Formononetin attenuates psoriasiform inflammation by regulating interferon signaling pathway.

BACKGROUND: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis. OBJECTIVE: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis. MATERIALS AND METHODS: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC). RESULTS: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-ß, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group. CONCLUSIONS: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.

A fast and efficient method for screening and evaluation of hypoglycemic ingredients of Traditional Chinese Medicine acting on PTP1B by capillary electrophoresis.

As a pivotal enzyme that regulates dephosphorylation in cell activities and participates in the insulin signaling pathway, protein tyrosine phosphatase 1B (PTP1B) is considered to be an important target for the therapy of diabetes. In this work, a rapid and efficient inhibitor screening method of PTP1B was established based on capillary electrophoresis (CE), and used for screening and evaluating the inhibition effect of Traditional Chinese Medicine on PTP1B. Response Surface Methodology was used for optimizing the conditions of analysis. After method validation, the enzyme kinetic study and inhibition test were performed. As a result, the IC50 of PTP1B inhibitors Ⅳ and ⅩⅧ were consistent with reported values measured by a conventional method. It was found that the extracts of Astragalus membranaceus (Fisch) Bunge and Morus alba L. showed prominent inhibition on the activity of PTP1B, which were stronger than the positive controls. Meanwhile, on top of the excellent advantages of CE, the whole analysis time is less than 2 min. Thus, the results demonstrated that a fast and efficient screening method was successfully developed. This method could be a powerful tool for screening inhibitors from complex systems. It can also provide an effective basis for lead compound development in drug discovery.

Astragalus membranaceus Polysaccharide Regulates Small Intestinal Microbes and Activates IL-22 Signal Pathway to Promote Intestinal Stem Cell Regeneration in Aging Mice.

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.

Rapid analysis of Radix Astragali using a portable Raman spectrometer with 1064-nm laser excitation and data fusion with PLS-DA.

Radix Astragali is a medicinal herb with various physiological activities. There were high similarities among Radix Astragali samples from different regions owing to similarities in their major chemical compositions. Raman spectroscopy is a non-invasive and non-des- tructive technique that can be used in in-situ analysis of herbal samples. Dispersive Raman scattering, excited at 1064 nm, produced minimal fluorescence background and facilitated easy detection of the weak Raman signal. By moving the portable Raman probe point-by- point from the centre of the Radix Astragali sample to the margin, the spectral fingerprints, composed of dozens of Raman spectra representing the entire Radix Astragali samples, were obtained. Principal component analysis and partial least squares discriminant analysis (PLS-DA) were applied to the Radix Astragali spectral data to compare classification results, leading to efficient discrimination between genuine and counterfeit products. Furthermore, based on the PLS-DA model using data fusion combined with different pre- processing methods, the samples from Shanxi Province were separated from those belonging to other habitats. The as-proposed combination method can effectively improve the recognition rate and accuracy of identification of herbal samples, which can be a valuable tool for the identification of genuine medicinal herbs with uneven qualities and various origins.

Research progress of the effective active ingredients of Astragalus mongholicus in the treatment of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent consequences of diabetes, with a high incidence and disability rate. The DPN's pathogenesis is extremely complex and yet to be fully understood. Persistent high glucose metabolism, nerve growth factor deficiency, microvascular disease, oxidative stress, peripheral nerve cell apoptosis, immune factors, and other factors have been implicated in the pathogenesis of DPN. Astragalus mongholicus is a commonly used plant used to treat DPN in clinical settings. Its rich chemical components mainly include Astragalus polysaccharide, Astragalus saponins, Astragalus flavones, etc., which play a vital role in the treatment of DPN. This review aimed to summarize the pathogenesis of DPN and the studies on the mechanism of the effective components of Astragalus mongholicus in treating DPN. This is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.

Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the long-term effectiveness of Huangqi (Radix Astragali Mongolici, HQ)-based Traditional Chinese Medicine (TCM) in the treatment of diabetic peripheral neuropathy (DPN). METHODS: Nine databases were searched to retrieve available randomized controlled trials that compared HQ-based TCM and Western Medicines in the treatment of DPN. The methodological quality of the included studies was assessed using the Cochrane bias risk tool, and RevMan 5.4 was used for data analysis. The effect estimates of interest were risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM [RR = 1.30, 95% CI (1.21, 1.40), P < 0.000 01] or HQ-based TCM combined with Western Medicines [RR = 1.25, 95% CI (1.19, 1.31), P < 0.000 01] exhibited higher total efficacy rates than individuals who received Western Medicine alone. The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores [MD =－1.50, 95% CI (－1.83, －1.17), P < 0.000 01], and reduced serum interleukin 6 [SMD = －0.57, 95% CI (－0.87, －0.27), P = 0.0002] and tumor necrosis factors-α levels [SMD = －0.60, 95% CI (－0.95, －0.25), P = 0.0009]. In addition, both HQ-based TCM and HQ-based TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone. In terms of blood lipids, oxidative stress and adverse drug reactions, there were no significant differences between the HQ-based TCM groups and the Western Medicine control group. CONCLUSION: The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN, although further well-designed RCTs are required to validate these findings.

Protective effect of modified Huangqi Chifeng decoction on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway.

OBJECTIVE: To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction (, MHCD) in immunoglobulin A nephropathy (IgAN) rats. METHODS: To establish the IgAN rat model, the bovine serum albumin, lipopolysaccharide, and carbon tetrachloride 4 method was employed. The rats were then randomly assigned to the control, model, telmisartan, and high-, medium-, and low-dose MHCD groups, and were administered the respective treatments via intragastric administration for 8 weeks. The levels of 24-h urinary protein, serum creatinine (CRE), and blood urea nitrogen (BUN) were measured in each group. Pathological alterations were detected. IgA deposition was visualized through the use of immunofluorescence staining. The ultrastructure of the kidney was observed using a transmission electron microscope. The expression levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-ß1 (TGF-ß1) were examined by immunohistochemistry and quantitative polymerase chain reaction. Levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) P65, were examined by immunohistochemistry, Western blotting, and quantitative polymerase chain reaction. RESULTS: The 24-h urine protein level in each group increased significantly at week 6, and worsen from then on. But this process can be reversed by treatments of telmisartan, and high-, medium-, and low-dose of MHCD, and these treatments did not affect renal function. Telmisartan, and high-, and medium-dose of MHCD reduced IgA deposition. Renal histopathology demonstrated the protective effect of high-, medium-, and low-dose of MHCD against kidney injury. The expression levels of MCP-1, IL-6, and TGF-ß1 in kidney tissues were downregulated by low, medium and high doses of MHCD treatment. Additionally, treatment of low, medium and high doses of MHCD decreased the protein and mRNA levels of TLR4, MyD88, and NF-κB. CONCLUSIONS: MHCD exerted nephroprotective effects on IgAN rats, and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway, thereby alleviating renal inflammation by inhibiting MCP-1, IL-6 expressions, and ameliorating renal fibrosis by inhibiting TGF-ß1 expression.

Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application.

Astragali Radix (A. Radix) is the dried root of Astragalus membranaceus var. mongholicus (Bge) Hsiao or Astragalus membranaceus (Fisch.) Bge., belonging to the family Leguminosae, which is mainly distributed in China. A. Radix has been consumed as a tonic in China for more than 2000 years because of its medicinal effects of invigorating the spleen and replenishing qi. Currently, more than 400 natural compounds have been isolated and identified from A. Radix, mainly including saponins, flavonoids, phenylpropanoids, alkaloids, and others. Modern pharmacological studies have shown that A. Radix has anti-tumor, anti-inflammatory, immunomodulatory, anti-atherosclerotic, cardioprotective, anti-hypertensive, and anti-aging effects. It has been clinically used in the treatment of tumors, cardiovascular diseases, and cerebrovascular complications associated with diabetes with few side effects and high safety. This paper reviewed the progress of research on its chemical constituents, pharmacological effects, clinical applications, developing applications, and toxicology, which provides a basis for the better development and utilization of A. Radix.

Dual-channel hypergraph convolutional network for predicting herb-disease associations.

