The American journal of Chinese medicine最新文献

Diabetic kidney disease (DKD) is one of the most common microvascular complications associated with diabetes mellitus. However, the existing treatment approaches, aimed at delaying the onset of DKD, exhibit limited efficacy. The flavonoid nobiletin has demonstrated substantial lipid-lowering and insulin-sensitizing effects in mice exhibiting metabolic dysfunction, but the therapeutic potential and mechanism of nobiletin in the context of DKD remains to be comprehensively elucidated. In this study, the active components of polymethoxylated flavonoids (PMFs) were identified via UPLC. A DKD rat model was established through a high-fat diet and the administration of streptozotocin via intraperitoneal injection. The effect and mechanism of nobiletin on DKD was evaluated by histological, biochemical, molecular, and multi-omics analysis. We found that treatment with PMFs and nobiletin inhibited ferroptosis and EMT in high glucose and insulin-induced models, protected the glomerular filtration barrier integrity, and concurrently suppressed ROS, Fe[Formula: see text], and MDA while increasing the GSH level. Animal experiments indicated that nobiletin treatment markedly impeded the progression of DKD and alleviated both EMT and endothelial dysfunction. Moreover, nobiletin significantly preserved the integrity of the intestinal barrier and enriched the diversity of gut microbiota. In conclusion, our findings indicate that nobiletin could attenuate DKD and concomitantly limit ferroptosis and EMT, and that the gut-kidney axis played an important role in its effects.

The activation of the NLRP3 inflammasome is critical to inducing microglial activation and pyroptosis following cerebral ischemia/reperfusion (I/R). Suppressing the neurotoxicity of activated microglia has become an effective approach for treating cerebral I/R injury. Rhein is an anthraquinone compound found in rheum, and possesses anti-inflammatory, antagonistic, and antifibrotic effects. This study assessed whether rhein influences NLRP3 inflammasome activation, pyroptosis, and the polarization of microglia after cerebral I/R or oxygen-glucose deprivation and reoxygenation (OGD/R). Cerebral I/R models were established in Sprague-Dawley rats via transient middle cerebral artery occlusion (tMCAO) surgery, and OGD/R models were established in BV-2 cells using a hypoxic chamber. After treatment with rhein, the infarction/edema ratio, BV-2 cell viability, expression of NLRP3 inflammasome, and levels of microglial polarization and pyroptosis were detected. Finally, NLRP3 inhibitors (MCC950) were used to assess whether rhein exerted its effects by inhibiting the activation of the NLRP3 inflammasome in regulating pyroptosis and polarization of microglia. Rhein permeated the blood-brain barrier of rats after tMCAO, protected against tMCAO-induced brain injury, and inhibited microglial NLRP3 inflammasome activation and pyroptosis after tMCAO or OGD/R. It also suppressed tMCAO- or OGD/R-induced polarization of the M1 phenotype in microglia, and skewed them toward the M2 phenotype. Moreover, co-administration of rhein and MCC950 synergistically enhanced both the inhibition of the NLRP3 inflammasome activation/pyroptosis axis and the regulation of microglial polarization after tMCAO or OGD/R. Rhein exerts neuroprotective effects by regulating microglial pyroptosis and polarization through inhibiting the activation of NLRP3 inflammasome after tMCAO or OGD/R.

Myocardial infarction (MI) is a severe cardiovascular disorder characterized by an irreversible myocardial necrosis caused by acute ischemia. The typical manifestations of MI include persistent substernal chest pain, dyspnea, nausea, vomiting, and diaphoresis. Astragaloside IV (AS-IV), a major bioactive component of Astragalus membranaceus, has been extensively investigated over the past decade. Evidence indicates that AS-IV exerts multifaceted protective effects against MI by modulating various key signaling pathways involved in anti-inflammatory, anti-oxidative stress, and antifibrotic activities, the inhibition of cardiomyocyte apoptosis, and the maintenance of mitochondrial homeostasis. These pathways include TLR4/NF-κB, PI3K/AKT, TGF-β/Smad2, ROS/caspase-1/GSDMD, Wnt/β-catenin, AMPK/ACSS2/PPARα, Sirt3/Drp1, and PINK1/Parkin. Although mechanistic studies have substantially advanced, the clinical application of AS-IV in MI remains in the exploratory stage. Further well-designed clinical trials are necessary in order to validate the therapeutic efficacy and safety of AS-IV, thereby facilitating its translation from experimental research to clinical practice, and offering new insights and potential strategies for MI management.

