Menadione, a synthetic naphthoquinone, can be converted to active vitamin K2 in vivo.Target: OthersMenadione (Vitamin K3) is a synthetic analogue of of 1,4-naphthoquinone with a methyl group in the 2-position. Menadione is used as a phosphatase inhibitor and an inhibitor of mitochondrial DNA polymerase γ (pol γ). Menadione can be used as an oxidative injury (free radical generator) inducing agent [1].
Aloin(Aloin-A; Barbaloin-A) is a natural antitumor anthraquinone glycoside with iron chelating and non-atherogenic activities.IC50 value:Target:in vitro: Aloin significantly inhibited HUVECs proliferation, migration and tube formation in vitro. suppressed activation of VEGF receptor (VEGFR) 2 and STAT3 phosphorylation in endothelial cells. In addition, the constitutively activated STAT3 protein, and the expression of STAT3-regulated antiapoptotic (Bcl-xL), proliferative (c-Myc), and angiogenic (VEGF) proteins were also down-regulated in response to AL in human SW620 cancer cells [1]. aloin exerted inhibition of cell proliferation, adhesion and invasion abilities of B16-F10 melanoma cells under non-cytotoxic concentrations. Furthermore, aloin induced melanoma cell differentiation through the enhancement of melanogenesis and transglutaminase activity [2].in vivo: Aloin substantially reduced tumor volumes and weight in vivo mouse xenografts, without obviously toxicity [1]. Aloin (10, 30 mg/kg bw) or vehicle was given by gavage to mice after each alcohol administration. Alcohol elevated the serum transaminases alanine aminotransferase, aspartate aminotransferase, total cholesterol and triglyceride levels which were significantly attenuated by the co-administration of aloin (p < 0.05) [3].
Cryptotanshinone is a natural compound extracted from the root of Salvia miltiorrhiza Bunge that shows antitumor activities. Cryptotanshinone inhibits STAT3 with an IC50 of 4.6 μM.
Phloretin(NSC 407292; RJC 02792) is a dihydrochalcone, a type of natural phenols. Phloretin inhibits the active transport of glucose into cells by SGLT1 and SGLT2.IC50 Value: 49 +/- 12 microM [4]Target: SGLT1/2in vitro: Phlorizin blocks glucose transport across the renal tubule at concentrations in renal blood and tissue in the range of 10-5 to 10-7 M [1]. PT significantly enhanced glycerol release and inhibited the adipogenesis-related transcription factors. PT also promoted phosphorylation of AMP-activated protein kinase and increased activity of adipose triglyceride lipase and hormone-sensitive lipase in 3T3-L1 cells [2]. Phloretin induced obvious cytotoxicity against BEL-7402 cells with IC50 of 89.23 microg/mL. The growth curve demonstrated decreased growth of the cells as phloretin concentration increased [3]. D-glucose-transport activity was observed with a Km for D-glucose of 3.4 +/- 0.2 mM (mean +/- S.E.M.) and was inhibited by cytochalasin B (IC50= 0.44 +/- 0.03 microM), HgCl2 (IC50)= 3.5 +/- 0.5 microM), phloretin (IC50= 49 +/- 12 microM) and phloridzin (IC50= 355 +/- 67 microM) [4].in vivo: The effect of phloridzin orally doses 5, 10, 20 and 40 mg/kg body weight on diabetes was tested in a streptozotocin-induced rat model of diabetes type 1. From beneficial effect of this compound is significant reduction of blood glucose levels and improve dyslipidemia in diabetic rats [5].
Tanshinone IIA sulfonate (sodium) is a water-soluble derivative of tanshinone IIA, which acts as an inhibitor of store-operated Ca2+ entry (SOCE), and is used to treat cardiovascular disorders.
