Tanshinol Alleviates Osteoporosis and Myopathy in Glucocorticoid-Treated Rats

Planta Medica ◽  
2017 ◽  
Vol 83 (16) ◽  
pp. 1264-1273 ◽  
Author(s):  
Guanghua Chen ◽  
Xinle Zhang ◽  
Han Lin ◽  
Guizhi Huang ◽  
Yahui Chen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Salvia Miltiorrhiza ◽  
Healing Process ◽  
Water Soluble ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Model Group ◽  
Mineral Density

AbstractTanshinol is a major water-soluble active component of Salvia miltiorrhiza. In this study, we aimed to investigate whether tanshinol has potential therapeutic effects against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy. Ninety-six female Sprague-Dawley rats were randomly assigned to five groups: a control group, a model group, and three model groups treated with 25 or 50 mg/kg of tanshinol, or calcitriol. All model groups received prednisone acetate for 90 days to induce glucocorticoid-induced osteoporosis. Afterwards, all animals underwent a surgical procedure to induce bone defects at the right proximal tibia. Prednisone treatment was stopped after surgery, but tanshinol or calcitriol treatment was continued to the endpoint. At the experimental endpoint, compared to the model group, 25 mg/kg tanshinol could significantly reverse glucocorticoid-induced loss of bone mineral density by 12.5 %, while enhancing mechanical bone strength, causing a significant 11 % increase in trabecular number, and reducing trabecular separation by 28 %. In addition, tanshinol improved the bone microarchitecture and prevented glucocorticoid-induced bone loss by promoting bone formation and inhibiting bone resorption. Moreover, results of bone defect repair and muscle weight measurements revealed that tanshinol accelerated the bone fracture healing process and attenuated muscle atrophy caused by glucocorticoid. Furthermore, qRT-PCR analysis showed a 1-fold upregulation in mRNA levels of transforming growth factor beta and roughly 6-fold increases in vascular endothelial growth factor mRNA expression in calluses from the tanshinol groups. Tanshinol also preserved muscular ubiquitin mRNA levels from glucocorticoid-induced elevation. These findings demonstrate the potential benefits of tanshinol against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy, which warrants further investigation in future studies.

scholarly journals Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

2021 ◽  
Vol 40 (1) ◽  
pp. 29
Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Difference ◽  
T1 And T2

Introduction<br />Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase.<br /><br />Methods<br />In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. <br /><br />Results<br />The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p&lt;0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.<br /><br />Conclusion<br />MSCs can suppress TGF levels in liver fibrosis induced rats.

scholarly journals Collagen extract obtained from Nile tilapia (Oreochromis niloticus L.) skin accelerates wound healing in rat model via up regulating VEGF, bFGF, and α-SMA genes expression

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Zizy I. Elbialy ◽  
Ayman Atiba ◽  
Aml Abdelnaby ◽  
Ibrahim I. Al-Hawary ◽  
Ahmed Elsheshtawy ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Rat Model ◽  
Nile Tilapia ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Control Group ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Genes Expression

Abstract Background Collagen is the most abundant structural protein in the mammalian connective tissue and represents approximately 30% of animal protein. The current study evaluated the potential capacity of collagen extract derived from Nile tilapia skin in improving the cutaneous wound healing in rats and investigated the underlying possible mechanisms. A rat model was used, and the experimental design included a control group (CG) and the tilapia collagen treated group (TCG). Full-thickness wounds were conducted on the back of all the rats under general anesthesia, then the tilapia collagen extract was applied topically on the wound area of TCG. Wound areas of the two experimental groups were measured on days 0, 3, 6, 9, 12, and 15 post-wounding. The stages of the wound granulation tissues were detected by histopathologic examination and the expression of vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-ß1) were investigated using immunohistochemistry. Moreover, relative gene expression analysis of transforming growth factor-beta (TGF-ß1), basic fibroblast growth factor (bFGF), and alpha-smooth muscle actin (α-SMA) were quantified by real-time qPCR. Results The histopathological assessment showed noticeable signs of skin healing in TCG compared to CG. Immunohistochemistry results revealed remarkable enhancement in the expression levels of VEGF and TGF-β1 in TCG. Furthermore, TCG exhibited marked upregulation in the VEGF, bFGF, and α-SMA genes expression. These findings suggested that the topical application of Nile tilapia collagen extract can promote the cutaneous wound healing process in rats, which could be attributed to its stimulating effect on recruiting and activating macrophages to produce chemotactic growth factors, fibroblast proliferation, and angiogenesis. Conclusions The collagen extract could, therefore, be a potential biomaterial for cutaneous wound healing therapeutics.

