Huangqi Decoction Research Articles

Integrative multi-omics and network pharmacology reveal the mechanisms of Fangji Huangqi Decoction in treating IgA nephropathy

Ethnopharmacological relevanceFangji Huangqi Decoction (FJHQD), a classical Chinese herbal formulation, has demonstrated significant clinical efficacy in the treatment of IgA nephropathy (IgAN), although its mechanisms remain poorly understood. Aim of the studyThis study aims to investigate the renal protective mechanisms of FJHQD using an integrated approach that combines transcriptomics, proteomics, and network pharmacology. MethodsRenal glomerular structure changes were assessed via hematoxylin and eosin (H&E) and Masson staining. IgA expression in the glomeruli was quantified using immunofluorescence. Furthermore, the potential mechanisms underlying the effects of FJHQD were explored through a combined strategy of network pharmacology, transcriptomics, and proteomics. The expression of signaling pathway-related proteins was detected using Western blot. ResultsFJHQD inhibited mesangial cell proliferation and renal interstitial fibrosis, and significantly reduced excessive IgA deposition in the glomerular mesangium. Network pharmacology identified 113 important active components and 8 common active components in FJHQD, with quercetin, isorhamnetin, jaranol, and kaempferol having the highest number of target interactions. Integration of network pharmacology with multi-omics approaches revealed that 44 active components regulated numerous immune and inflammatory signaling pathways through 17 hub targets. These pathways include the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. Subsequent in vivo experiments demonstrated that FJHQD effectively regulates the identified pathways in IgAN mice. Ultimately, molecular docking results further validated the reliability of the network pharmacology combined with multi-omics analyses. ConclusionThe findings suggest that FJHQD exerts a renal protective effect, potentially through modulation of the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. These insights offer valuable support for the clinical use of FJHQD and open new avenues for exploring the active compounds and molecular mechanisms of Traditional Chinese Medicines (TCMs).

Huangqi Decoction reduces liver fibrosis in rats by modulating PI3K/Akt/mTOR signaling and promoting autophagy.

Liver fibrosis is a chronic condition caused by various factors, and currently, there are no widely effective treatments. Autophagy plays a crucial role in maintaining liver energy homeostasis, and its disruption can contribute to the development of liver fibrosis. This study investigates the effects and molecular mechanisms of Huangqi Decoction, a traditional Chinese medicine, on autophagy and apoptosis in fibrotic liver tissue. Tissue staining indicated that Huangqi Decoction mitigated CCL4-induced liver injury and apoptosis in rats. Western blot analysis of liver fibrosis markers revealed that Huangqi Decoction significantly reduced the expression levels of alpha-smooth muscle actin (α-SMA), type I collagen, matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). Additionally, serum markers of liver fibrosis and biochemical indicators of hepatocyte injury showed that Huangqi Decoction effectively lowered serum levels of hyaluronic acid (HA), lymph node (LN), type I collagen, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Furthermore, Western blot analysis confirmed that Huangqi Decoction alleviated hepatocyte injury by promoting autophagy and inhibiting the PI3K/Akt/mTOR signaling pathway. In conclusion, Huangqi Decoction enhances autophagy and inhibits apoptosis through the PI3K/Akt/mTOR pathway in rats with liver fibrosis.

Screening bioactive compounds from Fangji Huangqi decoction for treating rheumatoid arthritis via COX-2 magnetic ligand fishing combined with in vivo validation

