Phytotherapy Research最新文献

The most prevalent and bioactive cucurbitacin is Cucurbitacin B (CuB, C₃₂H₄₆O₈), which is a tetracyclic triterpene chiefly present in the Cucurbitaceae family. CuB has a wide spectrum of pharmacological properties namely antioxidant, anticancer, hepatoprotective, anti-inflammatory, antiviral, hypoglycaemic, insecticidal, and neuroprotective properties, owing to its ability to regulate several signaling pathways, including the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), AMP-activated protein kinase (AMPK), nuclear factor (NF)-κB, nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), Hippo-Yes-associated protein (YAP), focal adhesion kinase (FAK), cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt and Notch pathways. The present review highlights the medicinal attributes of Cucurbitacin B (CuB) with special emphasis on their signaling pathways to provide key evidence of its therapeutic utility in the near future.

Background and aim: Gastrodin, an active compound derived from the traditional Chinese herbal medicine Gastrodia, demonstrates a variety of pharmacological effects, particularly in the enhancement of neural functions. Thus, the aim of this study is to explore the therapeutic effects of gastrodin on Alzheimer's disease (AD) and its underlying molecular mechanisms.

Experimental procedure: Cognitive function was assessed via Morris water maze and Y-maze tests. Tau pathology, neuroinflammation, and BBB dysfunction were analyzed using various techniques, including Western blot, immunohistochemistry, and ELISA. ADRA1 overexpression was induced by lentiviral infection, and gastrodin's impact on NF-κB p65, NLRP3, IL-1β, and IL-18 levels was evaluated.

Key results: In the in vivo experiment, gastrodin enhanced learning and spatial memory in 3xTg-AD mice, as well as reducing p-Tau protein expression in the hippocampus and cortex. Gastrodin inhibited the ADRA1/NF-κB/NLRP3 pathway, which decreased glial cell activation and inflammatory cytokines IL-1β and IL-18, improving neuron and BBB function. In the in vitro experiment, gastrodin inhibited the activation of the NF-κB/NLRP3 pathway due to ADRA1 overexpression and prevented the Aβ₄₂-induced increase in ADRA1/NF-κB/NLRP3 protein expression in SH-SY5Y cells. It also reduced IL-1β and IL-18 cytokine release, restoring tight junction protein expression in bEnd.3 cells.

Conclusions and implications: gastrodin ameliorates learning and memory abilities by alleviating neuroinflammation and tau pathology, restoring the structure and function of neurons and BBB, suggesting that gastrodin may serve as an effective drug for the treatment of AD.

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition with limited effective treatments. This study investigated the therapeutic effects of Aurantio-obtusin (AO), a bioactive compound from Cassiae Semen, on obesity-associated NAFLD. An obesity-related NAFLD model was established in ApoE^-/- mice fed a high-fat diet (HFD) for 24 weeks, with AO administered during the last 16 weeks. Mouse body weight, adipose tissue weights, liver weights, serum lipid levels, hepatic steatosis, inflammatory damage, and colonic tissue barrier integrity were evaluated. Gut microbial communities and serum metabolic profiles were analyzed using 16S rRNA sequencing and untargeted metabolomics. Hepatic lipid metabolism-related gene expression was assessed using molecular biology techniques. AO treatment significantly ameliorated HFD-induced adiposity, hyperlipidemia, and NAFLD symptoms. It preserved intestinal barrier integrity, modulated gut microbial composition by enriching beneficial taxa, and improved serum metabolic profiles. AO favorably adjusted hepatic lipid metabolism by upregulating PPARα and CPT1A while downregulating SREBP1, FASN, and SCD1. Correlation analysis revealed significant associations among gut microbial composition, serum metabolites, and disease indicators. AO's therapeutic benefits in NAFLD might be attributed to its ability to modulate gut microbial community composition and serum metabolic profile, enhance intestinal barrier function, and regulate hepatic lipid metabolism gene expression. AO presents a promising therapeutic agent for obesity-associated NAFLD, warranting further investigation into its potential clinical applications.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous subtype of non-Hodgkin lymphoma, with two-thirds of patients relapsing or resisting existing therapies, highlighting the urgent need for effective treatments. Toosendanin (TSN), a triterpenoid from Meliae Cortex, exhibits significant anti-cancer activity by modulating cell survival and proliferation. This study investigates the anti-lymphoma effects and underlying mechanisms of TSN, proposing it as a potential therapeutic agent to address the challenges of DLBCL. Network pharmacology, molecular docking, and transcriptome sequencing were employed to predict TSN's anti-DLBCL potential. Findings were validated through in vitro and in vivo experiments, including cell viability assays, flow cytometry, quantitative PCR, Western blotting, reverse experiments with small-molecule inhibitors or genetic editing, and a cell-derived xenograft (CDX) model. Bioinformatics analyses revealed TSN's strong binding affinity to PI3Kα/β and Polo-like kinase 1 (PLK1). Experiments showed that TSN downregulated the PI3K/Akt signaling pathway and reduced PLK1 mRNA and protein levels, inducing apoptosis, cell cycle arrest, and cell death in DLBCL cells. RNA sequencing and metabolic assays indicated TSN upregulated cholesterol biosynthesis in DLBCL cells. Co-treatment with a statin enhanced TSN's anti-DLBCL effects while mitigating hepatic and pulmonary toxicity. This study identifies TSN as a dual inhibitor of PI3K and PLK1 with significant therapeutic potential for DLBCL. It also proposes a lipid-modulating strategy to enhance TSN's cytotoxicity while reducing adverse effects, offering a promising approach to improve DLBCL treatment outcomes.

