Ciwujianoside C3

Comprehensive phytochemical analysis and sedative-hypnotic activity of two Acanthopanax species leaves.[Pubmed:33605281]

Food Funct. 2021 Mar 15;12(5):2292-2311.

Acanthopanax senticosus leaves (SCL) and Acanthopanax sessiliflorus leaves (SFL), which are usually made into functional teas, possess similar pharmacological activities. With the aim of revealing their chemical compositions and evaluating their sedative-hypnotic effects, comprehensive metabolite profiling analysis based on ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) and high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) as well as bioassay studies in mice were performed for the first time. Firstly, a total of 75 compounds (including 69 shared components) were identified or briefly characterized. Results indicated that the leaves of the two species were both rich in phytochemicals and contained similar structural types. Secondly, 20 and 7 chemical markers were identified from SCL and SFL, respectively. Five oleanane-type triterpene saponins (ciwujianoside C1, C3, D2, E and saniculoside N) and two lupine-type triterpene saponins (1-deoxychiisanoside and 24-hydroxychiisanoside) may be used for rapid identification of SCL and SFL. Thirdly, the contents of rutin, hederacoside D, ciwujianoside B, -C3, -E and ursolic acid in SCL (0.308%, 0.024%, 0.042%, 0.131%, 0.038%, and 0.255%, respectively) were higher than in SFL (0.067%, 0.005%, 0.012%, 0.015%, 0.002%, and 0.087%, respectively). Fourthly, an in vivo bioassay verified that both SCL and SFL could inhibit autonomous activity, shorten sleep latency and prolong sleep duration in a dose-dependent manner. To a certain degree, SCL showed a higher and more stable effect. The hypnotic effect could be inhibited by flumazenil (FLU). The two leaves not only had an obvious antagonism action of p-chlorophenoxyacetic acid (pCPA) but also showed a synergistic hypnotic effect with 5-hydroxytryptophan (5-HTP). The beneficial bioactivity may be mediated by 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA). Finally, network pharmacology analysis showed that the undifferentiated and differentiated compounds were the material basis for the similar and the different activities of two leaves. Some typical chemical markers (such as saniculoside N, hederacoside D, Ciwujianoside C3, -E and ursolic acid, 24-hydroxychiisanoside and 1-deoxyisochiisanoside) were the potential active compounds and could be used as quality markers in the future. The present study furnished a basis for the further development and utilization of the leaves of these two Acanthopanax species.

Memory Enhancement by Oral Administration of Extract of Eleutherococcus senticosus Leaves and Active Compounds Transferred in the Brain.[Pubmed:31121888]

Nutrients. 2019 May 22;11(5). pii: nu11051142.

The pharmacological properties of Eleutherococcus senticosus leaf have not been clarified although it is taken as a food item. In this study, the effects of water extract of Eleutherococcus senticosus leaves on memory function were investigated in normal mice. Oral administration of the extract for 17 days significantly enhanced object recognition memory. Compounds absorbed in blood and the brain after oral administration of the leaf extract were detected by LC-MS/MS analyses. Primarily detected compounds in plasma and the cerebral cortex were Ciwujianoside C3, eleutheroside M, ciwujianoside B, and ciwujianoside A1. Pure compounds except for ciwujianoside A1 were administered orally for 17 days to normal mice. Ciwujianoside C3, eleutheroside M, and ciwujianoside B significantly enhanced object recognition memory. These results demonstrated that oral administration of the leaf extract of E. senticosus enhances memory function, and that active ingredients in the extract, such as Ciwujianoside C3, eleutheroside M, and ciwujianoside B, were able to penetrate and work in the brain. Those three compounds as well as the leaf extract had dendrite extension activity against primary cultured cortical neurons. The effect might relate to memory enhancement.

Antiinflammatory effects of Ciwujianoside C3, extracted from the leaves of Acanthopanax henryi (Oliv.) Harms, on LPSstimulated RAW 264.7 cells.[Pubmed:27600484]

Mol Med Rep. 2016 Oct;14(4):3749-58.

The present study aimed to investigate the unknown mechanisms underlying the antiinflammatory activity of Ciwujianoside C3 (CJS C3), extracted from the leaves of Acanthopanax henryi Harms, on lipopolysaccharide (LPS)stimulated RAW 264.7 cells. Cells were treated with CJS C3 for 1 h prior to the addition of 200 ng/ml LPS. Cell viability was measured using the MTS assay. Nitric oxide levels were determined by Griess assay. Proinflammatory cytokine production was measured by enzymelinked immunosorbent assay. The expression levels of cyclooxygenase (COX)2, inducible nitric oxide synthase (iNOS), and mitogenactivated protein kinases (MAPKs) were investigated by western blotting, reverse transcription (RT)polymerase chain reaction (PCR) and RTquantitative PCR. Nuclear factor (NF)kappaB/p65 localization, and interaction of the TLR4 receptor with LPS was examined by immunofluorescence assay. The results indicated that CJS C3 exhibited no cytotoxicity at the measured concentrations. Treatment with CJS C3 inhibited NO production, proinflammatory cytokine levels, including interleukin (IL)6, tumor necrosis factor (TNF)alpha, and prostaglandin E2 (PGE2), and protein and mRNA expression levels of iNOS and COX2. Furthermore, CJS C3 suppressed phosphorylation of extracellular signalregulated kinases and cjun Nterminal kinases. It was also able to suppress activation of NFkappaB via inhibition of the TLR4 signaling pathway. These results suggested that CJS C3 exerts inhibitory effects on LPSinduced PGE2, NO, IL6 and TNFalpha production. In addition, iNOS and COX2 expression was decreased in murine macrophages. These inhibitory effects may be achieved via suppression of MAPKs and NFkappaB phosphorylation following inhibition of the TLR4 signaling pathway.