BRITISH JOURNAL OF PHARMACOLOGY
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2023
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IF 7.3
Fangzhou Lou,Zhenyao Xu,Jing Bai,Xing’e Zhao,Linlin Cui,Qun Li,Honglin Wang
Background and Purpose Psoriasis vulgaris is a refractory skin inflammatory disorder with 80% of the cases belonging to the mild-to-moderate type, which can be controlled by topical treatment. Nevertheless, the drugs for external use have not been upgraded for decades. We modified acetyl-11-keto-beta-boswellic acid (ABKA), a natural compound shown to treat psoriasis animal models, to achieve improved efficacy and solubility for external use. Experimental approach Eleven compounds were synthesized using AKBA as a lead compound, and their effects on T helper 17 (Th17) cell differentiation were screened. 3-O-cyclohexanecarbonyl-11-keto-β-boswellic acid (CKBA) potently inhibited Th17 cell differentiation and we investigated its efficacy on treating a mouse model of psoriasis along with its pharmacology and safety profile when topically or systemically delivered to several species. Key Results CKBA inhibited mouse and human Th17 cell differentiation with an IC 50 of 3.28 μM and 3.61 μM respectively and directly targeted acetyl-CoA carboxylase 1 (ACC1). Safety evaluation and toxicity tests suggested that systemically delivered high-dose CKBA for 14 days had no dose-associated adverse effects on the central nervous, hematopoietic, cardiovascular, respiratory, and digestive systems of cynomolgus monkeys. CKBA ointment permeated the skin and did not irritate or sensitize intact skin. CKBA ointment mediated dose-dependent suppression of imiquimod-induced psoriasis-like skin inflammation with slow absorption and limited bioavailability (<10% in rats and <1% in minipigs). Conclusions and Implications CKBA is safe when topically or systemically delivered to animals. The positive effects of CKBA ointment in treating a mouse model of psoriasis indicate that this is a promising psoriasis drug candidate for further development.
研究领域:
药理学
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皮肤病学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Huanzhu Qian,Zhen Ye,Yu Hu,Liulin Chen,Linzhen Li,Kaihua Qin,Qiaobo Ye,Xiaohong Zuo
Ethnopharmacological relevance Dahuang-Gancao decoction (DGD) is a traditional Chinese medicinal formula that is recorded in the Synopsis of the Golden Chamber , and is widely used to treat damp-heat in the body. Since the pathological factors of androgenetic alopecia (AGA) also reflect damp-heat blockage, DGD has great potential for the treatment of AGA and has been used effectively in clinical practice. Aim of the study The aim of the study was to investigate whether external application of DGD could promote the activation and proliferation of hair follicle stem cells (HFSCs) and improve AGA through the Wnt/β-catenin pathway. Materials and methods The main chemical components of DGD-contained serum were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and database search. Cell Counting Kit-8 (CCK8) was used to investigate the appropriate concentration. Hair regeneration was assessed by hair growth score and histopathological staining. The proliferation of HFSCs and the activation of Wnt/β-catenin pathway were detected by western blot, immunofluorescence staining, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The AGA mouse model was induced by external application of testosterone (T). Immunofluorescence staining was performed to localize HFSCs by CK15, followed by staining with Ki67, β-catenin, and Cyclin D1, respectively. Results The results illustrated that the 10% DGD group and the 10% DGD + HLY78 group could significantly promote the expression of Wnt10b and β-catenin and the proliferation of HFSCs in vitro , while the 10% DGD + IWR-1 group could reverse the promotion effect of DGD. Animal experiments showed that compared with the model group (T group), DGD promoted hair follicles to enter the anagen phase, as evidenced by an increase in hair growth score, an increase in the number of hair follicles in hematoxylin and eosin (HE) staining, and a significant increase in the ratio of the number of anagen follicles to the total number of hair follicles (AF/AF + TF). In addition, DGD upregulated the expression of Wnt/β-catenin signaling pathway proteins in the skin tissues of AGA mice. It also promoted the proliferation of HFSCs and the expression of β-catenin and Cyclin D1 cytokines in the region of HFSCs. Conclusion Both oral and external application of DGD can promote the proliferation of HFSCs by activating the Wnt/β-catenin signalling pathway. External application of DGD can promote the hair follicles to enter the anagen phase, which can ameliorate the symptoms of alopecia in AGA mice. Therefore, compared to oral DGD, external application of DGD is an effective and safer way of administration for the treatment of AGA.