Ethnopharmacological relevanceFangji Huangqi Decoction (FHD) is a classical Chinese compound formula for treating rheumatoid arthritis (RA) with satisfactory effects. FHD is reputed for its ability to tonify qi with strengthening exterior, and dispel wind while removing dampness, but its mechanisms and bioactive compounds for treating RA remain unclear. Aim of the studyThe aim of this study was to explore the key target and bioactive compounds that were responsible for FHD-mediated improvements in RA. Materials and methodsUsing network pharmacology, we discovered that cyclooxygenase-2 (COX-2) was the key target of FHD against RA. We utilized a ligand fishing technique with COX-2 immobilized magnetic beads to recognize the bioactive components that act on COX-2. Then we carried out an in vitro assay of COX-2 enzyme inhibition and in vivo assay of carrageenan-induced inflammation and collagen-induced arthritis (CIA) to validate the bioactive effects of these captured ingredients. In the CIA assay, micro-CT, hematoxylin‒eosin staining and safranin-O/fast green staining were employed to assess the influence of the captured ligand on bone damage, pathological injury and cartilage destruction, respectively. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assays (ELISAs) were used to detect the expression of COX-2 target in the ankle joint. interleukin-6 (IL-6) levels in the serum were also detected by ELISA. Molecular docking was used to reveal the binding mechanism of the COX-2 protein and the captured ligand. ResultsEleven ligands, including tetrandrine, fangchinoline, cyclanoline, licochalcone B, ononin, calycosin and liquiritin, were specifically bound to the COX-2 protein, as determined by ultrahigh-performance liquid chromatography–mass spectrometry (UPLC–MS), seven of which were present at high levels. One ligand, tetrandrine, not only had a great inhibitory effect on COX-2 enzyme activity but also significantly reduced carrageenan-induced inflammation. In the CIA assay, middle- and high-dose tetrandrine (25 and 50 mg/kg) had effects comparable to those of FHD and celecoxib on ameliorating RA symptoms in CIA mice via the COX-2 target. Furthermore, compared with the low-dose tetrandrine group (12.5 mg/kg), the FHD group exhibited significantly lower arthritis index scores and serum IL-6 expression, although the content of tetrandrine in FHD extract solution was approximately 0.1% of that in the low-dose tetrandrine group. ConclusionsHence, we inferred that tetrandrine was the main bioactive component responsible for the effects of FHD against RA by suppressing the expression of the COX-2 protein and inhibiting the enzyme catalytic activity of COX-2. The reason for these effects may be that tetrandrine can interact with the residue Tyr385 of COX-2, the enzymatic catalytic site of COX-2 to transform arachidonic acid (AA) to prostaglandin E2 (PGE2), and thereby reduce the production of prostaglandins and inflammatory metabolites. Moreover, in addition to tetrandrine, FHD contains other compounds that could supplement the activity of tetrandrine when FHD was used to treat RA, which is manifested the “multi-component” characteristic of how Traditional Chinese Medicine formulas treat diseases.

Network pharmacology analysis of the Huangqi-Gancao herb pair reveals quercetin as a therapeutics for allergic rhinitis via the RELA-regulated IFNG/IRF1 axis response.

Despite the complexity of allergic rhinitis (AR) pathogenesis, no FDA-approved drug has been developed to achieve optimal therapeutic effects. The present study explored the efficacy and mechanism of Huangqi (Hedysarum Multijugum Maxim)-Gancao (Glycyrrhizae Radix et Rhizoma or licorice) herb pair in treating AR by network pharmacology and experimental approaches. The bioactive ingredients of Huangqi and Gancao were identified and used to predict the targets of these herbs in AR and generate the pharmacological network. Ovalbumin (OVA)-induced AR mouse model was established to assess the anti-AR effect of the Huangqi decoction (HQD) prepared based on both herbs. We identified 90 active ingredients of the Huangqi-Gancao pair, targeting 69 AR-related genes. Quercetin (QUE) was identified as the hub ingredient of this pair, with 57 targets in AR. The protein-protein interaction (PPI) network analysis and molecular docking revealed IL1B, TNF, STAT1, IL6, PTGS2, RELA, IL2, NFKBIA, IFNG, IL10, IL1A, IRF1, EGFR, and CXCL10 as important targets of QUE in AR treatment. Experimentally, QUE or HQD significantly alleviated the AR-induced histopathological changes, AR symptoms, and IgE level and counteracted AR-induced expression changes of IFNG, IRF1, RELA, and NFKBIA. These effects were promoted by the NF-kB inhibitor helenalin, indicating that HQD and QUE counteracted AR in mice by regulating the IFNG/IRF1 signaling via the NF-κB pathway in AR mice. These findings shed light on the efficacy of the constituents of Huangqi-Gancao pair, their potential targets, and the molecular mechanisms of HQD in treating AR, which could advance the development of tailored therapeutic interventions for this disorder.

Network Pharmacology-Based Strategy Integrated with Molecular Docking and In Vitro Experimental Validation to Explore the Underlying Mechanism of Fangji Huangqi Decoction in Treating Rheumatoid Arthritis.

