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α-MSH
ACS Biomaterials Science & Engineering · 2023 · IF 5.8

Silk Fibroin-Based Hydrogel Microneedles Deliver α-MSH to Promote Melanosome Delivery for Vitiligo Treatment

Shubin Chong,Chengxiu Wei,Longbao Feng,Rui Guo

Microneedles have shown great advantages in subcutaneous drug delivery and skin disease treatment. Vitiligo is a difficult-to-cure skin disease characterized by the depigmentation of the epidermis. Melanosomes produced in melanocytes are transported through dendrites to adjacent keratinocytes, where they accumulate, resulting in skin pigmentation. However, melanocytes in vitiligo patients are functionally disrupted. Silk fibroin (SF) methacrylate hydrogel microneedle can deliver α-MSH to the epidermis directly, where α-MSH helps the protection of melanocytes, extension of melanocytic dendrites, and transfer of melanosomes. In addition, the expression of melanogenesis-related melanocyte-inducing transcription factor and tyrosinase-related protein 1 (TRP1) was up-regulated, and the number of hair follicle stem cells increased with good proliferative activity. This slow release α-MSH SF-based hydrogel microneedles provides a new idea for the treatment of vitiligo.

CAS / MDL: 85073-19-4
研究领域: 生物医学工程 · 皮肤病学 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC Complementary Medicine and Therapies · 2022 ·Vol. 22 ·期 1 ·1-13 · IF 2.838

Anti-melanogenesis effect from Wampee fruit pectin via α-MSH/TRY pathway in A375 cells

Fu Weiyu,Liao Xuehua,Zhang Qian,Zhu Yuzhen,Mei Si,Li Qian,Zhou Xin,Li Xiaojun,Luo Hui,Ye Hua,Wu Kefeng

Background Polysaccharides from wampee have been reported to process various biological activities, while the relationship between structure and bioactivities has been barely addressed. Pectin, an abundant water-soluble polysaccharide in wampee, showed significant antioxidant activity, which was associated with the anti-melanogenic activity. Therefore, this study investigated the physicochemical characteristics and the anti-melanogenesis effect of pectin extracted from wampee fruit in A375 cells.Methods The physicochemical characterization of pectin from wampee fruit was investigated by gel chromatography (GCP), FT-IR spectroscopy, and NMR spectroscopy methods. The anti-melanogenesis effects and mechanism were evaluated by mushroom tyrosine enzyme and human melanin cell model in vitro.Results The results showed that a molecular weight of 5.271 × 105 Da wampee fruit pectin (WFP) were mainly composed of mannose (Man), ribose (Rib), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galacturonic acid (Gal A), galactose (Gal), and arabinose (Ara), which linked with →4)-β-D-Galp-(1 → units. The current study revealed that WFP could significantly suppress mushroom TRY activity in vitro. Furtherly, WFP significantly reduced intracellular and extracellular melanin formation in A375 melanoma cells depending on the presence of alpha-melanocyte stimulating hormone (α-MSH). TRY activity was only inhibited in α-MSH treated A375 cells. Western blot analysis demonstrated that WFP reverse α-MSH induced melanogenesis in A375 melanoma cells, including in down-regulated TRY, TYRP-1, TYRP-2, MITF and CREB expressions.Conclusion These results indicated that WFP could inhibit α-MSH induced melanogenesis in A375 melanoma cells via α-MSH/TRY pathway. In conclusion, these data provided a new perspective to annotate WFP anti-melanogenesis activity mechanism.

研究领域: 药理学 · 生物化学 · 细胞生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2021 · IF 4.432

GW9508 ameliorates cognitive dysfunction via the external treatment of encephalopathy in Aβ1-42 induced mouse model of Alzheimer's disease

Yuhang Gong,Yanfeng Li,Xin Liu,Ling He

The functions and mechanisms of GPR40 receptor to ameliorating the Alzheimer's disease (AD) by external treatment of encephalopathy remain unknown. In present study, the typical Aβ 1-42 induced mice model was applied to explore the functions and mechanisms of GPR40 receptor by external treatment of encephalopathy in AD. GPR40 agonist GW9508 and antagonist GW1100 were given by i.g injection to activate/inhibit the GPR40 receptor respectively in the gut of AD mouse which illustrated the function and mechanism of GPR40 receptor in ameliorating AD symptoms by external treatment of encephalopathy. A series of behavioral experiments were used to investigate the cognitive function and memory ability of mice, while molecular biology experiments such as Western blot , ELISA , flow cytometry were used to detect the corresponding changes of signaling pathways. The results revealed that intragastric administrated GW9508 could significantly ameliorate cognitive deficits of AD mouse, up-regulate the expression levels of gut-brain peptides both in blood circulation and hypothalamus thus up-regulate the expression levels of α-MSH in hypothalamus, while the negative autophagy-related proteins and inflammation-related proteins were down-regulated correspondingly. Meanwhile, GW9508 could also inhibit the pathological process of neuroinflammation in microglia . GW1100 reversed the effects of GW9508 significantly. These results suggested that GPR40 was an underlying therapeutic target for the external treatment of encephalopathy related to AD and GPR40 agonist could be explored as the emerging AD therapeutic drug.

