The American journal of Chinese medicine最新文献

Liver cirrhosis is a critical stage in the progression of various chronic liver diseases, often leading to severe complications such as ascites, hepatic encephalopathy, and a high mortality rate, and it thus poses a serious threat to patient life. The activation of hepatic stellate cells is a central driver of disease progression. Cellular autophagy, a lysosome-mediated degradation process, plays a key role in maintaining cellular function and dynamic homeostasis. Research has shown that autophagy is closely associated with proteins like LC3, Beclin-1, P62, and mTOR, and is regulated through signaling pathways such as PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, and AMPK/mTOR. Additionally, the relationship between autophagy and apoptosis, as well as between autophagy and exosomes, has been further demonstrated. While modern medicine has made progress in treating cirrhosis, it still faces significant limitations. By contrast, numerous studies have demonstrated the efficacy of traditional Chinese medicine in preventing and treating liver cirrhosis by regulating autophagy, with fewer adverse effects. Chinese herbal monomers and formulations can modulate various autophagy-related signaling pathways, including PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, and AMPK/mTOR, and influence key autophagy proteins such as LC3 and Beclin-1. This modulation inhibits hepatic stellate cell activation, reduces extracellular matrix deposition, and exerts anticirrhotic effects. Moreover, Chinese medicine appears to reduce adverse reactions in cirrhosis treatment and lower the risk of disease recurrence. This review explores the mechanisms of autophagy in the prevention and treatment of liver cirrhosis through Chinese medicine, offering new insights for the development of Chinese medicinal therapies for cirrhosis and their rational clinical application.

Acetaminophen (APAP)-induced liver injury (AILI) is a universal liver disease and the predominant cause of acute liver failure in clinical practice. Autophagy is a highly conserved intracellular degradation pathway, with accumulating evidence indicating its involvement in APAP hepatotoxicity. Notably, the serine/threonine AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/unc-51-like kinase 1 (ULK1) pathway serves as the most classical autophagy pathway and engages in autophagy activation. Thus, pharmacological activation of the AMPK/mTOR/ULK1 pathway has emerged as a critical strategy for addressing AILI. Chlorogenic acid (CGA), a main bioactive constituent isolated from Lonicera japonica Thunb., is an autophagy regulator with potential for AILI therapy. However, whether and how CGA modulates autophagy to antagonize AILI has not yet been elucidated. In the present study, we aim to explore the impact of CGA on AILI, as well as the underlying mechanisms in vitro and in vivo. The results demonstrated that CGA could protect the mice and LO2 cells from oxidative stress and liver injury induced by APAP. Regarding mechanisms, CGA activated the AMPK/mTOR/ULK1 pathway, thereby promoting autophagy. This was evidenced by the degradation of p62/SQSTM1 (hereafter referred to as p62), as well as the up-regulation of LC3B, ATG5, and Beclin1. It is worth noting that the aforementioned, CGA-provided beneficial effects were abrogated by pharmacological inhibition of AMPK with Compound C (CC, an AMPK inhibitor). These [Formula: see text] that CGA alleviates oxidative stress and liver injury induced by APAP, which is contingent upon the regulatory effect of CGA on the AMPK/mTOR/ULK1 axis.

The pathogenesis of chronic hepatitis B (CHB) involves complex mechanisms, and hepatitis B virus (HBV)-induced immune responses play a central role in hepatocyte injury and inflammatory necrosis. CHB infection not only drives liver pathology but also demonstrates significant extrahepatic associations which include depression, cognitive dysfunction, diabetes mellitus, insomnia, non-alcoholic fatty liver disease, and thrombocytopenia. Conventional Western medicine primarily employs antiviral therapy but faces limitations which include low hepatitis B surface antigen clearance rates and frequent adverse drug reactions. In contrast, traditional Chinese medicine demonstrates therapeutic advantages in CHB management which are exemplified by Artemisia capillaris, Xiaochaihu Decoction and Fuzheng Huayu Tablet. Through its modulation of immune pathways and intervention in key HBV lifecycle targets, traditional Chinese medicine achieves a tripartite therapeutic synergy that combines immune reconstitution, viral suppression, and hepatic repair. Chinese medical interventions exhibit characteristic multi-ingredient, multi-target mechanisms that possess immunomodulatory effects in CHB management. Future research should employ modern technologies to elucidate these mechanisms further and thus facilitate the development of optimized treatment protocols. Standardized therapeutic approaches derived from such evidence will hold significant clinical value.

