Puerarin, a monomer of traditional Chinese medicine, is a key component of Pueraria radix. Both clinical and experimental researches demonstrated that puerarin has therapeutic effects on Parkinson\'s disease (PD). Puerarin\'s pharmacological mechanisms include: 1) Anti-apoptosis. Puerarin inhibits cell apoptosis through the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. Puerarin also exerts a hormone-like effect against cell apoptosis; 2) Anti-oxidative stress injury. Puerarin inhibits the Nrf2 nuclear exclusion through the GSK-3β/Fyn pathway to promote the Nrf2 accumulation in the nucleus, and then promotes the antioxidant synthesis through the Nrf2/ARE signaling pathway to protect against oxidative stress; 3) Neuroprotective effects by intervening in the ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP). Puerarin significantly enhances the activity of chaperone-mediated autophagy (CMA), which downregulates the expression of α-synuclein, reduces its accumulation, and thus improves the function of damaged neurons. Additionally, puerarin increases proteasome activity and decreases ubiquitin-binding proteins, thereby preventing toxic accumulation of intracellular proteins; 4) Alleviating inflammatory response. Puerarin inhibits the conversion of microglia to the M1 phenotype while inducing the transition of microglia to the M2 phenotype. Furthermore, puerarin promotes the secretion of anti-inflammatory factor and inhibits the expression of pro-inflammatory factors; 5) Increasing the levels of dopamine and its metabolites. Puerarin could increase the levels of dopamine, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum; 6) Promoting neurotrophic factor expression and neuronal repair. Puerarin increases the expression of glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), thereby exerting a neuroprotective effect. Moreover, the regulation of the gut microbiota by puerarin may be a potential mechanism for the treatment of PD. The current review discusses the molecular mechanisms of puerarin, which may provide insight into the active components of traditional Chinese medicine in the treatment of PD.

BACKGROUND: Neuroblastoma, a prevalent solid tumor in children, often manifests with hidden onset sites, rapid growth, and high metastatic potential. The prognosis for children with high-risk neuroblastoma remains poor, highlighting the urgent need for novel prognostic models and therapeutic avenues. In recent years, puerarin, as a kind of small molecule drug extracted from Chinese medicine Pueraria lobata, has demonstrated significant anticancer effects on various cancer cell types. In this study, through bioinformatics analysis and in vitro experiments, the potential and mechanism of puerarin in the treatment of neuroblastoma were investigated, and a prognostic model was established.
METHODS: A total of 9 drug-disease related targets were observed by constructing a database of drug targets and disease genes. Besides, GO and KEGG enrichment analysis was performed to explore the potential mechanism of its therapeutic effect. To construct the prognostic model, risk regression analysis and LASSO analysis were carried out for validation. Finally, the prognostic genes were identified. Parachute test and immunofluorescence staining were performed to verify the potential mechanism of puerarin in neuroblastoma treatment.
RESULTS: Three prognostic genes, i.e., BIRC5, TIMP2 and CASP9, were identified. In vitro studies verified puerarin\'s impact on BIRC5, TIMP2, and CASP9 expression, inhibiting proliferation in neuroblastoma SH-SY5Y cells. Puerarin disrupts the cytoskeleton, boosts gap junctional communication, curtailing invasion and migration, and induces mitochondrial damage in SH-SY5Y cells.
CONCLUSIONS: Based on network pharmacology and bioinformatics analysis, combined with in vitro experimental verification, puerarin was hereby observed to enhance GJIC in neuroblastoma, destroy cytoskeleton and thus inhibit cell invasion and migration, cause mitochondrial damage of tumor cells, and inhibit cell proliferation. Overall, puerarin, as a natural medicinal compound, does hold potential as a novel therapy for neuroblastoma.

