Protective effects of costunolide on mouse brain slice injury induced by oxygen glucose deprivation/reoxygenation

OBJECTIVE To investigate the protective effects and mechanisms of costunolide against mousebrain slice injury induced by oxygen-glucose deprivation/reoxygenation(OGD/R).METHODS Mouse brain slice injury was induced by OGD/R in vitro,and the degree ofinjury was evaluated by measuring the release of lactate dehydrogenase(LDH)and 2,3,5-triphenyltetrazolium chloride(TTC)staining.Western blotting was used to analyze the expression of Bax,Bcl-2,Cyt-c,caspase-9,caspase-7 and caspase-3.RESULTS Compared with OGD/R,1,5,and 10μmol·L^-1 costu⁃nolide decreased the LDH levels,increased the TTC staining intensity,inhibited Bax,Cyt-c,caspase-9,caspase-7,caspase-3 expression levels,and enhanced Bcl-2 expression level.CONCLUSION Costunolide has latent neuroprotective activi⁃ties by the regulation of apoptosis via the mitochondrial apoptosis pathway.

Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases

The NLRP3 inflammasome’s core and most specific protein,NLRP3,has a variety of functions in inflammation-driven diseases.Costunolide(COS)is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity,but the principal mechanism and molecular target of COS remain unclear.Here,we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3,altering the ATPase activity and assembly of NLRP3 inflammasome.We declare COS’s great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation.We also reveal that theα-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation.Taken together,NLRP3 is identified as a direct target of COS for its anti-inflammasome activity.COS,especially theα-methylene-γ-butyrolactone motif in COS structure,might be used to design and produce novel NLRP3 inhibitors as a lead compound.

Rapid Determination of Costunolide and Dehydrocostuslactone in Human Plasma Sample and Chinese Patent Medicine Xiang Sha Yang Wei Capsule Using HPLC-DAD Coupled with Second-order Calibration

A novel methodology that combines high performance liquid chromatography with photodiode-array detector （HPLC-DAD） coupled with second-order calibration method based on alternating trilinear decomposition （ATLD） algorithm was used in determination of the effective constituents such as costunolide and dehydrocostuslactone, in plasma sample and Chinese patent medicine Xiang Sha Yang Wei （XSYW） capsule. Complicated systems such as plasma and Chinese patent medicine which have intricate components are tedious to isolate and purify. The problem that chromatographic peaks are heavily overlapped among the analytes and interferents from the background matrices can be resolved, and the satisfactory quantification results have been gained with the help of the ATLD algorithm which utilized ＂mathematical separation＂ instead of partial ＂physical or chemical separation＂. Meanwhile, HPLC-MS/MS method was used to validate the accuracy of the proposed determination method.

Current Situation of Chinese Medicine Combined with MSCs for the Treatment of the Neurovascular Unit Injury After Cerebral lschemia

Stroke has been a common problem in the global public health because of its high incidence,recur-rence,disability rate and mortality,among which ischemic stroke accounts for about 80%of the total stroke.Cerebral ischemia reperfusion injury(CIRI)is one of the most important pathological injuries after ischemic stroke,and the effective treatment has always been a research focus at home and abroad.The proposal of the concept of neurovascular unit(NVU)which extends treatment ideas from local to holistic is in accordance with the holistic concept and treatment based on syndrome differentiation in Chinese medicine.Chinese medicine has many advantages,such as being multicomponent,multitarget,and multipath while stem cells are effective biological therapeutic means,both of which have been proved to exert comprehensive and definite effects on NVU injury caused by CIRI.This artide reviews the molecular mechanisms of NVU injury and the cerebropro-tective effects of Chinese medicine monomers or compound formulas combined with MSCs on NUV injury after cerebral ischemia,with a view to provide a theoretical basis for future studies.