Network pharmacology and molecular docking analysis on the mechanism of Tripterygium wilfordii Hook in the treatment of Sjögren syndrome.

Tripterygium wilfordii Hook. F (TWH) has significant anti-inflammatory and immunosuppressive effects, and is widely used in the inflammatory response mediated by autoimmune diseases. However, the multi-target mechanism of TWH action in Sjögren syndrome (SS) remains unclear. Therefore, the aim of this study was to explore the molecular mechanism of TWH in the treatment of SS using network pharmacology and molecular docking methods. TWH active components and target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. SS-related targets were obtained from the GeneCards database. After overlap, the therapeutic targets of TWH in the treatment of SS were screened. Protein-protein interaction and core target analysis were performed by STRING network platform and Cytoscape software. In addition, the affinity between TWH and the disease target was confirmed by molecular docking. Finally, the DAVID (visualization and integrated) database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of overlapping targets. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database shows that TWH contains 30 active components for the treatment of SS. Protein-protein interaction and core target analysis suggested that TNF, MMP9, TGFB1, AKT1, and BCL2 were the key targets of TWH in the treatment of SS. In addition, the molecular docking method confirmed that the bioactive molecules of TWH had a high affinity with the target of SS. Enrichment analysis showed that TWH active components were involved in multiple signaling pathways. Pathways in cancer, Lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications is the main pathway. It is associated with a variety of biological processes such as inflammation, apoptosis, immune injury, and cancer. Based on data mining network pharmacology, and molecular docking method validation, TWH is likely to be a promising candidate for the treatment of SS drug, but still need to be further verified experiment.

A relatively rare traditional Chinese medicine pattern of primary Sjögren syndrome: A case report.

RATIONALE: This report presents a unique case of a patient diagnosed with Primary Sjögren's syndrome and a relatively rare traditional Chinese medicine pattern, known as the combined cold and heat pattern and cold-dampness syndrome. The patient's condition was successfully managed using Chinese herbal medicine, specifically the modified Da-Chai-Hu decoction and Linggui Zhugan decoction. PATIENT CONCERNS: A 56-year-old woman had chronic dry eye and mouth for over 10 years. She was initially managed with traditional Chinese herbal medicine (TCHM) prescriptions, including the Zengye decoction, but the therapeutic effects were unsatisfactory. As the disease progressed, she was diagnosed with an anxiety disorder due to symptoms of vexation and insomnia. Treatment with alprazolam and venlafaxine failed to alleviate these symptoms. Recently, her general condition gradually worsened, with symptoms including a bitter taste in her mouth, dizziness, hot flashes, chills, poor appetite, chest discomfort, and constipation. DIAGNOSES: After a series of examinations, including a Schirmer test and labial gland biopsy, she was diagnosed with Sjögren's syndrome. INTERVENTIONS: Despite regular treatment with pilocarpine, sodium hyaluronate eye drops, venlafaxine, and alprazolam, the dry mouth symptoms intensified. Consequently, she sought further intervention through the TCHM. OUTCOMES: After 8 weeks of treatment with the modified Da-Chai-Hu decoction and Linggui Zhugan decoction, she reported a significant improvement in her dryness-related symptoms and sleep quality. LESSONS: This case report demonstrates that TCHM can effectively treat Primary Sjögren's syndrome, and should be considered for broader applications. Furthermore, this underscores the importance of tailoring treatment formulas to patients by identifying their specific syndrome differentiation in a clinical setting.

Regulation of STAT1 and STAT4 Expression by Growth Factor and Interferon Supplementation in Sjögren's Syndrome Cell Culture Models.

