Therapeutic potential of Angelica sinensis in addressing organ fibrosis: A comprehensive review.

Fibrosis-related diseases (FRD) include conditions like myocardial fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and others. The impact of fibrosis can be severe, causing organ dysfunction, reduced functionality, and even organ failure, leading to significant health issues. Currently, there is a lack of effective modern anti-fibrosis drugs in clinical practice. However, Chinese medicine has a certain beneficial effect on the treatment of such diseases. Angelica sinensis, with its considerable medicinal value, has garnered attention for its anti-fibrosis properties in recent investigations. In the past few years, there has been a growing number of experimental inquiries into the impact of angelica polysaccharide (ASP), angelica water extract, angelica injection, and angelica compound preparation on fibrosis-associated ailments, piquing the interest of researchers. This paper aims to consolidate recent advances in the study of Angelica sinensis for the treatment of fibrosis-related disorders, offering insights for prospective investigations. Literature retrieval included core electronic databases, including Baidu Literature, CNKI, Google-Scholar, PubMed, and Web of Science. The applied search utilized specified keywords to extract relevant information on the pharmacological and phytochemical attributes of plants. The investigation revealed that Angelica sinensis has the potential to impede the advancement of fibrotic diseases by modulating inflammation, oxidative stress, immune responses, and metabolism. ASP, Angelica sinensis extract, Angelica sinensis injection, and Angelica sinensis compound preparation were extensively examined and discussed. These constituents demonstrated significant anti-fibrosis activity. In essence, this review seeks to gain a profound understanding of the role of Angelica sinensis in treating fiber-related diseases. Organ fibrosis manifests in nearly all tissues and organs, posing a critical challenge to global public health due to its widespread occurrence, challenging early diagnosis, and unfavorable prognosis. Despite its prevalence, therapeutic options are limited, and their efficacy is constrained. Over the past few years, numerous studies have explored the protective effects of traditional Chinese medicine on organ fibrosis, with Angelica sinensis standing out as a multifunctional natural remedy. This paper provides a review of organ fibrosis pathogenesis and summarizes the recent two decades' progress in treating fibrosis in various organs such as the liver, lung, kidney, and heart. The review highlights the modulation of relevant signaling pathways through multiple targets and channels by the effective components of Angelica sinensis, whether used as a single medicine or in compound prescriptions.

Aerial parts of Angelica sinensis supplementation for improved broiler growth and intestinal health.

This research examined the impact of incorporating Angelica sinensis's aerial components (APA), commonly referred to as "female ginseng", into broilers' diet. Two hundred eighty-eight 1-day-old Cobb 500 broilers were randomly assigned to the 4 experimental groups with 6 replications and 12 birds/replicate. The 4 groups were fed the diets included 4 concentrations of APA (0, 1, 2, and 3%, respectively). The study spanned 42 d, categorized as the starter phase (1-21 d) and the finisher phase (22-42 d). Notably, broilers fed with 3% APA demonstrated a pronounced surge in feed consumption and weight gain during the 22 to 42 d and over the full 42-d period (P < 0.05). Furthermore, when examining the broilers' intestinal structure, there was a notable increase in the villus height and villi ratio across the duodenum, jejunum, and ileum, with a decrease in crypt depth upon 3% APA inclusion (P < 0.05). On a molecular note, certain genes connected to the intestinal mechanical barrier, such as Zona Occludens 1 and Claudin-2, saw significant elevation in the jejunum (P < 0.05). The jejunum also displayed heightened levels of antimicrobial peptides like lysozyme, mucin 2, sIgA, IgG, and IgM, showcasing an enhanced chemical and immune barrier (P < 0.05). Delving into the 16SrDNA sequencing of intestinal content, a higher microbial diversity was evident with a surge in beneficial bacteria, particularly Firmicutes, advocating a resilient and balanced microecosystem. The findings imply that a 3% APA dietary addition bolsters growth metrics and fortifies the intestinal barrier's structural and functional integrity in broilers.

Angelica Sinensis Polysaccharide-Based Nanoparticles for Liver-Targeted Delivery of Oridonin.

