Biological studies on Brazilian plants used in wound healing

Aim of the study

n-Hexanic and ethanolic extracts from twelve plants (Brugmansia suaveolens Brecht. et Presl., Eupatorium laevigatum Lam., Galinsoga parviflora Cav., Iresine herbstii Hook., Kalanchöe tubiflora Hamet-Ahti, Petiveria alliacea L., Pluchea sagittalis (Lam.) Cabrera, Piper regnellii DC., Schinus molle L., Sedum dendroideum Moç et Sessé ex DC., Waltheria douradinha St. Hill., Xanthium cavanillesii Schouw.) used in traditional South Brazilian medicine as wound healing agents were investigated in various biological assays, targeting different aspects in this complex process.

Materials and methods

The extracts were investigated on NF-κB DNA binding, p38α MAPK, TNF-α release, direct elastase inhibition and its release as well as on caspase-3. Fibroblasts migration to and proliferation into the wounded monolayers were evaluated in the scratch assay, the agar diffusion test for antibacterial and the MTT assay for cytotoxic effects.

Results

The hydrophilic extracts from Galinsoga parviflora, Petiveria alliacea, Schinus molle, Waltheria douradinha and Xanthium cavanillesii as well as the lipophilic extract of Waltheria douradinha turned out to be the most active ones.

Conclusions

These results increase our knowledge on the wound healing effects of the investigated medicinal plants. Further studies are necessary to find out the effective secondary metabolites responsible for the observed effects.     

Hypoglycaemic activity of four plant extracts traditionally used in South Africa for diabetes

Aim

To validate plant species for hypoglycaemic activity.

Materials and methods

Four plants were investigated for hypoglycaemic activity by evaluating inhibiting effects on carbohydrate-hydrolising enzymes: α-glucosidase and α-amylase. Acetone plant extracts were screened against C2C12 myocytes, 3T3-L1 preadipocytes and Chang liver cells by measuring glucose uptake. Cytotoxicity was done in preadipocytes and hepatocytes.

Results

Extract of Euclea undulata rootbark exhibited highest activity, displaying a glucose uptake of 162.2% by Chang liver cells at 50 μg/ml. An inhibition concentration of 50% for Euclea undulata was found to be 49.95 μg/ml for α-glucosidase and 2.8 μg/ml for α-amylase. No cytotoxicity was recorded for Euclea undulata, while Schkuhria pinnata and Elaeodendron transvaalense exhibited cytotoxicity at 12.5 μg/ml. α-Glucosidase and α-amylase assays showed inhibitory activity on enzymes for three plant extracts.

Conclusion

Euclea undulata, Schkuhria pinnata and Elaeodendron transvaalense showed in vitro hypoglycaemic activity. Schkuhria pinnata and Elaeodendron transvaalense indicated cytotoxicity on 3T3-L1 preadipocytes and Chang liver cells. Euclea undulata, Pteronia divaricata and Elaeodendron transvaalense inhibited α-glucosidase and α-amylase enzymes.

Ethnopharmacological relevance

Screening of plant extracts scientifically validated traditional use of Euclea undulata for treatment of diabetes. Cytotoxicity results revealed that acetone extracts of Schkuhria pinnata and Elaeodendron transvaalense are toxic and raise concern for chronic use.     

Anti-inflammatory effects of YeongyoSeungma-tang

Ethnopharmacological relevance

YeongyoSeungma-tang which includes Fructus Forsythia, has been used in oriental traditional medicine for treatment of early smallpox and atopic dermatitis.

Aim of the study

YeongyoSeungma-tang was carried out to investigate for anti-inflammatory effects.

Materials and methods

YeongyoSeungma-tang was tested for anti-inflammatory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor alpha (TNF-α) releases as well as nuclear factor kappa B (NF-κB) expression using RAW264.7 macrophage cells.

Results

YeongyoSeungma-tang significantly inhibited generation of NO (42% and 59% inhibition at doses of 5 μg/mL and 10 μg/mL, respectively), PGE₂ (46% and 80% inhibition at doses of 5 μg/mL and 10 μg/mL, respectively) and TNF-α (6% and 23% inhibition at doses of 5 μg/mL and 10 μg/mL, respectively) on LPS-stimulated RAW 264.7 cells in a concentration-dependent manner. Consistently in these observations, the expression of inducible NO synthase (iNOS) enzyme was also inhibited by YeongyoSeungma-tang. However, YeongyoSeungma-tang did not show any influence on the expression of cyclooxygenase-2. The cream containing 0.075% YeongyoSeungma-tang showed good skin moisturizing effect without any irritation.