Type 2 diabetes mellitus (T2DM), a globally prevalent chronic metabolic disorder, imposes a significant worldwide public health burden. As a vital "microbial organ" within the human body, the balance of the gut microbiota (GM) structure and function is crucial for maintaining host metabolic health. Short-chain fatty acids (SCFAs), the metabolic products of GM, serve as key signaling molecules that play central roles in maintaining intestinal homeostasis, regulating systemic energy metabolism, and improving insulin sensitivity. Dysregulation of the "GM-SCFA axis" has emerged as a core pathological mechanism in the onset and progression of T2DM. Traditional Chinese Medicine (TCM) possesses unique advantages in T2DM treatment through its "holistic regulation and multi-targeted intervention," which enables precise modulation of the GM-SCFA axis. This paper provides a systematic review of the pathological mechanisms by which dysregulation of the GM-SCFA axis induces T2DM, and specifically covers energy metabolism disorders, insulin resistance, intestinal barrier impairment, chronic low-grade inflammatory activation, abnormal bile acid metabolism regulation, and disrupted gut-pancreatic axis and gut-brain axis signaling. Using keywords such as TCM, GM, SCFAs, and T2DM, we conducted an extensive literature search across databases including PubMed, Google Scholar, and Web of Science for publications from the past decade. This systematic review examines the application of TCM in regulating the "GM-SCFA axis" from multiple perspectives: Chinese herbal compounds (e.g., Zuogui Jiangtang Qinggan Formula, Gegen Qinlian Decoction), Chinese patent medicines (e.g., Shouhui Tongbian Capsules, Compound Danshen Dripping Pills), single-herb Chinese medicines (e.g., Edgeworthia gardneri, Alpinia oxyphylla), single-component compounds from TCM (e.g., Cyclocarya paliurus polysaccharide, Achyranthes bidentata polysaccharide water-soluble 1), and other TCM therapies (e.g., tuina, acupuncture). This study aims to systematically explore the mechanisms by which dysregulation of the "GM-SCFA axis" induces T2DM while providing novel therapeutic strategies for T2DM prevention and treatment using TCM. It also seeks to establish scientific foundations for developing novel TCM intervention strategies targeting the "GM-SCFA axis" in T2DM management.

Polygonati Rhizoma (PR), a plant with dual medicinal and edible properties, has been utilized for over two millennia, and is widely distributed across temperate to frigid zones in the Northern Hemisphere. In ancient China, it was revered as the "immortals' surplus grain," and the classical medical text "Ming Yi Bie Lu" documents its health benefits. These benefits include "tonifying the middle jiao, replenishing qi, dispelling rheumatism, and harmonizing the five viscera," which particularly emphasizes the efficacy of PR in both nourishing the liver and kidneys and prolonging lifespan. Modern studies reveal that PR rhizomes are rich in fructans, non-starch polysaccharides, amino acids, and other nutritional components, and their primary active constituents include polysaccharides, saponins, flavonoids, and polyphenols. These compounds exhibit anti-aging, antidepressant, anti-osteoporotic, and neuroprotective activities. Notably, raw PR contains calcium oxalate raphides, which induce an irritating sensation in the throat. However, processing can not only mitigate this irritation but also enhance its anti-oxidant and anti-aging capacities. Although progress has been made toward understanding its polysaccharides and saponins, the mechanisms underlying its other critical components, such as flavonoids, polyphenols, and oligosaccharides, remain underexplored. This review systematically examines the geographic distribution, traditional and modern applications, and pharmacological activities of PR, and the transformation patterns of key bioactive constituents that occur during its processing. Furthermore, it critically addresses research gaps, and particularly addresses both the relative lack of mechanistic studies on functional components and the lack of correlation between processing-induced compositional changes, pharmacological efficacy, and quality control. These insights contribute to advancing PR exploration, promoting sustainable utilization, and establishing scientific evidence-based quality standards.