Herbs applicability in disease treatment has been verified through experiences over thousands of years. The understanding of herb-disease associations (HDAs) is yet far from complete due to the complicated mechanism inherent in multi-target and multi-component (MTMC) botanical therapeutics. Most of the existing prediction models fail to incorporate the MTMC mechanism. To overcome this problem, we propose a novel dual-channel hypergraph convolutional network, namely HGHDA, for HDA prediction. Technically, HGHDA first adopts an autoencoder to project components and target protein onto a low-dimensional latent space so as to obtain their embeddings by preserving similarity characteristics in their original feature spaces. To model the high-order relations between herbs and their components, we design a channel in HGHDA to encode a hypergraph that describes the high-order patterns of herb-component relations via hypergraph convolution. The other channel in HGHDA is also established in the same way to model the high-order relations between diseases and target proteins. The embeddings of drugs and diseases are then aggregated through our dual-channel network to obtain the prediction results with a scoring function. To evaluate the performance of HGHDA, a series of extensive experiments have been conducted on two benchmark datasets, and the results demonstrate the superiority of HGHDA over the state-of-the-art algorithms proposed for HDA prediction. Besides, our case study on Chuan Xiong and Astragalus membranaceus is a strong indicator to verify the effectiveness of HGHDA, as seven and eight out of the top 10 diseases predicted by HGHDA for Chuan-Xiong and Astragalus-membranaceus, respectively, have been reported in literature.

Astraoleanosides E-P, oleanane-type triterpenoid saponins from the aerial parts of Astragalus membranaceus Bunge and their ß-glucuronidase inhibitory activity.

Historically, Astragalus membranaceus Bunge has been used as a beneficial medicinal plant, particularly in the Asian traditional medical systems, for the treatment of various human diseases such as stomach ulcers, diarrhea, and respiratory issues associated with phlegm. In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent ß-glucuronidase inhibitory activities, with IC50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-saccharic acid 1,4-lactone (IC50 = 20.62 ± 1.61 µM). Enzyme kinetics studies were then conducted to investigate the type of inhibition exhibited by these active compounds. In addition, the binding mechanism, key interactions, binding stability, and dynamic behavior of protein-ligand complexes were investigated through in silico approaches, such as molecular docking and molecular dynamics simulations. These findings highlight the promising potential of triterpenoid saponins from A. membranaceus as lead compounds for ß-glucuronidase inhibitors, offering new possibilities for the development of therapeutic agents targeting various diseases where ß-glucuronidase plays a crucial role.

Exploration of the intestinal flora to reveal the important contribution of Radix Astragali to Huangqi Jianzhong Tang in treating chronic atrophic gastritis rats.

Radix Astragali (Huangqi in Chinese, HQ) is a commonly used Chinese herbal medicine for thousands of years. In this study, A classic prescription Huangqi Jianzhong tang (HQJZ) was selected to evaluate the important effect of HQ on rats with chronic atrophic gastritis (CAG) from the perspective of intestinal flora in cecal contents samples. Traditional pharmacological indicators, including weight change, pathological examination and biochemical indicators showed that HQ exerted favorable contribution to HQJZ against CAG, where the efficiencies of HQ and HQJZ were better than HY (HQJZ prepared without HQ). An accurate strategy was adopted to screen out the differential metabolites in the metabolomis analysis of intestinal flora in cecal contents samples based on the optimal screening factors, including VIP (importance of variables in projection), FC (fold change), AUROC (area under the receiver operating characteristic curve) and -ln(p-value), which were evaluated based on their interpreting, grouping, and predicting abilities of the performed orthogonal partial least-squares-discriminate analysis (OPLS-DA) models. Ten altered differential metabolites were obtained and associated with the intestinal flora, which HQ exerted the important metabolic contributions to HQJZ. The efficacy on the diversity of intestinal flora and their correlations with the altered metabolites further showed the important role of HQ in HQJZ composition. This work provided valuable approach for looking for potential biomarkers associated with metabolomics research with more accuracy, and provided new insights into the mechanisms to explain the efficacy of HQ contributing to HQJZ formula.

Rapid identification of Radix Astragali origin by using fluorescence probe combined with chemometrics.

