The chemopreventive effects of seven Chinese herbs against hepatocarcinogenesis were evaluated in vitro. The water extracts from Scutellaria barbata and Hedyotis diffusa among the seven herbs as well as Curcuma zedoaria (positive control), strongly inhibited cell growth of four human hepatoma cell lines; HuH-7 (p53 mutant), PLC/PRF/5 (p53 mutant), HepG2 (p53 wild-type) and Hep3B (p53 null). These two extracts also induced apoptotic cell death of these cell lines, as evaluated by DNA fragmentation and chromatin condensation. It is suggested that these Chinese herb extracts might contain active components which are able to induce apoptosis independent of the p53-induced process.
Although information about the mechanism of apoptosis is rapidly increasing, critical roles of mitochondria in the regulation of cell death remain to be elucidated. Recent studies revealed that reactive oxygen species (ROS) in cells increase prior to the onset of DNA fragmentation, a late phase event in apoptosis. An overload of Ca2+ induces a classic type of membrane permeability transition (CMPT) characterized by depolarization and swelling of mitochondria thereby releasing cytochrome c by a cyclosporin A-sensitive mechanism. In contrast, some agents induce apoptosis by increasing mitochondrial membrane permeability and swelling by some cyclosporin A- and Ca2+-insensitive mechanism; this phenomenon is defined as non-classic type of MPT (NCMPT). However, the role of ROS and antioxidants, such as α-tocopherol, in the mechanism of CMPT and NCMPT induction remains unclear. The present work overviews the role of ROS and α-tocopherol in the induction of CMPT and NCMPT.
Sesame seed and vitamin E are traditionally recognized to be the food components with anti-ageing effects. However, ninety eight percent of the vitamin E in sesame seed is γ-tocopherol, which has low vitamin E activity. We observed that sesame seed produced higher concentrations of vitamin E in the animal body, and could prove that the primary cause of high tocopherol concentrations in the animals fed sesame seed is that sesame lignan, characteristic components of sesame seed, inhibit the degradation of vitamin E to carboxyethylhydroxychroman. The inhibition of vitamin E metabolism is a unique characteristic of sesame seed lignans as compared with other plant lignans. We observed that tocotrienol is present specifically in the skin and adipose tissues. Dietary tocotrienol accumulated in the skin prevents oxidative damage induced by UVB irradiation. Sesame lignans induce higher tocotrienol concentrations in the skin, and act together with tocotrienol to prevent oxidative damage induced by UVB irradiation.
α-Tocopheryl succinate (TS), a succinyl ester of α-tocopherol (α-T), has no antioxidant activity, but it does have unique physicochemical properties and shows versatile biological functions. The physicochemical properties of TS affect the structure and function of lipid membranes, and the ability to form bilayer vesicles by itself suggests that TS can become a new carrier in the field of drug delivery systems. The ability to induce apoptosis is a most attractive property of TS. Because TS shows higher cytotoxicity on various cancer cells than on normal cells in vitro, prevents tumor growth, and extends survival in vivo, much attention has been paid to TS as a new type of anti-cancer drug. Activation of various signal transduction factors is also a well-known function of TS. In particular, protein kinase C (PKC), which acts in upstream in the signal transduction, is thought to play an important role in the effects of TS. Our theoretical computational study indicates that TS activates PKC by direct interaction with PKC due to its high structural flexibility.
It has been implicated that oxidative stress is involved in the development of aged-related and diabetic cataracts in humans and also in cataract development in a variety of in vivo experimental cataract models. Therefore, this article will review the possibility of the clinical application of vitamin E to cataract prevention, based on data concerning the level of vitamin E in normal and cataractous lenses of humans and experimental animals, the relationship between dietary vitamin E intake and the risk of cataracts, the effect of vitamin E supplementation on cataract development in humans, and the effect of oral or parenteral vitamin E treatment or topical vitamin E instillation on cataract development in a variety of in vivo experimental cataract models. These data reported so far may allow us to think of a possibility that vitamin E is clinically applied to cataract development.
We present here current data on the distribution and metabolism of vitamin E analogs in vivo. There are eight different naturally occurring forms of vitamin E: four tocopherols (α-, β-, γ-, and δ-Toc) and four tocotrienols (α-, β-, γ-, and δ-Toc-3). With regard to the bioavailability of vitamin E, it has been established that the affinity of various vitamin E analogs for α-tocopherol transfer protein (α-TTP), which may determine their plasma levels, is a major determinant of their biological activity. However, a novel function of Toc-3 has been noted as a result of its unique distribution in the skin and the adipose tissue. In addition, following the discovery that the final metabolites of Toc and Toc-3 are in the form of carboxyethyl hydroxychroman, it is now possible to examine the intermediary metabolites of vitamin E analogs. The metabolism of vitamin E is known to be involved in the actions of drug metabolic enzymes (CYP3A, CYP4F2). However, the relationship between α-TTP and the metabolic enzymes that are responsible for the regulation of vitamin E metabolism has yet to be clarified. Future research will focus on the elucidation of the vitamin E metabolic regulation system.