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Objective:To investigate the effect of combined treatment of hyperforin(HPF) and amlexanox(AM) on obesity and metabolic disorders.Methods:ob/ob mice were used as an obese mice model and treated with HPF alone(2.5 mg/kg intraperitoneal injection) or combined with AM(50 mg/kg, gavage administration) for 4 weeks. Their body weight and food intake were monitored, glucose tolerance test and insulin tolerance test were performed, serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels were detected. Nuclear magnetic resonance was used to detect the body composition and metabolic cage was used to detect the energy consumption. After sampling, HE staining was used to observed the pathological change of fat and liver tissues, Western blotting and enzyme-linked immunosorbent assay(ELISA) were used to detect the cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA) signaling pathway.Results:Compared to the vehicle-treated mice(54.07 g), HPF-treated mice showed attenuated body weight gain(51.33 g, P=0.042) and reduced total fat mass( P=0.011); while administration of HPF in combination with AM(HPF/AM) further reduced the body weight(47.61 g, P=0.041). HE staining analysis showed that HPF alone or HPF/AM treatment both decreased the diameters of adipocytes and infiltration of white fat( P=0.014, P=0.032) in brown adipose tissues, which resulted in a trend of browning. However, HPF/AM-treatment didn′t further diminish adipocytes or reduce lipid accumulation in brown adipose tissues compared to HPF-treated mice. In addition, the basal oxygen consumption rate(VO 2, P<0.001) and(VCO 2, P=0.002) of HPF-treated mice were mainly elevated in the light phase relative to that of control mice; while HPF/AM-treatment further promote the energy consumption both in the dark phase and light phase. Notably, cAMP-PKA signaling pathway was obviously activated under HPF/AM-treatment in inguinal white adipose tissue. Moreover, HPF/AM-treatment showed beneficial effects on glucose metabolism and fatty liver, as indicated by improved insulin resistance, reduced liver steatosis( P=0.049) and the serum ALT levels( P=0.008). Conclusion:Combined administration of HPF and AM is an effective strategy in the treatment of obesity, improvement of metabolic disorders and alleviation of catecholamine resistance.
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Abstract Cardiorenal syndrome is a life-threatening condition. The aim of the current study was to determine the cardioprotective effects of amlexanox in 5/6 nephrectomized rats. Rats were randomly assigned to three groups: sham, 5/6 nephrectomized rats, and amlexanox-treated 5/6 nephrectomized group. Amlexanox (25 mg/kg/day, i.p.) administration was started just after surgery and continued for 10 weeks. After treatment, kidney function (serum creatinine and urea) and blood pressure (systolic and diastolic) were measured. Heart weight (normalized to tibial length) and fibrosis area percentage were measured. Serum brain natriuretic peptide (BNP, heart failure marker) and cardiac levels of ß1-adrenergic receptor (ß1AR), ß-arrestin-2, phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol (DAG), pS473 Akt (a survival marker), and caspase-3 activity (an apoptosis marker) were also measured. The 5/6 nephrectomy caused renal impairment, cardiac fibrosis, apoptosis, and heart failure indicated by down- regulation of cardiac ß1AR down-stream signals compared with those in the sham group. Interestingly, amlexanox significantly reduced all cardiopathological changes induced after 10 weeks of 5/6 nephrectomy. Amlexanox showed potent cardiac antifibrotic and antiapoptotic effects in 5/6 nephrectomized rats, which were associated with reduced heart failure. To our knowledge, this is the first study that addresses the potent in vivo cardioprotective effects of amlexanox
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Animals , Male , Rats , Cardio-Renal Syndrome/pathology , beta-Arrestin 1/adverse effects , Aftercare/classification , Creatinine/adverse effects , Heart Failure/complicationsABSTRACT
Objective:To optimize the formula of amlexanox nasal thermosensitive gel spray and establish the quality control meth-od. Methods:Amlexanox nasal thermosensitive gel spray was prepared by a cold dissolving method, and poloxamer 407 (P407) and poloxamer 188 (P188) were used as the carrier materials. Central composite design-response surface methodology was used to optimize the formula with the amount of P407 and P188 as the influencing factors and the gel temperature and the viscosity before gelling as the indices. The content of amlexanox was determined by HPLC. According to Chinese Pharmacopoeia (2010 edition), the other indices of the preparation such as appearance, pH, viscosity, content, total spray times of each bottle and the content of each spray were deter-mined as well. Results:The optimum ratio of P407 and P188 was 17. 0% and 0. 9%,respectively . The average recovery of amlexanox was 98. 8% and RSD was 1. 7%(n=9). The quality of 3 batches of amlexanox nasal thermosensitive gel spray met the related require-ments. Conclusion:The formula and preparation process of amlexanox nasal thermosensitive gel spray are reasonable and feasible with controllable quality, which is worthy of further research.
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Objectives: The primary objective of the following study is to determine and secondary objective is to compare the efficacy and safety of 5% amlexanox oral paste in the treatment of recurrent minor aphthous ulcers and also to evaluate the recurrence rate of aphthous ulcers over a period of 1 year. Materials and Methods: The present study was conducted on 100 patients diagnosed to have recurrent minor aphthous ulcers of which, 50 patients were advised to apply 5% amlexanox oral paste directly on the ulcer 4 times a day for 6 days and the other 50 patients were given placebo paste for the same duration. The baseline parameters were recorded on the first visit which includes ulcer size, pain, erythema and exudation. Efficacy and safety evaluations were made on the 4 th day and 6 th day. In total 30 patients with increased frequency of ulcers were advised to use 5% amlexanox paste for one whole year and the number of ulcers per month was recorded to evaluate any decrease in the recurrence rate. Results: Male patients dominated the study with 73 males and 27 females. The mean age of the total sample was 26.6 years. The amlexanox group showed marked reduction in ulcer size (P < 0.001), significant reduction in the visual analog scale scores of pain (P < 0.001), significant lower scores of erythema and exudation (P < 0.001) when compared to the placebo group on the 6 th day of follow-up. The incidence of recurrence of ulcers was significantly reduced up to the 6 th month, but thereafter recurrence rate slowly increased. Conclusions: Almost 5% of Amlexanox oral paste is clinically beneficial in reducing the pain, erythema, exudation and size of the ulcer over a period of 6 days. There was no definite conclusion drawn with respect to its effect on the recurrence rate of aphthous ulcers over a period of 1 year.
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0.05), on the 4th day 7.56?6.87 and 10.00?7.07 (P0.05). After therapy all the data of electrocardiogram, blood routine examination and blood biochemical test of the cases were without clinical significance. Conclusion:50 g/L amlexanox is effective and safe in the treatment of RAU.
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OBJECTIVE:To study the effects and security of amlexanox oral coating for treatment of minor recurrent aphthous ulcer(MIAU). METHODS:A randomized double-blind experiment was carried on 42 patients with MIAU were randomly divided into experimental group(20 patients),and control group(22 patients),each group respectively administered with amlexanox coating and placebo,at the lesion site 4 times a day for 5 days.RESULTS:At 3 days,the effective rates of healing in the experimental and control group were 85.0% and 36.4%,respectively(P