The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver targeting drug delivery carrier for oridonin (ORI) in the treatment of hepatocellular carcinoma (HCC). ASP was reacted with deoxycholic acid (DOCA) via an esterification reaction to form an ASP-DOCA conjugate. ORI-loaded ASP-DOCA nanoparticles (ORI/ASP-DOCA NPs) were prepared by the thin-film water method, and their size was about 195 nm in aqueous solution. ORI/ASP-DOCA NPs had a drug loading capacity of up to 9.2%. The release of ORI in ORI/ASP-DOCA NPs was pH-dependent, resulting in rapid decomposition and accelerated drug release at acidic pH. ORI/ASP-DOCA NPs significantly enhanced the accumulation of ORI in liver tumors through ASGPR-mediated endocytosis. In vitro results showed that ORI/ASP-DOCA NPs increased cell uptake and apoptosis in HepG2 cells, and in vivo results showed that ORI/ASP-DOCA NPs caused effective tumor suppression in H22 tumor-bearing mice compared with free ORI. In short, ORI/ASP-DOCA NPs might be a simple, feasible, safe and effective ORI nano-drug delivery system that could be used for the targeted delivery and treatment of liver tumors.

Angelica sinensis polysaccharides modified selenium nanoparticles for effective prevention of acute liver injury.

As a global public health issue, the treatment of acute liver injury (ALI) is severely limited due to the lack of specific drugs. In order to address the challenges, innovative strategies for selenium nanoparticles (Se NPs) with excellent antioxidant properties have been actively developed to effectively prevent ALI. However, the functional activity of Se NPs is severely affected by poor stability and bioavailability. The aim of this work is to develop a stabilization system (ASP-Se NPs) for Angelica sinensis polysaccharides modified Se NPs. The results showed that ASP-Se NPs with smaller size (62.38 ± 2.96 nm) showed good stability, specific accumulation in liver and enhanced cell uptake, thus exerting strong antioxidant and anti-inflammatory functions. The results of in vivo experiments further confirmed that ASP-Se NPs effectively prevented CCl4-induced ALI by improving liver function, inhibiting oxidative stress and inflammatory response, and liver pathological damage. This work provides a new alternative method for effectively preventing ALI and improving liver function.

Fingerprint analysis of dang-gui-Si-Ni decoction and its anticoagulant activity in vivo-in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases (Shang Han Lun) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood. AIM OF THE STUDY: The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas. MATERIALS AND METHODS: The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by "Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro. Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo. Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model. RESULTS: The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1-S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro. Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 µg mL-1) in vivo. q-PCR data demonstrated that DGSN decoction (500 µg mL-1) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo. CONCLUSION: The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs.

Degradation of Angelica sinensis polysaccharide: Structures and protective activities against ethanol-induced acute liver injury.

Angelica sinensis polysaccharide (ASP) possesses diverse bioactivities; however, its metabolic fate following oral administration remains poorly understood. To intuitively determine its intestinal digestion behavior after oral administration, ASP was labeled with fluorescein, and it was found to accumulate and be degraded in the cecum and colon. Therefore, we investigated the in vitro enzymatic degradation behavior and identified the products. The results showed that ASP could be degraded into fragments with molecular weights similar to those of the fragments observed in vivo. Structural characterization revealed that ASP is a highly branched acid heteropolysaccharide with AG type II domains, and its backbone is predominantly composed of 1,3-Galp, →3,6)-Galp-(1→6)-Galp-(1→, 1,4-Manp, 1,4-Rhap, 1,3-Glcp, 1,2,3,4-Galp, 1,3,4,6-Galp, 1,3,4-GalAp and 1,4-GlcAp, with branches of Araf, Glcp and Galp. In addition, the high molecular weight enzymatic degradation products (ASP H) maintained a backbone structure almost identical to that of ASP, but exhibited only partial branch changes. Then, the results of ethanol-induced acute liver injury experiments revealed that ASP and ASP H reduced the expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and malondialdehyde (MDA) and increased the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels, thereby relieving ethanol-induced acute liver injury.

ASAP: a platform for gene functional analysis in Angelica sinensis.

