Ameliorative Effect of Hochu-ekki-to on Natural Skin Aging.

INTRODUCTION: Although it is beneficial to protect the skin from natural aging, especially in an aging society, the approach by which this can be achieved is still not well known. Hochu-ekki-to, a Chinese natural medicine, has various advantageous effects; however, there is no report about its influence on skin aging. OBJECTIVE: Therefore, we examined the effect of hochu-ekki-to against natural aging. METHODS: Hairless mice, bred without ultraviolet ray irradiation and physical stress, were orally administered huchu-ekki-to 3 times per week for 2 years. After that period, degree of skin hydration and permeability were measured. Furthermore, hematoxylin and eosin histochemistry was performed to determine the morphology and condition of the tissues. Lastly, levels of vitamin A, vitamin C, and reactive oxygen species (ROS) in plasma and skin, as well as concentration of hyaluronic acid in the skin, were measured. RESULTS: Signs of skin aging were ameliorated by administration of hochu-ekki-to, such as moisture retention, skin hydration, and the generation of wrinkles. Furthermore, vitamin A, vitamin C, collagen type I, collagen type III, fibroblasts, and hyaluronic acid levels in the skin increased, while levels of ROS decreased after hochu-ekki-to treatment. CONCLUSION: These results indicated that natural skin aging was ameliorated by treatment with hochu-ekki-to, specifically moisture retention, and skin hydration, and thickening, via the regulation of the vitamin C/fibroblast, collagen type III/collagen type I, and vitamin A/hyaluronic acid signaling pathways.

The comparison of skin rejuvenation effects of vitamin A, fractional laser, and their combination on rat.

BACKGROUND: Because of long-term exposure of skin, skin aging is an unavoidable natural law with age. Traditional Vitamin A and novel ablative fractional laser technique both have the effects of skin rejuvenation, and studies have demonstrated both of them have apparent clinical efficacy and histology-improving effects on photo-aging skin. MATERIALS AND METHODS: 45 female healthy Wistar rats were selected and the depilation areas of every rat were divided into four regions: control region(Region A), Vitamin A acid region(Region B), combination treatment region(Region C), and fractional laser region(Region D). 0.025% Vitamin A acid cream was applied to Region B and C every day for 3 weeks; Region C and D were irradiated once with 10600nm CO2 fractional laser on the first day of the trail. The skin tissue was dissected and placed into liquid nitrogen according to the design. The real-time quantitative PCR and western blotting methods were taken to detect the expression changes of miR-29a, Akt, TGF-ß, and mRNA of type III pre-collagen. RESULTS: It can be seen from the results of the real-time quantitative PCR that the mRNA expression levels of type III pre-collagen, Akt, and TGF-ß in the treatment regions are up-regulated and the expression levels of miR-29a mRNA are down-regulated compared to the Region A. The hybridization tests showed that changes of the expression of type III pre-collagen, Akt gene, miR-29a gene, and TGF-ß gene across the experiment regions are all significantly different in the third week, and the expression levels of them all achieve the highest value in the third week, the expression level of miR-29a gene achieves the lowest value in the third week, which are consistent with the results of real-time quantitative PCR. CONCLUSION: It is indicated that the combination region of Vitamin A acid and fractional laser may lead to low expression of miR-29a, thus the inhibition of downstream Akt activation is loss, Akt activation is enhanced, enhancement of the expression of TGF-ß is induced, leading to proliferation of fibroblasts, and promotion of the collagen proteins' synthesis in skin. Therefore miR-29a/Akt/TGF-ß signal pathway may participate in the skin rejuvenation mechanism of action Vitamin A acid and fractional laser. This may provide a new treatment approach for skin rejuvenation.

Red grape (Vitis vinifera L.) flavonoids down-regulate collagen type III expression after UV-A in primary human dermal blood endothelial cells.

