Terpenoids With Assembly Function Characteristics Derived From Hemsleya Penxianensis And Nepeta Bracteata Benth.

The isolation of single pharmacologically active natural product molecules(NPMs)from traditional Chinese medicine(TCM)has become the focus of traditional medicine modernization.However,these NPMs always have various defects which limited in application field and efficacy aspects.In recent years,NPMs have been improved through nanotechnology,structural modification and targeted delivery,etc.for breaking the inherent limitations of NPMs and fully exploiting the potential of their application.Despite the effect,the limitation of carrier-related toxicity and the complex formulation technology involved in these modified techniques undoubtedly add additional difficulty to putting into use for NPMs.Unlike the strategies of passive enhancement,we propose that NPMs in TCM have potential to achieve the enhancement of "self-efficiency" by virtue of the self-assembled characteristic conferred by unique structural features.β-sitosterol and 23 cucurbitane type triterpenoid analogues,including new compounds hemsleyacins P-R(6,7,13)and hemsleyaosides L-N(15-17),are isolated and identified from medicinal plant Hemsleya penxianensis.Digging further,hemslecin A(HA)and β-sitosterol(Sito),the principal components of H.penxianensis possess co-assembly properties which is another possible functioning mode of therapeutic effect for H.penxianensis.Therefore,the group explores the changes of morphology,properties and driving force as well as the mechanism of coassembled Sito-HA by chemical characterization and computer simulation for the first time.Furthermore,the Sito-HA exhibit a remarkably enhanced,synergistic efficacy against gastric cancer.The reasons could be that morphology and hydrophilicity are improved after their interaction,thus making co-assembly adhere to the cells more easily to exert its effects.This research not only expands the potential application of NPMs,but also provides the new sight of TCM(H.penxianensis)in therapeutic effect with their inner substance co-assemblies.Moreover,Nepeta bracteata Benth.,belonging to the genus Nepeta in the labiaceae family,functions on warming the lungs,relieving cough,removing phlegm,anti-inflammation and reducing swelling.Six diterpenoids are obtained through chemical separation,including nepebracteatalic Acid(NA),a novel labdane diterpenoid.Further study revealed that the diterpenoid molecule NA has the property of assembly,which can self-assemble into nanoparticles(NA NPs)through noncovalent interactions,including intermolecular hydrogen bonding,hydrophobic interaction and electrostatic interaction.Based on this self-assemble characteristic,NA NPs possesses a certain sustained release performance under the role of hydrogen bonds,lower inflammatory expression levels for IL-6 and TNF-α than clinical antiinflammatory drug Indometacin.And the effect of NA NPs on nuclear factor-κB(NFKB)signaling pathway is quantified to confirm the significantly enhanced antiinflammatory property relative to free NA.Meanwhile,NA self-assembly performs outstanding inflammation inhibition,collagen deposition,angiogenesis and wound closure during wound healing which is consistent with the clinical application of N.bracteate.In conclusion,from the perspective of structural assembly characteristics of NPMs,futher exploration of the assembly functions of triterpene HA and β-sitosterol as well as diterpene NA based on the study of chemical constituents of two medicinal plants,N.bracteata Benth.and H.penxianensis,provides a new research sight for clarifying the medicinal value of TCM or ethnic medicine,and also points out a new direction for the application and development of NPMs.