UNASSIGNED: Chemotherapy-induced peripheral neuropathy not only affects the tolerability of chemotherapy, but also causes intolerable and prolonged neuropathic pain in cancer patients. Currently, duloxetine is the only drug used to treat chemotherapy-induced peripheral neuropathy. However, the clinical use of this drug still faces several challenges. Therefore, we focused on traditional Chinese medicine to find an effective and safe alternative medicine. Huangqi Guizhi Wuwu Decoction is a traditional Chinese medicine that has been clinically used for treating nerve pain for thousands of years. This study aimed to investigate the neuroprotective effect of Huangqi Guizhi Wuwu Decoction on cisplatin-induced nerve injury in PC12 cells and to elucidate its potential mechanism of action.
UNASSIGNED: Huangqi Guizhi Wuwu Decoction-containing serum and blank serum were prepared from a rat model. The protective effects of Huangqi Guizhi Wuwu Decoction on cisplatin (10 µmol/L)-induced PC12 cell injury were assessed by a Cell Counting Kit-8 assay. RNA expression in Huangqi Guizhi Wuwu Decoction-protected PC12 cells was analyzed using RNA-seq, and subsequently, differentially expressed genes were further analyzed using Gene Ontology and Gene Set Enrichment Analysis.
UNASSIGNED: The Cell Counting Kit-8 results showed that pretreatment of PC12 cells with Huangqi Guizhi Wuwu Decoction-containing serum (5%, 10%, 15%) significantly increased cells\' viability to 10 µmol/L cisplatin-induced cell death. RNA-seq analysis revealed 843 differentially expressed genes in the chemotherapy-induced peripheral neuropathy group and 249 in the Huangqi Guizhi Wuwu Decoction group. The gene set enrichment analysis results in this study suggest that Huangqi Guizhi Wuwu Decoction may treat chemotherapy-induced peripheral neuropathy by enhancing axon guidance.
UNASSIGNED: This study provides valuable evidence for using Huangqi Guizhi Wuwu Decoction in treating chemotherapy-induced peripheral neuropathy, partially achieved by improving axon guidance pathways.

UNASSIGNED: Chemotherapy-induced peripheral neuropathy (CIPN) still lacks efficient therapeutic drugs. This study aimed to systematically evaluate the effects of Huangqi Guizhi Wuwu Decoction (HGWD) alone or combined with positive drugs on CIPN prevention and treatment.
UNASSIGNED: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal (VIP) and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) of HGWD for CIPN prevention and treatment. The search time ranged from database establishment to October 17, 2023. The Cochrane risk-of-bias assessment tool was used for quality assessment, Review Manager 5.3 and STATA 12.0 were used for meta-analysis, and GRADEprofiler was used for evidence level assessment.
UNASSIGNED: A total of 32 RCTs involving 1987 patients were included. The meta-analysis results revealed the following: 1. In terms of the total CIPN incidence, that in the HGWD group was lower than that in the blank control group. The incidence in both the HGWD and HGWD+positive drug groups was lower than that in the monotherapy-positive drug group. 2. In terms of the incidence of severe CIPN, that in the HGWD group was lower than that in the blank control and positive drug groups. There was no statistically significant difference between the HGWD+positive drug and positive drug groups. Sensitivity analysis revealed that the results of severe incidence in the HGWD group was lower than that in the positive drug group were unstable 3. HGWD did not increase the number of chemotherapy-related adverse events.
UNASSIGNED: HGWD can safely and effectively prevent CIPN, reduce symptoms, improve quality of life and reduce the impact of chemotherapy drugs on sensory nerve conduction. However, more high-quality RCTs are needed to compare the efficacy of HGWD with that of positive control drugs in preventing severe CIPN.

UNASSIGNED: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction (HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis (CIA) mouse model.
UNASSIGNED: DBA/1J female mice were used to establish the collagen-induced arthritis (CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay (ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors mRNA and protein levels after HGWD intervention in RAW 264.7 cells.
UNASSIGNED: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints, reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function. HGWD decreased the expression of mRNA for inflammatory factors and the protein expression levels of p-NF-кB and IL-17.
UNASSIGNED: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.