Red grape (Vitis vinifera L.) flavonoids including flavan-3-ols (eg, catechin and epicatechin), flavonols (eg, quercetin) and anthocyanins (eg, malvidin) exert anti-inflammatory and antioxidant activities. In the skin they also have a photoprotective action, and their effects have been extensively investigated in keratinocytes, melanocytes and fibroblasts. Despite their known effects also on blood vasculature, little is known on their activities on human dermal blood endothelial cells (HDBECs), which are critically involved in skin homeostasis as well as in the pathogenesis of neoplastic and inflammatory skin diseases. We sought to study the biological effects of selected red grape flavonoids in preventing the consequences of ultraviolet (UV)-A irradiation in vitro. Our results show that red grape flavonoids prevent UV-A-induced sICAM-1 release in HDBECs, suggesting that this cell type could represent an additional target of the anti-inflammatory activity of flavonoids. In addition, flavonoids effectively inhibited UV-A-induced synthesis of collagen type III at both RNA and protein level, indicating that dermal blood microvasculature could be actively involved in ECM remodelling as a consequence of skin photo-ageing, and that this can be prevented by red grape flavonoids.

Opuntia Extract Reduces Scar Formation in Rabbit Ear Model: A Randomized Controlled Study.

The purpose of this article is to investigate the effect of Opuntia stricta H (Cactaceae) extract on suppression of hypertrophic scar on ventral surface wounds of rabbit ears. Full thickness skin defection was established in a rabbit ear to simulate hypertrophic scar. Opuntia extract was sprayed on the wounds in the experimental group, and normal saline was used in the control group. After the wounds healed with scar formation, the hypertrophic scar tissue was harvested on days 22, 39, and 54 for histological analysis. The expression of type I and type III collagen and matrix metalloproteinase-1 (MMP-1) were evaluated by immunohistochemistry and real-time quantitative polymerase chain reaction. The results indicated that the scar of the control group is more prominent compared with the opuntia extract group. The expression of type I collagen in the opuntia extract group was lower than the control group, while type III collagen in opuntia extract group gradually increased and exceeded control group. The expression of MMP-1 decreased in the opuntia extract group, while the control group increased over time, but the amount of MMP-1 was much higher than that in the control group on day 22. In conclusion, opuntia extract reduces hypertrophic scar formation by means of type I collagen inhibition, and increasing type III collagen and MMP-1.T he novel application of opuntia extract may lead to innovative and effective antiscarring therapies.

LLLT improves tendon healing through increase of MMP activity and collagen synthesis.

The Achilles tendon has a high incidence of rupture, and the healing process leads to a disorganized extracellular matrix (ECM) with a high rate of injury recurrence. To evaluate the effects of different conditions of low-level laser (LLL) application on partially tenotomized tendons, adult male rats were divided into the following groups: G1, intact; G2, injured; G3, injured + LLL therapy (LLLT; 4 J/cm(2) continuous); G4, injured + LLLT (4 J/cm(2), 20 Hz); G5, injured; G6, injured + LLLT (4 J/cm(2) continuous); and G7, injured + LLLT (4 J/cm(2), 20 Hz until the 7th day and 2 kHz from 8 to 14 days). G2, G3, and G4 were euthanized 8 days after injury, and G5, G6, and G7 were euthanized on the 15th day. The quantification of hydroxyproline (HOPro) and non-collagenous protein (NCP), zymography for matrix metalloproteinase (MMP)-2 and MMP-9, and Western blotting (WB) for collagen types I and III were performed. HOPro levels showed a significant decrease in all groups (except G7) when compared with G1. The NCP level increased in all transected groups. WB for collagen type I showed an increase in G4 and G7. For collagen type III, G4 presented a higher value than G2. Zymography for MMP-2 indicated high values in G4 and G7. MMP-9 increased in both treatment groups euthanized at 8 days, especially in G4. Our results indicate that the pulsed LLLT improved the remodeling of the ECM during the healing process in tendons through activation of MMP-2 and stimulation of collagen synthesis.

