scholarly journals Tanshinol Alleviates Microcirculation Disturbance and Impaired Bone Formation by Attenuating TXNIP Signaling in GIO Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxiu Lai ◽  
Yulin Mo ◽  
Dongtao Wang ◽  
Ying Zhong ◽  
Lujiao Lu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Salvia Miltiorrhiza ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Migration Ability ◽  
Beneficial Effects ◽  
Western Blot Method ◽  
Mg63 Cells ◽  
Microcirculation Disturbance ◽  
And Function

Impaired bone formation is the main characteristics of glucocorticoid (GC)-induced osteoporosis (GIO), which can be ameliorated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. However, the underlying mechanism is still not entirely clear. In the present study, we determined the parameters related to microstructure and function of bone tissue, bone microcirculation, and TXNIP signaling to investigate the beneficial effects of tanshinol on skeleton and its molecular mechanism in GIO rats. Male Sprague-Dawley rats aged 4 months were administrated orally with distilled water (Con), tanshinol (Tan, 25 mg kg−1 d−1), prednisone (GC, 5 mg kg−1 d−1) and GC plus tanshinol (GC + Tan) for 14 weeks. The results demonstrated that tanshinol played a significant preventive role in bone loss, impaired microstructure, dysfunction of bone metabolism and poor bone quality, based on analysis of correlative parameters acquired from the measurement by using Micro-CT, histomorphometry, ELISA and biomechanical assay. Tanshinol also showed a significant protective effect in bone microcirculation according to the evidence of microvascular perfusion imaging of cancellous bone in GIO rats, as well as the migration ability of human endothelial cells (EA.hy926, EA cells). Moreover, tanshinol also attenuated GC-elicited the activation of TXNIP signaling pathway, and simultaneously reversed the down-regulation of Wnt and VEGF pathway as manifested by using Western-blot method in GIO rats, EA cells, and human osteoblast-like MG63 cells (MG cells). Collectively, our data highlighted that tanshinol ameliorated poor bone health mediated by activation of TXNIP signaling via inhibiting microcirculation disturbance and the following impaired bone formation in GIO rats.

scholarly journals Inhibitory Effects of Prunella vulgaris L. Extract on 11β-HSD1 in Human Skin Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Kyung-Baeg Roh ◽  
Deokhoon Park ◽  
Eunsun Jung
Keyword(s):  
Biological Activities ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Herbaceous Plant ◽  
Prunella Vulgaris ◽  
Beneficial Effects ◽  
Skin Cells ◽  
Promising Therapeutic Target ◽  
And Function

Glucocorticoids are a risk factor for age-induced skin structure and function defects, and the glucocorticoid-activating enzyme, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), represents a promising therapeutic target. Prunella vulgaris L. (PV) is a perennial and an edible herbaceous plant normally cultivated in Asia and Europe. A recent study demonstrated a broad range of biological activities of PV including immune modulatory, antiviral, antiallergic, anti-inflammatory, antioxidant, and antidiabetic. However, little is known about the inhibitory effect of PV on 11β-HSD1. In this study, we investigated the inhibitory effect of Prunella vulgaris L. extract (PVE) and the underlying mechanism of 11β-HSD11 inhibition. Consistent with these results, cortisol levels were also reduced by PVE in vitro. The cortisone-induced translocation of glucocorticoids receptor (GR) was also attenuated. In addition, PVE inhibited a cortisone-mediated decrease in collagen content in skin. Collectively, these results suggest the beneficial effects of PVE in maintaining skin integrity.

scholarly journals Losartan increases NO release in afferent arterioles during regression of l-NAME-induced renal damage

2010 ◽  
Vol 298 (5) ◽  
pp. F1170-F1177 ◽  
Author(s):  
Frank Helle ◽  
Bjarne M. Iversen ◽  
Christos Chatziantoniou
Keyword(s):  
Blood Pressure ◽  
Recovery Period ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
No Release ◽  
Afferent Arterioles ◽  
And Function ◽  
Dose Responses

Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of NG-nitro-l-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 ± 4 vs. 146 ± 5 mmHg, P < 0.01), reduced protein/creatinine ratio more (proteinuria decrease: Δ1,836 ± 214 vs. Δ1,024 ± 180 mg/mmol, P < 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 ± 0.05 vs. 2.09 ± 0.08, P < 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10−7 M ACh (118 ± 4 vs. 90 ± 7%, t = 560 s, P < 0.001) and 10−9 M ET (123 ± 4 vs. 101 ± 5%, t = 560 s, P < 0.001). There was also a blunted contractile response to 10−7 M ET in AAs from losartan-treated animals compared with untreated animals (Δ4.01 ± 2.9 vs. Δ14.6 ± 1.7 μm, P < 0.01), which disappeared after acute NOS inhibition (Δ10.7 ± 3.7 vs. Δ12.5 ± 2.9 μm, not significant). Contractile dose responses to ET (10−9, 10−8, 10−7 M) were enhanced by NOS inhibition and blunted by exogenous NO (10−2 mM S-nitroso- N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial effects of AT1aR antagonism during the recovery of renal function after long-term NOS inhibition in rats.