Huangqi Guizhi Wuwu Decoction (HQGZWWD) has shown promising potential in treating various cardiovascular diseases. This study aimed to elucidate the molecular basis and therapeutic role of HQGZWWD in the treatment of doxorubicin (DOX)-induced myocardial injury. The HPLC fingerprint of HQGZWWD was used to analyze the active components. A DOX-induced myocardial damage rat model was developed, and the therapeutic effects of HQGZWWD were evaluated using echocardiography, myocardial enzyme levels, and hematoxylin and eosin staining. Network pharmacology was used to screen treatment targets, and western blotting and immunohistochemistry were performed to assess cellular pyroptosis levels. Oxidative stress levels were measured using assay kits, and mitochondrial damage was examined using transmission electron microscopy. An in vitro model of DOX-induced cell damage was established, and treatment was administered using serum containing HQGZWWD and N-acetylcysteine (NAC). Oxidative stress levels were detected using assay kits and DCFH-DA, whereas cellular pyroptosis levels were assessed through WB, immunofluorescence, and ELISA assays. HQGZWWD ameliorated DOX-induced myocardial injury. Network pharmacology identified IL-1β and IL-18 as crucial targets. HQGZWWD downregulated the protein levels of the inflammatory factors IL-1β and IL-18, inhibited the expression of GSDMD-NT, and simultaneously suppressed the synthesis of Caspase-1, ASC, NLRP3, and Caspase-11. Additionally, HQGZWWD inhibited oxidative stress, and the use of NAC as an oxidative stress inhibitor resulted in significant inhibition of the GSDMD-NT protein in H9C2 cells. These findings highlight the myocardial protective effects of HQGZWWD by inhibiting oxidative stress and suppressing both canonical and non-canonical pyroptotic pathways.

Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside Ⅳ, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.

Huangqi Guizhi Wuwu decoction (HGWWD) is a widely used traditional Chinese medicine (TCM) preparation for the treatment of ischemic stroke and diabetes peripheral neuropathy. However, the material basis for the efficacy of HGWWD remains unclear. In this study, a rapid, sensitive and selective ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed to separate and identify the absorbed components and metabolites of HGWWD in rat plasma after oral administration for the first time. By comparing the retention time, high-resolution mass spectrometry primary and secondary mass spectrometry data of blank plasma and drug-containing plasma, a total of 42 constituents, including 24 prototype compounds and 18 metabolites, were identified or tentatively characterized. The results indicated that monoterpenes, flavonoids, organic acids, amino acids, gingerols and alkaloids were main prototype compounds in rat plasma, and flavonoid-related metabolites, organic acid-related metabolites and gingerol-related metabolites were major metabolites. It is concluded the developed UHPLC-Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the absorbed components and metabolites of HGWWD, and the results will provide important data for further study on the relationship between the chemical constituents and pharmacological activities of HGWWD.

BACKGROUND: Huangqi Guizhi Wuwu Decoction (HGWD), a classical Chinese formula originally recorded in Jin Kui Yao Lue, was used for the treatment of human \"blood impediment\" (a type of \"Bi\" syndrome). In clinical practice, HGWD has been applied to treat rheumatoid arthritis (RA).
OBJECTIVE: The characterization of chemical markers reflecting both efficacy and chemical characteristics is of great significance for TCM quality control. With the anti-RA effects of HGWD as an example, the aim of this study was to develop a comprehensive strategy combining the overall chemical profile and biological activity data to identify chemical markers.
METHODS: First, an ultra-performance liquid chromatography-diode array detector (UPLC-DAD) fingerprint was established and validated to evaluate the holistic quality of HGWD of different origins. Characteristic markers associated with HGWD from different geographical origins were screened by a combination of UPLC-DAD fingerprint and chemometrics methods. Second, the chemical profiles of the 15 batches of HGWD samples were characterized by UPLC coupled tohybrid linear ion trap-Orbitrap mass spectrometry (UPLC-HRMS). The in vitro anti-RA activities of the 15 HGWD samples were then evaluated. Third, spectrum-effect relationship analysis was performed to identify bioactive compounds that could potentially be used as quality markers. Finally, a UPLC-triple quadrupole tandem mass spectrometry approach was optimized and established for quantitative analysis of the characteristic and quality markers in 15 batches of HGWD.
RESULTS: In total, 30 common peaks were assigned in the UPLC-DAD fingerprint. Nine peaks were recognized and considered characteristic markers: protocatechuic acid, coumarin, cinnamic acid, oxypaeoniflorin, paeoniflorin, calycosin, formononetin, catechin, and albiflorin. Furthermore, ninety-five common compounds were identified in the UPLC-HRMS chemical profile. The pharmacological analysis indicated that the anti-RA activities of the 15 HGWD samples were vastly different. The spectrum-effect relationship analysis revealed 30 potential bioactive constituents positively correlated with anti-RA activity. Among them, five compounds with relative amounts >1%, paeoniflorin, astragaloside IV, hexahydrocurcumin, formononetin and calycosin-7-glucoside, were selected as quality markers, and their activity was verified in LPS-induced RAW264.7 macrophages. Finally, the above 12 representative components were simultaneously quantified in the 15 batches of HGWD samples.
CONCLUSIONS: Combining a holistic chemical profile with representative component evaluation, this systematic strategy could be a reliable and effective method to improve quality evaluations of HGWD.

