The American journal of Chinese medicine最新文献

With the continuous advancements in modern medicine, significant progress has been made in the treatment of lung cancer. Current standard treatments, such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, have notably improved patient survival. However, the adverse effects associated with these therapies limit their use and impact the overall treatment process. Traditional Chinese medicine (TCM) has shown holistic, multi-target, and multi-level therapeutic effects. Numerous studies have highlighted the importance of TCM's role in the comprehensive management of lung cancer, demonstrating its benefits in inhibiting tumor growth, reducing complications, mitigating side effects, and enhancing the efficacy of conventional treatments. Here, we review the main mechanisms of TCM in combating lung cancer, inducing cancer cell cycle arrest and apoptosis. These include inhibiting lung cancer cell growth and proliferation, inhibiting cancer cell invasion and metastasis, suppressing angiogenesis and epithelial-mesenchymal transition (EMT), and modulating antitumor inflammatory responses and immune evasion. This paper aims to summarize recent advancements in the application of TCM for lung cancer, emphasizing its unique advantages and distinctive features. In promoting the benefits of TCM, we seek to provide valuable insights for the integrated treatment of lung cancer.

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.

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.

Palmatine (PAL) and berberine are both classified as protoberberine alkaloids, derived from several traditional Chinese herbs such as Coptis chinensis Franch. and Phellodendron chinense Schneid. These compounds are extensively used in treating dysentery and colitis. PAL is one of the crucial quality markers for these plants in the Chinese Pharmacopoeia. A key metabolite of PAL, 8-Oxypalmatine (OPAL), shows favorable anti-inflammatory activity and better safety compared to PAL, though its mechanisms in ulcerative colitis (UC) are not fully understood. This study used a dextran sodium sulfate-induced colitis mouse model to explore OPAL's effects. The results indicated that OPAL provided superior therapeutic effects to those of PAL, alleviating colitis symptoms and reducing colon inflammation by modulating pro-inflammatory (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and anti-inflammatory (transforming growth factor-β and interleukin-10) cytokines. Additionally, OPAL helped rebuild the mucus barrier and upregulated tight junction proteins, thereby restoring intestinal integrity. Notably, OPAL inhibited the M1 macrophages infiltration while promoting M2 macrophage distribution in the colon. Its role in fostering M2 polarization and modulating the inflammatory cytokine profile was further confirmed in vitro. Importantly, the anti-inflammatory effects were primarily linked to AMP-activated protein kinase activation, which subsequently inhibited the nuclear factor-kappa B pathway. These findings highlight OPAL as a crucial active metabolite responsible for the therapeutic effects of PAL against UC, emphasizing its potential as a novel treatment for this condition.

Colorectal cancer, characterized by its high incidence, concealed early symptoms, and poor prognosis at advanced stages, ranks as the third leading cause of cancer-related deaths worldwide. Astragalus membranaceus (AM) refers to the dried roots of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao and Astragalus membranaceus (Fisch.) Bge. In the theory of Traditional Chinese Medicine (TCM), it is believed to have the functions of tonifying qi and lifting yang, as well as generating body fluids and nourishing blood. It can effectively treat cancer caused by the deficiency of vital energy and susceptibility to external diseases. Modern research has confirmed that the active components of AM, including Astragalus polysaccharides, flavonoids (formononetin and calycosin), Astragalus saponins (Astragaloside I and Astragaloside III), and Astragalus nanovesicles, are effective in the treatment of colorectal cancer. The mechanisms mainly involve inducing apoptosis, inhibiting tumor angiogenesis and the metastasis of cancer cells, regulating the cell cycle and tumor microenvironment, and reversing drug resistance. Moreover, it offers a synergistic enhancement when used in combination with chemotherapy, radiotherapy, targeted therapy, or surgical treatment. AM also has great potential in treating colorectal cancer when combined with other herbs. This review summarizes the relevant research findings on the treatment of colorectal cancer with AM, as well as its main pharmacological effects and molecular mechanisms, aiming to provide guidance for the development of new drugs, and offer direction for the conduct of more related research and promoting the development and application of AM.

