Redundant role of OsCNGC4 and OsCNGC5 encoding cyclic nucleotide-gated channels in rice pollen germination and tube growth.

In staple crops, such as rice (Oryza sativa L.), pollen plays a crucial role in seed production. However, the molecular mechanisms underlying rice pollen germination and tube growth remain underexplored. Notably, we recently uncovered the redundant expression and mutual interaction of two rice genes encoding cyclic nucleotide-gated channels (CNGCs), OsCNGC4 and OsCNGC5, in mature pollen. Building on these findings, the current study focused on clarifying the functional roles of these two genes in pollen germination and tube growth. To overcome functional redundancy, we produced gene-edited rice plants with mutations in both genes using the CRISPR-Cas9 system. The resulting homozygous OsCNGC4 and OsCNGC5 gene-edited mutants (oscngc4/5) exhibited significantly lower pollen germination rates than the wild type (WT), along with severely reduced fertility. Transcriptome analysis of the double oscngc4/5 mutant revealed downregulation of genes related to receptor kinases, transporters, and cell wall metabolism. To identify the direct regulators of OsCNGC4, which form a heterodimer with OsCNGC5, we screened a yeast two-hybrid library containing rice cDNAs from mature anthers. Subsequently, we identified two calmodulin isoforms (CaM1-1 and CaM1-2), NETWORKED 2 A (NET2A), and proline-rich extension-like receptor kinase 13 (PERK13) proteins as interactors of OsCNGC4, suggesting its roles in regulating Ca2+ channel activity and F-actin organization. Overall, our results suggest that OsCNGC4 and OsCNGC5 may play critical roles in pollen germination and elongation by regulating the Ca2+ gradient in growing pollen tubes.

Enhancing viability and angiogenic efficacy of mesenchymal stem cells via HSP90α and HSP27 regulation based on ROS stimulation for wound healing.

Light-based therapy has been reported as a potential preconditioning strategy to induce intracellular reactive oxygen species (ROS) signaling and improve the angiogenic properties of various types of cells. However, bio-stimulation mechanisms of light therapy in terms of ROS-heat shock proteins (HSPs) mediated anti-apoptotic and angiogenic pathways in human adult stem cells have not been fully delineated yet. Commonly used light sources such as light-emitting diode (LED) and laser are accompanied by drawbacks, such as phototoxicity, thermal damage, and excessive ROS induction, so the role and clinical implications of light-induced HSPs need to be investigated using a heat-independent light source. Here, we introduced organic LED (OLED) at 610 nm wavelength as a new light source to prevent thermal effects from interfering with the expression of HSPs. Our results showed that light therapy using OLED significantly upregulated anti-apoptotic and angiogenic factors in human bone marrow mesenchymal stem cells (hMSCs) at both gene and protein levels via the activation of HSP90α and HSP27, which were stimulated by ROS. In a mouse wound-closing model, rapid recovery and improved re-epithelization were observed in the light-treated hMSCs transplant group. This study demonstrates that the upregulation of Akt (protein kinase B)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, caused by HSP90α and HSP27 expression, is the mechanism behind the anti-apoptotic and angiogenic effects of OLED treatment on stem cells.

Molecular Characteristics of Catalytic Nitrogen Removal from Coal Tar Pitch over γ-Alumina-Supported NiMo and CoMo Catalysts.

The removal of nitrogen from coal tar pitch (CTP) through the hydrodenitrogenation (HDN) of CTP and its molecular behavior were evaluated in the presence of NiMo/γ-alumina and CoMo/γ-alumina catalysts. Fourier transform ion cyclotron resonance mass spectrometry with atmospheric pressure photoionization was used to analyze the complicated chemical classes and species of CTP and the treated products at the molecular level. Nitrogen species were qualitatively analyzed before and after hydrotreatment. A single-stage hydrotreatment with an HDN catalyst resulted in a high sulfur removal performance (85.6-94.7%) but a low nitrogen removal performance (26.8-29.2%). Based on relative abundance analyses of nitrogen and binary nitrogen species, CcHh-NnSs was the most challenging species to remove during HDN treatment. Furthermore, prior hydrodesulfurization was combined with HDN treatment, and the dual hydrotreatments yielded a significantly improved nitrogen removal performance (46.4-48.7%).

