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Isoliquiritigenin (ISL) is a chalcone that has shown great potential in the treatment of cancer. However, its relatively weak activity and low water solubility limit its clinical application. In this study, we designed and synthesized 21 amino acid ester derivatives of ISL and characterized the compounds using 1H NMR and 13C NMR. Among them, compound 9 (IC50 = 14.36 μM) had a better inhibitory effect on human cervical cancer (Hela) than ISL (IC50 = 126.5 μM), and it was superior to the positive drug 5-FU (IC50 = 33.59 μM). The mechanism of the action experiment showed that compound 9 could induce Hela cell apoptosis and autophagy through the PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

In this study, we aimed to demonstrate the therapeutic effect of Ligustri Lucidi Fructus on chemotherapy‐induced myelosuppression and elucidate its mechanism. A pharmacological study was conducted to investigate the mechanism of the inhibiting effects of Ligustri Lucidi Fructus on cyclophosphamide‐induced bone marrow suppression in mice. HPLC was used to measure the chemical components. We demonstrated that medium and high doses of Ligustri Lucidi Fructus increased the amount of white blood cells and bone marrow nucleated cells (p < 0.05) in the cyclophosphamian‐induced mouse model, and at the same time reduced granulocyte–macrophage–colony stimulating factor and thrombopoietin in the serum of myelosuppression mice (p < 0.01). Medium and high doses of Ligustri Lucidi Fructus can also adjust the thymus index and spleen index(p < 0.05). Ligustri Lucidi Fructus regulates the balance of bcl‐2/bax, inhibits the expression of Caspase‐3 and meanwhile stimulates the expression of mitogen‐activated protein (MEK) and phospho extracellular regulated protein kinases (p‐ERK) on the MAPK pathway. Five chemical constituents of Ligustri Lucidi Fructus, which may be related to myelosuppression, were analyzed. The content of specnuezhenide was 0.281%, that of ligustroflavone was 0.004%, that of salidroside was 0.094%, that of hydroxytyrosol was 0.060% and that of tyrosol was 0.069%. The effect of Ligustri Lucidi Fructus on myelosuppression after chemotherapy may be related to its multicomponent and multitarget nature. Ligustri Lucidi Fructus may be a promising potential drug for treatment after chemotherapy. [ABSTRACT FROM AUTHOR]

Background: 20(R)-ginsenoside Rg3 (R-Rg3) is a kind of ginseng glycol tetracyclic triterpenoid saponin, which is a recognized traditional Chinese medicine monomer and has the action of inhibiting the proliferation of tumor cells. Objectives: The goal of our experiment was to investigate the protective function of R-Rg3 on chemotherapy-induced myelosuppression in mice. Materials and Methods: Cyclophosphamide (CTX) was injected into the intraperitoneal (i.p.) to establish the mice myelosuppression model. We measured the number of peripheral blood cells (PBCs), and the number of bone marrow nucleated cells (BMNCs) was counted. Hematopoietic progenitor cells (HPCs) were cultured in vitro, and the amount of cell colonies was recorded at different times. Then ELISA was used to detect the levels of hematopoietic-related cytokines and flow cytometry was employed to test cell cycle. The network pharmacology was used to predict the main pathways of action. Furthermore, the expression of p-JAK2 and p-STAT5 was detected via western blotting. Results: The experimental outcomes showed that R-Rg3 could improve the amount of PBCs in mice with myelosuppression, increase the quantity of karyota cells in bone marrow, and enhance the proliferation of HPCs and adjust the content of hematopoietic-related cytokines. Moreover, the JAK–STAT signaling pathway may be the key to the role of R-Rg3. Conclusion: All of these results implied that R-Rg3 might be a therapeutic agent for myelosuppression after chemotherapy. [ABSTRACT FROM AUTHOR]