Neurodegenerative diseases (NDDs), characterized by a progressive neuronal loss that leads to cognitive and motor deficits, both pose a significant global health challenge and have limited treatment options. This review explores the therapeutic potential of gastrodin (GAS) and gastrodigenin (HBA), which are the key bioactive constituents of Gastrodia elata Blume (GEB). These compounds demonstrate significant neuroprotective effects across various NDD models which include Alzheimer's disease (AD) and Parkinson's disease (PD). Their mechanisms involve multi-target actions such as inhibiting pathological protein aggregation (Aβ, tau, α-synuclein), attenuating neuroinflammation via the TLR4/NF-κB and NLRP3 pathways, reducing oxidative stress through Nrf2 activation, mitigating mitochondrial dysfunction, inhibiting ferroptosis, and counteracting glutamate excitotoxicity. While pharmacokinetic studies reveal favorable brain distribution for HBA, its clinical translation faces challenges including blood-brain barrier penetration and the need for human trials. Advances in delivery systems, like focused ultrasound, show promise. This review both synthesizes the current evidence on GAS and HBA to highlight their multifaceted mechanisms and potential as multi-target agents for NDD intervention, and outlines future research directions for their clinical development.

Breast cancer (BC) is a major cause of cancer-related mortality worldwide. While mainstream anticancer therapies have improved clinical outcomes, they are often associated with significant toxicity and drug resistance. Traditional Chinese medicine (TCM) has received increasing recognition as a valuable complementary approach in oncology. This review summarizes the current evidence supporting the integrative use of TCM in BC management. Clinical studies indicate that TCM formulations can alleviate the adverse effects induced by chemotherapy and targeted therapy to thereby enhance patients' quality of life and treatment adherence. As an adjuvant, TCM also shows the potential to improve both the efficacy of conventional treatments and survival outcomes. Preclinical investigations reveal that bioactive herbal compounds exert multi-target antitumor effects by modulating key mechanisms such as programmed cell death, proliferation, metastasis, cell-cycle progression, drug resistance, aerobic glycolysis, and antitumor immunity. Furthermore, advanced drug delivery systems are being developed to overcome the inherent limitations of herbal compounds. However, challenges which warrant further investigation, including heterogeneous study designs, the standardization of formulations, and potential herb-drug interactions, remain under-explored. Overall, TCM represents a promising complementary strategy for BC. Future efforts should prioritize well-designed clinical trials, mechanistic elucidation, and the development of integrated precision medicine models to optimize patient care.

Ulcerative colitis (UC) is a growing global health concern, but there remains a lack of natural food sources and multi-targeted drugs to effectively it. Codonopsis pilosula (dangshen, DS), a medicinal food used in traditional Chinese medicine, offers more comprehensive benefits than conventional drugs due to the numerous active compounds, such as lobetyolin, tangshenoside I, codonopsine, succinic acid, and raffinose, it contains. DS can be safely incorporated into diets to enhance UC treatment compliance and continuous management. This study explored the therapeutic effects and mechanisms of DS using microbial sequencing, metabolomics, and experimental validation. DS alleviated UC symptoms in mice to ultimately achieve reduced weight loss, colon shortening, disease activity, and histopathology scores. It lowered pro-inflammatory cytokine levels (IL-6, IL-1β, TNF-[Formula: see text], balanced Th17 and Treg cells, and enhanced the intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin, E-cadherin). In addition, DS significantly reduced the abundance of pathogenic Escherichia-Shigella by modulating the composition of the intestinal flora and increasing the production of tryptophan metabolites (5-hydroxyindole-3-acetic acid (5-HIAA) and kynurenic acid (KYNA)) through probiotic bacteria, like Alistipes and Lactobacillus, which act as aromatic hydrocarbon receptor (AhR) ligands. We found that Alistipes onderdonkii cultured in vitro produced 5-HIAA, and that DS could further increase 5-HIAA levels. In addition, both 5-HIAA and DS activated AhR in turn. The diminished efficacy of DS in UC after colony clearance was accompanied by a decrease in the level of AhR, which suggests the importance of bacterial-derived metabolites as mediators of the efficacy of DS. The metabolomics results showed that DS mainly exerted its regulatory effects by modulating arachidonic acid metabolism and tryptophan metabolism. Based on our data, which elucidated the relationship between AhR and anti-inflammatory effects, we identified the AhR/NF-κBp65 signaling pathway as a potential pharmacological mechanism by which DS is associated with UC amelioration.

