Astragalus Membranaceus Extract Research Articles

Identification of Astragalus Polysaccharide as a Neuroprotective Agent via Activating Klotho-mediated Nrf2 Pathway

Background Neurodegenerative diseases (NDs) have become a significant public health problem, and oxidative stress (OS) serves as a pivotal factor in the pathological progression of NDs. Pharmacological research indicates that Astragalus polysaccharide (APS, extract of Astragalus membranaceus) has antioxidant and antiaging effects, closely related to NDs. Purpose The potential of APS in treating NDs remains uncertain. Herein, the neuroprotective effect of APS was evaluated. Methods The H2O2-induced PC12 cell damage model was established to assess the neuroprotection of APS. Cell viability was determined by MTT. Cell images were observed using ImageXpress Micro Confocal analysis. Apoptosis of the cells and intracellular levels of reactive oxygen species (ROS) were detected using flow cytometry. The expression of Klotho, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), thioredoxin reductase 1 (TrxR1), and NAD(P)H quinone oxidoreductase 1 (NQO1) was determined by Western blot (WB). Results APS exerted significant protection against H2O2-caused cell death dose-dependently, and APS could significantly reduce the intracellular ROS and relieve cell apoptosis. Furthermore, we found that APS could upregulate the expression of Klotho and Nrf2 dose-dependently, and the expression levels of Nrf2-mediated antioxidant proteins increased significantly, including HO-1, TrxR1, and NQO1. Moreover, we found that APS upregulated Klotho and Nrf2-mediated antioxidant proteins time-dependently. The expression of klotho peaked at 6 hours after treatment with APS (400 mg/L). Subsequently, the protein level of Nrf2 reached the maximum at 12 hours, and the downstream NQO1, HO-1, and TrxR1 levels peaked at 24 hours. Conclusion This study demonstrates that APS is promising for further development against oxidative stress-related NDs.

The impact of Codonopsis Pilosulae and Astragalus Membranaceus extract on growth performance, immunity function, antioxidant capacity and intestinal development of weaned piglets.

The objective of this study was to examine the impact of Codonopsis pilosula and Astragalus membranaceus extract (CA) on the growth performance, diarrhea rate, immune function, antioxidant capacity, gut microbiota, and short-chain fatty acids (SCFAs) in weaned piglets. A total of forty-eight 31-day-old weaned piglets, were divided into four groups randomly based on the treatment type: control group (CON), low dose group (LCA, 0.5% CA), medium dose group (MCA, 1.0% CA), and high dose group (HCA, 1.5% CA), and were fed for a duration of 28 days. On the morning of the 1st and 29th day, the piglets were assessed by weighing them on an empty stomach, recording their daily feed intake and diarrhea rate. CA increased the average daily weight gain and reduced F/G without significant differences, and the diarrhea rate was reduced in the LCA and MCA groups. Furthermore, the levels of T-AOC, SOD, GSH-Px, and MDA were increased. The levels of T-AOC in the LCA group and the MCA group, SOD in the MCA group, and GSH-Px in the HCA group were significantly higher compared with the CON group (p < 0.05). Additionally, CA significantly increased IgM, IgG, and IgA levels (p < 0.05). The results of gut microbiota analysis showed that the bacterial population and diversity of faeces were changed with the addition of CA to basal diets. CA increased the abundance of the beneficial bacterial Firmicutes and Lactobacillus. Additionally, Compared with the CON group, CA significantly increased the SCFAs content of weaned piglets (p < 0.05). CA can alleviate oxidative stress, improve immunity and antioxidant capacity, increase the abundance of beneficial bacteria, and the content of SCFAs for improving the intestinal barrier of piglets, thus promoting growth and reducing diarrhea rate in weaned piglets.

Investigation of the Lipid-Lowering Activity and Mechanism of Three Extracts from Astragalus membranaceus, Hippophae rhamnoides L., and Taraxacum mongolicum Hand. Mazz Based on Network Pharmacology and In Vitro and In Vivo Experiments.

