{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:01:03Z","timestamp":1790269263406,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants"},{"name":"CUHK, by the Innovation"},{"name":"Technology Commission, Hong Kong"},{"name":"Li Dak Sum Yip Yio Chin R&amp;D Centre for Chinese Medicine, the Chinese University of Hong Kong"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dry eye is one of the most common ocular surface diseases caused by tear film instability and ocular surface damage due to an abnormal quality or quantity of tears. Inflammatory factors can initiate relevant transduction signalling pathways and trigger the inflammatory cascade response, resulting in ocular surface inflammation. It has been shown that the active ingredients in Dendrobium, such as polysaccharides, alkaloids and phenols, have anti-inflammatory, anti-tumour and immunity-boosting effects, and Dendrobium officinale extract can improve glandular secretion function, increase salivary secretion and increase the expression level of water channel protein in salivary glands in patients with dry eye syndromes. We investigated the in vitro cytoprotective effect of Dendrobium extracts in sodium chloride induced hyperosmotic conditions in human cornea keratocytes (HKs). Results showed that Dendrobium officinale Kimura et Migo water extract (DOW) and Dendrobium loddigesii Rolfe water extract (DLW) could upregulate the expression of aquaporins (AQP)5 protein, thus exerting a repairing effect by promoting cell migration. Furthermore, oral administration of DOW and DLW enhanced tear production in rats and exerted a protective effect on ocular surface damage. DOW and DLW could upregulate the expression of AQP5 and mucin (muc)5ac proteins in the lacrimal gland and reduce the inflammatory response. DOW and DLW inhibited the activation of the corresponding mitogen-activated protein kinases (MAPK) and NF-KB pathway, thereby playing a role in improving dry eye symptoms. This study provides a new perspective on dry eye treatment, and DOW and DLW may be potential therapeutic agents for dry eye.<\/jats:p>","DOI":"10.3390\/ijms231911195","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T23:13:27Z","timestamp":1664147607000},"page":"11195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The Extracts of Dendrobium Alleviate Dry Eye Disease in Rat Model by Regulating Aquaporin Expression and MAPKs\/NF-\u03baB Signalling"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7252-217X","authenticated-orcid":false,"given":"Jiawei","family":"Ling","sequence":"first","affiliation":[{"name":"State Key Laboratory of Research on Bioactivities, Institute of Chinese Medicine, Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-1065","authenticated-orcid":false,"given":"Chung-Lap","family":"Chan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Research on Bioactivities, Institute of Chinese Medicine, Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Yan","family":"Ho","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Research on Bioactivities, Institute of Chinese Medicine, Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Gao","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing 211189, China"},{"name":"Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-0714","authenticated-orcid":false,"given":"Sin-Man","family":"Tsang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Research on Bioactivities, Institute of Chinese Medicine, Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0195-4688","authenticated-orcid":false,"given":"Ping-Chung","family":"Leung","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Research on Bioactivities, Institute of Chinese Medicine, Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9013-8489","authenticated-orcid":false,"given":"Jiang-Miao","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5637-8331","authenticated-orcid":false,"given":"Chun-Kwok","family":"Wong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Research on Bioactivities, Institute of Chinese Medicine, Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Li Dak Sum Yip Yio Chin R & D Centre for Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"DEWS (2007). The definition and classification of dry eye disease: Report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul. Surf., 5, 75\u201392. Available online: https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17508116.","DOI":"10.1016\/S1542-0124(12)70081-2"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II Definition and Classification Report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Roszkowska, A., Oliverio, G., Aragona, E., Inferrera, L., Severo, A., Alessandrello, F., Spinella, R., Postorino, E., and Aragona, P. (2021). Ophthalmologic Manifestations of Primary Sj\u00f6gren\u2019s Syndrome. Genes, 12, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33806489.","DOI":"10.3390\/genes12030365"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ajpath.2020.10.013","article-title":"Modulation of Oxidative Stress and Inflammation in the Aged Lacrimal Gland","volume":"191","author":"Yu","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/sj.eye.6703101","article-title":"Prevalence of dry eye among adult Chinese in the Beijing Eye Study","volume":"23","author":"Jie","year":"2009","journal-title":"Eye"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.mam.2004.02.003","article-title":"Aging