Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator–activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats

Ge, Jingping; Miao, Jing; Sun, Xiance; Yu, Jiangyi

doi:10.1016/j.jep.2016.05.033

Cited by 71 publications

(68 citation statements)

References 40 publications

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“…8,[11][12][13]23 Previous studies have reported their successful use in the treatment of kidney and inflammatory diseases. [5][6][7]9,14 In the current study, in vivo results revealed that the oral administration of HKC improved the survival rates of 5T MM syngeneic mice (Figure 8). To the best of our knowledge, the current study is the first to report the effects of HKC, a modern Chinese patent medicine, on MM.…”

Section: Discussionsupporting

confidence: 52%

“…The following pathways were determined to be enriched following RNA-sequencing and KEGG analysis ( Figure 4): osteoclast differentiation (ko04380), chemokine signaling pathway (ko04062), hematopoietic cell lineage (ko04640), TNF signaling pathway (ko04668) and Cell adhesion molecules (ko04514), therefore, these pathways involved in environmental information processing and cell-cell interaction were to some extent supporting the reports of HKC's anti-inflammatory effects. [5][6][7]9,14 Additionally, the enriched pathways of riboflavin metabolism (ko00740), drug metabolismcytochrome P450 (ko00982), metabolism of xenobiotics by cytochrome P450 (ko00980) and glutathione metabolism (ko00480) may reflect the intermediate processes of first metabolite transformation from the flavonoid extracts from Flos A. manihot. According to previously performed experiments on rats, the flavonoid extracts of Flos A. manihot were rapidly absorbed and reached peak blood plasma concentrations within 20-30 min after oral administration.…”

Section: Discussionmentioning

confidence: 99%

“…In 1999, HKCs received regulatory approval from China State Food and Drug Administration as a Class III drug (approval no. Z19990040) for the treatment of chronic glomerulonephritis [5][6][7] and other inflammatory diseases. 8,9 Various flavonoids have been determined as the major chemical constituents of Flos A. manihot via spectroscopy, 10 chromatography, 11 and high-performance liquid chromatography (HPLC).…”

Section: Introductionmentioning

confidence: 99%

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Bioactive Compounds from Abelmoschus manihot L. Alleviate the Progression of Multiple Myeloma in Mouse Model and Improve Bone Marrow Microenvironment

Hou

Qian

et al. 2020

OTT

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Abelmoschus manihot (L.) Medik. (Malvaceae) derived Huangkui capsules (HKC) represent a traditional Chinese medicine that has been widely applied to the clinical therapy of kidney and inflammatory diseases. The present study aimed to determine the potential therapeutic effects and underlying mechanisms of the ingredients on Multiple Myeloma (MM), an incurable disease that exhibits malignant plasma cell clonal expansion in the bone marrow. Methods: A 5TMM3VT syngeneic MM-prone model was established and treated with HKC. Murine pre-osteoblast MC3T3-E1 and pre-osteoclast Raw264.7 cells were treated with nine flavonoid compounds extracted from the flowers of Abelmoschus manihot. MC3T3-E1 and Raw264.7 cells were then examined by alizarin red staining and tartrate-resistant acid phosphatase activity staining, respectively. The proliferation of two human MM cells (ARP1, H929) was examined by performing an MTT assay following treatment with flavonoid compounds. Additionally, the cell cycle was analyzed via staining and flow cytometry. The differential expressions of certain proteins were detected via Western blotting, transcriptomic RNA-sequencing as well as RT-qPCR. Results: The results revealed that MM-prone animals appeared to be protected following HKC treatment, as evidenced by a prolonged survival rate. Furthermore, four of the nine flavonoid compounds [Hyperin/Hyperoside, HK-2; Cannabiscitrin, HK-3; 3-O-kaempferol-3-O-acetyl-6-O-(p-coumaroyl)-β-D-glucopyranoside, HK-11; 8-(2''-pyrrolidione-5''-yl)quercetin, HK-B10] induced the differentiation of murine pre-osteoblast MC3T3-E1 cells. In addition, two compounds [Isomyricitrin, HK-8; quercetin-8-(2''-pyrrolidione-5"-yl)-3ʹ-O-β-D-glucopyranosid, HK-E3] suppressed osteoclastogenesis in murine Raw264.7 cells. HK-11 directly inhibited MM cells (ARP1 and H929) proliferation and induced G0/G1 cell cycle arrest, which may have involved the suppressing β-catenin protein, increasing expressions of IL-6 and TNF-α, as well as activating mature TGF-β1 and some other metabolic pathways. Conclusion: These results of the present study indicated that the bio-active ingredients of HKC exerted protective effects on MM mouse survival through promoting osteoblastogenesis and suppressing osteoclastogenesis, thus improving the bone marrow microenvironment to inhibit MM cell proliferation.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bioactive Compounds from Abelmoschus manihot L. Alleviate the Progression of Multiple Myeloma in Mouse Model and Improve Bone Marrow Microenvironment

