Mechanisms of action of Lycium barbarum polysaccharide in protecting against vitiligo mice through modulation of the STAT3-Hsp70-CXCL9/CXCL10 pathway.

CONTEXT: Vitiligo is a common skin disease with a complex pathogenesis, and so far, no effective treatment is available. Lycium barbarum L. (Solanaceae) polysaccharide (LBP), the main active ingredient of goji berries, has been demonstrated to protect keratinocytes and fibroblasts against oxidative stress. OBJECTIVE: This study explored the effects and mechanism of LBP on monobenzone-induced vitiligo in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into five groups (n = 6): negative control that received vaseline, vitiligo model group induced by monobenzone that treated with vaseline, positive control that received tacrolimus (TAC), LBP groups that received 0.3 and 0.6 g/kg LBP, respectively. We quantified the depigmentation by visual examination and scores, detected the expression of CD8+ T cells, pro-inflammatory cytokines and analysed the STAT3-Hsp70-CXCL9/CXCL10 pathway. RESULTS: LBP 0.3 and 0.6 g/kg groups can significantly reduce depigmentation scores and the infiltration of local inflammatory cells in the skin lesions. Moreover, the expression of CXCL9, CXCL3, CXCL10 and HSP70 decreased by 54.3, 20.3, 48.5 and 27.2% in 0.3 g/kg LBP group, which decreased by 62.1, 26.6, 58.2 and 34.5% in 0.6 g/kg LBP group. In addition, 0.3 and 0.6 g/kg LBP decreased the release of IL-8 (9.7%, 22.8%), IL-6 (40.8%, 42.5%), TNF-α (25.7%, 35%), IFN-γ (25.1%, 27.6%) and IL-1ß (23.7%, 33.7%) and inhibited the phosphorylation expression of STAT3 by 63.2 and 67.9%, respectively. CONCLUSION: These findings indicated LBP might be recommended as a new approach for vitiligo which provide a theoretical basis for the clinical application of LBP in treating vitiligo patients.

Curcumin Improves Keratinocyte Proliferation, Inflammation, and Oxidative Stress through Mediating the SPAG5/FOXM1 Axis in an In Vitro Model of Actinic Dermatitis by Ultraviolet.

Background: Chronic actinic dermatitis (CAD) is an abnormally proliferating photoallergic skin disease. Dysregulated inflammation and oxidative stress are the immediate factors in the abnormal proliferation of keratinocytes. This study aimed to investigate the effect of curcumin on the aberrant proliferation of keratinocytes in an in vitro (actinic dermatitis) AD model and the possible molecular mechanisms. Methods: The keratinocytes were irradiated with ultraviolet (UV) to construct an in vitro AD model and then processed with different concentrations of curcumin. Cell viability, oxidative stress markers (SOD, GSH-PX, and MDA), activated oxygen species (ROS), and inflammation markers (IL-1ß, IL-6, IL-18, and TNFα) were determined, respectively. Western blot was applied to assay the profiles of apoptosis-related proteins (Bax, Bcl-xL, Caspase3, Caspase8, and Caspase9), oxidative stress proteins (Keap1, Nrf2, HO-1, COX2, and iNOS), and inflammatory proteins (NF-κB, MMP1, and MMP9) and SPAG5/FOXM1. Functionally, SPAG5 or FOXM1 overexpression and knockdown models were constructed in keratinocytes to characterize their influence on UV irradiation-mediated keratinocyte dysfunction. Results: Curcumin weakened UV-mediated inflammation, proliferation, and oxidative stress and impaired apoptosis in keratinocytes. UV boosted SPAG5/FOXM1 expression in cells, while curcumin concentration-dependently retarded SPAG5/FOXM1 expression. Overexpression of SPAG5/FOXM1 fostered UV-mediated inflammation, proliferation, oxidative stress, and intensified apoptosis, whereas curcumin mostly reversed the SPAG5/FOXM1-mediated effects. In addition, knocking down SPAG5/FOXM1 ameliorated UV-mediated keratinocyte dysfunction, whereas curcumin failed to exert further protective effects in cells with knockdown of SPAG5/FOXM1. Conclusion: Curcumin modulated proliferation, inflammation, oxidative stress, and apoptosis of keratinocytes by restraining the SPAG5/FOXM1 axis.