Fangji Huangqi decoction (FHD), as a classic traditional Chinese medicine formula, has been clinically proven effective against rheumatoid arthritis (RA), yet its therapeutic mechanism remains unclear. This study employed network pharmacology and molecular docking methods to explore the major active components, biological targets, and signaling pathways of FHD. Subsequently, lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used as the in vitro model to validate the modulating effects of FHD on molecules/inflammatory mediators using various biomedical techniques/kits such as MTT assay, Griess reagents, flow cytometry, RT-qPCR, and immunoblotting. Network pharmacology analyses indicated a total of 20 major active components and 30 core biological targets of FHD against RA. Pathway enrichment analyses demonstrated the involvement of mitogen-activated protein kinase (MAPK) signaling pathways in the efficacy of the formula. Furthermore, experimental evidence demonstrated that FHD dose-dependently and significantly inhibited the productions of nitric oxide (NO) and reactive oxygen species; lowered the mRNA expression levels of proinflammatory mediators including iNOS, COX-2, TNF-α, ΙL-1β, and IL-6; decreased protein levels of the phosphorylated forms of p38, ERK, JNK, and NF-κB p65. Additionally, the results of molecular docking showed that tetrandrine, licochalcone A, oxonantenine, isorhamnetin, and kaempferol in FHD exerted the potent capability of binding to target molecules in the focused signaling pathway, probably being the potential effective substances for FHD. Our network pharmacology study integrated with cellular validation has elucidated that FHD exerts downregulating effects of the MAPK and NF-κB signaling pathway, ultimately leading to inhibitory effects on the productions of proinflammatory mediators in LPS-stimulated RAW264.7 cells. This work comprehensively demonstrated the effective substances, key targets, and signaling pathways involved in the anti-RA effects of the formula, and these findings provide a further understanding of the underlying mechanism of FHD in managing RA.

Mairin from Huangqi Decoction Mitigates Liver Cirrhosis through Suppression of Pro-inflammatory Signaling Pathways: A Network Pharmacology and Experimental Study

Background:: Liver cirrhosis is a consequence of various chronic liver conditions and may lead to liver failure and cancer. Huangqi Decoction (HQD) is a Traditional Chinese Medicine (TCM) effective for treating liver conditions, including cirrhosis. Therefore, both the active ingredients and the pharmacological actions of HQD deserve further exploration. The active components and pharmacological actions of HQD in preventing and treating liver cirrhosis were investigated using network pharmacology. The actions of the principal active ingredient, Mairin, were investigated empirically. Methods:: Using network pharmacology, the critical components of HQD were identified from multiple databases, and UPLC screening and targets were investigated using Swiss Target Prediction. Targets associated with liver cirrhosis were identified using the GeneCards database. GO and KEGG enrichment analysis of targets that overlapped between HQD and cirrhosis were analyzed in DAVID, and a “component-target-pathway” network for HQD was created in Cytoscape 3.7.2. The biological functions of the key active component, Mairin, were investigated using in silico docking, cell experiments, and evaluation in a carbon-tetrachloride (CCl4)-induced mouse model of liver cirrhosis. CCK-8 and F-actin assays were used to measure cell viability and hepatic stellate cell (HSC) activation, respectively; fibrosis was measured by histological and immunohistochemical evaluations, and the levels of the cirrhosis-related protein α-SMA and predicted essential target proteins in the PI3KAKT, NFκB-IκBα, and NLRP3-IL18 pathways were determined by western blotting. Results:: Fourteen active HQD components, 72 targets, and 10 pathways common to HQD and cirrhosis were identified. Network analysis indicated the association of Mairin with most targets and with inflammation through the PI3K/Akt, NF-κB, and NLRP3 pathways. Dose-dependent reductions in the activation and proliferation of LX-2 cells after Mairin treatment were observed. Mairin reversed the histopathological changes in the livers of cirrhosis model mice. Mairin also significantly reduced the α-SMA, NF-κB, IκBα, NLRP3, and IL-18 protein levels while increasing those of p- PI3K and p-Akt, suggesting that Mairin mitigates liver cirrhosis through modulation of the PI3KAKT, NFκB-IκBα, and NLRP3-IL18 pathways. Conclusions:: Using a comprehensive investigative process involving network pharmacology, bioinformatics, and experimental verification, it was found that Mairin, an active component of HQD, may be useful for developing specific treatments for preventing and treating liver cirrhosis.

Modified Fangji Huangqi Decoction alleviates renal interstitial fibrosis by inhibiting TGF-β1/Smad/Snail signaling pathway during epithelial-mesenchymal transition

