Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice

Zhang, Xinru; Fu, Xiujuan; Zhu, Dasheng; Zhang, Chaozai; Hou, Shi; Li, Min; Yang, Xiaohong

doi:10.1016/j.ejphar.2016.03.011

Cited by 51 publications

(38 citation statements)

References 19 publications

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“…Examining the functional roles of miRNAs upregulated by prednisolone, we found that all are upregulated in states consistent with known side effects of prednisolone treatment. These include insulin resistance ( 27 , 73 , 81 ), behavior changes ( 43 , 81 ), fibrosis ( 45 , 69 ), increased risk for heart failure ( 22 , 77 ), stress ( 43 , 84 ), and hypertension ( 11 ). Together, these data indicate that prednisone specifically activated a separate set of miRNAs in a manner that is consistent with the negative side effects of currently prescribed steroids.…”

Section: Resultsmentioning

confidence: 99%

“…It is best characterized in humans where this cluster is on chromosome 14q32 and encodes 54 miRNAs ( 63 ). All six of the miRNAs increased from this locus are also known to be elevated in conditions that are consistent with prednisone side effects, including insulin resistance ( 27 , 76 , 81 ), mood disturbances ( 43 , 81 ), stress ( 43 , 84 ), and hypertension ( 11 ). Because prednisolone increases mdx heart fibrosis ( 9 ) and heart failure is a leading cause of death in DMD, increases here in miR-433 and miR-134 are interesting as they are a regulator of heart fibrosis and a serum biomarker indicative of increased risk of heart failure, respectively ( 22 , 69 ).…”

Section: Discussionmentioning

confidence: 95%

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Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone

Fiorillo

Tully

Damsker

et al. 2018

Physiological Genomics

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Corticosteroids are highly prescribed and effective anti-inflammatory drugs but the burden of side effects with chronic use significantly detracts from patient quality of life, particularly in children. Developing safer steroids amenable to long-term use is an important goal for treatment of chronic inflammatory diseases such as Duchenne muscular dystrophy (DMD). We have developed vamorolone (VBP15), a first-in-class dissociative glucocorticoid receptor (GR) ligand that shows the anti-inflammatory efficacy of corticosteroids without key steroid side effects in animal models. miRNAs are increasingly recognized as key regulators of inflammatory responses. To define effects of prednisolone and vamorolone on the muscle miRNAome, we performed a preclinical discovery study in the mdx mouse model of DMD. miRNAs associated with inflammation were highly elevated in mdx muscle. Both vamorolone and prednisolone returned these toward wild-type levels (miR-142-5p, miR-142-3p, miR-146a, miR-301a, miR-324-3p, miR-455-5p, miR-455-3p, miR-497, miR-652). Effects of vamorolone were largely limited to reduction of proinflammatory miRNAs. In contrast, prednisolone activated a separate group of miRNAs associated with steroid side effects and a noncoding RNA cluster homologous to human chromosome 14q32. Effects were validated for inflammatory miRNAs in a second, independent preclinical study. For the anti-inflammatory miRNA signature, bioinformatic analyses showed all of these miRNAs are directly regulated by, or in turn activate, the inflammatory transcription factor NF-κB. Moving forward miR-146a and miR-142 are of particular interest as biomarkers or novel drug targets. These data validate NF-κB signaling as a target of dissociative GR-ligand efficacy in vivo and provide new insight into miRNA signaling in chronic inflammation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone

Fiorillo

Tully

Damsker

et al. 2018

Physiological Genomics

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“…The first two weeks after skin tumor initiation with DMBA, animals in the DMBA/TPA and DMBA/TPA+SR groups were further exposed to 4 µg TPA twice a week for a total of 20 weeks ranging from week 3 to week 23. In addition, the mice treated with SR (20 and 40 mg/kg) were topically treated 30 min before each DMBA/TPA treatment five times a week until the sacrifice of the animals at week 22 ( 32 – 35 ). DMBA and TPA were purchased from Sigma-Aldrich (St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Salidroside prevents skin carcinogenesis induced by DMBA/TPA in a mouse model through suppression of inflammation and promotion of apoptosis

