The Active Compounds and Therapeutic Target of Tripterygium wilfordii Hook. f. in Attenuating Proteinuria in Diabetic Nephropathy: A Review

Liu, Peng; Zhang, Jing; Wang, Yun; Shen, Zhengri; Wang, Chen; Chen, Dan-Qian; Qiu, Xinping

doi:10.3389/fmed.2021.747922

Cited by 18 publications

(12 citation statements)

References 101 publications

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“…Tripterygium Wilfordii Polyglycosides (TWPs) is the main compound of Tripterygium Wilfordii Hook. F. (TWHF) showing anti-fibrosis activity by reducing IL-1, IL-17, interferon-γ (IFN-γ), and TNF-α ( Liu et al, 2021 ). Previous studies show that Abelmoschus manihot reduces proteinuria and lessens kidney damage and tubulointerstitial fibrosis so that it improves kidney function.…”

Section: Discussionmentioning

confidence: 99%

Quercetin prevents chronic kidney disease on mesangial cells model by regulating inflammation, oxidative stress, and TGF-β1/SMADs pathway

Widowati

Prahastuti

Tjokropranoto

et al. 2022

PeerJ

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Background Chronic kidney disease (CKD) happens due to decreasing kidney function. Inflammation and oxidative stress have been shown to result in the progression of CKD. Quercetin is widely known to have various bioactivities including antioxidant, anticancer, and anti-inflammatory activities. Objective To evaluate the activity of quercetin to inhibit inflammation, stress oxidative, and fibrosis on CKD cells model (mouse mesangial cells induced by glucose). Methods and Material The SV40 MES 13 cells were plated in a 6-well plate with cell density at 5,000 cells/well. The medium had been substituted for 3 days with a glucose-induced medium with a concentration of 20 mM. Quercetin was added with 50, 10, and 5 µg/mL concentrations. The negative control was the untreated cell. The levels of TGF-β1, TNF-α, and MDA were determined using ELISA KIT. The gene expressions of the SMAD7, SMAD3, SMAD2, and SMAD4 were analyzed using qRT-PCR. Results Glucose can lead to an increase in inflammatory cytokines TNF-α, TGF-β1, MDA as well as the expressions of the SMAD2, SMAD3, SMAD4, and a decrease in SMAD7. Quercetin caused the reduction of TNF-α, TGF-β1, MDA as well as the expression of the SMAD2, SMAD3, SMAD4, and increased SMAD7. Conclusion Quercetin has anti-inflammation, antioxidant, antifibrosis activity in the CKD cells model. Thus, quercetin is a promising substance for CKD therapy and further research is needed to prove this in CKD animal model.

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Section: Discussionmentioning

confidence: 99%

Quercetin prevents chronic kidney disease on mesangial cells model by regulating inflammation, oxidative stress, and TGF-β1/SMADs pathway

Widowati

Prahastuti

Tjokropranoto

et al. 2022

PeerJ

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“…DKD progression is normally considered irreversible, while Chinese herbal medicine gives us hope. Reliable evidences from RCTs show that Tangshen Formula and T. wilfordii Hook extract significantly reduce proteinuria and elevate eGFR compared with ARB or ACEI ( Ge et al, 2013 ; Li et al, 2015 ; Liu et al, 2021a ). Chinese herbal medicine normally targets multiple and synergetic targets to alleviate DKD due to multiple active compounds, including the improvement of metabolism regulation, the inhibition of oxidative stress and inflammation, the modulation of mitochondrial dysfunction, and the regulation of gut microbiota and related metabolism.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic mechanism and clinical application of Chinese herbal medicine against diabetic kidney disease

Chen

Wu²,

2022

Front. Pharmacol.

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Diabetic kidney disease (DKD) is the major complications of type 1 and 2 diabetes, and is the predominant cause of chronic kidney disease and end-stage renal disease. The treatment of DKD normally consists of controlling blood glucose and improving kidney function. The blockade of renin-angiotensin-aldosterone system and the inhibition of sodium glucose cotransporter 2 (SGLT2) have become the first-line therapy of DKD, but such treatments have been difficult to effectively block continuous kidney function decline, eventually resulting in kidney failure and cardiovascular comorbidities. The complex mechanism of DKD highlights the importance of multiple therapeutic targets in treatment. Chinese herbal medicine (active compound, extract and formula) synergistically improves metabolism regulation, suppresses oxidative stress and inflammation, inhibits mitochondrial dysfunction, and regulates gut microbiota and related metabolism via modulating GLP-receptor, SGLT2, Sirt1/AMPK, AGE/RAGE, NF-κB, Nrf2, NLRP3, PGC-1α, and PINK1/Parkin pathways. Clinical trials prove the reliable evidences for Chinese herbal medicine against DKD, but more efforts are still needed to ensure the efficacy and safety of Chinese herbal medicine. Additionally, the ideal combined therapy of Chinese herbal medicine and conventional medicine normally yields more favorable benefits on DKD treatment, laying the foundation for novel strategies to treat DKD.

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“…Modern pharmacology suggests that T. wilfordii exerts anti-tumor, anti-inflammatory, and immunosuppressive effects ( 5 , 6 ), and its main active ingredients are triptolide, celastrol, and total alkaloids of T. hypoglaucum ( 7 ). Its excellent curative effect is accompanied by some side effects; thus, scientists have conducted several studies to identify its toxic components and side effects and develop strategies to reduce them ( 8 , 9 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: A rare case of death due to end-stage renal disease caused by Tripterygium wilfordii-induced myelosuppression

et al. 2022

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Tripterygium wilfordii—a traditional Chinese herbal medicine—is used to treat several diseases, including chronic kidney disease, rheumatic autoimmune disorder, and skin disorders. With the development of modern pharmacology, scientists have gradually realized that T. wilfordii has side effects on several organs and systems of the human body, including the liver, kidney, reproductive system, hematopoietic system, and immune system. Our understanding of its toxicity remains unclear. The incidence of problems in the hematopoietic system is not low but few related studies have been conducted. The serious consequences need to be of concern to clinicians and scientists. To ensure the safety of patients, it is important to elucidate the mechanism underlying the damage to the hematopoietic system caused by T. wilfordii and strategies to reduce its toxicity. Routine blood and biochemical tests should be conducted when administering T. wilfordii, and in case of any abnormality, the medication should be terminated in time along with a comprehensive symptomatic treatment. Herein, we report the case of a 50-year-old Chinese female with end-stage renal disease (ESRD) who developed severe bone marrow suppression after taking a short-term normal dose of a T. wilfordii-containing decoction. She died of sepsis and septic shock, although timely therapeutic measures (e.g., stimulating hematopoiesis, anti-infection treatment, and hemodialysis) were administered. To the best of our knowledge, this is the first report of death by T. wilfordii-induced myelosuppression from a short term, conventional dose in an adult female with ESRD. Although the underlying mechanism remains unclear, this case contradicts the notion that side effects on the hematopoietic system are non-lethal.

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The Active Compounds and Therapeutic Target of Tripterygium wilfordii Hook. f. in Attenuating Proteinuria in Diabetic Nephropathy: A Review

Cited by 18 publications

References 101 publications

Quercetin prevents chronic kidney disease on mesangial cells model by regulating inflammation, oxidative stress, and TGF-β1/SMADs pathway

Quercetin prevents chronic kidney disease on mesangial cells model by regulating inflammation, oxidative stress, and TGF-β1/SMADs pathway

Therapeutic mechanism and clinical application of Chinese herbal medicine against diabetic kidney disease

Case report: A rare case of death due to end-stage renal disease caused by Tripterygium wilfordii-induced myelosuppression

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