Suspension culture is superior to planar culture in efficiently growing large numbers of cells. It also greatly improves cell functions by mimicking the in vivo environment. Although several methods are available to diff...Suspension culture is superior to planar culture in efficiently growing large numbers of cells. It also greatly improves cell functions by mimicking the in vivo environment. Although several methods are available to differentiate human induced pluripotent stem (iPS) cells into hepatocyte-like cells, their differentiation by suspension culture by using functional polymers remains unreported. We developed a suspension culture system using the functional polymers FP001 and FP003 to generate hepatocyte-like cells with superior phenotypes than human iPS cell-derived hepatocyte-like cells generated in planar culture. Specifically, optimizing the initial spheroid size and utilizing FP003 effectively maintained appropriate spheroid structures, resulting in higher albumin production compared to FP001. In 3D sphere culture, the mRNA expression of albumin (ALB), drug-metabolizing enzymes and transporters, and the activity of CYP1A2 were increased in the presence of 0.01% FP003. Additionally, immunofluorescence analysis confirmed uniform hepatic differentiation throughout the spheroids. These findings suggest that differentiation in 3D sphere culture with the functional polymer FP003 improved the function of human iPS cell-derived hepatocyte-like cells. Therefore, we conclude that this system may be an effective strategy to generate human iPS cell-derived hepatocyte-like cells with enhanced functions.
We investigated effects of rice-memolin on neural oscillations in the medial prefrontal cortex (mPFC) during sleep in mice. Spectral analysis revealed that rice-memolin treatment significantly attenuated theta power in t...We investigated effects of rice-memolin on neural oscillations in the medial prefrontal cortex (mPFC) during sleep in mice. Spectral analysis revealed that rice-memolin treatment significantly attenuated theta power in the mPFC during rapid eye movement (REM) sleep. Furthermore, the power of beta and high gamma oscillations was significantly attenuated in the mPFC during non-REM sleep. Cardiac and autonomic functions remained unchanged. These findings suggest that rice-memolin modulates cortical network dynamics via specific oscillatory bands, potentially affecting local and global information processing underlying its procognitive properties.
The TGF-β/Smad signaling pathway plays a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and is modulated by sphingolipid metabolism. Ceramide, a key intermediate in this pathway, is synthesized i...The TGF-β/Smad signaling pathway plays a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and is modulated by sphingolipid metabolism. Ceramide, a key intermediate in this pathway, is synthesized in various acyl-CoA chain lengths by ceramide synthases (CerS). However, the specific role of ceramide synthase 5 (CerS5) in pulmonary fibrosis remains unclear. Therefore, this study aimed to elucidate the role of CerS5 in fibrotic responses using human lung fibroblasts (HFL1), IPF-derived myofibroblasts (IPF-MyoFs), and a bleomycin-induced mouse model of pulmonary fibrosis. CerS5 knockdown attenuated TGF-β1-induced expression of α-smooth muscle actin (αSMA), collagen I, fibronectin, and phosphorylated Smad2/3 in both HFL1 cells and IPF-MyoFs. It also suppressed TGF-β1-induced nuclear translocation of Smad2/3. Notably, CerS5 knockdown reduced protein levels of Smad3 and Smad4 even in the absence of TGF-β1 stimulation. Smad4 knockdown replicated the effects of CerS5 knockdown by decreasing TGF-β1-induced expression of fibrotic markers, phosphorylated Smad2/3, and total Smad3 levels. In vivo, CerS5 knockout significantly reduced bleomycin-induced lung fibrosis and Smad3/4 expression. These findings suggest that CerS5 regulates fibrotic responses via modulation of Smad4 and the TGF-β1/Smad signaling pathway. Targeting CerS5 may therefore represent a promising therapeutic strategy for the treatment of IPF.