Total Flavonoids of Fructus Chorspondiatis inhibits collagen synthesis of cultured rat cardiac fibroblasts induced by angiotensin II: correlated with NO/cGMP signaling pathway.

AIM: To investigate the molecular mechanism of Total Flavonoids of Fructus Chorspondiatis (TFFC) on preventing cardiac fibroblasts collagen synthesis induced by angiotensin II. METHODS: Collagen synthesis was determined by measuring (3)H-proline incorporation cardiac fibroblasts and hydroxyproline content in the culture mediums. The expression of collagen types I and III mRNA and protein was measured by RT-PCR and western blot, respectively. NO level in the culture medium was measured by the Griess reagent. NOS level in the culture medium was measured by chemical colorimetric method. The cellular concentration of cyclic GMP (cGMP) was measured by radioimmunoassay. RESULTS: TFFC (25, 50, and 100mg/L) inhibited collagen synthesis in cardiac fibroblasts in a dose-dependent manner compared with angiotensin II group (P<0.01), and the inhibitory effects were blocked by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) and 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ). TFFC increased nitric oxide (NO) and nitric oxide synthase (NOS) levels in the culture medium, increased intracellular cGMP level in cardiac fibroblasts, decreased collagen types I and III protein level in cardiac fibroblasts. The mRNA expression of collagen type I and III was suppressed by TFFC. CONCLUSIONS: These results suggested that TFFC inhibited collagen synthesis induced by angiotensin II in cardiac fibroblasts, and the inhibitory effect might associate with the activation of the NO/cGMP signaling pathway.

Topical application of Acalypha indica accelerates rat cutaneous wound healing by up-regulating the expression of Type I and III collagen.

ETHNOPHARMACOLOGICAL RELEVANCE: Acalypha indica Linn. (Acalypha indica) vernacularly called Kuppaimeni in Tamil, has been used as a folklore medicine since ages for the treatment of wounds by tribal people of Tamil Nadu, Southern India. The present study investigates the biochemical and molecular rationale behind the healing potential of Acalypha indica on dermal wounds in rats. MATERIAL AND METHODS: Acalypha indica extract (40 mg/kg body weight) was applied topically once a day on full-thickness excision wounds created on rats. The wound tissue was removed and used for estimation of various biochemical and biophysical analyses and to observe histopathological changes with and with-out extract treatment. The serum levels of pro-inflammatory cytokine tumor necrosis factor (TNF-α) was measured at 12 h, 24 h, 48 h and 72 h post-wounding using ELISA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed to study the expression pattern of transforming growth factor [TGF-ß1], collagen 1 α (I) [Col 1 α (I)] and collagen 3 α (I) [Col 3 α (I)]. Likewise, linear incision wounds were created and treated with the extract and used for tensile strength measurements. RESULTS: Wound healing in control rats was characterized by less inflammatory cell infiltration, lack of granulation tissue formation, deficit of collagen and significant decrease in biomechanical strength of wounds. Acalypha indica treatment mitigated the oxidative stress and decreased lipid peroxidation with concomitant increase in ascorbic acid levels. It also improved cellular proliferation, increased TNF-α levels during early stages of wound healing, up-regulated TGF-ß1 and elevated collagen synthesis by markedly increasing the expression of Col 1 α (I) and Col 3 α (I). Increased rates of wound contraction, epithelialization, enhanced shrinkage temperature and high tensile strength were observed in the extract treated rats. CONCLUSION: Acalypha indica extract was shown to augment the process of dermal wound healing by its ability to increase collagen synthesis through up-regulation of key players in different phases of wound healing and by its antioxidative potential.

[Effects of Bushen Huoxue Fang on rat cardiac fibroblast proliferation and collagen production in vitro].

