ErHuang Formula Improves Renal Fibrosis in Diabetic Nephropathy Rats by Inhibiting CXCL6/JAK/STAT3 Signaling Pathway

Shen, Yu-Li; Jiang, Yi-Ping; Li, Xiaoqin; Wang, Sujuan; Ma, Ming-Hua; Zhu, Jian; Rahman, Khalid; Zhang, Lijun; Luan, Xin; Zhang, Hong

doi:10.3389/fphar.2019.01596

Cited by 26 publications

(14 citation statements)

References 34 publications

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“…DN model was induced using HFD and STZ injection as described previously ( Shen et al, 2020 ). Briefly, rats were fed with HFD for 8 weeks.…”

Section: Methodsmentioning

confidence: 99%

San-Huang-Yi-Shen Capsule Ameliorates Diabetic Nephropathy in Rats Through Modulating the Gut Microbiota and Overall Metabolism

Su¹,

Yu²,

Liu³

et al. 2022

Front. Pharmacol.

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San-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic nephropathy (DN) in clinic. However, the mechanisms of SHYS on DN remain unknown. In this study, we used a high-fat diet (HFD) combined with streptozotocin (STZ) injection to establish a DN rat model. Next, we used 16S rRNA sequencing and untargeted metabolomics to study the potential mechanisms of SHYS on DN. Our results showed that SHYS treatment alleviated the body weight loss, hyperglycemia, proteinuria, pathological changes in kidney in DN rats. SHYS could also inhibite the oxidative stress and inflammatory response in kidney. 16S rRNA sequencing analysis showed that SHYS affected the beta diversity of gut microbiota community in DN model rats. SHYX could also decrease the Firmicutes to Bacteroidetes (F to B) ratio in phylum level. In genus level, SHYX treatment affected the relative abundances of Lactobacillus, Ruminococcaceae UCG-005, Allobaculum, Anaerovibrio, Bacteroides and Candidatus_Saccharimonas. Untargeted metabolomics analysis showed that SHYX treatment altered the serum metabolic profile in DN model rats through affecting the levels of guanidineacetic acid, L-kynurenine, prostaglandin F1α, threonine, creatine, acetylcholine and other 21 kind of metabolites. These metabolites are mainly involved in glycerophospholipid metabolism, tryptophan metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, tricarboxylic acid (TCA) cycle, tyrosine metabolism, arginine and proline metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and D-glutamine and D-glutamate metabolism pathways. Spearman correlation analysis showed that Lactobacillus, Candidatus_Saccharimonas, Ruminococcaceae UCG-005, Anaerovibrio, Bacteroides, and Christensenellaceae_R-7_group were closely correlated with most of physiological data and the differential metabolites following SHYS treatment. In conclusion, our study revealed multiple ameliorative effects of SHYS on DN including the alleviation of hyperglycemia and the improvement of renal function, pathological changes in kidney, oxidative stress, and the inflammatory response. The mechanism of SHYS on DN may be related to the improvement of gut microbiota which regulates arginine biosynthesis, TCA cycle, tyrosine metabolism, and arginine and proline metabolism.

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“…DN model was induced using HFD and STZ injection as described previously ( Shen et al, 2020 ). Briefly, rats were fed with HFD for 8 weeks.…”

Section: Methodsmentioning

confidence: 99%

San-Huang-Yi-Shen Capsule Ameliorates Diabetic Nephropathy in Rats Through Modulating the Gut Microbiota and Overall Metabolism

Su¹,

Yu²,

Liu³

et al. 2022

Front. Pharmacol.

