BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Lei Qian,Hu Xu,Ruqiang Yuan,Weijing Yun,Yufang Ma
Formononetin, an isoflavone compound, has been extensively researched due to its various biological activities, including a potent protective effect on the cardiovascular system. However, the impact of formononetin on cardiac fibrosis has not been investigated. In this study, C57BL/6 mice were used to establish cardiac fibrosis animal models by subcutaneous injecting of isoproterenol (ISO) and formononetin was orally administrated. The results showed that formononetin reversed ISO-induced heart stiffness revealed by early-to-atrial wave ratio (E/A ratio). Masson staining, western blot, immunohistochemistry and real-time PCR exhibited that the cardiac fibrosis and fibrosis-related proteins (collage III, fibronectin, TGF-β1, α-SMA, and vimentin) and genes ( Col1a1 , Col3a1 , Acta2 and Tgfb1 ) induced by ISO were significantly suppressed by formononetin. Furthermore, by combining metabolomics and network pharmacology, we found three important targets ( ALDH2 , HADH , and MAOB ), which are associated with mitochondrial function, were involved in the beneficial effect of formononetin. Further validation revealed that these three genes were more abundance in cardiomyocyte than in cardiac fibroblast. The mRNA expression of ALDH2 and HADH were decreased, while MOAB was increased in cardiomyocyte upon ISO treatment and these phenomena were reversed by formononetin. In addition, we investigated mitochondrial membrane potential and ROS production in cardiomyocytes, the results showed that formononetin effectively improved mitochondrial dysfunction induced by ISO. In summary, we demonstrated that formononetin via regulating the expressions of ALDH2 , HADH, and MAOB in cardiomyocyte to improve mitochondrial dysfunction and alleviate β-adrenergic activation cardiac fibrosis.
研究领域:
药理学
·
心脏病学
·
分子生物学
·
细胞生物学
·
代谢组学
·
网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
·
2025
·
IF 3.8
Yang Lingyan,He Shan,Tang Chen,Shi Lei,Liu Zhenhua,Tian Zejie,Li Hui,He Xufeng,Liao Jiding,Liu Yunmei
Photodynamic therapy (PDT) has received much attention in cancer treatment because of its low toxicity and side effects. In this study, we successfully synthesized 14 novel porphyrin-formononetin derivatives. In reactive oxygen species detection experiments, the target compounds 4a–6d caused a significant decrease in the fluorescence intensity of DPBF compared with the porphyrin parent and formononetin feedstock after illumination, and it was found that the target compound had a higher ROS quantum yield, among which the quantum yield of compound 6c was higher. In the in vitro anti-tumor activity assay, the target compounds 4a–6d exhibited a certain degree of growth inhibition against six cancer cells (A549, MDA-MB-231, HCT-116, HGC-27, DU145, and TCCSUP) under light conditions, whereas the cytotoxicity of the target compounds against the normal cells H9c2 was less. The results of the scratch assay showed that 6c could inhibit the growth of tumor cells by inhibiting the migration of DU145 cells. The experimental results indicate that the target compounds achieve the synergistic effect of PDT and chemotherapy. Graphical abstract
研究领域:
药理学
·
肿瘤学
·
有机化学
✓ 已验证
DOI
PubMed
高影响因子
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
·
2025
·Vol. 51
·期 5
·2152-2169
·
IF 1.7
Luo Zeping,Pan Liwei
Objective: With the molecular formula C 16 H 12 O 4 , formononetin (FMN) is an appealing synthon exhibiting a wide range of biological activities, including antioxidant, anti-infective, and anti-apoptotic effects. Due to increasing interest in the mechanisms of action of antioxidants, our group aimed to identify the cellular target sites of these compounds. Methods: Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM), TdT-mediated dUTP nick end labeling (TUNEL) staining, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot were used to analyze the effects of oxidative stress on PC12 cell survival, antioxidant enzyme activity, mitochondrial morphology, apoptosis, key intracellular proteins, and signaling pathways. The potential roles of candidate targets were further investigated using proteomics, molecular docking, kinetic simulation, and cellular thermal shift assay (CETSA). Results and Discussion: One of the compounds, ( VI ) (5-(8-(((1-(benzyloxy)-3-hydroxy-1-oxopropan-2-yl)amino)methyl)-7-hydroxy-4-oxo-4 H -chromen-3-yl)-2-methoxybenzenesulfonic acid), was highly active. It enhanced PC12 cell proliferation, reduced lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, effectively inhibiting apoptosis and ameliorating mitochondrial damage. Meanwhile, ( VI ) upregulated the expression of PI3K/Akt and Nrf2/HO-1 proteins. The study also demonstrated that ( VI ) binds significantly to the oxidative stress-related protein HO-1. Conclusions: Compound ( VI ) effectively protects PC12 cells against H 2 O 2 -induced oxidative damage. Its protective mechanism may involve activation of the PI3K/Akt and Nrf2/HO-1 signaling pathways, with HO-1 serving as a potential key target of its action.