Melatonin is a pineal hormone that regulates circadian rhythms primarily through melatonin receptors. We recently demonstrated that melatonin inhibits the voltage-gated potassium K4.2 channel (IC = 479 μM) through a mela...Melatonin is a pineal hormone that regulates circadian rhythms primarily through melatonin receptors. We recently demonstrated that melatonin inhibits the voltage-gated potassium K4.2 channel (IC = 479 μM) through a melatonin receptor-independent mechanism. However, it remains unclear whether this inhibitory effect is specific to melatonin or shared by structurally related compounds. In the present study, we examined the effects of melatonin-related compounds on K4.2 channels using human embryonic kidney 293 cells stably expressing K4.2 channels. Whole-cell patch-clamp recordings showed that luzindole, a melatonin receptor antagonist, inhibited K4.2 currents (IC = 33 μM). Notably, ramelteon, a melatonin receptor agonist, also inhibited K4.2 currents (IC = 177 μM). These results indicate that the inhibitory effects of luzindole and ramelteon are mediated by direct interactions with K4.2 channels rather than through melatonin receptors. In addition, luzindole inhibited K1.5 channels. In contrast, melatonin biosynthetic precursors failed to inhibit K4.2 currents, suggesting that the indole or indole-like structural motif alone is insufficient for K4.2 channel inhibition. Instead, specific structural features, including the methoxy group in melatonin and the furan ring in ramelteon, together with increased hydrophobicity, may be critical determinants of K4.2 channel blockade. Collectively, these findings reveal previously unrecognized pharmacological properties of melatonin-related compounds.
This study evaluated glyoxal fixation for whole-brain serial section imaging using the FAST (block-face serial microscopy tomography) system. Glyoxal-fixed mouse brains exhibited slight shrinkage compared with paraformal...This study evaluated glyoxal fixation for whole-brain serial section imaging using the FAST (block-face serial microscopy tomography) system. Glyoxal-fixed mouse brains exhibited slight shrinkage compared with paraformaldehyde-fixed brains but showed no appreciable variations over time. Notably, glyoxal provided an ∼11-fold higher autofluorescence, facilitating precise focal plane identification and high-contrast label-free structural imaging. We observed that 4 days of fixation ensured tissue rigidity for smooth sectioning and intact section retrieval. Furthermore, the application of an autofluorescence quenching reagent enabled clear post hoc c-Fos immunostaining. Thus, glyoxal fixation is a powerful tool for multiscale label-free 3D brain mapping.
Sepsis, a life-threatening disorder driven by a dysregulated host response to infection, is frequently accompanied by acute lung injury (ALI), worsening disease severity, and mortality. Excessive macrophage-mediated infl...Sepsis, a life-threatening disorder driven by a dysregulated host response to infection, is frequently accompanied by acute lung injury (ALI), worsening disease severity, and mortality. Excessive macrophage-mediated inflammation is central to its pathogenesis. Given emerging evidence that mitochondria-endoplasmic reticulum (ER) crosstalk drives inflammatory injury, we investigated whether modulating this interaction could mitigate sepsis-induced damage. Using LPS-stimulated THP-1 macrophages and a murine model of LPS-induced sepsis, we evaluated the anti-inflammatory and organ-protective effects of dendrobine, a bioactive alkaloid from Dendrobium nobile Lindl. Dendrobine suppressed glycolysis-induced mitochondria-ER crosstalk, thereby reducing macrophage-driven inflammation and tissue injury. In vivo, dendrobine lowered circulating interleukin (IL)-1β and IL-18 levels and alleviated ALI. Mechanistically, dendrobine decreased reactive oxygen species production and mitochondrial DNA (mtDNA) release, leading to downregulation of NLRP3 and cleaved caspase-1. These effects stemmed from inhibition of hypoxia-inducible factor-1α (HIF-1α) and hexokinase 2 (HK2)-mediated glycolysis, preventing HK2 dissociation from voltage-dependent anion channel 1 (VDAC1) and disrupting IP3R-GRP75-VDAC1 complex formation. Collectively, these findings demonstrate that dendrobine protects against sepsis-induced organ injury by targeting the IP3R-GRP75-VDAC1-HK2 axis in macrophages, highlighting its therapeutic potential for sepsis.
Vascular cognitive impairment (VCI) comprises cognitive dysfunction caused by vascular pathology and is associated with various forms of dementia. VCI is typically caused by chronic cerebral hypoperfusion (CCH), which is...Vascular cognitive impairment (VCI) comprises cognitive dysfunction caused by vascular pathology and is associated with various forms of dementia. VCI is typically caused by chronic cerebral hypoperfusion (CCH), which is accompanied by oxidative stress, central nervous system inflammation, microglial activation, and white matter injury. Therapeutic targets for VCI remain largely unknown. Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in the brain, where it senses changes in oxygen levels and is activated by hypoxia and hyperoxia. We investigated the pathophysiological roles of TRPA1 stimulation during late-stage CCH that was induced using bilateral common carotid artery stenosis (BCAS) in a mouse model of VCI. Cinnamaldehyde-induced TRPA1 stimulation improved CCH-induced white matter injury and cognitive impairment. However, cinnamaldehyde failed to improve CCH-related outcomes in astrocyte-specific TRPA1-deficient mice, which indicated that the protective effects of cinnamaldehyde are mediated by astrocytic TRPA1. The administration of cinnamaldehyde suppressed the CCH-induced increase in Iba1-positive microglia. These results suggest that the activation of astrocytic TRPA1 by cinnamaldehyde contributes to disease amelioration in advanced stages of VCI, potentially through astrocyte-derived factors, including leukemia inhibitory factor, IL6 family cytokines, and other mediators, that suppress microglial activation.
