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CHEMISTRY & BIODIVERSITY · 2021 ·Vol. 18 ·期 10 ·e2100388 · IF 2.408

Two New Alkaloids from Fuzi and Their Metabolites Study

Sisi Liu,Pei Deng,Yihong Long,Shushu Yang,Junshuo Zhu,Kunsheng Li,Changjiangsheng Lai,Weiran Yang,Jinlong Chen

Former study suggests alkaloids from herbs of Aconitum genus plants possess excellent bioactivities, which exert great value for related deeper chemical constituent investigation. Herein, chemical isolation was performed and four alkaloids were isolated from Fuzi , of which two were new ones, and the other two were reported NMR data for the first time. Their chemical structures were identified by NMR data, high resolution MS, UV and IR analysis. Additionally, the MS fragmentation patterns were explored, formerly, that of hetisane alkaloid was rarely reported, and fragmentation mechanism of the diagnostic ion was proposed. Based on these fragment pathway, metabolites and metabolic pathways of four compounds were investigated in rat liver microsomes using UPLC−Q/TOF−MS, and dehydrogenation product was firstly found from metabolites of hetisane alkaloid. Graphical

研究领域: 药理学 · 天然产物化学
✓ 已验证 DOI 高影响因子
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JOURNAL OF PHARMACY AND PHARMACOLOGY · 2021 ·Vol. 73 ·期 4 ·535-544 · IF 3.765

Pharmacokinetics-based chronoefficacy of Fuzi against chronic kidney disease

Yang Zemin,Lin Yanke,Su Chong,Wang Shuai,Gao Lu,Lin Jingpan,Wang Zhigang,Wu Baojian

ObjectivesIdentifying drugs with time-varying efficacy or toxicity, and understanding the underlying mechanisms would help to improve treatment efficacy and reduce adverse effects. In this study, we uncovered that the therapeutic effect of Fuzi (the lateral root of Aconitum carmichaelii Debeaux) depended on the dosing time in mice with adenine-induced chronic kidney disease (CKD).MethodsThe Fuzi efficacy was determined by biomarker measurements [i.e. plasma creatinine (CRE), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG)], as well as inflammation, fibrosis and histological analyses. Circadian regulation of Fuzi pharmacokinetics and efficacy was evaluated using brain and muscle Arnt-like protein-1 (Bmal1)-deficient (Bmal1−/−) mice.Key findingsThe Fuzi efficacy was higher when the drug was dosed at ZT10 and was lower when the drug was dosed at other times (ZT2, ZT6, ZT14, ZT18 and ZT22) according to measurements of plasma CRE, BUN and urinary NAG. Consistently, ZT10 (5 PM) dosing showed a stronger protective effect on the kidney (i.e. less extensive tubular injury) as compared to ZT22 (5 AM) dosing. This was supported by lower levels of inflammatory and fibrotic factors (IL-1β, IL-6, Tnf-α, Ccl2, Tgfb1 and Col1a1) at ZT10 than at ZT22. Pharmacokinetic analyses showed that the area under the curve (AUC) values (reflective of systemic exposure) and renal distribution of aconitine, hypaconitine and mesaconitine (three putative active constituents) for Fuzi dosing at ZT10 were significantly higher than those for herb dosing at ZT22, suggesting a role of circadian pharmacokinetics in Fuzi chronoefficacy. Drug efficacy studies confirmed that aconitine, hypaconitine and mesaconitine possessed a kidney-protecting effect. In addition, genetic knockout of Bmal1 in mice abolished the time-dependency of Fuzi pharmacokinetics and efficacy. This reinforced the existence of chronoefficacy for Fuzi and supported the role of circadian pharmacokinetics in Fuzi chronoefficacy.ConclusionsThe efficacy of Fuzi against CKD depends on the dosing time in mice, which is associated with circadian pharmacokinetics of the three main active constituents (i.e. aconitine, hypaconitine and mesaconitine). These findings highlight the relevance of dosing time in the therapeutic outcomes of herbal medicines.