Embelin is a cell-permeable benzoquinone compound that exhibits antitumor properties. Specifically antagonizes XIAP-mediated inhibition of caspase-9 activation by directly targeting the Smac and caspase-9 binding domain BIR3 (IC50 = 4.1 uM in a competitive binding assay with Smac peptide).IC50 value: 4.1 uM [1]Target: XIAPin vitro: Embelin induced activation of caspase-9 and embelin-induced apoptosis was prevented by caspase inhibitors [2]. Treatment with subtoxic doses of Embelin broadly sensitized malignant glioma cells to TRAIL-mediated apoptosis. Notably, human astrocytes were not significantly affected by the combined treatment consisting of Embelin and TRAIL. Combined treatment with Embelin and TRAIL augmented the activation of initiator caspases-8/-9 and effector caspases-3/-7, respectively [3]. in vivo: Embelin inhibited topical edema in the mouse ear, leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase activity, and various histopathological indicators. Furthermore, embelin was effective at reducing inflammatory damage induced by chronic TPA exposure [4]. Embelin (10, 30 or 50mg/kg body weight) was administrated daily per oral route for 7days. Embelin significantly attenuated DSS-induced DAI scores and tissue MPO accumulation, which implied that it suppressed weight loss, diarrhea, gross bleeding, and the infiltrations of immune cells. Embelin administration also effectively and dose-dependently prevented shortening of colon length and enlargement of spleen size [5].
Rhein is a lipophilic anthraquinone extensively found in medicinal herbs, and has many pharmacological effects, including epatoprotective, nephroprotective, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. IC50 value:Target:In vitro: Rhein (0.1 and 1 mg/mL) evidently suppressed cell proliferation and mitogen-activated protein (MAP) kinase activation in human colon adenocarcinoma cells (Caco-2) but significantly lessened H2O2-induced DNA damage and the elevated MDA and ROS levels induced by H2O2/Fe2+ at the concentrations of 0.1–10 mg/mL [1].In vivo: Oral administration of rhein (150 mg/kg/d) evidently ameliorated renal interstitial fibrotic lesions and attenuated the expression of α-SMA and deposition of fibronectin (FN) in mice with renal interstitial fibrosis induced by unilateral ureteral obstruction. Rhein also suppressed TGF-β1 and its type I receptor expression in obstructed kidneys [1]. The biochemical parameters results of IgAN model rats showed that rhein-prevented and rhein-treated both improved the biochemical parameters and relieved renal pathological injury. The expressions of renal tissue TLR4, TGF-β1, but not TLR9 were significantly elevated in IgAN model rats (P < 0.05). Rhein-prevented and rhein-treated both inhibited TLR4 and TGF-β1 expressions [2].
Tanshinone IIA (Tan IIA) is one of the main fat-soluble compositions in the root of red-rooted salvia. Tanshinone IIA may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2.
Tanshinone I is an inhibitor of type IIA human recombinant sPLA2 (IC50=11 μM) and rabbit recombinant cPLA2 (IC50=82 μM).
Shikonin is a major component of a Chinese herbal medicine named zicao. Shikonin has shown various biological activities, including inhibition of TNF-α, NF-κB, HIV-1.
Daunorubicin hydrochloride is a topoisomerase II inhibitor with potent antineoplastic activities.
Vitamin K1 a fat-soluble, naturally occurring vitamin required for blood coagulation and bone and vascular metabolism.
Diacerein, a interleukin-1 beta inhibitor, is a slow-acting medicine of the class anthraquinone used to treat joint diseases.Target: IL-1 betaDiacerein, a interleukin-1 beta inhibitor, is a slow-acting medicine of the class anthraquinone used to treat joint diseases. Diacerein works by blocking the actions of interleukin-1 beta, a protein involved in the inflammation and destruction of cartilage that play a role in the development of symptoms of degenerative joint diseases such as osteoarthritis. Due to its specific mode of action, which does not involve the inhibition of prostaglandin synthesis, diacerein has been shown to have anti-osteoarthritis and cartilage stimulating properties in vitro and animal models, together with analgesic and anti-inflammatory properties. Due to its excellent gastro-intestinal tolerance, a combination therapy with an analgesic or a NSAID may be recommended during the first 2-4 weeks of treatment. From Wikipedia.
Aloin B is one isomer of Aloin; Aloin is a physiologically active anthraquinone present in aloe.
Dihydroisotanshinone I is a bioactive compound present in a widely used traditional Chinese medicine named danshen.