Retraction: M. Moradzadeh, A. Roustazadeh, A. Tabarraei, S. Erfanian, and A. Sahebkar, "Epigallocatechin-3-Gallate Enhances Differentiation of Acute Promyelocytic Leukemia Cells via Inhibition of PML-RARα and HDAC1," Phytotherapy Research 32, no. 3 (2018): 471-479, https://doi.org/10.1002/ptr.5990. The above article, published online on 29 November 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Angelo A. Izzo; and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate image panel duplications between this article (Figure 4 a, b) and other articles published by an overlapping group of authors, in which the images represent different experimental conditions. The explanation provided by the authors could not address these concerns. Thus, the editors have lost confidence in the presented data and consider the conclusions of this manuscript substantially compromised. A. Sahebkar disagrees with the retraction, the other co-authors remained unresponsive.

In recent years, immunotherapy has become a novel antitumor strategy in addition to traditional surgery, radiotherapy, and chemotherapy and has exhibited promising results in clinical applications. Despite significant breakthroughs in immunotherapy, such as immune checkpoint blockade and CAR-T cell therapy, it remains necessary to develop more efficacious, safer, and cheaper immunotherapeutic drugs due to factors including small reaction populations, acquired resistance, adverse side effects, and high costs. Natural killer (NK) cells are preeminent cytotoxic lymphocytes of the innate immune system that act as the first line of defense against tumors and synergistically enhance the adaptive immune response of T lymphocytes. Therefore, boosting the antitumor function of NK cells is an important direction in the development of immunotherapy. For decades, various immunotherapies such as adoptive cell therapy, antibody drugs, cytokines supplement, and chemical immunomodulators have been developing rapidly to improve the function of NK cells. Compared to biological immunotherapy, immunomodulators derived from natural products have outstanding advantages of low immunogenicity, multi-targeting, and cost-effectiveness. Currently, increasing attention is being focused on discovering NK cell-stimulating agents from natural products, such as polysaccharides, alkaloids, terpenoids, saponins, phenolics, and quinones. This review aims to categorize and summarize the comprehensive research progress on these natural products, discuss their potential molecular mechanisms in regulating NK cells, and explore their clinical applications as standalone treatments or in combination with conventional chemotherapy regimens.