Our goal was to investigate the effects of epidermal growth factor (EGF) and interferons (IFNs) on signal transducer and activator of transcription STAT1 and STAT4 mRNA and active phosphorylated protein expression in Sjögren's syndrome cell culture models. iSGECs (immortalized salivary gland epithelial cells) and A253 cells were treated with EGF, IFN-alpha, -beta, -gamma, or mitogen-activated protein kinase p38 alpha (p38-MAPK) inhibitor for 0-24-48-72 h. STAT1 and STAT4 mRNA expression was quantified by qRT-PCR. Untreated and treated cells were compared using the delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) normalized relative fold changes. phospho-tyrosine-701-STAT1 and phospho-serine-721-STAT4 were detected by Western blot analysis. STAT4 mRNA expression decreased 48 h after EGF treatment in A253 cells, immortalized salivary gland epithelial cells iSGECs nSS2 (sicca patient origin), and iSGECs pSS1 (anti-SSA negative Sjögren's Syndrome patient origin). EGF and p38-MAPK inhibitor decreased A253 STAT4 mRNA levels. EGF combined with IFN-gamma increased phospho-STAT4 and phospho-STAT1 after 72 h in all cell lines, suggesting additive effects for phospho-STAT4 and a major effect from IFN-gamma for phospho-STAT1. pSS1 and nSS2 cells responded differently to type I and type II interferons, confirming unique functional characteristics between iSGEC cell lines. EGF/Interferon related pathways might be targeted to regulate STAT1 and STAT4 expression in salivary gland epithelial cells. Further investigation is required learn how to better target the Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) pathway-mediated inflammatory response in Sjögren's syndrome.

Network pharmacology identifies the inhibitory effect of Yiqiyangyinquyu prescription on salivary gland inflammation in Sjögren's syndrome.

This study aimed to explore the mode of action of Yiqiyangyinquyu prescription (YP) against Sjögren's syndrome (SS) by combining network pharmacology with molecular docking techniques. YP's active components and target proteins were identified using the BATMAN-traditional Chinese medicine database. Concurrently, targets associated with SS were extracted from databases, including Genecards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The standard targets were then imported into the STRING database to construct a protein-protein interaction network. We then conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, which were succeeded by molecular docking studies to validate core active components and key targets. Finally, in vitro experiments and molecular dynamics simulation were conducted to substantiate the therapeutic efficacy of YP in treating SS. A total of 206 intersection targets and 46 active compounds were identified. Gene ontology analysis unveiled that YP targets were primarily enriched in cellular responses to chemical stress, inflammation, and cell proliferation. Key enriched signaling pathways encompassed the interleukin 17, hypoxia-inducible factor-1, tumor necrosis factor (TNF-α), and advanced glycation end products-receptor for AGEs (AGE-RAGE) signaling pathways. Molecular docking results demonstrated high-affinity between neotanshinone C, tanshiquinone B, miltionone I, TNF-α, interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). Noteworthy, TNF-α, considered the most important gene in YP against SS, binds to YP most stably, which was further validated by molecular dynamics simulation. In vitro experiments confirmed YP's capacity to reduce TNF-α, IL-1ß, and IL-6 expression, effectively alleviating SS-related inflammation. YP demonstrated a significant anti-inflammatory effect by suppressing inflammatory cytokines (TNF-α, IL-6, and IL-1ß), providing experimental evidence for its clinical application in treating SS.

Safety and Efficacy of Oral Hydroxychloroquine in the Treatment of Ophthalmic Disease Associated with Sjögren's Syndrome.

Background: Dry eye disease is common among patients with primary Sjögren's syndrome (pSS). Hydroxychloroquine (HCQ), known for its immunomodulatory effects and minimal adverse effects, has emerged as a pivotal treatment option for pSS. Nonetheless, conflicting evidence exists regarding the therapeutic efficacy of HCQ in managing dry eye disease associated with pSS. Objectives: To evaluate the safety and efficacy of oral hydroxychloroquine in treating dry eye disease associated with pSS. Methods: A prospective randomized controlled study was conducted, enrolling pSS patients with moderate to severe dry eye disease. Participants were randomly assigned to an oral HCQ group and an observation group. Various scales (ESSDAI, ESSPRI, OSDI, and SPEED questionnaire score), dry eye-related tests (OSS score, TBUT, and Schirmer test I), ophthalmology-specific tests (BCVA, SD-OCT RT, field of view, latency and amplitudes for multifocal ERG ring 1 and ring 2), whole body protein levels (serum IgA, IgG, and IgM), and blood glucose were assessed before and after 12 months of treatment. Results: Pairwise comparison of the observed indicator baseline revealed no statistical significance (P > .05). After 12 months, the HCQ group exhibited notable improvements in ESSPRI, serum IgA, and Schirmer test I results compared to the control group (P < .05). Both groups demonstrated significant improvements in BCVA, OSDI, SPEED scores, and dry eye-associated examinations compared to baseline (P < .05). Serum IgG and IgM levels decreased in the HCQ group after 12 months of treatment, but without statistical significance (P > .05). None cases of HCQ retinopathy were reported during follow-up. Conclusions: Oral HCQ was demonstrated safety and efficacy in managing pSS-related dry eye disease. Treatment with Oral HCQ markedly reduced the ESSPRI score, improve patients' systemic dryness symptoms, and greatly decreased blood IgA levels. Combined with topical cyclosporin, HCQ improved Schirmer test I scores and alleviated ocular surface inflammation and dry eye signs and symptoms.

