Interestingly, the IMQ + ACE cream group exhibited lower expression level of ICAM-1 in skin lesions than that of the IMQ group

Interestingly, the IMQ + ACE cream group exhibited lower expression level of ICAM-1 in skin lesions than that of the IMQ group. groups on day 4 ( 0.05). The results of the hematoxylin and eosin staining of skin tissues revealed that this epidermal thickness value of the IMQ + ACE cream group was significantly lower than those of the other experimental groups ( 0.05). The expression level of intracellular adhesion molecule-1 (ICAM-1), which indicates the leukocyte infiltration into the skin and subsequent interactions with keratinocytes, was also lower in the IMQ + ACE cream group than in the IMQ group. These results indicate that ACE cream formulation could be used safely and conveniently for psoriasis treatment. 1. Introduction Psoriasis is an autoimmune disease characterized by itchy, reddish, and scaly skin patches [1]. There are several main types of psoriasis: plaque, pustular, inverse, napkin, and guttate. The pathogenesis of psoriasis entails the abnormally quick growth of the skin epidermis. MLT-747 Fast replacement of psoriatic skin cells compared to normal cells may be due to the presence of premature keratinocytes, resulting from inflammatory cascades in the dermis [2]. The transfer of immune cells (i.e., dendritic, macrophage, and T cells) from your dermis to the epidermis and secretion of cytokines (i.e., interleukin- [IL-] 1antagonists (e.g., adalimumab, etanercept, and infliximab), monoclonal antibodies (mAb) of the p40 subunit of IL-12 and IL-23 (e.g., ustekinumab), and anti-IL-17 brokers (e.g., secukinumab) have been used as targeted immunosuppressive methods [5]. Recently, Janus kinase (JAK) inhibitors (e.g., tofacitinib and baricitinib), phosphodiesterase 4 (PDE4) inhibitors (e.g., apremilast), vitamin A derivatives (e.g., alitretinoin), adenosine A3 receptor antagonists, oxidized phospholipids, fumaric acid derivatives, and sphingosine 1-phosphate receptor-1 (SIP1) modulators (e.g., ponesimod) have been developed as emerging therapeutic compounds [5]. Except for synthetic and biological brokers, several natural product-based (e.g.Baphicacanthus cusiaCapsicum frutescensCurcuma longaHypericum perforatumIndigo naturalisMahonia aquifoliumStrobilanthes formosanusPersea americanaArtemisia capillaris(AC) extract (ACE) were demonstrated in HaCaT cells (a spontaneously transformed aneuploid immortal keratinocyte cell line) and an imiquimod- (IMQ-) induced psoriasis-like mouse model. However, the poor water-solubility of ACE might restrict its suitability for topical application. Although organic solvents (e.g., alcohols) could be used to solubilize the diverse ingredients in ACE, their clinical use may induce toxicity. Therefore, a cream formulation of ACE was prepared for clinical application. Cream formulations have been widely used for topical and transdermal delivery of herbal medicines [9C11]. In this study, the antipsoriatic potential of ACE cream was evaluated in a mouse model by evaluating the severity of psoriasis symptoms and the histological staining patterns. 2. Materials and Methods 2.1. Materials 6,7-Dimethoxycoumarin (scoparone, 98% purity) was purchased from Sigma-Aldrich Corp., (St. Louis, MO, USA). Chlorogenic acid ( 98% purity), 3,5-dicaffeoylquinic acid ( 98% purity), and 4,5-dicaffeoylquinic acid ( 97% purity) were obtained from ChemFaces (Wuhan, Hubei, China). IMQ cream (Aldara?, 5%) was acquired from 3M Pharmaceuticals (Leicestershire, UK). Tacrolimus (TAC) ointment (Protopic?, 0.1%) was purchased from Astellas Pharma Inc. (Tokyo, Japan). Phosphate-buffered saline (PBS) was obtained from Gibco Life Technologies, Inc. (Grand Island, NY, USA). All solvents were of high-performance liquid chromatography (HPLC) grade and the other chemicals were of analytical grade. 2.2. Preparation of ACE AC was purchased from a local market in Yeongcheon (Gyeongsangbuk-do, Korea) and the ACE was prepared and provided by Radiant. Inc., (Chuncheon, Korea) as reported [8]. AC was identified by Prof. Heejung Yang (Kangwon National University, Chuncheon, Korea). For the extract preparation, fresh AC (20 kg) was added to 70% (v/v) ethanol (EtOH, 200 L) and heated at 65C70C for 3 h. The resulting extract was filtered through a polypropylene membrane and the organic solvent was removed using a rotary evaporator. The extracted materials were lyophilized and stored for further use. 2.3. Preparation and Characterization of ACE Cream Formulation A cream formulation was developed for the skin delivery of ACE (2%, w/w) and was kindly provided by Hankook Korus Pharm Co., Ltd. (Chuncheon, Korea). The contents of four representative markers of ACE in the cream formulations were.It is expected that the inclusion of ACE in the cream may downregulate epidermal proliferation. Open in a separate window Figure 5 H&E staining of dissected skin tissues. ( 0.05). The results of the hematoxylin and eosin staining of skin tissues revealed that the epidermal thickness value of the IMQ + ACE cream group was significantly lower than those of the other MLT-747 experimental groups ( 0.05). The expression level of intracellular adhesion molecule-1 (ICAM-1), which indicates the leukocyte infiltration into the skin and subsequent interactions with keratinocytes, was also lower in the IMQ + ACE cream group than in the IMQ group. These results indicate that ACE cream formulation could be used safely and conveniently for psoriasis treatment. 