The American journal of Chinese medicine最新文献

Oxidative stress serves as a driving force for myofibroblast activation in pulmonary fibrosis (PF). As a main enzymatic source of reactive oxygen species (ROS), NADPH oxidase 4 (Nox4) plays a critical role in modulating myofibroblast activation, and has thus emerged as a potential therapeutic target for PF. Tanshinone IIA (Tan-IIA), the most abundant fat-soluble component found in the root and rhizome of Salvia miltiorrhiza Bge., has been demonstrated to suppress ROS-mediated myofibroblast activation by inhibiting Nox4, and thereby ameliorating PF. However, the mechanism through which Tan-IIA regulates Nox4 to prevent myofibroblast activation remains unclear. This study aimed to investigate the protective effects of Tan-IIA against myofibroblast activation in PF, and to elucidate the upstream molecular mechanisms involved in Nox4 regulation. Tan-IIA inhibited myofibroblast activation by reducing extracellular matrix deposition in a mouse model of bleomycin-induced PF. Furthermore, Tan-IIA enhanced the expression of Sestrin2 (Sesn2), while concurrently suppressing Nox4 expression. This effect was verified using an in vitro model of transforming growth factor beta 1 (TGF-β1)-stimulated myofibroblast activation. We further demonstrated that Sesn2 was required for Tan-IIA to act against TGF-β1-induced myofibroblast activation by inhibiting Nox4-mediated oxidative stress. Additionally, both in vitro and in vivo studies revealed that Tan-IIA activates AMP-activated protein kinase (AMPK) and inhibits mammalian target of rapamycin (mTOR) via the upregulation of Sesn2. The findings indicate that Tan-IIA suppresses Nox4 by regulating the Sesn2/AMPK/mTOR signaling pathway, which highlights the crucial effect Sesn2 has in modulating Nox4 expression to prevent myofibroblast activation during PF.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily characterized by cognitive decline. Its etiology and pathogenesis are complex and multifactorial, with neurotoxicity induced by the abnormal aggregation of amyloid-beta (A[Formula: see text]) protein widely recognized as a central pathological hallmark. Current pharmacological treatments provide only limited symptomatic relief and are often associated with dose-dependent adverse effects. In contrast, Traditional Chinese Medicine (TCM) has garnered growing attention due to its distinctive therapeutic profile, and in particular, its multi-target and multi-pathway synergistic mechanisms. The Wnt/[Formula: see text]-catenin signaling pathway plays a crucial role in intracellular signal transduction and is closely associated with several key pathological processes involved in AD. This review provides a comprehensive analysis of the molecular interplay between the Wnt/[Formula: see text]-catenin signaling pathway and the pathogenesis of AD, as well as a specific focus on how natural compounds, herbal monomers, and classical TCM formulations modulate this pathway. Accumulating evidence suggests that TCM exerts neuroprotective effects by regulating Wnt/[Formula: see text]-catenin signaling to thereby suppress A[Formula: see text] deposition, preserve synaptic structure and tissue homeostasis, modulate cell proliferation and apoptosis, and maintain metabolic and redox homeostasis. Additionally, the review discusses key challenges, such as improving blood-brain barrier permeability and enhancing bioavailability, and outlines future directions involving advanced delivery systems and optimized administration routes. These insights provide a robust scientific foundation for the development of Wnt/[Formula: see text]-catenin-targeted therapies and highlight the potential of TCM in the clinical treatment of AD.

This paper comprehensively examines the anticancer mechanisms and therapeutic potential of β-sitosterol, a naturally occurring phytosterol found in various plants. β-Sitosterol has shown significant efficacy in inhibiting tumor growth and metastasis through various biological pathways, including inducing apoptosis, arresting cell cycle progression, and suppressing cell proliferation, invasion, and migration. We highlight the key mechanisms by which β-sitosterol exerts its effects, such as modulating apoptosis-related signaling pathways like those of the Bcl-2 family proteins and reactive oxygen species production. Furthermore, β-sitosterol's role in disrupting the epithelial-mesenchymal transition and its impact on tumor metabolism, particularly in cholesterol and glucose regulation, are discussed. The article also explores the potential of β-sitosterol to enhance chemotherapy sensitivity, making it a promising adjunct in cancer treatment. Additionally, we incorporate a bibliometric analysis and network pharmacology approach to identify potential therapeutic targets and pathways influenced by β-sitosterol, providing new insights into its multifaceted anticancer activities. These findings underscore the potential of β-sitosterol as a novel anticancer agent, warranting further research and clinical investigation to optimize its future therapeutic application.