BACKGROUND: Angelica sinensis (Danggui), a renowned medicinal orchid, has gained significant recognition for its therapeutic effects in treating a wide range of ailments. Genome information serves as a valuable resource, enabling researchers to gain a deeper understanding of gene function. In recent times, the availability of chromosome-level genomes for A. sinensis has opened up vast opportunities for exploring gene functionality. Integrating multiomics data can allow researchers to unravel the intricate mechanisms underlying gene function in A. sinensis and further enhance our knowledge of its medicinal properties. RESULTS: In this study, we utilized genomic and transcriptomic data to construct a coexpression network for A. sinensis. To annotate genes, we aligned them with sequences from various databases, such as the NR, TAIR, trEMBL, UniProt, and SwissProt databases. For GO and KEGG annotations, we employed InterProScan and GhostKOALA software. Additionally, gene families were predicted using iTAK, HMMER, OrholoFinder, and KEGG annotation. To facilitate gene functional analysis in A. sinensis, we developed a comprehensive platform that integrates genomic and transcriptomic data with processed functional annotations. The platform includes several tools, such as BLAST, GSEA, Heatmap, JBrowse, and Sequence Extraction. This integrated resource and approach will enable researchers to explore the functional aspects of genes in A. sinensis more effectively. CONCLUSION: We developed a platform, named ASAP, to facilitate gene functional analysis in A. sinensis. ASAP ( www.gzybioinformatics.cn/ASAP ) offers a comprehensive collection of genome data, transcriptome resources, and analysis tools. This platform serves as a valuable resource for researchers conducting gene functional research in their projects, providing them with the necessary data and tools to enhance their studies.

Protective effect of Angelica sinensis polysaccharide on pregnant rats suffering from iron deficiency anemia via regulation of the hepcidin-FPN1 axis.

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with deleterious maternal and fetal outcomes. Angelica sinensis polysaccharide (ASP) has been shown to reduce hepcidin expression in IDA rats. However, the role of ASP in the treatment of IDA during pregnancy and its potential mechanisms have not been investigated. Moreover, the effect of ASP on duodenal iron absorption is not clear. The aim of this study was to investigate the preventive efficacy of ASP against IDA during pregnancy and clarify the underlying mechanisms. Our results showed that ASP improved maternal hematological parameters, increased serum iron, maternal tissue iron, and fetal liver iron content, and improved pregnancy outcomes. Additionally, ASP combated oxidative stress caused by iron deficiency by improving the body's antioxidant capacity. Western blot results demonstrated that ASP downregulated hepcidin expression by blocking the BMP6/SMAD4, JAK2/STAT3 and TfR2/HFE signaling pathways, which in turn increased the expression of FPN1 in the liver, spleen, and duodenum and promoted iron cycling in the body. Furthermore, ASP increased the expression of DMT1 and Dcytb in the duodenum, thereby facilitating duodenal iron uptake. Our results suggest that ASP is a potential agent for the prevention and treatment of IDA during pregnancy.

Volatile oil of Angelica sinensis Radix improves cognitive function by inhibiting miR-301a-3p targeting Ppp2ca in cerebral ischemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica Sinensis Radix (ASR) is a commonly used Chinese medicine known for its effects on tonifying blood, promoting blood circulation, and alleviating pain associated with menstrual regulation. Additionally, it has been used in the treatment of vascular cognitive impairment (VCI). The primary pharmacodynamic agent within ASR is volatile oil of Angelica Sinensis Radix (VOASR), which has demonstrated efficacy in combating cognitive impairment, although its mechanism remains unclear. OBJECTIVE: This study aimed to elucidate the potential molecular mechanisms underlying VOASR's improvement of cognitive function in cerebral ischemic mice. METHODS: A model of cerebral ischemic mice was established through unilateral common carotid artery occlusion (UCCAO) surgery, followed by intervention with VOASR. Cognitive function was assessed using the Morris water maze (MWM) test, while RT-qPCR was utilized to measure the differential expression of miR-301a-3p in the hippocampus. To evaluate cognitive function and hippocampal protein differences, wild-type mice and miR-301a-3p knockout mice were subjected to the MWM test and iTRAQ protein profiling. The relationship between miR-301a-3p and potential target genes was validated through a Dual-Luciferase Reporter experiment. RT-qPCR and Western blot were employed to determine the differential expression of Ppp2ca and synaptic plasticity-related proteins in the mouse hippocampus. RESULTS: Intervention with VOASR significantly improved cognitive impairment in cerebral ischemic mice and reduced the expression of miR-301a-3p in the hippocampus. Our findings suggest that miR-301a-3p may regulate cognitive function by targeting Ppp2ca. Furthermore, VOASR intervention led to an increase in the expression of Ppp2ca and synaptic plasticity-related proteins. CONCLUSION: Our study indicates that VOASR may be involved in regulating cognitive function by inhibiting miR-301a-3p, consequently increasing the expression of Ppp2ca and synaptic plasticity proteins. These results provide a new target and direction for the treatment of cognitive dysfunction.