CAS / MDL: 9004-32-4
研究领域: 药理学 · 生物钟学 · 中医 · 肾病
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2022 · IF 5.988

Compatibility of Fuzi and Ginseng Significantly Increase the Exposure of Aconitines

Chen Ze-Yan,Wei Xu-Ya,Qiu Zi-Dong,Huang Yun,Tan Ting,Feng Yu-Lin,Guo Juan,Cui Guang-Hong,Huang Lu-Qi,Lai Chang-Jiang-Sheng

The herb-pair ginseng-Fuzi (the root of Aconitum carmichaelii) is the material basis of Shenfu prescriptions and is popular in traditional Chinese medicine for the treatment of heart failure, and even shock with severe-stage of COVID-19. A narrow therapeutic window of Fuzi may cause significant regional loss of property and life in clinics. Therefore, systemic elucidation of active components is crucial to improve the safety dose window of Shenfu oral prescriptions. A high performance liquid chromatography-mass spectrometry method was developed for quantification of 10 aconitines in SD rat plasma within 9 min. The limit of detection and the limit of quantification were below 0.032 ng/ml and 0.095 ng/ml, respectively. Furthermore, a systemic comparison with their pharmacokinetic characteristics after oral administration of a safe dosage of 2 g/kg of Fuzi and ginseng-Fuzi decoction for 24 h was conducted. Eight representative diester, monoester, and non-ester aconitines and two new active components (i.e., songorine and indaconitine) were all adopted to elucidating the differences of the pharmacokinetic parameters in vivo. The compatibility of Fuzi and ginseng could significantly increase the in vivo exposure of active components. The terminal elimination half-life and the area under the concentration-time curve of mesaconitine, benzoylaconitine, benzoylmesaconitine, benzoylhypaconitine, and songorine were all increased significantly. The hypaconitine, benzoylmesaconitine, and songorine were regarded as the main active components in vivo, which gave an effective clue for the development of new Shenfu oral prescriptions.

研究领域: 中药学 · 药理学 · 分析化学
✓ 已验证 DOI 高影响因子
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Heliyon · 2023 · IF 4

Fuzi polysaccharides improve immunity in immunosuppressed mouse models by regulating gut microbiota composition

Ran Tu,Cheng Zhou,Wenfeng Huang,Zhengping Feng,Qiufang Zhao,Xiaofei Shi,Langjun Cui,Keke Chen

Rationale and objectives Fuzi, the dried root of Aconitum carmichaelii Debx, is one of the widely used traditional Chinese medicines. Fuzi polysaccharides are considered the most bioactive compounds with immunomodulatory functions, however, the mechanisms have not been evaluated. This study aims to systematically investigate the effects of Fuzi polysaccharides on the gut microbiota and immune function using a mouse model immunosuppressed with cyclophosphamide. Methods The short-chain fatty acid levels in cecal contents were measured by gas chromatography-mass spectrometry. The gut microbiota 16S rRNA gene were sequenced by next generation sequencing. The mRNA expression levels of NF-κB, IL-6, TNF-α, iNOS and COX-2 were measured using quantitative real-time polymerase chain reaction. The protein expression of occludin and zonula occludens-1 were analyzed by Western blot. The white blood cells were counted using automated hematology analyzer, and CD4 + FOXP3 + /CD4 + ratio was measured by flow cytometry. Results and Conclusions Fuzi polysaccharides had the function of elevating the concentration of acetic acid, propionic acid, isobutyric acid, and n-butyric acid in the cecum. Meanwhile, Fuzi polysaccharides could decrease the relative abundance of Helicobacter , Anaerotruncus , Faecalibacterium , Lachnospira , Erysipelotrichaceae _UCG-003, Mucispirillum , and Mycoplasma , and increase the relative abundance of Rhodospirillales , Ruminococcaceae _UCG-013, Mollicutes _RF39, Ruminococcus _1, Christensenellaceae _R-7_group, and Muribaculaceae in the gut. Furthermore, Fuzi polysaccharides exhibited the function of increasing spleen and thymus indices and number of white blood cells and lymphocytes. Fuzi polysaccharides could reverse the decreased mRNA expression of NF-кB, IL-6, and iNOS, differentiation of CD4 + FOXP3 + regulatory T cells as well as protein expression of occludin and zonula occludens-1 induced by cyclophosphamide. In addition, the mRNA and protein expression of cytokines were significantly correlated with the abundance of gut microbiota under Fuzi polysaccharides treatment. Collectively, the above results demonstrated that Fuzi polysaccharides could regulate inflammatory cytokines and gut microbiota composition of immunosuppressive mice to improve immunity, thereby shedding light on revealing the molecular mechanism of polysaccharides of traditional Chinese medicines in the future.