This study investigated the effects of modified Fangji Huangqi Decoction on the expression of proteins related to epithelial-mesenchymal transition(EMT) in a mouse model of unilateral ureteral obstruction( UUO) and in a rat renal tubular epithelial cell(NRK-52E) model of fibrosis induced by transforming growth factor β1(TGF-β1). It aims to decipher the molecular mechanism by which modified Fangji Huangqi Decoction alleviates renal interstitial fibrosis. C57/BL mice were subjected to UUO.After the surgery, the mice were treated with 0. 5-fold and 2-fold concentrations of modified Fangji Huangqi Decoction and fosinopril sodium(positive control) for 7 days. The interstitial collagen deposition in the kidney was assessed by Masson staining. Western blot and RT-qPCR were employed to determine the expression levels of TGF-β1, phosphorylated Smad2/3(p-Smad2/3), Smad2/3, Snail,epithelial cadherin(E-cadherin), alpha smooth muscle actin(α-SMA), and vimentin. The NRK-52E cell model induced by TGF-β1was treated with the serum samples collected from SD rats treated with different concentrations of modified Fangji Huangqi Decoction.The CCK-8 assay was employed to examine the effects of the serum samples on NRK-52E cell proliferation. The cell morphology in different groups was observed under a microscope. Furthermore, the modeled cells were treated with the serum containing 1-fold decoction. Western blot and RT-qPCR were then employed to measure the expression levels of p-Smad2/3, Smad2/3, Snail,E-cadherin, α-SMA, and vimentin in the cells. Under the same conditions, sh RNA was used to silence the Snail gene, and measurements were repeated before and after treatment with the serum containing 1-fold decoction. The results indicated that modified Fangji Huangqi Decoction alleviated the fibrotic injury in the mouse model of UUO and the fibrosis in the NRK-52E cell model. The treatment with the decoction down-regulated the protein and m RNA levels of EMT-related indicators including p-Smad2/3, α-SMA,Snail, and vimentin, while it up-regulated the expression of E-cadherin. After sh RNA silencing of the Snail gene, the protein and m RNA levels of E-cadherin, α-SMA, and vimentin showed no significant differences before and after treatment with the serum containing the decoction. The results suggest that modified Fangji Huangqi Decoction may alleviate renal interstitial fibrosis by inhibiting the TGF-β1/Smad/Snail signaling pathway and regulating the EMT process.

Effect of Cox’s Interaction Model of Client Health Behavior Combined with Huangqi and Dangshen Decoction on Female Pelvic Floor Dysfunction

Huangqi and Dangshen have significant medicinal and medical value as natural bio-based materials, but there are few studies on female pelvic floor dysfunction. We aimed to explore the effect of the Cox’s interaction model of client health behavior (Cox-IMCHB) combined with Huangqi and Dangshen decoction on female pelvic floor dysfunction. 166 postpartum patients with Qi-deficiency syndrome of pelvic floor dysfunction were selected from Tongren Hospital of Wuhan University hospital and divided into two groups, Group A and Group B, each consisting of 83 cases. The allocation was done using the random number table method. Patients in Group A received routine nursing and biofeedback electrical stimulation treatment, while patients in Group B received Cox-IMCHB combined with Huangqi and Dangshen decoction based on Group A. We compared the clinical efficacy, syndrome efficacy, pelvic floor muscle strength scores, sexual life quality scores, VAS score, pelvic floor functional exercise compliance score, and the incidence of urinary incontinence and pelvic organ prolapse between the two groups. The results showed that Group B had better clinical efficacy and syndrome efficacy, as well as a higher total effective rate (clinical efficacy: 91.57% vs. 72.29%; syndrome efficacy: 95.18% vs. 74.70%). Moreover, compared to Group A, Group B had higher scores of pelvic floor muscle strength and sexual life quality, a lower proportion of mild pain (85.54% vs. 71.08%), and higher scores of pelvic floor functional exercise compliance. The scores of pelvic floor functional exercise compliance in both groups tended to increase with time, and there was an interactive effect between groups and time (intergroup effect: F = 322.900, time effect: F = 186.200, interaction effect: F = 27.410). The incidence of urinary incontinence (2.41% vs. 14.46%, ϰ2 = 6.319) and pelvic organ prolapse (3.61% vs. 16.87%, ϰ2 = 9.608) in group B was lower (all P > 0.05). The combination of Cox-IMCHB with Huangqi and Dangshen decoction can improve the pelvic function and exercise compliance of patients with pelvic floor dysfunction, relieve pain, and have significant clinical effects, which are worthy of promotion and application.

Oral bacteriome and mycobiome of patients with idiopathic membranous nephropathy with different tongue coatings treated with a Chinese herbal formula

Ethnopharmacological relevanceMoshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined. Aim of the studyIn this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome. Materials and methodsWe enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing. ResultsThe therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN. ConclusionThe regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.

