Chemical constituents and bioactivities of fermented rose (from Yunnan) extract.

Natural plant extracts have gained significant attention in research due to their low toxicity, and potent antioxidant, and anti-aging properties. The present study investigated the phytochemical composition of a fermented rose extract (FRE), and evaluated its antioxidant, skin whitening, and anti-aging activities in vitro. The results showed that the FRE was rich in polyphenols and flavonoids. A total of 13 major compounds were identified by Liquid Chromatography-Mass Spectrometry (LC-MS), with astragalin as the primary component. In vitro, analysis of antioxidant activity showed that FRE effectively eliminated 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and dose-dependent reduced intracellular reactive oxygen species (ROS) levels. The FRE dose-dependent inhibited tyrosinase, collagenase, and hyaluronidase activity, reduced intracellular melanin synthesis, up-regulated the expression of collagen type I alpha 1 (COL1A1) and collagen type III alpha 1 (COL3A1), and down-regulated matrix metalloproteinases (MMPs) expression. Additionally, treatment with FRE significantly downregulated the expression of mitogen-activated protein kinase 1 (MAPK1), suggesting that FRE may modulate MAPK signaling pathways for skin anti-aging.

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.

Establishing aqueous two-phase flotation coupled with preparative high performance liquid chromatography and its application for the purification of astragalin from Flaveria bidentis.

The strategy of aqueous two-phase flotation (ATPF) followed by preparative high performance liquid chromatography (prep-HPLC) was established and used for the separation of astragalin from Flaveria bidentis. In the ATPF, the effects of sublation solvent, solution pH, (NH4)2SO4 concentration in aqueous solution, cosolvent, N2 flow rate, flotation time and volumes of the PEG phase on the recovery of astragalin were investigated in detail, and the optimal conditions of ATPF were selected: 50 wt% PEG1000 ethanol solvent as the flotation solvent, pH 4, 350 g/L of (NH4)2SO4 concentration in 5 % ethanol aqueous phase, 40 mL/min of N2 flow rate, 30 min of flotation time, 10.0 mL of flotation solvent volume and twice. After ATPF enrichment, the flotation product was further purified by prep-HPLC. As determined by HPLC, the purity of astragalin was 98.8 %.

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.

Antidiabetic effectiveness of Phyllanthus niruri bioactive compounds via targeting DPP-IV.

Phyllanthus niruri Linn. (Euphorbiaceae) is a small herb and is categorised as one of the rich medicinal plants throughout the world. This study aimed to evaluate the P. niruri L. whole plant extract (PNE) for secondary metabolite assay (total phenolic and terpenoid content) followed by the potential antioxidant activity (ABTS diammonium salt radical assay, DPPH· activity, superoxide anion (O2-) radicals' assay, and nitric oxide (NO) radical generation) and antidiabetic activity in vivo and in vitro in streptozotocin (STZ) induced albino mice. PNE showed good scavenging activity with a value of 286.45 ± 6.55 mg TE/g and 194.54 ± 4.64 mg TE/g in ABTS and DPPH assays respectively. In the superoxide anion assay, the PNE caused a dose-dependent inhibition at the lowest IC25 value of 0.17 ± 0.00 mg/mL compared to ascorbic acid (IC25 of 0.25 ± 0.02 mg/mL). The scavenging ability of PNE against nitric oxide showed an IC25 of 1.13 ± 0.04 mg/mL compared to ascorbic acid (IC25 4.78 ± 0.09 mg/mL). Unlike diabetic control mice, the PNE-treated diabetic mice presented significant amelioration of glycaemia and lipid dysmetabolism. Phytochemicals like Astragalin, Gallocatechin, Ellagic acid, Gallic acid, Brevifolin carboxylic acid, Phyllnirurin, and Hypophyllanthin showed significant docking score (> -4) of inhibitory potential with DPP-IV protein. Results indicated that PNE phytochemicals could be a promising antidiabetic agent by targeting DPP-IV.

Discovering a New Drug Against Acute Kidney Injury by Using a Tailored Photoacoustic Imaging Probe.

Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB-DiOH) which can reversibly respond to hypochlorite (ClO-)/glutathione (GSH) with high specificity and sensitivity. This probe enables the real-time monitoring of AKI by noninvasive PA imaging, with better detection sensitivity than the blood test. Furthermore, this probe is utilized for screening nephroprotective drugs among natural products. For the first time, astragalin is discovered to be a potential new drug for the treatment of AKI. After oral administration, astragalin can be efficiently absorbed by the animal body, alleviate kidney injury, and meanwhile induce no damage to other normal tissues. The treatment mechanism of astragalin has also been revealed to be the simultaneous inhibition of oxidative stress, ferroptosis, and cuproposis. The developed PA imaging probe and the discovered drug candidate provide a promising new tool and strategy for the early diagnosis and effective treatment of AKI.

