Huangkui Capsule Ameliorates Renal Fibrosis in a Unilateral Ureteral Obstruction Mouse Model Through TRPC6 Dependent Signaling Pathways

Gu, Li; Ge, Haitao; Zhao, Lei; Wang, Yujing; Zhang, Fan; Tang, Haitao; Cao, Zhengyu; Yu, Boyang; Chai, Chee‐Yin

doi:10.3389/fphar.2020.00996

Cited by 20 publications

(12 citation statements)

References 52 publications

(75 reference statements)

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“…For the mechanistic studies, the Huangkui capsule has been shown to improve kidney inflammation and glomerular injury in ADR-induced nephropathy through inhibition of the p38 MAPK signaling pathway and AC inhibits ROS-ERK1/2-mediated NLRP3 inflammasome activation ( Tu Y. et al, 2013 ; Li W. et al, 2019b ). Recent research demonstrated that Huangkui capsule protection against renal fibrosis is dependent on the transient receptor potential channel 6 (TRPC6) pathway ( Gu et al, 2020 ). In detail, the Huangkui capsule inhibited the expressions of a plethora of pro-inflammatory mediators in UUO mice by suppressing both canonical (Smad2/3) and noncanonical (MAPK) signaling pathways and the TRPC6/calcineurin A/nuclear factor of the activated T-cells signaling axis, which were possible through direct inhibition of TRPC6 activity in a heterologous expression system and indirect suppression of TRPC6 expression in both WT and TRPC6 knockout mice.…”

Section: Tcm For Treating Ckdmentioning

confidence: 99%

Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms

Wang

Feng

et al. 2022

Front. Pharmacol.

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Chronic kidney disease (CKD) is a common and progressive disease that has become a major public health problem on a global scale. Renal fibrosis is a common feature in the pathogenesis of CKD, which is mainly related to the excessive accumulation and deposition of extracellular matrix caused by various inflammatory factors. No ideal treatment has yet been established. In recent years, based on the traditional Chinese medicine (TCM) theory of CKD and its molecular mechanism, clinical evidence or experimental studies have confirmed that a variety of Chinese materia medica (CMM) and their effective components can delay the progress of CKD. TCM believes that the pathogenesis of CKD is the deficiency in the root and excess in the branch, and the deficiency and excess are always accompanied by the disease. The strategies of TCM in treating CKD are mainly based on invigorating Qi, tonifying the kidneys, promoting blood circulation, removing stasis, eliminating heat and dampness, removing turbidity, and eliminating edema, and these effects are multitargeted and multifunctional. This review attempts to summarize the theories and treatment strategies of TCM in the treatment of CKD and presents the efficacy and mechanisms of several CMMs supported by clinical evidence or experimental studies. In addition, the relationship between the macroscopic of TCM and the microscopic of modern medicine and the problems faced in further research were also discussed.

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Section: Tcm For Treating Ckdmentioning

confidence: 99%

Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms

Wang

Feng

et al. 2022

Front. Pharmacol.

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“…Blockade of TRPC6 with another selective inhibitor BI-749327 observed similar protection in obstructed kidneys ( Lin et al, 2019 ). Indeed, TRPC6-dependent elevation of cellular solute Ca 2+ activates calcineurin, which stimulates the nuclear factor of activated T cells (NFAT) transcriptional pathway to induce fibroblast differentiation ( Davis et al, 2012 ; Lin et al, 2019 ; Gu et al, 2020 ). Studies have demonstrated that TRPC6 and NFAT form a mutual positive feedback loop that aggravates the renal fibrosis ( Nijenhuis et al, 2011 ).…”

Section: Ca 2+ Channelsmentioning

confidence: 99%

Ion channels as a therapeutic target for renal fibrosis

Yan

Fang

2022

Front. Physiol.

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Renal ion channel transport and electrolyte disturbances play an important role in the process of functional impairment and fibrosis in the kidney. It is well known that there are limited effective drugs for the treatment of renal fibrosis, and since a large number of ion channels are involved in the renal fibrosis process, understanding the mechanisms of ion channel transport and the complex network of signaling cascades between them is essential to identify potential therapeutic approaches to slow down renal fibrosis. This review summarizes the current work of ion channels in renal fibrosis. We pay close attention to the effect of cystic fibrosis transmembrane conductance regulator (CFTR), transmembrane Member 16A (TMEM16A) and other Cl− channel mediated signaling pathways and ion concentrations on fibrosis, as well as the various complex mechanisms for the action of Ca2+ handling channels including Ca2+-release-activated Ca2+ channel (CRAC), purinergic receptor, and transient receptor potential (TRP) channels. Furthermore, we also focus on the contribution of Na+ transport such as epithelial sodium channel (ENaC), Na+, K+-ATPase, Na+-H+ exchangers, and K+ channels like Ca2+-activated K+ channels, voltage-dependent K+ channel, ATP-sensitive K+ channels on renal fibrosis. Proposed potential therapeutic approaches through further dissection of these mechanisms may provide new therapeutic opportunities to reduce the burden of chronic kidney disease.

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“…inflammatory response to tubular atrophy and tissue fibrosis. [16][17][18] After day 10 until day 28, the healthy and control group were given aquadest (0.2 ml/day) with a probe, while the intervention group was given a combination of propolis extract and vitamin D3 orally every day. On day 28, rats were euthanized by the cervical dislocation method.…”

Section: Original Articlementioning

confidence: 99%

Exploring the role of the combination of propolis and vitamin D3 on VCAM-1 and Caspase-3 expression in preventing atherosclerosis in chronic kidney disease rats

et al. 2022

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Background: Increased blood pressure that occurs in chronic kidney disease (CKD) is influenced by the occurrence of thickening of blood vessels. This study evaluates the utilization of propolis which acts as an anti-inflammatory and vitamin D3 which plays a role in calcium-phosphate metabolism, that when combined are expected to prevent atherosclerosis. Methods: This experimental research used a post-test only group design with a total of 24 male rats divided into 3 groups. Subjects were induced to develop CKD with unilateral ureteral obstruction. A combination of 50mg/kgBW of propolis and 0.126mcg/kgBW of vitamin D3 was given orally every morning in the intervention group. Hemodynamics and atherosclerosis status were observed using sonography until week 4. Inflammatory markers with vascular cell adhesion molecule 1 (VCAM-1) and Caspase-3 were evaluated weekly via plasma and target organ samples were immunohistochemically examined at the study’s end. Results: Propolis and vitamin D3 significantly reduced blood pressure from 156 mmHg at the beginning of the study to 117mmHg at week 4 (p=0.000). Thickening of the aorta occurred in the control and intervention groups but the thickening in the control group (0.90mm) was statistically significantly (p=0.000) higher than the intervention group (0.30mm). There were decreased VCAM-1 and Caspase-3 levels in the intervention group compared to the control group, both in plasma and target organ levels Conclusion: Utilization of propolis and vitamin D3 combined has a good effect on lowering inflammation, improving hemodynamics and preventing atherosclerosis in chronic kidney disease rat models.

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Huangkui Capsule Ameliorates Renal Fibrosis in a Unilateral Ureteral Obstruction Mouse Model Through TRPC6 Dependent Signaling Pathways

Cited by 20 publications

References 52 publications

Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms

Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms

Ion channels as a therapeutic target for renal fibrosis

Exploring the role of the combination of propolis and vitamin D3 on VCAM-1 and Caspase-3 expression in preventing atherosclerosis in chronic kidney disease rats

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