研究领域:
药理学
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民族药理学
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皮肤科
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
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IF 9.6
Yuhui Lu,Liying Zhou,Alu Ouyang,Xin Wang,Xiaoyang Wei,Shangping Xing,Feifei Nong,Jinquan Lin,Haotong Wang,Yuan Li,Jie Deng,Yilu Bao,Jie Yang,Ronghua Jin,Zhuo Luo
Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen primarily transmitted through skin-to-skin contact. Traditional antiviral drugs like acyclovir (ACV) have limitations due to viral resistance and side effects, necessitating the development of alternative therapeutic strategies. Drug-loaded hydrogels have emerged as a promising approach for managing various skin infections. Considering the low-pH microenvironment following HSV-1 infection, a pH-responsive baicalein@chitosan (B@C) hydrogel is developed for the topical treatment of HSV-1 skin infections. This hydrogel is synthesized by incorporating baicalein, a natural flavonoid, into a chitosan matrix modified with 4-formylphenylboronic acid and protocatechualdehyde to achieve potent anti-HSV-1 activity and pH-responsiveness. In vitro results demonstrated the hydrogel's pH-dependent inhibitory effect on HSV-1 infections, including ACV-resistant strains. Subsequent investigations confirmed its efficacy in multiple murine infection models. Mechanistically, the B@C hydrogel inhibited viral replication by modulating the phosphorylation of inhibitor of nuclear factor kappa-B kinase subunit beta, promoted collagen synthesis, and decreased reactive oxygen species generation. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis revealed a sustained release of baicalein from the hydrogel, ensuring long-term drug retention in HSV-1-infected skin tissues. Collectively, these findings suggest that the B@C hydrogel holds significant potential for the therapeutic management of HSV-1 skin infections.
研究领域:
药剂学
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病毒学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2021
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IF 5.194
Wei Li,Zhen Wang,Xiaoyu Wang,Xiaowei Cao,Caili Bi,Lili Jiang,Shuna Cui,Yong Liu
The drug-drug interaction (DDI) risk of phenytoin with several topical formulations of miconazole is still unclear. The present investigation conducted in vitro - in vivo extrapolation to predict the potential risks. Our data indicated that miconazole potently inhibited phenytoin hydroxylation in both pooled human liver microsomes (HLMs) and recombinant cytochrome P450 2C9 (CYP2C9) with the K i values of 125 ± 7 nM and 30 ± 2 nM, respectively. Quantitative prediction of DDI risk suggests that, beside intravenous administration or swallowed tablet, combination of phenytoin and miconazole high dose oral gel or buccal tablet may also result in a clinically significant increase of phenytoin AUC (>53%) by the inhibition of miconazole against phenytoin hydroxylation, consequently a higher frequency of adverse events, while the coadministration of miconazole vaginal formulation and phenytoin will be safe.
研究领域:
药理学
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临床药学
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药物代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2018
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IF 2.297
Xia Lv,Zhongxiao Cong,Zhihao Liu,Xiaodong Ma,Ming Xu,Yan Tian,Xinyi Zhang,Bingqing Xu,Jianbin Zhang,Zeyao Tang
Topical application of trans -resveratrol was limited due to its insolubility and instability problems. In this work, three kinds of essential oil based microemulsions containing rose oil (RO-ME), jasmine oil (JO-ME) and lemon oil (LO-ME) were prepared, constituted of Cremophor EL/1,2-propanediol/essential oils (47: 23: 30, w/w). All the three microemulsions could significantly improve the solubility and photostability of trans -resveratrol. Moreover, they could sustain the release of trans -resveratrol. Antioxidant activity study demonstrated that trans -resveratrol loaded microemulsions exhibited higher scavenging activities than both trans -resveratrol and blank microemulsions. The cell experiments demonstrated that RO-ME and JO-ME had lower cytotoxicity on HaCaT cells than LO-ME. The trans -resveratrol loaded RO-ME and JO-ME could significantly protect the cells from UVB damage. Finally, the in vitro skin permeation study exhibited that the microemulsions could enhance the skin permeation of trans -resveratrol in comparison to the aqueous solution. In summary, the essential oil based microemulsions could improve the solubility, photostability, antioxidant activity and UVB photoprotection of trans -resveratrol, which will be beneficial to its topical application.