研究领域:
药理学
·
分子生物学
·
神经科学
·
药物化学
·
细胞生物学
·
抗氧化研究
·
信号转导
✓ 已验证
产品关联
DOI
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2018
·Vol. 41
·期 8
·1194-1202
·
IF 1.694
Xiong Zhang,Qi Ni,Ying Wang,Hongwei Fan,Yingbin Li
Temozolomide (TMZ) is currently the first-line drug used for clinical postoperative or non-surgical chemotherapy for glioma, but acquired and intrinsic resistance to TMZ limits its application. The anti-proliferative effect of formononetin on human glioma cells had been confirmed. To improve therapeutic effects of TMZ, we studied the effect of formononetin in combination with TMZ on C6 glioma cells. The anti-proliferative effect of C6 cells was tested by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The synergy was evaluated by Chou–Talalay method. Morphological changes were observed by hematoxylin–eosin (HE) staining. The effect of formononetin in combination with TMZ on apoptosis of C6 cells was investigated by flow cytometry. The effect of formononetin in combination with TMZ on migration of cells was investigated by wound healing assay and transwell assay. The expression of proteins related to apoptosis and migration were detected by Western blot. These results showed that formononetin or TMZ alone could inhibit the growth of C6 cells in dose-dependent manner and formononetin in combination with TMZ had synergy effect on C6 cells. Further changes in cell morphology could be observed in drug combination by HE staining. Drug combination enhanced the expression of Bax, Cleaved Caspase-3, Cleaved Caspase-9, decreased the expression of Bcl-2, and promoted tumor cells apoptosis. In addition, the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were down-regulated via drug combination which resulted into inhibiting migration of C6 cell. In conclusion, formononetin in combination with TMZ can play a synergistic role in anti-C6 cells, the mechanisms of synergy depended on multiple pathways.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Chinese Medicine
·
2023
·Vol. 18
·期 1
·1-12
·
IF 4.9
Yang Jun,Sha Xiaowei,Wu Di,Wu Bo,Pan Xiaohua,Pan Li-Long,Gu Yuanlong,Dong Xiaoliang
Background Acute pancreatitis (AP) is a recurrent inflammatory disease. Studies have shown that intestinal homeostasis is essential for the treatment of AP. Formononetin is a plant-derived isoflavone with antioxidant properties that can effectively treat a variety of inflammatory diseases. This study aims to investigate the role of formononetin in protecting against AP and underlying mechanism.Methods Caerulein was used to induce AP. The inflammatory cytokines were detected using Quantitative real-time PCR and commercial kits. Histological examination was applied with hematoxylin and eosin staining. Western blot was conducted to detect expression of intestinal barrier protein and signaling molecular. Molecular docking was performed to assess protein-ligand interaction.Results In this study, we found formononetin administration significantly reduced pancreatic edema, the activities of serum amylase, lipase, myeloperoxidase, and serum endotoxin. The mRNA levels of inflammatory cytokines such as tumor necrosis factor α, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1 beta (IL-1β) in pancreas were also significantly decreased by formononetin. The following data showed formononetin pretreatment up-regulated the expressions of tight junction proteins in the colon, and decreased Escherichia coli translocation in the pancreas. In addition, formononetin inhibited the activation of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 in pancreatic and colonic tissues of AP mice. Moreover, formononetin activated Kelch Like ECH Associated Protein 1 (Keap1) / Nuclear factor erythroid2-related factor 2 (Nrf2) signaling pathway to reduce reactive oxygen species (ROS) levels. Docking results showed that formononetin interact with Keap1 through hydrogen bond.Conclusion sThese findings demonstrate that formononetin administration significantly mitigate AP through reducing oxidative stress and restoring intestinal homeostasis, and provide insights into the new treatment for AP.