Hyperlipidemia is a metabolic disorder characterized by abnormal lipid metabolism, resulting in lipid accumulation in the plasma. According to reports, medicinal and edible plants can reduce the risk of metabolic diseases such as hyperlipidemia. This study investigates the effects and mechanisms of Astragalus membranaceus extract (AME), Hippophae rhamnoides L. extract (HRE), and Taraxacum mongolicum Hand. Mazz extract (TME) on hyperlipidemia. Active compounds and potential gene targets of AME, HRE, and TME were screened using LC-MS and TCMSP databases, and hyperlipidemia targets were detected from the OMIM and DisGeNet databases. A drug-target pathway disease network was constructed through protein interactions, GO enrichment, and KEGG pathway analysis. Finally, the lipid-lowering effects of three extracts were validated through in vitro HepG2 cell and in vivo animal experiments. The results show that LC-MS and network pharmacology methodologies identified 41 compounds and 140 targets. KEGG analysis indicated that the PI3K-Akt and MAPK signaling pathways significantly treat hyperlipidemia with AHT. In vitro experiments have shown that AHT is composed of a ratio of AME:HRE:TME = 3:1:2. HepG2 cell and animal experiments revealed that AHT exhibits strong lipid-lowering and antioxidant properties, significantly regulating the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). It is worth noting that AHT can effectively downregulate the protein expression levels of p-AKT/AKT and p-PI3K/PI3K and upregulate the protein expression levels of p-AMPK/AMPK and SIRT1, verifying the results predicted by network pharmacology. This study presents a novel approach to utilizing these natural plant extracts as safe and effective treatments for hyperlipidemia.

Non-targeted metabolomics analysis of fermented traditional Chinese medicine and its impact on growth performance, serum biochemistry, and intestinal microbiome of weaned lambs

Fermented traditional Chinese medicines (TCMs) have been identified as a low-cost and promising feed additive to to alleviate weaning stress in young livestock and poultry effectively. This study investigated the impact of probiotic fermentation on the metabolite content of BanQi (Radix Isatidis and Astragalus membranaceus) extract while also examined the effects of both fermented-BanQi (FBQ) and unfermented-BanQi (UBQ) on growth performance, serum biochemistry, intestinal villi, and gut microbiota in weaned lambs. This study demonstrated that compared with UBQ, FBQ contained significantly higher levels of free amino acids (e.g., phenylalanine and isoleucine), short peptides (e.g., Val–Leu–Pro–Val–Pro–Gln and Gly–Leu), and the active ingredients (e.g., vindesine and reserpine) (P < 0.05). The addition of FBQ to the diet significantly increased the final body weight and average daily gain of weaned lambs (P < 0.05). In addition, FBQ significantly increased the total protein level in the serum and the villus length of the jejunum and ileum in lambs, while significantly reduced the levels of aspartate aminotransferase (AST) and urea (P < 0.05). Sequencing of the intestinal flora showed that FBQ improved the diversity of intestinal flora and promoted the enrichment of beneficial bacteria in the lamb intestine, such as Mogibacterium and Butyrivibrio, compared to NC or UBQ groups (P < 0.05). Fermentation with Bacillus subtilis can enhance the content of free amino acids, peptides, and active ingredients in BanQi extract, making it an effective method to improve the efficacy of traditional Chinese medicine. Adding FBQ to the diet can improve the growth performance of weaned lambs, and its mechanism may be related to increasing the height of intestinal villi and increasing the diversity of intestinal flora.

Astragaloside IV inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of oral cancer cells by aggravating autophagy

Oral cancer is one usual tumor that sorely affects the health of people and even result into death. Astragaloside IV (AS-IV) is one of the major components of Astragalus membranaceus extract, and has been identified to exhibit ameliorative functions in some cancers. Nevertheless, the regulatory impacts and correlative pathways of AS-IV in oral cancer remain vague. In this study, it was discovered that cell growth was gradually weakened with the increased dose of AS-IV (25, 50 and 100 μM). Additionally, it was uncovered that AS-IV restrained the EMT progress in oral cancer. The cell migration and invasion abilities were both gradually alleviated after AS-IV treatment in a dose-dependent manner. Moreover, AS-IV accelerated autophagy through intensifying LC3II/LC3I level and LC3B fluorescence intensity. At last, it was clarified that AS-IV triggered the AMPK pathway and retarded the AKT/mTOR pathway. In conclusion, AS-IV restrained cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progress in oral cancer by aggravating autophagy through modulating the AMPK and AKT/mTOR pathways. This work may offer novel evidence on AS-IV in the treatment of oral cancer.