Fangji Huangqi Decoction alleviates rheumatoid arthritis through regulating HIF-1α mediated the angiogenesis and the balance between autophagy and apoptosis

Ethnopharmacological relevanceFangji Huangqi Decoction (FHD) is frequently prescribed for the clinical treatment of wind-cold and wind-dampness pathogenic superficial deficiency syndrome. It also has a notable curative effect on rheumatoid arthritis (RA). Aim of the studyThe study aimed to explore the possible mechanism of FHD against RA and provided a theoretical basis for alternative therapies for RA. Materials and methodsWe used UPLC-Q-TOF-MS to analysis the ingredients and absorbed blood components of FHD. At the same time, the collagen-induced arthritis (CIA) rat model was established to estimate the therapeutic effects on FHD by considering body weight, arthritis score, paw swelling, autonomous movement ability, and synovial microvessel counts. Subsequently, immunofluorescence, immunohistochemistry, and Western blot were employed to detect the anti-angiogenic capacity of FHD in vivo, as well as the levels of apoptosis and autophagy in the synovial tissue. In addition, flow cytometry and Western blot were used to assess the effects of FHD on apoptosis and autophagy in MH7A cells. The effects of FHD on the proliferation and migration of MH7A cells were measured by CCK8 assay, cell migration and, invasion experiments. Finally, a tube formation assay was performed to evaluate the angiogenic capacity of FHD in co-cultures of MH7A cells and HUVEC cells. ResultsThrough testing of FHD's original formula, a total of 26 active ingredients have been identified, with 17 of them being absorbed into the bloodstream. FHD significantly improved the pathological symptoms and synovial hyperplasia of CIA rats. FHD could suppress the expression of HIF-1α, promote apoptosis in CIA rat synovial tissue, and suppress autophagy and angiogenesis. In vitro experiments showed that serum containing FHD inhibited the proliferation, migration, and invasion of MH7A cells, and also suppressed the expression of autophagy-related proteins while promoting apoptosis. FHD markedly repressed the expression of HIF-1α protein in TNF-α-stimulated MH7A cells and inhibited the tube formation capacity induced by MH7A cells in HUVEC cells. ConclusionsThe study had proven that FHD played an excellent anti-RA role, which may be attributed to its potential mechanism of regulating the balance between autophagy and apoptosis in RA FLS by suppressing the HIF-1α, thus contributing to its anti-angiogenic activities.

The Potential of Huangqi Decoction for Treating Diabetic Kidney Disease

ABSTRACT Diabetic kidney disease (DKD) is a prevalent complication of diabetes mellitus that primarily affects the kidney microvasculature. According to the Traditional Chinese Medicine (TCM) theory, early-stage DKD is characterized by deficiencies in essence and Qi and is often accompanied by spleen and kidney deficiencies. Huangqi decoction (HQD), a classic Chinese herbal formula with historical use in treating thirst-related ailments, is described in Shiyin Yang's Renzhai Zhizhi Fang Lun. This review aimed to investigate the potential molecular mechanisms, pharmacological effects, and key targets of HQD to establish a theoretical and scientific foundation for further research and clinical applications. The bioactive compounds and targets of HQD were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and compound-target and protein-protein interaction networks were constructed using Cytoscape and BisoGent, respectively. A total of 172 bioactive compounds were identified in HQD. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the hub targets indicated associations between diverse biological processes, cellular components, and molecular functions. These findings signify a promising avenue for the development of evidence-based treatments for DKD by leveraging the potential of TCM to enhance patient outcomes.

Evaluation of the Efficacy of Auricular Acupoint Pressure Patch Combined with Modified Huangqi Decoction in Treating Diabetic Nephropathy

Objective: To explore the efficacy of auricular acupoint pressure patch combined with modified Huangqi Decoction in treating diabetic nephropathy. Methods: 60 patients with diabetic nephropathy treated in our hospital from January 2021 to December 2022 were selected for this study. The patients were randomly divided into two groups using the random number table method, with 30 patients in each group. Among them, the control group was treated with conventional Western medicine, while the experimental group was treated with auricular acupoint pressure patches combined with modified Huangqi Decoction. The patients’ fasting blood glucose (FPG), 2-hour postprandial blood glucose (2hPG), glycated hemoglobin (HbA1c), urinary protein quantification, urea nitrogen (BUN), serum creatinine (SCr), and other indicators were detected and recorded before and after treatment. Results: Before treatment, there was no statistically significant difference in the FPG, the 2hPG, and the HbA1c between the two groups of patients (P > 0.05); after treatment, the FPG, the 2hPG, and the HbA1c of the patients in the experimental group were significantly lower than those in the control group (P < 0.05). Before treatment, there was no statistically significant difference in the urinary protein quantification, the BUN, and the SCr between the two groups of patients (P > 0.05); after treatment, the urinary protein quantification, BUN, and SCr of the patients in the experimental group were significantly lower than those in the control group (P < 0.05). The experimental group showed better improvement in symptoms such as fatigue, backache, and frequency of nocturia (P < 0.05). Conclusion: Auricular acupoint pressure patch combined with modified Huangqi Decoction effectively treats diabetic nephropathy and it helps control blood sugar and renal function indicators and improve clinical symptoms, therefore improving the patients’ quality of life.