研究领域:
药剂学
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化妆品学
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药理学
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化学
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
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IF 10
Jie Tang,Yu Li,Xuefeng Hu,Wei Hua,Haoning Xu,Li Li,Fujian Xu
The systemic use of tranexamic acid (TA) as an oral drug could bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies, are suffering from low drug load rates, plus its synthesis complexity, time-consumption etc., adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) was developed. The encapsulation efficiency of TA@ZIF-8 reached nearly 25% through physical adsorption and chemical bonding of TA indicated by theoretical simulation and the improved TA penetration was elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments have demonstrated the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials have demonstrated the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration. This article is protected by copyright. All rights reserved
研究领域:
药学
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皮肤病学
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纳米技术
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药理学
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临床研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Noor Ul Ain,Bibimaryam Khan,Kehan Zhu,Wen Ji,He Tian,Xiaoxiao Yu,Lin Yi,Duxin Li,Zhenqing Zhang
Glycyrrhizae Radix et rhizome/licorice is a precious herb in traditional Chinese medicine (TCM). TCM's polysaccharides are medicinally active. But herbal polysaccharides pose some limitations for topical applications. Therefore, this study aimed to utilize licorice polysaccharide via mesoporous silica nanoparticles (MSN) for anti-acne efficacy in topical delivery. The polysaccharide (GGP) was extracted with a 10 % NaOH solution. Chemical characterization suggested that GGP possesses an Mw of 267.9 kDa, comprised primarily of Glc (54.1 %) and Ara (19.12 %), and probably 1,4-linked Glc as a backbone. Then, MSN and amino-functionalized MSN were synthesized, GGP entrapped, and coated with polydopamine (PDA) to produce nanoparticle cargo. The resulted product exhibited 76 % entrapment efficiency and an in vitro release of 89 % at pH 5, which is usually an acne-prone skin's pH. Moreover, it significantly increased Sebocytes' cellular uptake. GGP effectively acted as an anti-acne agent and preserved its efficacy in synthesized nanoparticles. In vivo , the results showed that a 20 % gel of MSN-NH 2 -GGP@PDA could mediate an inflammatory response via inhibiting pro-inflammatory cytokines and regulating anti-inflammatory cytokines. The MSN-NH 2 -GGP@PDA inhibited TLR2-activated-MAPK and NF-κB pathway triggered by heat-killed P. acnes . In conclusion, fabricated MSN entrapped GGP for biomimetic anti-acne efficacy in topical application.
研究领域:
药学
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纳米技术
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皮肤科
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传统中药
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2023
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IF 4.1
Yi Chen,Yongfang Wang,Shasha Song,Xiaoli Zhang,Lili Wu,Jianbing Wu,Xinyu Li
Baicalin (BAI), the main active component of Scutellaria baicalensis, has significant anti-inflammatory and antibacterial effects. Echinacoside (ECH), an active component from Echinacea purpurea, has significant antiangiogenesis and antioxidant effects. In previous studies, BAI or ECH has been used for some skin inflammation problems by topical treatment. Psoriasis (PSO) is a common inflammatory skin disease with typical features such as excessive inflammatory response and vascular proliferation in skin lesions. Because of the anti-inflammatory effect of BAI and the antiangiogenic activity of ECH, it is proposed that the combination of BAI and ECH can ameliorate psoriatic skin lesions better than a single component. This study aims to explore the effects and potential mechanisms of BAI combined with ECH on imiquimod (IMQ)-induced psoriatic skin lesions by topical treatment. Transcriptome analysis first showed that the TNF signaling pathway and the VEGF signaling pathway were significantly enriched in IMQ-induced psoriatic skin lesions. Topical application of BAI combined with ECH could ameliorate IMQ-induced skin lesions in mice, especially the better effects of B2-E1 (BAI/ECH = 2:1). Network pharmacology analysis and molecular docking indicated that BAI-treated PSO on the skin by regulating the TNF signaling pathway, and ECH treated PSO on the skin by regulating the VEGF signaling pathway. Meanwhile, the ELISA test and the qPCR assay showed that BAI combined with ECH could inhibit the expression of key cytokines and genes related to the TNF signaling pathway and the VEGF signaling pathway. Zebrafish experiments demonstrated the anti-inflammatory and antiangiogenic effects of BAI combined with ECH and revealed the potential mechanisms associated with regulating the inflammation-related TNF signaling pathway and the angiogenesis-related VEGF signaling pathway. This suggested that BAI combined with ECH may be a promising topical agent to ameliorate psoriatic skin lesions in the future.
研究领域:
药理学
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皮肤病学
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分子生物学
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炎症研究
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血管生成研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Muhammad Sohail,Bin Xie,Bingzhi Li,He Huang
The significance of antioxidant activity determination in health sciences and food technology has become a hot research area as it is directly related to oxidative stress which is affiliated with several diseases and food deterioration. Herein, we fabricated a Zn-CDs-based (Zn-doped carbon dots-based) bioanalytical probe for the estimation of antioxidant activity index (AAI) to cope with the truncated robustness, high interference effect in complex samples, photo-bleaching, and low stability of the traditional techniques. Besides, the novel AAI standardized the presentation of the results by considering the transducer, Zn-CDs, concentration as reported results vary diversely for the same sample. In principle, free radicals quenched the fluorescence of the probe via inner filter effect and dynamic quenching. The presence of antioxidants hindered the fluorescence quenching by sequestering the free radicals from the reaction. The designed nanoreagent was validated for its applications using ascorbic acid , human serum, topical cosmetic formulation, and tomato juice samples. The bioanalytical probe demonstrated precise linearity, high robustness, low interference effect, and analytical equivalence when compared to the DPPH free radical assay. Hence, it can be used for the diagnosis and follow-up of oxidative stress-related ailments, developing and characterizing cosmeceuticals, analysis of antioxidant-containing formulations, and assessing and controlling the quality of food products. It is the first report to explore the antioxidant feature of Zn-CDs and its advantage for the estimation of AAI.
