Symphytine is a natural inducer of hepatic tumors. Symphytine interacts with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development.
Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities, including antibacterial, anticancer, antiplatelet, and antioxidant properties.1,2,3,4It is active against Gram-positive (MICs = 5-160 µg ml) and Gram-negative bacteria (MICs = 136-200 µg ml), as well as yeasts (MICs = 10-20 µg ml).1Ajoene is cytotoxic to mouse melanoma cells (IC50= 18 µM), as well as human colon, lung, mammary, and pancreatic cancer cells (IC50s = 7-41 µM).2It reduces tumor growth in a B16 BL6 mouse model of melanoma when administered at a dose of 25 mg kg every other day and decreases the number of lung metastases when administered prior to tumor cell inoculation at doses ranging from 1-25 mg kg. It inhibits ADP- or collagen-induced platelet aggregation in isolated baboon platelets when used at concentrations ranging from 75 to 150 µg ml and in platelet-rich plasma isolated from baboons when administered at a dose of 25 mg kg.3Ajoene (25 mg kg) prevents thrombus formation on damaged arterial walls in heparinized pigs in anin situmodel of thrombogenesis.5It also reduces high-fat diet-induced hepatic steatosis, histopathological markers of liver damage, thiobarbituric acid reactive substances (TBARS) formation, and protein oxidation in a mouse model of non-alcoholic fatty liver disease (NAFLD).4 1.Naganawa, R., Iwata, N., Ishikawa, K., et al.Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlicAppl. Environ. Microbiol.62(11)4238-4242(1996) 2.Taylor, P., Noriega, R., Farah, C., et al.Ajoene inhibits both primary tumor growth and metastasis of B16 BL6 melanoma cells in C57BL 6 miceCancer Lett.239(2)298-304(2006) 3.Teranishi, K., Apitz-Castro, R., Robson, S.C., et al.Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoeneXenotransplantation10(4)374-379(2003) 4.Han, C.Y., Ki, S.H., Kim, Y.W., et al.Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activationAntioxid. Redox Signal.14(2)187-202(2011) 5.Apitz-Castro, R., Badimon, J.J., and Badimon, L.A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental modelThromb. Res.75(3)243-249(1994)
6(5H)-Phenanthridinone is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2. It decreases radiation-induced PARP activity and proliferation of RDM4 murine lymphoma cells. 6(5H)-Phenanthridinone reduces NF-κB-induced transcription of the genes encoding TNF-α, IL-2, and IFN-γ in rat lymphocytes. In vivo, 6(5H)-phenanthridinone reduces spinal cord expression of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, IL-2, and IFN-γ and reduces disease score in a rat model of experimental autoimmune encephalomyelitis (EAE). It also decreases serum levels of lactate dehydrogenase as well as hepatic lipid peroxidation, oxidative DNA damage, and PARP levels.
8,12-iso-iPF2α-VI, an isoprostane, arises from non-enzymatic, free radical-induced peroxidation of membrane lipids. It is the predominant isoprostane formed during lipid peroxidation and serves as a biomarker for oxidative stress. Detectable in hepatic tissue post CCl4-induced oxidative damage, 8,12-iso-iPF2α-VI levels are also elevated in the urine, blood, and cerebrospinal fluid of Alzheimer’s disease patients.
Daturaolone has potency in reducing the harmful effects or in maintaining the normal hepatic physiological mechanisms in both acute and chronic hepato-toxic induced liver damage in rats. Daturaolone also possesses in vivo anti-inflammatory and antinocicep