Effects of tea polyphenols on UVA-induced melanogenesis via inhibition of α-MSH-MC1R signalling pathway.

Introduction: Ultraviolet (UV) irradiation is a major environmental factor affecting photoaging, which is characterized by skin wrinkle formation and hyperpigmentation. Although many factors are involved in the melanogenesis progress, UV is thought to play a major role in tanning. The pathway of α-melanocyte-stimulating hormone (α-MSH)-melanocortin receptor 1 (MC1R) is associated with UV-induced melanogenesis. Thus, α-MSH antagonists may have applications in the prevention of melanogenesis. Aim: To investigate the effects of tea polyphenols (TPS) on pigmentation, and further explore the underlying mechanism. Material and methods: Human keratinocyte cell line (HaCaT) cells and Human epidermal melanocytes (HEM) were exposed to UVA and treated with different concentrations of TPS or Nonapeptide-1 acetate salt (N-1A). Then, cell viability, melanin content, and tyrosinase activity of both kinds of cells were detected. Quantification of α-MSH in HaCaT cells and HEM cells determined by ELISA assays. Immunohistochemistry of HEM cells was employed to further investigate the expression of melanogenesis-related proteins. Results: The different concentrations of TPS were found to decrease the melanin content, tyrosinase activity and melanogenesis-related proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein (TRP)1, and TRP2. Besides, TPS inhibited α-MSH-MC1R signalling through directly suppressed α-MSH expression rather than the down-regulated expression level of MC1R. Conclusions: Our findings indicate that TPS may be a potential whitening agent for use in cosmetics and the medical treatment of hyperpigmentation disorders.

Green Tea Polyphenols Cause Apoptosis and Autophagy in HPV-16 Subgene-Immortalized Human Cervical Epithelial Cells via the Activation of the Nrf2 Pathway.

Infection with human papillomavirus (HPV) is relatively common and certain high-risk HPV strains can induce epithelial dysplasia, increasing the risk of cervical cancer. Green tea polyphenol (GTP) preparations exhibit diverse anti-inflammatory, antioxidative, and antitumor properties In Vitro and In Vivo. Topical GTP application has been recommended as a treatment for genital warts, but the effect of GTP treatment on HPV infection and HPV-associated cancer remains to be established. The present study aimed to explore the mechanism by which GTP affected HPV type 16 (HPV-16)-positive immortalized human cervical epithelial cells. Survival, apoptosis, and autophagocytosis of these cells following GTP treatment was assessed using CCK-8 assay, flow cytometry, and monodansylcadaverine (MDC) staining. These cells were further transfected with an shRNA specific for Nrf2 to generate stable Nrf2-knockdown cells. The levels of Caspase-3, Bcl-2, Bax, P53, Rb, HPV-16 E6, HPV-16 E7, P62, Beclin1 and LC3B were determined via Western blotting. These analyses revealed that GTP treatment induced autophagy and apoptosis in HPV-16-positive cells, while Nrf2 gene knockdown reversed GTP-induced autophagic and apoptotic effects. Together, these results suggested that GTP could alleviate HPV infection and HPV-associated precancerous lesions In Vitro by regulating the Nrf2 pathway, highlighting the therapeutic potential of GTP in treating HPV infection.

Lycium barbarum polysaccharide promotes proliferation of human melanocytes via activating the Nrf2/p62 signaling pathway by inducing autophagy in vitro.

Vitiligo is a skin disease characterized by lack of functional melanocytes. Lycium barbarum polysaccharide (LBP) has been demonstrated to preserve keratinocytes and fibroblasts against oxidative stress. This study aimed to explore the efficacy and underlying mechanisms of LBP on autophagy in H2 O2 -damaged human melanocytes. Cellular viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin V-fluorescein isothiocyanate/propidium iodide double staining. Reverse transcription-polymerase chain reaction, western blotting and electron microscopy were performed to detect autophagy. The protein expression level of Nrf2 and p62 were assessed by western blotting. Plasmid transfection and lentiviral infection were used to overexpress and silence Nrf2 in PIG1 cells. LBP promoted the proliferation and inhibited apoptosis of H2 O2 -damaged PIG1 cells. LBP increased the proliferation of H2 O2 -damaged PIG1 cells via induction of autophagy, and Nrf2 shRNA experiment confirmed that LBP activated the Nrf2/p62 signal pathway. These results suggest that LBP may be used for the treatment of vitiligo. PRACTICAL APPLICATIONS: Goji berry is the mature and dried fruit of Lycium barbarum L., which is a common food with a long history in China, as well as a Traditional Chinese Medicine. Our previous research found that LBP could activated the Nrf2/ARE pathway in an ultraviolet (UV)-induced photodamage model of keratinocytes, and increase the levels of phase II detoxification and antioxidant enzymes. We firstly confirmed the anti-vitiligo effects of L. barbarum polysaccharide (LBP) by inducing autophagy and promoted proliferation of human melanocytes, and LBP induced autophagy via activating the Nrf2/p62 signaling pathway in this study. These results proved that LBP can be an effective therapy for vitiligo treatment.