Conclusion

The present study may support the fact that YeongyoSeungma-tang can have the good possibility as an anti-inflammatory agent for troubled skins.     

Vitapex诱导实验性根尖周炎小鼠血清中TNF-α和TGF-β1的表达分析

目的分析Vitapex诱导鼠实验性根尖周炎中肿瘤坏死因子α(TNF-α)和转化生长因子-β1(TGF-β1)的表达。方法 24只SPF级C57BL/6小鼠随机平分为三组:模型组、Vitapex组、对照组。模型组、Vitapex组小鼠均建立实验性根尖周炎模型,对照组小鼠不进行处理,建模后3周Vitapex组小鼠同时进行Vitapex处理3周。术后3周与术后6周检测各组小鼠TNF-α和TGF-β1表达情况。术后3周与术后6周拍摄所有小鼠的牙根尖X线片,测量与计算牙根长度增加值与管壁厚度增加值。记录三组小鼠术后6周根尖孔闭合、根管壁新组织形成、根内牙髓样组织形成等发生率。结果模型组、Vitapex组术后3周与术后6周的血TNF-α和TGF-β1表达水平都显著高于对照组(P<0.05),且与术后3周相比,两组术后6周TNF-α水平显著降低,TGF-β1水平显著升高(P<0.05);术后Vitapex组TNF-α的表达水平低于模型组,TGF-β1表达水平显著高于模型组(P<0.05)。术后6周,模型组牙根长度增加值、管壁厚度增加值、根尖孔闭合、根管壁新组织形成、根内牙髓样组织形成等发生率均显著低于对照组(P<0.05),而Vitapex组的牙根长度增加值、管壁厚度增加值、根尖孔闭合、根管壁新组织形成、根内牙髓样组织形成等发生率均显著高于模型组,差异均有统计学意义(P<0.05)。结论 Vitapex在诱导鼠实验性根尖周炎中的应用能抑制TNF-α的表达,并促进牙根尖组织中TGF-β1的分泌,可促进根管壁增厚和根尖孔闭合,也促进形成新的牙骨质样和牙髓样组织。     

WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1α accumulation in Myc-dependent and independent pathways

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慢性病贫血患者细胞因子变化的研究

目的　探讨肿瘤坏死因子α(tumornecrosisfactor α,TNF α)、干扰素γ(interferonγ ,INF γ)、白细胞介素 6 (interleukin 6 ,IL 6 )在慢性病贫血 (anemiaofchronicdiseases ,ACD)发生机制中的作用。方法　测定31例ACD患者的铁代谢指标 (血清铁、血清铁蛋白、骨髓铁 ) ,采用双抗体酶联免疫吸附法 (ELISA)检测ACD患者血清中TNF α、INF γ、IL 6。结果　与对照组比较 ,ACD组血清中TNF α、INF γ、IL 6均显著增高 (P <0 0 1)。TNF α、IL 6与血清铁、血红蛋白浓度呈负相关。结论　免疫及炎症反应所产生的细胞因子INF γ、TNF α、IL 6等可能通过干扰铁代谢和抑制EPO(erythropoietin)生成、钝化对EPO的反应等途径介导了慢性病贫血的发生和发展过程     

