hydroxysafflor-yellow-a and Body-Weight

Allergic reaction is the most common nasal conditions worldwide and it will remain throughout life. The symptoms of an allergic reaction include sneezing, itching, hives, swelling, difficulty breathing, and a runny nose. Hydroxysafflor yellow A (HYA) is a flavonoid compound which is the active phyto-constituent of flower of Carthamus tinctorius L., and exhibited the various medicinal activities like antioxidant, anti-inflammatory and cardiovascular protective effects. This study aimed to assess the efficacy and mode of action of HYA against the allergic rhinitis induced by ovalbumin in mice. HYA was given orally to the Swiss BALB/s mice once daily, 1 h before, they were challenged with ovalbumin (OVA) via intranasal administration, after that the mice were sensitized via intraperitoneal injection of OVA. Allergic nasal symptoms, body weight, spleen weight, OVA-specific immunoglobulins, inflammatory cytokines, Th17 cytokines and Th17 transcription factors also estimated. HYA had a significant (p < .001) effect on body weight and reduced spleen weight. It effectively decreased the nasal symptoms of allergy such as sneezing, rubbing, and redness. HYA significantly reduced the level of malonaldehyde (MDA) and improved levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH). It also remarkably decreased the levels of Th2 cytokines and Th17 transcription factors like RAR-related orphan receptor gamma (ROR-γ), signal transducer and activator of transcription 3 (STAT3) and phosphor signal transducer and activator of transcription 3 (p-STAT3), while increasing levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The treatment with HYA improved the lung histology in mice with allergic rhinitis. The results suggest that HYA may have therapeutic potential against ovalbumin-induced allergic rhinitis in mice, by altering the Th17/Treg balance and improving the Nrf2/HO-1 signaling pathway.

Topics: Animals; Body Weight; Cytokines; Disease Models, Animal; Heme Oxygenase-1; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-E2-Related Factor 2; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Sneezing; STAT3 Transcription Factor

Our previous studies found that safflower yellow (SY) and its main component hydroxysafflor yellow A (HSYA) could alleviate obesity and improve leptin resistance in high-fat diet (HFD) induced obese mice. Therefore, our present study aimed to investigate whether the above effect of SY/HSYA was a direct effect or follow-up effect of weight loss and whether leptin was essential for the anti-obesity effect of SY/HSYA or not. HFD-induced obese mice were treated with SY or HSYA for 4 weeks, while ob/ob mice were treated with SY for 10 weeks. Body weight, food intake, fat mass, and serum leptin levels were measured. The leptin sensitivity experiment was conducted in HFD-induced obese mice. The expressions of leptin and its signaling-related genes were detected by RT-qPCR and Western blot methods. SY/HSYA treatment had no effect on food intake, energy expenditure, body weight, fat mass, and serum leptin levels in HFD-induced obese mice. However, the leptin sensitivity experiment showed that the food intake decreased by 18.4% in the HFD-SY group and the body weight gain decreased by 104.6% in the HFD-HSYA group, respectively (both P < 0.05). Furthermore, the expressions of leptin and leptin signaling inhibitory regulators were significantly decreased, while the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) were notably increased in WAT of HFD-induced obese mice, fully differentiated 3T3-L1 adipocytes after SY/HSYA intervention (all P < 0.05). Interestingly, SY treatment was ineffective on body weight, fat mass, and glucose metabolism in leptin-deficient ob/ob mice. SY/HSYA administration could firstly improve peripheral leptin resistance in adipose tissue of HFD-induced obese mice before their body weight was significantly changed, and leptin was essential for the anti-obesity effect of SY.

Topics: Animals; Body Weight; Chalcone; Diet, High-Fat; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Quinones

Hydroxysafflower yellow A (HSYA) protects against acute kidney injury through TLR4/NF-κB pathway. However, the effect and potential mechanism of HSYA in ulcerative colitis (UC) have been rarely reported, which is thus investigated in this research. An in vivo UC model was established by oral administration of 5% dextran sulfate sodium (DSS) in Sprague-Dawley rats. After HSYA treatment, the daily body weight and colon length of rats were measured. Then rat colon tissues, myeloperoxidase (MPO) activity, and the levels of inflammatory cytokines were examined by histopathological examination (HE) staining, immunohistochemistry, ultraviolet spectrophotometry, and enzyme-linked immune sorbent assay (ELISA) respectively. The activated TLR4/NF-κB pathway was detected by Western blot. RAW 264.7 cell viability was detected by MTT assay after lipopolysaccharide (LPS) treatment, and ELISA and Western blot were performed again to investigate the effects of HSYA on LPS-treated cells. DSS administration increased body weight and colon length of rats and induced colon tissue injury. DSS or LPS treatment up-regulated the levels of TNF-α, IL-1β, and IL-6 and activated TLR4/NF-κB pathway of colon tissues and cells, respectively. HSYA partially reversed the above effect of DSS and LPS treatment, and the effects of the drug were improved with the dosage. Taken together, HSYA alleviates UC by suppressing TLR4/NF-κB signaling pathway, which may provide a new insight for the treatment of UC.

Topics: Animals; Body Weight; Chalcone; Colitis, Ulcerative; Colon; Disease Models, Animal; Lipopolysaccharides; NF-kappa B; Quinones; Rats; Rats, Sprague-Dawley; Signal Transduction; Toll-Like Receptor 4

Hydroxysafflor yellow A (HSYA) is the main segment of the safflower yellow pigments, and its second clinical study has been approved by the China SFDA for the treatment of brain blood vessel disease. Present studies were conducted to demonstrate the subchronic toxicity of HSYA. Sprague-Dawley (SD) rats were tested by daily intraperitoneal (IP) injection of HSYA at the doses of 180, 60, 20 mg/kg for 90 days. HSYA at high dose of 180 mg/kg and at middle dose of 60 mg/kg (90-day daily injection) induced a prolonged blood coagulation time without influencing the normal blood coagulation process. No animal died from hemorrhaging. The prolonged blood coagulation time was recovered to a normal level on the 28th day after withdrawing the drug. Kidney injury, including round tubular figures and a breaking-off of the tubular epithelium in histological slices under the microscope scenic, was only observed in the rats given by HSYA at 180 mg/kg. HSYA at dose of 180 mg/kg also increases the liver index without an obvious pathological change in liver histological analysis. There was no other organ injury found in this study. In conclusion, 90 days of HSYA treatment at a dose of 180 mg/kg, not at a dose of 60 mg/kg, induces a slight nephrotoxicity.

Topics: Animals; Blood Cell Count; Blood Chemical Analysis; Blood Coagulation; Body Weight; Chalcone; Eating; Injections, Intraperitoneal; Quinones; Rats; Rats, Sprague-Dawley