Hou

Qian

et al. 2020

OTT

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“…Irb elevated PPAR-γ levels and activated AMPK/Akt/mTOR signaling in the liver Irb treatment can upregulate the expression of PPAR-α in the tissues of db/db mice; however, Irb is a known PPAR-γ agonist, but its ability as a PPAR-α agonist requires further elucidation. Moreover, PPAR-γ is also a member of the nuclear receptor superfamily and is an important regulator of lipid and glucose homeostasis; these processes control lipid mobilization into adipocytes by promoting adipogenesis and regulating the expression of adipocyte-secreted proteins and adipocytokines such as leptin and adiponectin, thereby reducing lipotoxicity [19,20]. In db/db mice, the level of PPAR-γ protein was dramatically decreased, but Irb treatment significantly increased the protein expression of PPAR-γ as shown by Western blot analysis ( Figure 3A and 3B).…”

Section: 5mentioning

confidence: 99%

Irbesartan ameliorates hyperlipidemia and liver steatosis in type 2 diabetic db/db mice via stimulating PPAR-γ, AMPK/Akt/mTOR signaling and autophagy

Zhong

Gong

et al. 2017

International Immunopharmacology

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Irbesartan (Irb), a unique subset of angiotensin II receptor blockers (ARBs) with PPAR-γ activation function, has been reported to play a role in renal dysfunction, glucose metabolism, and abnormal lipid profile in diabetic animal models and humans. However, the underlying mechanisms that improve hyperlipidemia and liver steatosis are unclear. This study investigated the effects of Irb on lipid metabolism and hepatic steatosis using the spontaneous type 2 diabetic db/db mouse model. The results demonstrated body and liver weight, food consumption, lipid content in serum and liver tissue, and liver dysfunction as well as hepatic steatosis were increased in db/db mice compared with db/m mice, whereas the increases were reversed by Irb treatment. Moreover, Irb administration resulted in an increase in LC3BII as well as the LC3BII/I ratio through activating PPAR-γ and p-AMPK and inhibiting p-Akt and p-mTOR, thereby inducing autophagy in the db/db mouse liver. Therefore, our findings suggest that Irb can ameliorate hyperlipidemia and liver steatosis by upregulating the expression of PPAR-γ, activating the AMPK/Akt/mTOR signaling pathway and inducing liver autophagy.

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“…In this way, it can maintain normal physiological function of cells. PPAR-γ is a type of ligand-activated nuclear transcription factor (21) that is associated with fat differentiation, obesity and insulin resistance (22). Furthermore, PPAR-γ is the target molecule of euglycemic agents, such as thiazolidnediones (22).…”

Section: Discussionmentioning

confidence: 99%

Trigonelline reduced diabetic nephropathy and insulin resistance in type�2 diabetic rats through peroxisome proliferator‑activated receptor‑γ

Wang

et al. 2019

Exp Ther Med

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Trigonelline has been reported to serve an important role in cell cycle control, oxidative and ultraviolet stress and DNA methylation. In the present study, the effects of trigonelline were examined on type-2 diabetes mellitus (T2DM)-induced renal dysfunction, and its possible mechanism was investigated. Sprague-Dawley rats were fed with high-fat diet (HFD) for 4 weeks and intraperitoneally injected with 35 mg/kg of streptozotocin for 4 weeks. As a result, trigonelline increased body weight, inhibited the kidney weight/body weight ratio and blood glucose levels, and reduced the levels of blood urea nitrogen, creatinine and albumin in type 2 diabetic rats. In addition, trigonelline also reduced inflammation, oxidative stress and kidney cell apoptosis in T2DM rats. In terms of the molecular mechanisms involved, trigonelline induced the protein expression of peroxisome proliferator-activated receptor (PPAR)-γ and suppressed glucose transporter 4 but suppressed the protein expression of tumor necrosis factor-α and leptin in T2DM rats. The present results demonstrated that trigonelline reduced diabetic nephropathy and insulin resistance in T2DM rats through PPAR-γ.

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Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator–activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats

Cited by 71 publications

References 40 publications

<p>Bioactive Compounds from <em>Abelmoschus manihot L</em>. Alleviate the Progression of Multiple Myeloma in Mouse Model and Improve Bone Marrow Microenvironment</p>

<p>Bioactive Compounds from <em>Abelmoschus manihot L</em>. Alleviate the Progression of Multiple Myeloma in Mouse Model and Improve Bone Marrow Microenvironment</p>

Irbesartan ameliorates hyperlipidemia and liver steatosis in type 2 diabetic db/db mice via stimulating PPAR-γ, AMPK/Akt/mTOR signaling and autophagy

Trigonelline reduced diabetic nephropathy and insulin resistance in type�2 diabetic rats through peroxisome proliferator‑activated receptor‑γ

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