scholarly journals The Skeletal Effects of Tanshinones: A Review

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2319
Author(s):  
Sophia Ogechi Ekeuku ◽  
Kok-Lun Pang ◽  
Kok-Yong Chin
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Literature Search ◽  
Web Of Science ◽  
Bone Remodelling ◽  
Salvia Miltiorrhiza ◽  
Hormone Deficiency ◽  
Inclusion Criteria ◽  
Beneficial Effects ◽  
Skeletal Effects

Background: Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a class of lipophilic phenanthrene compounds found in the roots of Salvia miltiorrhiza with antioxidant and anti-inflammatory activities, which contribute to its anti-osteoporosis effects. This systematic review aims to provide an overview of the skeletal beneficial effects of tanshinones. Methods: A systematic literature search was conducted in January 2021 using Pubmed, Scopus and Web of Science from the inception of these databases. Original studies reporting the effects of tanshinones on bone through cell cultures, animal models and human clinical trials were considered. Results: The literature search found 158 unique articles on this topic, but only 20 articles met the inclusion criteria and were included in this review. The available evidence showed that tanshinones promoted osteoblastogenesis and bone formation while reducing osteoclastogenesis and bone resorption. Conclusions: Tanshinones modulates bone remodelling by inhibiting osteoclastogenesis and osteoblast apoptosis and stimulating osteoblastogenesis. Therefore, it might complement existing strategies to prevent bone loss.

scholarly journals Enhancement of Bone-Forming Ability on Beta-Tricalcium Phosphate by Modulating Cellular Senescence Mechanisms Using Senolytics

2021 ◽  
Vol 22 (22) ◽  
pp. 12415
Author(s):  
Xinchen Wang ◽  
Yoshitomo Honda ◽  
Jianxin Zhao ◽  
Hidetoshi Morikuni ◽  
Aki Nishiura ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cellular Senescence ◽  
Tricalcium Phosphate ◽  
Bone Diseases ◽  
Immunofluorescent Staining ◽  
Tartrate Resistant Acid Phosphatase ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Beta Tricalcium Phosphate ◽  
And Function

Various stresses latently induce cellular senescence that occasionally deteriorates the functioning of surrounding tissues. Nevertheless, little is known about the appearance and function of senescent cells, caused by the implantation of beta-tricalcium phosphate (β-TCP)—used widely in dentistry and orthopedics for treating bone diseases. In this study, two varying sizes of β-TCP granules (<300 μm and 300–500 μm) were implanted, and using histological and immunofluorescent staining, appearances of senescent-like cells in critical-sized bone defects in the calvaria of Sprague Dawley rats were evaluated. Parallelly, bone formation in defects was investigated with or without the oral administration of senolytics (a cocktail of dasatinib and quercetin). A week after the implantation, the number of senescence-associated beta-galactosidase, p21-, p19-, and tartrate-resistant acid phosphatase-positive cells increased and then decreased upon administrating senolytics. This administration of senolytics also attenuated 4-hydroxy-2-nonenal staining, representing reactive oxygen species. Combining senolytic administration with β-TCP implantation significantly enhanced the bone formation in defects as revealed by micro-computed tomography analysis and hematoxylin-eosin staining. This study demonstrates that β-TCP granules latently induce senescent-like cells, and senolytic administration may improve the bone-forming ability of β-TCP by inhibiting senescence-associated mechanisms.

Effect of Steroidal Hormone Pregnenolone on Proliferation and Differentiation of MC3T3-E1 Osteoblast like Cells

2020 ◽  
Vol 17 (9) ◽  
pp. 1139-1145
Author(s):  
Serene Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Bushra Taj Muhammad ◽  
Muhammad Iqbal Choudhary
Keyword(s):  
Bone Formation ◽  
Hormone Replacement ◽  
The Elderly ◽  
Underlying Mechanism ◽  
Bone Fragility ◽  
Bone Homeostasis ◽  
Rankl Expression ◽  
Beneficial Effects ◽  
Complex Process ◽  
Proliferation And Differentiation