Fluorescent probes for metal ion recognition can be divided into selective probes, weakly selective probes, and non-selective probes roughly. Weakly selective probes are not often used for quantitative analysis of metal ions due to their overlapping spectra resulting from simultaneous interactions with multiple metal ions. Conversely, the different metal ions contained in herbal medicine extracts from different geographical origins will produce corresponding fluorescence fingerprint profiles after interaction with weakly selective fluorescence probes. The performance can be used in the study of origin tracing of food or Chinese herbal medicine. Weakly selective fluorescent probes of benzimidazole derivatives have been synthesized and attempted to be used in the origin tracing of Radix Astragali in this work. Radix Astragali from different origins will produce different fluorescence fingerprint spectra due to the difference of metal ions and content in combination with the probe. Excitation-emission matrix (EEM) fluorescence spectroscopy in conjunction with N-way partial least squares discriminant analysis (N-PLS-DA), and unfolded partial least squares discriminant analysis (U-PLS-DA) were used to identify the origin of 150 Radix Astragali samples from five geographical origins. The prediction results showed that the correct recognition rates of the U-PLS-DA model and N-PLS-DA model are 95.92% and 93.88%, respectively. In comparison, the results of U-PLS-DA are slightly better than those of N-PLS-DA. These findings indicate that EEM fluorescence spectroscopy based on weakly selective fluorescent probes combined with multi-way chemometrics provides a good idea for the origin tracing of traditional Chinese medicine.

Research state of the herbal medicine Huangqi (Radix Astragali): A global and bibliometric study.

BACKGROUND: Huangqi (Radix Astragali) is a natural medicine with a wide range of uses. The research related to Huangqi is getting hotter and the number of publications is gradually increasing. This study aims to explore the current status and emerging trends of Huangqi-related research. METHOD: Huangqi-related literature was systemically obtained from the Web of Science database. The CiteSpace, VOSviewer, and, R package "Bibliometrix" tools were used to analyze the number of publications, countries, research institutions, journals, authors, keywords, references, and trends. RESULTS: A total of 2255 papers were retrieved for analysis. These papers were written by 11,247 authors from 1927 institutions in 71 countries, published in 570 journals, and cited 73,534 references from 11,553 journals. From 1999 to 2022, the number of publications gradually increased. China was the country with the highest number of publications. The most prolific institution was Shanghai University of Chinese Medicine. Evidence-Based Complementary and Alternative Medicine was the journal publishing the most Huangqi-related literature. Dr Karl Wah Keung Tsim was the authors with the most output publications. The Review, entitle "Review of the Botanical Characteristics, Phytochemistry, and Pharmacology of Astragalus membranaceous (Huangqi)," was the reference being cited most frequently. The major keywords were apoptosis, oxidative stress, and inflammation. Gut microbiota and epithelial-mesenchymal transitions were new research hotspots in recent years. CONCLUSION: This study used quantitative and visual analysis of Huangqi to provide insights into the research priorities, frontier research hotspots, and future research trends in this field.

Evaluating traditional Chinese medicine (TCM) Jie Geng and Huang Qi combination on reducing surgical site infections in colorectal cancer surgeries: A systematic review and meta-analysis.

Postoperative wound infections (PWIs) pose a significant challenge in colorectal cancer surgeries, leading to prolonged hospital stays and increased morbidity. This systematic review and meta-analysis evaluated the efficacy of the traditional Chinese medicine (TCM) combination of Jie Geng and Huang Qi in reducing PWIs following colorectal cancer surgeries. Adhering to PRISMA guidelines, we focused on seven randomized controlled trials (RCTs) involving 1256 patients, examining the incidence of PWIs within 30 days post-surgery, alongside secondary outcomes such as length of hospital stay and antibiotic use. The analysis revealed a significant reduction in PWI incidence in the TCM-treated group compared to controls, with a Risk Ratio of 0.21 (95% CI: 0.14 to 0.30, p < 0.01), a notable decrease in hospital stay (Mean Difference: 1.2 days, 95% CI: 0.15 to 1.28 days, p < 0.01) and a significant reduction in antibiotic use (Risk Ratio: 0.24, 95% CI: 0.16 to 0.36, p < 0.01). These findings suggest that Jie Geng and Huang Qi in TCM could be an effective adjunct in postoperative care for colorectal cancer surgeries, underscoring the need for further high-quality RCTs to substantiate these results and explore the underlying mechanisms.

Rapid preparation and proton NMR fingerprinting of polysaccharides from Radix Astragali.

The purity, content, and structure of the polysaccharides prepared from a specific medicinal plant are the fundamental basis to interpret the observed biological activities. An ultrafiltration-based method has been developed for rapid preparation of total and fractional polysaccharides from Radix Astragali in high yield and purity. This method involves extraction of plant material by hot water, treatment with Sevag reagent, and ultrafiltration using molecular weight cutoff concentrators. The prepared polysaccharides were assessed by 1H NMR spectroscopy, providing general purity, fingerprinting, and structural information. This method may be used to efficiently screen polysaccharides in plants.

