Chaeeun Lee

Can aged Camellia oleifera Abel oil truly be used to treat atopic dermatitis?

Abstract

Xi-Lin Ouyang1, Zhang-Lin Yuan1, Xiao-Bing Chen1, Hong-Wan Gan2, Sen-Hui Guo1, Juan Cai1 and Jing-Jing Zhong2
1Department of Pharmacy, Gannan Healthcare Vocational College, Ganzhou, China, 2Department of
Dermatology, Ganzhou People’s Hospital, Ganzhou, China

Atopic dermatitis is an inflammatory skin condition characterized by erythema,
eruption, lichenification, and pruritus. Aged Camellia oleifera Abel oil, an effective
empirical plant oil utilized by the Gannan Hakka people in China to alleviate the
symptomsofatopicdermatitis.However,noscientificstudieshavebeenreported
to prove whether this oil is truly effective. We conducted this study to confirm
whether aged C. oleifera oil could alleviate the symptoms of 2,4
dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Differences
in the thickness and weight of the right and left ears were measured. ELISA
wasusedtodeterminetheserumlevelsoftheinflammatoryfactorsIL-4,IgE,IFN
γ, and TNF-α. HEstaining was performed to observe inflammatory cell infiltration
in the mouseskinlesions.Inaddition, themetabolitesofagedC.oleiferaoils were
analyzed, and molecular docking was used to assess the binding affinity of the
major metabolites to filaggrin, a protein involved in skin barrier function. Animal
studies showed that aged C. oleifera oil significantly improved the symptoms of
atopic dermatitis. HE staining and measurement of inflammatory factor levels
revealed similar results. A total of 41 metabolites were tentatively identified in the
oil, with fatty acids emerging as the major metabolites. Molecular docking
confirmed that the three most abundant fatty acids, i.e., oleic acid,
n-hexadecanoic acid, and octadecanoic acid, bind well to filaggrin. Our
results suggest that aged C. oleifera oils can be used to ameliorate the
symptoms of atopic dermatitis. Fatty acids may be the major active
metabolites responsible for the observed therapeutic effects by reducing
transdermal water loss, increasing skin hydration, alleviating DNCB-induced
skin barrier alterations, and eliminating itchy scratching caused by dry skin.

Tussilagone inhibits MRGPRX2-mediated mast cell degranulation and suppresses pseudo-allergic reactions

Highlights

• •Tussilagone attenuates Tween 80 and Substance P-induced pseudoallergic reactions.
• •Tussilagone targets the downstream signaling pathway of MRGPRX2.
• •Tussilagone suppresses pseudo-allergic reactions via Lyn-Btk-PLCγ-Ca²⁺ and p38/NF-κB pathways.

Abstract

Mas-related G protein-coupled receptor X2 (MRGPRX2) is a crucial target in pseudo-allergic reactions. Tussilagone (Tus), the main bioactive component derived from Tussilago farfara, has anti-inflammatory effects, but its potential inhibitory effects on pseudo-allergic responses remain unclear. This research aimed to evaluate the inhibitory role of Tus on pseudo-allergic reactions and its underlying mechanism. In vivo Systemic pseudo-allergic reactions and passive cutaneous anaphylaxis (PCA) models were established to assess the effects of Tus. In vitro, mast cell (LAD2) degranulation, inflammatory cytokine release, and signaling pathway protein expression were assessed. Calcium influx was measured in MRGPRX2-expressing HEK293 cells. The results showed that Tus significantly attenuated Tween 80- and substance P (SP)-induced systemic pseudo-allergy and PCA reactions. It also suppressed mast cell degranulation and decreased production of tumor necrosis factor-alpha (TNF-α), Interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1). In MRGPRX2-expressing HEK293 cells, Tus suppressed Tween 80- and SP-induced Ca²⁺ influx. Mechanistically, Tus inhibited tolimidone-induced Lyn kinase activation and suppressed SP-and Tween 80-induced β-hexosaminidase release, exhibiting an inhibitory profile comparable to that of the Lyn/Btk antagonist bosutinib. Additionally, Tus attenuated the phosphorylation levels of MRGPRX2 downstream signal molecules, including Btk, PLCγ1, PKC, p38 MAPK, IκB-α and NF-κB (p65). In conclusion, Tus attenuates SP-and Tween 80-induced mast cell activation and pseudo-allergic reactions by targeting the Lyn/Btk/PLCγ1 and p38/NF-κB pathways, highlighting its therapeutic potential for pseudo-allergy.

