Introduction: The functions of S1P receptors have been revealed using genetic and pharmacological tools, including the potent non-selective modulator FTY720. However, studies on subtype-specific agonists and antagonists are limited; hence, the role of S1P4 remains unclear. Objectives: To identify a novel function of S1P4 as a pathogenic factor in stroke using a newly developed S1P4-selective modulator and S1P4 knockdown. Methods: Heteroaromatic analogs of FTY720 were synthesized, a β-arrestin assay was conducted against S1P receptors, and the developed compound (NXC736) was characterized as a functional S1P4 antagonist. To clarify the function of S1P4, the therapeutic potential of NXC736 in ischemic stroke was determined using a transient middle cerebral artery occlusion (tMCAO) mouse model, which was validated using S1P4 knockdown. The S1P4-dependent pathogenic mechanisms were determined using immunohistochemical and biochemical analyses. Results: Molecular modeling studies provide valuable clues for understanding S1P4 selectivity of NXC736. NXC736 contains a triazole ring instead of a phenyl ring and exhibits S1P4-selective activity as a functional antagonist. Its action on S1P4 does not require phosphorylation by sphingosine kinase 2. Notably, NXC736 exhibited substantial therapeutic activity against ischemic stroke by attenuating tMCAO-induced acute brain injuries, including brain infarction, neurological deficits, and neuronal apoptosis. This suggested that S1P4 is a pathogenic factor in ischemic stroke. This function was confirmed using AAV-based S1P4 knockdown. NXC736 or S1P4 knockdown attenuated blood–brain barrier disruption, neutrophil infiltration, microglial activation and proliferation, and the upregulation of pro-inflammatory cytokines, thereby demonstrating that S1P4 influences neuroinflammatory responses in ischemic stroke. The underlying mechanisms were activation of NLRP3 inflammasome, NF-κB, and MAPKs. S1P4 also contributed to chronic brain injuries caused by ischemic stroke because NXC736 exerted long-term neuroprotective effects against tMCAO challenge. Conclusion: Using a functional S1P4 antagonist (NXC736) and a genetic tool for S1P4 knockdown, we identified S1P4 as a novel pathogenic factor in ischemic stroke.

Background/Objectives: Effectively targeting treatment-resistant tumor cells, particularly cancer stem cells (CSCs) involved in tumor recurrence, remains a major challenge in immunotherapy. This study examines the potential of combining mechanical high-intensity focused ultrasound (M-HIFU) with dendritic cell (DC) vaccines to enhance immune responses against OLFM4-expressing tumors, a CSC marker linked to immune evasion and tumor growth. Methods: M-HIFU was applied to induce immunogenic cell death by mechanically disrupting tumor cells, releasing tumor-associated antigens and creating an immunostimulatory environment. DC vaccines loaded with OLFM4 were then administered to boost the immune response within this primed environment. Results: The combination of M-HIFU and DC vaccine significantly inhibited tumor growth and metastasis, with enhanced T-cell activation and increased recruitment of immune cells due to elevated chemokines CCL19 and CCL21. This synergy promoted immune memory, reducing the likelihood of recurrence. Conclusions: M-HIFU effectively promotes the migration of DC vaccines through CCL19/21, presenting a promising approach for cancer treatment. Further studies are recommended to optimize this combination for clinical applications, with potential to improve patient outcomes in challenging cancer types.

Stroke is the leading cause of death and long-term disability worldwide, with ischemic stroke accounting for nearly 87% of all cases. Vascular occlusion, a key pathological event in ischemic stroke, has been reliably reproduced in preclinical studies using permanent ischemic stroke models. This study demonstrated the neuroprotective effect of NXC736, a functional antagonist of sphingosine-1-phosphate receptor 4 (S1P4, currently in phase II clinical trials for alopecia areata), against acute injury in mice with permanent middle cerebral artery occlusion (pMCAO). pMCAO-challenged mice received oral NXC736 1 h after occlusion. NXC736 demonstrated substantial therapeutic activity against permanent ischemic stroke by attenuating pMCAO-induced acute brain infarction, neurological deficits, and apoptosis. Additionally, NXC736 reduced blood–brain barrier disruption and edema in the injured brain. Moreover, NXC736 reduced microglial activation and proliferation, oxidative stress, and suppressed pro-inflammatory cytokine expression, suggesting that the efficacy of NXC736 in permanent ischemic stroke is associated with the suppression of neuroinflammatory responses. Mechanistically, we found that NXC736-mediated neuroprotective effects were dependent on the inactivation of NF-κB and MAPKs, including ERK1/2, JNK, and p38. Collectively, our findings indicate that NXC736 is an effective neuroprotective drug for permanent ischemic brain stroke, highlighting S1P4 as a promising therapeutic target for ischemic stroke.