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show abstract

“…After 4 weeks, mice fed a high-fat–high-glucose diet were intraperitoneally injected with 50 mg/kg STZ (Sigma-Aldrich, St. Louis, MO, United States) for 5 consecutive days, while those in the normal control were injected with the same volume of normal saline. Four weeks after injection, the mice with blood glucose concentration above 16.7 mmol/L were considered to be type 2 diabetics [Shen et al ( 15 )]. The diabetic mice were divided into five different groups ( n = 8 each group), including control group (Diabetic group), calcium dobesilate group (CAD, 0.25 g/kg.day –1 ), low-dose group (LDG, 1.6 g/kg.day –1 BJ) group, medium-dose group (MDG, 3.2 g/kg.day –1 BJ), and high-dose group (HDG, 6.4 g/kg.day –1 BJ).…”

Section: Methodsmentioning

confidence: 99%

Bie-Jia-Ruan-Mai-Tang, a Chinese Medicine Formula, Inhibits Retinal Neovascularization in Diabetic Mice Through Inducing the Apoptosis of Retinal Vascular Endothelial Cells

Liu

Chen

et al. 2022

Front. Cardiovasc. Med.

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Proliferative diabetic retinopathy (PDR) is one of the main complications of diabetes, mainly caused by the aberrant proliferation of retinal vascular endothelial cells and the formation of new blood vessels. Traditional Chinese medicines possess great potential in the prevention and treatment of PDR. Bie-Jia-Ruan-Mai-Tang (BJ), a Chinese medicine formula, has a good therapeutic effect on PDR clinically; however, the mechanism of action involved remains unclear. Therefore, we investigated the effect of BJ on PDR through in vitro and in vivo experiments. A diabetic mouse model with PDR was established by feeding a high-fat–high-glucose diet combined with an intraperitoneal injection of streptozotocin (STZ), while high-glucose-exposed human retinal capillary endothelial cells (HRCECs) were employed to mimic PDR in vitro. The in vivo experiments indicated that BJ inhibited the formation of acellular capillaries, decreased the expression of VEGF, and increased the level of ZO-1 in diabetic mice retina. In vitro experiments showed that high glucose significantly promoted cell viability and proliferation. However, BJ inhibited cell proliferation by cycle arrest in the S phase, thus leading to apoptosis; it also increased the production of ROS, decreased the mitochondrial membrane potential, reduced the ATP production, and also reduced the expressions of p-PI3K, p-AKT, and Bcl-xL, but increased the expressions of Bax and p-NF-κB. These results suggest that BJ induces the apoptosis of HRCECs exposed to high glucose through activating the mitochondrial death pathway by decreasing the PI3K/AKT signaling and increasing the NF-κB signaling to inhibit the formation of acellular capillaries in the retina, thus impeding the development of PDR.

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“…Rats were fed a high‐fat diet for 4 weeks, fasted for 12 hr, and subjected to an intraperitoneal injection of 35 mg/kg STZ solution to prepare the DN model (Shen et al., 2020 ). After 72 hr, the 2‐hr postglucose load plasma glucose (PG) levels of rats were measured, and the successful establishment of the DN model was verified by PG levels >11.1 mmol/L.…”

Section: Methodsmentioning

confidence: 99%

Dandelion sterol improves diabetes mellitus–induced renal injury in in vitro and in vivo study

Tian

Zhou

et al. 2021

Food Science & Nutrition

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ErHuang Formula Improves Renal Fibrosis in Diabetic Nephropathy Rats by Inhibiting CXCL6/JAK/STAT3 Signaling Pathway

Abstract: CXCL6/JAK/STAT3 signal pathway, which is associated with inflammation and fibrosis of the tissue. These findings may have clinical implications for the treatment of DN.

Cited by 26 publications

References 34 publications

San-Huang-Yi-Shen Capsule Ameliorates Diabetic Nephropathy in Rats Through Modulating the Gut Microbiota and Overall Metabolism

San-Huang-Yi-Shen Capsule Ameliorates Diabetic Nephropathy in Rats Through Modulating the Gut Microbiota and Overall Metabolism

Bie-Jia-Ruan-Mai-Tang, a Chinese Medicine Formula, Inhibits Retinal Neovascularization in Diabetic Mice Through Inducing the Apoptosis of Retinal Vascular Endothelial Cells

Dandelion sterol improves diabetes mellitus–induced renal injury in in vitro and in vivo study

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