Hematological profile, rumen fermentation, antioxidant state, and immune response of Egyptian Nubian goats fed on Astragalus membranaceus root extract supplemented ration

Background In recent years, Astragalus membranaceus extract has been widely used in animals due to their antimicrobial activities, ability to enhance immunity, and antioxidant functions. Objective We aimed to determine the antioxidant and inhibitory activities of A. membranaceus root powder (AMP) and its cytotoxicity and effects on hematological profile, rumen fermentation, antioxidant status, and immune response in Egyptian Nubian goats. Materials and methods Twenty-five goats are used in this study were received 20 g/animal/day of AMP mixed with their basic diet for 28 days. The study involved measuring the antioxidant activity of AMP using the 2-diphenyl-1-picrylhydrazyl radical scavenging assay and determining the viability and cytotoxicity percentage using the methyl-thiazolyl tetrazolium protocol. Results After 14 and 28 days of the daily feeding with 20 g of AMP, there was a significant increase in hematological profile, leukocyte count, total volatile fatty acid, and rumen ammonium concentrations with an enhancement in protozoal activity. Also, there was an increase in catalase and total antioxidant capacities along with promoting immunoglobulin (A, M, and G) contents with no significant effect on the insulin level compared with 0 days. Malondialdehyde contents decreased significantly. For all examined concentrations, A. membranaceus showed antioxidant and anti-inflammatory activities. It also showed a high cytotoxicity percentage in cancer cells. Discussion and conclusions A. membranaceus root extract supplementation significantly increases hematology parameters and rumen fermentation, and improves immune status and antioxidant activity both in-vitro and in live animals. It also exhibits potent cytotoxicity on cancer cells.

The protective effect of dietary extract of Astragalus membranaceus on the high stocking density, copper and trichlorfon in Jian carp (Cyprinus carpio var. Jian)

This study was designed to examine the protective effects of extract of Astragalus membranaceus (EAM) against stress, which induced by high stocking density, Cu and trichlorfon exposure in Jian carp (Cyprinus carpio var. Jian). The husbandry period (23.0 ± 1 °C) for high stocking density (0.97 fish/L) was 60 days with the initial fish weight 7.2 ± 0.2 g, and Cu (0.7 mg/L) and trichlorfon (2.2 mg/L) exposure was 4 days after feeding trial (30 days) with the initial fish weight 10.5 ± 0.3 g. Stress of high stocking density and Cu exposure decrease 48.2 % of fish weight gain and reduced 97.6 % of feed intake. Meanwhile, trichlorfon exposure induced 100 % fish rollover. High stocking densities and Cu exposure decreased activities of amylase, trypsin, as well as Na+/K+-ATPase and alkaline phosphatase and increased malonaldehyde content in fish digestive organs (P < 0.05), indicating an interruption of digestive ability and antioxidant status. Furthermore, trichlorfon exposure decreased activities of lactate dehydrogenase, superoxide dismutase, catalase, glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase in fish muscles (P < 0.05), indicating an interruption on bioenergetic homeostasis and antioxidant status. Dietary EAM supplementation relieved these detrimental effect, which induced by high stocking density, Cu and trichlorfon exposure. The optimum dietary EAM supplementation were 5.23, 4.79 and 5.12 g kg/diet for Jian carp under high stocking densities, Cu and trichlorfon exposure, respectively. Our study indicates that dietary EAM supplementation offers a feasible way for relieving the stress which induced by inappropriate high stocking densities, Cu, as well as trichlorfon.