Rice pollen-specific OsRALF17 and OsRALF19 are essential for pollen tube growth.

Pollen tube growth is essential for successful double fertilization, which is critical for grain yield in crop plants. Rapid alkalinization factors (RALFs) function as ligands for signal transduction during fertilization. However, functional studies on RALF in monocot plants are lacking. Herein, we functionally characterized two pollen-specific RALFs in rice (Oryza sativa) using multiple clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9-induced loss-of-function mutants, peptide treatment, expression analyses, and tag reporter lines. Among the 41 RALF members in rice, OsRALF17 was specifically expressed at the highest level in pollen and pollen tubes. Exogenously applied OsRALF17 or OsRALF19 peptide inhibited pollen tube germination and elongation at high concentrations but enhanced tube elongation at low concentrations, indicating growth regulation. Double mutants of OsRALF17 and OsRALF19 (ralf17/19) exhibited almost full male sterility with defects in pollen hydration, germination, and tube elongation, which was partially recovered by exogenous treatment with OsRALF17 peptide. This study revealed that two partially functionally redundant OsRALF17 and OsRALF19 bind to Oryza sativa male-gene transfer defective 2 (OsMTD2) and transmit reactive oxygen species signals for pollen tube germination and integrity maintenance in rice. Transcriptomic analysis confirmed their common downstream genes, in osmtd2 and ralf17/19. This study provides new insights into the role of RALF, expanding our knowledge of the biological role of RALF in regulating rice fertilization.

Proteomic Analysis Reveals a Critical Role of the Glycosyl Hydrolase 17 Protein in Panax ginseng Leaves under Salt Stress.

Ginseng, an important crop in East Asia, exhibits multiple medicinal and nutritional benefits because of the presence of ginsenosides. On the other hand, the ginseng yield is severely affected by abiotic stressors, particularly salinity, which reduces yield and quality. Therefore, efforts are needed to improve the ginseng yield during salinity stress, but salinity stress-induced changes in ginseng are poorly understood, particularly at the proteome-wide level. In this study, we report the comparative proteome profiles of ginseng leaves at four different time points (mock, 24, 72, and 96 h) using a label-free quantitative proteome approach. Of the 2484 proteins identified, 468 were salt-responsive. In particular, glycosyl hydrolase 17 (PgGH17), catalase-peroxidase 2, voltage-gated potassium channel subunit beta-2, fructose-1,6-bisphosphatase class 1, and chlorophyll a-b binding protein accumulated in ginseng leaves in response to salt stress. The heterologous expression of PgGH17 in Arabidopsis thaliana improved the salt tolerance of transgenic lines without compromising plant growth. Overall, this study uncovers the salt-induced changes in ginseng leaves at the proteome level and highlights the critical role of PgGH17 in salt stress tolerance in ginseng.

Multiple low-dose radiation-induced neuronal cysteine transporter expression and oxidative stress are rescued by N-acetylcysteine in neuronal SH-SY5Y cells.