Inhalation toxicity assessment is a crucial tool for the identification and classification of hazardous materials like volatile organic carbons, aerosols, and particulate matter. Unlike traditional acute inhalation toxicity studies that use mortality as an endpoint, the Fixed Concentration Procedure (FCP) emphasizes "evident toxicity" by monitoring behavior, weight, and food intake. This reduces reliance on mortality but doesn't directly address respiratory system impact. The present study introduced a respirometer-based inhalation toxicity and respiratory status assessment method. The toxicity evaluation system integrated a respirometric system with an animal exposure chamber, enabling real-time monitoring of oxygen consumption. The ICR mice were exposed to various concentrations of benzene (10, 20, 40, and 80 mg/L of air), toluene (7.5, 15, 30, and 60 mg/L of air), and xylene (7.5, 15, 30, and 60 mg/L of air). The respiration rate decreased by 70 % and 69 % for benzene (80 mg/L of air) and toluene (60 mg/L of air), respectively, with EC50 values of 32.5 mg/l and 21.2 mg/L based on oxygen consumption. Xylene did not exhibit EC50 values at the tested concentrations. However, the oxygen consumption rate significantly decreased (46 %) at high concentrations (60 mg/L of air), indicating sub-lethal toxicological effects. Furthermore, the present study was also validated in the bleomycin-induced idiopathic pulmonary fibrosis (IPF) model, demonstrating its reliability as a respiratory impairment marker. The results exhibited a strong correlation between weight loss and less oxygen consumption in the BLM group (bleomycin-induced) as compared to the SHAM group (control), which was confirmed by histological examination and protein marker analysis. The results suggest the potential use of oxygen consumption as an endpoint measurement in inhalation toxicity assessment tests without animal sacrifice, and the present study could be useful for providing valuable insights into disease progression and pharmacological interventions.

Lysophosphatidic acid receptor 1 (LPA1) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA1 could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA1 antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood -brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro -inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF -KB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA1-dependent pathogenesis. Collectively, these results demonstrate that LPA1 can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.

Compared to other organs, the brain has limited antioxidant defenses. In particular, the hippocampus is the central region for learning and memory and is highly susceptible to oxidative stress. Glial cells are the most abundant cells in the brain, and sustained glial cell activation is critical to the neuroinflammation that aggravates neuropathology and neurotoxicity. Therefore, regulating glial cell activation is a promising neurotherapeutic treatment. Quinic acid (QA) and its derivatives possess anti -oxidant and anti-inflammatory properties. Although previous studies have evidenced QA's benefit on the brain, in vivo and in vitro analyses of its anti -oxidant and anti-inflammatory properties in glial cells have yet to be established. This study investigated QA's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment. Orally administering QA restored social impairment and LPS-induced spatial and fear memory. In addition, QA inhibited proinflammatory mediator, oxidative stress marker, and mitogen-activated protein kinase (MAPK) activation in the LPS-injected hippocampus. QA inhibited nitrite release and extracellular signal -regulated kinase (ERK) phosphorylation in LPS-stimulated astrocytes. Collectively, QA restored impaired neuroinflammation-induced behavior by regulating proinflammatory mediator and ERK activation in astrocytes, demonstrating its potential as a therapeutic agent for neuroinflammation-induced brain disease treatments.

Naturally occurring homoisoflavonoids isolated from some Liliaceae plants have been reported to have diverse biological activities (e.g., antioxidant, anti-inflammatory, and anti-angiogenic effects). The exact mechanism by which homoisoflavonones exert anti-neuroinflammatory effects against activated microglia-induced inflammatory cascades has not been well studied. Here, we aimed to explore the mechanism of homoisoflavonoid SH66 having a potential anti-inflammatory effect in lipopolysaccharide (LPS)-primed BV2 murine microglial cells. Microglia cells were pre-treated with SH66 followed by LPS (100 ng/mL) activation. SH66 treatment attenuated the production of inflammatory mediators, including nitric oxide and proinflammatory cytokines, by down-regulating mitogen-activated protein kinase signaling in LPS-activated microglia. The SH66-mediated inhibition of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex and the respective inflammatory biomarker-like active interleukin (IL)-1β were noted to be one of the key pathways of the anti-inflammatory effect. In addition, SH66 increased the neurite length in the N2a neuronal cell and the level of nerve growth factor in the C6 astrocyte cell. Our results demonstrated the anti-neuroinflammatory effect of SH66 against LPS-activated microglia-mediated inflammatory events by down-regulating the NLRP3 inflammasome complex, with respect to its neuroprotective effect. SH66 could be an interesting candidate for further research and development regarding prophylactics and therapeutics for inflammation-mediated neurological complications.