Screening of potential α-glucosidase inhibitors from astragalus membranaceus by affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS method

Astragalus membranaceus is a traditional Chinese medicine with multiple pharmacological activities. Modern pharmacological research has found that Astragalus membranaceus extract has an inhibitory effect on α-glucosidase, however, which component can inhibit the activity of α-glucosidase and its degree of inhibition are unknown. To address this issue, this study used affinity ultrafiltration screening combined with UPLC-ESI-Orbitrap-MS technology to screen α-glucosidase inhibitors in Astragalus membranaceus. Using affinity ultrafiltration technology, we obtained the active components, and using UPLC-ESI-Orbitrap-MS technology, we quickly analyzed and identified them. As a result, a total of 8 ingredients were selected as α-glucosidase inhibitors.

Accelerated Method for Determining Ischemic Brain Damage in Rats and Assessment the Neuroprotective Effect of a Complex Herbal Remedy.

The severity of ischemic injury was evaluated by densitometry of brain samples stained with 2,3,5-triphenyltetrazolium chloride (TTC) on a rat model of cerebral ischemia/reperfusion (common carotid artery occlusion) and the neuroprotective activity of an extract of Astragalus membranaceus, Scutellaria baicalensis, and Phlojodicarpus sibiricus was assessed. Occlusion of the common carotid arteries led to a weakening of TTC staining of the brain tissue: densitometric indicators of the staining intensity for the cortex and striatum were lower than the corresponding indicators of sham-operated rats by 18.3 and 10.4%. The mean intensity of staining of brain samples did not differ in rats treated with the extract and sham-operated animals, which attested to its neuroprotective effect. The applied method is convenient for evaluation of the severity of ischemic brain damage at the early stages and screening potential neuroprotective agents.

Dietary Supplementation of Astragalus membranaceus Extract Affects Growth Performance, Antioxidant Capacity, Immune Response, and Energy Metabolism of Largemouth Bass (Micropterus salmoides).

The present study investigated the effects of Astragalus membranaceus extract (AME) on growth performance, immune response, and energy metabolism of juvenile largemouth bass (Micropterus salmoides). Seven diets containing 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, and 0.6% AME (Con, AME0.1, AME0.2, AME0.3, AME0.4, AME0.5, and AME0.6 groups) were formulated and fed to M. salmoides for 8 weeks. Final body weight (FBW), feed intake (FI), weight gain (WG), and specific growth rate (SGR) were all significantly higher in AME0.4 group than in Con group (P < 0.05). Feed conversion rate (FCR) was significantly improved in AME0.5 group compared with Con group (P < 0.05). Whole-body crude protein contents were significantly increased in AME0.2 group (P < 0.05). Whole-body crude lipid contents were significantly lower in AME0.2 and AME0.3 groups, while muscle lipid was upregulated by dietary AME (P < 0.05). Hepatic malondialdehyde (MDA) contents were significantly lowered in AME0.3 and AME0.4 groups, and catalase (CAT) activities were significantly increased in AME0.1 and AME0.2 groups (P < 0.05). Plasma aspartate aminotransferase (AST) level was significantly lowered in AME0.5, and AME0.6 groups, and alanine aminotransferase (ALT) level was lowered in AME0.5 groups (P < 0.05). Plasma triglyceride was declined in AME0.6 group, and glucose was decreased by 0.3%-0.5% AME (P < 0.05). Significantly higher hepatocyte diameter, lamina propria width, and submucosal layer thickness were recorded in AME0.6 groups, while the longest villi height was obtained in AME0.2 and AME0.3 groups (P < 0.05). The mRNA expression levels of insulin-like growth factor 1 (igf1) revealed the growth-promoting effect of AME. The anti-inflammatory and antiapoptotic effects of AME were demonstrated by transcription levels of interleukin 8 (il-8), tumor necrosis factor-alpha (tnf-a), caspase, B-cell lymphoma-xl (Bcl-xl), bcl-2 associated x (Bax), and bcl-2-associated death protein (Bad). The transcription levels of lipid metabolism and gluconeogenesis related genes, including acetyl-CoA carboxylase alpha (acc1), fatty acid synthase (fasn), fatty acid binding protein 1 (fabp1), phosphoenolpyruvate carboxykinase 2 (pepck2), and glucose-6-phosphatase catalytic subunit 1a (g6pc), were reduced by AME treatment, while the levels of glycolysis-related genes, including glucokinase (gck) and pyruvate kinase (pk), were the highest in AME0.2 and AME0.3 groups (P < 0.05). According to polynomial regression analysis of SGR, WG, FCR, whole-body crude lipid, MDA, and ALT, the optimal AME supplementation level was estimated to be 0.320%-0.429% of the diet. These results provided insights into the roles of AME in regulating immunity and metabolism, which highly indicated its potential as immunostimulants and metabolic regulators in diverse aquatic animals.

Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers.

Although Astragalus membranaceus is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of Astragalus membranaceus extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of Astragalus membranaceus (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased cytotoxicity and the sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase 3), and attenuated the expression of B-cell lymphoma 2 (Bcl-2) in LNCaP cells after 24 h of exposure. Consistently, WAM significantly increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive LNCaP cells. WAM decreased the phosphorylation of HSP27 on Ser82 and inhibited the expression of the AR and prostate-specific antigen (PSA), along with reducing the nuclear translocation of p-HSP27 and the AR via the disturbed binding of p-HSP27 with the AR in LNCaP cells. WAM consistently inhibited the expression of the AR and PSA in dihydrotestosterone (DHT)-treated LNCaP cells. WAM also suppressed AR stability, both in the presence and absence of cycloheximide, in LNCaP cells. Taken together, these findings provide evidence that WAM induces apoptosis via the inhibition of HSP27/AR signaling in prostate cancer cells and is a potent anticancer candidate for prostate cancer treatment.

Effects of dietary Astragalus membranaceus and Codonopsis pilosula extracts on growth performance, antioxidant capacity, immune status, and intestinal health in broilers.

The objective of this study was to examine the effects of dietary Chinese herbal medicine (CHM) consisting of Astragalus membranaceus (Fisch.) Bunge (AMT) and Codonopsis pilosula (Franch.) Nannf (CPO) extracts on growth performance, antioxidant capacity, immune status, and intestinal health of broiler chickens. Two groups were formed, each consisting of six replicates of 12 one-day-old healthy male 817 white feather broilers. Broilers were fed either a basal diet (CON group) or a basal diet supplemented with 500 mg/kg CHM. The trial lasted 50 days. The results showed that CHM supplementation resulted in enhanced feed efficiency and antioxidant capacity in both the serum and liver, while it reduced uric acid and endotoxin levels, as well as diamine oxidase activity (p < 0.05). Additionally, CHM treatment increased the height of jejunum villi and upregulated Claudin-1 expression in the jejunal mucosa accompanied by an increase in the mRNA levels of interleukin-6 (IL-6), interferon-γ (IFN-γ), interferon-β (IFN-β), tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokine interleukin-10 (IL-10) (p < 0.05). The presence of dietary CHM caused an increase in the proportions of Bacteroidetes and unclassified Bacteroidales but led to a decrease in those of Firmicutes and Alistipes (p < 0.05). The composition of the jejunal mucosa microbiota was correlated with the feed conversion ratio, serum metabolites, and gene expression based on Spearman correlation analysis. The findings indicated that the consumption of dietary CHM improved the utilization of feed, increased the mRNA expression of pro-inflammatory cytokines in the jejunal mucosa, and decreased the endotoxin level and activities of diamine oxidase and lactate dehydrogenase in the serum, which could potentially be linked to changes in the gut microbiota of broiler chickens.