Split-face comparison of the efficacy of picosecond 532 nm Nd:YAG laser and Q-switched 755 nm Alexandrite laser for treatment of freckles.

To date, there has been little study of comparison between picosecond 532 nm laser and 755 nm Q-switched Alexandrite lasers in the treatment of freckles. To evaluate the efficacy and safety of picosecond 532 nm laser (PS 532) and 755 nm Q-switched Alexandrite laser (QSAL) for treatment of freckles in a split-face manner. Eighteen patients with freckles were enrolled in the study. The right and left sides of their faces were randomly assigned to either a QSAL-treated group or PS 532-treated group. The degree of pain, satisfaction with the results, and adverse events associated with the laser treatment were evaluated using a questionnaire. All of the patients were followed up at 4 and 12 weeks after one treatment session. Among the 18 patients, PS 532 was found to be associated with less pain (3.56 ± 2.431) than QSAL (3.94 ± 1.893), but the difference was not statistically significant. The curative effect and satisfaction associated with 755 nm Q-switched Alexandrite laser was greater than that of picosecond 532 nm laser (P < .001). Both picosecond 532 nm laser and QSAL are effective in the treatment of freckles, and QSAL has a greater rate of satisfaction and curative effect.

Curcumin protection against ultraviolet-induced photo-damage in Hacat cells by regulating nuclear factor erythroid 2-related factor 2.

Curcumin suppressed ultraviolet (UV) induced skin carcinogenesis and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. However, whether curcumin protects skin injury caused by UV is still unknown. A vitro model was established and curcumin effects on Hacat cells were detected. Nrf2 was knocked down in Hacat cells to verify the Nrf2 role in the protective effect of curcumin. Results indicated that ultraviolet A (UVA) (or ultraviolet B (UVB)) irradiation would lead to decreased cell proliferation, increased cell apoptosis, decreased catalase, heme oxygenase 1, and superoxide dismutase expression, and increased levels of protein carbonylation and malondialdehyde (p < 0.05). These adverse events could be reversed by adding 5-µM curcumin. Meanwhile, we found that the application of curcumin effectively induced Nrf2 nuclear accumulation in Hacat cells. While in the Nrf2 knockdown cells, the protective effects of curcumin against UVA (or UVB) were attenuated. Conclusively, curcumin protects Hacat cells against UV exposure-induced photo-damage by regulating Nrf2 expression.

Efficacy of NB-UVB as Add-on Therapy to Antihistamine in the Treatment of Chronic Urticaria: A Systematic Review and Meta-analysis.

INTRODUCTION: Narrow-band ultraviolet B (NB-UVB) phototherapy has been used for the treatment of chronic urticaria (CU), but the clinical efficacy of this treatment modality requires further evidence. A systematic review and meta-analysis of randomized clinical trials were conducted to evaluate the efficacy and safety of NB-UVB as add-on therapy in the treatment of CU. METHODS: A literature search was conducted in the Cochrane, Embase, PubMed, Web of Science, CNKI, CBM, VIP and WanFang databases up to October 2020. A total of nine studies involving 713 participants met the inclusion criteria. RESULTS: Two trials showed a significant difference in the Urticaria Activity Score between therapy with NB-UVB + antihistamines and that with antihistamines alone (mean difference 8.23, 95% confidence interval [CI] 5.78-10.68, p < 0.00001). Six trials (563 participants) showed a significant benefit of NB-UVB as add-on therapy to antihistamines in the total effective rate (risk ratio [RR] 1.56, 95% CI 1.39-1.75, p < 0.00001). In terms of adverse events, no statistically significant differences were found for NB-UVB + antihistamines versus antihistamines alone (RR 1.10, 95% CI 0.67-1.79, p = 0.71). Combination therapy of NB-UVB + antihistamines yielded a significantly lower risk of recurrence (RR 0.25, 95% CI 0.14-0.44, p < 0.00001). CONCLUSION: Our meta-analysis suggests that combination therapy of NB-UVB + antihistamines is significantly more effective in treating CU than antihistamines alone.