研究领域:
药理学
·
胃肠病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Lin Cheng,Zhirui Du,Xueqiao Yan,Manju Che,Guoguo Zhi,Xiuying Ma,Funeng Geng,Baojie Li
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited effective treatment. Sophora flavescens Aiton (Kushen) exhibits anti-inflammatory properties, but its key active components and mechanisms against AD remain unclear. This study aimed to identify its therapeutic compounds and the underlying molecular mechanisms. Network pharmacology and ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry were applied to screen for the potential bioactive compounds from Kushen, which were validated in AD mouse models. Formononetin (FMN) was topically administered to evaluate its curative efficacy through histopathological and immunofluorescent staining of skin lesions. Transcriptomic profiling explored the molecular mechanisms, with subsequent validation of neutrophil extracellular traps (NETs)-associated markers by immunofluorescent staining and western blotting. Co-treatment with PAD4 inhibitor GSK484 and molecular docking were used to study the underlying mechanisms. The study identified FMN as an important active component in Kushen, which showed therapeutic effects comparable to dexamethasone in AD models. FMN normalized cutaneous hyperplasia, reduced infiltration of CD3 + T cells, mast cells, and neutrophils, and suppressed inflammatory cytokine expression. Mechanistically, FMN inhibited NETs formation evidenced by decreased levels of citrullinated histone H3 (citH3), myeloperoxidase (MPO), and peptidylarginine deiminase 4 (PAD4). GSK484 co-treatment showed non-synergistic effects, suggesting that FMN suppresses NETs formation primarily through PAD4/MPO inhibition, which was confirmed by molecular docking. These findings highlight FMN as a primary anti-AD constituent of Kushen, therapeutically suppressing NETs-driven crosstalk of innate and adaptive immunity. FMN's multitarget mechanisms provide mechanistic insights and position it as a candidate for AD treatment.
研究领域:
药理学
·
免疫学
·
皮肤科学
·
生物信息学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF VIROLOGY
·
2021
·Vol. 166
·期 9
·2443-2450
·
IF 2.574
Cui Zhanding,Wang Qian,Li Dengliang,Zhao Shihui,Zhang Qian,Tan Yuxin,Gong Qianwen,Liu Ting,Shao Jiang,Zhang Shuang,Huang Hailong,Wang Junzheng,Pei Zhihua,Dong Hao,Wang Kai,Hu Guixue,Li Zhiyong
Cats infected with feline calicivirus (FCV) often display oral ulcers and inflammation of the upper respiratory tract, which can lead to death in severe cases. Antiviral therapy is one of the most effective ways to control FCV infection. Natural compounds in Chinese herbal medicines and medicinal plants provide abundant resources for research on antiviral drugs. In this study, we found that icariin (ICA), formononetin (FMN) and caffeic acid phenethyl ester (CPAE) show low cytotoxicity towards F81 cells, that the three natural compounds have apparent antiviral effects on FCV in vitro , and that they can inhibit different FCV strains. Then, we found that ICA and FMN mainly function in the early stage of FCV infection, while CAPE can function in both the early and late stages of FCV infection. Finally, we found that ICA has an antagonistic effect on FMN and CAPE in FCV infection, and FMN has a synergistic effect with CAPE against FCV infection. Our results showed that ICA, FMN and CAPE may be potential drug candidates for FCV-induced diseases.
