Potential therapeutic efficacy of pachymic acid in chronic kidney disease induced in rats: role of Wnt/β-catenin/renin–angiotensin axis

Abstract

Objectives Chronic kidney disease (CKD) is a major public health problem associated with high mortality. The therapeutic effects of pachymic in CKD management and its underlying mechanisms have not been studied. Therefore, we aimed to investigate the possible inhibitory effect of PA on renal Wnt/β-catenin signalling in CKD. Methods CKD was induced in rats by doxorubicin (DOX; 3.5 mg/kg i.p., twice weekly for 3 weeks). Rats were treated orally with PA (10 mg/kg/day), LOS (10 mg/kg/day) or their combination (PA + LOS) for 4 weeks starting after the last dose of DOX. Key findings DOX-induced renal injury was characterized by high serum cystatin-C, and urine albumin/creatinine ratio, renal content of podocin and klotho were decreased. Tumour necrosis factor-α, interleukin-6, interleukin-1β, Wnt1, active β-catenin/total β-catenin ratio and fibronectin along with mRNA expression of RENIN, ACE and AT1 were increased in renal tissues. Treatment with either PA or LOS ameliorated all DOX-induced changes. The combined treatment was more effective in improving all changes than monotherapy. Conclusions These results suggest a new therapeutic benefit of PA in ameliorating CKD in rats through its up-regulatory effect on renal klotho thereby preventing Wnt/β-catenin reactivation and RAS gene expression. PA/LOS combination provided an additional inhibition of Wnt/β-catenin signalling and its downstream targets.

Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis

“…Ginsenoside (Rg1, Rg2, Rg3, etc.) [ 16 – 18 ], paeonol [ 19 , 20 ], gallic acid [ 21 ], loganin [ 22 ] and pachymic acid [ 23 ] showed activities in kidney fibrosis and other kidney diseases. Cornuside [ 24 ], loganic acid [ 25 ] and rehmannioside A [ 26 ] have anti-inflammatory activities, which further proved that the key constituents in the “constituents-targets-pathways” network may be used as the pharmacodynamic material basis of RSGB in the treatment of renal fibrosis.…”

Vanillin and pentoxifylline ameliorate isoproterenol-induced myocardial injury in rats via the Akt/HIF-1α/VEGF signaling pathway

“…To quantify the fibrosis percentage, the Masson's trichrome-stained sections were captured at ×200 magnification, where the blue color indicated collagen deposition. 32,40–43…”

“…To quantify the fibrosis percentage, the Masson's trichrome-stained sections were captured at ×200 magnification, where the blue color indicated collagen deposition. 32,[40][41][42][43] The paraffin-embedded heart sections were also used for immunohistochemical staining of CD31. The heart sections were deparaffinized with xylene and rehydrated with ethanol.…”

Pharmacological profiles and therapeutic applications of pachymic acid (Review)

“…Gui et al ( 64 ) reported that PA alleviates LPS-induced lung injury by relieving LPS-inflammation, such as TNF-α, IL-6, monocyte chemoattractant protein 1 and IL-1β, reducing cell numbers in bronchoalveolar lavage fluid, and inhibiting LPS-induced apoptosis. Additionally, PA ameliorates renal injury in vivo by inhibiting renal inflammation, reducing the levels of TNF-α, IL-6 and inducible nitric oxide synthase, enhancing the expression of Nrf2 and HO-1, and preventing renal Wnt/β-catenin signaling ( 65 , 66 ).…”

“…PA alone or as adjuvant therapy with losartan can lower serum B-type natriuretic peptide and improve systolic function and cardiac fiber diameter to attenuate doxorubicin-induced heart failure in vivo ( 86 ). Moreover, PA ameliorates doxorubicin-induced renal injury by regulating of serum cystatin-C, urine albumin/creatinine ratio, renal podocin and klotho content, TNF-α, IL-6 and IL-1β ( 66 ).…”