SMAD3 x TGF-β1 x TNF-α

Renal fibrosis is a key pathological process in the progression of chronic kidney disease (CKD). Panaxatriol saponins (PTS), the main bioactive compounds extracted from Panax notoginseng (Burk.) F.H. Chen, have demonstrated antioxidative and anti-inflammatory activities. This study aimed to investigate the potential protective effects of PTS against renal fibrosis and explore the underlying pharmacological mechanisms. A unilateral ureteral obstruction (UUO) model was established in Sprague-Dawley (SD) rats to induce renal fibrosis. Histopathological changes were assessed using hematoxylin and eosin (HE) staining, Masson's trichrome staining, and transmission electron microscopy (TEM). Network pharmacology and molecular docking approaches were employed to identify potential signaling molecules through which PTS may mitigate renal fibrosis. Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry were utilized to validate the involvement of specific signaling pathways in PTS-mediated anti-fibrotic effects. Our data demonstrated that PTS alleviated renal dysfunction and provided protective effects against renal fibrosis, primarily through the TNF-α and TGF-β1 signaling pathways. Moreover, PTS treatment significantly downregulated pro-inflammatory cytokines such as TNF-α, IL-6, and Smad3 activity. Additionally, PTS inhibited the expression of key fibrosis markers, including α-SMA, collagen I, and fibronectin. Our study suggests that PTS exert a prevention effect in renal fibrosis by blocking the TGF-β1/Smad3 signaling pathway.

Cardiovascular diseases represent major concerns in postmenopause. This study explores the therapeutic potential of naringenin nano-emulsion (nNAR) in mitigating postmenopausal cardiovascular complications induced by estrogen deficiency and a high-fat diet in rats. The methodology integrated network pharmacology, molecular docking, and in vivo experiments to accomplish this objective.

Molecular targets of naringenin (NAR), alongside those linked to estrogen deficiency and hypertension, were sourced from relevant databases. The intersecting targets were identified to construct the "drug-target-disease" network that delineates core targets. Subsequently, molecular docking was conducted to evaluate the interaction between NAR and the primary target. In the in vivo study, adult female rats underwent ovariectomy and were placed on a high-fat diet for 30 weeks. For the last 6 weeks, NAR suspension and nNAR were administered orally on a daily basis, in conjunction with estradiol injections given every four days. Endpoint assessments included measurements of blood pressure, cardiac function, and cardiac oxidative and inflammatory status. Additionally, levels of angiotensin II (Ang II), its receptor (AT1R), cardiac transforming growth factor beta-1 (TGF-β1), mothers against decapentaplegic homolog 3 (Smad-3), and matrix metalloproteinase-9 (MMP-9) were quantified, accompanied by cardiovascular histological analysis.

nNAR significantly mitigated hypertension and molecular cardiomyopathy, downregulated the Ang II/AT1R/TNF-α/TGF-β1/Smad-3/MMP-9 signaling pathway and ameliorated oxidative stress. Overall, the efficacy of nNAR was comparable to that of estradiol and surpassed that of NAR suspension.

nNAR exhibits anti-hypertensive action through antioxidant, anti-inflammatory and anti-profibrotic activities in the hearts of ovariectomized rats by inhibiting Ang II, AT1R, TNF-α, TGF-β1, Smad-3 and MMP-9.

The revolution in the 21st century has witnessed the development of the industrial and healthcare systems. Human health and well‐being are still global challenges despite this modernization and advancement. Cancer is extensively affecting people, demanding special attention and an effective dietary approach. Bioactive compound‐based natural therapies are a significant strategy to reduce the cancer burden. Naringenin, a bioactive compound widely distributed in the citrus family and is known for several health‐promoting properties, including anticancer activity. The current review highlights the anticancer potential of Naringenin by exploring recent studies through various databases like Google Scholar, PubMed, ScienceDirect, and Web of Science. The analyses revealed that Naringenin can inhibit cell proliferation and oncogenesis through different molecular mechanisms and signaling pathways like apoptosis induction, cell cycle arrest, and modulation of P13K/AKT/mTOR, TGF‐β1/Smad3, NF‐κB, TLR4, and MAPK pathways. Moreover, it can inhibit inflammatory markers (IL‐6, TNF‐α, and IL‐1β), downregulate oncogenes (Ras, HER2, MYC, and BCR/ABL1), and upregulate tumor suppressor genes (TSGs) such as TP53, PTEN, and BRCA1 and BRCA2 expression. Combining Naringenin with other bioactive compounds, chemotherapy drugs, and nanoformulations is a novel way to enhance its anticancer activity. However, poor bioavailability, stability, and lack of clinical trials and in silico studies hinder its therapeutic potential. Therefore, advanced techniques to enhance its stability and clinical trials regarding anticancer potential are required to validate its promising efficacy. The current review focuses on Naringenin's bioavailability, antioxidant, and anticancer potential through possible mechanisms.