Danggui Buxue Tang Attenuates Tubulointerstitial Fibrosis via Suppressing NLRP3 Inflammasome in a Rat Model of Unilateral Ureteral Obstruction

Abstract

Inflammation significantly contributes to the progression of chronic kidney disease (CKD). This study aimed to characterize Danggui Buxue Tang (DBT) renoprotection and relationship with NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome expression in rats with unilateral ureteral obstruction (UUO). Sprague-Dawley rats were subjected to UUO and randomly assigned to untreated UUO, enalapril-treated (10 mg/kg/day), and DBT-treated (9 g/kg/day) groups. Sham-operated rats served as controls, with 8 rats in each group. All rats were sacrificed for blood and renal specimen collection at 14 days after UUO. Untreated UUO rats exhibited azotemia, intense tubulointerstitial collagen deposition, upregulations of tubulointerstitial injury index, augmentation levels of collagen I (Col I), α-smooth muscle actin (α-SMA), NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), pro-caspase-1, caspase-1, IL-1β, and pro-IL-1β. DBT treatment significantly attenuated interstitial collagen deposition and tubulointerstitial injury, lowering Col I and α-SMA levels. Synchronous expressions of NLRP3, ASC, pro-caspase-1, caspase-1, pro-IL-1β, and IL-1β decreased in renal tissue. In comparison to enalapril, DBT significantly reduced tubulointerstitial injury, interstitial collagen deposition, and expressions of Col I and IL-1β. Thus, DBT offers renoprotection in UUO rats, which was associated with suppressing NLRP3 inflammasome expression and following reduction of the secretion of cytokine IL-1β. The mechanisms of multitargets of traditional Chinese medicine can be better used for antifibrotic treatment.

Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via TGF-β1-Smad-ILK pathway in unilateral ureteral obstruction rats

“…UUO is recognized as an ideal experimental model of renal interstitial fibrosis. Ureteral obstruction leads to a significant inflammatory and fibrotic response, followed by infiltration of inflammatory cells, renal interstitial myofibroblast proliferation, and ECM accumulation in the renal interstitium (27). We established the UUO model successfully and administered Ad-P311 into UUO rats by the tail vein.…”

The Combination of Astragalus membranaceus and Angelica sinensis Inhibits Lung Cancer and Cachexia through Its Immunomodulatory Function

“…The suppression of these two molecules slows down angiogenesis inside the tumor microenvironment, thus ameliorating tumor progression and distant metastasis. In addition to inhibition of inflammation and angiogenesis in the model of organ fibrosis [36], we further determined that the combined AM and AS therapy can attenuate cancer-related inflammation and tumor angiogenesis.…”

Danggui buxue tang inhibited mesangial cell proliferation and extracellular matrix accumulation through GAS5/NF-κB pathway

“…DGT is an ancient Chinese herbal decoction that has been demonstrated to possess hematopoietic function and has important values in glucose homeostasis, which may be a valid therapy for the control of diabetes and its complications [31]. Besides, protective effects of DGT on renal glomerular mesangium and renal function in STZ-induced rats were also explored [28,32]. Previous report has concluded that DGT could attenuate extracellular matrix components, such as FN or Col IV [9].…”