Celastrol attenuates collagen-induced arthritis via inhibiting oxidative stress in rats

Gao, Qiang; Qin, Haihui; Zhu, Lei; Li, Da‐Jin; Hao, Xiuwei

doi:10.1016/j.intimp.2020.106527

Cited by 37 publications

(31 citation statements)

References 33 publications

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“…Intriguingly, in our experimental conditions, the reduction of cortical ROS amount and lipid peroxidation induced by early celastrol administration was accompanied by increased levels of SOD1, GSH and CAT with respect to mice receiving only ketamine in postnatal life. Supporting our hypothesis, previous preclinical evidence have reported that celastrol could attenuate oxidative damage by increasing levels and activity of SOD, GSH, glutathione peroxidase, glutathione reductase, and CAT ( Shaker et al, 2014 ; Wang et al, 2014 ; Boran et al, 2019 ; Gao et al, 2020 ). Although still speculative, the effects of celastrol on cortical ROS levels and lipid peroxidation, at least in our experimental conditions, might be explained by a concomitant action of this compound on ROS production and their degradation, finally resulting in the recovery of the redox balance, early altered by ketamine.…”

Section: Discussionsupporting

confidence: 84%

Postnatal Antioxidant and Anti-inflammatory Treatments Prevent Early Ketamine-Induced Cortical Dysfunctions in Adult Mice

et al. 2020

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Early brain insult, interfering with its maturation, may result in psychotic-like disturbances in adult life. Redox dysfunctions and neuroinflammation contribute to long-term psychiatric consequences due to neurodevelopmental abnormalities. Here, we investigated the effects of early pharmacological modulation of the redox and inflammatory states, through celastrol, and indomethacin administration, on reactive oxygen species (ROS) amount, levels of malondialdehyde (MDA) and antioxidant enzymes (superoxide dismutase 1, SOD1, glutathione, GSH, and catalase, CAT), as well as of pro-inflammatory cytokines (tumor necrosis factor-alpha, TNF-α, interleukin-6, IL-6, and interleukin-1 beta, IL-1β), in the prefrontal cortex of adult mice exposed to a neurotoxic insult, i.e. ketamine administration, in postnatal life. Early celastrol or indomethacin prevented ketamine-induced elevations in cortical ROS production. MDA levels in ketamine-treated mice, also administered with celastrol, were comparable with the control ones. Indomethacin also prevented the increase in lipid peroxidation following early ketamine administration. Whereas no significant differences were detected in SOD1, GSH, and CAT levels between ketamine and saline-administered mice, celastrol elevated the cortical amount of these antioxidant enzymes and the same effect was induced by indomethacin per se . Both celastrol and indomethacin prevented ketamine-induced enhancement in TNF-α and IL-1β levels, however, they had no effects on increased IL-6 amount resulting from ketamine exposure in postnatal life. In conclusion, our data suggest that an early increase in cortical ROS scavenging and reduction of lipid peroxidation, via the enhancement of antioxidant defense, together with inhibition of neuroinflammation, may represent a therapeutic opportunity against psychotic-like disturbances resulting, later in life, from the effects of a neurotoxic insult on the developing brain.

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Section: Discussionsupporting

confidence: 84%

Postnatal Antioxidant and Anti-inflammatory Treatments Prevent Early Ketamine-Induced Cortical Dysfunctions in Adult Mice

et al. 2020

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“…24 The CIA model was established in Wistar rats according to the reference methods. 37,38 Briefly, bovine CII was dissolved in 0.1 M acetic acid and emulsified in an equal volume of IFA at 4°C to obtain a final CII concentration of 1 mg/mL. In the first day, all rats (except for those in the normal group) were injected with 0.2 mL CII emulsion intradermally as the primary immunostimulation.…”

Section: Nano-hplc-ms/ms Analysis Of Jtgmentioning

confidence: 99%

Jintiange Capsule Alleviates Rheumatoid Arthritis and Reverses Changes of Serum Metabolic Profile in Collagen-Induced Arthritic Rats