1. Introduction Psoriasis is an autoimmune disease characterized by itchy, red, and scaly skin patches [1]. There are several main types of psoriasis: plaque, pustular, inverse, napkin, and guttate. The pathogenesis of psoriasis involves the abnormally rapid growth of the skin epidermis. Fast replacement of psoriatic skin cells compared to normal cells may be due to the presence of premature keratinocytes, resulting from inflammatory cascades in the dermis [2]. The transfer of immune cells (i.e., dendritic, macrophage, and T cells) from the dermis to the epidermis and secretion of cytokines (i.e., interleukin- [IL-] 1antagonists (e.g., adalimumab, etanercept, and infliximab), monoclonal antibodies (mAb) of the p40 subunit of IL-12 and IL-23 (e.g., ustekinumab), and anti-IL-17 agents (e.g., secukinumab) have been used as targeted immunosuppressive methods [5]. Recently, Janus kinase (JAK) inhibitors (e.g., tofacitinib and baricitinib), phosphodiesterase 4 (PDE4) inhibitors (e.g., apremilast), vitamin A derivatives (e.g., alitretinoin), adenosine A3 receptor antagonists, oxidized phospholipids, fumaric acid derivatives, and sphingosine 1-phosphate receptor-1 (SIP1) modulators (e.g., ponesimod) have been developed as emerging therapeutic compounds [5]. Except for synthetic and biological agents, several natural product-based (e.g.Baphicacanthus cusiaCapsicum frutescensCurcuma longaHypericum perforatumIndigo naturalisMahonia aquifoliumStrobilanthes formosanusPersea americanaArtemisia capillaris(AC) extract (ACE) were demonstrated in HaCaT cells (a spontaneously transformed aneuploid immortal keratinocyte cell line) and an imiquimod- (IMQ-) induced psoriasis-like mouse model. However, the poor water-solubility of ACE might restrict its suitability for topical application. Although organic solvents (e.g., alcohols) could be used to solubilize the diverse ingredients in ACE, their clinical use may induce toxicity. Therefore, a cream formulation of ACE was prepared for clinical application. Cream formulations have been widely used for topical and transdermal delivery of herbal medicines [9C11]. In this study, the antipsoriatic potential of ACE cream was evaluated in a mouse model by evaluating the severity of psoriasis symptoms and the histological staining patterns. 2. Materials and Methods 2.1. Materials FRP-2 6,7-Dimethoxycoumarin (scoparone, 98% purity) was purchased from Sigma-Aldrich Corp., (St. Louis, MO, USA). Chlorogenic acid ( 98% purity), 3,5-dicaffeoylquinic acid ( 98% purity), and 4,5-dicaffeoylquinic acid ( 97% purity) were obtained from ChemFaces (Wuhan, Hubei, China). IMQ cream (Aldara?, 5%) was acquired from 3M Pharmaceuticals (Leicestershire, UK). Tacrolimus (TAC) ointment (Protopic?, 0.1%) was purchased from Astellas Pharma Inc. (Tokyo, Japan). Phosphate-buffered saline (PBS) was obtained from Gibco Life Technologies, Inc. (Grand Island, NY, USA). All solvents were of high-performance liquid chromatography (HPLC) grade and the other chemicals were of analytical grade. 2.2. Preparation of ACE AC was purchased from a local market in Yeongcheon (Gyeongsangbuk-do, Korea) and the ACE was prepared and provided by Radiant. Inc., (Chuncheon, Korea) as reported [8]. AC was identified by Prof. Heejung Yang (Kangwon National University, Chuncheon, Korea). For the extract preparation, fresh AC (20 kg) was added to 70% (v/v) ethanol (EtOH, 200 L) and heated at 65C70C for 3 h. The resulting extract was filtered through a polypropylene membrane and the organic solvent was removed using a rotary evaporator. The extracted materials were lyophilized and stored for further use. 2.3. Preparation and Characterization of ACE Cream Formulation A cream formulation was.The weight of the spleens harvested from the IMQ + ACE cream group on day 4 was also lower than those of the IMQ and IMQ + ACE groups. ( 0.05). The expression level of intracellular adhesion molecule-1 (ICAM-1), which indicates the leukocyte infiltration into the skin and subsequent interactions with keratinocytes, was also lower in the IMQ + ACE cream group than in the IMQ group. These results indicate that ACE cream formulation could be used safely and conveniently for psoriasis treatment. 