Fangji Huangqi decoction ameliorates membranous nephropathy through the upregulation of BNIP3-mediated mitophagy

Ethnopharmacological relevanceFangji Huangqi Decoction (FJHQ), a traditional Chinese medicinal formula outlined in Zhang Zhongjing's “Jin Gui Yao Lue” during the Han Dynasty, is often used to treat conditions characterized by symptoms like edema and dysuria, including membranous nephropathy (MN). Despite its proven clinical effectiveness, the exact mechanisms through which FJHQ acts on MN remain elusive. Aim of the studyThis study aimed to investigate whether FJHQ enhances BNIP3-mediated mitophagy in podocytes by promoting BNIP3 expression and whether this improvement leads to the amelioration of MN. Materials and methodsIn this study, by establishing passive Heymann nephritis (PHN) rats, an experimental rat model of MN induced by sheep anti-rat Fx1A serum, we evaluated the effects of FJHQ in vivo. In vitro experiments were carried out by treating primary podocytes with experimental rat serum. Furthermore, the potential mechanism by which FJHQ acts through BNIP3 was further examined by transfecting primary podocytes with the siRNA of BNIP3 or the corresponding control vector. ResultsAfter 4 weeks, significant kidney damage was observed in the rats in the model group, comparatively, FJHQ markedly decreased urine volume, 24-h urinary protein, blood urea nitrogen (BUN), creatinine (Scr), and increased serum total albumin (ALB). Histology showed that FJHQ caused significant improvements in glomerular hyperplasia, and IgG immune complex deposition in MN rats. JC-1 fluorescence labelling and flow cytometry analysis showed that FJHQ could significantly increase mitochondrial membrane potential in vivo. In the mitochondria of MN model rats, FJHQ was able to down-regulate the expression of P62 and up-regulate the expression of BNIP3, LC3B, and LC3 II/LC3 I, according to Western blot and immunofluorescence studies. Furthermore, FJHQ has been shown to significantly up-regulate mitochondrial membrane potential, down-regulate P62 expression in mitochondria, and up-regulate the expression of BNIP3, LC3B, and LC3 II/LC3 I in mitochondria at the cellular level. After the administration of the autophagy inhibitor chloroquine, the serum of rats treated with FJHQ further increased the expression of LC3 II/LC3 I in primary podocytes, showing higher autophagy flow. After the interference of BNIP3 in podocytes, the effect of FJHQ on mitochondrial membrane potential and autophagy-related proteins almost disappeared. ConclusionFJHQ enhanced mitophagy in podocytes by promoting the expression of BNIP3, thereby contributing to the amelioration of MN. This work reveals the possible underlying mechanism by which FJHQ improves MN and provides a new avenue for MN treatment.

Investigation of the mechanism of huangqi and danggui decoction in treating non-small-cell lung cancer based on network pharmacology

Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases, which is a leading cause of cancer mortality worldwide. While therapies such as chemotherapy, radiation, immunotherapy and targeted drugs have shown efficacy, resistance remains a major obstacle. Traditional Chinese medicine (TCM) offers a multi-target approach that may help overcome resistance. This study analyzed the active ingredients of Huangqi and Danggui decoction (HQDGD), a classic TCM formula, and their effects on NSCLC using network pharmacology and experimental validation. Active compounds were identified from TCM databases and linked to gene targets using prediction tools and were compared to NSCLC-related genes to find shared targets. Protein-protein interaction network analysis and pathway enrichment analysis were used to find HQDGDs pharmacology and experiments on lung cancer A549 cells validated that key HQDGD compounds curcumin, quercetin and -angelicalactone inhibited proliferation and migration, suppressed JAK2/STAT3 activation, and downregulated downstream HIF1A and VEGF. The multi-target actions of HQDGD may overcome resistance in NSCLC. Our integrated computational and experimental approach elucidated the compound-target-pathway mechanisms of a TCM formula against NSCLC, supporting future drug development and research.