Cepharanthine (CEP), a natural compound derived from the plant Stephania cephalantha Hayata, demonstrates pharmacological properties including anti-inflammatory, immuno-regulatory, antiviral, antitumor and antiparasitic effects. Due to its insidious progression and drug resistance, gastric cancer (GC) continues to have a high incidence and mortality rate worldwide. While the great potential of ferroptosis in cancer therapy is well-established, and CEP has shown potential antitumor activity, the role of ferroptosis in CEP's impact on GC remains unknown. Our aim in this study is to uncover what role ferroptosis has in the impact of CEP on GC. To investigate this, cell viability was measured by CCK-8 assay, and the effect of CEP on GC cell ferroptosis was assessed by Fe2[Formula: see text], DCFH-DA, and TEM. Integrated transcriptomic analyses revealed the critical pathways involved in CEP-induced ferroptosis, and JC-1, MitoSOX Red, Mito-Tracker, and immunofluorescence staining were used to evaluate mitophagy. The interaction between CEP and PINK1 was further confirmed by molecular docking, CETSA, and DARTS, and a xenograft tumor was used both to evaluate the effect of CEP on GC and to verify its mechanism through immunohistochemistry and western blotting. It was found that CEP could induce ferroptosis in GC cells by inducing an increase in reactive oxygen species, malondialdehyde, and intracellular Fe[Formula: see text] levels, and that it had little effect on normal gastric epithelial cells. Mechanistically, CEP binds directly to RUNX2, PINK1, and FUNDC1 to thereby activate PINK1-mediated mitophagy, prompt FUNDC1 to recruit GPX4 into mitochondria, and ultimately lead to the autophagic degradation of GPX4 and ferroptosis. A subcutaneous tumor model in nude mice confirmed the ferroptosis-associated antitumor efficacy of CEP in vivo. This study highlights that the natural compound CEP exerts its antitumor effects by activating mitophagy-dependent ferroptosis through a multi-target effect. CEP thus shows great promise as a potential drug candidate for GC treatment.

Programmed death (PD-1) is an important immune checkpoint receptor expressed on the surface of T cells, B cells and natural killer (NK) cells. PD-L1 (B7-H1) is a critical ligand for PD-1, and is widely expressed in a variety of cancer cells, immune cells, and normal histocytes. It has been established that the PD-1/PD-L1 interaction can produce an immunosuppressive effect by suppressing T cell proliferation, cytokine secretion, and cytotoxicity. Currently, PD-1 and PD-L1 inhibitors are known to be promising anticancer agents that reverse the antitumor immune function of T cells by inhibiting the PD-1/PD-L1 axis. The monotherapy of PD-1/PD-L1 blockade, while effective in treating cancers, is limited by a low response rate, immune-related adverse events (irAEs), and drug resistance. Their combinations with surgery, chemotherapy, radiotherapy, immunotherapy, hormone therapy, and traditional Chinese medicine (TCM), due to a synergistic effect, have broadened the frontier of cancer research. Following a holistic principle, TCM serves as an adjuvant therapy with PD-1/PD-L1 blockade, and provides benefits through complicated mechanisms. We specifically focused on the profound significance of TCM's assistance of PD-1/PD-L1 blockade, and the opportunities and challenges of treating cancers with both TCM and PD-1/PD-L1 blockade.