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.

Astragalin: a food-origin flavonoid with therapeutic effect for multiple diseases.

Naturally occurring flavonoids have long been utilized as essential templates for the development of novel drugs and as critical ingredients for functional foods. Astragalin (AG) is a natural flavonoid that can be isolated from a variety of familiar edible plants, such as the seeds of green tea, Morus alba L., and Cuscuta chinensis. It is noteworthy that AG has a wide range of pharmacological activities and possesses therapeutic effects against a variety of diseases, covering cancers, osteoarthritis, osteoporosis, ulcerative colitis, mastitis, obesity, diabetes mellitus, diabetic complications, ischemia/reperfusion injury, neuropathy, respiratory diseases, and reproductive system diseases. This article reviewed the natural source and pharmacokinetics of AG and systematically summarized the pharmacological activities and potential mechanisms of AG in treating diverse diseases in order to promote the development of AG as a functional food, in doing so providing references for its clinical application in disease therapy.

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.

Identification and Characterization of CtUGT3 as the Key Player of Astragalin Biosynthesis in Carthamus tinctorius L.

Safflower (Carthamus tinctorius L.) is a multipurpose economic crop that is distributed worldwide. Flavonoid glycosides are the main bioactive components in safflower, but only a few UDP-glycosyltransferases (UGT) have been identified. Three differentially expressed UGT genes related with the accumulation of 9 flavonoid O-glycosides were screened from metabolomics and transcriptome analysis. Safflower corolla protoplasts were used to confirm the glycosylation ability of UGT candidates in vivo for the first time. The astragalin content was significantly increased only when CtUGT3 was overexpressed. CtUGT3 also showed flavonoid 3-OH and 7-OH glycosylation activities in vitro. Molecular modeling and site-directed mutagenesis revealed that G15, T136, S276, and E384 were critical catalytic residues for the glycosylation ability of CtUGT3. These results demonstrate that CtUGT3 has a flavonoid 3-OH glycosylation function and is involved in the biosynthesis of astragalin in safflower. This study provides a reference for flavonoid biosynthesis genes research in nonmodel plants.

Astragalin attenuates diabetic cataracts via inhibiting aldose reductase activity in rats.

AIM: To investigate the aldose reductase (AR) inhibition capacity of astragalin (AST) against streptozoticin-induced diabetic cataracts (DCs) in rats. METHODS: Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor (AAH) of pH 7.8 at room temperature with cataract-causing substance (55 mmol/L of galactose) and in vivo studies were performed on rats via induction with streptozotocin. AST was administered at different dose levels and scrutinize for DC activity. RESULTS: In diabetic rats, AST improved the body weight, blood insulin, and glucose as well as the levels of galactitol in a dose-dependent way, other biochemical parameters i.e. inflammatory mediators and cytokines, and also suppress AR activity. The level of the antioxidant parameters such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activity were also altered on a diabetic lens after the administration of the AST. CONCLUSION: AST protects against lens opacification to avoid cataracts and polyols formation, indicating that it could be used as a potential therapeutic agent for diabetes.

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.

In silico Prediction of Malvaviscus arboreus Metabolites and Green Synthesis of Silver Nanoparticles - Opportunities for Safer Anti-Bacterial and Anti-Cancer Precision Medicine.

