ReferenceID 4444
Studies on the metabolism and mechanism of acteoside in treating chronic glomerulonephritis
J Ethnopharmacol
Ethnopharmacological relevance: Acteoside (ACT) is the main ingredient derived from the leaves of Rehmannia glutinosa (Dihuangye). Dihuangye has the function of clearing heat, replenishing qi and activating blood, nouris
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4444
- Evidence Id
- 21034
- Core Evidence Id
- 21034
- Source Reference Id
- 2171
- Herb2 Reference Id
- HBREF002968
- Subject Paper Key
- HBIN014630_36332760
- Pubmed Id
- 36332760
- Doi
- 10.1016/j.jep.2022.115866
- Paper Title
- Studies on the metabolism and mechanism of acteoside in treating chronic glomerulonephritis
- Paper Abstract
- Ethnopharmacological relevance: Acteoside (ACT) is the main ingredient derived from the leaves of Rehmannia glutinosa (Dihuangye). Dihuangye has the function of clearing heat, replenishing qi and activating blood, nourishing yin and tonifying kidney in traditional Chinese medicine. Recent studies have demonstrated that Dihuangye can be used to treat nephritis and ACT is a promising antinephritic agent. Aim of the study: To clarify the metabolites of ACT in biological samples and investigate the renoprotective effect and mechanism of ACT in rats with chronic glomerulonephritis (CGN). Materials and methods: In this study, the biotransformation of ACT in rat biological samples was clarified by quadrupole time-of-flight tandem mass spectrometry. The metabolites were validated by urine samples in nephropathy model rats. The effect of ACT and its metabolites was evaluated by glomerular podocyte injury due to high glucose. Based on an analysis of the ingredients in vivo, the potential therapeutic targets in the treatment of CGN were investigated by using network pharmacological analysis and molecular docking. Then, the renoprotective effect and mechanism of ACT were determined in rats in a passive Heymann nephritis (PHN) model. Results: A total of 49 metabolites of ACT were detected and identified. Meanwhile, 21 metabolites were detected in nephropathy model rats. ACT was absorbed rapidly and transferred from the kidney, and the metabolites were eliminated via urine. The whole process lasted approximately 8 h. ACT had a significant protective effect on glomerular podocytes damaged by high glucose and 3,4-dihydroxyphenylacetic acid might be the main metabolite of ACT underlying its functions in vivo. The network pharmacology and molecular docking results showed 84 ACT-CGN targets, among which MAPK1, HRAS, AKT1, EGFR, and others were a highly correlated. In the PHN rat model, ACT significantly reduced the 24-h urine protein and serum creatinine concentrations, suppressed the leukocyte CD18 expression levels, decreased the serum tumor necrosis factor α (TNF-α) levels and tended to reduce serum interleukin 6 (IL-6) levels. ACT significantly reduced the platelet aggregation rate and inhibited the proliferative activity of splenic lymphocytes in response to the mitogen concanavalin A. Meanwhile, ACT inhibited transforming growth factor-β and fibronectin expression in renal tissues and dose-dependently inhibited TNF-α and IL-6 production in RAW264.7 mouse macrophages at doses ranging from 1.8 to 1330 μg/mL. Conclusions: ACT had therapeutic effects on PHN rats, and its mechanism might be related to the inhibition of intercellular or intercellular-matrix adhesion, suppression of inflammatory response, regulation of immune function, improvement of tissue hemodynamics and hemorheology, and relief of fibrotic lesions.
- Journal
- J Ethnopharmacol
- Publish Year
- 2022
- Experiment Subject
- mouse; rat; raw264.7 mouse macrophages
- Experiment Type
- Animal Experiment
- Phenotype Related
- Nephritis; Heymann Nephritis; Hemorheology; Nephropathy; Fibrotic Lesions; Tumor; Chronic Glomerulonephritis
- Paper Title Cn
- Paper Title En
- Studies on the metabolism and mechanism of acteoside in treating chronic glomerulonephritis
- Bilingual Status
- semi_complete