Cancer stem cells (CSCs) can self-renew and differentiate, contributing to tumor heterogeneity, metastasis, and recurrence. Their resistance to therapies, including immunotherapy, underscores the importance of targeting them for complete remission and relapse prevention. Olfactomedin 4 (OLFM4), a marker associated with various cancers such as colorectal cancer, is expressed on CSCs promoting immune evasion and tumorigenesis. However, its potential as a target for CSC-specific immunotherapy remains underexplored. The primary aim of this study is to evaluate the effectiveness of targeting OLFM4 with dendritic cell (DC)-based vaccines in inhibiting tumor growth and metastasis. To improve antigen delivery and immune response, OLFM4 was conjugated with a protein-transduction domain (PTD) from the antennapedia of Drosophila called penetratin, creating a fusion protein (P-OLFM4). The efficacy of DCs pulsed with P-OLFM4 (DCs [P-OLFM4]) was compared to DCs pulsed with OLFM4 (DCs [OLFM4]) and PBS (DCs [PBS]). DCs [P-OLFM4] inhibited tumor growth by 91.2 % and significantly reduced lung metastasis of OLFM4+ melanoma cells by 97 %, compared to the DCs [PBS]. DCs [OLFM4] also demonstrated a reduction in lung metastasis by 59.7 % compared to DCs [PBS]. Immunization with DCs [P-OLFM4] enhanced OLFM4-specific T-cell proliferation, interferon-γ production, and cytotoxic T cell activity in mice. The results indicate that OLFM4 is a viable target for CSC-focused immunotherapy. DC [P-OLFM4] vaccines can elicit robust immune responses, significantly inhibiting tumor growth and metastasis. This strategy holds promise for developing more effective cancer treatments that specifically target CSCs, potentially leading to better patient outcomes by reducing the likelihood of tumor relapse and metastasis.

The NLRP3 inflammasome is upregulated by various agents, such as nuclear factor-kappa B (NF-κB), lipopolysaccharide (LPS), and adenosine triphosphate (ATP). The NLRP3 inflammasome facilitations the maturation of interleukin (IL)-1β, a proinflammatory cytokine that is critically involved in the pathogenesis of atopic dermatitis (AD). Although the NLRP3 inflammasome clearly exacerbates AD symptoms such as erythema and pruritus, drugs for AD patients targeting the NLRP3 inflammasome are still lacking. Based on the previous findings that Mentha arvensis essential oil (MAEO) possesses strong anti-inflammatory and anti-AD properties through its inhibition of the ERK/NF-κB signaling pathway, we postulated that MAEO might be capable of modulating the NLRP3 inflammasome in AD. The aim of this research was to investigate whether MAEO affects the inhibition of NLRP3 inflammasome activation in murine bone marrow-derived macrophages (BMDMs) stimulated with LPS + ATP in vitro and in a murine model displaying AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in vivo. We found that MAEO inhibited the expression of NLRP3 and caspase-1, leading to the suppression of NLRP3 inflammasome activation and IL-1β production in BMDMs stimulated with LPS + ATP. In addition, MAEO exhibited efficacy in ameliorating AD symptoms in a murine model induced by DNCB, as indicated by the reduction in dermatitis score, ear thickness, transepidermal water loss (TEWL), epidermal thickness, and immunoglobulin E (IgE) levels. Furthermore, MAEO attenuated the recruitment of NLRP3-expressing macrophages and NLRP3 inflammasome activation in murine dorsal skin lesions induced by DNCB. Overall, we provide evidence for the anti-AD effects of MAEO via inhibition of NLRP3 inflammasome activation.