Keywords

pseudo-allergic reactions; Tussilagone; Mast cell; Lyn; MRGPRX2

https://doi.org/10.1016/j.taap.2026.117763

Oxidative stress induced TSLP production via TRPV4 regulates type 2 inflammation and pruritus in MC903 induced atopic dermatitis mouse model

Author links open overlay panelKeiji Kosaka ^a, Akihiko Uchiyama ^a, Yuta Inoue ^a, Mai Ishikawa ^a, Takeshi Araki ^a, Shintaro Saito ^a, Akiko Sekiguchi ^a, Yoko Yokoyama ^a, Sachiko Ogino ^a, Ryoko Torii ^a, Yuki Watanuki ^a, Sei-ichiro Motegi ^a

^aDepartment of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan^bLaboratory of Neurochemistry, Department of Nutrition Science, University of Nagasaki, Nagasaki, Japan

Received 3 September 2025, Revised 4 December 2025, Accepted 28 January 2026, Available online 31 January 2026.

Abstract

Background

Transient receptor potential vanilloid 4 (TRPV4) is a calcium ion channel that is widely expressed in various cells, and it regulates multiple physiological and pathological processes. In skin, TRPV4 senses temperature, mechanical and chemical stimuli. Although TRPV4 has been shown to regulate inflammatory in psoriasis, its role in atopic dermatitis (AD) remains unclear.

Objective

We aimed to elucidate the role of TRPV4 is AD pathogenesis and its potential as therapeutic target.

Methods

We used human skin samples from healthy and patients with AD for immunostaining. TRPV4 knock out (KO) mice and MC903-induced AD mouse models were used in vivo. HaCaT cells were used in vitro.

Results

TRPV4 was highly expressed in keratinocytes in lesional skin site of AD. TRPV4 KO mice had less severe dermatitis, barrier dysfunction and pruritus than WT mice in MC903-treated mouse model. TRPV4 KO mice had significantly decreased mRNA expression of type 2 inflammatory cytokines, including TSLP, interleukin (IL)-4, IL-13, and IL-31 via qPCR, and reduced protein levels of TSLP and IL-4 by ELISA. In vitro, oxidative stress promoted expression and activation of TRPV4, following enhanced TSLP expression in HaCaT cells. However, stimulation with IL-4 and IL-13 inhibited TRPV4 activation in HaCaT cells. Finally, treatment with selective TRPV4 antagonist HC-067047 significantly reduced the severity of MC903-induced AD-like dermatitis.

Conclusion

Our findings showed that TRPV4 mediates the expression of keratinocyte-derived TSLP and increases Th2 immunity and pruritus, highlighting TRPV4 as a novel therapeutic strategy for the treatment of AD.

Key words

Atopic dermatitis, Th2, TRPV4, TSLP, Keratinocyte

Azelaic acid potentiates TRPV3 activity as a mechanism for skin irritation

Diwas Rawal ^{1 2}, Wook-Joo Lee ^{1 2}, Won-Sik Shim ^{1 2*}

¹College of Pharmacy, Gachon University, Incheon, Republic of Korea ²Gachon Institute of Pharmaceutical Sciences, Incheon, Republic of Korea

*Corresponding author e-mail: wsshim@gachon.ac.kr

https://doi.org/10.1016/j.jid.2026.01.022

Palmitic acid aggravates atopic dermatitis by regulating SGK1/NEDD4L-involved cutaneous neuroimmune inflammation throughdriving TRPV1 and MRGPRB2 S-palmitoylation