OBJECTIVE: To investigate the effects of Bushen Huoxue Fang on the proliferation of rat cardiac fibroblasts and collagen production in the cells. METHODS: Rat cardiac fibroblasts were isolated and cultured in DMEM containing 10% (group A) or 20% (group B) or no (group C) serum from rats treated with Bushen Huoxue Fang, with cells cultured in DMEM containing 10% FBS as the control (group D). After 72 h of cell culture, the proliferation of the fibroblasts was detected using CCK-8 kit, and collagen mRNA and protein expressions were examined using RT-PCR and Western blotting, respectively. RESULTS: Compared with that in groups C and D, the cell proliferation decreased significantly in groups A and B, and especially in the latter (P<0.05). RT-PCR demonstrated significant reductions of the mRNAs of type 1 and 3 collagens in groups A and B (P<0.05), and their protein levels were also significantly lowered (P<0.05). CONCLUSION: Bushen Huoxue Fang can effectively inhibit the proliferation of rat cardiac fibroblasts and reduced collagen type 1 and 3 productions in the cells in vitro.

The role of vascular endothelial growth factor in fractional laser resurfacing with the carbon dioxide laser.

The aim of this study was to analyze the role of vascular endothelial growth factor (VEGF) in mechanisms of cutaneous remodeling induced by fractional CO(2) laser treatment. The dorsal skin of Kunming mice was exposed to a single-pass fractional CO(2) laser treatment. Biopsies were taken 1 h, and 1, 3, 7, 14, 28 and 56 days after treatment. Skin samples VEGF expression was evaluated by immunohistochemistry and ELISA, fibroblasts by hematoxylin-eosin staining, and types I and III collagen by ELISA. Staining for VEGF was found in many types of cell including fibroblasts. The amount of VEGF in the skin of laser-treated areas had increased significantly compared to that in the control areas on days 1 and 3 (P < 0.05, P < 0.01, respectively), then decreased by day 7 after treatment and returned to the baseline level. The number of fibroblasts in the skin of the laser-treated areas had increased significantly compared to that in control areas on days 3, 7, 14, 28 and 56 after irradiation (P < 0.05, P < 0.01, P < 0.01, P < 0.01, P < 0.01, respectively). The amount of type I collagen was significantly higher in the skin of the laser-treated areas compared to that in control areas from day 28 to day 56 (P < 0.05, respectively), and type III collagen was significantly higher from day 3 to day 56 (P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01, respectively). There was a positive correlation between the level of VEGF and fibroblast proliferation early stage after laser treatment (r = 0.853, P < 0.01), but there was no correlation after the first week (r = -0.124, P > 0.05). The amounts of type I and III collagen showed no significant correlations with the expression of VEGF in the late stages after laser treatment (r = 0.417, P > 0.05 and r = 0.340, P > 0.05, respectively). The results suggest that VEGF might be mainly involved in the early stages of wound healing, including the stages of acute inflammation, fibroblast proliferation and vessel formation induced by fractional CO(2) laser resurfacing.

Qiliqiangxin improves cardiac function in spontaneously hypertensive rats through the inhibition of cardiac chymase.

BACKGROUND: This study was designed to investigate the effects and mechanism of action of the traditional Chinese drug formula, qiliqiangxin (QLQX), on cardiac function in spontaneously hypertensive rats (SHRs). METHODS: We evaluated the effects of oral high-dose (4 g/kg/day, n = 7) and low-dose (1 g/kg/day, n = 7) QLQX on cardiac function in SHRs aged between 8 compared to control, the 8-week-old Wistar-Kyoto (WKY) rats. Echocardiography was performed to evaluate cardiac function and hemodynamic parameters. Hematoxylin and eosin (HE) and Masson's trichrome staining were performed, and the expression of myocardial angiotensin (Ang)-converting enzyme, chymase, transforming growth factor (TGF)-ß, and collagen-type I and III were evaluated with real-time reverse transcription-PCR. Myocardial chymase, Ang-converting enzyme (ACE), and Ang II activities were measured with radioimmunoassay (RIA) techniques. Cardiac mast cells were detected with toluidine blue staining. RESULTS: In SHRs, the number of chymase enzyme-positive mast cells increased in the left ventricle (LV) compared with WKY rats. QLQX significantly decreased mast cell density and cardiac chymase levels, and it improved ejection fraction values and cardiac systolic function compared with vehicle. Moreover, QLQX decreased left atrial diameters and improved the E/A ratio. QLQX suppressed collagen-type I and III and TGF-ß mRNA levels, and Ang II activity, in a dose-dependent manner. Whereas no difference in ACE activity was found between SHRs, chymase expression and activity were significantly decreased with QLQX. CONCLUSIONS: These data suggest that QLQX improves both systolic and diastolic cardiac function in SHRs through downregulating the cardiac chymase signaling pathway and chymase-mediated Ang II production.

