Isobavachalcone (IBC) or (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)-phenyl]-3-(4-hydroxyphenyl)-2-propen-1-one or (E)-4,2',4'-trihydroxy-3'-prenylchalcone; 2',4,4'-trihydroxy-3'-prenyl-transchalcone, is a prenylated chalcone of the class flavonoid, firstly isolated from Psoralea corylifolia in 1968. IBC is known to possess a wide spectrum of biological activities, antibacterial, antifungal, anticancer, anti-reverse transcriptase, antitubercular and antioxidant. The compound was isolated from plant families, mostly Moraceae and Fabaceae. This review brings out together the knowledge on IBC, and can serve as the start point for future research and valorization accomplishments.
Animals ; Biosynthetic Pathways ; drug effects ; Cell Death ; drug effects ; Chalcones ; biosynthesis ; chemistry ; pharmacology ; Humans

Licochalcone A (LCA), as a major flavonoid in Glycyrrhiza inflate, has attracted wide attention in recent years. Studies showed that LCA has multiple pharmacological effects such as anti-tumour, anti-inflammation, anti-bacteria and anti-parasite. We made a summary for domestic and foreign study literatures for various pharmacological effects of LCA.
Animals ; Anti-Infective Agents ; pharmacology ; Anti-Inflammatory Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Chalcones ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Glycyrrhiza ; chemistry ; Humans

During the screening of a traditional Chinese folk herb library against HepG2 and Hep3B cell lines, the EtOAc extract from the Tibetan medicine, Caragana tibetica (CT-EtOAc) exhibited potential anti-hepatocellular carcinoma (anti-HCC) activity. HPLC-based activity profiling was performed for targeted identification of anti-HCC activity from CT-EtOAc by MS-directed purification method. CT-EtOAc was separated by time-based fractionation for further anti-HCC bioassay by a semipreparative HPLC column (150 mm × 10 mm i.d., 5 μm) with a single injection of 5 mg. Bioassay-guided and ESIMS-directed large scale purification was performed with a single injection of 400 mg of CT-EtOAc by peak-based fractionation. A 1.4-mm heavy wall micro NMR tube with z-gradient was used to measure one and two dimensional NMR spectra for the minor or trace amounts of components of the extract. Two active compounds could be elucidated as naringenin chalcone (CT-1) and 3-hydroxy-8, 9-dimethoxypterocarpan (CT-2) relevant to anti-HCC effects for the EtOAc extract of C. tibetica rapidly and unambiguously by this protocol.
Acetates ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Caragana ; chemistry ; Carcinoma, Hepatocellular ; drug therapy ; Cell Line, Tumor ; Chalcones ; pharmacology ; Chromatography, High Pressure Liquid ; Hep G2 Cells ; Humans ; Liver Neoplasms ; drug therapy ; Medicine, Tibetan Traditional ; Plant Extracts ; chemistry ; pharmacology ; Plant Roots ; chemistry

To study the mechanisms of total flavonoid from Glycyrrhizae Radix et Rhizoma (TFGR) and its ingredient isoliquiritigenin (ISL) on their regulation of M2 phenotype polarization of macrophages. IL-4 (60 μg x L(-1)) induced RAW264.7 cells for 6 h to establish the M2 macrophage model. TFGR and ISL restrained breast cancer cells migration with the aid of M2 macrophages in vitro. TFGR and ISL inhibited gene and protein expression of Arg-1, up-regulated gene of HO-1 and protein expression of iNOS, enhanced the expression of microRNA 155 and its target gene SHIP1, meanwhile down-regulated.the phosphorylation of STAT3 and STAT6. So TFGR and ISL were the bioactive fraction and ingredient in Glycyrrhizae Radix et Rhizoma to reverse M2 phenotype macrophages polarization. TFGR and ISL inhibited the promotion of M2 macrophages to breast cancer cells migration in vitro, STAT signal pathways and miR155 were partly involved.
Animals ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Polarity ; drug effects ; Chalcones ; pharmacology ; Flavonoids ; pharmacology ; Glycyrrhiza ; chemistry ; Interleukin-4 ; genetics ; metabolism ; Macrophages ; cytology ; drug effects ; metabolism ; Mice ; RAW 264.7 Cells ; Rhizome ; chemistry