A rich of 3,4-seco-lupane triterpenoids (3,4-SLT), including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA), chiisanogenin (CSG), sessiligenin (SSG), were isolated from the ethanol extract of the leaves of Eleutherococcus sessiliflorus (LES). The present study was performed to explore the cytotoxic and anti-tumor effects of the isolated five ones, as well as potential molecular mechanisms. The results of a CCK-8 assay demonstrated that these 3,4-SLT can inhibit the growth of HepG2 cells, and SSG showed the most significant cytotoxicity. Hoechst 33258 fluorescence staining and Annexin V-FITC/PI staining indicated that 3,4-SLT in LES can induce HepG2 cell apoptosis effectively. The AutoDock Vina program was used to simulate molecular docking of drugs and targets to discuss possible pharmacological mechanisms. Besides, western blot and qRT-PCR results indicated that SSG can inhibit PI3K/AKT signaling pathway through controlling multi-targets. This study suggested that 3,4-SLT might become a new research hotspot for antineoplastic drugs. [ABSTRACT FROM AUTHOR]

A new 3,4-seco-lupane triterpene, named sessiligenin (1), along with four known 3,4-seco-lupane triterpene derivatives (chiisanogenin 2, chiisanoside 3, divaroside 4, and sessiliside-A1 5) were isolated from the ethanol extract of the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S.Y. Hu by silica gel column chromatography, and their structures were determined by spectroscopic data. Furthermore, all these compounds were tested for their cytotoxicities against cancer cell lines HepG2, B16-F10, Lewis and YAC-1, as well as normal cell lines NCTC1469 and HL-7702, and significant cytotoxicities had been found for this new compound (sessiligenin 1) which exhibited much lower cytotoxicities against normal cell lines NCTC1469 and HL-7702. It was deduced that the reduce of glycosyl from the structures of these 3,4-seco-lupane triterpenoids enhanced the cytotoxicities. Furthermore, with the complete removal of glycosyl group and the 11-hydroxyl and 3-carboxyl formed by the opening of the lactone ring, the cytotoxicity increased significantly. [ABSTRACT FROM AUTHOR]

Armillaria mellea, also known as Hazel mushroom, is a delicious food material and traditional herbal medicine in East Asia. Protoilludane sesquiterpenoid aromatic esters from A. mellea (PSAM) are the main active components with antibacterial and anticancer activities. This study explored the antidepressant-like activities of PSAM and its possible mechanisms of action using the open field test (OFT), tail suspension test (TST) and forced swimming test (FST) in mice for the first time. The results revealed that PSAM (1 mg/kg, i.p.) exhibited markedly antidepressant-like activity, which could be reversed by pretreatment with haloperidol (a non-selective D2 receptor antagonist), bicuculline (a competitive GABA antagonist), NMDA (an agonist at the glutamate site). Meanwhile, PSAM also effectively increased the hippocampus dopamine (DA) and γ-aminobutyric acid (GABA) and decreased the hippocampus glutamate (Glu) levels of mice, indicating that the antidepressant-like effect of PSAM might be mediated by the DAergic, GABAergic and Gluergic systems. [ABSTRACT FROM AUTHOR]

A new minor 3,4-seco-lupane triterpenene glycosyl ester, named sessiloside-A1 (1), along with three known 3,4-seco-lupane triterpenenes were isolated from the which alcohol extract of the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S.Y. Hu by silica gel column chromatography, and their structures were determined by spectroscopic methods (UV, IR, NMR and HRMS). Compound 1 was elucidated to be β-D-glucopyranosyl ester of chiisanogenin. At the same time, a new efficient two-step enzymatic hydrolysis method was established to transform chiisanoside (2) → divaroside (3) → 1. [ABSTRACT FROM AUTHOR]

The present study explored the antidepressant-like activity of α-mangostin (α-MG) and the possible mechanism in this process in the tail suspension test (TST) in mice. The results revealed that α-MG (5 mg/kg, i.p.) exhibited markedly antidepressant-like activity, which could be reversed by pretreatment with haloperidol (a non-selective D2 receptor antagonist), bicuculline (a competitive GABA antagonist), p-chlorophenylalanine (an inhibitor of 5-HT synthesis). Meanwhile, α-MG also effectively increased the brain DA, 5-HT and GABA levels in mice exposed to TST, indicating that the antidepressant-like effect of α-MG might be mediated by the GABAergic, serotonergic and dopaminergic systems. [ABSTRACT FROM AUTHOR]