Pharmacokinetic of nasal curcumin:An approach for asthma medication

OBJECTIVE The study aims to evaluate intranasal(i.n.)curcumin at 5mg·kg-1,its absorption through nasal mucosa reaching blood and lungs and investigate its anti-allergic and anti-asthmatic potentiality in ameliorating ovalbumin induced asthma in mouse model.METHODS A simple and sensitive high performance liquid chromatography method using UV detection(HPLC-UV)was developed and validated for the determination of nasal curcumin 5mg·kg-1 in nasal mucosa,plasma and lungs from 15min-6hof post dosing and further applied to determine the pharmacokinetics parameter.Further,for the anti-asthmatic study,BALB/c mice were sensitized(day 1,7and 14)and challenged with ovalbumin(day 19-22)and treated with intranasal curcumin 5mg·kg-1(in the form of nasal drops)before an hour of challenge(day 19-22)to investigate its therapeutic effect on various parameters of airway inflammation as detected in the bronchoalveolar lavage fluid,serum and lung tissue.Serum was also used to study the liver kidney function test for the toxicity.RESULTS The validated method of HPLC was sensitive with a lower limit of quantitation of 5μg·mL-1 and the calibration curve represented good linearity(r2≥0.999)over the linear range of 5-50μg·mL-1.HPLC study reveals,absorption and quantification of curcumin as 1.9μg·mL-1 in the nasal mucosal scrapping at 15 min elevating to 4.9μg·mL-1 till 1h and declining to 3.2μg·mL-1 till 3h after intranasal administration of curcumin(5mg·kg-1).The plasma showed 0.9μg·mL-1 after 15 min spiking upto 1.5μg·mL-1 till 3h while lung homogenate retained up to 3.6μg·mL-1 of curcumin till 3h,which was detectable from 15min(0.27μg·mL-1)and was on higher side as compared to earlier studies.The same pharmacological dose(5mg·kg-1,i.n.)has shown anti-asthmatic potential by inhibiting airway inflammation(eosinophilic inflammation),bronchoconstriction and modulation in cytokines level of Th2(IL-4,IL-5),Th1(IFN-γ)and proinflammatory(TNF-α)cytokines in ovalbumin induced asthma without having any side effect as detected by liver kidney function test.CONCLUSION The study reveals nasal mucosa as a viable route for the absorption of intranasal curcumin and accommodating increased transportation to the blood and lungs.Also,the nasal route is effective in retaining the level of curcumin till 6h without any degradation and hence could be a promising route to improve its biological activities.Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops or through nebulizer in human subjects.Further,pharmacodynamic study is in progress to prove its effectiveness not only in pulmonary disorders but also for systemic disorders.     

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study北大核心CSCD

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Discriminative stimulus and antinociceptive effects of dihydroetorphine in rhesus monkeys

Abstract Rationale. Although dihydroetorphine has μ opioid agonist activity there is evidence to suggest that it is not identical to that of morphine. Objective. This study compared dihydroetorphine to other opioids under behavioral conditions that are sensitive to μ opioid agonism. Methods. The acute effects of dihydroetorphine, etorphine and morphine were evaluated using two procedures. In one procedure, monkeys received 3.2 mg/kg per day of morphine and discriminated naltrexone from saline while responding under a fixed-ratio 5 schedule of stimulus shock termination. In addition, a warm-water, tail-withdrawal procedure was used in untreated monkeys. Results. When acutely deprived of morphine, monkeys responded on the naltrexone lever, and this effect was reversed by dihydroetorphine, etorphine and morphine. Each agonist produced the maximum (20-s latency) antinociceptive effect in 50°C water. Naltrexone antagonized the discriminative stimulus and antinociceptive effects of dihydroetorphine and etorphine, although Schild analyses yielded large variability in slopes and pA₂ values. Naltrexone reversed established effects of dihydroetorphine and morphine in both procedures and pretreatment with dihydroetorphine (2, 6 or 24 h) did not alter the discriminative stimulus effects of morphine. Conclusions. Taken together, these data support the notion that dihydroetorphine is a μ agonist with a short duration of action; however, variability in antagonism of dihydroetorphine and morphine might be a manifestation of differences that have been reported for these drugs at the cellular level. Electronic Publication     