Recently, several studies have demonstrated that low-dose radiation (LDR) therapy has positively impacts on the treatment of Alzheimer's disease (AD). LDR suppresses the production of pro-neuroinflammation molecules and improves cognitive function in AD. However, it is unclear whether direct exposure to LDR causes beneficial effects and what mechanism is involved in neuronal cells. In this study, we first determined the effect of high-dose radiation (HDR) alone on C6 cells and SH-SY5Y cells. We found that SH-SY5Y cells were more vulnerable than C6 cells to HDR. Moreover, in neuronal SH-SY5Y cells exposed to single or multiple LDR, N-type cells showed decreased cell viability with increasing radiation exposure time and frequency, but S-type cells were unaffected. Multiple LDR increased proapoptotic molecules such as p53, Bax and cleaved caspase-3, and decreased anti-apoptotic molecule (Bcl2). Multiple LDR also generated free radicals in neuronal SH-SY5Y cells. We detected a change in the expression of the neuronal cysteine transporter EAAC1. Pretreatment with N-acetylcysteine (NAC) rescued the increased in EAAC1 expression and the generation of ROS in neuronal SH-SY5Y cells after multiple LDR. Furthermore, we verified whether the increased in EAAC1 expression induces cell defense or cell death promotion signaling. We showed that transient overexpression of EAAC1 reduced the multiple LDR-induced p53 overexpression in neuronal SH-SY5Y cells. Our results indicate that neuronal cells can be injured by increased production of ROS not only by HDR but also by multiple LDR, which suggests that combination treatment with anti-free radical agents such as NAC may be useful in multiple LDR therapy.

Effect of A. polygama APEE (Actinidia polygama ethanol extract) or APWE (Actinidia polygama water extract) on wrinkle formation in UVB-irradiated hairless mice.

BACKGROUND: Actinidia polygama (silver vine) is considered a medical plant which has been used in oriental medicine. It has been used for the treatment of pain, gout, rheumatoid arthritis, and inflammation. Few studies reported on the effect of Actinidia polygama (silver vine) on skin photoaging. OBJECTIVE: To evaluate the anti-photoaging effect of the ethanol and water extracts of A. polygama (APEE and APWE, respectively) in UVB-irradiated hairless mice. METHODS: SKH-1 hairless mice were exposed to UVB irradiation (30-60 mJ/cm2 ), following orally APEE or APWE oral administration for 10 weeks. We examined the effect on winkle improvement by a measuring Fullscope, PRIMOS, Craniometer, and Cutometer. Furthermore, we analyzed histological changes in mouse dorsal skin through hematoxylin and eosin (H&E) and Masson's trichrome (MT) staining. The expression of matrix metalloproteinase (1, 3, and 9) was analyzed by immunoblotting. RESULTS: Oral administration of APEE or APWE at 100 or 200 mg/kg in UVB-irradiated mice alleviated the symptoms of skin aging, such as wrinkling, epidermal hyperplasia, and water loss. In addition, the APEE or APWE oral administration increased skin elasticity by enhancing the production of type I collagen, elastin, and hyaluronic acid synthase and downregulating matrix metalloproteinase (1, 3, and 9) expression. CONCLUSION: Based on results for our study, APEE or APWE could protect the UVB-mediated skin wrinkle and is new target for the developing anti-wrinkle cosmetics.

Phytochemistry of ginsenosides: Recent advancements and emerging roles.

Ginsenosides, a group of tetracyclic saponins, accounts for the nutraceutical and pharmaceutical relevance of the ginseng (Panax sp.) herb. Owing to the associated therapeutic potential of ginsenosides, their demand has been increased significantly in the last two decades. However, a slow growth cycle, low seed production, and long generation time of ginseng have created a gap between the demand and supply of ginsenosides. The biosynthesis of ginsenosides involves an intricate network of pathways with multiple oxidation and glycosylation reactions. However, the exact functions of some of the associated genes/proteins are still not completely deciphered. Moreover, ginsenoside estimation and extraction using analytical techniques are not feasible with high efficiency. The present review is a step forward in recapitulating the comprehensive aspects of ginsenosides including their distribution, structural diversity, biotransformation, and functional attributes in both plants and animals including humans. Moreover, ginsenoside biosynthesis in the potential plant sources and their metabolism in the human body along with major regulators and stimulators affecting ginsenoside biosynthesis have also been discussed. Furthermore, this review consolidates biotechnological interventions to enhance the biosynthesis of ginsenosides in their potential sources and advancements in the development of synthetic biosystems for efficient ginsenoside biosynthesis to meet their rising industrial demands.