研究领域:
兽医学
·
药理学
·
病毒学
·
天然产物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-14
·
IF 10.435
Xiong Wei,Lan Qiumei,Liang Xiaonan,Zhao Jinmin,Huang Hanji,Zhan Yanting,Qin Zainen,Jiang Xianfang,Zheng Li
Intra-articular (IA) injection is an efficient treatment for osteoarthritis, which will minimize systemic side effects. However, the joint experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with an average diameter about 218 nm. The in vitro test using IL-1β stimulated chondrocytes indicated that PCFMN was biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide a reference for clinical OA therapy.
研究领域:
药剂学
·
纳米技术
·
骨科
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
BURNS
·
2024
·
IF 3.2
Meiyue Yang,Zhibo Yang,Xiangjun Huang,Xiaoping Li,Fangqin Chou,Shuiqing Zeng
The aim of this study was to explore the effect and mechanism of formononetin (FMNT) in thermal-injured fibroblast proliferation, apoptosis, and oxidative stress. After the thermal injury, HSF cells showed inhibited proliferation, migration, and ECM synthesis, whereas increased apoptosis, ROS production, and inflammation. Specifically, after thermal injury, cell viability, migration distance, and protein levels of Collage I, Collage III, α-SMA, MMP1, and MMP3 were reduced; cell apoptosis rate and TUNEL-positive cell numbers were increased; the levels of Bax and Cleaved caspase-3 showed to be elevated, while Bcl-2 level showed to be reduced. Moreover, the thermal injured-HSF cells showed increased levels of ROS, MDA, LDH, TNF-α, and IL-1β, and decreased GSH, SOD, GSH-Px, and CAT. FMNT levels can partially eliminate the effects of thermal injury on HSF cells, as shown by promoting thermal injured-HSF cell proliferation and migration, and inhibiting cell apoptosis, ROS production, and inflammation. FMNT exerted no significant effect on normal HSF cells. Additionally, the level of the P13K/AKT/mTOR signaling-related proteins (p-P13K, p-AKT, and p-mTOR) was reduced in thermal injured-HSF cells, whereas FMNT could promote p-P13K, p-AKT, and p-mTOR levels. FMNT can partially alleviate the thermal injury-induced inhibition of fibroblast proliferation and migration; FMNT also inhibited the apoptosis, ROS level, and inflammation in thermal-injured cells. The effects of FMNT may be mediated by regulating the P13K/AKT/mTOR pathway.
研究领域:
药理学
·
细胞生物学
·
伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 4.8
Jun Rao,Xing Wang,Tanxiu Chen,Mingzi Mo,Conglong Xu,So-Yi Chang,Ssu-Wei Hsu,Xiaoqun Han,Ching-Hsien Chen,Zhi Zheng
Background: Hedysari Radix (HR), commonly known as Hong-Qi in Chinese, is a traditional Chinese herbal medicine recognized for possessing anti-inflammatory and anti-tumor properties. While the polysaccharides in HR have been extensively studied, other HR metabolites and their potential anti-tumor properties remain largely unknown.Methods: We employed a multi-omics strategy integrating metabolomics, network analysis, proteomics, phosphoproteomics, and molecular docking to identify HR metabolites with anti-colorectal cancer (CRC) property and investigate underlying mechanisms.Results: Using mass spectrometry-based metabolomics, we identified 1,292 metabolites across eight processed HR products. Key metabolites including medicarpin, formononetin, naringenin, and quercetin were validated via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Notably, formononetin-derived metabolites were significantly enriched during HR processing. The metabolite-metabolite correlation analysis revealed key compounds such as flavonoids and formononetin. Subsequent network analysis combined with label-free data-independent acquisition (DIA) proteomics and phosphoproteomics in colon cancer cells identified 194 potential targets, 291 differentially expressed proteins, and 1,535 phosphorylated proteins that were regulated by formononetin. Cell-surface enzymes carbonic anhydrase IX (CA9) and membrane metalloendopeptidase (MME) were consistently identified in different analyses as key targets, and molecular docking results confirmed their strong binding to formononetin. Bioinformatics analyses further revealed significant enrichment of cancer-associated pathways, including PI3K-Akt, Hippo, HIF-1 signaling, and cholesterol metabolism upon formononetin treatment.Conclusion: The findings provide novel insights into the HR metabolome and reveal the multi-targeting roles of formononetin in CRC development, laying the foundation for developing new CRC therapeutic strategies.
