Nature Communications
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2025
·Vol. 16
·期 1
·1-16
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IF 15.7
Li Yang,Lu Xuteng,Cheng Xufeng,Xia Keyu,Hu Junyan,Wang Peiyu,Pang Peiyuan,Gao Bomin,Sun Demeng,Zhang Zhuzhen,Li Dongdong,Deng Zengqin,Tian Changlin,Xie Chang,Yao Jing
Our skin safeguards the body homeostasis for health and also provides psychological consolation in social life. Natural essential oils are widely used for skin maintenance, while the molecular target and mechanism of action remain largely unknown. Here, we report that citronellal, a plant-derived acyclic monoterpene commonly used for personal care, stimulates skin renewal by promoting keratinocyte proliferation through the activation of TRPV3. We further present cryo-EM structures of human TRPV3 in complex with acyclic monoterpenes, including citronellal, citral, linalool and isodihydrolavandulal, determined at resolutions of 3.1-3.6 Å. Our structural and functional analysis unmasks consistent yet subtly different binding modes within the TRPV3 vanilloid site. Our results elucidate that essential oil ligands activate TRPV3 channels by competitively displacing endogenous lipids from the vanilloid site. Together, these findings identify TRPV3 as the molecular target of natural acyclic monoterpenes for skin renewal, and delineate the structural basis of action, thus being instrumental for moving forward skin healthcare.
研究领域:
生物化学
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结构生物学
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皮肤病学
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PubMed
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Sijia Lu,Quanxin Jiang,Peihui Zhou,Limin Yin,Ning Wang,Junting Xu,Qiqi Qian,Mijia Tao,Hanrui Yin,Liu Han,Yunqing Gu,Fei Gao,Junli Liu,Suzhen Chen
Introduction Promoting adipose thermogenesis is considered as a promising therapeutic intervention in obesity. However, endeavors to develop anti-obesity medications by targeting the canonical thermogenesis regulatory pathway, particularly β3-adrenergic receptor (β3-AR)-dependent mechanism, have failed due to the off-target effects of β3-AR agonists, exacerbating the risk of cardiovascular disease. Hyperforin (HPF), a natural compound extracted from the traditional herbal St. John’s Wort, binds to Dihydrolipoamide s-acetyltransferase (Dlat) and exerts effective anti-obesity properties through promoting adipose thermogenesis. Objectives The objective of this study was to investigate the oral efficacy and pharmacokinetics profile of HPF, and explore the detailed mechanism by which Dlat modulates HPF-mediated adipose thermogenesis. Methods To assess the anti-obesity efficacy of orally administered HPF in vivo , Dlat heterozygous knockout (Dlat +/- ) mice and wild-type (WT) mice, both fed a high-fat diet (HFD), underwent a validation process that involved the use of metabolic cages, NMR analysis, and infrared imaging. Sprague Dawley rats were employed to determine the pharmacokinetic parameters of HPF. Seahorse assays, JC-1 staining, qPCR, and immunoblotting were performed to evaluate cellular thermogenic efficacy of HPF and Dlat in vitro . Results Our study uncovered a non-canonical thermogenesis pathway involving Dlat, transient receptor potential vanilloid 3 (Trpv3, a calcium channel) and AMPK. Dlat interacted with Trpv3 to activate it, resulting in an increase in intracellular calcium (Ca 2+ ) and the activation of Camkkβ. Camkkβ then stimulated AMPK, leading to elevated Ucp1 expression and initiating adipose thermogenesis. HPF promoted thermogenesis in adipose tissues through enhancing the Dlat-Trpv3 interaction independently of β3-AR, causing minimal cardiac side effects. Notably, HPF’s thermogenic effects were reduced in Dlat +/- mice. Moreover, HPF exerted favorable oral bioavailability, a relatively long half-life, and extensive distribution within adipose tissues. Conclusion In summary, our study demonstrates that HPF targets a novel mechanism for promoting adipose thermogenesis and exhibits potent and safe anti-obesity efficacy.
研究领域:
药理学
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分子生物学
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代谢
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 15
·7061
·
IF 5.6
Gang-Ning Tan,Wen-Sheng Zhang,Yu-Sang Li,He-Bin Tang
In traditional Chinese medicine, frankincense is widely recognized for its anti-inflammatory and immunomodulatory capacities and has been conventionally applied to manage multiple chronic inflammatory skin disorders. Nevertheless, its therapeutic potency and molecular mechanisms against atopic dermatitis (AD) remain poorly clarified. This study aimed to explore the protective efficacy of frankincense oil extract (FOE) and its active constituents in AD mouse models, thereby clarifying underlying regulatory mechanisms. Two classic AD models induced by 2,4-dinitrochlorobenzene (DNCB) and carvacrol were established to evaluate the therapeutic performance of FOE and its bioactive components. Hematoxylin–eosin and toluidine blue staining were applied to characterize lesional histopathological alterations, immunohistochemistry was used to detect expression profiles of TRPV3, β-catenin, and COX-2 in skin lesions, and calcium fluorescence imaging was applied to monitor TRPV3-mediated intracellular calcium dynamics. The results showed that FOE markedly alleviated typical AD-like manifestations, reducing inflammatory injury, ear edema and splenomegaly in DNCB- and carvacrol-challenged mice. Histological evaluation confirmed that FOE improved pathological lesions, mitigated epidermal hyperplasia, and reduced mast cell infiltration. Meanwhile, FOE remodeled the abnormal expression patterns of TRPV3, β-catenin, and COX-2 triggered by AD stimulation. Additionally, FOE effectively regulated carvacrol-evoked calcium influx mediated by TRPV3 activation. Collectively, FOE and its active components exert anti-inflammatory effects, restraining epidermal over-proliferation and ameliorating epidermal structural disorders, thereby supporting the restoration of epidermal tissue morphology. Such benefits are attributed to modulating TRPV3 activity and remodeling the cutaneous inflammatory microenvironment. This work highlights FOE as a promising novel candidate for atopic dermatitis intervention.
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