S-21007,强效5-羟色胺3受体部份激动剂,对小鼠焦虑的作用(英文)

AIM: To study the effect of S-21007, a 5-HT_3partial agonist in different animal models of anxiety inmice. METHODS: S-21007 effects were evaluatedin the behavior tests after intraperitioneal and oral acutetreatment or in the light/dark test after both acute andchronic treatments. RESULTS: S-21007 presentedanxiolytic-like properties after acute administration inthe light/dark box test, the mirrored chamber test, andthe elevated plus-maze at be doses 10 ng·kg~(-1)-100μg·kg~(-1), 1-100 μg·kg~(-1) and 10-100 μg·kg~(-1),respectively. In the light/dark box test, S-21007 wasactive orally after acute treatment at 100 ng·kg~(-1)-10mg·kg~(-1) and after chronic treatment (14 d) at 1-10μg·kg~(-1). S-21007 was devoid of sedative or stimula-     

Autophagy-dependent removal of α-synuclein: a novel mechanism of GM1 ganglioside neuroprotection against Parkinson’s disease

GM1 ganglioside is particularly abundant in the mammalian central nervous system and has shown beneficial effects on neurodegenerative diseases.In this study,we investigated the therapeutic effect of GM1 ganglioside in experimental models of Parkinson’s disease(PD)in vivo and in vitro.Mice were injected with MPTP(30 mg·kg-1·d?1,i.p.)for 5 days,resulting in a subacute model of PD.PD mice were treated with GM1 ganglioside(25,50 mg·kg^?1·d^?1,i.p.)for 2 weeks.We showed that GM1 ganglioside administration substantially improved the MPTP-induced behavioral disturbance and increased the levels of dopamine and its metabolites in the striatal tissues.In the MPP⁺-treated SH-SY5Y cells andα-synuclein(α-Syn)A53T-overexpressing PC12(PC12^(α-Syn A53T))cells,treatment with GM1 ganglioside(40μM)significantly decreasedα-Syn accumulation and alleviated mitochondrial dysfunction and oxidative stress.We further revealed that treatment with GM1 ganglioside promoted autophagy,evidenced by the autophagosomes that appeared in the substantia nigra of PD mice as well as the changes of autophagy-related proteins(LC3-II and p62)in the MPP⁺-treated SH-SY5Y cells.Cotreatment with the autophagy inhibitor 3-MA or bafilomycin A1 abrogated the in vivo and in vitro neuroprotective effects of GM1 ganglioside.Using GM1 ganglioside labeled with FITC fluorescent,we observed apparent colocalization of GM1-FITC andα-Syn as well as GM1-FITC and LC3 in PC12^(α-Syn A53T)cells.GM1 ganglioside significantly increased the phosphorylation of autophagy regulatory proteins ATG13 and ULK1 in doxycycline-treated PC12^(α-Syn A53T)cells and the MPP⁺-treated SH-SY5Y cells,which was inhibited by 3-MA.Taken together,this study demonstrates that the anti-PD role of GM1 ganglioside resulted from activation of autophagy-dependentα-Syn clearance.     