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Boshu Ouyang,Lingling Deng,Fangyong Yang,Hanlin Shi,Na Wang,Weifeng Tang,Xi Huang,Yaolong Zhou,Hang Yu,Ying Wei,Jingcheng Dong
Pulmonary fibrosis that occurs following lung injury is a progressive and fatal disease since continual damage to lung tissue triggers the dysregulated inflammation response and accompanying abnormal healing process. Pyroptosis of alveolar macrophages has been found to play an essential role in the deterioration of lung injury and fibrosis. However, the lack of inhibitors against this inflammatory cell death in macrophages and the dense stroma pose major barriers to lung injury and fibrosis treatment. Herein, we developed an albumin-based nanoformulation to realize active delivery of formononetin (FMN) to improve the treatment of lung injury and fibrosis. The obtained nanoparticle, [email protected] NPs, could efficiently accumulate at the impaired lesion benefiting from the leaky vasculatures and the affinity between albumin and the overexpressed SPARC protein. Through blocking the NLRP3 inflammasome-involved pyroptosis process of macrophages, [email protected] NPs remarkably improved lung function and prolonged animal survival in the bleomycin (BLM)-induced lung injury and fibrosis model without noticeable side effects. Meanwhile, we proved FMN as a pyroptosis inhibitor and the corresponding lipid metabolism-related mechanisms through multi-omics analysis. This study first employed an albumin-based nanoparticle to deliver the pyroptosis inhibitor to the impaired lung tissue actively, providing a promising strategy for lung injury and fibrosis treatment.
研究领域:
药学
·
肺科学
·
纳米技术
·
炎症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscience and Nanotechnology Letters
·
2020
·Vol. 12
·期 8
·1022-1029
·
IF 1.128
Liu Ming,Lin Chen,Huang Xiaoqing,Lin Yuxiang
Natural flavonoid formononetin (FN) has anticancer effects, but the hydrophobic structure, characteristics of the short half-life in vivo, limiting its clinical wide-ranging application. In this study, FN loaded Pluronic (PF)@folic acid (FA) micelles (FN-PF@FA), were prepared
to improve the solubility, bioavailability and targeting. FA coupling PF was prepared by carbodiimide crosslinker chemical method, FN-PF@FA micelles were prepared by modified film hydration method, and compared the antitumor activity of FN loaded micelles with free FN In Vitro. The
spherical smooth surface of FN-PF@FA micelles had smaller particle size (112.3±5.3 nm), high encapsulation efficiency (86.14±2.68%), high negative zeta potential (-25.8±0.57 mV), low critical concentration CMC (0.03 mg/mL), and better sustained release profile. In addition,
FN-PF@FA micelles have a positive targeting effect on oral squamous cell carcinoma cells (SCC3). In 48 hours, the growth inhibition of 50% (GI50) was 28.6±1.2 μg/mL for FN and 17.4±0.78 μg/mL for FN-PF, the dose dropped by nearly 38.46%. In addition, the GI50
value of FN-PF@FA was 9.5±0.3 μg/mL, 66.43% lower than FN and 44.83% lower than FN-PF. Furthermore, the laser scanning confocal microscopy revealed that the conjugation of FA significantly improves the active targeting ability of micelles. FN-PF@FA micelles have the potential
to target the release of anticancer drugs with higher bioavailability, further provides a new avenue for the application of traditional Chinese medicine extract in oral malignant tumor.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）