Pterostilbene's protective effects against photodamage caused by UVA/UVB irradiation.

Aim: The aim of this study was to further elucidate the mechanism of pterostilbene against UVA/UVB irradiation and the Nuclear factor E2-related factor 2 (Nrf2) signal pathway. Methods: A photo-damage model with UVA/UVB irradiation in HaCat cells was established and used in this study. The dose of pterostilbene was selected through MTS assay. Cell proliferation and apoptosis in Nrf2 and knockdown Nrf2 cells was detected by MTS assay. Expression of CAT, HO-1, and SOD in Nrf2 and knockdown Nrf2 cells was explored by qPCR. Western blot was used to analysis of Nrf2 nuclear translocation changes in Nrf2 and knockdown Nrf2 cells. Protein carbonyl content and MDA content was tested. Results: Our photo-damage model was successfully established and 20J/cm² UVA and 57mJ/cm² UVB irradiation was the suitable dose for HaCaT cell damage study. UVA/UVB irradiation would affect Nrf2 protein location, especial for 9.75 µM pterostilbene dose. In addition, cell proliferation could be significantly inhibited by UVA/UVB treatments (P<0.05), whereas, 9.75 µM pterostilbene treatment can alleviate the photo-damage. UVA/UVB irradiation would lead to decreased expressions of CAT, HO-1, and SOD. Carbonyl content and MDA was significantly changed by UVA/UVB treatments (P<0.05). The adverse events could be reversed by adding 9.75 µM pterostilbene. Western blot analysis showed that Nrf2 cytoplasm content in UVA/UVB treated cells was reduced and Nrf2 nuclear content was increased, which are different with the normal HaCaT cells without knockdown Nrf2 treatment (P<0.05). The results of cell proliferation, apoptosis, and cell antioxidant capacity in knockdown Nrf2 treated HaCaT cells were also significantly different with the normal HaCaT cells without knockdown Nrf2 treatment (P<0.05). Conclusion: We hypothesize that pterostilbene could play an anti-oxidation role via the Nrf2 signal pathway.

Lycium barbarum polysaccharide protects HSF cells against ultraviolet-induced damage through the activation of Nrf2.

BACKGROUND: Lycium barbarum polysaccharide (LBP) is considered an antioxidant agent. NF-E2-related factor-2 (Nrf2) is an important regulator for protection against UV damage. In this study, we verified the performance of LBP and the correlation between LBP and Nrf2. METHODS: HSF cells were treated with LBP to determine dose and time dependencies. An antioxidant response element (ARE) reporter was designed to monitor the activity of the Nrf2 antioxidant pathway. RESULTS: For HSF cells, the optimal LBP treatment was 300 µg/ml for 3 h. The ARE-reporter assay showed that LBP could increase the robustness of p-Nrf2. Treatments with genistein and LY294002 reduced of nuclear p-Nrf2 after 24 h. LBP increased the level of nuclear Nrf2, which functions by both phosphorylation and nuclear translocation. Silencing Nrf2 led to increased reactive oxygen species (ROS) levels, lower cell viability, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSP-PX) levels. This induced a higher level of lipid peroxide (LPO). However, LBP could decrease the levels of ROS and LPO and enhance the levels of SOD and GSP-PX. CONCLUSION: LBP protects HSF cells against UV damage via the regulation of Nrf2.

Pterostilbene protects against UVB-induced photo-damage through a phosphatidylinositol-3-kinase-dependent Nrf2/ARE pathway in human keratinocytes.