Hydrolysable tannins of tropical almond show antifibrotic effects in TGF-ß1-induced hepatic stellate cells.

BACKGROUND: Persistent activation of hepatic stellate cells (HSC-T6) has been known to cause liver fibrosis. In this study, our objective was to investigate the effects of chebulagic acid and chebulinic acid, two hydrolysable tannins of tropical almond (Terminalia chebula) fruits, on collagen synthesis and signal transduction in transforming growth factor-ß1-stimulated HSC-T6 cells. The expression of Smad2, Smad3, Smad4, collagen I(α1)/III, and plasminogen activator inhibitor 1 (PAI-1) mRNAs was determined by reverse-transcription polymerase chain reaction and their protein levels were assessed by western blotting. RESULTS: Results showed that chebulagic acid and chebulinic acid at 20 µmol L(-1) exhibited cytotoxic and anti-proliferative effects on HSC-T6 cells. They also significantly decreased the expression of Smd2, Smad3 and Smad4, and the synthesis of collagen, procollagen I (α1) and III, as well as suppressing the activation of PAI-1; these events consequently facilitated the resolution of fibrosis. CONCLUSION: These results indicate that both chebulagic acid and chebulinic acid possess antifibrotic activity, and their mechanism of action could be through the inhibition of the Smad pathway.

[Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs].

OBJECTIVE: To investigate collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction (AMI) and the effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. METHODS: AMI model of Wistar rat was established by ligating left anterior descending coronary artery. The model rats were randomly divided into untreated group, perindopril group (0.36 mg/kg), Yiqi Yangyin Huoxue (YQYYHX) group (Shengmai Capsule 0.24 g/kg and Compound Chuanxiong Capsule 0.40 g/kg), and Jiedu Huoxue (JDHX) group (Compound Chuanxiong Capsule 0.40 g/kg and berberine 0.16 g/kg), with 10 rats in each group. The latter three groups were treated with corresponding drugs by gastric gavage once a day for 4 weeks after modeling. Sham-operated (puncture without ligation) group and normal control group with 10 rats in each group were given normal saline by gastric gavage. Left ventricular mass index (LVMI) was measured, and pathologic changes in myocardium were observed by hematoxylin-eosin staining 4 weeks later. Contents of procollagen type III and collagen type IV in serum were measured by radioimmunoassay, and expressions of collagen types I and III in ischemic myocardium were measured by immunohistochemical methods. RESULTS: Compared with rats in the sham-operated group, weight of left ventricle and LVMI of rats in the model group increased significantly; content of procollagen type III in serum increased; contents of collagen types I and III in ischemic myocardium increased significantly (P<0.01). Compared with rats in the untreated group, LVMI and content of procollagen type III in serum of rats treated with herbs decreased significantly, and expressions of collagen types I and III in ischemic myocardium were inhibited (P<0.05, P<0.01). The effect of detoxifying and blood-activating herbs on collagen type III in ischemic myocardium is better than perindopril. CONCLUSION: Both qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs have beneficial effects on rats with AMI in decreasing LVMI and procollagen type III content, and inhibiting expressions of collagen types I and III in ischemic myocardium, thus protecting ischemic myocardium after AMI. It may explain the machanism of Chinese herbal medicine inhibiting ventricular remodeling after AMI.

Intense pulsed light effects on the expression of extracellular matrix proteins and transforming growth factor beta-1 in skin dermal fibroblasts cultured within contracted collagen lattices.