The purpose of the present study is to investigate the effect of isoliquiritigenin (ISL) on the cerebral basilar artery in spontaneously hypertensive rats (SHR). The change of SHR systolic pressure was measured by tail artery pressure measurement instrument before and after ISL intervention. After perfusion with 1 × 10(-5) mol/L phenylephrine (PE), 1 × 10(-5) mol/L PE + 1 × 10(-4) mol/L ISL and 1 × 10(-5) mol/L PE, the diameter of the cerebral basilar artery separated from SHR was measured by pressure myograph. The current of large-conductance calcium-activated potassium (BKCa) channel of SHR single vascular smooth muscle cell (VSMC) was recorded by whole-cell patch-clamp technique and the cGMP levels of basilar artery was evaluated by ELISA. The results showed that 1) after intervention with ISL for 14 days, the systolic pressure of SHR was decreased from (218.3 ± 1.6) mmHg to (119.2 ± 1.9) mmHg (P < 0.01), but there was no difference in systolic pressure between ISL-treated SHR and Wistar-Kyoto (WKY) rat; 2) 1 × 10(-4) mol/L ISL relaxed the SHR cerebral basilar artery (P < 0.01); 3) ISL significantly increased the outward current density of VSMC from SHR cerebral basilar artery (P < 0.01, n = 6), and the effect could be reversed by 1 × 10(-3) mol/L TEA (a BKCa channel inhibitor), but 3 × 10(-4) mol/L 4-AP (a Kv channel inhibitor) had no effect on the enhanced current density induced by ISL in VSMC; 4) 1 × 10(-5) mol/L Methylene blue (a sGC inhibitor) significantly inhibited the ISL-enhanced current density in VSMC (P < 0.05, n = 6); 5) ISL significantly increased the cGMP level of SHR basilar artery (P < 0.05, n = 6). The results suggest that the role of the ISL in relaxing the SHR cerebral basilar artery may be related to its effect in enhancing BKCa current by increasing the levels of cGMP in the VSMC.
Animals ; Basilar Artery ; drug effects ; Blood Pressure ; Cerebral Arteries ; drug effects ; Chalcones ; pharmacology ; Cyclic GMP ; physiology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; physiology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Systole

OBJECTIVEIsoliquiritigenin (ISL), a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells.

METHODSCell viability was evaluated using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit. The intracellular ROS levels were assessed using a 2, 7-dichlorofluorescein probe assay. The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5, 5', 6, 6'-tetra-chloro-1, 1', 3, 3'-tetraethyl-imidacarbocyanine iodide (JC-1). The degradation of poly-ADP-ribose polymerase (PARP) protein, the phosphorylation of PKR-like ER kinase (PERK), the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α), the expression of the 78 kD glucose-regulated protein (GRP 78), and the activation of caspase-12 were analyzed via western blot analysis.

RESULTSISL significantly inhibited the proliferation, the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner. Moreover, ISL induced mitochondrial dysfunction, caspase activation, and PARP cleavage, which displayed features of mitochondria dependent on apoptotic signals. Besides, exposure of HeLa cells to ISL triggered endoplasmic reticulum (ER) stress, as indicated by the increase in p-eIF2α and GRP78 expression, ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12.

CONCLUSIONThe findings from our study suggest that ISL-induced oxidative stress causes HeLa cell apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.

Aldehyde Reductase ; antagonists & inhibitors ; Apoptosis ; drug effects ; Cell Survival ; drug effects ; Chalcones ; pharmacology ; therapeutic use ; Chemoprevention ; Drug Screening Assays, Antitumor ; Endoplasmic Reticulum Stress ; drug effects ; HeLa Cells ; Humans ; Mitochondria ; drug effects ; Neoplasms ; prevention & control ; Reactive Oxygen Species ; metabolism