Identification of Fangji Huangqi Tang as a potential herbal formula for Sjogren syndrome treatment via network pharmacology and experimental validation.

Fangji Huangqi Tang (FHT) is a well-known Chinese herbal formula that is prescribed as treatment for rheumatoid diseases. In this study, we aimed to investigate the potential therapeutic targets, efficacy, and safety of FHT in the treatment of Sjogren's syndrome (SS). The Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in SS. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential biological functions of the DEGs. Subsequently, an FHT-herb-active compound-target network was constructed to identify the relationship between the active compounds in FHT and the related targets. Then, enrichment analysis involving the DEGs and protein-protein interaction (PPI) network analysis were performed to analyze the biological functions of potential targets and screen hub genes. Further, molecular docking was employed to verify the binding affinity between the active compounds and the hub targets, and in vivo experiments involving NOD/LtJ mice were conducted to verify the therapeutic effects of FHT on SS-like symptoms. Finally, inhibition of PIK3CK/Akt pathway by FHT was validated by WB and rt-qPCR. A total of 1836 DEGs were identified in SS based on the GSE159574 dataset, and 114 targets of the active compounds in FHT were screened. Further, via network pharmacology analysis and molecular docking, six active compounds and five hub targets were obtained, and enrichment analysis showed that the anti-SS effect of FHT was predominantly associated with immune cells, such as T cells and neutrophils. In vivo, FHT effectively reduced lymphocyte infiltration foci, increased saliva flow rate, and inhibited increases in the levels of SS-related autoantibodies (anti-SSA and anti-SSB). Furthermore, the biosafety of FHT was verified via the serological examination of liver and kidney function. WB and rt-qPCR analysis confirmed that FHT could inhibit the expression of PIK3CG and the activation of PIK3CG/Akt pathway. Via network pharmacological analysis, molecular docking, and in vivo verification, we demonstrated the multicomponent and multitarget characteristics of FHT in SS treatment, thereby providing novel insights into the pathogenesis of SS and the therapeutic targets of FHT for SS.

Efficacy of Lushi Runzao decoction on ameliorating Sjogren's syndrome: a network pharmacology and experimental verification-based study.

OBJECTIVE: To investigate the possible mechanism underlying the effect of the Lushi Runzao decoction on Sjogren's syndrome using network pharmacology and to verify the mechanismsanimal experiments. METHODS: Available biological data on each drug in the Lushi Runzao decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the target proteins of Sjogren's syndrome were retrieved from the GeneCards database. Information regarding Sjogren's syndrome and the targets of the drugs were compared to obtain overlapping elements. This information was imported into the STRING platform to obtain a protein-protein interaction network diagram, following which a "component-target" network diagram was constructed using screened drug components and target informationCytoscape software. The database for annotation, visualization, and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses. Pathway information predicted by network pharmacology was verified using animal experiments. RESULTS: The Lushi Runzao decoction ameliorated Sjogren's syndrome mainly by influencing tumor necrosis factor as well as certain cytokines and chemokines. The decoction also influenced the interleukin-17 and advanced glycosylation end products (AGE)-receptor for AGE signaling pathways. CONCLUSION: The Lushi Runzao decoction ameliorates Sjogren's syndromemultiple targets and multiple signaling pathways. Network pharmacology is useful for making a comprehensive prediction regarding the efficacy of the Lushi Runzao decoction, and this information may be helpful in clinical research.

[Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine].

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

Huoxue Jiedu Recipe represses mitochondrial fission to alleviate submandibular gland inflammation in Sjögren's syndrome.

Sjögren's syndrome (SS) is the second most common autoimmune rheumatism. Huoxue Jiedu Recipe (HXJDR) is a kind of traditional Chinese medicine with a variety of pharmacological functions; however, its biological function in SS has not been studied yet. Peripheral blood mononuclear cells (PBMCs) and serum samples were isolated from healthy controls and patients with SS. NOD/Ltj mice were used for developing the SS mouse model. The levels of inflammatory cytokines and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers as well as dynamin-related protein 1 (Drp1) were determined by ELISA, quantitative real-time PCR, and western blot analysis, respectively. Hematoxylin and eosin and TUNEL staining detected the pathological damage. A transmission electron microscope was used to observe the mitochondrial microstructure. Inflammatory cytokines IL-18, IL-1ß, B-cell activating factor (BAFF), BAFF-receptor (BAFF-R), IL-6, and TNF-α in serum samples and NLRP3 inflammasome-related makers (NLRP3, cysteinyl aspartate-specific proteinase 1 [caspase-1], apoptosis-associated speck-like protein containing a caspase-1 recruitment domain [ASC], IL-1ß) in PBMCs were greatly upregulated in patients with SS. Furthermore, cytoplasmic phosphorylation of Drp1 and mitochondrial Drp1 level were significantly increased in PBMCs, while mitochondrial swelling and fuzzy inner ridge were observed in PBMCs of patients with SS, suggesting increased mitochondrial fission. Compared with control mice, SS mice showed decreased salivary flow rate, increased submandibular gland index, and more severe inflammatory infiltration and damage as well as mitochondrial fission in submandibular gland tissues. After HXJDR administration, these effects were significantly reversed. HXJDR treatment could alleviate the inflammatory infiltration and pathological damage in submandibular glands of SS mice by inhibiting Drp-1-dependent mitochondrial fission.

Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren's syndrome: evidence- and practice-based guidance.

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.

Relationship between Chinese Herbal Medicine Use and Risk of Sjögren's Syndrome in Patients with Rheumatoid Arthritis: A Retrospective, Population-Based, Nested Case-Control Study.

Background and Objectives: Sjögren's Syndrome (SS) is a common extra-articular feature among subjects with rheumatoid arthritis (RA). While Chinese herbal medicine (CHM) has been used to treat symptoms of RA for many years, few studies have examined its efficacy in guarding against the SS onset. This study aimed to compare risk of SS for RA patients with and without use of CHM. Materials and Methods: Data obtained for this nested case-control study were retrieved from Taiwanese nationwide insurance database from 2000-2013. Cases with SS claims were defined and matched to two randomly selected controls without SS from the recruited RA cohorts. Risk of SS in relation to CHM use was estimated by fitting multiple conditional logistic regression. Results: Patients aged between 20 and 80 years were included and 916 patients with incident SS were matched to 1832 non-SS controls by age, sex and index year. Among them, 28.1% and 48.4% cases ever received CHM therapy, respectively. After adjusting for baseline characteristics, CHM use was found to be related to a lower risk of SS among them (adjusted odds ratio = 0.40, 95% confidence interval: 0.34-0.47). A dose-dependent, reverse association, was further detected between the cumulative duration of CHM use and SS risk. Those receiving CHM therapy for more than 730 days showed a significantly reduced risk of SS by 83%. Conclusions: Findings of this study indicated that the add-on CHM formula, as part of RA care, may be a beneficial treatment for prevention against the incident SS.

Effectiveness and Safety of Traditional Chinese Medicine in Treatment of Primary Sjögren's Syndrome Patients: A Meta-analysis.