and oxidative stress","volume":"25","author":"Junqueira","year":"2004","journal-title":"Mol. Asp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1167\/tvst.9.5.25","article-title":"The DREAM Study Research Group Climatic and Environmental Correlates of Dry Eye Disease Severity: A Report From the Dry Eye Assessment and Management (DREAM) Study","volume":"9","author":"Berg","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.immuni.2004.08.009","article-title":"Receptor-Specific Signaling for Both the Alternative and the Canonical NF-\u03baB Activation Pathways by NF-\u03baB-Inducing Kinase","volume":"21","author":"Ramakrishnan","year":"2004","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared principles in nf-kb signaling","volume":"132","author":"Hayden","year":"2008","journal-title":"Cell"},{"key":"ref_10","first-page":"266","article-title":"Research progress of nf-\u03bab in the field of ophthalmology","volume":"17","author":"Lou","year":"2017","journal-title":"Int. Eye Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.freeradbiomed.2013.05.006","article-title":"Effects of ozone exposure on the ocular surface","volume":"63","author":"Lee","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.biopha.2017.10.032","article-title":"A mouse dry eye model induced by topical administration of the air pollutant particulate matter","volume":"96","author":"Li","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/jnr.23354","article-title":"MLK3-MKK3\/6-P38MAPK cascades following N-methyl-D-aspartate receptor activation contributes to amyloid-\u03b2 peptide-induced apoptosis in SH-SY5Y cells","volume":"92","author":"Zhou","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.intimp.2014.10.024","article-title":"Blockade of p38 mitogen-activated protein kinase pathway ameliorates delayed gastric emptying in streptozotocin-induced diabetic rats","volume":"23","author":"Yang","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.3892\/mmr.2014.2041","article-title":"Decreased PPAR-\u03b3 expression in the conjunctiva and increased expression of TNF-\u03b1 and IL-1\u03b2 in the conjunctiva and tear fluid of dry eye mice","volume":"9","author":"Chen","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tjomsland, V., Bojmar, L., Sandstr\u00f6m, P., Bratth\u00e4ll, C., Messmer, D., Sp\u00e5ngeus, A., and Larsson, M. (2013). IL-1\u03b1 Expression in Pancreatic Ductal Adenocarcinoma Affects the Tumor Cell Migration and Is Regulated by the p38MAPK Signaling Pathway. PLoS ONE, 8, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23951028.","DOI":"10.1371\/journal.pone.0070874"},{"key":"ref_17","first-page":"s0034","article-title":"The Roles of MAPKs in Rabbit Nucleus Pulposus Cell Apoptosis Induced by High Osmolality","volume":"4","author":"Dong","year":"2014","journal-title":"Glob. Spine J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"808228","DOI":"10.3389\/fpls.2021.808228","article-title":"Research advances in multi-omics on the traditional chinese herb dendrobium officinale","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Plant Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s13659-021-00305-0","article-title":"Traditional Uses and Pharmacologically Active Constituents of Dendrobium Plants for Dermatological Disorders: A Review","volume":"11","author":"Wang","year":"2021","journal-title":"Nat. Prod. Bioprospecting"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112530","DOI":"10.1016\/j.ejmech.2020.112530","article-title":"Recent research progress on natural small molecule bibenzyls and its derivatives in Dendrobium species","volume":"204","author":"He","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"112839","DOI":"10.1016\/j.jep.2020.112839","article-title":"Anti-aging properties of Dendrobium nobile Lindl.: From molecular mechanisms to potential treatments","volume":"257","author":"Nie","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.phymed.2010.05.002","article-title":"Dendrobium candidum extract increases the expression of aquaporin-5 in labial glands from patients with Sj\u00f6gren\u2019s syndrome","volume":"18","author":"Xiao","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.fitote.2014.04.002","article-title":"The laxative effect of emodin is attributable to increased aquaporin 3 expression in the colon of mice and HT-29 cells","volume":"96","author":"Zheng","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jtos.2018.11.003","article-title":"The impact of dry eye disease treatment on patient satisfaction and quality of life: A review","volume":"17","author":"Gomes","year":"2018","journal-title":"Ocul. Surf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e412","DOI":"10.1111\/aos.13526","article-title":"Dry eye disease and oxidative stress","volume":"96","author":"Seen","year":"2018","journal-title":"Acta Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"DES163","DOI":"10.1167\/iovs.17-23402","article-title":"Potential Role of Oxidative Stress in Ocular Surface Inflammation and Dry Eye Disease","volume":"59","author":"Dogru","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1038\/s41433-020-0832-1","article-title":"A systematic review of simulation-based training tools for technical and non-technical skills in ophthalmology","volume":"34","author":"Lee","year":"2020","journal-title":"Eye"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.ophtha.2017.08.029","article-title":"Inflammation