Systematic Pharmacology and Experimental Validation to Reveal the Alleviation of Astragalus membranaceus Regulating Ferroptosis in Osteoarthritis.

Background: Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear. Methods: We validated AM's protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM's active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments. Results: AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM's ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis. Conclusion: This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM's scientific application.

Huangqi-Guizhi-Wuwu decoction regulates differentiation of CD4+ T cell and prevents against experimental autoimmune encephalomyelitis progression in mice.

BACKGROUND: Multiple sclerosis (MS) is a demyelination disorder caused by an overactive immune response. Its pathological characteristics include CNS inflammation, white matter demyelination, glial cell proliferation, and so on. Huangqi-Guizhi-Wuwu Decoction (HGWD), which is recorded in the Synopsis of the Golden Chamber, is used clinically for the therapy of MS, but its mechanism is still elusive. PURPOSE: This study was aimed to investigate the impact of HGWD on the classical animal model for MS, experimental autoimmune encephalomyelitis (EAE), and explore the underlying action mechanism. RESULTS: HGWD ameliorated the pathogenesis of EAE mice, and improved their neurobehavior and pathological tissue damage. Network pharmacology predictions revealed the action mechanism of HGWD in EAE mice might be related to its effect on the immune system of mice. HGWD effectively suppressed the inflammatory infiltration in CNS, while also preventing the elevation of CD4+T cells of mice with EAE. HGWD could increase the ratio of Treg cells, up-regulate the secretion of IL-10 and Foxp3 mRNA expression, inhibit the ratio of Th1 and Th17 cells, down-regulate the IFN-γ and IL-17 protein expression, as well as the RORγT and T-bet gene expression in EAE mice. In addition, HGWD-containing serum modulated Th1/Th17/Treg cell differentiation in vitro. Moreover, HGWD inhibited the p-JAK1, p-JAK2, p-STAT1, p-STAT3 and p-STAT4 proteins and elevated the p-STAT5 protein in lymphoid tissues of EAE mice. CONCLUSION: HGWD improved the progress of EAE by regulating the proportion of CD4+T cell subtype differentiation, which might be exerted through JAK/STAT signaling pathway, providing a pharmacological basis for the clinical treatment of MS.

Fabrication of a bio-based polymer adsorbent and its application for extraction and determination of glycosides from Huangqi Liuyi decoction.

Huangqi Liuyi Decoction, a famous classical Chinese prescription, shows significant curative effect on diabetes and its complications, in which calycosin-7-glucoside, liquiritin and glycyrrhizic acid are the main components that playing these mentioned pharmacological activity, under the synergistic action of various other ingredients in the decoction. However, there are significant differences in the content of active compounds in Chinese medicinal materials, which mainly due to origin, picking seasons, and processing methods. Hence, the accurate content of the glycosides is the prerequisite for ensuring the pharmacological efficacy. Aiming at establishing an efficient extraction and determination method for accurate quantitative analysis of calycosin-7-glucoside, liquiritin and glycyrrhizic acid in Huangqi Liuyi Decoction, an on line solid-phase extraction-high-performance liquid chromatography method was developed, using a homemade bio-based monolithic adsorbent. The bio-based adsorbent was prepared in a stainless steel tube, using bio-monomers of methyleugenol and S-allyl-L-cysteine, which effectively reduced the dependence of the polymer field on non-renewable fossil resources and reduced carbon emissions. Furthermore, the prepared adsorbent owned abundant chemical groups, which can produce interactions of hydrogen bond, dipole-dipole, π-π and hydrophobic force with the target glycosides, thus improving the specific recognition ability of the adsorbent. The experiments were carried out on an LC-3000 HPLC instrument with a six-way valve. Methodology validation indicates that the recovery is in the range of 97.0%-103.4% with the RSD in the range of 1.6%-4.0%, due to the specific selectivity of the bio-based monolithic adsorbent for these three glycosides, and good matrix-removal ability for Huangqi Liuyi decoction. The limit of detection is 0.17, 0.50 and 0.33 µg/mL for calycosin-7-glucoside, liquiritin and glycyrrhizic acid, respectively, and the limit of quantitation is 0.50, 1.50 and 1.00 µg/mL, respectively, with the linear range of 2-200 µg/mL for calycosin-7-glucoside, and 5-500 µg/mL for liquiritin and glycyrrhizic acid. The present work provided a simple and efficient method for the extraction and determination of glycosides in complex medicinal plants.