The Extract of Astragalus membranaceus Inhibits Lipid Oxidation in Fish Feed and Enhances Growth Performance and Antioxidant Capacity in Jian Carp (Cyprinus carpio var. Jian)

In this study, a linoleic and linolenic acid were incubated with petroleum ether extract, ethyl acetate extract, acetone extract (AE) and aqueous extract of Astragalus membranaceus. The phenolic content and total antioxidant capacity (T-AOC) were determined in the extracts of Astragalus membranaceus (EAms) above. Results showed that EAms decreased the levels of malonaldehyde, conjugated diene, and peroxide value levels in material above. Of all of EAms, AE showed the strongest T-AOC and inhibitory effect on the lipid oxidation. Next, fish feeds were incubated with graded levels of AE. The results showed that AE inhibited lipid oxidation in fish feed. The appropriate dosage for reducing lipid oxidation was 6.74 g AE kg−1 feeds. The effect of EAms on the lipid oxidation may be closely associated with their phenolic content. Then, juvenile Jian carp (Cyprinus carpio var. Jian, 10.2 ± 0.3 g) were fed with diets containing graded levels of AE (0.0, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, and 7.0 g kg−1) for 60 days. Current data displayed that dietary AE increased the growth performance of fish. The optimum dosage for growth promotion was 5.15 g AE kg−1 diet. This result of AE may be ascribed to its enhancing effect on the activity of digestive and absorptive enzymes and antioxidant capacity in digestive organs of fish. Our present study indicated that EAm holds promise as a natural antioxidant for fish and their feed.

The Effects of Natural Product-Derived Extracts for Longitudinal Bone Growth: An Overview of In Vivo Experiments

Approximately 80% of children with short stature are classified as having Idiopathic Short Stature (ISS). While growth hormone (GH) treatment received FDA approval in the United States in 2003, its long-term impact on final height remains debated. Other treatments, like aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), have been explored, but there is no established standard treatment for ISS. In South Korea and other Asian countries, East Asian Traditional Medicine (EATM) is sometimes employed by parents to potentially enhance their children’s height growth, often involving herbal medicines. One such product, Astragalus membranaceus extract mixture HT042, claims to promote height growth in children and has gained approval from the Korean Food and Drug Administration (KFDA). Research suggests that HT042 supplementation can increase height growth in children without skeletal maturation, possibly by elevating serum IGF-1 and IGF-binding protein-3 levels. Preclinical studies also indicate the potential benefits of natural products, including of EATM therapies for ISS. The purpose of this review is to offer an overview of bone growth factors related to ISS and to investigate the potential of natural products, including herbal preparations, as alternative treatments for managing ISS symptoms, based on their known efficacy in in vivo studies.

Can We Slow Down Biological Age Progression? Study Protocol for the proBNPage Reduction (PBAR) Randomized, Double-Blind, Placebo-Controlled Trial (Effects of 4 "Anti-Aging" Food Supplements in Healthy Older Adults).

The availability of a simple and reliable marker of biological age might allow an acceleration of the research in the field of longevity extension. Previous studies suggest that this marker might be the N-terminal of B-type natriuretic peptide precursor (NT-proBNP), from which proBNPage, a biological age surrogate, can be calculated. Objectives of the study: 1) To fine-tune the method of proBNPage progression assessment and 2) To establish whether 4 "anti-aging" treatments, which provided promising results in previous studies, can modify proBNPage progression. This is a double-blind randomized placebo-controlled clinical trial on 120 adults aged 65-80 years, free of cardiovascular diseases. Participants will be randomized into 3 groups: A) Coenzyme Q10 100 mg bid + Selenium 100 mcg; B) Resveratrol 350 mg bid + TA-65 (Astragalus Membranaceus extract) 100U; C) Placebo-1 bid + Placebo-2. They will be followed for 2 years and checked 8 times, to assess both proBNPage progression and treatment safety. Secondary variables (handgrip strength, aerobic capacity at the step test and quality of life) will also be assessed. Primary outcome will be the demonstration of significant changes of proBNPage, compared to baseline, in the 3 groups at 6, 12, 18 and 24 months. Secondary outcome will be the demonstration of similar changes of secondary variables. Statistical analyses will be mainly performed by repeated measures ANOVA (both according to intention to treat and per protocol) and paired t tests. The study was approved by the Ethics Committee Area Vasta Emilia Centro, Emilia-Romagna Region, ID: 64/2022/Sper/AOUBo. Trial registration: ClinicalTrials.gov, NCT05500742. The use of proBNPage as a surrogate of biological age may prove an easy method to select anti-aging treatments worthy of further, more complex assessments.