Pericytes are multifunctional mural cells that contribute to vascular stability, inflammation, and fibrosis in the central nervous system. Phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PK...Pericytes are multifunctional mural cells that contribute to vascular stability, inflammation, and fibrosis in the central nervous system. Phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), is widely used to induce cellular activation and inflammatory responses in various cell types. In this study, we investigated how PMA affects human brain pericyte phenotypes and gene expression. PMA stimulation increased Bromodeoxyuridine (BrdU) incorporation in cultured human brain pericytes, but did not alter migration capacity. Phalloidin staining revealed an altered aspect ratio without changes in cell area. Traction force microscopy showed no significant differences in traction stress after PMA treatment. RNA sequencing analysis revealed robust transcriptional changes, particularly in pathways associated with proliferation, mechanical stimulus response, and inflammation. These findings suggest that PKC contributes to diverse pericyte functions, including proliferation, mechanical responses, and inflammation, through transcriptomic changes.
Animals must balance reward seeking against potential danger, and impairments in such conflict decision-making are common in psychiatric disorders. Here, we examined how chronic corticosterone exposure and ketamine affec...Animals must balance reward seeking against potential danger, and impairments in such conflict decision-making are common in psychiatric disorders. Here, we examined how chronic corticosterone exposure and ketamine affect conflict behavior in mice by presenting them with a three-compartment conflict task. Three weeks of corticosterone increased conflict levels without inducing anhedonia, selectively prolonging action initiation. Ketamine reduced conflict in control mice but not in corticosterone-treated mice, indicating that stress abolishes its anticonflict effect. These findings suggest that chronic stress biases conflict-related behavior and disrupts ketamine-responsive mechanisms.
Acetylcholine-mediated modulation of pain-associated behaviors has been progressively well described. The mechanisms of cholinergic antinociception have been reported to involve the activation of nAChRs or mAChRs modulat...Acetylcholine-mediated modulation of pain-associated behaviors has been progressively well described. The mechanisms of cholinergic antinociception have been reported to involve the activation of nAChRs or mAChRs modulating GABAergic and/or glycinergic inhibitory transmissions. However, the functional activity of cholinesterase in pain signaling, which catabolizes ACh to choline, is not well established. We found that ACh increased the frequency and amplitude of spontaneous IPSCs in the presence of the cholinesterase inhibitor neostigmine in the rat substantia gelatinosa of the spinal trigeminal nucleus caudalis. In the absence of neostigmine, even a high concentration of ACh had no significant effect on the frequency of IPSCs. The non-hydrolysable agonist muscarine, but not nicotine, significantly increased IPSC frequency in the absence of neostigmine. The increase in IPSC frequency with ACh was blocked by strychnine, atropine, or tetrodotoxin. These results suggest that activation of the mAChR increases glycine receptor-mediated IPSC frequency in a manner dependent on an action potential generation, only when the activity of cholinesterase is inhibited by neostigmine in the substantia gelatinosa of the spinal trigeminal nucleus caudalis. The inhibition of ACh breakdown by a cholinesterase inhibitor might be important for producing analgesia through the cholinergic modulations of the nociceptive network. (200 words).