BACKGROUND: Huangqi Guizhi Wuwu Decoction (HGWD) is a classic traditional Chinese herbal formula from \"Synopsis of Golden Chamber,\" which is used to treat blood stagnation and has been used for alleviating diabetic peripheral neuropathy (DPN) in the clinic. However, the mechanisms of HGWD intervention DPN are still to be discovered.
OBJECTIVE: This study aims to explore the mechanism of HGWD intervention DPN by integrating plasma metabolomics and gut microbiome.
METHODS: BKS Cg-m+/+Leprdb/J (db/db) mice with DPN were at 16 weeks of age. The indices of DPN phenotypes in db/db mice, pathomorphology of the sciatic nerve, intraepithelial nerve fibers (IENF) of the foot pad, levels of blood lipids and oxidative stress, and inflammatory reaction were used to appraise the HGWD efficacy. Finally, the pharmacological mechanisms of HGWD intervening DPN were explored by metabolomics and 16S rRNA gene sequencing.
RESULTS: HGWD reversed DPN phenotypes in db/db mice, improved peripheral nerve structure, ameliorated the level of blood lipids and nerve growth factor in plasma, enhanced antioxidant capacity, and alleviated inflammatory responses. Plasma metabolomics disclosed that HGWD remarkably regulated the unusual levels of thirty-seven metabolites involved in sphingolipid metabolism, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and amino acid biosynthesis pathways. The gut microbiome showed that nine bacteria were highly correlated with the efficacy of HGWD in DPN. Integrating analysis of microbiome and metabolomics demonstrated that the interaction of four bacteria with four metabolic pathways might be the significant mechanism of HGWD intervention in DPN.
CONCLUSIONS: The mediation of gut microbiota and plasma metabolism may be the potential mechanism of HGWD ameliorating DPN in db/db mice. The interaction of Lactobacillus, Alloprevotella, Bacteroides, and Desulfovibio with four metabolic pathways might be the critical mechanism for HGWD treating DPN.

Huangqi Guizhi Wuwu Decoction (HGWD) has a definite effect on neuropathic pain (NP), whereas the specific mechanism has not been elucidated. The components and targets in HGWD were collected and identified through System Pharmacology Database (Traditional Chinese Medicine Database and Analysis Platform). Genecards and Online Mendelian Inheritance in Man databases were used to search for NP-related genes. The Venn diagram was drawn to get the intersection target. Cytoscape 3.8.0 software was used to construct the compound-disease-target-pathway networks. STRING database was applied to analyze protein-protein interaction of potential targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were used to identify the function of genes related to NP. Finally, molecular docking was performed to visualize the binding mode and affinity between proteins and active ingredients. According to the intersection target of the Venn diagram, the network graph is constructed by Cytoscape and the results show the five compounds, β-sitosterol, (+)-catechin, quercetin, Stigmasterol, kaempferol, and 15 genes (CASP3, FOS, GSK3B, HSP90AA1, IKBKB, IL6, MAPK8, RELA, ICAM1, SELE, ELK1, HSPB1, PRKACA, PRKCA, RAF1) were highly correlated with NP. KEGG and GO of 15 genes results that TNF, IL-17 and MAPK signaling pathway were Significantly related to the pathological mechanism of NP. Molecular docking showed that core genes in this network were IL-6 (TNF and IL-17 signaling pathways), ICAM1 (TNF signaling pathway), and CASP3 (three signal pathways). This study found that the five active compounds, three core genes, and three signaling pathways may be the key to the treatment of NP by HGWD.

Huangqi Guizhi Wuwu decoction (HGWD), as a classical formula, has been used for thousands of years in China. In this work, a comprehensive strategy was proposed for characterizing the chemical profile of HGWD based on online two-dimensional hydrophilic interaction and reversed-phase liquid chromatography coupled with hybrid linear ion trap-Orbitrap mass spectrometry (online HILIC × RP-ESI/HRMS/MSn). The compounds in HGWD were first separated by the combined use of an XBridge amide column (150 × 4.6 mm, 3.5 μm) and Accucore C18 column (50 mm × 4.6 mm, 2.6 μm). Modulation with assistant technology, including trap columns and online dilution, was optimized and developed to decrease potential analyte loss and improve the resolution of the system. Subsequently, the accurate mass was determined by high-resolution Orbitrap and MSn fragment data by a hybrid linear ion trap (LTQ). In total, 170 chemical constituents were unambiguously identified or tentatively characterized in both positive and negative ion modes. Our study demonstrated that the proposed online HILIC × RP system coupled to the LTQ-Orbitrap MS platform is an efficient analytical technique for characterizing the chemical profile of multicomponent systems.