The American journal of Chinese medicine最新文献

Wilson's disease (WD) is a hereditary condition marked by abnormalities in copper metabolism, which precipitate a spectrum of neurological symptoms and cognitive impairments. Emerging research has highlighted ferroptosis (FPT) as a distinct type of programmed cell death, potentially linked to various cognitive dysfunctions. Nevertheless, the connection between FPT and cognitive impairment in Wilson's disease (WDCI) remains largely enigmatic. In our study, we utilized a multifaceted approach, combining reverse network pharmacology, data mining, and molecular docking techniques to explore the potential for treating WDCI via FPT-related pathways. This thorough analysis revealed a series of proteins, including P38[Formula: see text], GSK3[Formula: see text], P53, GPX4, and PTGS2, as pivotal targets for WDCI treatment. Notably, Diosgenin (DG) has been identified as a prospective core component in this therapeutic framework. In the WD copper-loaded rat model, evaluations using the Morris water maze (MWM), Y maze, hematoxylin and eosin staining, transmission electron microscopy (TEM), and immunofluorescence (IF) detection showed that DG significantly enhanced cognitive function recovery, reduced structural damage to hippocampal neurons, and protected mitochondrial integrity. In addition, Western blot (WB) and quantitative reverse transcription PCR (qRT-PCR) analysis showed that DG significantly upregulated the expression levels of proteins and mRNA such as P38[Formula: see text], GSK3[Formula: see text], P53, GPX4, and PTGS2 in animal and cell models. Furthermore, DG effectively reversed the dysregulated expression of oxidative stress markers, including [Formula: see text], malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS). This study elucidates the neuroprotective effect of DG on hippocampal neurons by activating the P38[Formula: see text]-mediated FPT pathway, highlighting its efficacy as a potent monomer in traditional Chinese medicine and illuminating its potential role in the clinical treatment of WDCI.

Cinnamon is one of the world's oldest and most popular spices, and is derived from the inner bark of several tree species from the genus Cinnamomum. During the last two decades, cinnamon has demonstrated beneficial metabolic effects not only in animal experiments but also in clinical trials. Even recent meta-analyses have shown the protective effects of cinnamon on different components of metabolic syndrome and their complications. In the last 5 years, several experimental studies have unraveled the intricate molecular mechanisms underlying the antihypertensive, antihyperglycemic, lipid-lowering, weight-lowering, and cardioprotective properties of cinnamon. This review paper will discuss how cinnamon and its active components, particularly cinnamaldehyde, suppress inflammation and oxidative stress, modulate mitochondrial dysfunction, and regulate glucose uptake, insulin resistance, lipogenesis, beta-oxidation, Ca2+ signaling, and other cellar events at the molecular level. Specifically, we will delve into the molecular mechanisms involved in the metabolic effects of cinnamon to provide a deeper insight into how cinnamon can bring such beneficial effects. This review hopes to encourage the use of cinnamon in clinical settings, guide the combination of cinnamon with other drugs used to treat different components of metabolic syndrome based on their mechanism of action, and support the concept of complementary medicine for metabolic diseases.

Hemorrhagic shock (HS) is a critical condition with high mortality caused by acute blood loss. Cardiac injury and dysfunction induced by HS is a major factor associated with the poor prognosis of affected patients. Schisandrin A (Sch A), a dibenzocyclooctadiene lignan extracted from Fructus schisandrae, exhibits multiple biological activities, including anti-inflammatory, and antioxidant effects. However, the effect of Sch A on HS-caused cardiac injury and its underlying mechanism still lack research. In this study, we established an HS rat model through blood loss from the femoral artery and monitoring mean arterial pressure (MAP) followed by fluid resuscitation. Our findings suggested that cardiac dysfunction and pathological injury were induced by HS and attenuated by Sch A treatment in a dose-dependent manner. Apoptosis in cardiac tissue was promoted by HS, but suppressed after administration of Sch A by decreasing the protein expressions of cleaved-caspase-3 and -9. Moreover, excessive ROS production induced by HS was mitigated by Sch A, and the levels of oxidative stress indicators were improved by Sch A. Additionally, HS triggered the reduction of mitochondrial membrane potential (MMP), and led to mitochondrial dysfunction. Sch A reversed this effect of HS on mitochondria. The transformation of cytochrome c (Cyto c) induced by HS was also restored by Sch A. Importantly, the activation of the Nrf2 signaling pathway mediated the protective effects of Sch A against cardiac injury induced by HS. In conclusion, it was found that Sch A ameliorated HS-induced cardiac injury and dysfunction through suppressing apoptosis and oxidative stress, as well as alleviating mitochondrial dysfunction via the Nrf2 signaling pathway.

Atherosclerosis (AS) is a major cause of mortality worldwide. Geniposide (GP) has lipolytic and anti-inflammatory effects and is widely administered for the treatment of cardiovascular disease. There is considerable evidence for the importance of autophagy in the cardiovascular system, and GP can promote autophagy and improve AS. However, the underlying mechanism is still unclear; network pharmacology and molecular docking suggest that GP may play anti-atherosclerotic roles by regulating the PI3K/Akt/mTOR pathway, which is a typical autophagy signal transduction approach. We further hypothesized that GP ameliorates AS by regulating autophagy through the PI3K/Akt/mTOR pathway. Oil Red O, Sirius Red, and Masson's trichrome staining revealed that GP can inhibit atherosclerotic lipid accumulation and stabilize plaques. Macrophages absorb lipids, form foam cells, and destabilize plaques. Immunohistochemical staining revealed that GP reduces the expression of F4/80, a major macrophage marker. We used western blotting (WB) and immunofluorescence (IF) to measure the protein levels of PI3K/Akt/mTOR, sequestosome-1, Beclin1, and long-chain base 3 (LC3). The experimental results revealed that GP can increase the expression of LC3, increase the expression of Beclin1, and decrease P62. Additionally, it inhibits the phosphorylation of PI3K/Akt/mTOR. In conclusion, GP can effectively treat AS by enhancing autophagy through the PI3K/Akt/mTOR pathway.