Spinocerebellar ataxia type 34 (SCA34) is an autosomal dominant neurodegenerative disease primarily characterized by progressive cerebellar atrophy and ataxia, frequently accompanied by cognitive dysfunction and erythrok...Spinocerebellar ataxia type 34 (SCA34) is an autosomal dominant neurodegenerative disease primarily characterized by progressive cerebellar atrophy and ataxia, frequently accompanied by cognitive dysfunction and erythrokeratodermia variabilis. SCA34 is caused by missense mutations of elongation of very long chain fatty acids protein 4 (ELOVL4). To investigate its pathogenesis, we established an SCA34 mouse model by expressing mutant ELOVL4 in cerebellar neurons using adeno-associated virus vectors. Expression of W246G mutant ELOVL4 successfully induced progressive motor dysfunction beginning at two weeks post-injection. Immunohistochemical analyses revealed that the loss of cerebellar Purkinje cells and neurons in the deep cerebellar nuclei (DCN) paralleled the observed motor decline. Importantly, microglial activation was detected in the molecular layer of the cerebellar cortices and the DCN prior to the loss of cerebellar neurons and the onset of motor dysfunction. Furthermore, after the onset of motor symptoms, the SCA34 model mice exhibited decreased expression of presynaptic proteins in climbing fibers to Purkinje cells, as well as disturbance of innervation from Purkinje cells to DCN neurons. These findings suggest that early microglial activation and the resulting synaptic disturbance are critical preceding events that lead to the progressive cerebellar neurodegeneration and motor dysfunction observed in this SCA34 mouse model.
The orexin system has been demonstrated to play various physiological roles, such as in feeding, sleep, and autonomic neural function. Clinically, orexin receptor antagonists are used as hypnotics, and several clinical t...The orexin system has been demonstrated to play various physiological roles, such as in feeding, sleep, and autonomic neural function. Clinically, orexin receptor antagonists are used as hypnotics, and several clinical trials have suggested their efficacy in major depressive disorder. We investigated the orexin system using juvenile-stressed (3-week foot shock) rats, an animal model of depression. 3-week foot shock rats had significantly reduced prepro-orexin mRNA in the hypothalamus, but not orexin A protein or orexin A -like immunoreactive cells. In contrast, orexin receptor type 1 mRNA and its protein were significantly increased in the dorsal hippocampus, suggesting that some abnormality in orexin neurotransmission in this region due to 3wFS led to changes in orexin receptor type 1. Microinjection of a selective orexin receptor type 1 antagonist, SB334867, and a selective orexin receptor type 2 antagonist, TCS OX2 29, into the dorsal hippocampus in naïve rats reduced depressive-like behaviors, suggesting that the hippocampus is a target brain site for the antidepressant effects of orexin receptor antagonists. Furthermore, 3-week foot shock rats showed a slight enhancement of the hypothalamus-pituitary-adrenal axis, a decrease in daily variations in body temperature, and increased behavioral activity.
Vascular calcification (VC) is a major complication of type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Myricetin, a natural flavonoid with reported cardiovascular protective properti...Vascular calcification (VC) is a major complication of type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Myricetin, a natural flavonoid with reported cardiovascular protective properties, has not been fully evaluated in the context of diabetic VC. In this study, the effects of myricetin were examined in vascular smooth muscle cells (VSMCs) exposed to hyperglycemic and phosphate (Pi) conditions in vitro. Myricetin attenuated calcification in VSMCs under hyperglycemic/Pi conditions. It decreased the expression of osteogenic markers RUNX2 and BMP-2, while restoring the expression of contractile markers α-SMA and SM22-α. Myricetin also reduced inflammatory responses, as indicated by decreased interleukin-6 mRNA and NLRP3 protein expression. In addition, myricetin reduced oxidative stress by lowering intracellular reactive oxygen species and malondialdehyde levels, decreasing the Fe/Fe ratio, and increasing the GSH/GSSG ratio. Furthermore, myricetin restored the expression of ferroptosis-related regulators, including SLC7A11, GPX4, and FTH1, which were reduced under hyperglycemic/Pi conditions. The protective effects of myricetin were partially reversed by ferroptosis inducers, suggesting the involvement of ferroptosis-related mechanisms. Collectively, these findings suggest that myricetin may inhibit vascular calcification in vitro and has therapeutic potential for diabetic vascular complications.
Hallucinogens, such as lysergic acid diethylamide, act primarily through the 5-hydroxytryptamine 2A (5-HT2A) receptor, but their regulatory mechanisms remain unclear. G protein-coupled receptor 143 (GPR143), an L-3,4-dih...Hallucinogens, such as lysergic acid diethylamide, act primarily through the 5-hydroxytryptamine 2A (5-HT2A) receptor, but their regulatory mechanisms remain unclear. G protein-coupled receptor 143 (GPR143), an L-3,4-dihydroxyphenylalanine (L-DOPA) receptor, modulates specific GPCRs. We examined the role of GPR143 in the action of 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). DOI-induced hyperlocomotion and c-Fos expression in the nucleus accumbens were enhanced in GPR143 knockout mice. In Chinese hamster ovary cells expressing 5-HT2A receptor, DOI-induced extracellular signal-regulated kinase phosphorylation was suppressed by co-expression of GPR143. These findings suggest that GPR143 negatively regulates 5-HT2A receptor signaling and attenuates behavioral responses to hallucinogens.
