The Abilities of Salidroside on Ameliorating Inflammation, Skewing the Imbalanced Nucleotide Oligomerization Domain-Like Receptor Family Pyrin Domain Containing 3/Autophagy, and Maintaining Intestinal Barrier Are Profitable in Colitis

Abstract

Salidroside (Sal), as a major glycoside extracted from Rhodiola rosea L., has exhibited its mighty anti-aging, anti-oxidant, anti-cancer, anti-inflammation, and neuroprotective effects in many diseases. Recently, it has showed its protective effect in colitis mice by activating the SIRT1/FoxOs pathway. Whereas, it is not known whether Sal has other protective mechanisms on dextran sulfate sodium (DSS)-induced colitis in mice. In this study, we investigated the protective effects and mechanisms of Sal on DSS-induced colitis in mice. The results demonstrated Sal was a competent candidate in the treatment of ulcerative colitis (UC). Sal remitted DSS-induced disease activity index (DAI), colon length shortening, and colonic pathological damage. Simultaneously, Sal alleviated excessive inflammation by reversing the IL-1β, TNF-α, and IL-10 protein levels in DSS-treated mice. Western blot analysis revealed that Sal inhibited p65 and p38 activation together with peroxisome proliferator-activated receptor (PPARγ) up-regulation. In addition, Sal skewed the imbalanced activation of nucleotide oligomerization domain-like receptor family pyrin domain containing 3 inflammasome and autophagy contributing to colitis recovery. The damaged intestinal barrier induced by DSS was also alleviated along with plasma lipopolysaccharides (LPS) reduction after Sal treatment. In vitro, Sal showed PPARγ-dependent anti-inflammatory effect in LPS-stimulated RAW264.7 cells. In summary, our results demonstrated that Sal might be an effective factor for UC treatment and its pharmacological value deserved further development.

Salidroside Suppresses the Proliferation and Migration of Human Lung Cancer Cells through AMPK‐Dependent NLRP3 Inflammasome Regulation

“…Similarly, SAL administration improved mechanical ventilation-induced lung injury in mice through the Sirt1-dependent inhibition of the NLRP3 inflammasome [ 40 ]. In dextran sulfate sodium-induced ulcerative colitis models, the protective effects of SAL were in part dependent on its inhibitory effects on the NLRP3 inflammasome [ 41 ]. Moreover, SAL has been shown to regulate the NLRP3 inflammasome through the TXNIP-NLRP3 pathway, providing protection against high glucose exposure, due to the accumulation of the extracellular matrix in glomerular mesangial cells [ 42 ] or through insulin resistance in hepatocytes [ 25 ].…”

Salidroside Attenuates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice and Modulates Inflammation of the Gut-Brain Axis

“…Recent evidence has revealed that SAL provides neuroprotection by modulating mitochondrial biogenesis and microglial polarization ( Barhwal et al, 2015 ; Liu et al, 2018 ). Notably, SAL exhibits significant anti-inflammatory effects in multiple diseases, such as osteoarthritis ( Chen et al, 2019 ), colitis ( Liu et al, 2019 ), skeletal muscle atrophy ( Huang et al, 2019 ), renal interstitial fibrosis, ( Li et al, 2019 ) and CNS diseases ( Liu et al, 2018 ; Wang et al, 2018 ). Furthermore, recent findings have suggested that SAL alleviates liver injury by maintaining the balance of the gut microbiota ( Yuan et al, 2019 ).…”

NLRP3 inflammasome in digestive diseases: From mechanism to therapy

“…SAL reduced obesity, abnormal blood glucose and liver lipid deposition in NAFLD mouse model by regulating ROS and AMPK-dependent TXNIP/NLRP3 pathways (201). Moreover, SAL also showed therapeutic potential in UC and CCl 4 -induced liver injury models (202,203). Dihydromyricetin (DHM) is a polyphenol which isolates from Ampelopsis grossedentata.…”