Rosmanol and Carnosol Synergistically Alleviate Rheumatoid Arthritis through Inhibiting TLR4/NF-κB/MAPK Pathway

Li, Lianchun; Pan, Zheng‐Hong; Dong, Ning; Fu, Yu-Xia

doi:10.3390/molecules27010078

Cited by 32 publications

(17 citation statements)

References 35 publications

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“…Schwager et al also showed that CS inhibits cytokine production and NFκB activation in murine macrophages and human chondrocytes [ 87 ]. In addition to its in vitro effects, CS also reduced serum or tissue levels of cytokines with inhibition of the NFκB pathway in animal models of inflammatory diseases such as spinal cord injury [ 16 ], atopic dermatitis [ 19 ] and rheumatoid arthritis [ 88 ]. In this study, we also found that CS suppressed infiltration of neutrophils and macrophages in kidneys of UUO mice, as indicated by reduced MPO activity and decreased numbers of Ly6B.2-positive cells and F4/80-positive cells.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

2022

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Renal fibrosis is a common feature of chronic kidney disease and is a promising therapeutic target. However, there is still limited treatment for renal fibrosis, so the development of new anti-fibrotic agents is urgently needed. Accumulating evidence suggest that oxidative stress and endoplasmic reticulum (ER) stress play a critical role in renal fibrosis. Carnosol (CS) is a bioactive diterpene compound present in rosemary plants and has potent antioxidant and anti-inflammatory properties. In this study, we investigated the potential effects of CS on renal injury and fibrosis in a murine model of unilateral ureteral obstruction (UUO). Male C57BL/6J mice underwent sham or UUO surgery and received intraperitoneal injections of CS (50 mg/kg) daily for 8 consecutive days. CS improved renal function and ameliorated renal tubular injury and interstitial fibrosis in UUO mice. It suppressed oxidative injury by inhibiting pro-oxidant enzymes and activating antioxidant enzymes. Activation of ER stress was also attenuated by CS. In addition, CS inhibited apoptotic and necroptotic cell death in kidneys of UUO mice. Furthermore, cytokine production and immune cell infiltration were alleviated by CS. Taken together, these findings indicate that CS can attenuate renal injury and fibrosis in the UUO model.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

2022

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“…; the current treatment of such diseases is still mainly to relieve the clinical symptoms by using anti-inflammatory analgesics and immunosuppressants [ 4 ]. With the continuous development of molecular studies, some studies have pointed out that the activation of TLRs can promote human immune defense function, among which Toll-like Receptor 4 (TLR4) plays an important role in regulating immune response and promoting the secretion of inflammatory factors, and can activate Nuclear Factor kappa-B (NF- κ B) to promote gene transcription [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

[Retracted] Investigation on the Inhibitory Effect of Methotrexate on Rheumatoid Synovitis via the TLR4‐NF‐κB Pathway in a Rat Model

Zhang

Liu

et al. 2022

Contrast Media & Molecular Imaging

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Rheumatoid arthritis (RA) is a rheumatoid immune system disease characterized by joint inflammation, resulting in synovial hyperplasia, articular cartilage damage or distortion, and extra-articular involvement. The morbidity is higher and the treatments are not effective in clinical, and also no unified to the pathogenesis of such diseases. The aim of this paper is to establish a rat model of rheumatoid synovitis and observe the inhibitory effect of methotrexate on this disease. A total of 100 SD rats are selected and randomly divided into 5 groups, with 20 rats in each group. The cold and damp factors of rheumatoid arthritis are induced by cold water and the arthritis score is used to verify the model. ELISA is used to measure the protein expression of Toll-like Receptor 4 (TLR4), Nuclear Factor kappa-B (NF-κB) and inflammation-related factors, and SPSS25.0 is used for statistical analysis. The results show that there is no significant difference in inflammatory scores among the four groups except the control group. However, after 3 months of intervention, the inflammatory scores in the methotrexate groups are significantly lower than those in the model group, and in the methotrexate group, the higher the dose, the lower the inflammatory scores. The experimental results show that the messenger ribonucleic acid (mRNA) and protein expressions of TLR4 and NF-κB from high to low are in the order of model group > low dose > middle dose > high dose > control group, and the expression trend of inflammation-related factors is the same as mentioned above. These results indicate that methotrexate can repair rheumatoid synovitis by inhibiting the inflammatory signaling pathway TLR4-NF-κB.

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“…RA reduced the arthritic index by reducing the frequency of COX‐2‐expressing cells 67 . In addition, RO and CA could decrease the serum pro‐inflammatory cytokine levels of IL‐6, MCP‐1, and TNF‐α by blocking the activation of the TLR‐4/NF‐κB/JNK pathways in rheumatoid arthritis mice 93 . Another study showed that RA significantly decreased the arthritic score and levels of TNF‐α in Wistar albino rats 68 .…”

Section: Resultsmentioning

confidence: 98%

Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases

et al. 2022

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This review aimed to identify preclinical and clinical studies examining the effects of rosmarinic acid (RA), carnosic acid (CaA), rosmanol (RO), carnosol (CA), and ursolic acid (UA) against allergic and immunologic disorders. Various online databases, including PubMed, Science Direct, EMBASE, Web of Sciences, Cochrane trials, and Scopus, were searched from inception until October 2022. Due to the suppression of the nuclear factor-κB (NF-κB) pathway, the main factor in allergic asthma, RA may be a promising candidate for the treatment of asthma. The other ingredients comprising CA and UA reduce the expression of interleukin (IL)-4, IL-5, and IL-13 and improve airway inflammation. Rosemary's anti-cancer effect is mediated by several mechanisms, including DNA fragmentation, apoptosis induction, inhibition of astrocyte-upregulated gene-1 expression, and obstruction of cell cycle progression in the G1 phase. The compounds, essentially found in Rosemary essential oil, prevent smooth muscle contraction through its calcium antagonistic effects, inhibiting acetylcholine (ACH), histamine, and norepinephrine stimulation. Additionally, CA exhibits a substantially greater interaction with the nicotinic ACH receptor than a family of medications that relax the smooth muscles, making it a potent antispasmodic treatment. The components have

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Rosmanol and Carnosol Synergistically Alleviate Rheumatoid Arthritis through Inhibiting TLR4/NF-κB/MAPK Pathway

Cited by 32 publications

References 35 publications

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

[Retracted] Investigation on the Inhibitory Effect of Methotrexate on Rheumatoid Synovitis via the TLR4‐NF‐κB Pathway in a Rat Model

Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases

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