This study aimed to clarify the protective effect of Glycyrrhizic acid (GL) against Diosbulbin B (DB) - induced liver injury in mice and investigate its mechanisms of action. A liver injury DB was established in mice through the oral administration of DB for 15 days. At the same time, GL was administered to the mice for treatment. After the experiment, the pharmacodynamics and mechanisms of GL in ameliorating DB-induced liver injury were explored using biochemical indexes, non-targeted metabolomics, targeted metabolomics, Western blotting analysis of protein expression, 16S rDNA sequencing, and Spearman correlation analysis. The results show reduced liver function indices and improved DB-induced hepatic pathological changes. It also attenuated DB-induced hepatic inflammation and oxidative stress. Hepatic metabolomics revealed that GL regulated ABC transporters and bile secretion. Targeted bile acid (BA) metabolomics and Western blotting demonstrated that GL improved DB-induced reduction in BA efflux by regulating FXR-mediated efflux transporters. Furthermore, analysis of 16S rDNA gene sequencing revealed that GL effectively restored the relative abundance of beneficial bacteria, reduced the relative abundance of harmful bacteria, and reinstated the structure of the intestinal flora. Additionally, correlation analyses between BA and intestinal flora indicated that Firmicutes, Bacteroidota, TDGA, DGA, UDGA, GDGA, THDGA, and HDGA could serve as major markers for DB-induced liver injury. In conclusion, GL significantly improved DB-induced liver injury by increasing the expression of Nrf2/FXR-BSEP/MRP2/P-gp/UGT1A1, promoting BA efflux, regulating intestinal flora, and alleviating inflammation and oxidative stress.

Osteoarthritis (OA) is the most common chronic degenerative joint disease, characterized by cartilage damage, synovial inflammation, subchondral bone sclerosis, marginal bone loss, and osteophyte development. Clinical manifestations include inflammatory joint pain, swelling, osteophytes, and limitation of motion. The pathogenesis of osteoarthritis has not yet been fully uncovered. With ongoing research, however, it has been gradually determined that OA is not caused solely by mechanical injury or aging, but rather involves chronic low-grade inflammation, metabolic imbalances, dysfunctional adaptive immunity, and alterations in central pain processing centers. The main risk factors for OA include obesity, age, gender, genetics, and sports injuries. In recent years, extensive research on gut microbiota has revealed that gut dysbiosis is associated with some common risk factors for OA, and that it may intervene in its pathogenesis through both direct and indirect mechanisms. Therefore, gut flora imbalance as a pathogenic factor in OA has become a hotspot topic of research, with potential therapeutic connotations. In this paper, we review the role of the gut microbiota in the pathogenesis of OA, describe its relationship with common OA risk factors, and address candidate gut microbiota markers for OA diagnosis. In addition, with focus on OA therapies, we discuss the effects of direct and indirect interventions targeting the gut microbiota, as well as the impact of gut bacteria on the efficacy of OA drugs.

Ginseng is a well-established functional food for brain health. However, its active ingredients have not yet been identified. Gintonin is a promising compound isolated from white/red ginseng. Its lysophosphatidic acid (LPA) is an exogenous G protein-coupled LPA receptor (LPAR) agonist. Korean red ginseng marc (KRGM) is a by-product after KRG extractions. In a previous study, we demonstrated that KRGM-derived gintonin (KRGM-G) contains LPA C[Formula: see text], a major functional component of both white and red ginseng. [Formula: see text] transgenic mice and SH-SY5Y cells were used to determine molecular mechanisms involved in KRGM-G-mediated anti-Alzheimer's disease (AD) effects. KRGM-G improved cognition impairment associated with alleviation of amyloid-β accumulation in the brain (hippocampus and cortex) in [Formula: see text] mice. KRGM-G inhibited activation of inflammatory cells (Iba-1-positive microglia and GFAP-positive astrocyte) and expression of pro-inflammatory mediators (IL-1β, IL-6, iNOS, or NO) in the brains of [Formula: see text] mice, increased the viability of H₂O₂-induced SH-SY5Y cells, and down-regulated the p38 MAPK, NF-κB p65, and STAT3 signaling pathways. KRGM-G also prevented the formation of reactive oxygen species and stimulated the Nrf2-HO-1/4-HNE signaling pathway in the brains of [Formula: see text] mice and SH-SY5Y cells. Interestingly, these positive effects of KRGM-G on AD-related symptoms and immunopathology were associated with up-regulation of LPAR1 in the brains of [Formula: see text] mice. These results suggest that KRGM-G might improve AD-related cognitive dysfunction by stimulating the anti-oxidant pathway (Nrf2) and inhibiting inflammatory pathways (p38/NF-κB/STAT3) through LPAR1.