Osteoporosis is characterized by bone loss and deterioration in bone microstructure, leading to bone fragility. It is strongly correlated with menopause in women. Previously, we reported that diets supplemented with a kudzu (Pueraria lobata) vine extract suppressed bone resorption in ovariectomized (OVX) mice, a postmenopausal model. The main isoflavone in kudzu is puerarin (daidzein-8-C-glycoside). Puerarin (daidzein-8-C-glycoside), which is main isoflavone of kudzu, probably contributes to the beneficial effect. However, the underlying mechanism is unclear. Therefore, the nutrikinetics of puerarin and the comparison with the suppressive effects of kudzu isoflavones on osteoclast differentiation was examined in this study. We demonstrated that orally administered puerarin was absorbed from the gut and entered the circulation in an intact form. In addition, puerarin accumulated in RAW264.7 pre-osteoclast cells in a time-dependent manner. Tartrate-resistant acid phosphatase activity was decreased by puerarin treatment in a concentration-dependent manner in RAW264.7 cells stimulated with the receptor activator of nuclear factor kappa-B ligand. Ovariectomy-induced elevated bone resorption was suppressed, and the fragile bone strength was improved by puerarin ingestion in the diet. These findings suggested that orally administered puerarin was localized in bone tissue and suppressed bone resorption and osteoclastogenesis in ovariectomized mice.

BACKGROUND: Acute kidney injury (AKI) is a clinically common and serious renal dysfunction, characterized by inflammation and damage to tubular epithelial cells. Puerarin, an isoflavone derivative isolated from Pueraria lobata, has been proven to possess exceptional effectiveness in reducing inflammation. However, the effects and underlying mechanisms of puerarin on AKI remain uncertain.
OBJECTIVE: This study investigated the possible therapeutic effects of puerarin on AKI and explored its underlying mechanism.
METHODS: The effects of puerarin on AKI and macrophage polarization were investigated in lipopolysaccharide (LPS)-induced or unilateral ureteral obstruction (UUO)-induced mouse models in vivo and LPS-treated macrophages (Raw264.7) in vitro. Additionally, the effects of puerarin on inflammation-related signaling pathways were analyzed.
RESULTS: Administration of puerarin effectively alleviated kidney dysfunction and reduced inflammatory response in LPS-induced and UUO-induced AKI. In vitro, puerarin treatment inhibited the polarization of M1 macrophages and the release of inflammatory factors in Raw264.7 cells stimulated by LPS. Mechanistically, puerarin downregulated the activities of NF-κB p65 and JNK/FoxO1 signaling pathways. The application of SRT1460 to activate FoxO1 or anisomycin to activate JNK eliminated puerarin-mediated inhibition of JNK/FoxO1 signaling, leading to suppression of macrophage M1 polarization and reduction of inflammatory factors. Further studies showed that puerarin bound to Toll/interleukin-1 receptor (TIR) domain of MyD88 protein, hindering its binding with TLR4, ultimately resulting in downstream NF-κB p65 and JNK/FoxO1 signaling inactivation.
CONCLUSIONS: Puerarin antagonizes NF-κB p65 and JNK/FoxO1 activation via TLR4/MyD88 pathway, thereby suppressing macrophage polarization towards M1 phenotype and alleviating renal inflammatory damage.

