Free radical biology & medicine · 2026
Ginkgolide B-loaded detachable microneedles attenuate androgenetic alopecia by suppressing endoplasmic reticulum stress via the Nrf2/HO-1 pathway.
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Wang Zhan, Zheng Cheng, Li Wenzhen, Kyaw Kaung Myat, Zhu Yunmin, Lin Yihan, Lin Zhen, Wu Di, Hu Zhiqi, Sun Yang, Li Kaitao
Аннотация
INTRODUCTION: Androgenetic alopecia (AGA), the most common form of hair loss, lacks ideal therapies due to the limitations of current drugs. Natural compounds with low toxicity and good biocompatibility present promising alternatives. Ginkgolide B (GB), a bioactive component of Ginkgo biloba, possesses multiple biological activities, yet its efficacy and mechanism against AGA remain unexplored.
OBJECTIVES: This study aimed to investigate the hair growth-promoting effect of GB in a dihydrotestosterone (DHT)-induced hair loss model and to elucidate the underlying molecular mechanism. Additionally, a novel detachable microneedle delivery system was developed and evaluated to overcome GB's poor transdermal permeability, thereby enhancing its therapeutic efficacy.
METHODS: The AGA microenvironment was first simulated using DHT-stimulated human dermal papilla cells (HDPCs) in vitro. The molecular mechanism by which GB improves the secretory function of HDPCs was investigated through network pharmacology, western blot, transmission electron microscopy, and immunofluorescence. Subsequently, a detachable microneedle system was designed, in which GB was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres and integrated with the sulfobutylether-β-cyclodextrin (SCD)-based matrix (GB@MS-MN). The therapeutic efficacy of this system was evaluated in a DHT-induced hair loss model.
RESULTS: GB rescued DHT-induced dysfunction in HDPCs, reversing the aberrant secretion of hepatocyte growth factor (HGF) and dickkopf-1 (DKK1). Mechanistically, GB alleviated DHT-induced endoplasmic reticulum stress (ERS) in HDPCs by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. And GB promoted hair growth in DHT-induced hair loss mice. The GB@MS-MN system demonstrated excellent mechanical properties and targeted follicular delivery and showed superior hair growth promotion compared to free GB and minoxidil. It effectively suppressed follicular ERS, with no observed systemic toxicity.
CONCLUSION: In summary, this study confirms that GB protects HDPCs function by suppressing DHT-induced ERS through activation of the Nrf2/HO-1 pathway. Furthermore, a detachable microneedle delivery system based on a PLGA-SCD composite effectively overcomes the transdermal barrier of GB and demonstrates superior hair-promoting efficacy.
OBJECTIVES: This study aimed to investigate the hair growth-promoting effect of GB in a dihydrotestosterone (DHT)-induced hair loss model and to elucidate the underlying molecular mechanism. Additionally, a novel detachable microneedle delivery system was developed and evaluated to overcome GB's poor transdermal permeability, thereby enhancing its therapeutic efficacy.
METHODS: The AGA microenvironment was first simulated using DHT-stimulated human dermal papilla cells (HDPCs) in vitro. The molecular mechanism by which GB improves the secretory function of HDPCs was investigated through network pharmacology, western blot, transmission electron microscopy, and immunofluorescence. Subsequently, a detachable microneedle system was designed, in which GB was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres and integrated with the sulfobutylether-β-cyclodextrin (SCD)-based matrix (GB@MS-MN). The therapeutic efficacy of this system was evaluated in a DHT-induced hair loss model.
RESULTS: GB rescued DHT-induced dysfunction in HDPCs, reversing the aberrant secretion of hepatocyte growth factor (HGF) and dickkopf-1 (DKK1). Mechanistically, GB alleviated DHT-induced endoplasmic reticulum stress (ERS) in HDPCs by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. And GB promoted hair growth in DHT-induced hair loss mice. The GB@MS-MN system demonstrated excellent mechanical properties and targeted follicular delivery and showed superior hair growth promotion compared to free GB and minoxidil. It effectively suppressed follicular ERS, with no observed systemic toxicity.
CONCLUSION: In summary, this study confirms that GB protects HDPCs function by suppressing DHT-induced ERS through activation of the Nrf2/HO-1 pathway. Furthermore, a detachable microneedle delivery system based on a PLGA-SCD composite effectively overcomes the transdermal barrier of GB and demonstrates superior hair-promoting efficacy.