研究领域:
分析化学
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生物化学
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生物技术
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食品科学
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健康科学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Feng Li,Liming Lin,Jiaying Chi,Hui Wang,Minqun Du,Disang Feng,Liqing Wang,Rui Luo,Hangping Chen,Guilan Quan,Jianfeng Cai,Xin Pan,Chuanbin Wu,Chao Lu
Focal bacterial infections are often difficult to treat due to the rapid emergence of antibiotic-resistant bacteria, high risk of relapse, and severe inflammation at local lesions. To address multidrug-resistant skin and soft tissue infections, a bacteria-absorbing sponge was prepared to involve a “trap-and-kill” mechanism. The system describes a guanidinium-rich lipopeptide functionalized lyotropic liquid-crystalline hydrogel with bicontinuous cubic networks. Amphiphilic lipopeptides can be spontaneously anchored to the lipid-water interface, exposing their bacterial targeting sequences to enhance antibacterial trapping/killing activity. Computational simulations supported our structural predictions, and the sponge was confirmed to successfully remove ∼98.8% of the bacteria in the medium. Release and degradation behavior studies indicated that the bacteria-absorbing sponge could degrade, mediate enzyme-responsive lipopeptide release, or generate ∼200 nm lipopeptide nanoparticles with environmental erosion. This implies that the sponge can effectively capture and isolate high concentrations of bacteria at the infected site and then sustainably release antimicrobial lipopeptides into deep tissues for the eradication of residual bacteria. In the animal experiment, we found that the antibacterial performance of the bacterial-absorbing sponge was significant, which demonstrated not only a long-term inhibition effect to disinfect and avoid bacterial rebound, but also a unique advantage to protect tissue from bacterial attack. Statement of significance Host defense peptides/peptidomimetics (HDPs) have shown potential for the elimination of focal bacterial infections, but the application of their topical formulations suffers from time-consuming preparation processes, indistinctive toxicity reduction effects, and inefficient bacterial capture ability. To explore new avenues for the development of easily prepared, low-toxicity and high-efficiency topical antimicrobials, a guanidinium-rich lipopeptide was encapsulated in a lyotropic liquid-crystalline hydrogel (denoted as “bacteria-absorbing sponge”) to achieve complementary superiorities. The superior characteristic of the bacteria-absorbing sponge involves a “trap-and-kill” mechanism, which undergoes not only a long-term inhibition effect to disinfect and avoid bacterial rebound, but also effective bacterial capture and isolating action to confine bacterial diffusion and protect tissues from bacterial attack.
研究领域:
药学
·
微生物学
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材料科学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2017
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IF 4.3
Xia-Rong Wang,Si-Qian Gao,Xiao-Qian Niu,Long-Jian Li,Xiao-Ying Ying,Zhong-Jie Hu,Jian-Qing Gao
Capsaicin has been used in clinical applications for the treatment of pain disorders and inflammatory diseases. Given the strong pungency and high oil/water partition coefficient of capsaicin, capsaicin-loaded nanolipoidal carriers (NLCs) were designed to increase permeation and achieve the analgesic, anti-inflammatory effect with lower skin irritation. Capsaicin-loaded NLCs were prepared and later optimized by the Box–Behnken design. The physicochemical characterizations, morphology, and encapsulation of the capsaicin-loaded NLCs were subsequently confirmed. Capsaicin-loaded NLCs and capsaicin-loaded NLCs gel exhibited sustained release and no cytotoxicity properties. Also, they could significantly enhance the penetration amount, permeation flux, and skin retention amounts of capsaicin due to the application of NLCs. To study the topical permeation mechanism of capsaicin, 3,3′-dioctadecyloxacarbocyanine perchlorate (Dio) was used as a fluorescent dye. Dio-loaded NLCs and Dio-loaded NLCs gel could effectively deliver Dio up to a skin depth of 260 and 210 μm, respectively, primarily through the appendage route on the basis of version skin sections compared with Dio solution, which only delivered Dio up to 150 μm. In vivo therapeutic experiments demonstrated that capsaicin-loaded NLCs and capsaicin-loaded NLCs gel could improve the pain threshold in a dose-dependent manner and inhibit inflammation, primarily by reducing the prostaglandin E2 levels in the tissue compared with capsaicin cream and capsaicin solution. Meanwhile, skin irritation was reduced, indicating that application of NLCs could decrease the irritation caused by capsaicin. Overall, NLCs may be a potential carrier for topical delivery of capsaicin for useful pain and inflammation therapy.
研究领域:
药剂学
·
药学
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药物递送系统
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）