Stroke is a major global health problem that causes significant mortality and long-term disability. Post-stroke neurological impairment is a complication that is often underestimated with the risk of persistent neurological deficits. Although traditional Chinese medicines have a long history of being used for stroke, their scientific efficacy remains unclear. Scutellaria baicalensis, an herbal component known for its anti-inflammatory and antioxidant properties, has traditionally been used to treat brain disorders. This study investigated the therapeutic effects of the Scutellaria baicalensis extraction (SB) during the acute stage of ischemic stroke using photothrombotic (PTB)-induced and transient middle cerebral artery occlusion (tMCAO) model mice. We found that SB mitigated ischemic brain injury, as evidenced by a significant reduction in the modified neurological severity score in the acute stage of PTB and both the acute and chronic stages of tMCAO. Furthermore, we elucidated the regulatory role of SB in the necroptosis and pyroptosis pathways during the acute stage of stroke, underscoring its protective effects. Behavioral assessments demonstrated the effectiveness of SB in ameliorating motor dysfunction and cognitive impairment compared to the group receiving the vehicle. Our findings highlight the potential of SB as a promising therapeutic candidate for stroke. SB was found to help modulate the programmed cell death pathways, promote neuroprotection, and facilitate functional recovery.

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addi-tion, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

Memory-enhancing agents have long been required for various reasons such as for obtaining a good score in a test in the young and for retaining memory in the aged. Although many studies have found that several natural products may be good candidates for memory enhancement, there is still a need for better agents. The present study investigated whether rubrofusarin, an active ingredient in Cassiae semen, enhances learning and memory in normal mice. Passive avoidance and Morris water maze tests were performed to determine the memory-enhancing ability of rubrofusarin. To investigate synaptic function, hippocampal long-term potentiation (LTP) was measured. Western blotting was performed to determine protein levels. To investigate neurite outgrowth, DCX immunohistochemistry and cell culture were utilised. Rubrofusarin (1, 3, 10, 30 mg/kg) enhanced memory in passive avoidance and Morris water maze tests. Moreover, rubrofusarin ameliorated scopolamine-induced memory impairment. In the rubrofusarin-treated group, high-frequency stimulation induced higher LTP in the hippocampal Schaffer-collateral pathway compared to the control group. The rubrofusarin-treated group showed a higher number of DCX-positive immature neurons with an increase in the length of dendrites compared to the control group in the hippocampal dentate gyrus region. In vitro experiments showed that rubrofusarin facilitated neurite outgrowth in neuro2a cells through extracellular signal-regulated kinase (ERK). Finally, we found that extracellular signal-regulated kinase (ERK) is required for rubrofusarin-induced enhancement of neurite outgrowth, learning and memory. These results demonstrate that rubrofusarin enhances learning and memory and neurite outgrowth, and these might need activation of ERK pathway.

Ischemia-reperfusion injury (IRI) is a process in which damage is induced in hypoxic tissue when oxygen supply is resumed after ischemia. During IRI, restoration of reduced nitric oxide (NO) levels may alleviate reperfusion injury in ischemic organs. The protective mechanism of NO is due to anti-inflammatory effects, antioxidant effects, and the regulation of cell signaling pathways. On the other hand, it is generally known that S-nitrosylation (SNO) mediates the detrimental or protective effect of NO depending on the action of the nitrosylated target protein, and this is also applied in the IRI process. In this review, the effect of each change of NO and SNO during the IRI process was investigated.

BACKGROUND & AIMS:Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear.METHODS:We investigated which type of S1PR isoforms is activated in various murine models of NASH. The mechanism of action of S1PR4 was examined in hepatic macrophages isolated from high-fat, high-cholesterol diet (HFHCD)-fed mice. We developed a selective S1PR4 functional antagonist by screening the fingolimod (2-amino-2-[2-(4- n -octylphenyl)ethyl]-1,3- propanediol hydrochloride)-like sphingolipid-focused library.RESULTS:The livers of various mouse models of NASH as well as hepatic macrophages showed high expression of S1pr4. Moreover, in a cohort of NASH patients, expression of S1PR4 was 6-fold higher than those of healthy controls. S1pr4+/- mice were protected from HFHCD-induced NASH and hepatic fibrosis without changes in steatosis. S1pr4 depletion in hepatic macrophages inhibited lipopolysaccharide-mediated Ca++ release and deactivated the Nod-like receptor pyrin domain-containning protein 3 (NLRP3) inflammasome. S1P increased the expression of S1pr4 in hepatic macrophages and activated NLRP3 inflammasome through inositol trisphosphate/inositol trisphosphate-receptor-dependent [Ca++] signaling. To further clarify the biological function of S1PR4, we developed SLB736, a novel selective functional antagonist of SIPR4. Similar to S1pr4+/- mice, administration of SLB736 to HFHCD-fed mice prevented the development of NASH and hepatic fibrosis, but not steatosis, by deactivating the NLRP3 inflammasome.CONCLUSIONS:S1PR4 may be a new therapeutic target for NASH that mediates the activation of NLRP3 inflammasome in hepatic macrophages.

