Table 2.

Application of RSV in the treatment of inflammatory diseases

Diseases	Species	Routes and doses	Results	References
Lung inflammation (PM-induced)	C57BL/6J mice	Mice were exposed to ambient PM, and treated with RSV (50 mg/kg; 100 mg/kg)	RSV inhibited the activation of NLRP3 inflammasomes, and the expression of related inflammatory factors, which improved lung inflammation and fibrosis	[78]
Skeletal muscle inflammation (obesity-induced)	C57/BL6 mice	Mice were fed with normal chow die (NCD) and high fat diet (HFD)-supplemented with 0.4% RSV (4 g/kg)	RSV improved inflammation by reducing macrophage recruitment, increasing M2 polar cell count, inducing Treg cell ratio, reducing M1 polar cell number, and downregulating the expression of pro-inflammatory cytokines	[79]
Secondary damage after SCI	Sprague Dawley rats/ PC-12 cells	SCI rats received RSV treatment via intraperitoneal injection (200 mg/kg)/ PC-12 cells were cultured in media with RSV (10 µM ~ 50 µM)	RSV inhibited NF-κB and p38MAPK signaling pathways, inhibited inflammatory responses, and upregulated miR-132 expression to improve polysaccharide-induced cell damage	[80]
Asthma-induced airway inflammation and remodeling	Sprague Dawley rats	Asthma rats received RSV via intraperitoneal injection (10 µmol/l; 50 µmol/l)	RSV reduced asthma-induced airway inflammation by inhibiting HMGB1/TLR4/NF-κB pathway	[81]
Non-alcoholic steatohepatitis (high-fat diet-induced)	Sprague Dawley rats	Rats were fed high-fat diet (HFD) with RSV (100 mg/kg)	RSV maintained intestinal barrier integrity, stability of intestinal microbial community, and inhibited intestinal inflammation to alleviate chronic steatohepatitis.	[82]
Diabetic nephropathy	HBZY-1 cells (the rat glomerular mesangial cell line)	HBZY-1 cells were cultured in media with RSV (5 µM; 10 µM; 20 µM )	RSV inhibited proliferation, accumulation of extracellular matrix, and cellular inflammation of lipopolysaccharide-induced HBZY-1 cells by blocking SphK1/S1P2/NF-κB signaling pathway.	[83]
Polycystic ovary syndrome (PCOS)	Humans	PCOS patients received 800 mg/day of RSV orally	RSV inhibited the expression of NF-κB signaling pathway-related factors, and reduced endoplasmic reticulum stress to inhibit the occurrence of inflammatory reactions, thereby exerting therapeutic effects on PCOS patients.	[84]
Radiation-induced brain injury	Wistar rats	Rats of radiation-induced brain injury received RSV by intraperitoneal injection (100 mg/kg; 250 mg/kg)	RSV significantly reduced oxidative stress response, and expressions of inflammation/ apoptosis-related factors to protect brain tissues	[85]
Spontaneous Ulcerative Colitis	Winnie mice	Winnie mice were treated with β-lactoglobulin-RSV nanoparticles (50 mg/kg)	The stability and solubility of RSV encapsulated in β -lactoglobulin nanospheres were enhanced, and the incidence of colonic inflammation was significantly reduced.	[86]
Skin inflammation (PM-induced)	Normal human epidermal keratinocytes	Cells were cultured in media with various concentrations of PM and RSV (0; 0.01 µM; 0.1 µM; 1 µM; 10 µM; 50 µM; 100 µM)	RSV alleviated inflammatory response in human keratinocytes by inhibiting the expression of pro-inflammatory factors, and PM-induced oxidative stress.	[87]
Age-related macular degeneration	ARPE-19 human retina pigment epithelial cells	Cells were cultured in media with RSV (10 µM)	RSV downregulated the expression of inflammatory and apoptotic factors, and other cytokines, thus inducing autophagy, promoting survival, and anti-inflammatory stimuli of ARPE-19 cells.	[88]
Retinal inflammation (diabetes-induced)	Human retinal vascular endothelial cells (HRVECs)	HRVECs were cultured in media with high glucose and RSV (1 µmol/L; 10 µmol/L)	RSVS inhibited the infectious metabolic memory and increased HRVECs viability by activating the SIRT1/ AMPK signaling pathway.	[89]
Cirrhotic inflammation (neurological sequelae)	CD-1 mice	Cirrhotic-induced mice received daily RSV through oral gavage (10 mg/kg)	RSV significantly reduced inflammatory signaling factors, effectively relieved cell damage caused by oxidative stress, and upregulated the expression of tight junction protein in CCl4-induced cirrhotic mice.	[90]
Experimental autoimmune encephalomyelitis (EAE)	C57BL/6 mice	EAE-induced C57BL/6 mice received RSV via intraperitoneal injection (100 mg/kg)	RSV attenuated neuroinflammatory in EAE by regulating key miRNAs involved in cell cycle progression and apoptosis in activated encephalitogenic T-cells.	[91]
Neonatal hypoxic-ischemic brain injury (HIBI)	Pups (from timed-pregnant ICR mice)	HIBI-induced mice received RSV via by intraperitoneal injection (100 mg/kg)	RSV reduced neuroinflammatory responses in neonatal HIBI by activating SIRT1 to inhibit HMGB1/TLR4/MyD88/NF-κB signaling pathway.	[92]
Neuropathic pain	Sprague Dawley rats	Rats constructed for neuropathic pain were treated with RSV by intraperitoneal injection (300 ug/day)	RSV reduced neuroinflammation and neuropathic pain in rats by inhibiting autophagy via downregulating the TREM2 signaling pathway.	[93]