Bisantrene is a highly effective antitumor drug, targets eukaryotic type II topoisomerases.
β-Lapachone is a naturally occurring O-naphthoquinone, acts as a topoisomerase I inhibitor, and induces apoptosis by inhibiting cell cycle progression.
Emodin is a broad-spectrum anticancer agent. Emodin inhibits casein kinase II (CKII) activity with IC50 of 2 μM.
Coenzyme Q10 is an essential cofactor of the electron transport chain and a potent antioxidant agent.
Daunorubicin is a topoisomerase II inhibitor.
Coenzyme Q9, a nine isoprenyl group-containing member of the ubiquinone family, is a normal constituent of human plasma.
Dihydrotanshinone I is a natural compound extracted from Salvia miltiorrhiza Bunge which has been widely used for treating cardiovascular diseases.
Aloe emodin is a hydroxyanthraquinone present in Aloe vera leaves, has a specific in vitro and in vivo antitumor activity.IC50 value:Target:in vitro: aloe-emodin treatment led to the dissociation of heat shock protein 90 (HSP90) and ER α and increased ER α ubiquitination. Protein fractionation results suggest that aloe-emodin tended to induce cytosolic ER α degradation [1]. Aloe-emodin, a natural compound found in aloe, inhibited both proliferation and anchorage-independent growth of PC3 cells. Protein content analysis suggested that activation of the downstream substrates of mTORC2, Akt and PKCα, was inhibited by aloe-emodin treatment. Pull-down assay and in vitro kinase assay results indicated that aloe-emodin could bind with mTORC2 in cells and inhibit its kinase activity [2]. Of three anthraquinone derivatives, aloe-emodin, with a lower cytotoxicity showed concentration-dependently reducing virus-induced cytopathic effect and inhibiting replication of influenza A in MDCK cells. Galectin-3 also inhibited influenza A virus replication. Proteomic analysis of treated cells indicated galectin-3 up-regulation as one anti-influenza A virus action by aloe-emodin. Since galectin-3 exhibited cytokine-like regulatory actions via JAK/STAT pathways, aloe-emodin also restored NS1-inhibited STAT1-mediated antiviral responses in transfected cells: e.g., STAT1 phosphorylation of interferon (IFN) stimulation response element (ISRE)-driven promoter, RNA-dependent protein kinase (PKR) and 2'5',-oligoadenylate synthetase (2'5',-OAS) expression [3]. AE downregulated mRNA expression and promoter/gelatinolytic activity of Matrix Metalloproteinase (MMP)-2/9, as well as the RhoB expression at gene and protein level. AE suppressed the nuclear translocation and DNA binding of NF-κB [4].in vivo: Aloe-emodin also exhibited tumor suppression effects in vivo in an athymic nude mouse model [2].
Chrysophanol (Chrysophanic acid) is a natural anthraquinone, which inhibits EGF-induced phosphorylation of EGFR and suppresses activation of AKT and mTOR/p70S6K.
Idebenone is a synthetic variant of coenzyme Q10 (CoQ10), which initially developed for the treatment of Alzheimer's disease and other cognitive defects.Target: OthersIdebenone is a synthetic variant of coenzyme Q10 (CoQ10), which initially developed for the treatment of Alzheimer's disease and other cognitive defects. Idebenone was generally well tolerated with similar numbers of adverse events in each group. One child receiving high-dose idebenone developed neutropenia after 6 months, which resolved after discontinuation of treatment. 8OH2′dG concentrations were not increased, and did not significantly change with idebenone treatment [1]. The 2-year efficacy and safety of idebenone were studied in a prospective, randomized, double-blind multicentre study in 3 parallel groups of patients with dementia of the Alzheimer type (DAT) of mild to moderate degree. A total of 450 patients were randomized to either placebo for 12 months, followed by idebenone 90 mg tid for another 12 months (n = 153) or idebenone 90 mg tid for 24 months (n = 148) or 120 mg tid for 24 months (n = 149). idebenone showed statistically significant dose-dependent improvement in the primary efficacy variable ADAS-Total and in all the secondary efficacy variables [2].