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

The investigation on the leaves of Morus alba L. was carried out to find the relationship of the constituents and the pharmacological activities. The isolation and purification were performed by various chromatographies such as silica gel, Sephadex LH-20, RP-C18 column chromatography and so on. Further detailed investigation on the fraction of the ethanol extract of leaves of Morus alba yielded four Diels-Alder type adducts mulberrofuran F1 (1), mulberrofuran F (2), chalcomoracin (3), kuwanon J (4), together with two chalcones morachalcone A (5), isobavachalcone (6), and three flavones norartocarpetin (7), kuwanon C (8), 6-geranylapigenin (9). Their structures were elucidated by the spectral analysis such as NMR, MS etc. Compounds 1, 6 were isolated from this plant for the first time, compounds 4-5, 7-9 were isolated from the leaves of Morus alba L. for the first time, among which 1 was a new compound. Compounds 1-5 were evaluated for the cytotoxicity against A549, Be17402, BGC823, HCT-8 and A2780 cell lines in vitro by MTT method, but only compounds 1-3 showed cytotoxicity against several human cancer cell lines.
Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; pharmacology ; Benzofurans ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chalcones ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Flavonoids ; chemistry ; isolation & purification ; pharmacology ; Humans ; Morus ; chemistry ; Plant Leaves ; chemistry ; Terpenes ; chemistry ; isolation & purification ; pharmacology

AIM: To investigate the active constituents of Lignum Sappan (Caesalpinia sappan L.) on growth-related signaling and cell mitosis. METHOD: The influence of the ethyl acetate (EtOAc) extract of Lignum Sappan and its constituents on growth-related signaling were evaluated by a luciferase assay in cells stably-transfected with NF-κB, STAT1, or STAT3 responsive luciferase reporter plasmid. The inhibitory effect on the cell cycle was determined by flow cytometric analysis. The anti-tumor activities were assessed in vitro and in vivo. RESULTS: The EtOAc extract of Lignum Sappan had inhibitory activities on growth-related signaling and cell mitosis. Three major active compounds were sappanchalcone, brazilin, and butein. Sappanchalcone blocked cell cycle progression in the G2/M phase, brazilin inhibited TNFα/NF-κB signaling, while butein inhibited IL-6/STAT3 signaling, as well as TNFα/NF-κB signaling. The three compounds all demonstrated cytotoxic activities against human tumor cells in vitro. In a S180 tumor cell-bearing mice model, the anti-tumor efficacy of the EtOAc extract was better than the individual compounds acting alone. CONCLUSION These results indicate that Lignum Sappan contains multiple active compounds with different antitumor activities, which act synergistically to enhance their anti-tumor effects. The EtOAc extract of Lignum Sappan may be better than individual active constituent as a novel medicine for the treatment of cancer.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Benzopyrans ; pharmacology ; therapeutic use ; Caesalpinia ; Cell Cycle Checkpoints ; drug effects ; Chalcones ; pharmacology ; therapeutic use ; Hep G2 Cells ; Humans ; Interleukin-6 ; metabolism ; Male ; Mice, Inbred BALB C ; Mitosis ; drug effects ; NF-kappa B ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; STAT3 Transcription Factor ; metabolism ; Sarcoma ; drug therapy ; metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the antiproliferation effect of cardamonin (CAR) and its possible mechanisms on human umbilical artery smooth muscle cells (HUASMCs) cultured in the mimicking insulin resistance (IR) medium.

METHODProliferation of HUASMCs was assayed by MTT method. The mRNA expression of mTOR, Raptor and Rictor was detected by a real-time PCR. The expression content was calculated by Livak method using internal control of beta-actin.

RESULTThe proliferation of HUASMCs cultured in the mimicking IR medium was significantly increased. Both in normal and mimic IR culture medium, cells proliferation was inhibited by CAR (1 x 10(-5), 1 x 10(-4) mol x L(-1)). Pretreated with PD98059 and LY294002, cell proliferation induced by phosphatidic acid (PA) was inhibited, and the mRNA expression of mTOR, Raptor and Rictor was significantly decreased by CAR in the mimic IR medium.

CONCLUSIONIt is implicated that antiproliferation of CAR is involved in mRNA expression decrease of mTOR and its relative protein Raptor and Rictor.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Carrier Proteins ; genetics ; metabolism ; Cell Proliferation ; drug effects ; Cells, Cultured ; Chalcones ; pharmacology ; Gene Expression Regulation ; drug effects ; Growth Inhibitors ; pharmacology ; Humans ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rapamycin-Insensitive Companion of mTOR Protein ; Regulatory-Associated Protein of mTOR ; TOR Serine-Threonine Kinases ; genetics ; metabolism