Nrf2 knockout attenuates the astragaloside IV therapeutic effect on kidney fibrosis from liver cancer by regulating pSmad3C/3L pathways.

Fibrotic kidney injury from hepatocarcinogenesis seriously impacts treatment effect. Astragaloside IV (AS-IV), an extract of Astragalus membranaceus, has several pharmacological activities, which are useful in the treatment of edema and fibrosis. Nrf2/HO-1 is a key antioxidant stress pathway and help treatment of kidney injury. Smad3 phosphorylation is implicated in hepatocarcinogenesis. Our previous study clarified that Smad3 is differentially regulated by different phosphorylated forms of Smad3 on hepatocarcinogenesis. Therefore, we investigated the contribution of AS-IV on the therapy of kidney fibrosis from hepatocarcinogenesis. And the focus was on whether the phosphorylation of Smad3 and the regulation of Nrf2/HO-1 pathway were involved during AS-IV therapy and whether there is an effect of Nrf2 knockout on the phosphorylation of Smad3. We performed TGF-β1 stimulation on HK-2 cells and intervened with AS-IV. Furtherly, we investigated renal injury of AS-IV on Nrf2 knockout mice during hepatocarcinogenesis and its mechanism of action. On the one hand, in vitro results showed that AS-IV reduced the ROS and α-SMA expression of HK-2 by promoting the expression pSmad3C/p21 of and Nrf2/HO-1 and suppressed the expression of pSmad3L/PAI-1. On the other hand, the in vivo results of histopathological features, serological biomarkers, and oxidative damage indicators showed that Nrf2 knockout aggravated renal injury. Besides, Nrf2 deletion decreased the nephroprotective effect of AS-IV by suppressing the pSmad3C/p21 pathway and promoting the pSmad3L/PAI-1 pathway. The experimental results were as we suspected. And we identify for the first time that Nrf2 deficiency increases renal fibrosis from hepatocarcinogenesis and attenuates the therapeutic effects of AS-IV via regulating pSmad3C/3L signal pathway.

Effects of Astragalus membranaceus extract and Eucommia ulmoides leaf extract on growth performance, blood biochemistry, and antioxidant capacity of gibel carp juveniles (Carassius auratus gibelio var. CAS V)

The study aims to investigate the effects of dietary Astragalus membranaceus extract (AME) and Eucommia ulmoides leaf extract (ELE) supplementation on the growth performance, blood biochemistry, and antioxidant capacity of gibel carp (Carassius auratus gibelio var. CAS V, 10.01 g ± 0.24 g). Six experimental diets supplemented were marked as A0E0 (basic diet, 0% AME and 0% ELE), A0E0.1 (0% AME and 0.1% ELE), A0.02E0, A0.02E0.05, A0.02E0.1, A0.02E0.2 (0.02% AME with 0%, 0.05%, 0.1%, and 0.2% ELE). After 8 weeks, A0.02E0 diet significantly increased the final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), and decreased the glucose (GLU), triglyceride content (TG), and total cholesterol (TC) of the plasma, the malonaldehyde (MDA) content of the liver, the A0E0.1 group significantly increased the total protein (TP) and albumin (ALB) content of the plasma, decreased the alanine aminotransferase (ALT) content of the plasma when compared with A0E0 group (Independent T-test: P < 0.05). A0.02E0.1 group significantly increased the FBW, WGR, SGR, and decreased the moisture of the whole body when compared with A0E0.1 group (Independent T-test: P < 0.05). One-way ANOVA analysis showed that 0.02% AME with different levels of ELE (0.05%, 0.1% and 0.2%) significantly increased FBW, SGR, WGR, the crude protein and crude lipid of whole body, the GLU, TP, ALB, TC, and TG content of the plasma, and the activities of the lysozyme, total superoxide dismutase, and catalase (CAT) of the liver when compared with A0.02E0 diet (Tukey’s test: P < 0.05). Two-way ANOVA analysis showed that the AME and ELE showed significantly interaction effect on FBW, WGR, SGR, GLU content, TG content, TC content, ALT content, CAT activity. In conclusion, it could be recommended that AME and ELE interaction can be used for growth promotion and antioxidant capacity improvement in aquaculture animals.

