The American journal of Chinese medicine最新文献

Previous studies have reported inconsistent effects of green tea and its extract, epigallocatechin gallate (EGCG), on cancer prevention. We aimed to uncover the protective effects of green tea or EGCG against cancer, and to assess the dose-response relationship between cancer risk and green tea consumption by performing a comprehensive meta-analysis of cohort studies. A systematic search of the PubMed, Embase, CENTRAL, AMED, CancerLit, AACR, and CBM databases was conducted from the date of database creation to October 26, 2023, to collect randomized controlled trials (RCTs) and cohort studies on the association between green tea or green tea extract EGCG intake and the risk of cancer occurrence. Meta-analysis was performed using the RevMan 5.4 software and Stata 16 after an independent screening of the literature, extraction of information, and evaluation by two investigators of the risk of bias in included studies. Funnel plots were used to evaluate the publication bias. Dose-response relationships were evaluated using a two-stage restricted cubic spline regression model. The study protocol was registered in PROSPERO (CRD42023484787). The search yielded 2334 papers, and 43, including 7 RCTs and 36 cohort studies, were finally included. The results of the meta-analysis showed that green tea (relative risk [RR]: 0.91, 95% confidence interval [CI]: 0.86-0.96) and EGCG (RR: 0.72, 95% CI: 0.54-0.97) could reduce the risk of cancer to a certain extent compared to controls. It had an especially notable effect in reducing the risk of prostate cancer (RR: 0.43, 95% CI: 0.22-0.83), oral cancer (RR: 0.44, 95% CI: 0.01-0.87), gallbladder cancer (RR: 0.72, 95% CI: 0.51-0.94), and hematological cancers (RR: 0.72, 95% CI: 0.49-0.95), with statistically significant differences. Additionally, the dose-response meta-analysis revealed a significant negative linear correlation between high doses, long-term consumption of green tea, and cancer risk. Green tea or EGCG intake can prevent some cancers. High doses and long-term consumption of green tea could achieve better benefits, providing a basis for the dietary guidelines for green tea in preventing cancer. However, given the heterogeneity of the included studies, our findings still need to be validated by conducting higher-quality studies.

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.

Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum, is used in traditional Chinese medicine to treat aging-related symptoms. This study aimed to explore the regulatory effects of the n-butanol phenol glycosides-enriched fraction of FLL on muscular function and senescence-relevant biological events, such as fibrosis, senescence-associated secretory phenotypes (SASPs), activity of the renin-angiotensin system (RAS), and insulin resistance, in skeletal muscle. Naturally aging rats and D-gal-induced aging mice, both of which underwent bilateral ovariectomy, were orally administered with the n-butanol fraction of FLL for 8 weeks by intragastric gavage. Muscular functions were determined by the grip strength test and weight-loaded swimming test. The frozen sections of muscle tissue were subjected to several types of staining, and senescence-associated hallmarks, (pro)fibrotic factors, RAS components, and insulin signaling were detected in the serum and muscle by ELISA, PCR, and immunoblotting. The FLL fraction elevated muscle mass, improved muscle strength, and augmented the cross-sectional area of gastrocnemius fibers. It furthermore reversed changes in the expression of myogenic regulatory factors, inhibited the SASP and protein expression of senescent hallmarks, repressed the over-activity of muscular RAS (renin/Ang II), and reduced the fibrotic area and expression of type I and III collagens in the gastrocnemius. Moreover, abnormal alterations in protein expression (IRß/IRS-1/AKT/GSK-3ß signaling) were improved in the muscle. The in vivo study of 20-month-old ovariectomized rats confirmed the benefits of this fraction on muscle mass and myofiber area, as well as its inhibitory effects on both the accumulation of SA-ß-gal and collagen molecules and enhanced muscle myostatin levels and RAS activity. In addition, it promoted the distribution percentage of type IIb myofibers in the tibialis anterior muscle. Collectively, the n-butanol phenol glycosides-enriched fraction of FLL could be a potential source for novel and/or lead drugs for the treatment of muscle atrophy and sarcopenia in elderly women.

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.

Diabetes mellitus (DM) is considered to be the most widespread epidemic worldwide, and diabetic nephropathy (DN) is one of the most serious diabetic complications. Its complex pathogenesis makes treatment of DN an ongoing medical challenge. Ginseng (Panax ginseng. C. A Meyer) is a valuable medicinal herb with a long medicinal and culinary history. Ginsenoside Rg2 (Rg2), an important active component in ginseng, has effective inhibitory effects on lipogenesis and hepatic glucose production. However, the potential effect and mechanism of Rg2 on DN remain unclear. In this study, we investigated the effect of Rg2 on DN in high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice and high glucose (HG)-induced human kidney 2 (HK-2) cells. The results demonstrated that Rg2 significantly improved the levels of FBG, dyslipidemia and impaired kidney function in DN mice. Additionally, Rg2 decreased the phosphorylation levels of IKKβ, IκBα, and NF-κB p65, inhibited the activation of NLRP3 inflammasomes (NLRP3, ASC, and Caspase 1), and restrained release of inflammatory factors (IL-18 and IL-1[Formula: see text]. In HG-induced HK-2 cells, Rg2 showed similar inhibitory effects on pyroptosis via NF-κB/NLRP3 signaling pathways. Moreover, the effect of Rg2 on inhibiting the activation of NF-κB/NLRP3 signaling pathways may have a relationship to reducing the overproduction of reactive oxygen species (ROS), which is further supported by the ROS inhibitor N-acetylcysteine (NAC). In conclusion, our findings clearly indicated that Rg2 could prevent the progress of DN by inhibiting the activation of pyroptosis-related NF-κB/NLRP3 signaling pathways in vivo and in vitro, suggesting that Rg2 may be a novel and promising therapeutic agent in the treatment of DN.

Acupoint sensitization is characterized by a dynamic transition from a "resting state" to an "activated state". Research in this area holds significant implications not only for clinical acupoint selection but also for disease diagnosis. However, the biological mechanisms and material basis underlying this process require further investigation. In recent years, mast cells have been recognized as a key cellular foundation and an objective indicator of acupoint sensitization. When mechanical signals are transmitted to the subcutaneous tissue, mast cell aggregation and degranulation are induced. This leads to subsequent effects on the surrounding tissues, including blood vessels, muscles, and nerve endings, and thereby mediates the acupuncture effect. Evidence suggests that mast cells not only initiate acupuncture effects but also, through their released substances, reflect the dynamic and functional characteristics of acupoint sensitization. These cells also contribute to both central and peripheral sensitization processes. Despite recent advancements, several challenges remain in the study of acupoint sensitization, including the lack of dynamic monitoring methods, inconsistent indicators for measuring sensitization intensity, and an uncertainty regarding the potential of neurotransmitter-independent sensitization processes. This study provides an overview of mast cells and their role in the mechanism of acupoint sensitization, thereby aiming to establish a comprehensive network linking the central and peripheral systems to the neuroendocrine-immune system. The study aims to offer insights that will facilitate further exploration of the biological significance of acupoint sensitization and promote more in-depth research.