Hosta plantaginea (Lam.) Aschers flower modulates inflammation and amino acid metabolism by inhibiting NF-κB/MAPK/JAK-STAT/PI3K-Akt and AMPK pathways to alleviate benign prostatic hyperplasia in rats.
Huilei Wang, Zhenqiang Mu, Jian Liang, Xiaomei Li, Li Yang, Junwei He
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引用次数: 0
Abstract
Ethnopharmacological relevance: Benign prostatic hyperplasia (BPH) is the most common urogenital disease in men with no definitive treatment. Inflammation, androgen imbalance, and oxidative stress play crucial roles in the pathogenesis of BPH. The flower of Hosta plantaginea (Lam.) Ascher is a pivotal medicinal plant in China, used to treat BPH. However, its effect and mechanism against BPH have not been clear.
Aim of the study: Our aim was to decipher the pharmacodynamics and mechanisms of H. plantaginea flower against BPH.
Materials and methods: The extract yields and HPLC-based chemoprofile of ethanolic extract (HP) and total flavonoid (TF) of H. plantaginea flowers were used as reference standard to ensure their quality. The testosterone propionate-induced BPH rat model was used to assess the effects of HP and TF. Protein expression, metabolomics, and network pharmacology analyses were performed.
Results: Twenty constituents were identified in both HP and TF, with four quantitatively analyzed using the HPLC method. HP and TF demonstrated significant therapeutic effects on BPH, including reduced prostate size and prostatic index, improved pathological injury of prostate, as well as increased levels of testosterone, superoxide dismutase, glutathione, and glutathione peroxidase, along with decreased levels of dihydrotestosterone, 5 alpha-reductase, epidermal growth factor, TNF-α, IL-1β, IL-6, and malondialdehyde. Western blotting assay indicated that HP and TF prominently inhibited the protein expression of phosphorylated p65, IκBα, JNK, p38, Erk1/2, JAK1, STAT3, PI3K, Akt, and AMPKα1 in a dose-dependent manner. Integrating metabolomics and network pharmacology analyses revealed that HP and TF observably regulated 30 differential metabolites and 11 hub genes across the aforementioned pathways, which are closely associated with amino acid metabolism.
Conclusion: The proposed comprehensive strategy of in vivo experiments, metabolomics, and network pharmacology studies has demonstrated that HP and TF could alleviate BPH injury in rats by suppressing inflammation, androgen imbalance, oxidative stress, and amino acid metabolism through the inhibition of NF-κB, MAPK, JAK-STAT, PI3K-Akt, and AMPK pathways, which provides novel insights into the potential of H. plantaginea flower as a treatment for BPH.
期刊介绍:
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.