Huangqi Baihe Granules alleviate hypobaric hypoxia-induced acute lung injury in rats by suppressing oxidative stress and the TLR4/NF-κB/NLRP3 inflammatory pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Baihe Granules (HQBHG) are a modified formulation based on the traditional recipe "Huangqi Baihe porridge" and the Dunhuang medical prescription "Cistanche Cistanche Soup." The Herbal medicine moistens the lungs and tones the kidneys in addition to replenishing Qi and feeding Yin, making it an ideal choice for enhancing adaptability to high-altitude hypoxic environments. AIM OF THE STUDY: The purpose of this study was to examine a potential molecular mechanism for the treatment and prevention of hypoxic acute lung injury (ALI) in rats using Huangqi Baihe Granules. MATERIALS AND METHODS: The HCP-III laboratory animal low-pressure simulation chamber was utilized to simulate high-altitude environmental exposure and establish an ALI model in rats. The severity of lung damage was evaluated using a battery of tests that included spirometry, a wet/dry lung ratio, H&E staining, and transmission electron microscopy. Using immunofluorescence, the amount of reactive oxygen species (ROS) in lung tissue was determined. Superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) levels in lung tissue were determined using this kit. Serum levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta), and antiinflammatory cytokines like interleukin-10 (IL-10) were measured using an enzyme-linked immunosorbent assay kit. Gene expression changes in lung tissue were identified using transcriptomics, and the relative expression of proteins and mRNA involved in the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB p65)/Nod-like receptor protein 3 (NLRP3) pathway were determined using western blotting and quantitative real-time PCR. RESULTS: HQBHG was shown to enhance lung function considerably, decrease the wet/dry ratio of the lungs, attenuate lung tissue damage, suppress ROS and MDA formation, and increase SOD activity and GSH expression. The research also demonstrated that HQBHG inhibited the activation of the TLR4/NF-κB p65/NLPR3 signaling pathway in lung tissue, reducing the release of downstream pro-inflammatory cytokines. CONCLUSIONS: HQBHG exhibits potential therapeutic effects against ALI induced by altitude hypoxia through suppressing oxidative stress and inflammatory response. This suggests it may be a novel drug for treating and preventing ALI.

Identify production area, growth mode, species, and grade of Astragali Radix using metabolomics "big data" and machine learning.

BACKGROUND: Astragali Radix (AR) is a widely used herbal medicine. The quality of AR is influenced by several key factors, including the production area, growth mode, species, and grade. However, the markers currently used to distinguish these factors primarily focus on secondary metabolites, and their validation on large-scale samples is lacking. PURPOSE: This study aims to discover reliable markers and develop classification models for identifying the production area, growth mode, species, and grade of AR. METHODS: A total of 366 batches of AR crude slices were collected from six provinces in China and divided into learning (n = 191) and validation (n = 175) sets. Three ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods were developed and validated for determining 22 primary and 10 secondary metabolites in AR methanol extract. Based on the quantification data, seven machine learning algorithms, such as Nearest Neighbors and Gradient Boosted Trees, were applied to screen the potential markers and build the classification models for identifying the four factors associated with AR quality. RESULTS: Our analysis revealed that secondary metabolites (e.g., astragaloside IV, calycosin-7-O-ß-D-glucoside, and ononin) played a crucial role in evaluating AR quality, particularly in identifying the production area and species. Additionally, fatty acids (e.g., behenic acid and lignoceric acid) were vital in determining the growth mode of AR, while amino acids (e.g., alanine and phenylalanine) were helpful in distinguishing different grades. With both primary and secondary metabolites, the Nearest Neighbors algorithm-based model was constructed for identifying each factor of AR, achieving good classification accuracy (>70%) on the validation set. Furthermore, a panel of four metabolites including ononin, astragaloside II, pentadecanoic acid, and alanine, allowed for simultaneous identification of all four factors of AR, offering an accuracy of 86.9%. CONCLUSION: Our findings highlight the potential of integrating large-scale targeted metabolomics and machine learning approaches to accurately identify the quality-associated factors of AR. This study opens up possibilities for enhancing the evaluation of other herbal medicines through similar methodologies, and further exploration in this area is warranted.