Introduction: Biogenic silver nanoparticles (AgNPs) may be a feasible therapeutic option in the research and development towards selectively targeting specific cancers and microbial infections, lending a role in precision medicine. In-silico methods are a viable strategy to aid in drug discovery by identifying lead plant bioactive molecules for further wet lab and animal experiments. Methods: Green synthesis of M-AgNPs was performed using the aqueous extract from the Malvaviscus arboreus leaves, characterized using UV spectroscopy, FTIR, TEM, DLS, and EDS. In addition, Ampicillin conjugated M-AgNPs were also synthesized. The cytotoxic potential of the M-AgNPs was evaluated using the MTT assay on MDA-MB 231, MCF10A, and HCT116 cancer cell lines. The antimicrobial effects were determined using the agar well diffusion assay on methicillin-resistant S. aureus (MRSA) and S. mutans, E. coli, and Klebsiella pneumoniae. Additionally, LC-MS was used to identify the phytometabolites, and in silico techniques were applied to determine the pharmacodynamic and pharmacokinetic profiles of the identified metabolites. Results: Spherical M-AgNPs were successfully biosynthesized with a mean diameter of 21.8 nm and were active on all tested bacteria. Conjugation with ampicillin increased the susceptibility of the bacteria. These antibacterial effects were most predominant in Staphylococcus aureus (p < 0.0001). M-AgNPs had potent cytotoxic activity against the colon cancer cell line (IC50=29.5 µg/mL). In addition, four secondary metabolites were identified, Astragalin, 4-hydroxyphenyl acetic acid, Caffeic acid, and Vernolic acid. In silico studies identified Astragalin as the most active antibacterial and anti-cancer metabolite, binding strongly to the carbonic anhydrase IX enzyme with a comparatively higher number of residual interactions. Discussion: Synthesis of green AgNPs presents a new opportunity in the field of precision medicine, the concept centered on the biochemical properties and biological effects of the functional groups present in the plant metabolites used for reduction and capping. M-AgNPs may be useful in treating colon carcinoma and MRSA infections. Astragalin appears to be the optimal and safe lead for further anti-cancer and anti-microbial 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.

Ethnopharmacology of Rubus idaeus Linnaeus: A critical review on ethnobotany, processing methods, phytochemicals, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus idaeus Linnaeus (RI) is a Chinese herbal medicine that has been widely used in China for a long time to reinforce the kidney, nourish the liver, improve vision, and arrest polyuria. AIM OF THE STUDY: This work aims to evaluate the recent progress of the chemical composition, pharmacological activity, pharmacokinetics, metabolism, and quality control and of Rubus idaeus, which focuses on the insufficiency of existing research and will shed light on future studies of Rubus idaeus. METHODS: Literatures about "Rubus idaeus","Red raspberry" and "Fupenzi"are retrieved by browsing the database, such as Web of Science (http://www.webofknowledge.com/wos), Pubmed (https://pubmed.ncbi.nlm.nih.gov/), CNKI (http://www.cnki.net/), and Wanfang Data (http://www.wanfangdata.com.cn). In addition, related textbooks and digital documents are interrogated to provide a holistic and critical review of the topic. The period of the literature covered from 1981 to 2022. RESULTS: Approximately 194 compounds have been isolated from Rubus idaeus, which is rich in phenols, terpenoids, alkaloids, steroids, and fatty acids. Numerous investigations have demonstrated that Rubus idaeus exhibits many pharmacological activities, including hypoglycemic and hypolipidemic, anti-Alzheimer effect, anti-osteoporosis, hepatoprotective, anti-cancer, neuroprotective, anti-bacteria and skin care, etc. However, it is worth noting that most of the research is not associated with the conventional effect, such as reducing urination and treating opacity of the cornea. CONCLUSION: The effectiveness of Rubus idaeus has been proved by its long-term clinical application. The research on the pharmacological activity of Rubus idaeus has flourished. In many pharmacological experiments, only the high-dose group can achieve the corresponding efficacy, so the efficacy of Rubus idaeus needs to be further interrogated. Meanwhile, the relationship between pharmacological activity and specific compounds of Rubus idaeus has not been clarified yet. Last but not least, studies involving toxicology and pharmacokinetics are very limited. Knowledge of bioavailability and toxicological behavior of Rubus idaeus can help understand the herb's pharmacodynamic and safety profile.

