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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Amygdalin ameliorates alopecia areata on C3H/HeJ mice by inhibiting inflammation through JAK2/STAT3 pathway

Xun He,Jingsong Liu,Yugang Gong,Wei Lu,Xiaowei Sha,Chang Cao,Yanqun Li,Jiawei Wang

Background Evidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. Purpose Therefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. Study design The C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). Methods The optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4 + CD25 + FOXP3 + , CD4 + and CD8 + of skin tissue. And the levels of CD4 + and CD8 + , p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. Results Compared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4 + CD25 + FOXP3 + and CD4 + cells, while inhibited the number of CD8 + positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. Conclusion Amygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway.

CAS / MDL: 8006-54-0 8002-74-2
研究领域: 药理学 · 免疫学 · 皮肤科
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Frontiers in Pharmacology · 2025 · IF 4.8

Periplaneta americana extract (L.) promotes hair regrowth in Alopecia areata mice by reducing inflammation and modulating skin microbiota

Tangfei Guan,Xin Yang,Canhui Hong,Jiali Zhu,Peiyun Xiao,Yongshou Yang,Chenggui Zhang,Zhengchun He

Introduction: Alopecia areata (AA), an autoimmune hair-loss disease due to follicular inflammatory cell infiltration, lacks an ideal cure. The Periplaneta Americana (PA) extract (PA-011), a traditional Chinese medicine with anti-inflammatory, antioxidant, tissue-repair-promoting, and immune-regulating properties, was studied for its AA-treating effects.Methods: Guided by network pharmacology, AA model mice were treated with PA-011. Hair growth, skin tissue, inflammatory factors, and Wnt protein levels were examined. Transcriptomics, metabolomics, and 16S rRNA sequencing explored the hair-growth-promoting mechanisms.Results: Network pharmacology showed PA-011 could regulate AA-related targets and pathways. PA-011 intervention promoted hair follicle cell proliferation and hair growth in AA mice, reduced skin TNF-α, IL-23, and VCAM-1 expression. Transcriptomics and WB analysis indicated PA-011 downregulated inflammatory genes, activated Wnt3a, and modulated the TGF-β pathway. Metabolomics found PA-011 regulated metabolic pathways. 16S rRNA analysis showed it reversed AA-induced skin microbiota changes, inhibiting pathogens and promoting probiotics. Multi-omics analysis revealed PA-011 regulated skin microbiota and metabolic balance for hair growth.Discussion: In conclusion, PA-011 alleviates AA by reducing skin inflammation and modulating skin microbiota, suggesting its potential as an AA therapeutic.

CAS / MDL: 1313-82-2
研究领域: 药理学 · 皮肤病学 · 免疫学 · 微生物学 · 中医药学 · 系统生物学
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of tofacitinib for treating alopecia areata

Qibin Li,Yameng Wang,Qing Guo,Jie Cao,Yangjun Feng,Xue Ke

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8 + NKG2D + T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.

CAS / MDL: 57-11-4
研究领域: 药剂学 · 皮肤科 · 纳米技术 · 免疫学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Nanoparticle Adjuvants Incorporating Haptens Drive Potent Immune Tolerance to Accelerate Hair Regrowth

Ni An,Guzailinuer Yasen,Ximu Li,Xianbao Shi,Yongjun Wang,Hongzhuo Liu

Alopecia areata (AA) is a prevalent autoimmune condition that causes sudden hair loss and poses significant psychological challenges to affected individuals. Current treatments, including corticosteroids and Janus kinase inhibitors, fail to provide long-term efficacy due to adverse effects and relapse after cessation. This study introduces a nanoparticle (NP) system that codeliver diphenylcyclopropenone (DPCP) and rapamycin (RAPA) prodrugs to induce immune tolerance and promote hair regeneration. The results demonstrated that the coassembled NPs exhibited uniformity and stability, were efficiently taken up by antigen-presenting cells (APCs), and successfully induced dendritic cells (DCs) to differentiate into tolerogenic phenotypes in vitro. In vivo studies on a mouse model of alopecia showed that these NPs significantly accelerated the transition of hair follicles from the telogen phase to the anagen phase, promoting hair regrowth. This research presents a promising therapeutic strategy for AA and offers insights into treating autoimmune diseases where autoantigens are unclear.

研究领域: 免疫学 · 皮肤科 · 药学 · 自身免疫疾病
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Dual-continuous microneedle patch integrating transdermal delivery of pH-sensitive licorzinc MOFs and Zn2+ hydrogel sensors for treating alopecia areata

Hang Ruan,Yuwen Zhong,Huining Ding,Zehui He,Jiaqi Li,Meng Long,Zhi Wang,Qing Xia,Teng Guo,Chunyun Zhu,Tao Yang,Nianping Feng,Yongtai Zhang

Licorzinc is a commonly used immunomodulator, but faces poor water solubility, high oral dose, and side effects of zinc accumulation by long-term administration. Herein, a new licorzincform was developed by adsorbing glycyrrhizic acid (GA) into zeolitic imidazolate framework-8 (GA@ZIF-8) with superior solubility and acid-responsive drug release properties. Then, a dual-continuous microneedle patch was developed for simultaneous transdermal delivery of GA@ZIF-8 and monitoring Zn 2+ in local tissues, where dissolving microneedles as a drug delivery unit were fabricated from hyaluronic acid. In contrast, swollen hydrogel microneedles as a diagnostic unit were prepared from double cross-linking of N-acryloyl-glycinamide and α-methylacrylic acid and hybridized with Eu 3+ and terpyridine (TPy). The microneedles for transdermal GA@ZIF-8 delivery were completely dissolved in 2 min, which improved the cyclophosphamide-induced hair follicle recession in mice by reducing CD8 + NKG2D + T cells infiltration, inhibiting Jak receptor activation, and decreasing IL-15 and IFN-γ. Additionally, as a sensor unit, the microneedles rapidly absorbed water swelled when stabbed into the skin, and fluoresced red when exposed to 365 nm light. Zn 2+ in the inter tissue fluid competes with Eu 3+ in the TPy-Eu 3+ complex and coordinates with Tpy, which triggers a change in fluorescence. Notably, the detection Zn 2+ concentration range was 10 –8 M–10 –1 M, and it was not disturbed by metal ions including Na + , K + , Mg 2+ , and Ca 2+ , suggesting that it is competent to be applied as a real-time chemosensor of Zn 2+ . Collectively, this newly designed system with both therapeutic and diagnostic functions provides a new strategy for treating zinc-related diseases.

研究领域: 药学 · 材料科学 · 生物医学工程 · 皮肤科
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