Kong

2018

Oncol Rep

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Salidroside (SR) is a main component of Rhodiola rosea L. and exhibits a variety of pharmacologic properties. The present study was carried out to explore the potential effect of SR against skin cancer induced by 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) in female Institute for Cancer Research (ICR) mice and to reveal the underlying molecular targets regulated by SR. The mice were randomly divided into 4 groups: control, DMBA/TPA, DMBA/TPA+SR (20 mg/kg) and DMBA/TPA+SR (40 mg/kg). SR was administered to mice five times a week after DMBA treatments. In our study, we found that SR dose-dependently ameliorated skin cancer incidence and the multiplicity in the animal models by reducing the release of inflammation-related cytokines, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), cyclooxygenase 2 (COX2) and transforming growth factor β-1 (TGF-β1). Suppression of the nuclear factor (NF)-κB signaling pathway by SR was effective to prevent skin carcinogenesis. Furthermore, TUNEL analysis indicated that compared to the DMBA/TPA group, enhanced apoptosis was observed in the DMBA/TPA+SR group. In addition, p53 expression levels were increased by SR in the DMBA/TPA-induced mice. Therefore, SR was effective for inducing apoptosis during skin cancer progression triggered by DMBA/TPA. Consistently, p21, p53 upregulated modulator of apoptosis (PUMA), Bax and caspase-3 were highly induced by SR to enhance the apoptotic response for preventing skin cancer. Moreover, in vitro, we found that SR dramatically reduced the inflammatory response, while enhancing the aoptotic response by blocking NF-κB and activating caspase-3 pathways, respectively. In addition, flow cytometric analysis further confirmed the induction of apoptosis by SR in DMBA-treated cells in vitro. Taken together, the in vivo and in vitro studies illustrated that SR might be a promising compound to reduce skin cancer risk.

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“…The content of salidroside in the crude FLL power determined by HPLC ranges from 5.7 to 6.9 mg/g [ 42 ]. Currently, there are more than 400 publications investigating the biological activities of salidroside, including anti-diabetes [ 43 ], anti-obesity [ 44 ], anti-cancer [ 44 , 45 ], anti-osteoporosis [ 46 ], anti-arthritis-induced brain cognition deficits [ 47 ], anti-hypertension [ 48 , 49 ], and cardioprotective effects [ 50 ].…”

Section: Phytochemistry Of Fructus Ligustri Lucidimentioning

confidence: 99%

Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety

et al. 2017

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Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL. The initial inquiry was conducted for the presence of the following keywords combinations in the abstracts: Fructus Ligustri Lucidi, osteoporosis, phytochemistry, pharmacokinetics, pharmacology, osteoblasts, osteoclasts, salidroside. About 150 research papers and reviews were consulted. Results: FLL is assumed to exhibit anti-osteoporotic effects by improving liver and kidney deficiencies and reducing lower back soreness in Traditional Chinese Medicine (TCM). The data from animal and cell experiments demonstrate that FLL is able to improve bone metabolism and bone quality in ovariectomized, growing, aged and diabetic rats through the regulation of PTH/FGF-23/1,25-(OH)2D3/CaSR, Nox4/ROS/NF-κB, and OPG/RANKL/cathepsin K signaling pathways. More than 100 individual compounds have been isolated from this plant. Oleanolic acid, ursolic acid, salidroside, and nuzhenide have been reported to exhibit the anti-osteoporosis effect. The pharmacokinetics data reveals that salidroside is one of the active constituents, and that tyrosol is hard to detect under physiological conditions. Acute and subacute toxicity studies show that FLL is well tolerated and presents no safety concerns. Conclusions: FLL provides a new option for the prevention and treatment of osteoporosis, which attracts rising interests in identifying potential anti-osteoporotic compounds and fractions from this plant. Further scientific evidences are expected from well-designed clinical trials on its bone protective effects and safety.

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Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice

Cited by 51 publications

References 19 publications

Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone

Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone

Salidroside prevents skin carcinogenesis induced by DMBA/TPA in a mouse model through suppression of inflammation and promotion of apoptosis

Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety

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