研究领域: 神经科学 · 药理学 · 分子生物学 · 行为科学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

Debut of a novel AIE-based fluorescent probe as tyrosinase tracer to image skin pigmentary disorders

Xueyan Huang,Lan Zhang,Fan Zheng,Yanpeng Fang,Feng Gao,Qian Chen,Qinghai Zeng,Wenbin Zeng

Tyrosinase (TYR) functions as the critical enzyme in biosynthesis of melanin , and its abnormality is an important hallmark for skin pigmentary disorders. This renders the visualization of tyrosinase dynamics a strategically vital way to facilitate clinical diagnostic and monitoring. However, the use of small molecule fluorescent probes to assess tyrosinase levels and evaluate related therapeutics and drugs has been limited. This is mainly due to the aggregation-induced quenching (ACQ) effects of existing fluorescent probes. In this study, we introduce the first aggregation-induced emission (AIE) small molecule fluorescent probe , BTFTYR , for simple, highly sensitive, and effective detection of tyrosinase activity. The specific fluorescence signal generated by tyrosinase catalytic reaction enables the imaging of pigment cells. We demonstrate its application in visualizing tyrosinase with high contrast in living vertebrates, benefiting from the inherent photobleaching resistance of AIE materials, large Stokes shift , and considerable tissue permeability. We also show the outstanding skin penetration capability of BTFTYR in a skin model. Moreover, we present the first comprehensive evaluation of relevant clinical therapeutic approaches or drugs, including ultraviolet B (UVB) irradiation, kojic acid , and α-MSH, by interpreting the tyrosinase variation with BTFTYR . Finally, our studies confirm that BTFTYR neither causes skin inflammation nor produces visceral toxicity, making it a promising chemical tool for medical diagnosis and drug screening. This tool may further help elucidate the pathomechanisms associated with tyrosinase.

研究领域: 生物化学 · 药学 · 材料科学 · 医学成像
✓ 已验证 产品关联 DOI 高影响因子
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Applied Materials Today · 2021 · IF 10.041

Construction of a reactive oxygen species-responsive biomimetic multilayered titanium implant for in situ delivery of α-melanocyte-stimulating hormone to improve bone remolding in osteoporotic rats

Maohua Chen,Yan Hu,Yanhua Hou,Yuting Sun,Maowen Chen,Menghuan Li,Lu Tan,Zhong Luo,Kaiyong Cai

By exploiting the high reactive-oxygen-species(ROS) level in osteoporosis fractured sites, a ROS responsive biomimetic multilayer onto titanium(Ti) implant composed of gelatin(Gel)/dextran amine (DA) and α-melanocyte-stimulating hormone (α-MSH) has been constructed using layer-by-layer spin self-assembled technique, which was further cross-linked with 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2) benzyl carbonate (NBC)-grafted-polyethylene glycol (PEG-NBC) for in situ delivery of α-MSH. The PEG-NBC cross-linked Gel/DA multilayer onto Ti substrate (Ti/LBL NBC -MSH) could be broken down when exposed to ROS-rich pathological environment, thus leading to a sustained release of α-MSH from multilayer in a controlled manner. It could maintain the α-MSH concentration at a constant level to promote in situ MSCs differentiation and inhibit osteoclast activity through regulating GSK-3β/β-catenin signal pathways with Runx2 positive feedback regulation loop. Micro-CT analysis, hematoxylin/eosin (HE) staining and Masson's trichrome (MT) staining further confirmed that new bone has fused into mature lamellar bone and trabecularism along the interface of Ti/LBL NBC -MSH in osteoporotic rats. Therefore, this study offers a new perspective on the development of biofunctional Ti implants as supplementary treatment for osteoporotic fracture repair in a clinical context.

研究领域: 生物材料工程 · 组织工程 · 骨科 · 药剂学 · 材料科学
✓ 已验证 DOI 高影响因子
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