The p53/miR-29a-3p axis mediates the antifibrotic effect of leonurine on angiotensin II-stimulated rat cardiac fibroblasts

Cardiovascular diseases have become the leading cause of death in urban and rural areas. Myocardial fibrosis is a common pathological manifestation at the adaptive and repair stage of cardiovascular diseases, easily predisposing to cardiac death. Non-coding RNAs (ncRNAs), RNA molecules with no coding potential, can regulate gene expression in the occurrence and development of myocardial fibrosis. Recent studies have suggested that Chinese herbal medicine can relieve myocardial fibrosis through targeting various ncRNAs, mainly including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Thus, ncRNAs are novel drug targets for Chinese herbal medicine. Herein, we summarized the current understanding of ncRNAs in the pathogenesis of myocardial fibrosis, and highlighted the contribution of ncRNAs to the therapeutic effect of Chinese herbal medicine on myocardial fibrosis. Further, we discussed the future directions regarding the potential applications of ncRNA-based drug screening platform to screen drugs for myocardial fibrosis.

Section: Leonurinementioning

confidence: 75%

Section: Chinese Herbal Medicine Relieves Mf Through Regulating Ncrnasmentioning

confidence: 87%

Non-coding RNAs: targets for Chinese herbal medicine in treating myocardial fibrosis

Wang,

Yan,

Tan

et al. 2024

“…Another study exhibited that all mature miR-29 family members were downregulated in the myocardial tissue of post-MI mice induced by isoprenaline, while LEO treatment (25, 50, and 100 mg/kg/d for 48 days) not only inhibited fibroblast activation and collagen synthesis but also noticeably upregulated the expressions of miR-29a-3p and p53. However, the knockdown of miR-29a-3p or PFT-α (a p53 inhibitor) completely abolished the therapeutic effect of LEO on myocardial fibrosis, as evidenced by the upregulation of TGF-β, collagen type III, and collagen type I protein levels in CFs ( Li et al, 2022 ; Xi et al, 2023 ). Furthermore, a novel mechanism of LEO against myocardial fibrosis was discovered.…”

Section: Pharmacodynamics Of Leomentioning

confidence: 99%

Leonurine: a comprehensive review of pharmacokinetics, pharmacodynamics, and toxicology

Liu,

Sun,

Tang

et al. 2024

Leonurine is an alkaloid unique to the Leonurus genus, which has many biological activities, such as uterine contraction, anti-inflammation, anti-oxidation, regulation of cell apoptosis, anti-tumor, angiogenesis, anti-platelet aggregation, and inhibition of vasoconstriction. This paper summarizes the extraction methods, synthetic pathways, biosynthetic mechanisms, pharmacokinetic properties, pharmacological effects in various diseases, toxicology, and clinical trials of leonurine. To facilitate a successful transition into clinical application, intensified efforts are required in several key areas: structural modifications of leonurine to optimize its properties, comprehensive pharmacokinetic assessments to understand its behavior within the body, thorough mechanistic studies to elucidate how it works at the molecular level, rigorous safety evaluations and toxicological investigations to ensure patient wellbeing, and meticulously conducted clinical trials to validate its efficacy and safety profile.

“…Yu et al's study found that Leo can maintain the Cyclin D1-CDK4 complex at lower levels by reducing the expression of CDK4, thereby stalling the cell cycle. In studies using Leo-treated breast cancer cell lines, it was found that the expression levels of Cyclins A1, B1, and CDK1 decreased in the treated cells, while p53 and BAX were upregulated, resulting in a significant cell cycle arrest at the G2/ M phase, which subsequently leads to cell apoptosis (Chen et al, 2013a;Sitarek et al, 2021;Cao et al, 2022c;Xi et al, 2023). Li et al's study showed that Leo has antiinflammatory effects, can inhibit the transformation of lung adenocarcinoma, and ultimately inhibit the proliferation of lung adenocarcinoma cells.…”

Section: Leo Promotes Tumor Cell Cycle Arrestmentioning

confidence: 99%

A literature review: mechanisms of antitumor pharmacological action of leonurine alkaloid

Cao,

Wang,

et al. 2023

Leonurine refers to the desiccated aerial portion of a plant in the Labiatae family. The primary bioactive constituent of Leonurine is an alkaloid, Leonurine alkaloid (Leo), renowned for its substantial therapeutic efficacy in the treatment of gynecological disorders, in addition to its broad-spectrum antineoplastic capabilities. Over recent years, the pharmacodynamic mechanisms of Leo have garnered escalating scholarly interest. Leo exhibits its anticancer potential by means of an array of mechanisms, encompassing the inhibition of neoplastic cell proliferation, induction of both apoptosis and autophagy, and the containment of oncogenic cell invasion and migration. The key signal transduction pathways implicated in these processes include the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), the Phosphoinositide3-Kinase/Serine/Threonine Protein Kinase (PI3K/AKT), the Signal Transducer and Activator of Transcription 3 (STAT3), and the Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase (MAP/ERK). This paper commences with an exploration of the principal oncogenic cellular behaviors influenced by Leo and the associated signal transduction pathways, thereby scrutinizing the mechanisms of Leo in the antineoplastic sequence of events. The intention is to offer theoretical reinforcement for the elucidation of more profound mechanisms underpinning Leo’s anticancer potential and correlating pharmaceutical development.