Effects of Aconiti Lateralis Radix Praeparata via NO/mitochondrial energy metabolism signal pathway in deficiency cold and deficiency heat syndromes based on medicine-syndrome correspondence
Objective:To study the differences of NO/mitochondrial energy metabolism signal pathway changes by Aconiti Lateralis Radix Praeparata in different cold and heat syndromes,and reveal the biological effect mechanisms of traditional Chinese medicine(TCM)properties under different syndrome states from medicine-syndrome correspondence.Methods:The models of deficiency-cold and deficiency-heat syndrome were established by gavage with hydrocortisone and dexamethasone.Fifty-six SPF grade Kunming mice were randomly divided into a control group,a deficiency-cold model group,a deficiency-cold+low dose Fuzi group,a deficiency-cold+high dose Fuzi group,a deficiency-heat model group,a deficiency-heat+low dose Fuzi group,a deficiency-heat+high dose Fuzi group,with 8 mice in each group.The mice were continuously administered for 14 days.The levels of cAMP,cGMP,NO and ROS in serum of mice were measured by ELISA.The levels of MPTP and ROS in primary cardiac cells of mice were detected by flow cytometry.The protein expression levels of Bcl-2,Bax,Caspase-3 and Caspase-9 in primary cardiac cells of mice were detected by Western Blot.Results:Compared with the control group,the mice in the deficiency-cold model group showed weight loss,decreased cAMP/cGMP,decreased serum NO content,increased ROS content,increased ROS and MPTP levels in cardiac cells,increased Bax and Caspase-3 protein expression in primary cardiac cells,and decreased Bcl-2 protein expression(P<0.05,P<0.01).The mice in the deficiency-heat model group showed weight loss,elevated cAMP/cGMP,elevated serum NO and ROS levels,increased expression of Bax and Caspase-9 proteins in primary cardiac cells,and decreased expression of Bcl-2 protein(P<0.05,P<0.01).Compared with the deficiency-cold model group,the body weight,cAMP/cGMP,serum NO,in vivo and in vitro ROS,cardiac cell MPTP,and expression of apoptotic proteins in the Aconite group mice all showed varying degrees of improvement(P<0.05,P<0.01).Compared with the deficiency-heat model group,the serum NO of mice in the Aconite group decreased(P<0.05).Conclusion:Based on the medicine-syndrome correspondence,it is revealed that the TCM Aconiti Lateralis Radix Praeparata,a hot and spicy herb,exhibits significant differences in biological expression under different syndrome states.It is found that its mechanism is related to the differences in regulating NO/mitochondrial energy metabolism signal pathways.Rreating cold with heat,and Aconiti Lateralis Radix Praeparata can reverse the stress state of primary cardiac cells in mice with deficiency-cold syndrome.Conversely,Aconiti Lateralis Radix Praeparata can exacerbate the degree of stress and apoptosis of primary cardiac cells in mice with deficiency-heat syndrome.
Traditional Chinese medicinal propertyMedicine-syndrome correspondenceAconiti Lateralis Radix PraeparataNitric oxide(NO)MitochondrialEnergy metabolism