The Role of Autologous PRP on Deep Partial-Thickness Burn Wound Healing in Bama Pigs

2020 ◽  
Vol 41 (3) ◽  
pp. 657-662 ◽  
Author(s):  
Yanwei Sun ◽  
Yongqian Cao ◽  
Ran Zhao ◽  
Famei Xu ◽  
Dan Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Healing Process ◽  
Control Group ◽  
Therapeutic Effects ◽  
Partial Thickness ◽  
Partial Thickness Burn ◽  
The Mean ◽  
Partial Thickness Burns

Abstract In this study, we aimed to evaluate the therapeutic effects of autologous platelet-rich plasma (PRP) on deep partial-thickness burns in Bama pigs. Deep partial-thickness burn wounds were created on the back of Bama pigs. The reepithelialization time was compared between the PRP and control groups. The mean score of Ki67 (+) cells and α-SMA (+) vessels, the mean thickness of epidermis and dermis of the healing wounds were determined via H&E staining and immunohistochemical assay. The levels of the growth factors epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were examined by ELISA. Our data showed that the time to wound reepithelialization was shorter in the PRP group compared with the control group. The thickness of the epidermis was larger in the PRP group compared with the control group. On the 7th and 14th days after the treatment, the mean score of Ki67 (+) cells and α-SMA (+) vessels were higher in the PRP group compared with the control group. The PRP group showed higher levels of growth factors (EGF, bFGF, and VEGF) compared with the control group by ELISA. The results indicated that PRP could improve wound healing process of deep partial-thickness burns in Bama pigs. The PRP increased the thickness of epidermis of the healed wounds, cell proliferation, and angiogenesis. We demonstrated that applying PRP had a greater potential for the treatment of deep partial-thickness burns.

scholarly journals Chinese Herbal Tanshinol Prevents Osteoporosis via Coordinately Promoting Osteogenesis and Inhibiting Osteoclastogenesis

2021 ◽  
Author(s):  
tailin wu ◽  
jianchao wang ◽  
jianzhou luo ◽  
haitao lin ◽  
fei wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Oral Delivery ◽  
Salvia Miltiorrhiza ◽  
Chinese Herb ◽  
Water Soluble ◽  
Control Group ◽  
Group Model ◽  
Three Dimension ◽  
Mineral Density ◽  
Water Soluble Compound

Abstract Background: Osteoporosis severely affects patients’ life quality due to increased risks of fragility fractures. Tanshinol is a primary water-soluble compound purified from the Chinese herb Salvia Miltiorrhiza, which exhibits potent antioxidant and anti-inflammatory properties. However, whether Tanshinol functions in preventing and protecting osteoporosis remains unknown. Thus, current study proposed to systematically investigate the protective effects and the underlying mechanisms of Tanshinol in bone marrow mesenchymal stem cells (BM-MSCs) and ovariectomized (OVX) mice model. Materials and methods: Different concentrations of Tanshinol were given to induce differentiation of BM-MSCs respectively, and detected the expression of key markers of osteoclast and osteogenesis. The C57BL/6 mice were divided into control group, model group, low (80 mg/kg×day, i.g), medium (160 mg/kg×day, i.g) and high (240 mg/kg×day, i.g) concentrations Tanshinol groups. After 6 weeks treatment of Tanshinol, mice distal femurs were taken to measure bone mineral density (BMD) and three dimension parameters.Results: In the present study, we for the first time showed that Tanshinol could promote osteogenesis in the mouse BM-MSCs, as seen from the increase of the osteogenic markers such as ALP activity and collagen I. Meanwhile, Tanshinol inhibited the RANKL induced osteoclastogenesis in the bone marrow monocytes (BMMs). Animal studies showed that oral delivery of Tanshinol could attenuate in ovariectomy induced osteoporosis. Molecularly, Tanshinol activated Wnt signal pathway in MSCs while inhibited Akt in BMMs, suggesting these pathways might be involved in the osteoporosis protective role of Tanshinol. Conclusions: our study has revealed a potential application of Salvia miltiorrhiza derivative Tanshinol in the treatment of osteoporosis.

scholarly journals High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma

1997 ◽  
Vol 83 (1) ◽  
pp. 120-128 ◽  
Author(s):  
John T. Berg ◽  
Zhenxing Fu ◽  
Ellen C. Breen ◽  
Hung-Cuong Tran ◽  
Odile Mathieu-Costello ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Wall Stress ◽  
Lung Parenchyma ◽  
Control Group ◽  
High Peep ◽  
Mrna Levels ◽  
Lung Inflation ◽  
Pulmonary Capillaries

