ABSTRACT
Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks. Here, we used a comprehensive single-cell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins, and proteome-metabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism, amino acid metabolism and "Warburg effect". The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides. Furthermore, by applying affinity mass spectrometry (MS) screening and surface plasmon resonance fragment library screening, we confirmed that 20()-protopanaxatriol directly targeted adjacent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions, which further induced a series of omics changes.
ABSTRACT
Objective: To study the minor triterpenoid saponins from the roots of Panax notoginseng, which provided basis for the systematic research, quality control and safety evaluation of P. notoginseng. Methods The compounds were isolated and purified by MCI resin, ODS, along with Preparative-HPLC, and the structures were identified by spectroscopic analysis, and comparing with the pubished literature values. Results: Twelve monomeric compounds isolated from the roots of P. notoginseng, were identified as notoginsenoside P1 (1), notoginsenoside T5 (2), ginsenoside Rk3 (3), ginsenoside Rh4 (4), notoginsenoside T3 (5), 20(S)-protopanaxatriol (6), dammar 20 (21),24-diene-3β,6α,12β-triol (7), ginsenoside Rg3 (8), gypenoside XIII (9), ginsenoside Rk1 (10), ginsenoside Rg5 (11), and 20 (S)-ginsenoside Rh2 (12). Conclusion: Compound 1 is a new dammarane-type triterpenoid saponin
ABSTRACT
Objective To explore the excretion of the 20(S)-protopanaxatriol(PPT)and its metabolites ocotillol type epi?mers(M1 and M2)in urine,feces samples and the excretion of M1 and M2 in bile samples. Methods The concentration of PPT,M1 and M2 in urine,feces samples and the concentration of M1 and M2 in bile samples were determined by the LC-MS/MS methods with or without the hydrolization byβ-glucuronidase. Results After intragastric(ig)administration of PPT,the cumulative excretion rate for 72 h of PPT,M1 and M2 in feces were 14.88%,1.34%and 0.084%,respectively. With the hydrolization byβ-glucuronidase,the cumulative excretion rate for 72 h of PPT,M1 and M2 in feces were 14.77%,1.36%and 0.085%,respectively. However,the epimers and PPT were hardly detected in urine. After ig administration of M1 or M2,the accumulation excretion rate were 4.41%for M1 and 47.2%for M2 in feces,while both epimers were hardly detected in urine. After ig administration of M1 or M2,the 36 h cumulative bili?ary excretion rate was 3.01%for M1,and only 0.068%for M2. The 36 h cumulative biliary excretion rate of M1 was 8.80%after intra?venous administration ,while only 1.24%for M2. Conclusion After ig administration of PPT,a small amount of PPT and its metabo?lites(M1,M2)are excreted by the feces but little via urine ,and there are stereoselectivity differences in biliary excretion between M1 and M2.
ABSTRACT
Objective To explore the excretion of the 20 (S)-protopanaxatriol (PPT) and its metabolites ocotillol type epimers (M1 and M2) in urine, feces samples and the excretion of Ml and M2 in bile samples. Methods The concentration of PPT, Ml and M2 in urine, feces samples and the concentration of Ml and M2 in bile samples were determined by the LC-MS/MS methods with or without the hydrolization by β-glucuronidase. Results After intragastric(ig) administration of PPT, the cumulative excretion rate for 72 h of PPT, Ml and M2 in feces were 14.88%, 1.34% and 0.084%, respectively. With the hydrolization by β-glucuronidase, the cumulative excretion rate for 72 h of PPT, Ml and M2 in feces were 14.77%, 1.36% and 0.085%, respectively. However, the epimers and PPT were hardly detected in urine. After ig administration of M1 or M2, the accumulation excretion rate were 4.41% for M1 and 47.2% for M2 in feces, while both epimers were hardly detected in urine. After ig administration of M1 or M2, the 36 h cumulative biliary excretion rate was 3.01% for M1, and only 0.068% for M2. The 36 h cumulative biliary excretion rate of M1 was 8.80% after intravenous administration, while only 1.24% for M2. Conclusion After ig administration of PPT, a small amount of PPT and its metabolites (Ml, M2) are excreted by the feces but little via urine, and there are stereoselectivity differences in biliary excretion between M1 and M2.