Pulmonary hypertension (PH) still requires both elucidation of pathological mechanisms and development of new treatment agents. We previously reported that an intraperitoneal administration of minocycline prevented monoc...Pulmonary hypertension (PH) still requires both elucidation of pathological mechanisms and development of new treatment agents. We previously reported that an intraperitoneal administration of minocycline prevented monocrotaline-induced PH in rats. However, the direct vasodilatory effects of minocycline on isolated pulmonary artery are unclear. We then investigated them in rat isolated intrapulmonary arteries (IPAs). In both endothelium-intact and -denuded IPAs, minocycline (10 μg/ml) inhibited endothelin-1 (40 nM)- or high-K (72.7 mM)-induced precontraction. In endothelium-intact IPAs, indomethacin (10 μM) significantly inhibited the relaxation. We revealed for the first time that minocycline indues vasodilation through both endothelium-dependent and -independent mechanisms in isolated IPAs.
During the past quarter century, a series of global pandemics-caused by coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and influenza A (H1N1, H5N1)-has underscored that viral infection is not merely a transient invasion...During the past quarter century, a series of global pandemics-caused by coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and influenza A (H1N1, H5N1)-has underscored that viral infection is not merely a transient invasion but a systemic and temporal perturbation of the host life system. My research has sought to elucidate the principles by which the host organism senses, integrates, and regulates responses to viral stress, spanning molecular to organismal levels. Key discoveries include the identification of ACE2 as the functional receptor for SARS-CoV and a critical regulator of disease severity; elucidation of innate-immune overactivation ("cytokine storm") as a driver of fatal pathology; identification of lipid-mediated RNA regulation that restrains excessive inflammation; and discovery of neuro-immune and epigenetic mechanisms linking acute infection to long-term dysfunction. These findings reveal infection as a multi-layered biological reprogramming process involving immunity, metabolism, the nervous system, and chromatin architecture. Building on this mechanistic foundation, we established data-driven infrastructures-AI-assisted predictive models and Medical MLOps systems-that integrate clinical and molecular data for personalized infection medicine. This perspective summarizes the evolution of this integrative research and discusses future directions toward precision therapeutics for acute and post-infectious syndromes.
Citrate plays a crucial role in preventing calcium stone formation by chelating calcium and inhibiting crystal aggregation. Organic anion transporters (OATs), expressed in renal proximal tubules, mediate the transport of...Citrate plays a crucial role in preventing calcium stone formation by chelating calcium and inhibiting crystal aggregation. Organic anion transporters (OATs), expressed in renal proximal tubules, mediate the transport of various organic anions, including drugs. However, whether OATs transport citrate and oxalate-key metabolites involved in urinary stone formation-remains unclear. This study aimed to determine whether OATs contribute to citrate and oxalate transport and to clarify their underlying mechanisms. Uptake experiments were conducted using S2 cells stably expressing human OAT1, OAT3, or OAT4. Substrate uptake was measured using radiolabeled compounds, and [C]citrate uptake was evaluated for time and concentration dependence, and inhibition by various compounds. OAT4, localized to the apical membrane, exhibited significantly increased [C]citrate uptake under acidic conditions (pH 6.0), whereas OAT1 and OAT3 showed minimal pH dependence. OAT4-mediated citrate uptake increased in a time-dependent manner and showed biphasic kinetics. Citrate transport was unaffected by endogenous dicarboxylates but inhibited by diuretics and nonsteroidal anti-inflammatory drugs. These findings identify OAT4 as a novel citrate transporter. Enhanced OAT4 activity under acidic conditions may promote citrate reabsorption, thereby increasing the risk of calcium stone formation. Targeting OAT4 with specific inhibitors could represent a new therapeutic strategy for preventing urinary stone recurrence.
