Rosmarinic acid ameliorates renal interstitial fibrosis by inhibiting the phosphorylated-AKT mediated epithelial–mesenchymal transition <i>in vitro</i> and <i>in vivo</i>

Hsieh, Yi‐Hsien; Tsai, Jen-Pi; Ting, Yi-Hsuan; Hung, Tung-Wei; Chao, Wen-Wan

doi:10.1039/d2fo00204c

Cited by 13 publications

(3 citation statements)

References 41 publications

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“…Administration of RA can reduce the expression levels of TGF-β1, type I collagen, vimentin, fibronectin, phosphorylated AKT (p-AKT), and α-SMA. This study implies that RA may offer a viable therapeutic agent in effectively managing renal interstitial fibrosis (23).…”

Section: Discussionmentioning

confidence: 78%

Comparative effects of candesartan and losartan on mesangial expansion and glomerular volume in diabetes rat model receiving rosmarinic acid therapy

Samsu,

Sakti,

Rifai

2024

J Nephropathol

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Introduction: An oxidative stress and angiotensin II (Ang II) contribute significantly in the pathogenesis of diabetic nephropathy (DN). Therefore, interventions targeting these factors are anticipated to significantly contribute to inhibiting the progression of diabetic kidney disease. Objectives: The aim of this study was to assess the impact of a combination of rosmarinic acid (RA) and angiotensin receptor blockers (ARBs) in preventing mesangial expansion and reducing glomerular volume in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: We observed experimental animals, 16 adults male Wistar rats, which were randomly grouped into 4 groups (n=4 per group): negative and positive control groups and diabetic rats treated with RA 75 mg/kg and candesartan 1 mg/kg (treatment group 1) and RA therapy 75 mg/kg and losartan 2.5 mg/kg (treatment group 2). Following 8 weeks of therapy, the renal histology was assessed to evaluate mesangial expansion and glomerular volume. Results: In comparison to the positive control, treatment group 1 demonstrated a significant inhibition of mesangial expansion (MD: -19.92; 95% CI: -21.97, -17.87; P<0.001) and decreased glomerular volume (MD: 2669.06; 95% CI: 2066.31, 3271.80; P<0.001). Similarly, treatment group 2 significantly inhibited mesangial expansion (MD: -19.21; 95% CI: -21.26, -17.16; P<0.001) and decreased glomerular volume (MD: 2488.04; 95% CI: 1885.29, 3090.78; P<0.001) compared to the positive control. While treatment group 1 exhibited better effects than treatment group 2, although the difference was not statistically significant. Conclusion: In STZ-induced diabetic rats, combination therapy of RA with candesartan or losartan can inhibit mesangial expansion and decrease glomerular volume.

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Section: Discussionmentioning

confidence: 78%

Comparative effects of candesartan and losartan on mesangial expansion and glomerular volume in diabetes rat model receiving rosmarinic acid therapy

Samsu,

Sakti,

Rifai

2024

J Nephropathol

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“…Studies have demonstrated that tripterine could decrease lung tissue injury by reducing capillary permeability, inhibiting inflammatory cytokines or chemokines, and governing the expression of numerous inflammatory mediators ( Law et al, 2011 ). The pathogenesis of PF is typically characterised by excessive extracellular matrix (ECM) deposition and EMT, during which several factors change, including excessive accumulation of type I and type III collagens, the main components of the ECM, and the up-regulation of mesenchymal markers, such as α -SMA and vimentin ( Hsieh et al, 2022 ). Through in vivo experiments, we reported that tripterine could decrease lung pathology and collagen deposition in the lung tissues of the model mice.…”

Section: Discussionmentioning

confidence: 99%

Connective tissue disease-related interstitial lung disease is alleviated by tripterine through inhibition of the PI3K/Akt, apoptosis, and TNF-α signalling pathways

Zhu

Wang²,

Liu³

et al. 2022

Front. Pharmacol.