Vascular dementia (VD) is the second most common type of dementia after Alzheimer's disease (AD), and chronic cerebral hypoperfusion (CCH) is the main causative factor of VD. Previous reports have confirmed that there is a relationship between VD and gut microbiota, and that some plant-based foods can improve VD through the gut-brain axis (GBA). Panax notoginseng leaves are a specialty food in Yunnan, China, and saponin is its main bioactive component. In this study, we investigated the effects of the total saponins of Panax notoginseng leaves (TSPNL) on CCH-induced VD and their potential mechanisms. In this experiment, the model was replicated using bilateral common carotid artery occlusion (BCCAO) and divided into Sham, Model, TSPNL-L, TSPNL-H and Positive drug control. At the end of the treatment, behavior, brain-derived neurotrophic factor (BDNF), hypothalamic-pituitary-adrenal (HPA) axis-related indices, neuronal apoptosis-related indices, gut microbiota composition, and colon and brain pathology were tested. The results showed that TSPNL attenuated CCH-induced VD, promoted BDNF synthesis, and inhibited neuronal apoptosis. Predictions of network pharmacology and experiments demonstrated that these beneficial effects are mediated in part through BDNF-TrKB-PI3K/Akt signaling. In addition, TSPNL prevented intestinal dysbiosis by increasing the abundance of the probiotic Ligilactobacillus and decreasing the abundance of the deleterious bacterium Clostridia_ UCG_014_unclassified relative to the model group. TSPNL was also able to partially reverse intestinal barrier disruption and inhibit intestinal inflammation and the hyperactivation of the HPA axis. The results of this study support the conclusion that TSPNL has potential in the prevention of CCH-induced VD and warrants further investigation.

Cancer remains a major global health challenge, which drives the ongoing search for effective and less toxic treatment options. Due to its demonstrated anticancer properties, Artesunate (ART), a well-established antimalarial agent, has gained increasing attention as a promising candidate for oncological applications. This systematic review provides a comprehensive evaluation of ART's therapeutic potential by examining its anticancer efficacy, underlying molecular mechanisms, synergistic capacity, and pharmacological toxicity. An extensive search of the PubMed and Web of Science databases identified relevant peer-reviewed experimental and clinical studies that investigated ART's anticancer activity. The data were systematically extracted with an emphasis on research methodologies, treatment regimens, and mechanistic pathways. Evidence from in vitro and in vivo studies confirms ART's broad efficacy against a range of malignancies, including hematological cancers such as lymphoma, acute myeloid leukemia, and multiple myeloma, and various solid tumors such as lung, pancreatic, colorectal, hepatocellular, breast, ovarian, bladder, gastric, cervical, glioblastoma, melanoma, retinoblastoma, and esophageal cancers. ART exerts its anticancer effects through multiple pathways, including ROS-mediated programmed cell death, ferroptosis induction, mitochondrial dysfunction, the inhibition of proliferation, and the disruption of key signaling networks such as NF-κB, STAT3, and Wnt/β-catenin cascades. Additionally, ART has been shown to enhance the efficacy of conventional chemotherapeutic agents like cisplatin and gemcitabine while also reducing associated toxicities and overcoming drug resistance. These attributes highlight ART's considerable potential as a versatile anticancer agent that exhibits multiple - mechanisms of action and favorable compatibility with existing therapies. However, further rigorous clinical studies are essential to fully establish its therapeutic utility and facilitate its integration into modern oncology practice.

Colon adenocarcinoma (COAD) is characterized by the metabolic reprogramming, such as the Warburg effect, which drives tumor progression and immunosuppression. Hypoxia-inducible factor 1[Formula: see text] (HIF-1[Formula: see text] and lactate dehydrogenase A (LDHA) are critical regulators of this metabolic shift, but existing therapies are insufficiently specific to it. This study investigates the antitumor mechanisms of cannabidiol, a non-psychoactive phytocannabinoid, by using integrative multi-omics and functional validation. Single-cell transcriptomics revealed that cannabidiol reduced tumor cell proportions and suppressed glycolytic activity in COAD. Network pharmacology identified PTGS2 as a central target, with proteomic data confirming its overexpression in COAD tissues and association with poor prognosis. In vitro, cannabidiol inhibited COAD cell proliferation, migration, and colony formation while downregulating HIF-1[Formula: see text], LDHA, and GLUT1 expression. Metabolic assays demonstrated associated dose-dependent reductions in ATP production, glucose uptake, and lactate levels. Rescue experiments using the HIF-1[Formula: see text] agonist DMOG partially reversed cannabidiol's antiglycolytic and antitumor effects, and thus confirmed pathway dependency. Synergy with the glycolysis inhibitor 2-DG enhanced therapeutic efficacy, which highlighted cannabidiol's potential to overcome metabolic resistance. These findings establish cannabidiol as a novel inhibitor of HIF-1[Formula: see text]/LDHA-driven glycolysis, and thus provide a translational strategy for metabolic vulnerability in COAD.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatocellular injury, inflammation and fibrosis, which result from the accumulation of hepatic lipids. As one of the most prevalent chronic liver diseases globally, its pathogenesis remains complex. With the improvement in living standards, the incidence of NAFLD is expected to rise, drawing increasing attention to its development, prevention, and treatment from researchers worldwide. Currently, the therapeutic progress achieved by Western medicine in treating NAFLD remains limited, and its clinical efficacy is unsatisfactory. In contrast, Chinese medicine has a long history in the treatment of NAFLD, and possesses such advantages as fewer side effects, and multi-component, multi-target, and multi-pathway therapeutic actions. In recent years, several studies have demonstrated that Chinese medicine can modulate the progression of NAFLD by regulating relevant signaling pathways both in vivo and in vitro. However, comprehensive reviews on this topic remain scarce. Therefore, in this paper, a literature search was conducted using PubMed and Web of Science to summarize key signaling pathways implicated in Chinese medicine-mediated interventions in NAFLD, including AMPK, mTOR, PI3K/Akt, Toll-like receptor, NF-[Formula: see text]B, and MAPK pathways. Furthermore, the specific anti-NAFLD mechanisms of these pathways were elaborated. The objective of this paper is to provide an overview of the effective therapeutic pathways and mechanisms associated with Chinese medicine in the treatment of NAFLD, and to thereby offer a theoretical foundation and innovative perspectives for future research and clinical applications.