Protective Effects and Mechanisms of Huangqi Decoction Against Radiation-Induced Bystander Effects

Protective Effects and Mechanisms of Huangqi Decoction Against Radiation-Induced Bystander Effects

An efficient approach addressing the chemical complexity of Jiawei Fangji Huangqi decoction by integrating ultra-high-performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry and intelligent data processing workflows.

A challenge in the quality control of traditional Chinese medicine is the systematic multicomponent characterization of the compound formulae. Jiawei Fangji Huangqi, a modified form of Fangji Huangqi, is a prescription comprising seven herbal medicines. To address the chemical complexity of the Jiawei Fangji Huangqi decoction, we integrated ion mobility-quadrupole time-of-flight high-definition MSE coupled to ultra-high-performance liquid chromatography and intelligent data processing workflows available in the UNIFI software package. Good chromatographic separation was achieved on CORTECS UPLC T3 column within 52min, and high-accuracy MS2 data were acquired using high-definition MSE in the negative and positive modes. A chemical library of 1250 compounds was created and incorporated into the UNIFI software to enable automatic peak annotation of the high-definition MSE data. We identified or tentatively characterize 430 compounds in the Jiawei Fangji Huangqi decoction. The potential superiority of high-definition MSE over conventional MS data acquisition approaches was revealed in its spectral quality (MS2 ), differentiation of isomers, separation of coeluting compounds, and target mass coverage. The multiple components of the Jiawei Fangji Huangqi decoction were elucidated, offering insight into its improved pharmacological action compared with that of the Fangji Huangqi formula.

Comparison of two different integrated method of pharmacokinetics by the integrated pharmacokinetic research of fangji huangqi decoction

Traditional Chinese medicine (TCM) is characterized by its multiple components. The utilization of mathematical statistical methods to integrate the pharmacokinetics of monomer components can provide a comprehensive understanding of the holistic pharmacokinetic process of TCM. Two distinct integrated methods, namely the correlation coefficient method and the AUC-based weight coefficient method, were employed in this study to elucidate and compare their differences in the integrated pharmacokinetic research of Fangji Huangqi decoction (FHD). FHD is commonly used in clinical practice to treat the nephrotic syndrome. Firstly, one-dose FHD was given to doxorubicin-induced nephropathy (DN) rats, and the prototype compounds of FHD and their metabolites in plasma were qualitatively and semi-quantitatively analyzed by UHPLC-MS/MS. Secondly, the efficacy of FHD was quantitatively characterized by the relative distance method based on metabolomics. The correlation coefficients were obtained by analyzing the correlation between efficacy (relative distance values) and the content of compound, and they were subsequently used for the model integration (correlation coefficient method). Thirdly, the effective compounds of FHD treating DN were screened by integrating network pharmacology and molecular docking, and they were used for another integrated pharmacokinetic model by AUD-based weight coefficient method. Finally, the 2 integrated methods and the 2 integrated pharmacokinetic models were compared. In this study, 30 prototype compounds and 41 metabolites of FHD in plasma were identified, and the pharmacokinetic curve of 18 prototype compounds were built. The efficacy of FHD in the treatment of DN has been relatively quantitation. The 2 established integrated pharmacokinetic models of FHD indicated that the correlation coefficient method was the optimal approach for conducting the integrated pharmacokinetic research on the TCM with unknown effective compounds, whereas the AUC-based coefficient method was suitable for the TCM with the clear effective compounds. The integrated pharmacokinetic models indicated that FHD had high bioavailability and an absorption peak at about 6 h after administration, indicating that the 6 h after administration was the critical period of FHD treating DN. This research would be helpful for the pharmacological and pharmacokinetic research of FHD, and provide a method reference for the integrated pharmacokinetic research of TCM.

Astragaloside IV attenuates podocyte apoptosis through ameliorating mitochondrial dysfunction by up-regulated Nrf2-ARE/TFAM signaling in diabetic kidney disease.

Defective antioxidant system as well as mitochondrial dysfunction contributes to the pathogenesis and progression of diabetic kidney disease (DKD). Nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling is the central defensive mechanism against oxidative stress and therefore pharmacological activation of Nrf2 is a promising therapeutic strategy. In this study, using molecular docking we found that Astragaloside IV (AS-IV), an active ingredient from traditional formula of Huangqi decoction (HQD), exerted a higher potential to promote Nrf2 escape from Keap1-Nrf2 interaction via competitively bind to amino acid sites in Keap1. When podocyte exposed to high glucose (HG) stimulation, mitochondrial morphological alterations and podocyte apoptosis were presented and accompanied by Nrf2 and mitochondrial transcription factor A (TFAM) downregulation. Mechanistically, HG promoted a decrease in mitochondria-specific electron transport chain (ETC) complexes, ATP synthesis and mtDNA content as well as increased ROS production. Conversely, all these mitochondrial defects were dramatically alleviated by AS-IV, but suppression of Nrf2 with inhibitor or siRNA and TFAM siRNA simultaneously alleviated the AS-IV efficacy. Moreover, experimental diabetic mice exhibited significant renal injury as well as mitochondrial disorder, corresponding with the decreased expression of Nrf2 and TFAM. On the contrary, AS-IV reversed the abnormality and the Nrf2 and TFAM expression were also restored. Taken together, the present findings demonstrate the improvement of AS-IV on mitochondrial function, thereby resistance to oxidative stress-induced diabetic kidney injury and podocyte apoptosis, and the process is closely associated with activation of Nrf2-ARE/TFAM signaling.

Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway

PurposeThis study aims to investigate the mechanism underlying the beneficial effects of Huangqi decoction (HQD) on Diabetic kidney disease (DKD) in diabetic db/db mice.MethodsEight-week-old male diabetic db/db mice were randomly divided into four groups: Model (1% CMC), HQD-L (0.12 g/kg), HQD-M (0.36 g/kg), and HQD-H (1.08 g/kg) groups. Non-diabetic db/m mice were served as the control group. These mice received HQD treatment for 8 weeks. After treatment, the kidney function, histopathology, micro-assay, and protein expression levels were assessed.ResultsHQD treatment improved the albumin/creatine ratio (ACR) and 24 h urinary albumin excretion, prevented the pathological phenotypes of increased glomerular volume, widened mesangial areas, the of mesangial matrix proliferation, foot process effacement, decreased nephrin expression and reduced number of podocytes. Expression profiling analysis revealed global transcriptional changes that predicted related functions, diseases and pathways. HQD treatment activated protein expressions of BMP2, BMP7, BMPR2, and active-Rap1, while inhibiting Smad1 and phospho-ERK. In addition, HQD was associated with improvements in lipid deposition in the kidneys of db/db mice.ConclusionHQD ameliorated the progression of DKD in db/db mice by regulating BMP transcription and downstream targets, inhibiting the phosphorylation of ERK and the expression of Smad1, promoting Rap1 binding to GTP, and regulating the lipid metabolism. These findings provide a potential therapeutic approach for treating DKD.

Astragalus polysaccharide alleviates alcoholic-induced hepatic fibrosis by inhibiting polymerase I and transcript release factor and the TLR4/JNK/NF-κB/MyD88 pathway

Ethnopharmacological relevanceAstragali Radix (AR), the root of Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, known as Huangqi in traditional Chinese medicine, has been widely used in traditional Chinese medicine prescriptions for acute and chronic liver injury. AR was the most important medicine in a Chinese traditional prescription called Huangqi Decoction (HQD), has been used to treat chronic liver diseases since the 11th century. In particular, its major active ingredient, Astragalus polysaccharide (APS), has demonstrated promising effects on inhibiting hepatic fibrosis. However, to date, the effect of APS against alcohol-induced hepatic fibrosis and its underlying molecular mechanisms remains unknown. Aims of the studyThis study aimed to explore the effect and potential molecular mechanisms of APS against alcohol-induced hepatic fibrosis by using network pharmacology and experimental validation. Materials and methodsThe potential targets and underling mechanism of AR in alcoholic liver fibrosis were first predicted using network pharmacology, followed by experimental validation using SD rat model with alcohol-induced hepatic fibrosis. Further, the predicted candidate signaling pathways and potential target polymerase I and transcript release factor (PTRF) were combined to explore the multifaceted mechanism of APS against alcohol-induced hepatic fibrosis. Finally, overexpression of PTRF was explored to reveal the role of PTRF in the mechanism of APS against alcohol-induced hepatic fibrosis. ResultAPS exerted potent anti-hepatic fibrosis effects by downregulating genes involved in the Toll-like receptor 4 (TLR4)/JNK/NF-κB/MyD88 pathway. Notably, APS treatment ameliorated the hepatic damage by inhibiting the overexpression of PTRF and decreasing the co-localisation of TLR4/PTRF. Overexpression of PTRF induced reversal of the protective effects of APS on alcohol-induced hepatic fibrosis. ConclusionThis study indicated that APS may alleviate alcohol-induced hepatic fibrosis by inhibiting the activation of PTRF and TLR4/JNK/NF-κB/MyD88 pathway, which provides a scientific elucidation for the mechanisms of APS on the anti-hepatic fibrosis activity and presents a promising therapeutic approach for treating hepatic fibrosis.