Phototoxicity-free blue light for enhancing therapeutic angiogenic efficacy of stem cells.

Low-level light therapy (LLLT) is a safe and noninvasive technique that has drawn attention as a new therapeutic method to treat various diseases. However, little is known so far about the effect of blue light for LLLT due to the generation of reactive oxygen species (ROS) that can cause cell damage. We introduced a blue organic light-emitting diode (bOLED) as a safe and effective light source that could generate a low amount of heat and luminance compared to conventional light sources (e.g., light-emitting diodes). We compared phototoxicity of bOLED light with different light fluences to human adipose-derived stem cells (hADSC). We further explored molecular mechanisms involved in the therapeutic efficacy of bOLED for enhancing angiogenic properties of hADSC, including intracellular ROS control in hADSCs. Using optimum conditions of bOLED light proposed in this study, photobiomodulation and angiogenic properties of hADSCs were enhanced. These findings might open new methods for using blue light in LLLT. Such methods can be implemented in future treatments for ischemic disease.

Anti-inflammatory effect of Gyeji-tang in a chronic obstructive pulmonary disease mouse model induced by cigarette smoke and lipopolysaccharide.

CONTEXT: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with respiratory symptoms and narrowing of airways. Gyeji-tang (GJT) is a traditional Asian medicine that has been used to relieve early-stage cold symptoms, headache, and chills. OBJECTIVE: We examined the effect and potential molecular action mechanism of GJT in a mouse model of COPD induced by cigarette smoke (CS) plus lipopolysaccharide (LPS). MATERIALS AND METHODS: COPD was induced in C57BL/6J mice via daily exposure to CS for 1 h for 8 weeks and intranasal administration of LPS on weeks 1, 3, 5, and 7. GJT (100 or 200 mg/kg) or roflumilast (5 mg/kg) was administrated daily for the final 4 weeks of COPD induction. RESULTS: Administration of GJT significantly suppressed the CS/LPS-induced increases in: the numbers of total cells and macrophages in bronchoalveolar lavage fluid; the expression levels of tumour necrosis factor-α, interleukin (IL)-6, IL-1ß, and IL-8; the activities (phosphorylation) of nuclear factor kappa B and signal transducer and activator of transcription 3; and the expression levels of the structural remodelling markers, transforming growth factor beta, matrix metallopeptidase (MMP)-7, and MMP-9. DISCUSSION AND CONCLUSIONS: These results demonstrate that GJT prevents the lung inflammation and airway remodelling induced by CS plus LPS exposure in mice, suggesting that GJT may have therapeutic potential for the treatment of COPD.

Effects of Oral Administration of Lactiplantibacillus Plantarum APsulloc 331261 (GTB1TM) Isolated from Green Tea on Atopic Dermatitis (AD)-like Skin Lesion Mouse Models.

Background: Probiotics are known to improve atopic dermatitis (AD) by inhibiting T helper 2 (Th2)-related reactions, restoring the Th2/T helper1 (Th1) cytokine ratio. The most popular probiotic is Lactiplantibacillus plantarum (L. plantarum), which is widely used in the food and pharmaceutical industries. L. plantarum APsulloc 331261 (GTB1) used in this study was isolated from green tea. Materials and Methods: The effectiveness of oral GTB1 administration in improving AD was evaluated by visual evaluation, comparison of the lymph node sizes and spleen weights, histological evaluation, RT-qPCR, ELISA, and IHC analysis in the mouse model. Results: GTB1 improved AD symptoms, reduced epidermal thickness and mast cell numbers, decreased lymph node size and the spleen weight, increased filaggrin and loricrin protein levels, downregulated Th2 expression, and upregulated Th1 expression in a colony-forming unit-dependent manner. Conclusion: Oral administration of GTB1 isolated from green tea (Camellia sinensis) improved the AD symptoms, reduced hypersensitivity reaction, and increased the skin barrier function. Finally, it is involved in AD improvement by restoring the Th2/Th1 cytokine balance.

Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway.

Ovarian cancer is a carcinoma that affects women and that has a high mortality rate. Overcoming paclitaxel resistance is important for clinical application. However, the effect of amino acid metabolism regulation on paclitaxel-resistant ovarian cancer is still unknown. In this study, the effect of an amino acid-deprived condition on paclitaxel resistance in paclitaxel-resistant SKOV3-TR cells was analyzed. We analyzed the cell viability of SKOV3-TR in culture conditions in which each of the 20 amino acids were deprived. As a result, the cell viability of the SKOV3-TR was significantly reduced in cultures deprived of arginine, glutamine, and lysine. Furthermore, we showed that the glutamine-deprived condition inhibited mTORC1/S6K signaling. The decreased cell viability and mTORC1/S6K signaling under glutamine-deprived conditions could be restored by glutamine and α-KG supplementation. Treatment with PF-4708671, a selective S6K inhibitor, and the selective glutamine transporter ASCT2 inhibitor V-9302 downregulated mTOR/S6K signaling and resensitized SKOV3-TR to paclitaxel. Immunoblotting showed the upregulation of Bcl-2 phosphorylation and a decrease in Mcl-1 expression in SKOV3-TR via the cotreatment of paclitaxel with PF-4708671 and V-9302. Collectively, this study demonstrates that the inhibition of glutamine uptake can resensitize SKOV3-TR to paclitaxel and represents a promising therapeutic target for overcoming paclitaxel resistance in ovarian cancer.

A myosin XI adaptor, TAPE, is essential for pollen tube elongation in rice.

Pollen tube (PT) elongation is important for double fertilization in angiosperms and affects the seed-setting rate and, therefore, crop productivity. Compared to Arabidopsis (Arabidopsis thaliana L.), information on PT elongation in rice (Oryza sativa L.) is limited by the difficulty in obtaining homozygous mutants. In a screen of T-DNA insertional mutants, we identified a mutant in the Tethering protein of actomyosin transport in pollen tube elongation (TAPE) gene with an unusual segregation ratio by genotyping analysis. A CRISPR/Cas9 knockout mutant of TAPE that produced a short PT was sterile, and TAPE was expressed specifically in pollen grains. TAPE is a homolog of a myosin XI adaptor in Arabidopsis with three tetratricopeptide repeat and Phox and Bem1 protein domains. TAPE showed latrunculin B-sensitive, actin-dependent localization to the endoplasmic reticulum. Yeast two-hybrid screening and transcriptome analysis revealed that TAPE interacted with pollen-specific LIM protein 2b and elongation factor 1-alpha. Loss of TAPE affected transcription of 1,259 genes, especially genes related to cell organization, which were downregulated. In summary, TAPE encodes a myosin XI adaptor essential for rice PT elongation.

Comparative transcriptome analysis of pollen and anther wall reveals novel insights into the regulatory mechanisms underlying anther wall development and its dehiscence in rice.

To further understand the regulatory mechanism for anther dehiscence in rice, we carried out transcriptome analysis for the following two tissues: the anther wall and pollen at the anthesis stage. With the anatomical meta-expression data, in addition to these tissues, the differentially expressed genes (DEGs) between the two tissues were further refined to identify 1,717 pollen-preferred genes and 534 anther wall-preferred genes. A GUS transgenic line and RT-qPCR analysis for anther wall-preferred genes supported the fidelity of our gene candidates for further analysis. The refined DEGs were functionally classified through Gene Ontology (GO) enrichment and MapMan analyses. Through the analysis of cis-acting elements and alternative splicing variants, we also suggest the feature of regulatory sequences in promoter regions for anther wall-preferred expression and provide information of the unique splicing variants in anther wall. Subsequently, it was found that hormone signaling and the resulting transcriptional regulation pathways may play an important role in anther dehiscence and anther wall development. Our results could provide useful insights into future research to broaden the molecular mechanism of anther dehiscence or anther wall development in rice.