The accumulation of aging cells significantly contributes to chronic inflammatory diseases such as atherosclerosis. Human carotid artery single-cell sequencing has shown that large numbers of aging foam cells are present in the plaques of human patients. Berberine (BBR) has been shown to inhibit cell senescence, however, the mechanisms involved in its treatment of atherosclerotic senescence have not yet been determined. Changes in plaque morphology and blood chemistry were observed in ApoE[Formula: see text] mice fed with a high-fat diet before and after BBR treatment. Inflammatory proteins linked to the senescence-associated secretory phenotypes (SASP) were detected in RAW264.7 and peritoneal macrophage-derived foam cells. Smart-seq analysis was used to explore the pathways associated with BBR therapy for atherosclerosis. Finally, the effect of lentivirus-mediated knockdown of RXRα in macrophages in plaques on atherosclerosis treatment with BBR was determined. We found that BBR reduced inflammation linked to SASP in atherosclerosis through the RXRα/PPARγ/NEDD4 signaling pathway. BBR increased GATA4 binding to p62, promoted ubiquitination, and inhibited SASP-associated protein production in RAW264.7 and peritoneal macrophage-derived foam cells. Mechanistically, according to the Smart-seq results, BBR activated RXRα and PPARγ, synergistically increased NEDD4 transcription levels, and promoted ubiquitination-mediated degradation of the GATA4/p62 complex. Additionally, the anti-aging impact of BBR on atherosclerosis was negated when macrophage-specific RXRα was knocked down using lentivirus (pLVCD68-shRNA RXRα) in ApoE[Formula: see text] mice. BBR activated PPARγ through RXRα-PPARγ immune complex in macrophage-derived foam cells, increased NEDD4 transcriptional activity, promoted ubiquitination of GATA4-p62 complex, and inhibited SASP-related inflammation. These findings suggest the potential of BBR as a novel approach to addressing SASP-associated inflammation in atherosclerosis.

Panax notoginseng (PN) root is a renowned nutritional supplement, health food additive, and traditional medicine that maintains homeostasis within the human microcirculatory system. Notoginsenoside R1 (NG-R1), an active compound derived from PN root, has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidant, anticancer, antimicrobial, and angiogenic effects. However, NG-R1's pharmacokinetic properties and pharmacological activities have not been systematically elucidated. In this paper, the pharmacokinetic properties of NG-R1, its pharmacological effects, mechanisms of actions, and structure-activity relationship have been reviewed. Notably, NG-R1 inhibits tumor necrosis factor α (TNF-α) expression, enhances the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and enhances the expression of vascular endothelial growth factor receptor (VEGFR). The pharmacological effects of NG-R1 are associated with the modulation of several signaling pathways, such as mitogen-activated protein kinase (MAPK)/nuclear factor κ-B (NF-κB), NRF2/antioxidant response element (ARE), Wnt/β-catenin, and phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT). NG-R1 offers potentially protective effects against numerous diseases, including cardiovascular, neurological, renal, pulmonary, bone, and diabetes-related conditions. Although the pharmacological activities and diverse effects of NG-R1 have been demonstrated in various diseases, its clinical applications are limited by poor bioavailability. Several strategies have been explored to improve the pharmacokinetic profile of NG-R1, making it a promising candidate for drug development.