The aim of this study was to analyze the research hotspots and mechanisms of luteolin in tumor-related fields using bibliometric and bioinformatic approaches to guide future research. We conducted a comprehensive screening of all articles on luteolin and tumors in Web of Science from 2008 to 2023. The extracted words from these publications were visualized using VOSviewer, Scimago Graphica, and CiteSpace. Public databases were used to collect luteolin and tumor-related targets. GO and KEGG analyses of luteolin antitumor-related genes were performed using Metascape. Protein interaction networks were built with Cytoscape and STRING, identifying hub targets of luteolin in antitumor activity. Subsequently, the binding capacity of luteolin to these hub targets was assessed using molecular docking technology. We found that China dominated this field, the Egyptian Knowledge Bank published the most articles, and Molecules had the highest number of related publications. Recently, network pharmacology, target, traditional Chinese medicine, and nanoparticles have become research hotspots in luteolin's antitumor research. A total of 483 overlapping genes between luteolin and tumors were identified, and they were closely associated with the cancer-associated pathways, PI3K-Akt, and MAPK signaling pathways. Luteolin forms a complex network of antitumor-related genes, with TP53, TNF, STAT3, AKT1, JUN, IL6, and SRC playing key roles and showing strong binding affinity to luteolin. Computer technology is becoming increasingly integral to the discipline, and future research will focus on more precise antitumor mechanisms and effective clinical applications.

Panax notoginseng saponins (PNS), the primary medicinal ingredient of Panax notoginseng, mitigates cerebral ischemia–reperfusion injury (CIRI) by inhibiting inflammation, regulating oxidative stress, promoting angiogenesis, and improving microcirculation. Moreover, PNS activates nuclear factor erythroid 2-related factor 2 (Nrf2), which is known to inhibit ferroptosis and reduce inflammation in the rat brain. However, the molecular regulatory roles of PNS in CIRI-induced ferroptosis remain unclear. In this study, we aimed to investigate the effects of PNS on ferroptosis and inflammation in CIRI. We induced ferroptosis in SH-SY5Y cells via erastin stimulation and oxygen glucose deprivation/re-oxygenation (OGD/R) in vitro. Furthermore, we determined the effect of PNS treatment in a rat model of middle cerebral artery occlusion/reperfusion and assessed the underlying mechanism. We also analyzed the changes in the expression of ferroptosis-related proteins and inflammatory factors in the established rat model. OGD/R led to an increase in the levels of ferroptosis markers in SH-SY5Y cells, which were reduced by PNS treatment. In the rat model, combined treatment with an Nrf2 agonist, Nrf2 inhibitor, and PNS-Nrf2 inhibitor confirmed that PNS promotes Nrf2 nuclear localization and reduces ferroptosis and inflammatory responses, thereby mitigating brain injury. Mechanistically, PNS treatment facilitated Nrf2 activation, thereby regulating the expression of iron overload and lipid peroxidation-related proteins and the activities of anti-oxidant enzymes. This cascade inhibited ferroptosis and mitigated CIRI. Altogether, these results suggest that the ferroptosis-mediated activation of Nrf2 by PNS reduces inflammation and is a promising therapeutic approach for CIRI.

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.

Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-α, and IL-1β) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula: see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.

Asian ginseng, the root of Panax ginseng C.A. Meyer, occupies a prominent position in the list of best-selling natural products in the world. There are two major types of ginseng roots: white ginseng and red ginseng, each with numerous preparations. White ginseng is prepared by air-drying fresh Asian ginseng roots after harvest. Red ginseng is prepared by steaming roots in controlled conditions using fresh or raw Asian ginseng. Red ginseng is commonly used in Asian countries due to its unique chemical profile, different therapeutic efficacy, and increased stability. Compared with the widespread research on white ginseng, the study of red ginseng is relatively limited. In this paper, after a botanical feature description, the structures of different types of constituents in red ginseng are systematically described, including naturally occurring compounds and those resulting from the steam processing. In red ginseng phytochemical studies, the number of published reports on ginsenosides is significantly higher than that for other constituents. Up to now, 57 ginsenosides have been isolated and characterized in red ginseng. The structural transformation pathways during steaming have been summarized. In comparison with white ginseng, red ginseng also contains other constituents, including polyacetylenes, Maillard reaction products, other types of glycosides, lignans, amino acids, fatty acids, and polysaccharides, which have also been presented. Appropriate analytical methods are necessary for differentiating between unprocessed white ginseng and processed red ginseng. Specific marker compounds and chemical profiles have been used to discriminate red ginseng from white ginseng and adulterated commercial products. Additionally, a brief phytochemical profile comparison has been made between white ginseng and black ginseng, and the latter is another type of processed ginseng prepared from white or red ginseng by steaming several times. In conclusion, to ensure the safe and effective use of red ginseng, phytochemical and analytical studies of its constituents are necessary and even crucial.