BACKGROUND: Primary Sjögren's Syndrome (pSS) is an autoimmune disease. It can damage the salivary and lacrimal glands and is characterized by dry mouth and eye symptoms, which seriously affects people's normal life. Both modern medicine and Traditional Chinese medicine (TCM) have certain effects in treating SS. However, there are different theories about which treatment is more appropriate. OBJECTIVE: The aim of this research was to compare the efficacy and safety of TCM to Western Medicine in the treatment of pSS. METHODS: We collected randomized controlled trials (RCTs) of TCM, integrating traditional Chinese and Western medicine for the treatment of pSS in Chinese and foreign databases. RESULTS: A total of 13 articles were eventually included with 780 cases. The final results were expressed in odds ratio (OR), mean difference (MD), 95% confidence interval (CI), and overall effect (z). The effective rate was 86.03% in the TCM group and 67.75% in the western medicine group. Results of the effective rate were OR = 3.57; 95% CI = 2.44-5.23; z = 6.56; p＜0.00001, ESR were MD = -6.90; 95% CI = -10.76--3.05; z = 3.51; p = 0.0005＜0.05, Schirmer's test were MD = 3.39; 95% CI = 1.92-4.86; z = 4.5; p＜0.00001, salivary flow were MD = 0.62; 95% CI = 0.16-1.07; z = 2.63; p = 0.009＜0.05, and adverse reactions were OR = 0.35; 95% CI = 0.17-0.72; z = 2.84; p = 0.004. CONCLUSION: TCM has a remarkable effect on the treatment of pSS. Among them Yiguanjian decoction and Liuwei Dihuang decoction were effective prescriptions with the highest frequency of application. Rehmanniae Radix (Rehmannia glutinosa Libosch.) and Ophiopogonis Radix (Ophiopogon japonicus (L. f.) Ker-Gawl.) were the most frequently used TCM.

Targets of total glucosides of paeony in the treatment of Sjogren syndrome: A network pharmacology study.

BACKGROUND: We aimed to explore the underlying mechanism of the total glucoside of peony (TGP) in treating Sjogren syndrome (SS) using the network pharmacology approach. METHODS: The protein targets of TGP and SS were identified by database search. Then, the intersection of the two groups was studied. The drug-target network between TGP and the overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment were performed to analyze these genes. Finally, the predictions of potential targets were evaluated by docking study. RESULTS: Forty-six overlapping genes were discovered. The results suggested that TGP used in the treatment of SS is associated with cellular tumor antigen p53, neurotrophic tyrosine kinase receptor type 1, and epidermal growth factor receptor, as well as their related 3372 protein networks, which regulate intrinsic apoptotic signaling pathway, cellular response to oxidative stress, rhythmic process, and other processes. Molecular docking analysis proved that hydrogen bonding is the main form of interaction. CONCLUSION: Our research provided the protein targets affected by TGP in SS treatment. The key targets (caspase 3, vascular endothelial growth factor A, glyceraldehyde-3-phosphate dehydrogenase, etc.), which involve 3372 proteins, are the multitarget mechanism of TGP in SS treatment.

Blueberry Leaf Extract Prevents Lacrimal Hyposecretion in Sjögren's Syndrome-like Model of Non-obese Diabetic Mice.

BACKGROUND/AIM: This study evaluated the effect of blueberry leaf hot water extract (BLEx) on Sjögren's syndrome (SS)-like lacrimal hyposecretion in male non-obese diabetic (NOD) mice. MATERIALS AND METHODS: NOD or BALB/c mice were fed 1% BLEx or control (AIN-93G) for 2 weeks from the age of 4 to 6 weeks. Pilocarpine-induced tear volume was measured using a phenol red-impregnated thread. The lacrimal glands were evaluated histologically by H&E staining. The IL-1ß and TNF-α levels in the lacrimal gland tissue were measured by ELISA. The mRNA expression levels of secretion-related proteins were measured by real-time PCR. LC3 I/II and arginase 1 expression levels were measured by western blot. RESULTS: After feeding with BLEx, pilocarpine-induced tear secretion in NOD mice was increased. In contrast, the mRNA expression levels of the cholinergic muscarinic M3 receptor, aquaporin 5, and ion channels related to lacrimal secretion were not changed by BLEx administration. In addition, the protein expression of arginase 1, which was recently reported to be involved in tear hyposecretion in NOD mice, was also not improved by BLEx administration. Although infiltration in the lacrimal gland of NOD mice was not decreased, the levels of TNF-α and the autophagy-related protein LC3 were significantly suppressed by BLEx treatment. CONCLUSION: BLEx treatment may ameliorate lacrimal hyposecretion in NOD mice by delaying the progression of autoimmune disease by suppressing autophagy in lacrimal glands.