Sophora flavescens-Angelica sinensis in the treatment of eczema by inhibiting TLR4/MyD88/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Ait.-Angelica sinensis(Oliv.) Diels drug pairing (SA) is a transformed drug pairing from Shengui pill, a traditional Chinese medicine prescription in the ninth volume of Traditional Chinese Medicine classic "Gu Jin Yi Jian", which is famous for clearing heat, moistening dryness, and promoting blood circulation. It is commonly used in the treatment of eczema, a skin condition that causes itching and inflammation. Despite its widespread use, there is still limited research on the mechanism of how SA treats eczema. This paper aims to fill this gap by conducting animal experiments to uncover the mechanism behind SA's therapeutic effects on eczema. Our findings provide a solid foundation for the clinical use of this TCM prescription. AIM OF THE STUDY: The basic purpose of this study is to clarify the therapeutic mechanism of Sophora flavescens-Angelica sinensis (SA) in the treatment and control of eczema. MATERIALS AND METHODS: The chemical compositions of SA were analyzed using HPLC-Q-Orbitrap-MS. In vivo, a mouse model of eczema was created, and the serum levels of TNF-α and IL-1ß were quantified using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was performed to assess the pathological state of the mouse skin, and immunohistochemical technique (IHC) was employed to estimate the contents of TNF-α, TLR4, and NF-κB semi-quantitatively. The expression levels of TLR4, MyD88, and NF-κB mRNA were determined through real-time quantitative polymerase chain reaction (qRT-PCR). Western Blotting was utilized to identify the protein levels of TLR4, MyD88, and NF-κB in mouse skin tissue. RESULTS: SA identified 18 active chemicals, some of which were shown in vivo to inhibit the TLR4/MyD88/NF-κB signaling pathway while reducing serum levels of TNF-α and IL-1ß, making them ideal agents for the treatment of eczema. CONCLUSIONS: SA's anti-inflammatory properties are attributed to its ability to reduce serum levels of TNF-α and IL-1ß, likewise inhibit the TLR4/MyD88/NF-κB signaling pathway.

[Research progress in pharmacological effects and chemical components of processed Angelicae Sinensis Radix products].

Angelicae Sinensis Radix is one of the main Chinese medicinal materials with both medicinal and edible values. It has the functions of tonifying and activating blood, regulating menstruation and relieving pain, and moistening intestines to relieve constipation. It is mainly produced in the southeastern Gansu province, and that produced in Minxian, Gansu is praised for the best quality. The chemical components of Angelicae Sinensis Radix mainly include volatile oils, organic acids, and polysaccharides, which have anti-inflammatory, pain-relieving, anti-tumor, anti-oxidation, immunomodulatory and other pharmacological effects. Therefore, this medicinal material is widely used in clinical practice. By reviewing the relevant literature, this study systematically introduced the research status about the chemical constituents and pharmacological effects of processed Angelicae Sinensis Radix products, aiming to provide a theoretical reference and support for the future research, development, and clinical application of related drugs.

The Dynamic Accumulation Rules of Chemical Components during the Medicine Formation Period of Angelica sinensis and Chemometric Classifying Analysis for Different Bolting Times Using ATR-FTIR.