OBJECTIVE: Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of tablets containing Silybum marianum, Pueraria lobata, and Salvia miltiorrhiza (SPS) on NAFLD progression in Chinese adults.
METHODS: In this randomized, triple-blind, placebo-controlled clinical trial, 121 NAFLD patients (60 female and 61 male), diagnosed via magnetic resonance imaging (MRI) and aged 18-65 years, were enrolled. Participants were randomly allocated to receive SPS tablets (n = 60; three tablets per dose, twice daily) or placebo (n = 61) for 24 weeks. Each SPS tablet contained approximately 23.0 mg of silybin, 11.4 mg of puerarin, and 10.9 mg of salvianolic acid. There were no differences in appearance, taste and odour between the SPS tablets and placebo manufactured by BYHEALTH Co., LTD (Guangzhou, China). The primary endpoints were changes in the liver fat content (LFC) and steatosis grade from baseline to 24 weeks. Secondary outcomes included changes in biomarkers/scores of liver fibrosis and steatosis, oxidative stress, inflammatory cytokines, alcohol metabolism, and glucose metabolism.
RESULTS: A total of 112 participants completed the research. The intention-to-treat results showed a trend toward reduction in both absolute LFC (-0.52%) and percentage of LFC (-4.57%) in the SPS group compared to the placebo group after 24 weeks, but these changes didn\'t reach statistical significance (p > 0.05). The SPS intervention (vs. placebo) significantly decreased hypersensitive C-reactive protein level (-6.76%) and increased aldehyde dehydrogenase activity (+18.1%) at 24 weeks post-intervention (all p < 0.05). Per-protocol analysis further supported these effects. This trial is registered at Clinical Trials.gov (NCT05076058).
CONCLUSIONS: SPS supplementation may have potential benefits in improving NAFLD, but further larger-scale trials are necessary to confirm these findings.

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia, and its increasing prevalence is a global concern. Early diagnostic markers and therapeutic targets are essential for DM prevention and treatment. Pueraria, derived from kudzu root, is used clinically for various symptoms, and its active compound, Puerarin, shows promise in improving insulin resistance and reducing inflammation.
OBJECTIVE: This study aims to evaluate the protective effects of metformin and Puerarin at different doses in an STZ-induced DM mouse model. The intricate metabolites within the serum of STZ-induced diabetic mice were subjected to thorough investigation, thus elucidating the intricate mechanism through which Puerarin demonstrates notable efficacy in the treatment of diabetes.
METHODS: An STZ-induced DM mouse model is established. Mice are treated with metformin and puerarin at varying doses. Physiological, biochemical, and histomorphological assessments are performed. Metabolomics analysis is carried out on serum samples from control, DM, metformin, and medium-dose Puerarin groups. Western blot and qRT-PCR technologies are used to validate the mechanisms.
RESULTS: The DM mouse model replicates abnormal blood glucose, insulin levels, physiological, biochemical irregularities, as well as liver and pancreas damage. Treatment with metformin and Puerarin restores these abnormalities, reduces organ injury, and modulates AMPK, PPARγ, mTOR, and NF-κB protein and mRNA expression. Puerarin activates the AMPK-mTOR and PPARγ-NF-κB signaling pathways, regulating insulin signaling, glucolipid metabolism, and mitigating inflammatory damage.
CONCLUSIONS: This study demonstrates that Puerarin has the potential to treat diabetes by modulating key signaling pathways. The focus was on the finding that Puerarin has been shown to improve insulin signaling, glucolipid metabolism and attenuate inflammatory damage through the modulation of the AMPK-mTOR and PPARγ-NF-κB pathways. The discovery of Puerarin\'s favorable protective effect and extremely complex mechanism highlights its prospect in the treatment of diabetes and provides theoretical support for its comprehensive development and utilization.

In this paper, a novel mono-methacrylated β-cyclodextrin (β-CD) monomer mediated by disulfide bond was synthesized, and then thermal copolymerized with HEMA monomer in the presence of a little crosslinker to prepare redox-responsive hydrogel for regulated drug delivery. The structure of the monomer was confirmed by FTIR, 1H NMR, 13C NMR spectroscopy. The substitution degree of polymerizable methacrylated group grafted onto β-CD was about 1 by calculating by1H NMR (0.987) and element analysis (0.937). The mono-methacrylated β-CD monomer can well copolymerize with 2-hydroxyethyl methacrylate (HEMA) monomer with gel fraction over 80%. The hydrogel shows low cytotoxicity, and copolymerization of the mono-methacrylated β-CD monomer in the hydrogels increases its equilibrium swelling degree (ESD) and tensile strength, while its transmittance slightly decreases. Drug loading and release rate are dependent on the β-CD content. The hydrogel with high β-CD content of 13.83 wt% shows 1.8 and 8.5 folds puerarin (PUE) and curcumin (CUR) loading than pure pHEMA hydrogel, respectively. The incorporation of β-CD sustained drug release, especially CUR release was prolonged more than 24 h from 5 h of pure pHEMA hydrogel (80% release). The hydrogels are highly sensitive to reduced glutathione (GSH), and low concentration of GSH of 3 mM can significantly accelerate drug release rate. The higher of β-CD content, the more sensitive the hydrogels to GSH, resulting in rapider drug release rate.