研究领域: 免疫学 · 微生物学 · 药理学 · 中药学
✓ 已验证 DOI PubMed 高影响因子
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Endocrine Metabolic & Immune Disorders-Drug Targets · 2026 ·Vol. 26 ·期 1 ·E18715303465130 · IF 2

Modified Fuzi Lizhong Decoction Alleviates Colonic Lesions and Modulates Gut Microbiota in Diabetic Gastroparesis

Xiaoxia An,Jinxiu Lan,Yongxiang Xie,Jiwu Li,Yan Wang,Lingmin Wu,Cui Liang,Shijuan Liu,Guangnuo Liu,Zhiqian Jiang,Zhengang Wang

Introduction Diabetic gastroparesis (DGP) is a debilitating complication of diabetes mellitus. This study investigated the therapeutic effects of Modified Fuzi Lizhong decoction (MFZLZD) on DGP. Methods A DGP rat model was established through a high-fat diet combined with an irregular feeding schedule. Rats were treated with MFZLZD (5 or 20 g/kg) or mosapride (positive control; 1 mL/100 g) for 7 weeks. Body weight and gastric parameters (gastric emptying, peristalsis, and blood flow) were assessed. Histopathological alterations in gastric and colonic tissues were evaluated via HE staining, while goblet cell density was quantified by AB-PAS staining. The expression of tight junction proteins was analyzed using immunofluorescence. Finally, 16S rRNA sequencing of fecal samples was performed to characterize alterations in the gut microbiota. Results MFZLZD significantly increased body weight and effectively restored gastric function in DGP rats. Moreover, MFZLZD treatment attenuated gastric and colonic mucosal injury, preserved goblet cell populations, and upregulated tight junction protein expression. Gut microbiota diversity was altered in DGP rats and was partially restored following MFZLZD treatment. Changes in 33 key microbial taxa were observed between groups. Discussion MFZLZD improved gastric function and reinforced intestinal barrier integrity in DGP rats. The observed changes in gut microbiota composition suggest a potential association between alterations in the gut microbiota and the therapeutic effects of MFZLZD, although the underlying mechanisms remain unclear and require further investigation. Conclusion MFZLZD represents a promising therapeutic strategy for DGP and is associated with improvements in intestinal barrier integrity, gastric function, and gut microbiota composition.

✓ 已验证 DOI 高影响因子
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PHYTOMEDICINE · 2023 · IF 7.9

Modulation of cellular metabolism and alleviation of bacterial dysbiosis by Aconiti Lateralis Radix Praeparata in non-small cell lung cancer treatment

Wen Zhang,Menglei Ding,Yaru Feng,Shuhui Cai,Zichen Luo,Jinjun Shan,Liuqing Di

ABSTRACT Background Non-small cell lung cancer (NSCLC) is a highly prevalent and fatal form of lung cancer. In China, Aconiti Lateralis Radix Praeparata ( Fuzi in Chinese), derived from the lateral root of Aconitum carmichaeli Debx. (Ranunculaceae, Aconitum ), is extensively prescribed to treat cancer in traditional medicine and clinical practice. However, the precise mechanism by which Fuzi treats NSCLC remains unknown. Purpose This article aims to assess the efficacy of Fuzi against NSCLC and elucidate its underlying mechanism. Methods Marker ingredients of Fuzi decoction were quantified using UPLC-TSQ-MS. The effectiveness of Fuzi on NSCLC was evaluated using a xenograft mouse model. Subsequently, a comprehensive approach involving network pharmacology, serum metabolomics, and 16S rDNA sequencing was employed to investigate the anti-NSCLC mechanism of Fuzi . Results Pharmacological evaluation revealed significant tumour growth inhibition by Fuzi , accompanied by minimal toxicity. Network pharmacology identified 29 active Fuzi compounds influencing HIF-1, PI3K/Akt signaling, and central carbon metabolism in NSCLC. Integrating untargeted serum metabolomics highlighted 30 differential metabolites enriched in aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and the tricarboxylic acid (TCA) cycle. Targeted serum metabolomics confirmed elevated glucose content and reduced levels of pyruvate, lactate, citrate, α-ketoglutarate, succinate, fumarate, and malate following Fuzi administration. Furthermore, 16S rDNA sequencing assay showed that Fuzi ameliorated the dysbiosis after tumorigenesis, decreased the abundance of Proteobacteria, and increased that of Firmicutes and Bacteriodetes. PICRUSt analysis revealed that Fuzi modulated the pentose phosphate pathway of the gut microbiota. Spearman correlation showed that Proteobacteria and Escherichia_Shigella accelerated the TCA cycle, whereas Bacteroidota , Bacteroides, and Lachnospiraceae_NK4A136_group suppressed the TCA cycle. Conclusions This study firstly introduces a novel NSCLC mechanism involving Fuzi , encompassing energy metabolism and intestinal flora. It clarifies the pivotal role of the gut microbiota in treating NSCLC and modulating the TCA cycle. Moreover, these findings offer valuable insights for clinical practices and future research of Fuzi against NSCLC.