1. Introduction Psoriasis is an autoimmune disease characterized by itchy, red, and scaly skin patches [1]. There are several main types of psoriasis: plaque, pustular, inverse, napkin, and guttate. The pathogenesis of psoriasis involves the abnormally rapid growth of the skin epidermis. Fast replacement of psoriatic skin cells compared to normal cells may be due to the presence of premature keratinocytes, resulting from inflammatory cascades in the dermis [2]. The transfer of immune cells (i.e., dendritic, macrophage, and T cells) from the dermis to the epidermis and secretion of cytokines (i.e., interleukin- [IL-] 1antagonists (e.g., adalimumab, etanercept, and infliximab), monoclonal antibodies (mAb) of the p40 subunit of IL-12 and IL-23 (e.g., ustekinumab), and anti-IL-17 agents (e.g., secukinumab) have been used as targeted immunosuppressive methods [5]. Recently, Janus kinase (JAK) inhibitors (e.g., tofacitinib and baricitinib), phosphodiesterase 4 (PDE4) inhibitors (e.g., apremilast), vitamin A derivatives (e.g., alitretinoin), adenosine A3 receptor MLT-747 antagonists, oxidized phospholipids, fumaric acid derivatives, and sphingosine 1-phosphate receptor-1 (SIP1) modulators (e.g., ponesimod) have been developed as growing therapeutic compounds [5]. Except for synthetic and biological providers, several natural product-based (e.g.Baphicacanthus cusiaCapsicum frutescensCurcuma longaHypericum perforatumIndigo naturalisMahonia aquifoliumStrobilanthes formosanusPersea americanaArtemisia capillaris(AC) extract (ACE) were proven in HaCaT cells (a spontaneously transformed aneuploid immortal keratinocyte cell line) and an imiquimod- (IMQ-) induced psoriasis-like mouse magic size. However, the poor water-solubility of ACE might restrict its suitability for topical software. Although organic solvents (e.g., alcohols) could be used to solubilize the varied elements in ACE, their medical use may induce toxicity. Consequently, a cream formulation of ACE was prepared for clinical software. Cream formulations have been widely used for topical and transdermal delivery of herbal medicines [9C11]. With this study, the antipsoriatic potential of ACE cream was evaluated inside a mouse model by evaluating the severity of psoriasis symptoms and the histological staining patterns. 2. Materials and Methods 2.1. Materials 6,7-Dimethoxycoumarin (scoparone, 98% purity) was purchased from Sigma-Aldrich Corp., (St. Louis, MO, USA). Chlorogenic acid ( 98% purity), 3,5-dicaffeoylquinic acid ( 98% purity), and 4,5-dicaffeoylquinic acid ( 97% purity) were from ChemFaces (Wuhan, Hubei, China). IMQ cream (Aldara?, 5%) was acquired from 3M Pharmaceuticals (Leicestershire, UK). Tacrolimus (TAC) ointment (Protopic?, 0.1%) was purchased from Astellas Pharma Inc. (Tokyo, Japan). Phosphate-buffered saline (PBS) was from Gibco Existence Systems, Inc. (Grand Island, NY, USA). All solvents were of high-performance liquid chromatography (HPLC) grade and the additional chemicals were of analytical grade. 2.2. Preparation of ACE AC was purchased from a local market in Yeongcheon (Gyeongsangbuk-do, Korea) and the ACE was prepared and provided by Radiant. Inc., (Chuncheon, Korea) as reported [8]. AC was recognized by Prof. Heejung Yang (Kangwon National University or college, Chuncheon, Korea). For the draw out preparation, refreshing AC (20 kg) was added to 70% (v/v) ethanol (EtOH, 200 L) and heated at 65C70C for 3 h. The producing extract was filtered through a polypropylene membrane and the organic solvent was eliminated using a rotary evaporator. The extracted materials were lyophilized and stored for further use. 2.3. Preparation and Characterization of ACE Cream Formulation A cream formulation was developed for the skin delivery of ACE (2%, w/w) and was kindly provided by Hankook Korus Pharm Co., Ltd. (Chuncheon, Korea). The material of four representative markers of ACE in the cream formulations were quantitatively determined relating to a previously reported method [8]. The stock solutions of chlorogenic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, and 6,7-dimethoxycoumarin were prepared by dissolving each compound in methanol to a concentration of 1 1 mg/mL. ACE cream (300 mg) was dissolved in methanol (10 mL) and was filtered through a syringe filter (0.45-ad libitumt 0.05). The IMQ + ACE and IMQ + cream organizations did not show any significant reduction in the thickness of dorsal pores and skin compared with that of the IMQ group. In the IMQ + ACE group, ACE was not completely dissolved in the solvent; therefore it did not exert adequate pharmacological activities. The results of the IMQ + cream group display that the presence of pharmaceutical excipients in the cream formulation did not significantly switch the dorsal pores and skin thickness. Open in a separate window Number 1 The influences of ACE cream within the thickness of pores and skin in IMQ-induced psoriasis-like mouse models. Thickness (mm) of dorsal pores and skin in each experimental group.