Background: Bone remodeling is a complex process that includes continuous resorption by osteoclast cells and bone formation by osteoblast cells. Bone fragility is a common health issue of the elderly population, particularly in postmenopausal women. It has been established that steroidal hormones have an important role in bone homeostasis. Therefore hormone replacement therapy could have beneficial effects on bone health as compared to other treatments. Objectives: An imbalance between the rate of bone formation and bone resorption leads to the fragility of bones. During the current study, we aimed to explore the ability of pregnenolone (1) (PRE), on proliferation and differentiation of MC3T3-E1 cells. We further aimed to investigate the underlying mechanism of action for the anabolic effect of PRE (1). Methods: The effects of pregnenolone (1) on proliferation, differentiation, and mineralization of MC3T3 osteoblast-like cells were determined. Cell viability was analyzed using MTT assay and flow cytometry. ALP activity and alizarin staining were employed to evaluate the effect of pregnenolone on osteoblast differentiation. Moreover, western blot for analysis of certain important proteins, crucial for the regulation of bone homeostasis, such as BMP2 and RANKL, was also performed. Results: Our results showed that pregnenolone (1) at a concentration of 5 μM caused a significant (p< 0.05) rise in the growth of MC3T3-E1 cells, whereas a comparable effect was observed in osteoblast differentiating assays. A significant decrease in RANKL expression was observed at (0.04 – 1 .M). Our results, therefore, indicated the possible role of pregnenolone (1) in positive regulation of bone homeostasis by suppressing RANKL expression. Conclusion: Taken together, our results indicate that pregnenolone (1) has the potential to enhance osteoblast proliferation, as inferred from the increased number of cells. These results demonstrated that pregnenolone (1) could be a potential anabolic agent for the treatment of fragility related disorders.

Adrenal GRK2 lowering is an underlying mechanism for the beneficial sympathetic effects of exercise training in heart failure

2010 ◽  
Vol 298 (6) ◽  
pp. H2032-H2038 ◽  
Author(s):  
Giuseppe Rengo ◽  
Dario Leosco ◽  
Carmela Zincarelli ◽  
Massimo Marchese ◽  
Graziamaria Corbi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Underlying Mechanism ◽  
Therapeutic Modality ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Postmyocardial Infarction ◽  
Sprague Dawley Rats ◽  
Significant Amelioration ◽  
Response To Exercise

Exercise training has been reported to exert beneficial effects on cardiac function and to reduce morbidity and mortality of chronic heart failure (HF). Augmented sympathetic nervous system (SNS) activity, leading to elevated circulating catecholamine (CA) levels, is a hallmark of chronic HF that significantly aggravates this disease. Exercise training has been shown to also reduce SNS overactivity in HF, but the underlying molecular mechanism(s) remain unidentified. We recently reported that adrenal G protein-coupled receptor kinase-2 (GRK2), an enzyme that regulates the sympathoinhibitory α2-adrenoceptors (α2-ARs) present in the CA-producing adrenal medulla, is upregulated in HF, contributing to the chronically elevated CA levels and SNS activity of the disease. In the present study, we tested whether exercise training can affect the adrenal GRK2-α2-AR-CA production system in the context of HF. For this purpose, a 10-wk-long exercise training regimen of adult male Sprague-Dawley rats starting at 4 wk postmyocardial infarction (post-MI) was employed, and examination at the end of this treatment period revealed significant amelioration of β-AR-stimulated contractility in response to exercise training, accompanied by cardiac GRK2 reduction and restoration of circulating plasma CA levels. Importantly, adrenal GRK2 expression (72 ± 5% reduction vs. post-MI untrained) and α2-AR number were also restored after exercise training in post-MI animals. These results suggest that exercise training restores the adrenal GRK2-α2-AR-CA production axis, and this might be part of the mechanism whereby this therapeutic modality normalizes sympathetic overdrive and impedes worsening of the failing heart.

Dietary Quercetin Alleviated DSS-induced Colitis in Mice Through Several Possible Pathways by Transcriptome Analysis

2020 ◽  
Vol 21 (15) ◽  
pp. 1666-1673 ◽  
Author(s):  
Yuanyang Dong ◽  
Jiaqi Lei ◽  
Bingkun Zhang
Keyword(s):  
Antioxidant Capacity ◽  
Underlying Mechanism ◽  
Control Group ◽  
Sequencing Analysis ◽  
Colon Tissue ◽  
Beneficial Effects ◽  
Intestinal Integrity ◽  
Inflammatory Bowel ◽  
Vegetables And Fruits ◽  
Key Pathways

