Anhydroicaritin, a SREBPs inhibitor, inhibits RANKL-induced osteoclastic differentiation and improves diabetic osteoporosis in STZ-induced mice

Zheng, Zu-Guo; Zhang, Xin; Zhou, Yaping; Lu, Chong; Thu, Pyone Myat; Qian, Cheng; Zhang, Mu; Li, Ping; Li, Huijun; Xu, Xiaojun

doi:10.1016/j.ejphar.2017.05.017

Cited by 29 publications

(16 citation statements)

References 37 publications

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“…Consequently, SREBPs regulate cellular lipogenesis and lipid homeostasis [11]. SREBPs are divided into three isoforms: SREBP-1a, SREBP-1c, and SREBP2 [12]. SREBP-1 mainly controls the gene expression involved in fatty acid and triacylglycerol metabolism, while SREBP-2 regulates primarily cholesterol metabolism [13].…”

Section: Introductionmentioning

confidence: 99%

The anti-obesity effects of Tongbi-san in a high-fat diet-induced obese mouse model

Park

Lee²,

Cheon

et al. 2019

BMC Complement Altern Med

148

109

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BackgroundRecently, it has been noted that natural herbal medications may be effective in treating obesity. Tongbi-san (TBS) is a traditional medicine usually used for dysuria (i.e., painful urination), containing three herbs, Cyperus rotundus L., Citrus unshiu Markovich, and Poria cocos. In this study, we aimed to examine whether TBS can inhibit high-fat diet (HFD)-induced adipogenesis in the liver and epididymal adipose tissue of obese mice.MethodsMale C57BL/6 N mice were fed a normal diet, an HFD, an HFD plus orlistat 10 or 20 mg/kg, or an HFD plus TBS 50 or 100 mg/kg for 11 weeks. Body weight was checked weekly and histological tissue examinations were investigated. An expression of genes involved in adipogenesis was also assessed.ResultsOral administration of TBS significantly reduced body weight and decreased epididymal and visceral white adipose tissue (WAT) weight. In addition, we found that TBS enhanced the expression of the adenosine monophosphate-activated protein kinase (AMPK) and inhibited the expression of transcription factors, such as CCAAT/enhancer-binding proteins (C/EBPs), sterol regulatory element-binding protein 1 (SREBP1), and peroxisome proliferator-activated receptor γ (PPARγ) in the liver and epididymal WAT as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR).ConclusionThese findings demonstrate that the anti-obesity effects of TBS may be linked to the activation of AMPK.

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Section: Introductionmentioning

confidence: 99%

The anti-obesity effects of Tongbi-san in a high-fat diet-induced obese mouse model

Park

Lee²,

Cheon

et al. 2019

BMC Complement Altern Med

148

109

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“…Anhydroicaritin is a prenylated flavonoid found in several species of Epimedium . Anhydroicaritin is capable of suppressing osteoclast differentiation and improving bone loss in diabetic rats (12).…”

Section: Introductionmentioning

confidence: 99%

In Silico Interaction of the Active Compounds of Scurrula Atropurpurea with the RANK/RANKL/OPG System in Diabetoporosis

Akbar

Dewi²,

Setiawan

2019

Acta Inform Med

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Introduction: Diabetoporosis is a very complex health problem in Indonesia. One approach to the problem is through native Indonesian herbal medicine. The application of Scurrula atropurpurea in the treatment of diabetoporosis has not been revealed, so preliminary in silico study needs to be done. Aim: The purpose of the present study was to analyze the interaction between the active compound of Scurrula atropurpurea and the RANKL/RANK/OPG system in the pathomechanism of osteoporosis in diabetes mellitus. Methods: The procedures of the study included the search for the constituent amino acid of the RANK/RANKL/OPG system, the search for the structure of the active component of Scurrula atropurpurea , 3D modeling of protein structure, protein-ligand docking and visualization, and analysis of protein-ligand bonding interactions. Results: Those bond energies were RANKL-aviculin (–274.96 kJ/mol), RANKL-rutin (–263.12 kJ/mol), RANKL-quercitrin (–256.98 kJ/mol), RANKL-quercetin (–226,50 kJ/mol), RANKL-kaempferol (–221,65 kJ/mol), RANKL-catechin (–214,85 kJ/mol), RANKL-epicatechin (–211.66 kJ/mol), RANKL-caffeine (-171.73 kJ/mol), and RANKL-theobromine (-161.14 kJ/mol). The bond energies were RANK-rutin (-719.26 kJ/mol), RANK-catechin (-680.15 kJ/mol), RANK-caffeine (-654.48 kJ/mol), RANK-theobromine (-651.77 kJ/mol), RANK-quercitrin (-650.68 kJ/mol), RANK-kaempferol (-643.03 kJ/mol), RANK-epicatechin (-641.86 kJ/mol), RANK-quercetin (-641.76 kJ/mol), and RANK-aviculin (-628.62 kJ/mol). Those bond energies were OPG-epicatechin (-590.09 kJ/mol), OPG-theobromine (-578.08 kJ/mol), OPG-caffeine (-568.88 kJ/mol), RANKL-catechin (-560.63 kJ/mol), OPG-quercitrin (-554.50 kJ/mol), OPG-rutin (-547.91 kJ/mol), OPG-quercetin (-545.75 kJ/mol), OPG-kaempferol (-544.48 kJ/mol), and OPG-aviculin (-539.15 kJ/mol). Conclusion: The nine active ingredients of Scurrula atropurpurea do not interfere with the physiological function of RANKL to interact with RANK. The initial interaction of RANK with catechin or rutin will facilitate the bond of RANK to RANKL. When forming a complex with OPG, epicatechin will facilitate its interaction with RANKL.

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“…RANKL stimulates osteoclastic activity and differentiation and inhibits osteoclast apoptosis. OPG inhibits osteoclast formation by binding to RANKL [ 22 ]. The bone remodeling process is dependent on the balance of these two proteins, while a low ratio of OPG/RANKL characterizes the increased osteolytic process.…”

Section: Introductionmentioning

confidence: 99%

Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio

Zheng

Chen

2018

Molecules

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Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat model of osteoporosis to investigate the protective effects of salidroside on bone loss induced by ovariectomy combined with diabetes, also investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats were divided into three equal groups (10 rats in each group): control group (with sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats treated with salidroside (20 mg/kg body weight) by gavage. The results showed that after 60 consecutive days of treatment, the bone mineral density (BMD) of OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01). The level of serum bone turnover markers, including alkaline phosphatase (ALP), cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase 5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the bone histopathological changes were also attenuated, and the bone marrow adipogenesis was inhibited in salidroside treated rats. Moreover, protein and mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) was upregulated in ovariectomized diabetic rats by salidroside treatment. The results above indicated that the protective effect of salidroside on bone loss induced by ovariectomy and diabetes was mainly due to its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up-regulate the OPG/RANKL ratio.

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Anhydroicaritin, a SREBPs inhibitor, inhibits RANKL-induced osteoclastic differentiation and improves diabetic osteoporosis in STZ-induced mice

Cited by 29 publications

References 37 publications

The anti-obesity effects of Tongbi-san in a high-fat diet-induced obese mouse model

The anti-obesity effects of Tongbi-san in a high-fat diet-induced obese mouse model

In Silico Interaction of the Active Compounds of Scurrula Atropurpurea with the RANK/RANKL/OPG System in Diabetoporosis

Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio

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