抗高血压中草药罗布麻NO释放作用的内皮保护作用和机制（英文）

OBJECTIVE The extracts of the Apocynum venetumleaves(AVLE),also known as Luobuma,is an antihypertensive medicinal herb used widely in TCM.AVLE has been reported to exert antihypertensive action by dilating the blood vessels in an endothelium-dependent and concentration-dependent manner with optimal effect seen at as low as 10μg·mL.The present study seeks to further evaluate the free radical scavenging actions and cellular mechanism underlying the nitric oxide(NO)-releasing property of AVLE in rat aorta and human umbilical vein endothelial cells(HUVECs).METHODS Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of NG-nitro-L-arginine(LNAME,100μmol·L-1),endothelial NO synthase inhibitor(eNOS),ODQ(1μmol·L-1),soluble guanylyl cyclase inhibitor,polyethyleneglycol catalase(PP2,20μmol·L-1),inhibitor of Src kinase and wortmannin(30nmol·L-1),and LY294002(20μmol·L-1),PI3-Kinase inhibitor.Total nitrite and nitrate(NOx)level were measured by Greiss reagent.The cellular effects of AVLE was tested in HUVECs at different concentration with or without inhibitors.The phosphorylation level of Akt and eNOS were assessed by Western blotting.RESULTS In the rat aorta,AVLE(0.3-10μg·mL-1)dose-dependently inhibited the contraction to phenylephrine(1μmol·L-1)and significantly suppressed theβ-NADPH-induced generation of superoxide anion(SOA).Removal of endothelium,treatment with L-NAME or ODQ prevented the vasorelaxant effects of AVLE.Similarly,pre-treatment with PP2,wortmannin and LY294002 reduced the vasorelaxant effects of AVLE.AVLE significantly increased of total NOx level in rat aorta compared to control.It also caused phosphorylation of AKT and eNOS in cultured HUVECs in a dose-dependent manner and which were markedly suppressed by PP2,wortmannin and LY294002.CONCLUSION The present results suggest that the vasorelaxant effect of AVLE is due to its dual ability of releasing NO and protecting it from the scavenging actions of the SOA.Furthermore,AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway.     

Impairment of contraction and release of nitric oxide in rat arota by levothyroxine

AIM: To study the influence of levothyroxine on rat aorta contraction and nitric oxide (NO) release. METHODS: levothyroxine was administered 0.75 mg·g~(-1)×8d sc,and responses of isolated rat aorta rings were recorded and compared in the absence and presence of L-Argnine (LArg) and N~ω-Nitro-L-Argnine(L-NOARG) on norepinephrine (NE)-induced contraction. RESULTS: AUC     

一种红蜂胶提取物治银屑病、消炎及镇痛作用(英文)

AIM: To study the antipsoriatic, anti-inflammatory, and analgesic effects of ethanolic extract of red propolis. METHODS and RESULTS: This extract induced the formation of granular layer in the mouse tail test used as a model of psoriasis. Propolis 50 mg·kg-1 ig showed anti-inflammatory activity in the cotton-pellet granuloma assay in rats, in croton oil-induced edema in mice at a dose of 25 % (2.5μL), and in the peritoneal capillary permeability test in mice at a dose of 10 mg·kg-1. The extract (25 mg·kg-1 ig) showed analgesic effect in the model of acetic acid-induced writhings, whereas 40 mg·kg-1 was effective in the hot plate test in mice. CONCLUSION- Anti-inflammatory, analgesic, and antipsoriatic properties of Cuban red propolis were evident.     

A widespread expression of c-fos was induced following an intraperitoneal injection of LPS and attenuated by vagotomy

It has been proposed that some of CNS responses to peripheral immune challenge are activated by a neural route especially via afferent fibers in the vagal nerve.In the present study, the expression of early-immediate gene c-fos in rat brain following an intraperitoneal injection of lipopolysaccharides ( LPS, 20 μg·kg~(-1)) was observed and the effect of subdiaphragmatic vagotomy to the Fos expression as well as the existence of type Ⅰ of IL-1 receptor (IL-lRI) in nodose ganglion were examined by     

