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Abstract: SA-PO639

Rhein Attenuates D-Galactose Induced Renal Aging via Regulation of mTOR-Mediated Autophagy

Session Information

  • Pharmacology
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Tu, Yue, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
  • Chen, Diping, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
  • Gu, Yihuang, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
Background

In recent years, traditional Chinese herbal medications (TCHMs) are found to possess potent anti-aging activities. Rhubarb, derived from the root of Rheum palmatum, has been found to have anti-aging pharmacological effect. Rhein, a bioactive constituent of rhubarb, plays a vital role in its pharmacological effect. However, the potential mechanism of rhein in anti-aging remains unclear. Autophagy and its related signaling pathway mTOR play the important roles in aging.

Methods

In vitro, D-galactose (D-gal) was used to induce renal cellular aging in NRK-52E cells, following treating with or without rhein or vitamin E (VE). To measure renal cellular aging, the klotho protein expression was detected, and the senescence-associated-β-galactosidase (SA-β-gal) staining were observed. To study the changes of autophagy in the aging effects, several key autophagic markers protein expressions, including LC3 I/II, beclin1, SQSTM1/p62 and phospho-p62 (p-p62), were detected. Further, the changes of key protein expressions in mTOR signaling, including mTOR, and phospho-mTOR (Ser2448 and Ser2481), were detected in the same condition. The changes of the key protein expressions in mTOR-mediated autophagy were detected in NRK-52E cells exposed to D-gal and rhein or VE with or without mTOR inhibitor rapamycin (RAP) and mTOR activator MHY1485. In vivo, SD rats were divided into Normal, D-gal, Rhein-low dose, Rhein-high dose, VE, RAP and MHY1485 groups. The renal aging and mTOR-mediated autophagy related protein expressions and SA-β-gal staining were detected.

Results

Results showed that, renal tubular cellular aging in vitro and renal aging in vivo both induced by D-gal could be ameliorated by rhein and VE by inducing klotho protein expression, and attenuating the positive area of SA-β-gal staining. Rhein and VE could regulate mTOR-mediated autophagy by reducing autophagic related protein expressions and increasing mTOR signaling related protein expressions both in vitro and in vivo.

Conclusion

In this study, we demonstrated that rhein, similar to VE, could alleviate renal aging via regulating mTOR-mediated autophagy. These findings suggest that targeting autophagy and related signaling pathways may provide new strategies in the age-associated renal damage of the elderly patients.

Funding

  • Government Support - Non-U.S.