Abstract

Objective To determine how cutaneous palmitic acid (PA) modulates transient receptor potential vanilloid-1(TRPV1) in
nociceptor and dorsal-root-ganglions (DRGs), and Mas-related G protein-coupled receptor B2 (MRGPRB2) in mast cells
(MCs), and to investigate their associations with serum- and glucocorticoid-regulated kinase-1 (SGK1)/neural precursor cell
expressed developmentally down regulated 4-like (NEDD4L) in atopic dermatitis (AD).
Methods AD was induced in mice with nedd4l or sgk1 conditional knock-out(cKO) in nociceptor, mrgprb2, nedd4l, or sgk1
cKO in MCs. Intradermal PA, substance P(SP), or pan-palmitoylation inhibitor 2BP was administered. Isolated DRGs and
mouse bone-marrow-derived-MCs (mBMMCs) were used.
Results Cutaneous PA levels were increased in AD mice.PA intradermal injection promoted a TRPV1+ nociceptor-SP-MCs
MRGPRB2-tryptase-AD axis. nedd4l cKO in nociceptor up-regulated cutaneous SP expression, which was further enhanced
by PA. sgk1 cKO in nociceptor slightly reduced SP levels, which were further decreased by PA or 2BP. SP levels in mice with
nedd4l or sgk1 cKO in MCs were increased by PA. In DRGs, supernatants from MC903-treated keratinocytes induced SGK1
and NEDD4L phosphorylation, TRPV1 S-palmitoylation, and SP production, all of which were up-regulated by PA; total and
S-palmitoylated TRPV1 levels and SP production were increased following nedd4l knockdown, whereas they were slightly
reduced following sgk1 knockdown and further decreased by PA. SP induced weak phosphorylation of SGK1 and NEDD4L
in MCs. SP induced MRGPRB2 S-palmitoylation and tryptase release in wild-type, nedd4l or sgk1 knock-out MCs, and these
effects were enhanced by PA; 2BP caused MRGPRB2 reduction in wild-type and sgk1 knock-out MCs.
Conclusions The increased cutaneous PA exacerbates AD by promoting TRPV1 S-palmitoylation and SP production in nociceptor,
followed by MRGPRB2 S-palmitoylation and tryptase release in MCs. S-palmitoylation promotes TRPV1 whereas
inhibits MRGPRB2 reduction via lysosome when NEDD4L and its upstream SGK1 are not phosphorylated.

Keywords

S-palmitoylation · Palmitic acid · Atopic dermatitis · TRPV1 · MRGPRB2 · NEDD4L

Mast cell–expressed Mrgprb2/MRGPRX2
mediates gout pain and inflammation via
a neuroimmune axis

Dongyee Kim

Neuronal pentraxin 2 in peripheral sensory neurons drives chronic itch through potentiation of the interleukin-31/interleukin-31 receptor pathway in atopic dermatitis

Xue-Qiang Bai ^{a b 1}, Bing-Xin Wu ^{a 1}, Ji-An Wang ^{c 1}, Cheng He ^a, Yong-Liang Shen ^d, Xiao Wei ^a, Yu-Qi Zhang ^a, Xue-Wen Chen ^c, Rong Sun ^a, Qun-Feng Gui ^d, Juan Wang ^a,  Zhi-Jun Zhang ^{a e}