The dried roots of the perennial herb Angelica sinensis (Oliv.) Diels (AS) are commonly used as medicinal and edible resources. In commercial planting, early bolting and flowering (EB) of ca. 60% in the medicine formation period reduces root yield and quality, becoming a significant bottleneck in agricultural production. In the cultivation process, summer bolting (SB) occurs from June to July, and autumn bolting (AB) occurs in September. The AB root is often mistaken for the AS root due to its similar morphological characteristics. Few studies have involved whether the root of AB could be used as herbal medicine. This study explored and compared the accumulation dynamics of primary and secondary metabolites in AS and EB roots during the vegetative growth stage (from May to September) by light microscopy, ultraviolet spectrometry, and HPLC methods. Under a microscope, the amount of free starch granules and oil chamber in the AS root increased. On the contrary, they decreased further from EB-Jul to EB-Sep. By comparison, the wall of the xylem vessel was slightly thickened and stacked, and the cell walls of parenchyma and root cortex tissue were thickened in the EB root. Early underground bolting reduces soluble sugar, soluble protein, free amino acids, total C element, total N element, ferulic acid, and ligustilide accumulation, accompanied by the lignification of the root during the vegetative growth stage. Furthermore, a total of 55 root samples from different bolting types of AS root (29 samples), SB root (14 samples), and AB root (12 samples) were collected from Gansu Province during the harvesting period (October). The later the bolting occurred, the less difference there was between unbolted and bolted roots in terms of morphological appearance and efficacy components. Fourier transform infrared spectroscopy with the attenuated total reflection mode (ATR-FTIR) provides a "holistic" spectroscopic fingerprinting of all compositions in the tested sample. The ATR-FTIR spectrum of the AB root was similar to that of the AS root. However, the number and location of absorption peaks in the spectra of SB were different, and only one strong absorption peak at 1021 cm-1 was regarded as the characteristic peak of C-O stretching vibration in lignin. The ATR-FTIR spectra can be effectively differentiated based on their various characteristics using orthogonal partial least squares discrimination analysis (OPLS-DA). Results were assessed using multiple statistical techniques, including Spearman's correlation, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and OPLS-DA. Among these methods, the ATR-FTIR data demonstrated the most effective outcomes in differentiating between viable and non-viable roots for their application in herbal medicine. Essential substances are ferulic acid and flavonoid, which are much more abundant in the AB root. It provides a material basis for the pharmacological action of the AB roots and a theoretical basis for improving their availability.

Integrating genomic and multiomic data for Angelica sinensis provides insights into the evolution and biosynthesis of pharmaceutically bioactive compounds.

Angelica sinensis roots (Angelica roots) are rich in many bioactive compounds, including phthalides, coumarins, lignans, and terpenoids. However, the molecular bases for their biosynthesis are still poorly understood. Here, an improved chromosome-scale genome for A. sinensis var. Qinggui1 is reported, with a size of 2.16 Gb, contig N50 of 4.96 Mb and scaffold N50 of 198.27 Mb, covering 99.8% of the estimated genome. Additionally, by integrating genome sequencing, metabolomic profiling, and transcriptome analysis of normally growing and early-flowering Angelica roots that exhibit dramatically different metabolite profiles, the pathways and critical metabolic genes for the biosynthesis of these major bioactive components in Angelica roots have been deciphered. Multiomic analyses have also revealed the evolution and regulation of key metabolic genes for the biosynthesis of pharmaceutically bioactive components; in particular, TPSs for terpenoid volatiles, ACCs for malonyl CoA, PKSs for phthalide, and PTs for coumarin biosynthesis were expanded in the A. sinensis genome. These findings provide new insights into the biosynthesis of pharmaceutically important compounds in Angelica roots for exploration of synthetic biology and genetic improvement of herbal quality.

Network pharmacology and molecular docking study on the treatment of polycystic ovary syndrome with angelica sinensis- radix rehmanniae drug pair.

This study aimed to investigate the angelica sinensis - radix rehmanniae (AR) role in polycystic ovary syndrome (PCOS), employing network pharmacology and molecular docking techniques for active ingredient, targets, and pathway prediction. AR active components were obtained through TCMSP platform and literature search. The related targets of AR and PCOS were obtained through the disease and Swiss Target Prediction databases. An "active ingredient-target" network map was constructed using Cytoscape software, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was conducted through Hiplot. Finally, Auto Dock Tools software was used to conduct molecular docking between active ingredients and core targets. The main bioactive ingredients of AR in the treatment of PCOS are acteoside, baicalin, caffeic acid, cistanoside F, geniposide, etc. These ingredients involve 10 core targets, such as SRC, HSP90AA1, STAT3, MAPK1, and JUN. The effect of AR on anti-PCOS mainly involves the AGE-RAGE signaling pathway, Relaxin signaling pathway, TNF signaling pathway, and ErbB signaling pathway. Molecular docking results showed that the main active components and key targets of AR could be stably combined. AR can improve hyperandrogen status, regulate glucose homeostasis, and correct lipid metabolism and other physiological processes through multi-component, multi-target, and multi-pathway. Thus, it could play a significant role in PCOS treatment. The results of our study provide a scientific foundation for basic research and clinical applications of AR for the treatment of PCOS.

Synergistic inhibition of glioblastoma multiforme through an in-silico analysis of luteolin and ferulic acid derived from Angelica sinensis and Cannabis sativa: Advancements in computational therapeutics.