The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling

Cerebral ischemia-reperfusion (I/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of Astragalus membranaceus extract and ligustrazine (Ast+Lig) treatment could protect brain tissues against inflammation in rats with thrombolytic cerebral ischemia. Activation of N-methyl-D-aspartate receptors (NMDAR) is implicated in brain damage induced by cerebral I/R injury. We used in vivo and in vitro models of cerebral I/R injury for middle cerebral artery occlusion/reperfusion in mice and oxygen-glucose deprivation/reoxygenation in primary rat cerebral cortical neurons to evaluate the protective effects of Ast+Lig on cerebral I/R injury, and whether the protective mechanism was related to the regulation of NMDAR-ERK/CREB signaling. Treatment with Ast+Lig, or MK-801 (an inhibitor of NMDAR) significantly ameliorated neurological deficits, decreased infarct volumes, suppressed neuronal damage and Ca2+ influx, and maintained the mitochondrial membrane potential in vivo and in vitro following cerebral I/R injury based on 2,3,5-triphenyl tetrazolium chloride staining, immunohistochemistry, and immunofluorescent staining. Furthermore, treatment with Ast+Lig evidently prevented the upregulation of NR2B, but not NR2A, in vivo and in vitro following cerebral I/R injury based on western blotting and reverse transcription-quantitative PCR analyses. Moreover, treatment with Ast+Lig significantly increased the phosphorylation of ERK and CREB, as well as increasing their mRNA expression levels in vivo and in vitro following cerebral I/R injury. The overall results thus suggest that the Ast+Lig combination conferred neuroprotective properties against cerebral I/R injury via regulation of the NR2B-ERK/CREB signaling pathway.

Protective effect of astragalus membranaceus and its bioactive compounds against the intestinal inflammation in Drosophila.

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicines. Astragalus membranaceus (AM), also named Huangqi, is one of the most commonly used fundamental herbs in China. Here, we aimed to investigate mechanism and bioactive compounds of AM on treating sodium dodecyl sulfate (SDS)- induced colitis in Drosophila flies. Our data showed that AM extract (AME) supplementation had no toxic effect in flies, and protected flies against SDS-induced lifespan shortening, intestinal morphological damage, and colon length shortening. Moreover, AME supplementation remarkably rescued SDS-induced intestinal stem cell (ISC) overproliferation and increased reactive oxygen species (ROS) level in the intestine. Mechanistically, AME remarkably rescued the altered expression levels of genes and proteins in c-Jun N-terminal kinase (JNK) and JAK-STAT signaling pathways induced by SDS in gut. Additionally, formononetin, isoliquiritigenin, isorhamnetin, astragaloside I, astragaloside III, vanillic acid, and caffeic acid in AM had protection against SDS-induced inflammatory damage in flies. Taken together, AME could ameliorate the intestinal inflammation partially by suppressing oxidative stress-associated JNK signaling and JAK-STAT signaling pathways. AME may provide a theoretical basis for natural medicine toward treating intestinal inflammatory disease in human.

Strong Synergic Growth Inhibition and Death Induction of Cancer Cells by Astragalus membranaceus and Vaccaria hispanica Extract.

We present here a new, classification-based screening method for anti-cancer botanical combinations. Using this method, we discovered that the combination of Astragalus membranaceus and Vaccaria hispanica (AV) has strong synergic anti-proliferative and killing effects on cancer cells. We showed that AV induces the hyper activation of proliferation and survival pathways (Akt and ERK1/2) and strongly downregulates the cell cycle control proteins p21 and p27. Moreover, FACS analyses revealed that AV induces accumulation of cells in G2/M phase, supported by accumulation of cyclin A. Taken together, our results suggest that AV interferes with the cell cycle in cancer cells, leading to accumulation in G2/M and apoptosis. Further studies are needed to validate the generalizability of the anti-cancer effect of the AV combination, to fully understand its mechanism of action and to evaluate its potential as a new anti-cancer treatment.