Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes

He, Songqing; Huang, Sheng-Guang; Zhu, Huijun; Luo, Xiao; Liao, Kang-Han; Zhang, Jie-Yao; Tan, Ning; Li, Deyu

doi:10.1080/13880209.2020.1711783

Cited by 22 publications

(5 citation statements)

References 36 publications

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“…The inhibition of autophagy and increased apoptotic activation correlates with a favorable clinical outcome in RA patients treated with anti-tumor necrosis factor (TNF) drugs [19]. This finding suggests that reducing the expression levels of autophagy-related genes might become a new therapeutic target for active RA; the ATG5 suppressor oridonin was recently introduced as a potential therapeutic target for RA [20].…”

Section: Discussionmentioning

confidence: 99%

Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients

et al. 2021

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Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients. Methods We performed genome-wide association analyses in an entire JIA case–control sample (All-JIA) and in a case–control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls. Results We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10−6), LTBP1 (P = 9,45 × 10−6), and ELMO1 (P = 1,05 × 10−5). In the oligoarticular JIA analysis, the strongest associations were identified at NFIA (P = 5,05 × 10−6), LTBP1 (P = 9,95 × 10−6), MX1 (P = 1,65 × 10−5), and CD200R1 (P = 2,59 × 10−5). Conclusion This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points• Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition.• Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe.• The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci.• The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.

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Section: Discussionmentioning

confidence: 99%

Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients

et al. 2021

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“…On the other hand, (5R)-5-hydroxytriptolide can systemically affect the FLS and, in particular, in the process of immune-related processes at 100 nM concentration through a genome-wide microarray assay in RA patients [60]. IL-1 activates the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), apetala (AP)-1, and NF-B activating pathways, which stimulate MMP production and leukocyte adhesion to RA FLS [61], whereas oridonin (2-10 M for 24-72 h) suppress RA FLS proliferation in RA [62]. In RA FLS, (5R)-5hydroxytriptolide (50 and 100 nM) reduced proliferation and invasion, as well as cytokine production (MMP-3, IL-1, and -6) [63].…”

Section: Physiopathology In Ra: a Brief Overviewmentioning

confidence: 99%

Activities and Molecular Mechanisms of Diterpenes, Diterpenoids, and Their Derivatives in Rheumatoid Arthritis

Islam

Quispe

Herrera‐Bravo

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Diterpenes and their derivatives have many biological activities, including anti-inflammatory and immunomodulatory effects. To date, several diterpenes, diterpenoids, and their laboratory-derived products have been demonstrated for antiarthritic activities. This study summarizes the literature about diterpenes and their derivatives acting against rheumatoid arthritis (RA) depending on the database reports until 31 August 2021. For this, we have conducted an extensive search in databases such as PubMed, Science Direct, Google Scholar, and Clinicaltrials.gov using specific relevant keywords. The search yielded 2708 published records, among which 48 have been included in this study. The findings offer several potential diterpenes and their derivatives as anti-RA in various test models. Among the diterpenes and their derivatives, andrographolide, triptolide, and tanshinone IIA have been found to exhibit anti-RA activity through diverse pathways. In addition, some important derivatives of triptolide and tanshinone IIA have also been shown to have anti-RA effects. Overall, findings suggest that these substances could reduce arthritis score, downregulate oxidative, proinflammatory, and inflammatory biomarkers, modulate various arthritis pathways, and improve joint destruction and clinical arthritic conditions, signs, symptoms, and physical functions in humans and numerous experimental animals, mainly through cytokine and chemokine as well as several physiological protein interaction pathways. Taken all together, diterpenes, diterpenoids, and their derivatives may be promising tools for RA management.

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“…Recently, researcher relies on the fact that oridonin itself can act as a protective agent against LPS-induced inflammatory response, which the specific mechanisms involve in ROS accumulation, JNK activation, nuclear translocation of NF- κ B ( Huang et al, 2020 ). Oridonin also inhibits autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes ( He et al, 2020 ). In addition, oridonin can also resist a series of inflammatory reactions including LPS-induced inflammation in human gingival fibroblasts ( Yu et al, 2019 ), IL-1β-induced inflammation in human osteoarthritis chondrocytes ( Jia et al, 2019 ) and LPS-induced endometritis ( Zhou et al, 2019 ).…”

Section: Pharmacologymentioning

confidence: 99%

Oridonin: A Review of Its Pharmacology, Pharmacokinetics and Toxicity

Zhang

et al. 2021

Front. Pharmacol.

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Oridonin, as a natural terpenoids found in traditional Chinese herbal medicine Isodon rubescens (Hemsl.) H.Hara, is widely present in numerous Chinese medicine preparations. The purpose of this review focuses on providing the latest and comprehensive information on the pharmacology, pharmacokinetics and toxicity of oridonin, to excavate the therapeutic potential and explore promising ways to balance toxicity and efficacy of this natural compound. Information concerning oridonin was systematically collected from the authoritative internet database of PubMed, Elsevier, Web of Science, Wiley Online Library and Europe PMC applying a combination of keywords involving “pharmacology,” “pharmacokinetics,” and “toxicology”. New evidence shows that oridonin possesses a wide range of pharmacological properties, including anticancer, anti-inflammatory, hepatorenal activities as well as cardioprotective protective activities and so on. Although significant advancement has been witnessed in this field, some basic and intricate issues still exist such as the specific mechanism of oridonin against related diseases not being clear. Moreover, several lines of evidence indicated that oridonin may exhibit adverse effects, even toxicity under specific circumstances, which sparked intense debate and concern about security of oridonin. Based on the current progress, future research directions should emphasize on 1) investigating the interrelationship between concentration and pharmacological effects as well as toxicity, 2) reducing pharmacological toxicity, and 3) modifying the structure of oridonin—one of the pivotal approaches to strengthen pharmacological activity and bioavailability. We hope that this review can provide some inspiration for the research of oridonin in the future.

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Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes

Cited by 22 publications

References 36 publications

Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients

Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients

Activities and Molecular Mechanisms of Diterpenes, Diterpenoids, and Their Derivatives in Rheumatoid Arthritis

Oridonin: A Review of Its Pharmacology, Pharmacokinetics and Toxicity

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