OBJECTIVE: Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes. METHODS: Human keratinocytes were pretreated with Pter (5 and 10 µM) for 24 h prior to UVB irradiation (300 mJ/cm2). Harvested cells were analyzed by MTT, DCFH-DA, comet, western blotting, luciferase promoter, small interference RNA transfection, and quantitative real-time polymerase chain reaction assay. RESULTS: Pter significantly attenuated UVB-induced cell death and reactive oxygen species (ROS) generation, and effectively increased nuclear translocation of NF-E2-related factor-2 (Nrf2), expression of Nrf2-dependent antioxidant enzymes, and DNA repair activity. Moreover, the protective effects of Pter were abolished by small interference RNA-mediated Nrf2 silencing. Furthermore, Pter was also found to induce the phosphorylation of Nrf2 and the known phosphatidylinositol-3-kinase (PI3K) phosphorylated kinase, Akt. The specific inhibitor of PI3K, LY294002, successfully abrogated Pter-induced Nrf2 phosphorylation, activation of Nrf2-antioxidant response element pathway, ROS scavenging ability, and DNA repair activity. CONCLUSION: The present study indicated that Pter effectively protected against UVB-induced photodamage by increasing endogenous defense mechanisms, scavenging UVB-induced ROS, and aiding in damaged DNA repair through a PI3K-dependent activation of Nrf2/ARE pathway.

Lycium barbarum polysaccharide protects human keratinocytes against UVB-induced photo-damage.

Ultraviolet B (UVB) irradiation plays a key role in skin damage, which induces oxidative and inflammatory damages, thereby causing photoaging or photocarcinogenesis. Lycium barbarum polysaccharide (LBP), the most biologically active fraction of wolfberry, possesses significant antioxidative and anti-inflammatory effects on multiple tissues. In the present study, the photoprotective effects and potential underlying molecular mechanisms of LBP against UVB-induced photo-damage were investigated in immortalized human keratinocytes (HaCaT cells). The data indicated that pretreatment with LBP significantly attenuated UVB-induced decrease in cell viability, increase in ROS production and DNA damage. LBP also significantly suppressed UVB-induced p38 MAPK activation, and subsequently reversed caspase-3 activation and MMP-9 expression. Notably, LBP was found to induce Nrf2 nuclear translocation and increase the expression of Nrf2-dependent ARE target genes. Furthermore, the protective effects of LBP were abolished by siRNA-mediated Nrf2 silencing. These results showed that the antioxidant LBP could partially protect against UVB irradiation-induced photo-damage through activation of Nrf2/ARE pathway, thereby scavenging ROS and reducing DNA damage, and subsequently suppressing UVB-induced p38 MAP pathway. Thus, LBP can be potentially used for skincare against oxidative damage from environmental insults.

Topical treatment of green tea polyphenols emulsified in carboxymethyl cellulose protects against acute ultraviolet light B-induced photodamage in hairless mice.

Ultraviolet (UV) radiation causes skin injury and inflammation resulting in impaired immune response and increased risk of skin cancer. It has been shown that green tea polyphenols (GTPs) enhanced intracellular antioxidant defense and promoted the downregulation of proapoptotic genes, and they could be used to protect against the damage induced by UV irradiation. However, the high instability and poor bioavailability of GTPs impose restrictions on their potential pharmacological use. Here we show that carboxymethyl cellulose sodium (CMC-Na) had a stabilizing effect on GTPs under aqueous conditions and topical application of GTPs (emulsified in CMC-Na) had a strong photoprotective effect against acute UVB induced photodamage in uncovered (Uncv) hairless mice skin. After 8 h of incubation at 50 °C with CMC-Na, a percentage i.e. 93% of GTPs was preserved, while in the absence of CMC-Na, a percentage of only 61% was preserved. Topical treatment of emulsified GTPs effectively inhibited acute UVB-induced infiltration of inflammatory cells, increase of skin thickness, oxidative stress such as depletion of antioxidant enzymes and lipid oxidation, and induced nuclear accumulation of Nrf2 in the mice skin. We also discovered the ability of GTPs to simultaneously trigger accumulation of nuclear Nrf2 and export of nuclear Bach1. Altogether, our findings reinforced the putative application of GTPs in the prevention/minimization of the deleterious effects of UV on the skin.

Protective Effect of Curcumin Against Acute Ultraviolet B Irradiation-induced Photo-damage.