As reperfusion therapy becomes more common, cerebral ischemia-reperfusion (I/R) injury has emerged as a notable factor affecting the outcome of ischemic stroke. The intricate pathological mechanisms involved include oxidative stress, neuroinflammation, and various forms of cell death, characterized by interactions between multiple signaling pathways. Natural products, such as traditional Chinese medicines (TCMs), offer multi-targeted intervention effects through their diverse natural active compounds and integrate pharmacological and nutritional functions into 1 entity (Food and Medicine Homology), supporting their long-term use to prevent cerebral I/R injury. It was found that TCMs, such as Gastrodia elata Blume and Lycium barbarum L., potentially exert synergistic effects on redox imbalance, inflammation, apoptosis, and autophagy by concurrently modulating various pathways, including Nrf2/ARE, NF-κB, PI3K/Akt/mTOR, Bcl-2/Bax, and PARP-1. The prophylactic administration of TCMs may represent a novel approach for mitigating cerebral I/R injury. To advance the application of TCMs from the laboratory to clinical practice, it is essential to conduct clinical research to confirm their effectiveness and safety in preventing cerebral I/R injury.

Rhizoma Anemarrhenae, in which the primary active components are saponins, has shown potential in treating Alzheimer's disease (AD). However, the specific mechanisms of action and the active saponins responsible remain unclear. This study aimed to explore the mechanisms of action and identify the active components of Rhizoma Anemarrhenae saponins (RAS). First, 24 saponin components in RAS and eight absorbed saponins in rats were identified. Then, a component-target interaction network between eight saponins and 83 targets was constructed after target refinement and SPR validation. Bioinformatics analysis indicated that these targets were closely related to lipid metabolism, iron metabolism, and the AMPK signaling pathway. In addition, differentially expressed genes from RAS intervention were significantly enriched in the ferroptosis pathway. In vitro and in vivo assays demonstrated that RAS could inhibit neuronal ferroptosis and alleviate cognitive impairment. Notably, the ferroptosis inducer markedly reversed the neuroprotective effects of RAS. Moreover, silencing AMPK or Nrf2 using the siRNA or AMPK inhibitor abolished the neuroprotective and ferroptosis-inhibitory effects of RAS in vivo or in vitro. Silencing LKB1 reversed the RAS-induced activation of the AMPK/Nrf2 pathway, and co-immunoprecipitation assay revealed that RAS could promote the LKB1-AMPK interaction. Finally, a 2D comprehensive NC/CMC system was used to screen out four potential saponins that inhibit neuronal ferroptosis, with Timosaponin B-III, Timosaponin A-I, and Timosaponin A-III being validated. In conclusion, RAS exerts anti-AD effects by enhancing the LKB1-AMPK interaction, and activating the AMPK/Nrf2 pathway, inhibiting neuronal ferroptosis as a result. Three saponins are identified as the active components potentially responsible for this effect.

More than one billion people worldwide suffer from hypertension, and essential arterial hypertension is in particular a major risk factor for cardiovascular diseases. These conditions can lead to complications such as stroke, renal failure, cardiac hypertrophy, and heart failure. Despite extensive research on various antihypertensive drugs, an increasing number of people are unable to effectively control their hypertension. Further optimization of their treatment is required. Given the pathogenesis of hypertension, natural products (NPs) have emerged as a promising source of potential antihypertensive agents. NPs can prevent the development of hypertension by targeting oxidative stress, inflammation, vascular remodeling, and neurohormonal pathways. These targets provide the foundation for the application of NPs in clinical treatment. This review assesses NPs with potential antihypertensive activities published between 2019 and 2024. A total of 70 unique NPs were identified through PubMed and Web of Science. Seventy unique NPs were categorized into flavonoids (20 compounds), terpenoids (24 compounds), alkaloids (17 compounds), and plant-derived extracts (9 species). These products were classified according to their structural frameworks, and their bioactivities were briefly summarized. Future research should prioritize NPs with dual anti-oxidant/anti-inflammatory properties for clinical experiments, advanced delivery systems for improved bioavailability, and interdisciplinary approaches integrating synthetic biology for scalable production.

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.

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.

Myocardial infarction (MI) is a significant threat to human health worldwide. Following MI, cardiomyocytes (CMs) undergo pyroptosis, exacerbating the damage caused by infarction. Ginseng may play a role in alleviating CM pyroptosis. However, further exploration is needed regarding its main active ingredients and effects. By employing network pharmacology on the active ingredients of ginseng, MI and pyroptosis, and employing molecular docking between such ingredients and pyroptosis-related proteins, we screened for the main ingredient of ginseng. Through network pharmacology and molecular docking, we identified ginsenoside Rh2, which acts on MI and cell pyroptosis, as the most likely active ingredient that stably binds to pyroptosis-related proteins. We subsequently constructed a neonatal rat CM oxygen-glucose deprivation (OGD) model in vitro and an MI mouse model in vivo. Ginsenoside Rh2 was administered, with losartan used as a positive control. In the in vitro OGD model, ginsenoside Rh2 increased the viability of primary rat CMs and mitigated OGD-induced pyroptosis. In the in vivo MI model, ginsenoside Rh2 reduced CM pyroptosis, decreased infarct size, and subsequently improved cardiac function. Our study provides a novel therapeutic strategy for MI by attenuating CM pyroptosis.

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.