Cortex Mori Radicis Attenuates Streptozotocin-induced Diabetic Renal Injury in Mice via Regulation of Transient Receptor Potential Canonical Channel 6

Abstract

Objective: Cortex Mori Radicis (CMR) has been reported to possess anti-pyretic, anti-convulsant, anti-allergic, anti-inflammatory, and anti-diabetic effects. In this study, we aimed to investigate the effect of CMR on streptozotocin (STZ)-induced diabetic renal injury in mice and explore the underlying mechanism. Methods: Mice were gavaged with different doses of CMR for continuous 7 days. Then, STZ (50 mg/kg) was applied to induce renal injury associated with type 1 diabetes. Firstly, blood glucose levels and metabolic parameters were evaluated, including weight, food intake, and excrement. HE and PAS staining were performed to present renal histological changes. Renal inflammation, fibrosis, and oxidative stress were assayed by real time PCR and ELISA, separately. Additionally, podocyte-related markers, such as nephrin and wilms' tumor-1 (WT-1) were detected by immunohistochemical staining and Western blot separately. Lastly, expression of transient receptor potential canonical channel 6 (TRPC6) and activation of MAPK signaling pathways were assayed. Results: CMR pretreatment significantly lowered the blood glucose levels, suppressed renal inflammation, fibrosis and oxidative stress, and relieved renal pathological injury, accompanying the inhibition of nephrin and WT-1 expression in STZ-induced diabetic mice. Moreover, CMR decreased the expression of TRPC6 and suppressed phosphorylation of ERK, but not P38 MAPK and JNK. Notably, the application of hyperforin, a specific activator of TRPC6, significantly abrogated the hypoglycemic effect of CMR and reversed the suppression of CMR on TRPC6 expression and ERK activation in the diabetic mice. Conclution: Our findings indicated that CMR attenuated early renal injury in STZ-induced diabetic mice through inhibiting ERK signaling via regulation of TRPC6, which suggests that CMR can be considered as a promising candidate for the management of diabetes-related renal complications

Mutation analysis of TRPC6 gene in nephrotic syndrome in children from a single center

“…Focal glomerulosclerosis caused by mutations in the TRPC6 gene has been a hot research topic over the years [8,9].Since 2005, when winn et al [10] first cloned the TRPC6 gene that causes FSGS from patients with familial focal segmental glomerulosclerosis (FSGS), the TRPC6 gene and the TRPC6 cation channel protein have been continuously research [11].There are interactions between TRPC6 cation channel proteins and the cleavage septum molecules Nephrin and Podocin, which are jointly involved in physiological functions such as intercellular signaling between podocytes, cell polarization, and stabilization of the cytoskeleton [10].In 2018, scholars Chen Lei et al [12] observed by cryo-electron microscopy that TRPC6 consists of amino acids that are folded into two long helices, namely CH1 and CH2.CH1 runs from the periphery to the center of the channel and connects to CH2 through a 90° turn.And it was seen that TRPC6 protein is a 6-transmembrane protein consisting of 931 amino acids, with a small pore region between the 5th and 6th transmembrane proteins, which forms the cation channel.Wang Q et al [13] stated that in damaged podocytes, TRPC6 protein regulates cation channels through the Rho/ROCK dependent pathway regulates foot cell actin stress fiber formation and focal adhesions. New studies demonstrated that nephrin and TRPC6 proteins have direct or indirect interactions in podocytes [14].…”

The impact of Sangju Qingjie Decoction on the pulmonary microbiota in the prevention and treatment of chronic obstructive pulmonary disease

“…Herein, we constructed a COPD rat model and investigated the effects of SJQJD on the pulmonary microbiota of COPD rats through 16S rRNA sequencing. Modern pharmacology indicates that the extract of mori cortex has a regulatory effect on oxidative stress ( Zhai et al., 2022 ), chrysanthemi indici flos, trichosanthis pericarpium, pheretima, fritillariae cirrhosae bulbus, phragmitis rhizoma all exhibit anti-inflammatory activity ( Park et al., 2016 ; Liu et al., 2020 ; Tian et al., 2020 ; Li et al., 2022 ; Liu et al., 2024 ), plantaginis semen has the function of regulating lipid metabolism and immune response ( Sun et al., 2019 ; Ren et al., 2021 ), glycyrrhizae radix et rhizoma has anti-inflammatory and detoxifying effects ( Li et al., 2019 ; Jiang et al., 2022 ). These physiological processes are involved in various stages of physiological pathology.…”