Wang¹,

Shen²,

Zhuang³

et al. 2021

JIR

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Jintiange capsule (JTG), an approved drug developed as a substitute for tiger bone (TB), has been clinically applied for osteoporosis therapy since 2003. The drug is composed of bionic TB powder, in which peptides and proteins are primarily enriched from other bone extracts. However, as a precious material of traditional Chinese medicine (TCM), TB has been mainly understood and used in TCM to relieve osteoporosis, rheumatoid arthritis and bone injury. Inspired by those, the purpose of this study was to investigate whether JTG also had an effect on relieving rheumatoid arthritis in collagen-induced arthritic (CIA) rats and explore potential mechanism from the perspective of serum metabolic profile changes. Methods: JTG was analyzed using Nano LC-MS/MS and orally administered in CIA rats for 6 weeks. After administration, intervention effects of JTG on synovial inflammation, bone micro-architecture and bone metabolism were studied, and the impact of JTG on serum metabolic profiles in CIA rats was investigated by metabolomics. Results: Nine bioactive peptides were identified in JTG. In animal treatments, JTG alleviated paw swelling (P < 0.01), arthritic severity (P < 0.01) and synovial tissue proliferation, as well as inflammatory cell infiltration of ankle joint, decreased bone loss, improved microstructure of bone in CIA rats by regulating bone absorption and formation, specifically increasing bone mineral density (BMD) (P < 0.05), bone volume fraction (BVF) (P < 0.05), trabecular number (Tb.N) (P < 0.05) and decreasing trabecular separation (Tb.Sp) (P < 0.05). Besides, serum IL-6 was down-regulated remarkably in CIA rats (P < 0.05). Furthermore, metabolomics analysis revealed that 32 metabolites were regulated significantly (P < 0.05) by comparison between CIA model and JTG in 360 mg/kg dose. The pathway analysis implied that JTG was involved in regulation of biosynthesis of phenylalanine. Conclusion: JTG alleviates rheumatoid arthritis and reverses changes in serum metabolic profile in CIA rats.

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“…Hypoxia has been associated with RA; therefore, the suppression of oxidative stress may be a mechanism through which celastrol exerts its effect in RA treatment 152 . Recently, Gao et al 154 evaluated the antiarthritis effects of celastrol using collagen‐induced arthritis model rats. They measured the levels of paw swelling; arthritis scores; and the serum levels of TNF‐α, IL‐1β, IL‐6, and interferon (IFN)‐γ in the rats as well as overexpressed Nox4.…”

Section: Bioactivity and Mechanisms Of Action Of Celastrolmentioning

confidence: 99%

“…They measured the levels of paw swelling; arthritis scores; and the serum levels of TNF‐α, IL‐1β, IL‐6, and interferon (IFN)‐γ in the rats as well as overexpressed Nox4. The data indicated that celastrol alleviates arthritis by suppressing inflammatory cytokines and oxidative stress 154 . RA synovial fibroblasts (RASFs) are basic effector cells in the pathogenesis of RA, which also makes them a possible therapeutic target in RA therapy.…”

Section: Bioactivity and Mechanisms Of Action Of Celastrolmentioning

confidence: 99%

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

Lü

Liu

Zhou

et al. 2020

Medicinal Research Reviews

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Celastrol, a quinone‐methide triterpenoid, was extracted from Tripterygium wilfordii Hook. F. in 1936 for the first time. Almost 70 years later, it is considered one of the molecules most likely to be developed into modern drugs, as it exhibits notable bioactivity, including anticancer and anti‐inflammatory activity, and exerts antiobesity effects. In addition, the molecular mechanisms underlying its bioactivity are being widely studied, which offers new avenues for its development as a pharmaceutical reagent. Owing to its potential therapeutic effects and unique chemical structure, celastrol has attracted considerable interest in the fields of organic, biosynthesis, and medicinal chemistry. As several steps in the biosynthesis of celastrol have been revealed, the mechanisms of key enzymes catalyzing the formation and postmodifications of the celastrol scaffold have been gradually elucidated, which lays a good foundation for the future heterogeneous biosynthesis of celastrol. Chemical synthesis is also an effective approach to obtain celastrol. The total synthesis of celastrol was realized for the first time in 2015, which established a new strategy to obtain celastroid natural products. However, owing to the toxic effects and suboptimal pharmacological properties of celastrol, its clinical applications remain limited. To search for drug‐like derivatives, several structurally modified compounds were synthesized and tested. This review focuses primarily on the latest research progress in the biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of celastrol. We anticipate that this paper will facilitate a more comprehensive understanding of this promising compound and provide constructive references for future research in this field.

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Celastrol attenuates collagen-induced arthritis via inhibiting oxidative stress in rats

Cited by 37 publications

References 33 publications

Postnatal Antioxidant and Anti-inflammatory Treatments Prevent Early Ketamine-Induced Cortical Dysfunctions in Adult Mice

Postnatal Antioxidant and Anti-inflammatory Treatments Prevent Early Ketamine-Induced Cortical Dysfunctions in Adult Mice

Jintiange Capsule Alleviates Rheumatoid Arthritis and Reverses Changes of Serum Metabolic Profile in Collagen-Induced Arthritic Rats

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

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