CAS / MDL: 14913-33-8
研究领域: 肿瘤学 · 药理学 · 代谢组学 · 微生物组研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Mahuang Fuzi Xixin decoction alleviates allergic rhinitis by inhibiting NLRP3/Caspase-1/GSDMD-N-mediated pyroptosis

Mengze Ding,Xiaohan Wei,Changshun Liu,Xiaomei Tan

Ethnopharmacological relevance Allergic rhinitis (AR) is a prevalent nasal inflammatory disorder, and pyroptosis plays a crucial role in aggravating AR. Current medications for AR treatment still have deficiencies, and finding new agents is of great interest. Mahuang Fuzi Xixin decoction (MFXD), an ancient Chinese medicine, is now commonly used to treat AR, which has anti-inflammatory and immunomodulatory effects, but its underlying mechanism is unknown. Aim of this study This study aims to evaluate the effects of MFXD on AR and explore its potential mechanisms in view of the regulatory effect on pyroptosis. Methods MFXD, Mahuang, Fuzi, and Xixin water extracts were analyzed using ultra high performance liquid chromatography-Orbitrap-high-resolution accurate mass spectrometry. In in vivo study, the effects of MFXD on AR treatment were evaluated in an ovalbumin-induced mouse model. Mice were administered saline (control and model groups), MFXD (1.375, 2.75 g/kg), and dexamethasone (2.5 mg/kg) for 13 days. AR symptoms were evaluated by blinded observers. Immunoglobulin E (IgE) and histamine levels were measured using enzyme-linked immunosorbent assays. Expression of pyroptosis-related proteins (NLRP3, ASC, Caspase-1 p10/p20, GSDMD-N and IL-1β) in AR mouse nasal mucosa were estimated by immunohistochemistry. In in vivtro study, the effects of MFXD on pyroptosis were assessed in human nasal epithelial cells (HNEpCs) stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP), and incubated with MFXD (12.5, 25, and 50 μg/mL). Pyroptosis-related protein expression was measured by western blotting. Results Thirty-three compounds in MFXD were identified, including ephedrine, pseudoephedrine, higenamine, aconine, aconitine, benzoylmesaconitine, benzoylhypaconine and hypaconitine. In the in vivo study, oral taken of MFXD/dexamethasone significantly ameliorated AR symptoms, reduced swelling of the nasal mucosa, and decreased the levels of IgE and histamine in AR mice serum. MFXD/dexamethasone attenuated histopathological changes and reduced the expression of pyroptosis-related proteins in nasal mucosa, indicating the inhibitory effect on nasal epithelial pyroptosis. In the in vitro study, MFXD (50 μg/mL) significantly alleviated cytotoxicity, protected cells from swelling and rupture, and downregulated the expression of pyroptosis-related proteins in LPS/ATP-induced HNEpCs. Conclusion MFXD suppressed nasal epithelial pyroptosis by inhibiting the NLRP3/Caspase-1/GSDMD-N signaling pathway, which alleviates AR. Our results offer valuable insights into potential AR therapies and provide evidence for the clinical utilization of MFXD to treat AR.