Background: The prevalence of inflammatory bowel disease is rapidly increasing around the world. Quercetin is a flavonoid commonly found in vegetables and fruits and has been reported to exert numerous pharmacological activities such as enhancing antioxidant capacity or suppressing inflammation. Objective: We aimed to explore whether quercetin was effective for IBD and the underlying mechanism of quercetin for the ameliorative effects on the DSS-induced colitis in mice. Methods: Thirty-six mice were randomly assigned to three treatments, including the control group (Ctr), DSS-induced colitis group (DSS) and DSS-induced colitis supplemented with 500 ppm quercetin (DQ500). Colitis was induced by DSS intake, and body weight was recorded every day. After six days administration of DSS, intestinal permeability was measured, and the liver was taken for antioxidant enzyme tests. Colonic tissue was taken for the histopathlogical score and RNA-sequencing analysis. Results: In this experiment, dietary quercetin for 500ppm alleviated the DSS-induced colitis, possibly by strengthening intestinal integrity, liver antioxidant capacity. Based on the results of the transcriptome of colon tissue, several key genes were modulated by quercetin. ERK1/2-FKBP pathway and RXR-STAT3 pathway were involved in the development of IBD, furthermore, in the down-regulation of S100a8/9, FBN2 contributed to lowering the risk of colongenesis. Conclusion: We demonstrated that dietary quercetin alleviated the DSS-induced colitis in mice. This is most likely due to its beneficial effects on intestinal integrity and modulation of several key pathways. Based on our research, quercetin was a promising candidate for IBD and its pharmaceutical effects on both IBD and colongenesis need further research.

scholarly journals Expression and Function of C1orf132 Long-Noncoding RNA in Breast Cancer Cell Lines and Tissues

2021 ◽  
Vol 22 (13) ◽  
pp. 6768
Author(s):  
Afsaneh Malekzadeh Shafaroudi ◽  
Ali Sharifi-Zarchi ◽  
Saeid Rahmani ◽  
Nahid Nafissi ◽  
Seyed Javad Mowla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Migration Assay ◽  
And Function ◽  
Distal Promoter

miR-29b2 and miR-29c play a suppressive role in breast cancer progression. C1orf132 (also named MIR29B2CHG) is the host gene for generating both microRNAs. However, the region also expresses longer transcripts with unknown functions. We employed bioinformatics and experimental approaches to decipher C1orf132 expression and function in breast cancer tissues. We also used the CRISPR/Cas9 technique to excise a predicted C1orf132 distal promoter and followed the behavior of the edited cells by real-time PCR, flow cytometry, migration assay, and RNA-seq techniques. We observed that C1orf132 long transcript is significantly downregulated in triple-negative breast cancer. We also identified a promoter for the longer transcripts of C1orf132 whose functionality was demonstrated by transfecting MCF7 cells with a C1orf132 promoter-GFP construct. Knocking-out the promoter by means of CRISPR/Cas9 revealed no alterations in the expression of the neighboring genes CD46 and CD34, while the expression of miR-29c was reduced by half. Furthermore, the promoter knockout elevated the migration ability of the edited cells. RNA sequencing revealed many up- and downregulated genes involved in various cellular pathways, including epithelial to mesenchymal transition and mammary gland development pathways. Altogether, we are reporting here the existence of an additional/distal promoter with an enhancer effect on miR-29 generation and an inhibitory effect on cell migration.

scholarly journals Can Ultrasound Therapy Be an Environmental-Friendly Alternative to Non-Steroidal Anti-Inflammatory Drugs in Knee Osteoarthritis Treatment?

Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 2715
Author(s):  
Rodica Ana Ungur ◽  
Viorela Mihaela Ciortea ◽  
Laszlo Irsay ◽  
Alina Deniza Ciubean ◽  
Bogdana Adriana Năsui ◽  
...  
Keyword(s):  
Ultrasound Therapy ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Knee Oa ◽  
Environmental Friendly ◽  
Chemical Pollutants ◽  
Osteoarthritis Treatment ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
And Function

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in knee OA (osteoarthritis) treatment. Despite their efficiency in pain and inflammation alleviation, NSAIDs accumulate in the environment as chemical pollutants and have numerous genetic, morphologic, and functional negative effects on plants and animals. Ultrasound (US) therapy can improve pain, inflammation, and function in knee OA, without impact on environment, and with supplementary metabolic beneficial effects on cartilage compared to NSAIDs. These features recommend US therapy as alternative for NSAIDs use in knee OA treatment.

scholarly journals Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 850
Author(s):  
María Ángeles Martín ◽  
Sonia Ramos
Keyword(s):  
Immune System ◽  
Fruits And Vegetables ◽  
Metabolic Diseases ◽  
Nuclear Factor Κb ◽  
Low Grade ◽  
Beneficial Effects ◽  
Health And Disease ◽  
Immunological Reactions ◽  
And Function ◽  
Positive Properties

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.

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