Overexpression of the PanaxginsengCYP703 Alters Cutin Composition of Reproductive Tissues in Arabidopsis.

Cytochrome P450 (CYP) catalyzes a wide variety of monooxygenation reactions in plant primary and secondary metabolisms. Land plants contain CYP703, belonging to the CYP71 clan, which catalyzes the biochemical pathway of fatty acid hydroxylation, especially in male reproductive tissues. Korean/Asian ginseng (Panax ginseng Meyer) has been regarded as one of important medicinal plant for a long time, however the molecular mechanism is less known on its development. In this study, we identified and characterized a CYP703A gene in P. ginseng (PgCYP703A4), regarding reproductive development. PgCYP703A4 shared a high-sequence identity (81-83%) with predicted amino acid as CYP703 in Dancus carota, Pistacia vera, and Camellia sinensis as well as 76% of amino acid sequence identity with reported CYP703 in Arabidopsis thaliana and 75% with Oryza sativa. Amino acid alignment and phylogenetic comparison of P. ginseng with higher plants and known A. thaliana members clearly distinguish the CYP703 members, each containing the AATDTS oxygen binding motif and PERH as a clade signature. The expression of PgCYP704B1 was only detected in P. ginseng flower buds, particularly in meiotic cells and the tapetum layer of developing anther, indicating the conserved role on male reproduction with At- and Os- CYP703. To acquire the clue of function, we transformed the PgCYP703A4 in A. thaliana. Independent overexpressing lines (PgCYP703A4ox) increased silique size and seed number, and altered the contents of fatty acids composition of cutin monomer in the siliques. Our results indicate that PgCYP703A4 is involved in fatty acid hydroxylation which affects cutin production and fruit size.

Rice ß-glucosidase Os12BGlu38 is required for synthesis of intine cell wall and pollen fertility.

Glycoside hydrolase family1 ß-glucosidases play a variety of roles in plants, but their in planta functions are largely unknown in rice (Oryza sativa). In this study, the biological function of Os12BGlu38, a rice ß-glucosidase, expressed in bicellular to mature pollen, was examined. Genotype analysis of progeny of the self-fertilized heterozygous Os12BGlu38 T-DNA mutant, os12bglu38-1, found no homozygotes and a 1:1 ratio of wild type to heterozygotes. Reciprocal cross analysis demonstrated that Os12BGlu38 deficiency cannot be inherited through the male gamete. In cytological analysis, the mature mutant pollen appeared shrunken and empty. Histochemical staining and TEM showed that mutant pollen lacked intine cell wall, which was rescued by introduction of wild-type Os12BGlu38 genomic DNA. Metabolite profiling analysis revealed that cutin monomers and waxes, the components of the pollen exine layer, were increased in anthers carrying pollen of os12bglu38-1 compared with wild type and complemented lines. Os12BGlu38 fused with green fluorescent protein was localized to the plasma membrane in rice and tobacco. Recombinant Os12BGlu38 exhibited ß-glucosidase activity on the universal substrate p-nitrophenyl ß-d-glucoside and some oligosaccharides and glycosides. These findings provide evidence that function of a plasma membrane-associated ß-glucosidase is necessary for proper intine development.

The Psychosocial Effects of Taekwondo Training: A Meta-Analysis.

Taekwondo is a Korean martial art and international sport, and its psychosocial benefits for its trainees have been studied extensively. This review aims to systematically assess and meta-analyze the effects of Taekwondo training on sociality, character, etiquette, and school life adjustment. We searched the RISS, NDSL, and KISS electronic databases between January 1985 and December 2019. We also included gray literature, such as theses, in addition to peer-reviewed articles. R software (version 3.6.2, R Core Team, Vienna, Austria) was used to synthesize the effect sizes and perform moderation analyses. Twenty-eight studies (24 cross-sectional and four intervention studies) were included in the final meta-analysis. Significant positive effects of Taekwondo training were found on sociality (MD = 0.266, 95% CI: 0.191 to 0.341), character (MD = 0.446, 95% CI: 0.331-0.560), etiquette (MD = 0.562, 95% CI: 0.500-0.624), and school life adjustment (MD = 0.308, 95% CI: 0.195-0.421). Overall, the findings of this meta-analysis support that Taekwondo can have a positive impact on the psychosocial factors of trainees. Due to several limitations discussed, well-designed RCTs and multiple levels of Taekwondo intervention studies should be conducted in future research to validate the current findings.

