroylation of the 6"-OH position could therefore be regarded as a potential approach for improving the antioxidant and cytoprotective effects of flavonoid glycosides in MSC implantation therapy.

Screening of lipase inhibitors in Folium Mori with lipase-linked magnetic microspheres by high-performance liquid chromatography and evaluation in diabetic mice.

A new method for the screening of compounds with hypoglycemic effect from traditional Chinese medicines employing high-performance liquid chromatography and lipase-linked magnetic microspheres has been proposed. We hypothesized that the interaction of traditional Chinese medicine extracts with lipase-linked magnetic microspheres should decrease the concentration of compounds with hypoglycemic effect. Using this approach, the potential lipase inhibitors in Folium Mori extract were investigated. First, lipase was immobilized on magnetic microspheres by a chemical method. Then, by comparing the chromatograms of samples before and after the interaction with lipase-linked magnetic microspheres, seven compounds of Folium Mori extract were identified. It was found that protocatechuic acid, chlorogenic acid, protocatechualdehyde, rutin, isoquercitrin, astragalin, and dicaffeoylquinic acid B had evident combination with lipase-linked magnetic microspheres. Their hypoglycemic effects were verified in streptozocin-induced diabetic mice. In the present study, astragalin was verified to improve the glucose tolerance and lower the level of glucose in streptozocin-induced diabetic mice, which indicated that astragalin might be a new highly efficient lipase inhibitor. Based on these significant results, this method could be a convenient approach to screen potential lipase inhibitors from traditional Chinese medicines. Meanwhile, it also could be expanded to screen other active compounds in traditional Chinese medicines.

Astragalin, a Flavonoid from Morus alba (Mulberry) Increases Endogenous Estrogen and Progesterone by Inhibiting Ovarian Granulosa Cell Apoptosis in an Aged Rat Model of Menopause.

BACKGROUND: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause. METHODS: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using flow cytometry. In vitro, the effects of AST on cultured GCs were investigated using the MTT proliferation assay and western blot assays. RESULTS: Aged rats had significantly higher GC apoptosis as compared with young female rats. Treatment of aged rats with AST (all three doses; p < 0.01) or Progynova (p < 0.01) significantly reduced GC apoptosis as compared with the aged controls. The proportions of total apoptotic GCs was 25.70%, 86.65%, 47.04%, 27.02%, 42.09% and 56.42% in the normal, aged, 17ß-estradiol (E2), high dose AST, medium dose AST, and low dose AST-treated groups, respectively. Significant increases of serum E2 and P4 levels, as well as altered levels of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. In cultured rat GCs, AST stimulated GC proliferation, E2 and progesterone (P4) secretion, reduced apoptosis, reduced the level of the pro-apoptotic protein Bcl-2 (p < 0.01), but had no effect on BAX. CONCLUSIONS: AST enhanced ovarian function in aged female rats by increasing E2 and P4 levels, and reducing ovarian GC apoptosis via a mechanism involving Bcl-2. These data demonstrate a new pharmacological activity for AST, as well as a novel mechanism of action, and further suggest that AST may be a new therapeutic agent for the management of menopausal symptoms.

Separation of isorhamnetin 3-sulphate and astragalin from Flaveria bidentis (L.) Kuntze using macroporous resin and followed by high-speed countercurrent chromatography.

D4020 resin offered the best dynamic adsorption and desorption capacity for total flavonoids based on the research results from ten kinds of macroporous resin. A column packed with D4020 resin was used to optimize the separation of total flavonoids from Flaveria bidentis (L.) Kuntze extracts. The content of flavonoids in the product was increased from 4.3 to 30.1% with a recovery yield of 90%. After the treatment with gradient elution on D4020 resin, the contents of isorhamnetin 3-sulfate and astragalin were increased from 0.49 to 8.70% with a recovery yield of 74.1% and 1.16 to 30.8%, with a recovery yield of 92.2%, respectively. Further purification was carried out by one-run high-speed countercurrent chromatography yielding 4.5 mg of isorhamnetin 3-sulfate at a high purity of 96.48% and yielding 24.4 mg of astragalin at a high purity of over 98.46%.

Inhibitory effects of astragalin on lipopolysaccharide-induced inflammatory response in mouse mammary epithelial cells.

BACKGROUND: Tea brewed from the leaves of persimmon or Rosa agrestis have several medical functions including treating allergy, antiatopic dermatitis, and anti-inflammatory effects. The objective of this study was to investigate the molecular mechanisms of astragalin, a main flavonoid component isolated from these herbs, in modifying lipopolysaccharide (LPS)-induced signaling pathways in primary cultured mouse mammary epithelial cells (mMECs). MATERIALS AND METHODS: The mMECs were treated with LPS in the absence or presence of different concentrations of astragalin. The expression of proinflammatory cytokines tumor necrosis factor α, and interleukin 6, as well as nitric oxide production were determined by enzyme-linked immunosorbent assay and Griess reaction, respectively. Cyclooxygenase-2, inducible nitric oxide synthase, toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), inhibitor protein of NF-κB (IκBα), P38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase were measured by Western blot. RESULTS: The results showed that astragalin suppressed the expression of tumor necrosis factor α, interleukin 6, and nitric oxide in a dose-dependent manner in mMECs. Western blot results showed that the expression of inducible nitric oxide synthase and cyclooxygenase-2 was inhibited by astragalin. Besides, astragalin efficiently decreased LPS-induced TLR4 expression, NF-κB activation, IκBα degradation, and the phosphorylation of p38, extracellular signal-regulated kinase in BMECs. CONCLUSIONS: Our results indicated that astragalin exerts anti-inflammatory properties possibly via the inactivation of TLR4-mediated NF-κB and mitogen-activated protein kinases signaling pathways in LPS-stimulated mMECs. Thus, astragalin may be a potential therapeutic agent for bovine mastitis.