Terpenoids are widely distributed in nature, especially in the plant kingdom, and exhibit diverse pharmacological activities. In recent years, screening has revealed a wide variety of new terpenoids that are active against different psychiatric disorders. This review synthesized the current published preclinical studies of terpenoid use in psychiatric disorders. This review was extensively investigated to provide empirical evidence regarding the neuropharmacological effects of the vast group of terpenoids in translational models of psychiatric disorders, their relevant mechanisms of action, and treatment regimens with evidence of the safety and psychotropic efficacy. Therefore, we utilized nine (9) electronic databases and performed manual searches of each. The relevant data were retrieved from the articles published until present. We used the search terms "terpenoids" or "terpenes" and "psychiatric disorders" ("psychiatric disorders" OR "psychiatric diseases" OR "neuropsychiatric disorders" OR "psychosis" OR "psychiatric symptoms"). The efficacy of terpenoids or biosynthetic compounds in the terpenoid group was demonstrated in preclinical animal studies. Ginsenosides, bacosides, oleanolic acid, asiatic acid, boswellic acid, mono- and diterpenes, and different forms of saponins and triterpenoids were found to be important bioactive compounds in several preclinical studies of psychosis. Taken together, the findings of the present review indicate that natural terpenoids and their derivatives could achieve remarkable success as an alternative therapeutic option for alleviating the core or associated behavioral features of psychiatric disorders.

Breast cancer has a high risk of recurrence and distant metastasis after remission. Controlling distant metastasis is important for reducing breast cancer mortality, but accomplishing this goal remains elusive. In this study, we investigated the molecular pathways underlying metastasis using cells that mimic the breast cancer distant metastasis process. HCC1143 breast cancer cells were cultured under two-dimensional (2D)-adherent, tumor sphere (TS), and reattached (ReA) culture conditions to mimic primary tumors, circulating tumor cells, and metastasized tumors, respectively. ReA cells demonstrated increased TS formation and enhanced invasion capacity compared to the original 2D-cultured parental cells. In addition, ReA cells had a higher frequency of ESA+CD44+CD24− population, which represents a stem-cell-like cell population. RNA sequencing identified the cholesterol synthesis pathway as one of the most significantly increased pathways in TS and ReA cells compared to parental cells, which was verified by measuring intracellular cholesterol levels. Furthermore, the pharmacological inhibition of the cholesterol synthesis pathway decreased the ability of cancer cells to form TSs and invade. Our results suggest that the cholesterol synthesis pathway plays an important role in the distant metastasis of breast cancer cells by augmenting TS formation and invasion capacity.

Abnormal and excessive nitrosative stress contributes to neurodegenerative disease associated with the production of pathological levels of misfolded proteins. The accumulated findings strongly suggest that excessive NO production can induce and deepen these pathological processes, particularly by the S-nitrosylation of target proteins. Therefore, the relationship between S-nitrosylated proteins and the accumulation of misfolded proteins was reviewed. We particularly focused on the S-nitrosylation of E3-ubiquitin-protein ligase, parkin, and endoplasmic reticulum chaperone, PDI, which contribute to the accumulation of misfolded proteins. In addition to the target proteins being S-nitrosylated, NOS, which produces NO, and GSNOR, which inhibits S-nitrosylation, were also suggested as potential therapeutic targets for protein misfolding-associated diseases.

The mechanism of atopic dermatitis (AD) is modulated by the release of cytokines and chemokines through the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Topical steroids are used to treat AD, but some people need safer anti-inflammatory drugs to avoid side effects. Mentha arvensis has been used as a herbal plant with medicinal properties, but its anti-inflammatory effects have not been elucidated in an AD model. In this study, we investigated the anti-inflammatory effects of M. arvensis essential oil (MAEO) and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and HaCaT cells (human epidermal keratinocyte). Additionally, we examined the ameliorating effects of the MAEO in a dinitrochlorobenzene (DNCB)-induced murine model of AD. We found, in both RAW 264.7 cells and HaCaT cells, MAEO inhibited LPS-stimulated inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 and proinflammatory cytokines, including IL-1β and IL-6, due to the suppression of COX-2 and iNOS expression. In LPS-stimulated macrophages, we also observed that MAEO inhibited the phosphorylation of ERK and P65. Furthermore, MAEO treatment attenuated AD symptoms, including the dermatitis score, ear thickness, epidermal thickness and infiltration of mast cells, in a DNCB-induced animal model of AD. Overall, our findings suggest that MAEO exerts anti-inflammatory and anti-atopic dermatitis effects via inhibition of the ERK/NF-κB signaling pathway.