Ultraviolet B (UVB) irradiation is one of the most dangerous insults for skin and causes sunburn, erythema, photoaging and photocarcinogenesis. Curcumin (diferuloylmethane), a yellow spice derived from dried rhizomes of Curcuma longa, has been shown to possess significant anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant and anti-infective effects. However, the protective effects of curcumin against acute photo-damage are poorly understood. In this study, we investigated the photoprotective effects of curcumin against UVB-induced acute photo-damage in hairless mice and immortalized human keratinocytes (HaCaT). Topical application of curcumin significantly inhibited acute UVB (540 mJ cm-2 , for 3 successive days)-induced inflammatory cells, collagen accrementition derangement and lipid peroxidation, and effectively induced NF-E2-related factor 2 (Nrf2) nuclear accumulation in uncovered (Uncv) hairless mice skin. Treatment of HaCaT cells with curcumin significantly attenuated acute UVB (300 mJ cm-2 )-induced lactate dehydrogenase release, intracellular reactive oxygen species production and DNA damage, activated the expression of the phase II detoxifying enzymes and promoted DNA repair activity. The photoprotective effect provided by curcumin was potential associated with modulation of Nrf2-dependent antioxidant response. Our study suggested that curcumin is a potential agent for preventing and/or treating UV radiation-induced acute inflammation and photoaging.

Prevention of ultraviolet radiation­induced immunosuppression by sunscreen in Candida albicans­induced delayed­type hypersensitivity.

Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans­induced delayed­type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub­erythema dose of solar­simulated radiation. Delayed­type hypersensitivity was induced by immunization with Candida albicans. Changes in the skin thickness of the foot pads were measured, and immunosuppression rates were also evaluated. The expression levels of CD207, CD80 and CD86 in the Langerhans cells were semi­quantitatively detected using Western blotting and immunohistochemical assays. The delayed­type hypersensitivity mouse model was successfully established. The minimal erythema doses of UVA and UVB exposure to the mice were 2,000 and 145 mJ/cm2, respectively. The immunosuppression rates in the sunscreen group and non­sunscreen group were 24.39 and 65.85%, respectively (P<0.01). The results of the Western blotting and immunohistochemistry showed that the expression levels of CD207 (P<0.01), CD80 (P<0.05) and CD86 (P<0.01) were higher in the sunscreen group, compared with those in the non­sunscreen group. UV exposure reduced Candida albicans antigen­induced delayed­type hypersensitivity. Anthelios sunscreen was found to protect the skin from immunosuppression through the activation of epidermal Langerhans cells.

Activation of coagulation, anti-coagulation, fibrinolysis and the complement system in patients with urticaria.

BACKGROUND: Recently released studies indicate that activation of blood coagulation may be involved in causing urticaria. OBJECTIVE: To evaluate whether or not anticoagulation, fibrinolysis and the complement system are also involved in the pathogenesis of urticaria. METHODS: Coagulant factors, anticoagulant factors, fibrinolytic markers and complement components were analysed in patients with acute urticaria (AU) and chronic urticaria (CU). Conclusion: The activation of coagulation, anti-coagulation, fibrinolysis and the complement system may be involved in the pathogenesis of urticaria. It also indicates that coagulation conditions in CU patients can recover after antihistamine treatment, but do not immediately return to normal levels directly after administration. RESULTS: Plasma levels of activated factor VII (FVIIa) were higher in AU patients (P <0.01) but not significantly different in CU patients (P >0.05), while levels of the thrombin-antithrombin complex (TAT) and prothrombin fragment 1+2 (F1+2) were significantly higher in CU patients (P <0.01). Levels of factor IX (FIX) and tissue factor (TF) were lower in CU patients (P <0.01). Plasma levels of tissue factor pathway inhibitor/activated factor X (TFPI/Xa) were higher in CU patients (P <0.01) but not significantly different in AU patients (P >0.05), whereas levels of thrombomodulin (TM) were lower in CU patients (P <0.01). Plasma levels of D-dimer in AU and CU patients and levels of high molecular weight kininogen (HMWK) in CU patients were increased significantly (P <0.01), while levels of tissue-type plasminogen activator (t-PA) were decreased (P <0.01). Plasma concentrations of C5a in CU patients were superior to those in healthy controls (P <0.01). Serum levels of C4 also increased (P <0.01). CONCLUSION: The activation of coagulation, anti-coagulation, fibrinolysis and the complement urticaria. It also indicates that coagulation conditions in CU patients can recover after antihistamine treatment, but do not immediately return to normal levels directly after administration.