CAS / MDL: 50-02-2
研究领域: 药理学 · 免疫学 · 民族药理学 · 炎症 · 中医
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Chemistry · 2025 · IF 4.2

Deciphering structure-composition-efficacy transformation in processed Fuzi: an integrated SEM, XRD, metabolomics, and pharmacodynamics approach

Yang Yang,Xuemei Wei,Shuya Zhang,Yun Li,Jiazhen Wu,Suhua Cai,Biren Wang,Zhiming Yang,E. Yang,Junling Cao,Qinhua Chen,Guihong Chen

Background: Aconiti Lateralis Radix Praeparata (Fuzi), a vital yet toxic herbal medicine, faces significant challenges in standardization due to varied processing methods that undermine detoxification efficacy and hinder therapeutic optimization.Methods: An integrative analytical approach combining scanning electron microscopy (SEM), X-ray diffraction (XRD), metabolomics, and pharmacodynamic evaluation was employed to investigate the structural, compositional, and functional transformations during Fuzi processing.Results: SEM imaging and XRD data revealed that the morphological breakdown of starch granules varied according to processing technique. Metabolomics analysis based on mass spectrum identified 57 diterpenoid alkaloids, including 12 bioactive components, whose levels fluctuated across nine processing variants. Pharmacodynamic profiling revealed distinct efficacy-safety trade-offs across these variants, underscoring the pivotal role of processing methods in determining clinical risk profiles and therapeutic indices.Conclusion: This study elucidated the structure-composition-efficacy correlations in Fuzi processing, highlighting the relationship between starch reorganization, alkaloid modification, and therapeutic outcomes. These insights offer a mechanistic basis for refining traditional processing protocols, optimizing detoxification and therapeutic retention, and advancing standardization in herbal medicine.

CAS / MDL: 64-18-6 34819-78-8
研究领域: 中药炮制学 · 天然药物化学 · 代谢组学 · 药效动力学 · 晶体学 · 植物药标准化 · 药物安全性评价
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2025 · IF 5.4

CYP3A4 and MRP2 are predominant metabolic regulators attribute to the toxicity/efficacy of aconitine derived from Fuzi

Jingjing Yao,Yajuan Guo,Ting Wan,Shaofang Yu,Qinghong Shen,Min Huang,Yu Li,Fuping Xu,Huiyan Zeng,Zhongqiu Liu,Linlin Lu

Ethnopharmacological relevance Aconitum carmichaelii Debx. exhibits overwhelming efficacy against heart failure, inflammation and pain, but its clinical application is limited by concomitant cardiotoxicity and neurotoxicity. Aconitine (AC), the most abundant bioactive alkaloid, has narrow therapeutic window, with well-defined toxic and therapeutic thresholds. However, the overlapping molecular targets mediating dual toxicity and efficacy of AC remain poorly characterized. Aims of the study This study aimed to evaluate dual pharmacological and toxicological roles of AC through integrative pharmacology and transgenic mouse models. Materials and methods The overlapping targets of AC-related toxicity/efficacy were identified based on integrative pharmacology. By generating Cyp3a −/− transgenic mice expressing human CYP3A4 (hCYP3A4), Ugt1, P-gp, Mrp2, BCRP, and Nrf2 knockout mice, the effects of AC on toxicity, pain, inflammation, and heart failure were assessed. Results We identified 143 overlapping targets predominantly enriched in metabolic pathways. Symptom-based toxicity scores were strikingly elevated in AC-exposed hCYP3A4, Mrp2 −/− , P-gp −/− , BCRP −/− , and Nrf2 −/− mice compared to WT mice. Additionally, AC prolonged the latency of response by approximately 18s, 15s, 14s, and 5s, respectively, in hCYP3A4, Mrp2 −/− , P-gp −/− , and Nrf2 −/− mice by hot plate assay. Interestingly, both toxicity score and analgesic latency initially increased and subsequently decreased, peaking at 60 min. AC obviously decreased the acetic acid-induced writhing and permeability by 45.7% and 22.2% in hCYP3A4 mice, whereas these changes were amplified in Mrp2 −/− mice compared to WT mice. Furthermore, AC attenuated DOX induced heart failure in hCYP3A4 mice, with an effective rate of 20.9%, with Septin4 implicated in AC-related metabolism. Conclusions Metabolic targets may elucidate the mechanistic overlap between the toxicity and efficacy of AC. Notably, hCYP3A4 exhibited heightened toxicity, alongside enhanced analgesic, anti-inflammatory, and cardioprotective effects. Our findings position metabolic pathways as critical nodes for AC-related dual effect, and establish Septin4 as a candidate mediator of its metabolic regulation.

