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Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction by Alleviating Apoptosis through Regulating Transforming Growth Factor beta1 (TGF-β1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway.
Med Sci Monit. 2020 Mar 24; 26:e920720.MS

Abstract

BACKGROUND

Rhubarb and astragalus capsule (RAC) has been used in the clinical treatment of chronic kidney disease for decades. However, the mechanism of RAC has not been fully elucidated. This study aimed to investigate the protective effect and mechanisms of RAC on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis. MATERIAL AND

METHODS

The main components of RAC are detected by high-performance liquid phase (HPLC). A rat model of UUO was established, and a subset of rats underwent treatment with RAC. Renal function and renal pathology were examined at 14 days and 21 days after the UUO operation. Renal cell apoptosis was detected by TUNEL staining. The levels of Bcl-2 and Bax in the kidney were examined by western blotting, and the levels of collagen I, alpha-SMA, transforming growth factor (TGF)-β1, and p38 MAPK in the kidneys were detected by immunohistochemistry.

RESULTS

High-performance liquid phase chromatography showed that RAC contained 1.12 mg/g aloe-emodin, 2.25 mg/g rhein, 1.75 mg/g emodin, and 4.50 mg/g chrysophanol. Administration of RAC significantly decreased the levels of urinary N-acetyl-β-D-glucosaminidase (NAG), serum blood urea nitrogen (BUN), and creatinine (Scr) and also reduced renal tissue damages and interstitial fibrosis induced by UUO in rats. Moreover, the increased levels of collagen I, alpha-SMA, TGF-β1, p38 MAPK, and the Bax/Bcl-2 ratio, as well as cell apoptosis in the kidney, were induced by UUO, and were all found deceased by RAC treatment.

CONCLUSIONS

RAC can improve the renal interstitial fibrosis induced by UUO, and the mechanism may be related to inhibition of renal tubular cell apoptosis via TGF-β1/p38 MAPK pathway.

Authors+Show Affiliations

Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).Regenerative Medicine Research Center, Guangxi Medical University, Nanning, Guangxi, China (mainland).Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32205836

Citation

Zeng, Xian, et al. "Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats With Unilateral Ureteral Obstruction By Alleviating Apoptosis Through Regulating Transforming Growth Factor Beta1 (TGF-β1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway." Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, vol. 26, 2020, pp. e920720.
Zeng X, Cai G, Liang T, et al. Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction by Alleviating Apoptosis through Regulating Transforming Growth Factor beta1 (TGF-β1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway. Med Sci Monit. 2020;26:e920720.
Zeng, X., Cai, G., Liang, T., Li, Q., Yang, Y., Zhong, X., Zou, X., Qin, M., & Mi, Z. (2020). Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction by Alleviating Apoptosis through Regulating Transforming Growth Factor beta1 (TGF-β1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 26, e920720. https://doi.org/10.12659/MSM.920720
Zeng X, et al. Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats With Unilateral Ureteral Obstruction By Alleviating Apoptosis Through Regulating Transforming Growth Factor Beta1 (TGF-β1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway. Med Sci Monit. 2020 Mar 24;26:e920720. PubMed PMID: 32205836.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction by Alleviating Apoptosis through Regulating Transforming Growth Factor beta1 (TGF-β1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway. AU - Zeng,Xian, AU - Cai,Guozhen, AU - Liang,Taolin, AU - Li,Qingqing, AU - Yang,Yufang, AU - Zhong,Xiaobin, AU - Zou,Xiaoqin, AU - Qin,Mengyuan, AU - Mi,Zhengcheng, Y1 - 2020/03/24/ PY - 2020/3/25/entrez PY - 2020/3/25/pubmed PY - 2020/12/19/medline SP - e920720 EP - e920720 JF - Medical science monitor : international medical journal of experimental and clinical research JO - Med Sci Monit VL - 26 N2 - BACKGROUND Rhubarb and astragalus capsule (RAC) has been used in the clinical treatment of chronic kidney disease for decades. However, the mechanism of RAC has not been fully elucidated. This study aimed to investigate the protective effect and mechanisms of RAC on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis. MATERIAL AND METHODS The main components of RAC are detected by high-performance liquid phase (HPLC). A rat model of UUO was established, and a subset of rats underwent treatment with RAC. Renal function and renal pathology were examined at 14 days and 21 days after the UUO operation. Renal cell apoptosis was detected by TUNEL staining. The levels of Bcl-2 and Bax in the kidney were examined by western blotting, and the levels of collagen I, alpha-SMA, transforming growth factor (TGF)-β1, and p38 MAPK in the kidneys were detected by immunohistochemistry. RESULTS High-performance liquid phase chromatography showed that RAC contained 1.12 mg/g aloe-emodin, 2.25 mg/g rhein, 1.75 mg/g emodin, and 4.50 mg/g chrysophanol. Administration of RAC significantly decreased the levels of urinary N-acetyl-β-D-glucosaminidase (NAG), serum blood urea nitrogen (BUN), and creatinine (Scr) and also reduced renal tissue damages and interstitial fibrosis induced by UUO in rats. Moreover, the increased levels of collagen I, alpha-SMA, TGF-β1, p38 MAPK, and the Bax/Bcl-2 ratio, as well as cell apoptosis in the kidney, were induced by UUO, and were all found deceased by RAC treatment. CONCLUSIONS RAC can improve the renal interstitial fibrosis induced by UUO, and the mechanism may be related to inhibition of renal tubular cell apoptosis via TGF-β1/p38 MAPK pathway. SN - 1643-3750 UR - https://www.unboundmedicine.com/medline/citation/32205836/Rhubarb_and_Astragalus_Capsule_Attenuates_Renal_Interstitial_Fibrosis_in_Rats_with_Unilateral_Ureteral_Obstruction_by_Alleviating_Apoptosis_through_Regulating_Transforming_Growth_Factor_beta1__TGF_β1_/p38_Mitogen_Activated_Protein_Kinases__p38_MAPK__Pathway_ L2 - https://www.medscimonit.com/download/index/idArt/920720 DB - PRIME DP - Unbound Medicine ER -