The primary objective of this study is to uncover novel therapeutic agents for the treatment of Glioblastoma Multiforme (GBM), a highly aggressive form of brain cancer, and Alzheimer's Disease (AD). Given the complexity and resistance associated with both conditions, the study underscores the imperative need for therapeutic alternatives that can traverse the biological intricacies inherent in both neuro-oncological and neurodegenerative disorders. To achieve this, a meticulous, target-based virtual screening was employed on an ensemble of 50 flavonoids and polyphenol derivatives primarily derived from plant sources. The screening focused predominantly on molecular targets pertinent to GBM but also evaluated the potential overlap with neural pathways involved in AD. The study utilized molecular docking and Molecular Dynamic (MD) simulation techniques to analyze the interaction of these compounds with a key biological target, protein tyrosine phosphatase receptor-type Z (PTPRZ). Out of the 50 compounds examined, 10 met our stringent criteria for binding affinity and specificity. Subsequently, the highest value of binding energy was observed for the synergistic binding of luteolin and ferulic acid with the value of -10.5 kcal/mol. Both compounds exhibited inherent neuroprotective properties and demonstrated significant potential as pathway inhibitors in GBM as well as molecular modulators in AD. Drawing upon advanced in-silico cytotoxicity predictions and sophisticated molecular modeling techniques, this study casts a spotlight on the therapeutic capabilities of polyphenols against GBM. Furthermore, our findings suggest that leveraging these compounds could catalyze a much-needed paradigm shift towards more integrative therapeutic approaches that span the breadth of both neuro-oncology and neurodegenerative diseases. The identification of cross-therapeutic potential in flavonoids and polyphenols could drastically broaden the scope of treatment modalities against both fatal diseases.

Chemical composition analysis of Angelica sinensis (Oliv.) Diels and its four processed products by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry combining with nontargeted metabolomics.

Angelica sinensis (Oliv.) Diels. has been used for women to enrich the blood, prevent and treat blood deficiency syndrome in Traditional Chinese Medicine for thousands of years. Wine-processed Angelica sinensis, soil-processed Angelica sinensis, oil-processed Angelica sinensis, and charred-processed Angelica sinensis are the most significant four processed products used in Chinese clinic. However, there have been few studies aimed at comparing their chemical differences. Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry combining with nontargeted metabolomics was applied to investigate the diversity of processed products of Angelica sinensis. A total of 74 compounds with the variable importance in the projection value more than 1.5 and P less than 0.05 in ANOVA were highlighted as the compounds that contribute most to the discrimination of Angelica sinensis and four processed products. The results showed the metabolic changes between Angelica sinensis and its four processed products, there were 19 metabolites, 3 metabolites, 6 metabolites, and 45 metabolites were tentatively assigned in soil-processed Angelica sinensis, wine-processed Angelica sinensis, oil-processed Angelica sinensis, and charred-processed Angelica sinensis, respectively. These results suggested that the proposed metabolomics approach was useful for the quality evaluation and control of processed products of Angelica sinensis.

Angelica sinensis polysaccharides ameliorated 5-Fluorouracil-induced damage of early B cell progenitors by alleviating oxidative stress of IL-7 producing mesenchymal stem and progenitor cells.

B-lymphocytopenia among myelosuppression is the most intractable side effect of chemotherapy. Here, we investigated ways to alleviate 5-fluorouracil-caused stress hematopoietic impairment. We found that intraperitoneally injected ASP (Angelica sinensis polysaccharides) (100 mg/kg per day), one main active ingredient of Angelica sinensis, for consecutive 7 days, significantly recovered mouse bone marrow pro-B and pre-B cells, reversed the capacity of CFU-PreB colony forming, thus alleviating B cell reduction in the spleen and peripheral blood, as well as ameliorating immunoglobin from spleen and serum. The mechanism is related to the protective effects of ASP on IL-7 producing cells, including perivascular Leptin+ and CXCL12+ mesenchymal stem and progenitor cells (MSPCs), thus promoting IL-7 production, and activating IL-7R-mediated STAT5, PI3K-AKT signaling, including survival signals and EBF1, PAX5 transcription factor expression. Additionally, ASP's IL-7 promoting effect was demonstrated to be associated with maintaining osteogenesis/adipogenesis balance of MSPCs via the NRF2 antioxidant pathway. Collectively, our findings indicate that ASP reverse stress B-lymphocytopenia via improving Nrf2 signaling, promoting IL-7 production in MSPCs, and subsequently maintaining survival, proliferation, and differentiation of B cell progenitors, which may represent a promising therapeutic strategy.

