Rosa laevigata Michx. Polysaccharide Ameliorates Diabetic Nephropathy in Mice through Inhibiting Ferroptosis and PI3K/AKT Pathway-Mediated Apoptosis and Modulating Tryptophan Metabolism
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ABSTRACT:
SUBMITTER: Zhang T
PROVIDER: S-EPMC10569897 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:The effects of total flavonoids (TFs) from Rosa laevigata Michx fruit against liver damage and cerebral ischemia/reperfusion (I/R) injury have been reported, but its action on hepatic I/R injury remains unknown. In this work, the effects and possible mechanisms of TFs against hepatic I/R injury were examined using a 70% partial hepatic warm ischemia rat model. The results demonstrated TFs decreased serum aspartate transaminase (AST), alanine aminotransferase (ALT), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) activities, improved liver histopathology and ultrastructure through hematoxylin-eosin (HE) staining and electron microscope observation. In addition, TFs significantly decreased malondialdehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which indicated that TFs alleviated oxidative stress caused by I/R injury. RT-PCR results proved that TFs downregulated the gene levels of inflammatory factors including interleukin-1 beta (IL-1β), interleukin-1 (IL-6), and tumor necrosis factor alpha (TNF-α). Further research indicated that TF-induced hepatoprotection was completed through inhibiting TLR4/MyD88 and activating Sirt1/Nrf2 signaling pathways. Blockade of the TLR4 pathway by TFs inhibited NF-κB and AP-1 transcriptional activities and inflammatory reaction. Activation of Sirt1/Nrf2 pathway by TFs increased the protein levels of HO-1 and GST to improve oxidative stress. Collectively, these findingsconfirmed the potent effects of TFs against hepatic I/R injury, which should be developed as a candidate for the prevention of this disease.
| S-EPMC4963894 | biostudies-literature
Project description:In this study, the protective effect of the total saponins from Rosa laevigata Michx (RLTS) against liver fibrosis induced by carbon tetrachloride (CCl4) in rats was evaluated. The results showed that RLTS significantly rehabilitated the levels of alanine aminotransferase, aspartate aminotransferase, malondialdehyde, glutathione, glutathione peroxidase, catalase, superoxide dismutase, hydroxyproline, α-smooth muscle actin, collagen I, collagen III and fibronectin, which were confirmed using H&E, Sirius Red and Masson histopathological assays. Further research indicated that RLTS markedly reduced cytochrome P450 2E1 activity, attenuated oxidative stress, and suppressed inflammation. In addition, RLTS facilitated matrix degradation through down-regulation of matrix metalloproteinase2, matrix metalloproteinase 9 and metalloproteinases1, and exerted the anti-fibrotic effects through affecting transforming growth factor β/Smad, focal adhesion kinase/phosphatidylinositol-3-kinase/amino kinase terminal/70-kDa ribosomal S6 Kinase (FAK-PI3K-Akt-p70(S6K)) and mitogen-activated protein kinase (MAPK) signaling pathways. Taken together, our data indicate that RLTS can be applied as one effective candidate for the treatment of liver fibrosis in the future.
| S-EPMC4488818 | biostudies-literature
Project description:Rosa laevigata fruit, at present, is becoming increasingly popular as a functional foodstuff with several nutritional and medicinal properties. To explore the acetylcholinesterase (AChE) inhibitory activity of extracts from the Rosa laevigata Michx. fruit (RLMF), a simple and efficient enrichment purification technology based on microwave-assisted extraction (MAE) and multi vacuum extraction columns (VEC) was applied to screen and identify triterpenoids (TTs) in the RLMF extracts. The MAE conditions were optimized using the Box-Behnken design (BBD) with a quadratic regression model and the response surface method (RSM). The optimum conditions were as follows: ethanol concentration, 69%; extraction time, 12 min; ratio of liquid to raw material, 26 : 1 mL g-1; and microwave power, 528 W. Under these conditions, the maximum content of triterpenoids reached 62.48 ± 0.25 mg g-1, which was close to the predicted value of 62.69 mg g-1. In addition, two pure polyhydroxy triterpenoids: 2α,3β,19α,23-tetrahydroxyurs-12-en-28-oic acid (1) and 2α,3β,19α,23-tetrahydroxyurs-12-en-28-oic acid-28-O-β-d-glucopyrannoside (2) were isolated and enriched to more than 500 mg by a multi VEC method. Furthermore, the quantities of compounds 1 and 2 from RLMF were 5.36 and 10.37 mg g-1, respectively, as determined using HPLC. These compounds were further assessed for acetylcholinesterase inhibitory and neuroprotection properties. The results showed that 1 and 2 showed potent AChE inhibitory activities with IC50 values of 29.22 and 45.47 μg mL-1, respectively. At high concentration, compounds 1 and 2 produced a 92% and 89% inhibition on the target enzyme, which was consistent with docking results between AChE and each isolate. Moreover, both 1 and 2 exhibited potential neuroprotective activities against H2O2-induced SHSY5Y cell death.