Effect of norepinephrine on the antibody synthesis of rats in vitro

Norepinephrine (NE) has been supposed to be one of the important neurotransmitters modulating immune function.In the present study, the effect of NE on the antibody synthesis and the primary mechanism were investigated with the aid of the assay for antibody synthesis in vitro.Various concentrations of NE (10~(-10) to 10~(-6) mol·L~(-1)) with sheep red blood cells (SRBC) were simultaneously added to the lymphocyte suspension of mesenteric lymph node of rats and incubated for 5 d.NE at the concentrations of 10-9, 10-8, and 10~(-7) mol·L~(-1) significantly suppressed the antibody synthesis in vitro, having the strongest suppression at 10~(-8) mol·L~(-1). NE at 10~(-6) and 10~(-10) mol·L~(-1) did not cause remarked decrease in the antibody synthesis.NE     

Development of an in vitro cell model for LPS-and TNFα-induced airway inflammation

OBJECTIVE To develop an in vitro airway epithelial cell model suitable for the large-scale studies of compounds that can suppress lipopolysaccharide(LPS)-and tumor necrosis factor alpha(TNFα)-induced airway inflammation.METHODS We have optimized the protocols to culture BEAS-2B,a normal human bronchial epithelial cell line,in glass-bottom 384-well microtiter plates.The cells were stimulated with TNFαand LPS from Pseudomonas aeruginosa,a common lunginfection pathogen in cystic fibrosis and chronic obstructive pulmonary disease.We used ELISA to measure the secretion levels of two pro-inflammatory cytokines,interleukin(IL)-6and-8,after 0,4,8,16,24 hof stimulation;and immunofluorescence microscopy to measure the nuclear translocation of RelA,a subunit of the NF-κB complex,after 0,15,30,60,120 min of stimulation.To suppress the inflammatory response,we pre-treated the cells with a specific IκB kinase-2inhibitor,TPCA-1;the main bioactive component of Andrographis paniculata,andrographolide;and DMSO control for 1h.RESULTS We found that individual stimulant(either TNFα10ng·mL-1 or LPS 10μg·mL-1)increased the IL-6and IL-8 secretion levels by~12-17 foldsas compared to DMSO controls after 8h of stimulation.The combined stimulation(10ng·mL-1 TNFαand 10μg·mL-1 LPS)induced even higher IL-6 and -8 levels(~18-21 folds)at the same time points.Importantly,our imaging study shows that the NF-κB activation is early but transient under TNFαstimulation,late but sustained under LPS stimulation,and early and sustained under the combined stimulation.Finally,we also found that TPCA-1 10μmol·L-1 or andrographolide 30μmol·L-1 drastically reduced the IL-6 and -8 levels down to 4.5-9 folds as compared to the controls.CONCLUSIONThe combined TNFαand LPS stimulations induce faster and more sustained inflammatory responses,which can still be suppressed by anti-inflammatory compounds in our cell model.These more comprehensive activations of inflammatory signaling pathways will enable us to study and distinguish the mechanisms of different anti-inflammatory compounds or natural products.     

Study on pharmacodynamics of recombinant interferon α-2b suppository

Objective To investigate the antiviral activity of recombinant interferonα-2b suppository(IFNα-2b)in vivo and in vitro.Methods The cytopathic-effect inhibition assay was applied in this study to investigate the antiviral activity of this drug as well as yingtelong and axiluowei as positive control.The guinea pig model of vaginitis and skin infection caused by HSV-2 infection were established,treated with IFNα-2b suppository at dosages of 60000、180000、540000 IU,using IFNα-2b injection 180000 IU·kg-1 as controls.Score the pathological changes of appearance and skin,the virus activities of vaginal secretion and tissue sections of viginae were assayed after treatment.Results The TD50 of IFN α-2b and yingtelong for Vero cells was(>100)μg·mL-1 and(>100000)IU·mL-1,respectively.The IC50 of IFN α-2b and yingtelong and axiluowei for Herpes virus type 1 was(0.29±0.08)μg·mL-1 and(185.0±28.8)IU·mL-1 and(0.19±0.03)μg·mL-1,respectively.The mean scores for vaginal and skin lesion of the treated groups were lower than those of untreated group.Among these concentrations,the IFNα-2b suppository of 540000 IU·kg-1 group.Showed highest anti-viral activity.The virus activity in vaginal secretion of treated group was lower than that of untreated group too(P<0.01 or P<0.05).Tissue sections of viginae after treatment with IFNα-2b suppository showed significantly therapeutical effects on the degrees of vaginal lesion.At the same dosage,The anti-HSV activity of IFNα-2b suppository was also compared with IFNα-2b injection,the results showed that the activity of suppository of 540000 IU·kg-1 group was similar to that of the injection.Conclusions The IFNα-2b suppository has anti-viruses function both in vivo and in vitro.     

Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol

Kaempferol is a natural flavonol that possesses various pharmacological activities,including anti-arthritis effects,yet the underlying mechanisms remain controversial.To evaluate the anti-arthritis efficacy and the underlying mechanisms of kaempferol,collagen-induced arthritis(CIA)mice were treated with kaempferol intragastrically(200 mg·kg^−1·d^−1)and intraperitoneally(20 mg·kg^−1·d^−1).Pharmacodynamic and pharmacokinetic studies showed that the oral administration of kaempferol produced distinct anti-arthritis effects in model mice with arthritis in terms of the spleen index,arthritis index,paw thickness,and inflammatory factors;the bioavailability(1.5%,relative to that of the intraperitoneal injection)and circulatory exposure of kaempferol(Cmax=0.23±0.06 ng/mL)and its primary metabolite kaempferol-3-O-glucuronide(Cmax=233.29±89.64 ng/mL)were rather low.In contrast,the intraperitoneal injection of kaempferol caused marginal anti-arthritis effects,although it achieved a much higher in vivo exposure.The much higher kaempferol content in the gut implicated a potential mechanism involved in the gut.Analysis of 16S ribosomal RNA revealed that CIA caused imbalance of 14 types of bacteria at the family level,whereas kaempferol largely rebalanced the intestinal microbiota in CIA mice.A metabolomics study showed that kaempferol treatment significantly reversed the perturbation of metabolites involved in energy production and the tryptophan,fatty acid and secondary bile acid metabolisms in the gut contents of the CIA mice.In conclusion,we demonstrate for the first time that the high level of kaempferol in the gut regulates the intestinal flora and microbiotic metabolism,which are potentially responsible for the anti-arthritis activities of kaempferol.     

Sodium ferulate inhibits cardiomyocyte hypertrophy induced by Ang Ⅱ through enhancement of NO/cGMP signaling pathway

OBJECTIVE The present study is to investigate the effect of SF on neonatal rat cardiomyocytes of myocardial hypertrophy induced by 0.1 μmol · L~(-1) angiotensinⅡ(AngⅡ) and explore the underlying mechanism.METHODS The cultured cardiomyocytes from Sprague Dawley neonate rats were randomly divided into: normal,model(AngⅡ0.1 μmol·L~(-1)), L-arginine(1000 μmol·L~(-1))group and SF(50, 100, 200 μmol·L~(-1)) group. To observe whether SF had nonspecific injurious effect on the cells,SF 200 μmol·L~(-1)was added into the normal cardiomyocytes. To determine whether the effect of SF on cardiomyocyte hypertrophy is associated with NO release, another two groups[NG-nitro-L-arginine-methyl ester(L-NAME)]1500 μmol·L~(-1) combined with SF 200 μmol·L~(-1) and L-arginine 1000 μmol·L~(-1)) were established. RESULTS After administration, Ang Ⅱ decreased the NO content, NOS and e NOS activity in supernatant of cultured cardiomyocytes, and decreased the content of c GMP and increased the content of c AMP in cardiomyocytes, up-regulation the expression of PKC-β, Raf-1, ERK1/2 and down-regulated the expression of MKP-1 and e NOS. SF 200 μmol·L~(-1) and L-argininesignificantly ameliorated these changes.SF ameliorate the cardiomyocyte hypertrophy which can be inhibited by L-NAME. These results indicate that SF can inhibit cardiomyocyte hypertrophy induced by AngⅡand the probable mechanism involved to promote NO/c GMP signaling pathway and inhibit PKC and MAPK signaling pathway. CONCLUSION These results indicate that SF can inhibit cardiomyocyte hypertrophy induced by AngⅡ and the probable mechanism involved to promote NO/c GMP signaling pathway and inhibit PKC and MAPK signaling pathway.     