Fatigue represents a significant health concern. Chronic fatigue may contribute to mental health disorders and accelerated aging. Oxidative stress, characterized by excessive production of reactive oxygen species, is gen...Fatigue represents a significant health concern. Chronic fatigue may contribute to mental health disorders and accelerated aging. Oxidative stress, characterized by excessive production of reactive oxygen species, is generally considered to increase during physical exertion and to indicate fatigue. Although antioxidants are known to enhance endurance, effects of sea cucumber (SC) on physical fatigue remain undetermined and were explored in this study. We investigated the effects of SC on alterations in locomotor activity and expression levels of silent mating type information regulation 2 homolog peroxisome 1 (Sirt1), nuclear factor erythroid 2-related factor 2 (NRF2), and antioxidative-related proteins, including superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1), and catalase, in the soleus muscle following SC administration before and/or after forced walking. Administration of SC before and after forced walking, rather than at a single time point, mitigated the subsequent decrease in locomotor activity and enhanced expression of Sirt1, NRF2, SOD1, GPx1 and catalase in the soleus muscle of mice. In contrast, EX-527, the selective Sirt1 inhibitor, abolished the SC-induced anti-fatigue effect and the enhanced Sirt1/NRF2/SOD1-GPx1-catalase pathway in the soleus muscle. Consequently, we propose that SC attenuates fatigue by modulating the Sirt1/NRF2/SOD1-GPx1-catalase pathway in the soleus muscle.
This study evaluated the anti-rhinitic effects of ONO-6950, a novel dual antagonist of cysteinyl leukotriene 1 (CysLT) and 2 (CysLT) receptors, in guinea pig models of allergic rhinitis. First, in a conventional allergic...This study evaluated the anti-rhinitic effects of ONO-6950, a novel dual antagonist of cysteinyl leukotriene 1 (CysLT) and 2 (CysLT) receptors, in guinea pig models of allergic rhinitis. First, in a conventional allergic rhinitis model without S-hexyl glutathione (S-hexyl GSH), both ONO-6950 (3 mg/kg, orally (p.o.)) and montelukast (0.3, 1, or 3 mg/kg, p.o.), a selective CysLT antagonist, significantly suppressed the increases in nasal airway resistance and inflammatory cell infiltration induced by ovalbumin (OVA) challenge, with comparable efficacy. Subsequently, in a model with S-hexyl GSH treatment to inhibit LTC metabolism and enhance CysLT receptor-mediated responses, ONO-6950 (0.3, 1, or 3 mg/kg, p.o.) dose-dependently and almost completely inhibited both immediate and late increases in nasal airway resistance and inflammatory cell infiltration, whereas montelukast showed only partial or negligible inhibition. These results indicate that ONO-6950 is effective against both CysLT-and CysLT-mediated rhinitic responses, and may offer a novel therapeutic option for patients with allergic rhinitis, particularly in cases refractory to CysLT-selective antagonists.
BACKGROUND: Lycium ruthenicum (black goji berry) is rich in anthocyanins and proanthocyanidins with potent antioxidant and anti-inflammatory activities. This study evaluated whether Mongolian L. ruthenicum (LR) extract m...BACKGROUND: Lycium ruthenicum (black goji berry) is rich in anthocyanins and proanthocyanidins with potent antioxidant and anti-inflammatory activities. This study evaluated whether Mongolian L. ruthenicum (LR) extract modulates age-related allergic inflammation in murine models. METHODS: Female C57BL/6N mice received Mongolian LR extract (4 mg/mL in drinking water) under long-term (73 weeks) or short-term (4 weeks) regimens. Allergic asthma and allergic contact dermatitis (ACD) were induced by Dermatophagoides farinae extract and toluene-2,4-diisocyanate, respectively. Immune cell subsets, cytokine production, serum IgE levels, and histopathology were analyzed by flow cytometry, ELISA, and qPCR. RESULTS: Chronic LR administration significantly attenuated Th2-type inflammation in aged mice with asthma or ACD. In the asthma model, LR reduced perivascular lung inflammation, decreased interleukin (IL)-4, IL-5, and IL-13 secretion from lymph node cells, and decreased the numbers of CD4 effector/memory T cells, dendritic cells, and IgE B cells. In the ACD model, LR alleviated epidermal ulceration and reduced serum IgE levels. In contrast, short-term administration at either young or old age produced minimal effects. CONCLUSIONS: Prolonged intake of Mongolian L. ruthenicum extract suppressed age-associated Th2-skewed allergic inflammation without disturbing immune homeostasis. These findings suggest that sustained LR supplementation may counteract immunosenescence and help maintain immune balance during aging.