Exploring the Target and Mechanism of Radix Paeoniae Alba on Sjogren's Syndrome.

BACKGROUND: Radix Paeoniae Alba is a traditional Chinese herbal medicine. It can accelerate salivary secretion and alleviate the dry mouth of patients with Sjogren's syndrome (SS). Although it is widely used in clinical treatment, its target and mechanism remain unclear. OBJECTIVE: This study aims to analyze the main components of Radix Paeoniae Alba, explore the target genes, and propose the possible mechanism for Radix Paeoniae Alba's acceleration of salivary secretion. METHODS: The main active components and potential targets of Radix Paeoniae Alba were searched through the TCMSP database. Efforts were made to search for the related genes of Sjogren's syndrome in OMIM and GeneCards databases. Cytoscape v3.8.0 software was used to link target genes of active components and key genes of the disease. The software Autodock vina1.1.2. was adopted to simulate the interaction between active components and target genes. Human submandibular gland (HSG) cells were used in vitro experiments to verify the results of our analysis. RESULTS: ß-Sitosterol, the main component of Radix Paeoniae Alba, may intervene in the disease through CHRM3. Molecular docking shows ß-Sitosterol has a high affinity with CHRM3, and the interaction between CHRM3 and ß-Sitosterol is the basis of biological activity. The in vitro experiments showed that ß-Sitosterol could significantly up-regulate the mRNA and protein expression levels of both CHRM3 and secretion-related genes in HSG cells. CONCLUSION: Our study shows that the chemical components of Radix Paeoniae Alba have a positive effect on the related mechanism of salivary secretion. We found that ß-Sitosterol can promote the expression of CHRM3, stimulate salivary secretion, treat Sjogren's syndrome and potentially improve its prognosis.

Lacrimal Gland Histopathology and Secretory Function in Sjögren's Syndrome Mice Model Treated with Moringa oleifera Lam. Leaf Extract.

BACKGROUND: The pathogenesis of Sjögren's syndrome involves the activation of NF- κB, producing proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1α, IL- 1ß, IL-6, IL-17, and interferon-γ. Through oxidative stress, they will cause necrosis and apoptosis of lacrimal gland cells, resulting in impaired secretory function or reduced tear production. Moringa oleifera leaf extract is known to have strong anti-inflammatory and antioxidant activities. OBJECTIVE: To determine the effect of Moringa oleifera leaf extract on lacrimal gland histopathology and secretory function in Sjögren's syndrome mice model. METHODS: The experimental study had a post-test only control group design with 32 eight-week-old male mice of the BALB/c strain divided into four groups, negative control (C-), which was not induced by SS, positive control (C+), treatment 1 (T1), and treatment 2 (T2) induced by Sjögren's syndrome by immunizing with the 60-kD Ro antigen (SSA) as much as 100 µg. After 42 days, the T1 group was given dexamethasone 1.23 mg/kg BW/day orally for 14 days, whereas T2 was given dexamethasone 1.23 mg/kg BW/day and Moringa oleifera leaf ethanol extract 200 mg/kg BW/day orally for 14 days. At the end of the study, lacrimal gland histopathology and secretory function (tear production) were examined. Statistical analysis using F ANOVA/Kruskal-Wallis was followed by partial difference test with the Least Significant Difference post hoc test/Mann-Whitney. Significant if p < 0.05. RESULTS: The comparison of lacrimal gland histopathology in T1 (p = 0.044) and T2 groups (p = 0.020) obtained significant results (p < 0.05) when compared to C+. However, the comparison of tear production in T1 (p = 0.127) and T2 groups (p = 0.206) was not significant (p > 0.05) when compared to the C+ group. CONCLUSION: The administration of Moringa oleifera leaf extract 200 mg/kg BW for 14 days could significantly improve lacrimal gland histopathology but was not effective in increasing tear production in Sjögren's syndrome mice model.

Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine / 中国中药杂志

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

Sjögren's syndrome: shedding light on emerging and key drug targets.