吗啡胸段硬膜外给药对急性心肌缺血诱发大鼠肺组织肿瘤坏死因子-α表达的影响

目的 观察急性心肌缺血大鼠肺组织中肿瘤坏死因子-α(TNF-α)的表达变化以及吗啡硬膜外给药的干预效应.方法 将健康成年雄性SD大鼠18只随机分为假手术组(S组)、结扎冠状动脉(冠脉)缺血组(CAO组)和吗啡预处理组(M组),每组6只.S组动物仅开胸,不结扎左冠脉前降支;CAO组动物开胸后结扎左冠脉前降支;M组动物在结扎左冠脉前降支前15 min经硬膜外注射吗啡60μg/kg.各组在开胸或扎闭左冠脉前降支后3 h开胸取右肺下叶,采用免疫组化、酶联免疫吸附法(ELISA)检测肺组织中TNF-α表达变化.结果 免疫组化结果显示,与S组比较(8.68±0.29,1.609±0.050),CAO组(24.55±6.25,1.844±0.027)和M组(11.60±1.21,1.733±0.027)气管TNF-α阳性单位及平均吸光度(A)值均明显升高,而M组较CAO组明显降低,差异均有统计学意义(P均<0.01).ELISA结果显示:CAO组[(221.58±5.23)ng/L]和M组[(103.45±4.56)ng/L3肺组织TNF-α阳性免疫反应物质的表达水平均高于S组E(47.14±1.36)ng/L),且M组显著低于CAO组(P均<0.01).结论 急性心肌缺血能通过神经机制介导肺脏TNF-α表达上调;阿片类物质及其受体机制参与了机体内心脏伤害性神经信号转导的调节.     

生脉注射液对心肺复苏中肿瘤坏死因子-α、白细胞介素-8调控的临床研究

目的 将生脉注射液用于心肺复苏早期,探讨其通过调控细胞因子、非特异性抗炎、减轻缺血再灌注损伤的作用机制.方法40例均为心脏停搏后经心肺复苏心搏恢复≥24 h,需要进一步生命支持的患者,随机分为生脉组和对照组.2组患者在常规心肺复苏治疗基础上,生脉组于心肺复苏早期加用生脉注射液.动态观察比较生脉组与对照组复苏前和复苏后1、2、6、12、24h血清肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)指标的变化.结果 心肺复苏后2组患者血清TNF-α和IL-8水平较正常升高,且生脉组复苏后1、2、6、12、24h血清TNF-α和IL-8水平低于对照组,差异均有统计学意义(均P＜0.05).结论 生脉注射液可通过调控细胞因子,拮抗全身炎症反应而减轻缺血再灌注损伤.     

Effect of influenza vaccine on markers of inflammation and lipid profile

Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers. Because inflammatory markers such as C-reactive protein (CRP) are increasingly being used in conjunction with lipids for the clinical assessment of cardiovascular disease and in epidemiologic studies, we evaluated the effect of influenza vaccination on markers of inflammation and plasma lipid concentrations. We drew blood from 22 healthy individuals 1 to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P < .01 absolute values, P < .001 normalized values) on day 1 after receiving the influenza vaccine. The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05). No significant changes were seen in mean concentrations of IL-2 soluble receptor alpha, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. Of the lipids, significant decreases in mean concentrations of normalized triglyceride values were seen on days 1 (P < .05), 3 (P < .001), and 7 (P < .05) after vaccination. Our findings show that the influenza vaccination causes transient changes in select markers of inflammation and lipids. Consequently, clinical and epidemiologic interpretation of the biomarkers affected should take into account the possible effects of influenza vaccination.     

Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease

In this study we sought to determine whether molecular mechanisms involved in the pathogenesis of fulminant hepatic failure are present in rabbits experimentally infected with rabbit hemorrhagic disease virus (RHDV). The activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as bilirubin concentration, were found to be significantly increased 36 hours after infection. Infected animals also demonstrated significant decreases in factor VII activity, in the Fischer index, and in the deterioration of prothrombin time. The concentration of reduced glutathione was significantly decreased 36 hours after infection, and we noted a marked increase in the ratio of oxidized to reduced glutathione. Infected animals showed progressive decreases in liver activity of the antioxidant enzyme superoxide dismutase. Expression of hepatocyte growth factor and c-met was found to be progressively reduced from 24 hours after infection, during which time we detected no modification in messenger RNA (mRNA) levels of transforming growth factor (TGF)-alpha. TFG-beta 1 was overexpressed 24 and 36 hours after infection, and 36 hours after infection we detected a significant increase in TNF-alpha mRNA levels. Experimental RHDV infection also induced marked activation of nuclear factor-kappaB and a significant increase in inducible nitric oxide synthase mRNA levels from 24 hours after infection. Data obtained from this animal model support its usefulness in the investigation of potential novel therapeutical modalities aimed at neutralizing reactive oxygen species and hepatocyte growth inhibitors or enhancing hepatocyte responsiveness to mitogens.