Astragalin Inhibits Apoptosis of Cerebral Cortex Neurons in APP/PS1 Mice / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of Astragalin （AST） on apoptosis of cerebral cortex neurons in APP/PS1 transgenic mice. MethodsEighteen six-month-old male APP/PS1 transgenic mice were randomly divided into APP/PS1 group， APP/PS1+ 40 mg/kg AST group and APP/PS1+ 20 mg/kg Donepezil （DNP） group， with six mice in each group. At the same time， six male C57BL/6 mice were selected as the normal control group. After intraperitoneal injection of AST once a day and continuous administration for one month， we used Tunel staining to detect the apoptosis of neurons in the cerebral cortex of APP/PS1 mice； immunofluorescent staining to examine the expression of apoptosis-related proteins Bax， Bcl-2， Caspase9 and Cleaved-Caspase3 in the cerebral cortex neurons of APP/PS1 mice； Western blot method to evaluate the changes of the expression of Bax， Bcl-2， Caspase9 and Caspase3. ResultsTunel staining showed that 40 mg/kg AST and 20 mg/kg DNP both reduced the apoptosis of neurons in the cerebral cortex of APP/PS1 mice， AST with more significant inhibition effect. Immunofluorescent staining revealed that 40 mg/kg AST and 20 mg/kg DNP both inhibited the expression of Bax， Caspase9， and Cleaved-Caspase3， and icreased the expression of Bcl-2 in the cerebral cortex neurons of APP/PS1 mice. Western blot results further confirmed that 40 mg/kg AST and 20 mg/kg DNP both down-regulated the expression of Bax （P < 0.05， P < 0.05）， Caspase9 （P < 0.005， P < 0.05） and Caspase3 （P < 0.0001， P < 0.0001） ， and up-regulated the expresstion of Bcl-2 （P < 0.05， P < 0.05） in the cerebral cortex neurons of APP/PS1 mice. ConclusionsAST can inhibit the apoptosis of cerebral cortex neurons in APP/PS1 mice.

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.

Mixed computational-experimental study to reveal the anti-metastasis and anti-angiogenesis effects of Astragalin in human breast cancer.

BACKGROUND: Breast cancer is the most aggressive malignant tumor with high morbidity and mortality. Astragalin, a flavonoid widely found in a variety of edible and medicinal plants, is recorded to possess multiple biological and pharmacological activities. However, its effect of anti-breast cancer has been unknown. METHODS: Computational pharmacology was employed to explore the potential mechanism of anti-metastasis and anti-angiogenesis effects of Astragalin on breast cancer. The targets of Astragalin were obtained from TCMSP, Swiss Target Prediction, SEA, BATMAN-TCM, ChemMapper and STITCH databases, and targets of breast cancer were got from OMIM, GeneCards, and DisGeNET databases. Protein-protein interaction network (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the interactions of these two groups of targets. Moreover, the anti-metastasis and anti-angiogenesis effects of Astragalin were validated by in vitro and in vivo experiments using wound healing assay, transwell migration and invasion assay, gelatin zymography assay, tube formation assay, and chick embryo chorioallantoic membrane model. RESULTS: Computational pharmacology analysis indicated that the effects of Astragalin against breast cancer were mainly related to the regulation of the cell movement, migration, and angiogenesis, and taking AKT, ZEB1, VEGF, and MMP9 as the promising targets. Further experimental pharmacology indicated that Astragalin exerted anti-metastasis and anti-angiogenesis activities on breast cancer, and verified AKT, ZEB1, VEGF, and MMP9 as the key targets. CONCLUSION: Astragalin suppresses the metastasis and angiogenesis of breast cancer, and AKT, ZEB1, VEGF, and MMP9 are the promising targets for Astragalin against breast cancer. Thus, Astragalin is a potential therapeutic agent for breast cancer.

Astragalin mitigates inflammatory osteolysis by negatively modulating osteoclastogenesis via ROS and MAPK signaling pathway.

Inflammatory bone destruction has gradually attracted attention worldwide and has been observed in several kinds of pathological bone diseases, such as osteoarthritis, osteomyelitis, rheumatic arthritis, and other infectious clinical trials in the skeletal system. In this regard, excessive osteoclasts and bone resorption activity participate in osteolytic processes. Thus, negatively modulating osteoclast differentiation and bone erosion has been considered an effective therapeutic strategy to limit the poor progression of inflammatory osteolysis. Astragalin (AST) is a bioactive component of traditional Chinese drugs, such as Rosa agrestis, which presents anti-inflammatory and antioxidant effects. However, it is unclear how AST may play an essential role in regulating the dynamic balance of the bone matrix by affecting osteoclastogenesis. This study found that AST could inhibit osteoclastic formation and bone resorption activity in a dose-dependent manner without cytotoxicity. Administration of AST also inhibited the expression of cathepsin K, c-Fos, NFATc1, and TRAP at different stages of mRNA and protein levels during osteoclastogenesis. Reactive oxygen species (ROS) signalling could also be modulated by treatment with AST during RANKL-induced osteoclast differentiation through the Nrf2-HO1 signalling pathway. Additionally, AST could negatively regulate mitogen-activated protein kinase (MAPK) signalling in this process. In vivo, AST significantly reduced lipopolysaccharide (LPS)-induced bone loss in an osteolytic mouse model. AST might be a promising therapeutic candidate for treating osteolytic bone diseases in the future.

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.