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Background: Interstitial lung disease (ILD) is the major cause of morbidity and mortality in patients with various rheumatic diseases. However, more interventions need to be sought. Tripterine, an extract of Tripterygium wilfordii Hook. F, has been widely studied for its powerful anti-inflammatory effect. However, its mechanism of action in treating connective tissue disease-related (CTD)-ILD remains unclear.Purpose: To investigate the mechanism of tripterine in CTD-ILD treatment by combining network pharmacology and an in vivo experiment.Methods: The related targets of tripterine were obtained after searching the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform, Comparative Toxicogenomics Database, GeneCards, Search Tool for Interacting Chemicals database, and SymMap database. Following this, Online Mendelian Inheritance in Man, GeneCards, Genebank, and DrugBank were used to screen the targets of CTD-ILD. A target-signalling pathway network was constructed using Cytoscape. Additionally, topological analysis was performed. Protein interaction analysis was performed using the STRING online analysis platform. Following this, Gene Ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) signalling pathway enrichment analyses were performed. Subsequently, the molecular docking between tripterine and the core targets was verified. Finally, experimental verification was performed in bleomycin-induced model mice.Results: A total of 134 common targets and 10 core targets of tripterine, including signal transducer and activator of transcription 3, tumour necrosis factor (TNF), v-rel avian reticuloendotheliosis viral oncogene homolog A, protein kinase B (Akt) α (Akt1), mitogen-activated protein kinase (MAPK) 1, Jun transcription factor family, tumour protein 53, MAPK3, nuclear factor kappa B subunit 1, and caspase 8, were obtained. GO enrichment analysis revealed that, while treating CTD-ILD, tripterine was mainly involved in cytokine receptor binding, receptor-ligand activity, signal receptor activation, cytokine activity, protein ubiquitination, deoxyribonucleic acid transcriptase activity, etc. The KEGG pathway enrichment analysis revealed that the most significant signalling pathways were multiple viral infections and the phosphatidylinositol-3-kinase (PI3K)/Akt, TNF, and apoptosis signalling pathways. Molecular docking results revealed that tripterine had good docking activity with the core targets. Experimental studies also demonstrated that tripterine could inhibit the activation of PI3K/Akt, apoptosis, and TNF-α signalling pathways in lung tissue and significantly improve lung pathology and collagen deposition in the model mice.Conclusions: This study preliminarily revealed the potential molecular biological mechanism of tripterine while treating CTD-ILD might be related to inhibiting the PI3K/Akt, apoptosis, and TNF-α signalling pathways. Tripterygium wilfordii Hook. F. and its extract could be used clinically for treating CTD-ILD.

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“…The inhibitory effects of RA on kidney fibrosis and EMT were examined using a UUO mouse model and an indoxyl sulfate-stimulated NRK-52E cell model [75]. C57BL/6 mice were orally administered RA (10 or 20 mg kg −1 ) before and after UUO surgery.…”

Section: Kidney Fibrosismentioning

confidence: 99%

Therapeutic Potential and Mechanisms of Rosmarinic Acid and the Extracts of Lamiaceae Plants for the Treatment of Fibrosis of Various Organs

Boo

2024

Antioxidants

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Fibrosis, which causes structural hardening and functional degeneration in various organs, is characterized by the excessive production and accumulation of connective tissue containing collagen, alpha-smooth muscle actin (α-SMA), etc. In traditional medicine, extracts of medicinal plants or herbal prescriptions have been used to treat various fibrotic diseases. The purpose of this narrative review is to discuss the antifibrotic effects of rosmarinic acid (RA) and plant extracts that contain RA, as observed in various experimental models. RA, as well as the extracts of Glechoma hederacea, Melissa officinalis, Elsholtzia ciliata, Lycopus lucidus, Ocimum basilicum, Prunella vulgaris, Salvia rosmarinus (Rosmarinus officinalis), Salvia miltiorrhiza, and Perilla frutescens, have been shown to attenuate fibrosis of the liver, kidneys, heart, lungs, and abdomen in experimental animal models. Their antifibrotic effects were associated with the attenuation of oxidative stress, inflammation, cell activation, epithelial–mesenchymal transition, and fibrogenic gene expression. RA treatment activated peroxisomal proliferator-activated receptor gamma (PPARγ), 5′ AMP-activated protein kinase (AMPK), and nuclear factor erythroid 2-related factor 2 (NRF2) while suppressing the transforming growth factor beta (TGF-β) and Wnt signaling pathways. Interestingly, most plants that are reported to contain RA and exhibit antifibrotic activity belong to the family Lamiaceae. This suggests that RA is an active ingredient for the antifibrotic effect of Lamiaceae plants and that these plants are a useful source of RA. In conclusion, accumulating scientific evidence supports the effectiveness of RA and Lamiaceae plant extracts in alleviating fibrosis and maintaining the structural architecture and normal functions of various organs under pathological conditions.

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Rosmarinic acid ameliorates renal interstitial fibrosis by inhibiting the phosphorylated-AKT mediated epithelial–mesenchymal transition in vitro and in vivo

Abstract: Indoxyl sulfate (IS), a uremic toxin, causes chronic kidney disease (CKD) progression via renal fibrosis.

Cited by 13 publications

References 41 publications

Comparative effects of candesartan and losartan on mesangial expansion and glomerular volume in diabetes rat model receiving rosmarinic acid therapy

Comparative effects of candesartan and losartan on mesangial expansion and glomerular volume in diabetes rat model receiving rosmarinic acid therapy

Connective tissue disease-related interstitial lung disease is alleviated by tripterine through inhibition of the PI3K/Akt, apoptosis, and TNF-α signalling pathways

Therapeutic Potential and Mechanisms of Rosmarinic Acid and the Extracts of Lamiaceae Plants for the Treatment of Fibrosis of Various Organs

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