Ovarian cancer (OC) is a common malignancies of the female genitalia. P. montana var. lobata (Willd.), a herb with anti-tumor effects, is widely used in the clinical treatment of ovarian cancer (OC), but the ingredients and molecular mechanism of action remains to be explored. In this study, we extracted the main active ingredients of P. montana var. lobata (Willd.) from the TCMSP database, and predicted its potential targets of action against OC from the DisGeNET and GeneCards databases. Protein-protein interaction (PPI) was constructed using the STRING database, while pathway enrichment analyses were performed using the DAVID database. Next, we generated an Ingredient-Target-Pathway network using Cytoscape 3.7.2, then processed the key targets of action and main active ingredients for molecular docking. The results showed that seven active ingredients of P montana var. lobata (Willd.) were associated with treating for OC, namely beta-sitosterol, coumestrol, daidzein, formononetin, genistein, puerarin and scoparone, two important targets Casp3 and Jun, and signaling pathways of P. montana var. lobata (Willd.) against the progression of OC. TUNEL staining, enzyme-linked immunosorbent assay (ELISA), and Western blot assays, the pharmacodynamic effect of puerarin in the treatment of OC and the major targets were verified. Animal experiment demonstrated that application of puerarin at different times of modeling not only upregulated expression of Casp3, Smac, and c-jun proteins, but also promoted apoptosis in tumor cells, hence inhibiting progression of OC. This study demonstrates that P. montana var. lobata (Willd.) can thereby induce apoptosis in tumor cells and inhibit malignant progression through activating expression of Casp3, smac, and c-jun proteins to regulate related apoptosis pathways, as validated by network pharmacology predictions and animal experiments, and can be verifed by large-scale clinical trials in the future. This study also provides theoretical support and new research perspectives for this disease.

OBJECTIVE: This study aimed to investigate the impact of puerarin early intervention on growth parameters and Hepatic Fat Signal Fraction (HFF) quantification in Intrauterine Growth Restricted(IUGR)rats through Proton Magnetic resonance spectroscopy (1H-MRS).
METHODS: Pregnant rats were divided into three groups: control, IUGR with puerarin treatment, and IUGR without treatment. The treatment and nontreatment groups were received a low-protein diet during pregnancy, while the control group received a normal diet. After birth, pups in the treatment group received a unilateral intraperitoneal injection of 50 mg/kg/d puerarin. Male rats were evaluated at 3,8 and 12 weeks, including measurements of weight, body length and waist circumference and body mass index (BMI). Conventional magnetic resonance imaging and 1HMRS were conducted using a 3.0 T whole-body MR scanner.
RESULTS: Newborn pups in the treatment and non-treatment groups showed significantly lower body weight, BMI, and body length at 3 weeks compared to the control group. However, there were no significant differences in HFF and waist circumference between the three groups at 3 weeks. At 8 and 12 weeks post-delivery, significant differences in body weight, BMI, waist circumference were observed in newborn pups of IUGR non-treatment rats compared to the control group. In contrast, there were no significant differences in body weight, BMI, waist circumference between the treatment group and the control group at 8 and 12 weeks. Moreover, the treatment group exhibited notably higher HFF compared to the control group at both time points. At 12 weeks post-birth, a significant difference in HFF was observed between the IUGR non-treatment and treatment groups, although no significant difference was found at 8 weeks.
CONCLUSIONS: Early intervention with puerarin following birth has a significant impact on liver fat content and may potentially reduce adult obesity among IUGR rats.

Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin\'s beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin\'s potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities.