Quality analysis of commercial samples of Ziziphi spinosae semen(suanzaoren) by means of chromatographic fingerprinting assisted by principal component analysis

Due to the scarcity of resources of Ziziphi spinosae semen （ZSS）, many inferior goods and even adulterants are generally found in medicine markets. To strengthen the quality control, HPLC fingerprint common pattern established in this paper showed three main bioactive compounds in one chromatogram simultaneously. Principal component analysis based on DAD signals could discriminate adulterants and inferiorities. Principal component analysis indicated that all samples could be mainly regrouped into two main clusters according to the first principal component （PC1, redefined as Vicenin II） and the second principal component （PC2, redefined as zizyphusine）. PC1 and PC2 could explain 91.42%of the variance. Content of zizyphusine fluctuated more greatly than that of spinosin, and this result was also confirmed by the HPTLC result. Samples with low content of jujubosides and two common adulterants could not be used equivalently with authenticated ones in clinic, while one reference standard extract could substitute the crude drug in pharmaceutical production. Giving special consideration to the well-known bioactive saponins but with low response by end absorption, a fast and cheap HPTLC method for quality control of ZSS was developed and the result obtained was commensurate well with that of HPLC analysis. Samples having similar fingerprints to HPTLC common pattern targeting at saponins could be regarded as authenticated ones. This work provided a faster and cheaper way for quality control of ZSS and laid foundation for establishing a more effective quality control method for ZSS.

Caffeoylquinic acid derivatives extract of Erigeron multiradiatus alleviated acute myocardial ischemia reperfusion injury in rats through inhibiting NF-kappaB and JNK activations

Erigeron multiradiatus(Lindl.)Benth.,has been used in Tibet folk medicine to treat various inflammatory diseases.The aim of this study was to investigate anti-myocardial ischemia and reperfusion(I/R)injury effect of caffeoylquinic acids derivatives of E.multiradiatus(AE)in vivo and to explain underling mechanism.AE was prepared using the whole plant of E.multiradiatus and contents of 6 caffeoylquinic acid determined through HPLC analysis.Myocardial I/R were induced by left anterior descending coronary artery occlusion for 30 min followed by 24 h of reperfusion in rats.AE administration(10,20 and 40 mg·kg-1)inhibited I/R-induced injury as indicated by decreasing myocardial infarct size,reducing of CK and LDH activities and preventing ST-segment depression in dose-dependent manner.AE decreased cardiac tissue levels of pro-inflammatory factors TNF-αand IL-6 and attenuated leukocytes infiltration.AE was further demonstrated to significantly inhibit I-κB degradation,nuclear translocation of p-65 and phosphorylation of JNK.Our results suggested that cardioprotective effect of AE could be due to suppressing myocardial inflammatory response and blocking NF-κB and JNK activation pathway.Thus,caffeoylquinic acids might be the active compounds in E.multiradiatus on myocardial ischemia and be a potential natural drug for treating myocardial I/R injury.

Chemical derivatization strategies for enhancing the HPLC analytical performance of natural active triterpenoids

Triterpenoids widely exist in nature,displaying a variety of pharmacological activities.Determining triterpenoids in different matrices,especially in biological samples holds great significance.High-performance liquid chromatography(HPLC)has become the predominant method for triterpenoids analysis due to its exceptional analytical performance.However,due to the structural similarities among botanical samples,achieving effective separation of each triterpenoid proves challenging,necessitating significant improvements in analytical methods.Additionally,triterpenoids are characterized by a lack of ultraviolet(UV)absorption groups and chromophores,along with low ionization efficiency in mass spectrometry.Consequently,routine HPLC analysis suffers from poor sensitivity.Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance.Considering the structural characteristics of triterpenoids,various derivatization reagents such as acid chlorides,rhodamines,isocyanates,sulfonic esters,and amines have been employed for the derivatization analysis of triterpenoids.This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids.Moreover,the limitations and challenges encountered in previous studies are discussed,and future research directions are proposed to develop more effective derivatization methods.

Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl_4-induced liver injury

Phyllanthus Urinaria L.(PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl_4-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl_4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl_4-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis(OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl_4-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.

Drug Discovery Enters A New Era with Multi-Target Intervention Strategy

In the past century, as medical research has become increasingly precise, it has become clear that the incidence and progression of many diseases involve multiple factors and pathologies; this is particularly true for the degenerative and metabolic diseases facing industrialized societies. At the same time, it becomes increasingly clear that single-target action drugs cannot effectively treat these diseases. Researchers are looking toward the chemical industry as well as traditional herbal medicines to find multi-target interventions. Thus, a new era in drug discovery has begun. Specifically, three approaches have proven effective in seeking multi-target drugs. These are： （1） designing drugs with multiple components; （2） discovering drugs through the study of synergistic compound-compound interactions in medicinal herbs or among chemical drugs and herbal components; and （3） developing drugs to tackle complex multi-component diseases. The authors conclude that there is an increasing need for multi-component remedies to treat the complex chronic diseases afflicting modern populations. Given this situation and the growing body of evidence that these new approaches are effective, multi-target intervention appears to have great potential for discovering, designing, and developing effective new drugs for today＇s diseases.

Nobiletin and its derivatives overcome multidrug resistance(MDR) in cancer:total synthesis and discovery of potent MDR reversal agents

Our recent studies demonstrated that the natural product nobiletin(NOB)served as a promising multidrug resistance(MDR)reversal agent and improved the effectiveness of cancer chemotherapy in vitro.However,low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent.To tackle these challenges,NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy.All the compounds showed improved sensitivity to paclitaxel(PTX)in P-glycoprotein(P-gp)overexpressing MDR cancer cells.Among them,compound 29 d exhibited water solubility 280-fold higher than NOB.A drug-resistance A549/T xenograft model showed that 29 d,at a dose of 50 mg/kg co-administered with PTX(15 mg/kg),inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition.Moreover,Western blot experiments revealed that 29 d inhibited expression of NRF2,phosphorylated ERK and AKT in MDR cancer cells,thus implying 29 d of multiple mechanisms to reverse MDR in lung cancer.