| S-EPMC9089849 | biostudies-literature
Project description: In present study, the mitogenome of Rosa laevigata was assembled and characterized, with a total length of 281,693 bp and a GC content of 45.4%. The genome encompasses 53 genes, including 32 protein-coding genes, 3 rRNA genes and 18 tRNA genes. Furthermore, 19 MTPTs were identified, ranging from 48 to 1585 bp, covering 3.1% (8764 bp) of the mitogenome. Phylogenetic analysis of 34 Rosaceae species based on 21 common conserved protein-coding genes detected the monophyly of Rosa, with R. laevigata and R. chinensis forming a sister clade to R. rugosa. The mitogenome provides valuable genetic resources for R. laevigata utilization and for further phylogeny reconstruction of Rosa and Rosaceae.
| S-EPMC11578408 | biostudies-literature
Project description:We previously reported the effects of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride-induced liver damage, non-alcoholic fatty liver disease, and liver ischemia-reperfusion injury. However, there have been no papers reporting the role of R. laevigata TFs against lipopolysaccharide (LPS)-induced liver injury. In this paper, liver injury in mice was induced by LPS, and R. Laevigata extract was intragastrically administered to the mice for 7 days. Biochemical parameters in serum and liver tissue were examined, and pathological changes were observed by transmission electron microscopy, hematoxylin and eosin (H&E) and Oil Red O staining. The results showed that the TFs markedly reduced serum ALT (alanine transferase), AST (aspartate transaminase), TG (total triglyceride), and TC (total cholesterol) levels and relative liver weights and improved liver pathological changes. In addition, the TFs markedly decreased tissue MDA (malondialdehyde) level and increased the levels of SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase). A mechanistic study showed that the TFs significantly increased the expression levels of Nrf2 (nuclear erythroid factor2-related factor 2), HO-1 (heme oxygenase-1), NQO1 (NAD(P)H dehydrogenase (quinone 1), GCLC (glutamate-cysteine ligase catalytic subunit), and GCLM (glutamate-cysteine ligase regulatory subunit) and decreased Keap1 (Kelch-like ECH-associated protein 1) level by activating FXR (farnesoid X receptor) against oxidative stress. Furthermore, the TFs markedly suppressed the nuclear translocation of NF-κB (nuclear factor-kappa B) and subsequently decreased the expression levels of IL (interleukin)-1β, IL-6, HMGB-1 (high -mobility group box 1), and COX-2 (cyclooxygenase-2) by activating FXR and FOXO3a (forkhead box O3) against inflammation. Besides, the TFs obviously reduced the expression levels of SREBP-1c (sterol regulatory element-binding proteins-1c), ACC1 (acetyl-CoA carboxylase-1), FASN (fatty acid synthase), and SCD1 (stearoyl-coenzyme A desaturase 1), and improved CPT1 (carnitine palmitoyltransferase 1) level by activating FXR to regulate lipid metabolism. Our results suggest that TFs exhibited protective effect against LPS-induced liver injury by altering FXR-mediated oxidative stress, inflammation, and lipid metabolism, and should be developed as an effective food and healthcare product for the therapy of liver injury in the future.
| S-EPMC6025249 | biostudies-literature
Project description:Rosa laevigata Michx. is an ethnic medicine that have strong biological activities used in the traditional medicine system for the treatment of diabetes, nephropathy, myocardial damage, oxidative damage, liver damage and so on. Currently, The Chinese herb R. laevigata Michx. can be divided into two important medicines: Fructus R. laevigata and Radix R. laevigata, from which approximately 148 chemical components have been isolated, including flavonoids, lignans, polyphenols, steroids, triterpenoids, tannins as well as other components. Pharmacological studies have already confirmed that both of these herbs have antioxidant, anti-inflammatory, antiviral and anti-tumor activities, as well as renal protective, immunomodulatory, lipid-lowering, cardiovascular protective, bacteriostatic, and other pharmacological effects. Toxicological tests and quality control studies revealed the safety and nontoxicity of R. laevigata Michx. Therefore, this paper systematically summarizes the traditional uses, botanical, phytochemical, and pharmacology as well as the quality control and toxicology of Fructus and Radix, which in order to provide a comprehensive reference for its continued research.
| S-EPMC9582767 | biostudies-literature
Project description:Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Our previous studies have shown that the total flavonoids (TFs) from Rosa laevigata Michx fruit has various activities, however, there were no papers reporting the role of the TFs against renal IRI. In the present work, a hypoxia/reoxygenation (H/R) model in NRK-52E cells and ischemia-reperfusion model in rats were used. The results showed that the TFs significantly attenuated cell injury and markedly decreased serum creatinine (Cr) and blood urea nitrogen (BUN) levels in rats. Further investigation revealed that the TFs markedly decreased the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) and intracellular reactive oxygen species (ROS), up-regulated the levels of silent information regulator factor 2-related enzyme 1 (Sirt1), nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1), down-regulated the levels of Kelch like ECH-associated protein-1 (Keap1) and the nuclear translocation of nuclear factor-κBp65 (NF-κBp65), and decreased the mRNA levels of interleukine-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, inhibiting Sirt1 by siRNA showed that the role of the natural product in protecting renal IRI was significantly attenuated, suggesting that the effect of the extract against renal IRI depended on Sirt1. Taken together, the TFs has significantly nephroprotective effect against IRI by affecting Sirt1/Nrf2/NF-κB signaling pathway, which should be developed as a new therapeutic agent or food additives to treat acute kidney injury in the future.
| S-EPMC6272996 | biostudies-literature
Project description:Rosa laevigata Genome sequencing and assembly
| PRJNA1108017 | ENA