Keywords
Pruritus; NPTX2; Interleukin-31; Trigeminal ganglion; Atopic dermatitis

Abstract

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin conditions, primarily characterized by intense itching that leads to scratching and presents a challenging clinical issue with incompletely understood mechanisms. Neuronal pentraxin 2 (NPTX2) is associated with neurodevelopment, synaptic plasticity, and neuroinflammation in the central nervous system. In this study, we aimed to thoroughly investigate the peripheral role of NPTX2 in mediating chronic itch in AD. Real-time polymerase chain reaction (PCR), immunohistochemistry, ELISA assays, western blot, and small interfering RNA (siRNA) intervention were performed to explore the peripheral role of NPTX2 in an AD model. We demonstrated that NPTX2 was selectively upregulated in small- and medium-sized trigeminal ganglion (TG) neurons in the MC903-induced AD model, and was transported to peripheral nerve terminals. Importantly, protein expression of NPTX2 was significantly elevated in the skin nerves of patients with AD. Notably, NPTX2 administration alone, intradermally, provoked moderate scratching behavior in mice. However, Nptx2 and neuronal pentraxin receptor (NPTXR) siRNA intra-TG injection significantly attenuated scratching behaviors in AD mice. Critically, NPTXR, its cognate receptor, was specifically localized to pruriceptive calcitonin gene–related peptide-positive neurons (CGRP⁺) and isolectin B4 (IB4⁺) neuronal subsets. Mechanistically, NPTX2 synergizes with interleukin-31 (IL-31), a well-known pruritic cytokine in AD, to potentiate phosphorylated-extracellular signal-regulated kinase (p-ERK) signaling in primary sensory neurons. PD98059, the inhibitor of p-ERK, significantly alleviated the scratching induced by the combination of NPTX2 and IL-31. Additionally, PD98059 also significantly reduced the upregulation and release of NPTX2 caused by IL-31 stimulation. Our results offer a new understanding of the molecular mechanisms underlying chronic pruritus in the MC903-induced AD model, highlighting NPTX2-dependent signaling as a key therapeutic strategy for refractory itch disorders.

https://doi.org/10.1016/j.intimp.2026.116223

Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice

Hyoung-Gon Ko^1,2,  Hyunsu Jung^#3,4,  Seunghyo Han^#5,  Dong Il Choi^#4,  Chiwoo Lee^#4,  Ja Eun Choi⁴,  Jihae Oh⁴,  Chuljung Kwak³,  Dae Hee Han³,  Jun-Nyeong Kim⁵,  Sanghyun Ye⁴,  Jiah Lee⁴,  Jaehyun Lee⁴,  Kyungmin Lee⁶,  Jae-Hyung Lee⁷,  Min Zhuo^8,9 &  Bong-Kiun Kaang^10,11

¹Department of Anatomy and Neurobiology, School of Dentistry, Brain Science and Engineering Institute, Kyungpook National University, 2177 Dalgubeol-daero, Daegu, South Korea. hgko@khu.ac.kr.²Department of Oral Anatomy and Developmental Biology, Kyung Hee University College of Dentistry, Seoul, South Korea. hgko@khu.ac.kr.³Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, 34126, South Korea.⁴Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Seoul, South Korea.⁵Department of Anatomy and Neurobiology, School of Dentistry, Brain Science and Engineering Institute, Kyungpook National University, 2177 Dalgubeol-daero, Daegu, South Korea.⁶Laboratory for Behavioral Neural Circuitry and Physiology, Department of Anatomy, Brain Science and Engineering Institute, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Daegu, South Korea.⁷Department of Oral Microbiology, College of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Seoul, South Korea.⁸Department of Physiology, Faculty of Medicine, University of Toronto, 1 King’s College Circle, Toronto, Ontario, Canada.⁹International Institute for Brain Research, Qingdao International Academician Park, Qingdao, China.¹⁰Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, 34126, South Korea. kaang@ibs.re.kr.¹¹Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Seoul, South Korea. kaang@ibs.re.kr.^#Contributed equally.

• PMID: 40038260
• PMCID: PMC11880300
• DOI: 10.1038/s41467-025-57041-z

Abstract

Pain and itch are aversive sensations with distinct qualities, processed in overlapping pathways and brain regions, including the anterior cingulate cortex (ACC), which is critical for their affective dimensions. However, the cellular mechanisms underlying their processing in the ACC remain unclear. Here, we identify modality-specific neuronal populations in layer II/III of the ACC in mice involved in pain and itch processing. Using a synapse labeling tool, we show that pain- and itch-related neurons selectively receive synaptic inputs from mediodorsal thalamic neurons activated by pain and itch stimuli, respectively. Chemogenetic inhibition of these neurons reduced pruriception or nociception without affecting the opposite modality. Conversely, activation of these neurons did not enhance stimulus-specific responses but commonly increased freezing-like behavior. These findings reveal that the processing of itch and pain information in the ACC involves activity-dependent and modality-specific neuronal populations, and that pain and itch are processed by functionally distinct ACC neuronal subsets.