Rhizoma Corydalis (RC) is a traditional Chinese herbal medicine (TCM) known as Yan Hu Suo or Yuan Hu in China. This plant is a limited resource distributed in Zhe Jiang, Shaan Xi, Jiang Su, and other places of China. The aim of this paper is to provide a systematic review on the traditional uses, botany, phytochemistry, pharmacology, and pharmacokinetics of this plant. Furthermore, the potential development and perspectives for upcoming research on RC are also discussed. At present, over 160 compounds have been isolated and identified from RC, including alkaloids, anthraquinone, amino acids, organic acids, essential oils and microelements. RC was demonstrated to possess wide-reaching pharmacological properties, including effects on the nervous system, cardiovascular system, analgesic properties, sedative and anti-epileptic effects, antidepressive and anti-anxiety effects, antimyocardial ischemia/reperfusion (MIR) injury activities, anticerebral ischemia/reperfusion (CIR) injury activities, gastro-protective effects, and anticancer effects. In TCM clinical treatments, Angelicae Sinensis Radix, Myrrha, Cinnamomi Ramulus, and Paeoniae Radix Rubra were compatible with RC and frequently used to treat chest pain, lumbago, and abdominal pain. However, further research elucidating the signaling pathways between chemical compounds and targets in order to better understand the mechanism by which RC might be treated, and to optimize for quality control in processing products of RC is necessary.

Oxidative stress represents a pivotal mechanism in the pathogenesis of numerous chronic diseases. The Kelch-like ECH-associated protein 1-transcription factor NF-E2 p45-related factor 2 (KEAP1-NRF2) pathway plays a crucial role in maintaining redox homeostasis and regulating a multitude of biological processes such as inflammation, protein homeostasis, and metabolic homeostasis. In this paper, we present the findings of recent studies on the KEAP1-NRF2 pathway, which have revealed that it is aberrantly regulated and induces oxidative stress injury in a variety of diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, respiratory diseases, digestive diseases, and cancer. Given this evidence, targeting KEAP1-NRF2 represents a highly promising avenue for developing therapeutic strategies for chronic diseases, and thus the development of appropriate therapeutic strategies based on the targeting of the NRF2 pathway has emerged as a significant area of research interest. This paper highlights an overview of current strategies to modulate KEAP1-NRF2, as well as recent advances in the use of natural compounds and traditional Chinese medicine, with a view to providing meaningful guidelines for drug discovery and development targeting KEAP1-NRF2. Additionally, it discusses the challenges associated with harnessing NRF2 as a therapeutic target.

Epimedium has been widely used in traditional Chinese medicine for several thousands of years. This plant is known for tonifying kidney Yang, strengthening muscles and bones, and dispelling wind and dampness. It is worth noting that icaritin, a prenylated flavonoid isolated from Epimedium, has received increasing attention in recent years due to its wide range of pharmacological activities. Icaritin exhibits significant therapeutic potential against various diseases, such as osteoporosis, tumors (hepatocellular carcinoma, stomach cancer, breast cancer, and glioblastoma), cerebral ischemia skin injury, thrombocytopenia, and systemic lupus erythematosus. We review the pharmacological activities of icaritin and its potential molecular mechanisms for the treatment of related diseases. The data suggest that icaritin can have the pharmacological effects of mediating Wnt/[Formula: see text]-catenin, IL-6/JAK2/STAT3, AMPK/mTOR, PTEN/AKT, MAPK, NF-[Formula: see text]B, and other signaling pathways. This paper also discusses the progress of clinical trials of icaritin. Icaritin was approved by the State Food and Drug Administration in January 2022 for the treatment of advanced HCC, and has various clinical drug prospects. Although it has some disadvantages, including poor solubility, and low bioavailability, icaritin is still a prospective candidate for the development of naturally derived drugs, especially in the treatment of tumors and inflammatory diseases. This review aims to update and deepen the understanding of icaritin, and provide a theoretical basis for its further study.