ABSTRACT
Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmaco-logical mechanisms of AG underlying the prevention and treatment of ASCVD have not been corrobo-rated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound('old bottle')as a novel drug('novel wine')for the pre-vention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.
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The unique solution-gel transition property of in-situ gel makes it have advantages of good histocompatibility, long residence time, high local concentration, promising bioavailability and so on.This paper summarized the different types and the latest research progress in Chinese medicine targeting preparations of in-situ gel in order to provide reference for the application of in-situ gel in Chinese medicines.
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Aim To investigate the protective mechanism of anisodine hydrobromide against cerebral ischemia-reperfusion injury in rats.Methods In vivo: the cerebral ischemia-reperfusion injury model was established by middle cerebral artery occlusion(MCAO)via suture method in rats;the rats were injected anisodine hydrobromide(1.2,0.6,0.3,0.15 mg·kg-1);the morphological changes were detected by HE staining;the Nissl staining was used to count the number of surviving neurons;the activity of CAT and LDH,the LPO contents in the brain tissue were measured;the expressions of Bax,Bcl-2,caspase-3 and p-Akt in brain tissue were detected by Western blot.In vitro: Western blot assay was used to determine the expression of Bax,Bcl-2,caspase-3 and p-Akt protein expression in the OGD-R model of PC12 cells.The signal pathway of anisodine hydrobromide was identified.Results Anisodine hydrobromide with the dose of 0.15 mg·kg-1 could significantly lessen the morphological changes,and improve the number of surviving neurons;the dose of 0.3 and 0.15 mg·kg-1 could significantly improve the activity of CAT;the dose of 0.3 mg·kg-1 could significantly reduce the contents of LPO in the rat brain tissue;the dose of 1.2 mg·kg-1 could significantly decrease the activity of LDH;the dose of 0.15～1.2 mg·kg-1 could inhibit the expression of Bax,promote the expression of p-Akt in rat brain tissue.All the doses except 0.15 mg·kg-1 could promote the expression of Bcl-2 in rat brain tissue.In vitro,the results showed that anisodine hydrobromide in 25～100 μmol·L-1 could significantly improve the expression of Bcl-2 and the ratio of Bcl-2/Bax,and the dose of 50 μmol·L-1 could significantly improve the ratio of p-Akt/Akt.Conclusion The mechanism of anisodine hydrobromide against cerebral ischemia-reperfusion injury model rats might be related to its anti-oxidative activity and the activation of Akt.
ABSTRACT
OBJECTIVE:To compare the anti-inflammation,analgesia effects of decoctions extracted from Aconiti lateralis with different leaf shapes(dahua leaf,xiaohua leaf)from different producing areas(Jiangyou,Butuo). METHODS:Animals were randomly divided into blank group(distilled water),positive group,groups of Aconiti lateralis with dahua,xiaohua leaf from Ji-angyou,groups of Aconiti lateralis with dahua,xiaohua leaf from Butuo(with dose of 5 g/kg,calculated by crude drug). The an-ti-inflammation effect of decoctions extracted from Aconiti lateralis with different variety sources and leaf shapes was investigated by xylene-induced ear swelling test (n=12) in mice and egg white-induced toe swelling test (n=10) in rats (positive drug was Dexamethasone acetate tablet,0.005 g/kg). And its analgesic effect was investigated by acetic acid-induced writhing body reaction test(n=12)and hot-plate-induced pain test(n=12)in mice(positive drug was Morphine hydrochloride tablet,0.0025 g/kg). RE-SULTS:The decoctions extracted from Aconiti lateralis with dahua,xiaohua leaf from Butuo and xiaohua leaf from Jiangyou can significantly reduce the ear swelling degree(P<0.01). The decoctions extracted from Aconiti lateralis with dahua leaf from Jiangy-ou and Butuo can significantly decrease the toe swelling degree after 6 h of medication(P<0.05). And decoctions extracted from Aconiti lateralis with xiaohua leaf from Butuo can significantly reduce the number of writhing body in mice with acetic acid-in-duced pain and prolong the pain threshold of mice with hot-plate-induced pain (P<0.05 or P<0.01). CONCLUSIONS:Aconiti lateralis with dahua and xiaohua leaf from Butuo and with xiaohua leaf from Jiangyou show better anti-inflammation effect,and Aconiti lateralis with xiaohua leaf from Butuo shows better analgesic effect.
ABSTRACT
Objective Enzyme triggered multi unit colon targeting mini tablet of indomethacin were prepared,in order to improve the target treatment of colon disease.Methods Different proportion of enteric layer and chitosan layer were screened to optimize the prescription.The colon targeting mini tablets were prepared by direct compression method.The drug release properties were investigated in different release medium.Rats were used to investigate the distribution of tissue in vivo.The Beagle dogs were used to study the pharmacokinetics and bioavailability.Results The optimum chitosan layer prescription:coating liquid concentration was 2％,plasticizer three citric acid ethyl ester (TEC) was 15％,an anti sticking agent amount of talc was 30％,coating weight was 5％;Enteric layer prescription:coating liquid solid content was 20％,plasticizer content of TEC was 5％,anti sticking agent talc powder dosage was 40％,coating weight was 3％.The chitosan multi unit colon targeted preparation seldom released in rat stomach and small intestine,released slowly in colon.The pharmacokinetics parameters in Beagle dogs were:Cmax =(3.25 + 0.672) mg·L-1,tmax =(2.00 + 0.014) h,AUC(0.∞) =(10.2 +0.871) mg·L-1 ·h,MRT (0-∞) =(2.82 + 0.180) h,CL =(2.46 + 0.202) L·h-1 ·kg-1.The release time of mini tablets for colon targeted was significantly prolonged and preserved stable blood concentration.Conclusion The enzyme triggered multi unit colon targeting mini tablet of indomethacin showed good target to colon and sustained release effect,providing an important reference for the development of preparation of indomethacin for the treatment of colon disease.