Berg, John T., Zhenxing Fu, Ellen C. Breen, Hung-Cuong Tran, Odile Mathieu-Costello, and John B. West. High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma. J. Appl. Physiol. 83(1): 120–128, 1997.—Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for α1(III) and α2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-β1. In contrast, α2(I) procollagen and vascular endothelial growth factor mRNA levels were not changed. We conclude that high lung inflation for 4 h increases mRNA levels of ECM components and growth factors in lung parenchyma.

scholarly journals Increased Growth Factors Play a Role in Wound Healing Promoted by Noninvasive Oxygen-Ozone Therapy in Diabetic Patients with Foot Ulcers

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Zhang ◽  
Meiping Guan ◽  
Cuihua Xie ◽  
Xiangrong Luo ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Standard Therapy ◽  
Transforming Growth Factor ◽  
Ozone Treatment ◽  
Foot Ulcers ◽  
Control Group ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Ozone Therapy

Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 2~4, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β(TGF-β), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group was significantly higher than that of control group (92% versus 64%,P<0.05). The wound size reduction was significantly more in ozone group than in control group (P<0.001). After treatment, the expressions of VEGF, TGF-β, and PDGF proteins at day 11 were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-β, and PDGF at early stage of the treatment. (Clinical trial registry number isChiCTR-TRC-14004415).

scholarly journals Application of pomegranate (Punica granatum Linn.) fruit extract for accelerating post-tooth extraction wound healing

2018 ◽  
Vol 51 (4) ◽  
pp. 189
Author(s):  
Intan Nirwana
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Treatment Group ◽  
Tooth Extraction ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Punica Granatum ◽  
Control Group ◽  
Wound Healing Process ◽  
Significant Difference

Background: Trauma occurring during tooth extraction can cause complications such as bleeding, infection, fracture and dry socket and constitutes an inflammatory response trigger. Pomegranate (Punica granatum Linn.) extract, which contains large amounts of punicallagin and ellagic acid, possesses various qualities, including; anti-inflammatory, anti-bacterial and anti-oxidant. Pomegranate extract can inhibit proinflammatory cytokine production, while also suppressing inflammation response thereby accelerating wound healing. Purpose: This study aimed to analyze the effect of pomegranate extract application to the tooth extraction wounds of Cavia cobaya (C. cobaya) on the expression of fibroblast growth factor-2 (FGF-2) and transforming growth factor β (TGF-β) on the fourth day of the wound-healing process. Methods: This study used 12 C. cobaya, divided into two groups, namely; control and treatment. The subjects were anesthetized, before their lower left central incisor was extracted and the entire socket filled with CMC-Na 3% in members of the control group and pomegranate extract in those of the treatment group. The twelve C. cobaya were sacrificed on day 4, their lower jaw subsequently being removed and decalcified for approximately 30 days. The mandibula tissue was stained using a immunohistochemical technique. FGF-2 and TGF-β were used to evaluate the healing process in the extracted tooth socket. Differences in the expression of FGF-2 and TGF-β were evaluated statistically by means of a t-test. Results: This study indicated a significant difference between the control and the treatment groups (p<0.05). The treatment group members whose sockets were filled with pomegranate extract showed high FGF-2 and TGF-β expression. Conclusion: This study confirmed that the administration of pomegranate extract to post-extraction tooth wounds of C. cobaya increases the expression of FGF-2 and TGF-β on day 4, thereby accelerating the wound healing process.

scholarly journals Evaluation of the Therapeutic Effects of the Hydroethanolic Extract of Portulaca oleracea on Surgical-Induced Peritoneal Adhesion

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Ali Jaafari ◽  
Vafa Baradaran Rahimi ◽  
Nasser Vahdati-Mashhadian ◽  
Roghayeh Yahyazadeh ◽  
Alireza Ebrahimzadeh-Bideskan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Scoring Systems ◽  
Portulaca Oleracea ◽  
Control Group ◽  
Therapeutic Effects ◽  
Peritoneal Adhesion ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Tgf Β1

Objective. Peritoneal adhesion (PA) is an abnormal connective tissue that usually occurs between tissues adjacent to damaged organs during processes such as surgery. In this study, the anti-inflammatory and antioxidant effects of Portulaca oleracea (PO) were investigated against postoperative-induced peritoneal adhesion. Methods. Thirty healthy male Wistar rats ( 220 ± 20   g , 6-8 weeks) were randomly divided into four groups: (1) normal, (2) control (induced peritoneal adhesion), and (3) and (4) PO extracts (induced peritoneal adhesion and received 100 or 300 mg/kg/day of PO extract for seven days). Finally, macroscopic and microscopic examinations were performed using different scoring systems and immunoassays in the peritoneal lavage fluid. Results. We found that the levels of adhesion scores and interleukin- (IL-) 1β, IL-6, IL-10, tumour necrosis factor- (TNF-) α, transforming growth factor- (TGF-) β1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were increased in the control group. However, PO extract (100 and 300 mg/kg) notably reduced inflammatory (IL-1β, IL-6, and TNF-α), fibrosis (TGF-β1), angiogenesis (VEGF), and oxidative (MDA) factors, while increased anti-inflammatory cytokine IL-10, antioxidant factor glutathione (GSH), compared to the control group. Conclusion. Oral administration of PO improved postoperational-induced PA by alleviating the oxidative factors, fibrosis, inflammatory cytokines, angiogenesis biomarkers, and stimulating antioxidative factors. Hence, PO can be considered a potential herbal medicine to manage postoperative PA. However, further clinical studies are required to approve the effectiveness of PO.

scholarly journals Expression of fibroblast growth factor-β and transforming growth factor-β in mauli banana stem (Musa Acuminate) extract gel - treated traumatic ulcer

2021 ◽  
Vol 18 (3) ◽  
pp. 527-531
Author(s):  
Maharani Laillyza Apriasari ◽  
Selviana Rizky Pramitha ◽  
Dewi Puspitasari ◽  
Diah Savitri Ernawati
Keyword(s):  
Growth Factor ◽  
Treatment Group ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Control Group ◽  
Treatment Groups ◽  
Oral Ulcers ◽  
Group Ii ◽  
Banana Stem

Purpose: To investigate the effect of mauli banana (Musa acuminate) stem topical gel extract application on the expression of transforming growth factor - β (TGF - β) and fibroblast growth factor-β (FGF-β) during the healing process in traumatic oral ulcers. Methods: The work represented a true experimental study incorporating a post test - only control group design. Four groups of male Wistar rats (Rattus norvegivus) (n = 20) with traumatic oral ulcers were given mauli banana stem extract gel of varying concentrations the negative control group: 0 %; treatment group I: 25 %; treatment group II: 37.5 %; and treatment group III: 50 %. The animals were subsequently sacrificed prior to conducting biopsy on day 5. Immunohistochemical staining was performed in order to analyze the degree of FGF-β and TGF–β expressions. Results: TGF–β was strongly expressed in treatment group II (16.80 ± 1.30). TGF-β expression was significantly different, except between treatment groups II and III (Table 2). FGF-β was strongly expressed in treatment group II (15.60 ± 3.97). There was significant difference in FGF-β expression between all the groups with the exception of treatment groups I and III. Conclusion: Topical application of mauli banana stem extract gel (37.5 % concentration) stimulates FGF-β and TGF-β expression on day 5 of traumatic oral ulcer healing process. Thus, the extract gel has potentials for clinical application for the therapy of traumatic oral ulcers

scholarly journals Effects of different vardenafil doses on bone healing in a rat fracture model

2021 ◽  
Vol 32 (2) ◽  
pp. 313-322
Author(s):  
Tolgahan Atcı ◽  
Ender Alagöz ◽  
Elif Yaprak Saraç ◽  
Hakan Özbay ◽  
Mustafa Fatih Daşcı ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Early Period ◽  
Control Group ◽  
Late Period ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Primary Bone ◽  
Oxide Synthase

Objectives: We aimed to investigate the radiological, biomechanical, histopathological, histomorphometric, and immunohistochemical effects of different doses of vardenafil on fracture healing. Materials and methods: Fifty-one rats were divided into three groups. Group V5 was given 5 mg/kg/day of vardenafil; Group V10 was given 10 mg/kg/day of vardenafil; and the control group was given the same volume of saline. Six rats from each group were sacrificed on Day 14 (early period) and the remaining rats were sacrificed on Day 42 (late period). Callus/femoral volume and bone mineral density were measured using micro- computed tomography. Five femurs from each group in the late period were examined by biomechanical tests. In addition to the histopathological and histomorphometric evaluations, immunohistochemical analyses were performed to examine the levels of inducible nitric oxide synthase (iNOS), transforming growth factor-3 (TGF-β3), and nuclear factor kappa B (NF-κB) proteins. Results: Both doses of vardenafil increased primary bone volume and maximal bone fracture strength in late period, compared to the control group (p^lt;0.05). Histological healing scores of vardenafil groups were significantly higher in early period (p<0.001). While cartilaginous callus/total callus ratio in early period was higher, callus diameter/femoral diameter ratio in late period was lower in vardenafil groups (p<0.01). The NF-κB immunopositivity in V10 group decreased in early period, compared to control group (p<0.001). The TGF-β3 and iNOS immunopositivity increased in both V5 and V10 groups, compared to the control group in early period, but returned to normal in late period. Conclusion: During the first period of fracture healing process in which vasodilation is mostly required with increasing inflammation, vardenafil has ameliorating effects on the bone union and supports fracture healing.

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