Uptake of dopamine by rat hepatocytes in vitro

The present results showed that uptake of dopamine (DA) by rat isolated hep-atocytes was mediated, in addition to simple diffusion, mainly by a transporter-involved process, with Km of 66. 8 μmol and Vmax of 52. 3 pmol·min-1/105 cells. The process was pH- and temperature-dependent and required an activation energy of 4. 12 kcal ·mol-1(Q10 = 1.25) in the range of 2.0-12.7 C and 13.0 kcal·mol -1(Q10 = 2. 0) in the range of 12.7 -39.0C. Cysteine residue having free thiol group was. unrelated to the activity of the transporter. Catecholamines, serotonin, and cocaine inhibited the DA transport , but tyramine (TA) and tryptamine, as well as benztropine and imipramine (which are potent inhibitors for hepatic TA transporter and neuronal DA transporter), had no inhibitory effect on the transport of DA in these cells. These results indicated that DA was taken up into hepatocytes by a distinct carrier. NaF and mastoparan influenced the transport activity in these cells further, suggesting that signal transduci     

S-40 Effects of synthetic daurisoline and its three optical isomers on high potassium- and Bay k 8644-induced increase in free cytosolic calcium

AIM: To study the structure-activity relationships of daurisoline (Dau). METHODS: Attached PC12 cells were loaded with Fura 2-AM 3 μmol·L~(-1) and then incubated in standard medium (5 mmol·L~(-1)).Two rain before the addition of K~ 75 mmol·L~(-1) or Bay k 8644 1 mmol     

Role of a new-type polypeptide in regulation of oxidative stress in cardiac hypertrophy through ox-CaMK Ⅱ

OBJECTIVE Oxidative stress is the imbalance between the production and removal of reactive oxygen species(ROS), leading to cel and tissue damage.There is growing evidence that excessive ROS is induced in cardiac hypertrophy and heart failure. Over accumulation of ROS subsequently activates ROS-sensitive downstream signaling pathways associated with pathological myocardial hypertrophy. Angiotensin Ⅱ(Ang Ⅱ)increases ROS in ventricular myocardium by acting on oxidized CaMK Ⅱ(ox-CaMK Ⅱ). This study will explore the role of a new polypeptide targeting on CaMKⅡ in the regulation of oxidative stress in cardiac hypertrophy through ox-CaMKⅡ, and provide a new target and a new way for the treatment of cardiac hypertrophy. METHODS H9c2 cells were divided into three groups. The control group was given complete medium. The cardiac hypertrophy group was administered by 100 nmol·L~(-1) AngⅡ. After 24 h of administration of Ang Ⅱ, the polypeptide group was given a new type polypeptide, 5 μg· m L~(-1). Oxidative stress was estimated in vivo by measuring ROS level,ox-CaMK Ⅱ expression and superoxide dismutase(SOD)activity. RESULTS Compared with that of the control group, the SOD activity in the cardiac hypertrophy group was decreased, while the new polypeptide could significantly improve the SOD activity. Among the three groups, the expression of ox-CaMK Ⅱ in the cardiac hypertrophy group was the highest, demonstrating that this novel polypeptide could reduce ox-CaMKⅡ expression. CONCLUSION In conclusion, our newly designed CaMKⅡ-targeted polypeptide can inhibit ROS-mediated downstream pathway by inhibiting ox-CaMK Ⅱ expression and reducing excessive ROS accumulation, thereby reversing cardiac hypertrophy.