CAS / MDL: 64-19-7 1330-20-7
研究领域: 药理学 · 毒理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Aging Neuroscience · 2025 · IF 4.5

Exploring the Mahuang Fuzi Xixin Decoction’s mechanism for treating Alzheimer’s disease using molecular docking and network pharmacology

Che Chen,Qianfeng Shao,Sheng Zhou

Objective Explore the potential mechanism of Mahuang Fuzi Xixin Decoction (MFXD) in the treatment of Alzheimer’s disease (AD) using network pharmacology, molecular docking approaches, and test its efficacy by in vitro experiments. Methods Active components of MFXD were screened from TCMSP, BATMAN-TCM, and TCMID, with corresponding targets obtained from SwissTargetPrediction and TCMSP. AD-related differential genes were retrieved from GEO. Intersection targets were identified via Venn diagrams, followed by GO/KEGG enrichment analyses, PPI network construction, and molecular docking. In vitro validation experiments were carried out using PC12 cells induced by Aβ 25–35 to simulate the pathological state of AD. For the detection of cell viability, the CCK-8 assay was employed to evaluate the protective effect of MFXD and its active components on damaged PC12 cells. Western blot analysis was used to determine the protein expression levels of key molecules involved in AD-related signaling pathways, including phosphorylated p-NF-κB p65, NF-κB p65, p-GSK-3β, GSK-3β, MMP-9, p-Tau, and Tau. Additionally, the ELISA was utilized to measure the secretion level of TNF-α in the supernatant of Aβ 25–35 -induced PC12 cells, so as to assess the anti-inflammatory effect of MFXD. Results Thirty-seven active components and 230 targets of MFXD were identified, along with 4913 AD-related differentially expressed genes from GEO dataset GSE122063 , yielding 47 intersection targets. GO annotation enriched these targets in processes like reactive oxygen species metabolism, components like extracellular matrix, and functions like neurotransmitter binding; several pathways were enriched in the KEGG analysis, such as TNF signaling pathway, calcium signaling pathway, and NF-κB signaling pathway. The intersection target PPI network identified MMP9, EGFR, FOS as core targets. Molecular docking results indicated that quercetin binds to the three core targets (MMP9, EGFR, FOS), while luteolin binds preferentially to EGFR and MMP9. In vitro , Aβ 25–35 -induced PC12 cells treated with quercetin/luteolin had concentration-dependent viability increases (all P < 0.001); 15% MFXD-containing serum restored viability to ≥ 95% (P < 0.001 vs. AD model, comparable to DHCL). Western blot showed AD model had elevated p-NF-κB p65/NF-κB p65, MMP9/β-actin, p-Tau/Tau and reduced p-GSK-3β/GSK-3β (all P < 0.05); MFXD reversed these (all P < 0.05), while DHCL only inhibited p-NF-κB p65/NF-κB p65. ELISA showed MFXD and DHCL both reduced AD model’s TNF-α (all P < 0.001). Conclusion MFXD potentially exerts anti-AD effects through a multi-component, multi-target, multi-pathway approach. Its key active components (quercetin, luteolin) may act by modulating the core target MMP9. Also, MFXD can simultaneously regulate several pathways, such as the TNF signaling pathway, Calcium signaling pathway, and NF-κB signaling pathway, and target Tau protein-related pathology by restoring the phosphorylation level of GSK-3β to suppress abnormal hyperphosphorylation of Tau, and thereby alleviating pathological damage in AD.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2022 · IF 5.195

Untargeted metabolomics reveals the combination effects and mechanisms of Huangqi-fuzi herb-pair against doxorubicin-induced cardiotoxicity

Zhen Xue,Lingxin Zhuo,Bowen Zhang,Lingmeng Zhu,Xinran Xiang,Chunxia Zhang,Wenyuan Liu,Guangguo Tan,Wenting Liao