INTRODUCTION: Sjögren's syndrome (SS) is an immune-mediated inflammatory condition characterized by sicca syndrome, musculoskeletal pain, and fatigue. Extra-glandular manifestations are common and there is a markedly increased risk of lymphoma development. SS is associated with high health-economic burden driven largely by the symptom burden on patients. Currently, there is no approved disease-modifying treatment and management is based on empirical evidence. Progress in the understanding of SS pathogenesis has led to an expanding portfolio of more targeted therapies under development. AREAS COVERED: This review summarizes the key development in targeted biological therapies in SS including emerging targets. It also highlights the challenges in therapeutic development in SS such as disease heterogeneity and defining appropriate disease assessment tools to evaluate therapeutic efficacy. EXPERT OPINION: Early trials in SS failed to meet their primary outcomes which may in part due to the use of inappropriate or insensitive study endpoints. Recent trials targeting B-cells, B-T cell co-stimulation and IFN signaling have shown promising results. Development of composite endpoints including patient reported outcomes and objective disease measure may provide a more holistic approach to disease assessment. The impact of these new tools on therapeutic development that benefit patients remains to be fully evaluated.

Qing Zao Fang (QZF) Alleviates the Inflammatory Microenvironment of the Submandibular Gland in Sjögren's Syndrome Based on the PI3K/Akt/HIF-1α/VEGF Signaling Pathway.

Sjögren's syndrome (SS) which could lead to a disorder of our immune system is a chronic autoimmune disease characterized by invading exocrine glands such as salivary glands and lacrimal glands and other exocrine glands. Its common symptom is dry mouth and dry eyes, often accompanied by a large number of lymphocyte infiltrations and can involve other organs to cause complex clinical manifestations. In this study, we aimed at investigating the effect of QZF in SS, identifying the molecular mechanism in modulating autoimmune response, and determining the important roles of these factors' function as a modulator in the pathogenesis of SS. The NOD mice were utilized to establish the rats' model of Sjögren's syndrome. After 10 weeks' hydroxychloroquine and QZF in different dose interference, submandibular gland tissue was collected. The therapeutic effect of QZF on SS rats was identified, and the results suggest the comparable potential to hydroxychloroquine. In submandibular gland tissue, interleukin- (IL-) 17 was significantly lower in high-dose QZF than that in SS rats and the focal lymphocytes were highly attenuated. Moreover, we found that PI3K/Akt signals were activated and the downstream HIF-1α/VEGF signals were enhanced in SS rats whose protein expression could be inhibited by QZF treatment. In addition, QZF could modulate autophagy in submandibular gland tissue and then inhibit the inflammation response and therefore facilitate the tissue repair.

Sjogren's syndrome-An interesting case.

OBJECTIVE: To present a case of Sjogren syndrome with pulmonary manifestations in an adult female and discuss its assessment and management. DESIGN: Case Report. SETTING: Tertiary care hospital. PATIENT: One. RESULTS: A 50 yrs female admitted with complaints of dryness of eyes with decreased salivation causing difficulty in swallowing since last 3 years, with persistent dry cough since 10-15 days and progressive dyspnea since 4-5 days. Anti-nuclear antibody (ANA) profile revealed Anti- Ro/SS-A and Anti- La/SS-B Positive. Also, sub-lingual excisional biopsy was done which was consistent with findings of Sjogren's syndrome. Patient showed significant improvement after starting oral glucocorticoids, systemic anti inflammatory agents (Tab. HCQS), artificial tear drops, oral iron supplements and other supportive treatment. CONCLUSION: Sjögren syndrome (SS) is a chronic inflammatory disorder characterized by diminished lacrimal and salivary gland function and associated with lymphocytic infiltration of exocrine glands, and can affect extraglandular organ systems including the skin, lung, heart, kidney, neural, and hematopoietic systems. We present a case of Sjogren syndrome in an adult female presenting with xerostomia and dyspnea and was diagnosed upon detection of anti-Ro and anti-La antibodies and confirmed by histopathological examination of lip biopsy. Patient was started on oral steroids and other supportive treatment, General condition improved significantly and is doing very well on regular follow-up.