Preparation and evaluation of Angelica sinensis polysaccharide-modified chitosan sponge for acute liver injury protection.

In this study, a porous sponge material was formed by physically mixing chitosan (CS) and Angelica sinensis polysaccharide (ASP). After removing the water by freeze-drying, the CS/ASP sponge was obtained. The prepared sponges exhibited excellent swelling properties, thermal stability and biocompatibility as well as improvements over the insufficient mechanical properties of pure chitosan sponges. Notably, the ASP released from the CS/ASP sponge could be effectively absorbed by the liver, which endowed the CS/ASP sponge with effective liver-protective effects against CCl4-induced acute liver injury; these protective effects surpassed those of both blank CS and CS/Dextran sponges. The underlying protective mechanism may involve the activation of the Nrf2-mediated antioxidant signaling pathway and the inhibition of hepatocyte apoptosis. Understanding CS/ASP sponges may provide new insights and inspire new methods for the clinical application of ASP. At the same time, we hope to suggest future directions for the development of polysaccharide preparations.

Insights into the Mechanism of Supramolecular Self-Assembly in the Astragalus membranaceus-Angelica sinensis Codecoction.

Astragalus membranaceus (Fisch.) Bge. (AM) and Angelica sinensis (Oliv.) Diels (AS) constitute a classic herb pair in prescriptions to treat myocardial fibrosis. To date, research on the AM-AS herb pair has mainly focused on the chemical compositions associated with therapeutic efficacy. However, supermolecules actually exist in herb codecoctions, and their self-assembly mechanism remains unclear. In this study, supermolecules originating from AM-AS codoping reactions (AA-NPs) were first reported. The chemical compositions of AA-NPs showed a dynamic self-assembly process. AA-NPs with different decoction times had similar surface groups and amorphous states; however, the size distributions of these nanoparticles might be different. Taking the interaction between Z-ligustilide and astragaloside IV as an example to understand the self-assembly mechanism of AA-NPs, it was found that the complex could be formed with a molar ratio of 2:1. Later, AA-NPs were proven to be effective in the treatment of myocardial fibrosis both in vivo and in vitro, the in-depth mechanisms of which were related to the recovery of cardiac function, reduced collagen deposition, and inhibition of the endothelial-to-mesenchymal transition that occurred in the process of myocardial fibrosis. Thus, AA-NPs may be the chemical material basis of the molecular mechanism of the AM-AS decoction in treating isoproterenol-induced myocardial fibrosis. Taken together, this work provides a supramolecular strategy for revealing the interaction between effective chemical components in herb-pair decoctions.

Angelica sinensis polysaccharide improves mitochondrial metabolism of osteoarthritis chondrocytes through PPARγ/SOD2/ROS pathways.

Osteoarthritis (OA) is a common degenerative joint disease, which is characterized by wear of articular cartilage and narrow joint space, resulting in joint movement disorder. At present, accurate molecular mechanisms and effective interventions are still being explored. Here, we propose that angelica sinensis polysaccharide (ASP) alleviates OA progression by activating peroxisome proliferator-activated receptor gamma (PPARγ). Therapeutic effect of ASP improving mitochondrial metabolism of OA chondrocytes was evaluated in vitro and in vivo, respectively. During cell experiments, the concentration and time response of tert butyl hydroperoxide (TBHP) and ASP were determined by cell viability. Apoptosis was detected by flow cytometry. Mitochondrial metabolism was detected by reactive oxygen species (ROS), mitochondrial membrane potential (MMP), release of cytochrome C, adenosine triphosphate (ATP) production, and superoxide dismutase 2 (SOD2) activity. Expressions of Aggrecan, collagen type II (Col2a1), PPARγ, and SOD2 were detected by qRT-PCR and western blot. In animal experiments, we detected cell apoptosis and target protein expression separately through terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining and immunohistochemistry. Pretreatment of ASP significantly activated PPARγ and SOD2 in rat chondrocytes incubated with TBHP, cleared ROS, improved mitochondrial metabolism, increased chondrocytes viability, and alleviated chondrocytes apoptosis. In vivo, the administration of ASP could effectively ameliorate cartilage degeneration in OA rats, promote extracellular matrix synthesis, and decelerate the progress of OA. Our research identifies the role of ASP in mitochondrial metabolism of OA chondrocytes through PPARγ/SOD2/ROS pathways, which provides a new idea for the treatment of OA.