Ethnopharmacological relevance Qifu decoction (QFD) is a famous traditional Chinese medicine (TCM) composed of Astragali Radix (HuangQi) and Aconiti Lateralis Radix Praeparaia (Fuzi), which can alleviate doxorubicin (DOX)-induced cardiotoxicity (DIC). However, its protective mechanism remains obscured. Aim of the study The present study aimed to uncover the cardioprotective mechanism and the synergistic effect of QFD against DIC in mice. Materials and methods The cardioprotective activity of QFD against DIC was assessed by electrocardiogram, serum biochemical assays and histopathology. Mass spectrometry-based metabolomic approach was conducted to elucidate the preventive mechanisms of QFD, HuangQi decoction (HQD), and Fuzi decoction (FZD) against DIC. QFD, HQD, FZD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of QFD by computational systems analysis. Quantitative real-time PCR (qRT-PCR) was further employed to validate the key metabolic pathways at the level of the gene. Results The electrocardiogram combined with the biochemical analysis and histopathology showed that the protection effects were sorted as QFD > HQD ≈ FZD. A total of 41 metabolites contributing to DIC were identified in the mice serum, among which 32, 12 and 10 metabolites were significantly reverted by QFD, HQD and FZD, respectively. Metabolic pathway analysis revealed that DOX perturbed 12 metabolic pathways, and QFD, HQD, and FZD-treated groups could significantly reverse 12, 7 and 6 metabolic pathways of these 12 metabolic pathways. Metabolic pathway and qRT-PCR revealed that QFD could protect DIC mainly by regulating energy metabolism, amino acids metabolism, arachidonic acid metabolism and glycerophospholipid metabolism, and HQD and FZD mutually reinforced each other. Conclusion These evidences revealed that QFD was a promising drug candidate for DIC by maintaining metabolic homeostasis. Meanwhile, this work provided a useful approach for evaluating the efficacy and the synergistic effects of TCMs against cardiomyopathy .

CAS / MDL: 103616-89-3
研究领域: 药理学 · 中药学 · 代谢组学 · 心脏病学 · 系统生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2021 · IF 4.36

Metabolomics of Spleen-Yang deficiency syndrome and the therapeutic effect of Fuzi Lizhong pill on regulating endogenous metabolism

Zhen Zhang,Shasha Yang,Xia Lin,You Huang,Xinyi Wei,Jinwei Zhou,Rui Li,Bin Deng,Chaomei Fu

Ethnopharmacological relevance Spleen-Yang deficiency (SYD) is one of the primary causes of many digestive diseases , such as ulcerative colitis (UC), and irritable bowel syndrome (IBS), but its endogenous metabolic characteristics are still unclear. Fuzi Lizhong pill (FLZP) is well-known for its powerful capacity for treating SYD; however, its mechanisms require further study. Aim of the study Herein, our present study aimed to investigate the essence of SYD from the perspective of metabolomics, and tried to reveal the anti-SYD action mechanisms of FLZP. Materials and methods Firstly, the compound factor modeling method with the principle of “indiscipline in diet + excessive fatigue + intragastric administration of Senna water extracts” was used to establish Sprague Dawley (SD) rats as SYD model. Then, the visceral index, motilin (MTL), malonaldehyde (MDA), Interleukin 1 alpha (IL-1α), and Interleukin 6 (IL-6) levels were used to verify the anti-SYD effect of FLZP. In addition, serum samples were analyzed by UPLC-QE/MS metabolomics technique. Finally, the metabolic pathways associated with specific biomarkers were analyzed to research the possible mechanism underlying the action of FLZP. Results The expression of MTL, MDA, IL-1α, and IL-6 were regulated by FLZP, which suggested that it has relieved diarrhea and gastrointestinal motility disorder caused by SYD and had an anti-peroxidation, anti-inflammatory, and immune regulation effect. A total of 75 metabolites were found to be the potential biomarkers of SYD. Moreover, FLZP regulates 21 metabolites and 10 vital pathways including the tricarboxylic acid (TCA) cycle, sphingolipid metabolism, and histidine metabolism. Conclusion SYD primarily causes disorders of amino acid metabolism, lipid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, nucleotide metabolism, and translation. In addition, FLZP regulated carbohydrate, lipid, and amino acid metabolisms, gastrointestinal motility, digestive juice secretion, immune regulation, as well as antioxidant effects. Hence, FLZP had a good therapeutic effect on treatment of SYD. It might be a promising therapeutic agent for the treatment of SYD-related diseases.

CAS / MDL: 14091-11-3
研究领域: 民族药理学 · 药理学 · 代谢组学 · 中医
✓ 已验证 产品关联 DOI PubMed 高影响因子
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