BACKGROUND: Emerging clinical evidence suggests that intense pulsed light (IPL) treatment may exert some beneficial effects on photoaged skin. The molecular mechanisms underlying this IPL effect have not been fully elucidated. OBJECTIVE: To examine the effects of IPL irradiation on normal human dermal fibroblasts grown in contracted collagen lattices. METHODS: Human skin fibroblasts cultured in contracted collagen lattices were irradiated with IPL with triple pulses of 7 ms with a pulse interval of 70 ms and fluences of 20, 50, and 75 J/cm(2). Twenty-four hours after the irradiation, cell viability, messenger RNA (mRNA), and protein levels of extracellular matrix proteins (e.g., collagen I, collagen III, and fibronectin) and transforming growth factor beta-1 (TGF-beta1) were evaluated using dye exclusion, real-time reverse transcriptase polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. RESULTS: A dose-dependent increase in viable cells was demonstrated after the IPL irradiation. There was no significant change in mRNA levels of collagen I and fibronectin. Upregulated expression of collagen III and TGF-beta1 in dermal fibroblasts was verified. CONCLUSIONS: The analytical results presented here provide a potential mechanistic explanation for the mechanism of clinical photorejuvenation effects of IPL that involves the increase of extracellular matrix construction by upregulating the gene expressions of collagen III and TGF-beta1.

Pentoxifylline modifies three-dimensional collagen lattice model contraction and expression of collagen types I and III by human fibroblasts derived from post-burn hypertrophic scars and from normal skin.

Fibroblasts are thought to be partially responsible for the persisting contractile forces that result in burn contractures. Using a monolayer cell culture and fibroblast populated collagen lattice (FPCL) three-dimensional model we subjected hypertrophic scar and non-cicatricial fibroblasts to the antifibrogenic agent pentoxifylline (PTF - 1mg/mL) in order to reduce proliferation, collagen types I and III synthesis and model contraction. Fibroblasts were isolated from post-burn hypertrophic scars (HSHF) and non-scarred skin (NHF). Cells were grown in monolayers or incorporated into FPCL's and exposed to PTF. In monolayer, cell number proliferation was reduced (46.35% in HSHF group and 37.73% in NHF group, p<0.0001). PTF selectively inhibited collagen III synthesis in the HSHF group while inhibition was more evident to type I collagen synthesis in the NHF group. PTF also reduced contraction in both (HSHF and NHF) FPCL.

Chronic administration of ursodeoxycholic acid decreases portal pressure in rats with biliary cirrhosis.

Liver cirrhosis is characterized by increased IHR (intrahepatic resistance) and lipid peroxidation, and decreased antioxidative defence. The present study investigates the effects of administration for 1 month of the antioxidant UDCA (ursodeoxycholic acid) in BDL (bile-duct-ligated) cirrhotic rats. Splanchnic haemodynamics, IHR, hepatic levels of TBARS (thiobarbituric acid-reacting substances), GSH (glutathione), SOD (superoxide dismutase) activity, nitrite, PIIINP (N-terminal propeptide of type III procollagen) and collagen deposition, histological examination of liver, mRNA expression of PIIIP-alpha1 (type III procollagen) and TGF-beta1 (transforming growth factor-beta1), protein expression of TXS (thromboxane synthase) and iNOS (inducible NO synthase), and TXA2 (thromboxane A2) production in liver perfusates were measured. The results showed that portal pressure and IHR, hepatic levels of PIIINP, hepatic collagen deposition, mRNA expression of PIIIP-alpha1 and TGF-beta1, protein expression of iNOS and TXS, and production of TXA2 in liver perfusates were significantly decreased in UDCA-treated BDL rats. The increased levels of hepatic GSH and SOD activity and decreased levels of TBARS and nitrite were also observed in UDCA-treated BDL rats. In UDCA-treated BDL rats, the reduction in portal pressure resulted from a decrease in IHR, which mostly acted through the suppression of hepatic TXA2 production and lipid peroxidation, and an increase in antioxidative defence, leading to the prevention of hepatic fibrosis.