in Dry Eye Disease: How do we break the cycle?","volume":"124","author":"Rhee","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_29","first-page":"63","article-title":"Contribution of aquaporins in the transamniotic water flux","volume":"590","author":"Sierra","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.exer.2018.04.005","article-title":"Aquaporin 5 promotes corneal wound healing","volume":"172","author":"Kumari","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_31","first-page":"404","article-title":"An experimental of rabbit tear-deficient dry eye model by subcutaneous injection of scopolamine hydrobromide","volume":"18","author":"Qiu","year":"2009","journal-title":"Ophthalmol. China"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/01.ICL.0000162759.79740.46","article-title":"Hyperosmolar Saline Is a Proinflammatory Stress on the Mouse Ocular Surface","volume":"31","author":"Luo","year":"2005","journal-title":"Eye Contact Lens: Sci. Clin. Pr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.1167\/iovs.03-1145","article-title":"Experimental Dry Eye Stimulates Production of Inflammatory Cytokines and MMP-9 and Activates MAPK Signaling Pathways on the Ocular Surface","volume":"45","author":"Luo","year":"2004","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.exer.2006.02.004","article-title":"Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye","volume":"83","author":"Corrales","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.exer.2005.08.019","article-title":"JNK and ERK MAP kinases mediate induction of IL-1\u03b2, TNF-\u03b1 and IL-8 following hyperosmolar stress in human limbal epithelial cells","volume":"82","author":"Li","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"srep19408","DOI":"10.1038\/srep19408","article-title":"Blueberry Component Pterostilbene Protects Corneal Epithelial Cells from Inflammation via Anti-oxidative Pathway","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.2147\/OPTH.S308088","article-title":"Dry Eye Treatment with Topical Cyclosporine 0.1% in Chondroitin Sulfate Ophthalmic Emulsion","volume":"15","author":"Matossian","year":"2021","journal-title":"Clin. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s11095-018-2556-5","article-title":"Ocular Pharmacokinetics of a Topical Ophthalmic Nanomicellar Solution of Cyclosporine (Cequa\u00ae) for Dry Eye Disease","volume":"36","author":"Mandal","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jfo.2016.12.004","article-title":"Pan-European survey of the topical ocular use of cyclosporine A","volume":"40","author":"Baudouin","year":"2017","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1016\/j.jprot.2012.04.053","article-title":"In-depth analysis of the human tear proteome","volume":"75","author":"Zhou","year":"2012","journal-title":"J. Proteom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2147\/CIA.S190713","article-title":"Influence of diabetes mellitus on anterior segment of the eye","volume":"14","author":"Han","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1111\/1440-1681.13373","article-title":"Alpha-lipoic acid: A possible pharmacological agent for treating dry eye disease and retinopathy in diabetes","volume":"47","author":"Ajith","year":"2020","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1111\/febs.15691","article-title":"A tale of two proteins: PACT and PKR and their roles in inflammation","volume":"288","author":"Chukwurah","year":"2021","journal-title":"FEBS J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"evab289","DOI":"10.1093\/gbe\/evab289","article-title":"Rel\/NF-\u03baB Transcription Factors Emerged at the Onset of Opisthokonts","volume":"14","author":"Leger","year":"2022","journal-title":"Genome Biol. Evol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113851","DOI":"10.1016\/j.jep.2021.113851","article-title":"Traditional uses, chemical constituents, pharmacological activities, and toxicological effects of Dendrobium leaves: A review","volume":"270","author":"Wang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111571","DOI":"10.1016\/j.biopha.2021.111571","article-title":"Cevimeline-induced anti-inflammatory effect through upregulations of mucins in the ocular surface of a dry eye mouse model","volume":"139","author":"Kim","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.1167\/iovs.06-0728","article-title":"New Tools for the Evaluation of Toxic Ocular Surface Changes in the Rat","volume":"48","author":"Pauly","year":"2007","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_48","first-page":"438","article-title":"The execution and evaluation to several dry eye models","volume":"22","author":"Xiao","year":"2004","journal-title":"Chin. Ophthalmic Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-1-4939-7172-5_4","article-title":"Tissue Sampling and Processing for Histopathology Evaluation","volume":"1641","author":"Slaoui","year":"2017","journal-title":"Methods Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11195\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:02Z","timestamp":1760143082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":49,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911195"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911195","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]}}}