Gardenia jasminoides Attenuates Allergic Rhinitis-Induced Inflammation by Inhibiting Periostin Production.

Allergic rhinitis (AR) is a chronic inflammatory condition affecting the nasal mucosa of the upper airways. Herein, we investigated the effects of extracts from Gardenia jasminoides (GJ), a traditional herbal medicine with anti-inflammatory properties, on AR-associated inflammatory responses that cause epithelial damage. We investigated the inhibitory effects of water- and ethanol-extracted GJ (GJW and GJE, respectively) in an ovalbumin-induced AR mouse model and in splenocytes, differentiated Th2 cells, and primary human nasal epithelial cells (HNEpCs). Administering GJW and GJE to ovalbumin-induced AR mice improved clinical symptoms including behavior (sneezing and rubbing), serum cytokine levels, immune cell counts, and histopathological marker levels. Treatment with GJW and GJE reduced the secretion of Th2 cytokines in Th2 cells isolated and differentiated from the splenocytes of these mice. To investigate the underlying molecular mechanisms of AR, we treated IL-4/IL-13-stimulated HNEpCs with GJW and GJE; we found that these extracts significantly reduced the production of mitochondrial reactive oxygen species via the uncoupling protein-2 and periostin, a biomarker of the Th2 inflammatory response. Our results suggest that GJ extracts may potentially serve as therapeutic agents to improve the symptoms of AR by regulating the Th2 inflammatory response of the nasal epithelium.

Angelica gigas extract ameliorates allergic rhinitis in an ovalbumin-induced mouse model by inhibiting Th2 cell activation.

BACKGROUND: Allergic rhinitis (AR) is a well-documented type 2 helper T (Th2) cell-mediated allergic disease that is accompanied by symptoms such as nasal rubbing, sneezing, itching, and rhinorrhea. Angelica gigas (AG) is traditional oriental medicine, and its dried root is widely used for the treatment of anemia, as a sedative, and as a blood tonic. PURPOSE: The effects of AG on allergic diseases including AR are currently unclear; therefore, we aimed to investigate the effects of AG extract (AG-Ex) in ameliorating AR. STUDY DESIGN/METHODS: The cytotoxicity of AG-Ex was analyzed by EZ-Cytox or MTS assay in splenocytes, differentiated Th2 cells, and human nasal epithelial cells (HNEpC). The changes of Th2 cells activation were determined by the secretion levels of cytokines and chemokines using cytometric bead array in splenocytes and differentiated Th2 cells. The expression levels of eotaxin-3 and periostin were analyzed using an ELISA. AR was induced by ovalbumin in BALB/c mice and the ameliorating effects of AG-Ex were assessed by their clinical symptoms. RESULTS: The secretion of Th2 cytokines such as IL-4, IL-5, and IL-13 was inhibited by the AG-Ex treatment in the splenocytes and differentiated Th2 cells. The treatment also suppressed allergic responses including the secretion of eotaxin-3 and periostin in human nasal epithelial cells (HNEpC). Moreover, the administration of AG-Ex to the OVA-induced AR mice improved their clinical symptoms, including behavioral tests, immune cell counts, histopathological analysis, and changes in serum parameters. CONCLUSION: The results of this study suggest that AG-Ex ameliorates AR by inhibiting Th2 cell activation and could thus be utilized as a treatment for Th2-mediated allergic diseases in the future.