Saffron is a traditional herbal medicine used to treat conditions associated with metabolic syndrome (MetS). However, the conclusions of relevant clinical studies have been inconsistent. This study aimed to assess the impact of saffron supplementation on the metabolism of glycolipids and blood pressure in individuals with MetS and related disorders. Web of Science, PubMed, Cochrane Library, Scopus, and Embase were comprehensively searched for studies investigating saffron supplementation for MetS and related disorders up to February 2024. Stata 17.0 was used to conduct the Meta-analysis. Twenty-five randomized controlled trials (RCTs) were included in this study, involving 1486 participants with MetS and related conditions. Compared to placebo, saffron supplementation triggered significant reductions in fasting blood glucose (FBG) (WMD: -6.67 mg/dL; 95% CI: -10.55, -2.78; p = 0.001; I² = 50.0%), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.25%; 95% CI: -0.35, -0.14; p < 0.001; I² = 0.0%), total cholesterol (TC) (WMD: -4.77 mg/dL; 95% CI: -8.83, -0.71; p = 0.021; I² = 31.8%), systolic blood pressure (SBP) (WMD: -1.15 mmHg; 95% CI: -1.66, -0.64; p < 0.001; I² = 41.8%), and diastolic blood pressure (DBP) (WMD: -1.61 mmHg; 95% CI: -1.88, -1.34; p < 0.001; I² = 7.0%). However, no significant changes were observed for homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), and waist circumference (WC). Saffron supplementation has an improving effect on FBG, HbA1c, TC, DBP, and SBP in patients with MetS and related disorders. Nonetheless, additional high-quality RCTs involving diverse ethnic populations are necessary to validate this effect.

Osteoporosis is divided into primary and secondary types. Primary osteoporosis may result from estrogen deficiency in postmenopausal women, imbalanced bone remodeling in the elderly, or imbalanced adolescent-type bone development. Secondary osteoporosis can be caused by factors like long-term glucocorticoid treatment, chronic kidney disease (CKD), estrogen deprivation, oxidative stress, diabetes, and obesity. This review focuses on the therapeutic potential of soy isoflavones for osteoporosis. At the cellular level, soy isoflavones, as natural plant extracts and phytoestrogens, are crucial for osteoblastogenesis and differentiation, osteoclastogenesis, osteoclast mineralization, and bone marrow mesenchymal stromal cell differentiation. They also maintain calcium homeostasis by regulating extracellular calcium and vitamin D levels. In terms of oxidative stress, soy isoflavones mitigate it in the endoplasmic reticulum and mitochondria, thus regulating cellular senescence, autophagy, and bone remodeling processes. Moreover, soy isoflavones can relieve symptoms related to CKD and inhibit glucocorticoid secretion, which directly or indirectly benefits the treatment of osteoporosis. Overall, soy isoflavones have the potential to treat osteoporosis by enhancing bone health, regulating metabolism, and alleviating oxidative stress. Future research should explore the potential of soy isoflavones as phytoestrogens for treating osteoporosis. This exploration should focus on clarifying the safety, identifying potential side effects, determining the optimal dosage regimen, and developing strategies to mitigate any adverse reactions. In addition, further large-scale, multicenter human clinical trials are necessary to accurately evaluate the actual therapeutic effect of soy isoflavones on osteoporosis.

Endothelial progenitor cells (EPCs) provide a promising therapeutic choice for deep venous thrombosis (DVT). Their number is increased by epigallocatechin-3-gallate (EGCG) in patients with diabetes. Although EGCG is effective against doxorubicin-induced ferroptosis and cardiotoxicity, its efficacy in DVT treatment has not been well studied. This study was aimed at assessing the effects of EGCG on EPC ferroptosis and recanalization in a DVT model. EPCs were treated with EGCG, and their proliferation and migration, angiogenesis, and apoptosis were evaluated using cell counting kit-8 and colony formation, Transwell, tube formation, and flow cytometry assays. Levels of iron, ferroptosis markers, and reactive oxygen species (ROS), and mitochondrial membrane potential (ΔΨm) were measured. Expression of ferroptosis-related genes and proteins was analyzed using qRT-PCR and western blotting, respectively. Promoter activation was evaluated using a dual-luciferase reporter system. Thrombus recanalization was examined in the DVT mouse model via hematoxylin and eosin staining and digital subtraction angiography. EGCG promoted EPC proliferation, migration, and angiogenesis and suppressed apoptosis. It attenuated ferroptosis by reducing iron and ROS accumulation, increasing ΔΨm, and regulating the expression of ferroptosis-related genes and proteins (ALOX15, ACSL4, and FTH1). EGCG enhanced the expression of Nrf2 and its targets, Slc7A11, HO-1, and GPX4. EGCG inhibited thrombogenesis and promoted recanalization in DVT mice, an effect mediated through the Nrf2 pathway and enhanced upon EPC transplantation. Transplantation of EGCG-pretreated EPCs facilitates DVT resolution via ferroptosis blockade. EGCG-pretreated EPC-based therapy may provide a novel option for patients with DVT.