The effects of angiotensin-converting-enzyme inhibitors on the fibrous envelope around mammary implants.

BACKGROUND: Late capsular contraction around breast implants is one of the most difficult complications to prevent or resolve. The authors studied the mechanisms that control the fibrotic process in an animal model. Using angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonist, the authors previously described a significant reduction in fibrosis in different experimental models. METHODS: Four groups of six rats each had a mini breast implant, 12 with a smooth surface and 12 with a textured surface. In two groups, the angiotensin-converting enzyme inhibitor enalapril was administered in drinking water, ad libitum, to determine its effect on both implant types. Two control groups were given plain drinking water. Three months postoperatively, all of the rats were killed and the capsule sections were cut and stained with hematoxylin and eosin and Masson's trichrome. Immunolabeling of collagen III and transforming growth factor (TGF)-beta1 was performed using monoclonal antibodies. RESULTS: Significant differences were found between smooth and textured implants, with a uniformly low inflammatory response found on textured implants. For both surfaces, the enalapril-treated group had a significant reduction of the inflammatory process that was especially marked in the textured implants. Immunostaining for collagen III and TGF-beta1 showed a consistent reduction in both fibrous tissue and cytokine mediator. CONCLUSIONS: Enalapril lowers the expression of fibrotic mediators, TGF-beta1, inflammatory markers, anti-ED1, anti-collagen III monoclonals, and the periprosthetic fibrosis process. The reduction of TGF-beta1 indicates that the probable main cytokine mediator of the fibrotic cascade is attenuated. This hypothesis may provide the basis for a safe and cheap therapeutic strategy with which to modify the capsular contracture that sometimes affects women with mammary implants.

[Experimental study of Qishen Yiqi Dropping Pills on liver fibrosis in rats].

OBJECTIVE: To investigate the anti-fibrotic effects of Qishen Yiqi Dropping Pills (QYDP) in rats with liver fibrosis (LF). METHODS: The LF model was induced by intraperitoneal injection with dimethylnitrosamine (DMN). Sixty Wistar rats were randomly divided into the normal group, the model group A, the QYDP intervened group , the model group B , and the QYDP treated group B. The degree of LF was evaluated according to 6-phase grading method. The expressions of collagen type I and III and tissue inhibitor of metalloproteinase-1 (TIMP-1) in liver tissues were determined by immunohistochemistry and the levels of collagen type I and III and TIMP-1 mRNA determined by semi-quantitive RT-PCR. RESULTS: Compared with the model group A and B, the degree of LF, the positive expressions of TIMP-1 mRNA and the content of collagen type I and III in liver tissue in the QYDP intervened and treated groups were significantly lower. CONCLUSION: QYDP could reduce the pathological changes and degree of LF in rats, which may be partially through inhibiting the expressions of collagen type I and III and TIMP-1.

[Effects of Shengji Huayu Recipe and its decomposed formulas on synthesis of collagen types I and III in granulation tissue of rats in early wound healing].

OBJECTIVE: To study the effects of Shengji Huayu Recipe (a traditional Chinese medicine compound recipe for resolving stagnation and promoting granulation) and its decomposed formulas (Huayu Recipe for resolving stagnation and Shengji Recipe for promoting granulation) on the synthesis of collagen types I and III in granulation tissue of rats in early wound healing. METHODS: Twenty-four male Sprague-Dawley (SD) rats with full-thickness skin lesion were randomized into 4 groups: Shengji Huayu Recipe-treated group, Shengji Recipe-treated group, Huayu Recipe-treated group and untreated group. Collagen types I and III in granulation tissue of the rats were tested with immunohistochemical methods and image analysis. RESULTS: On the third day of wound healing, collagen I of the rats in both Shengji Huayu Recipe-treated group and Shengji Recipe-treated group was higher than that in the untreated group, and collagen I of the rats in Huayu Recipe-treated group was lower than that in the untreated group (P<0.05). Collagen III of the rats in the three treated groups were lower than that in the untreated group (P<0.05). On the seventh day of wound healing, Collagen I of the rats in both Shengji Huayu Recipe-treated group and Shengji Recipe-treated group was higher than that in the untreated group (P<0.05), and collagen III of the rats in both Shengji Recipe-treated group and Huayu Recipe-treated group was higher than that in the untreated group (P<0.05). CONCLUSION: Resolving stagnation and promoting granulation therapy can promote the wound healing in rats.

Pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuates angiotensin II/salt-induced aortic remodeling.

OBJECTIVE: To test the hypothesis that pharmacological plasminogen activator inhibitor (PAI)-1 inhibition protects against renin-angiotensin-aldosterone system-induced cardiovascular injury, the effect of a novel orally active small-molecule PAI-1 inhibitor, PAI-039, was examined in a mouse model of angiotensin (Ang) II-induced vascular remodeling and cardiac fibrosis. METHODS AND RESULTS: Uninephrectomized male C57BL/6J mice were randomized to vehicle subcutaneus, Ang II (1 mug/h) subcutaneous, vehicle+PAI-039 (1 mg/g chow), or Ang II+PAI-039 during high-salt intake for 8 weeks. Ang II caused significant medial, adventitial, and aortic wall thickening compared with vehicle. PAI-039 attenuated Ang II-induced aortic remodeling without altering the pressor response to Ang II. Ang II increased heart/body weight ratio and cardiac fibrosis. PAI-039 did not attenuate the effect of Ang II on cardiac hypertrophy and increased fibrosis. The effect of PAI-039 on Ang II/salt-induced aortic remodeling and cardiac fibrosis was comparable to the effect of genetic PAI-1 deficiency. Ang II increased aortic mRNA expression of PAI-1, collagen I, collagen III, fibronectin, osteopontin, monocyte chemoattractant protein-1, and F4/80; PAI-039 significantly decreased the Ang II-induced increase in aortic osteopontin expression at 8 weeks. CONCLUSIONS: This study demonstrates that pharmacological inhibition of PAI-1 protects against Ang II-induced aortic remodeling. Future studies are needed to determine whether the interactive effect of Ang II/salt and reduced PAI-1 activity on cardiac fibrosis is species-specific. In this study, the effect of pharmacological PAI-1 inhibition in a mouse model of Ang II-induced vascular remodeling and cardiac fibrosis was examined. PAI-1 inhibition significantly attenuated Ang II-induced aortic medial and wall thickening, but not cardiac hypertrophy, and enhanced Ang II/salt-induced cardiac fibrosis.

Effects of eplerenone, a selective aldosterone blocker, on the progression of left ventricular dysfunction and remodeling in rats with dilated cardiomyopathy.

Aldosterone blockade reduces morbidity and mortality in patients with heart failure. We studied the effects of eplerenone, a novel aldosterone blocker, on the progression of left ventricular dysfunction and remodeling in rats with dilated cardiomyopathy after autoimmune myocarditis. Twenty-eight days after immunization, the surviving Lewis rats were randomized to 1 month's oral treatment with low-dose eplerenone (group L), high-dose eplerenone (group H) or vehicle (group V). Five of 15 (33%) rats in group V and 3 of 15 (20%) rats in group L died during the course of treatment. High-dose eplerenone significantly reduced cardiomyocyte hypertrophy, heart weight and heart weight to body weight ratio. Eplerenone improved left ventricular function in a dose-dependent manner. Central venous pressure and left ventricular end-diastolic pressure were lower, and +/-dP/dt and fractional shortening were higher in group H than group V. Eplerenone also attenuated myocardial fibrosis and reduced left ventricular mRNA expressions of TGF-beta(1) and collagen-III. Our results indicate that treatment with eplerenone improved left ventricular dysfunction and attenuated left ventricular remodeling in rats with heart failure.