Diallyl disulphide, a beneficial component of garlic oil, causes a redistribution of cell-cycle growth phases, induces apoptosis and enhances butyrate-induced apoptosis in colorectal adenocarcinoma cells (HT-29)

Colon cancer is a leading and expanding cause of death worldwide. A major contributory factor to this disease is diet composition; some components are beneficial (e.g. dietary fibre) whilst others are detrimental (e.g. alcohol). Garlic oil is a prominent dietary constituent that prevents the development of colorectal cancer. This effect is believed to be mainly due to diallyl disulphide (DADS), which selectively induces redox stress in cancerous (rather than normal) cells which leads to apoptotic cell death. However, the detailed mechanism by which DADS causes apoptosis remains unclear. We show that DADS-treatment of colonic adenocarcinoma cells (HT-29) initiates a cascade of molecular events characteristic of apoptosis. These include a decrease in cellular proliferation, translocation of phosphatidylserine to the plasma-membrane outer-layer, activation of caspase-3, genomic-DNA fragmentation and G2/M phase cell-cycle arrest. Short-chain fatty acids (SCFAs), particularly butyrate (abundantly produced in the gut by bacterial fermentation of dietary polysaccharides), enhance colonic cell integrity but, in contrast, inhibit colonic-cancer cell growth. Combining DADS with butyrate augmented the effect of butyrate on HT-29 cells. These results suggest that the anti-cancerous properties of DADS afford greater benefit when supplied with other favourable dietary factors (SCFA/polysaccharides) that likewise reduce colonic tumour development.

Challenge testing the lactoperoxidase system against a range of bacteria using different activation agents

Lactoperoxidase (LP) exerts antimicrobial effects in combination with H2O2 and either thiocyanate (SCN-) or a halide (e. g., I-). Garlic extract in the presence of ethanol has also been used to activate the LP system. This study aimed to determine the effects of 3 LP activation systems (LP+SCN-+H2O2; LP+I-+H2O2; LP + garlic extract + ethanol) on the growth and activity of 3 test organisms (Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus cereus). Sterilized milk was used as the reaction medium, and the growth pattern of the organisms and a range of keeping quality (KQ) indicators (pH, titratable acidity, ethanol stability, clot on boiling) were monitored during storage at the respective optimum growth temperature for each organism. The LP+I-+H2O2 system reduced bacterial counts below the detection limit shortly after treatment for all 3 organisms, and no bacteria could be detected for the duration of the experiment (35 to 55 h). The KQ data confirmed that the milk remained unspoiled at the end of the experiments. The LP + garlic extract + ethanol system, on the other hand, had no effect on the growth or KQ with P. aeruginosa, but showed a small retardation of growth of the other 2 organisms, accompanied by small increases (5 to 10 h) in KQ. The effects of the LP+SCN-+H2O2 system were intermediate between those of the other 2 systems and differed between organisms. With P. aeruginosa, the system exerted total inhibition within 10 h of incubation, but the bacteria regained viability after a further 5 h, following a logarithmic growth curve. This was reflected in the KQ indicators, which implied an extension of 15 h. With the other 2 bacterial species, LP+SCN-+H2O2 exerted an obvious inhibitory effect, giving a lag phase in the growth curve of 5 to 10 h and KQ extension of 10 to 15 h. When used in combination, I- and SCN- displayed negative synergy.

Interactions between herbal and conventional medicines

Herb-drug interactions are subject to much interest at present, but for various reasons reports may be unreliable or unsubstantiated. Herbal medicines are variable in composition and quality, which may affect their interaction profile as well as the reliability of reports concerning them. In this review, clinical and experimental reports have been collated, evaluated and summarised, and the theoretical and clinical evidence presented. There is an explanation of the particular issues involved with herbal medicines as compared with conventional drugs, and reasons why comparisons may or may not be valid, which is intended for those without specialist experience in herbal products. It has become apparent that only a few herbal drugs have so far been cited in interaction reports, for example St John's Wort, Ginkgo biloba, Dan Shen, liquorice, Ma huang and garlic, and that the main drugs involved are those which are already susceptible to interactions with many other conventional drugs, such as warfarin, protease inhibitors and anti-cancer drugs. An attempt has been made to put the matter into perspective and recommendations have been given for health professionals to advise or develop strategies to safeguard patients, without resorting to speculation or scaremongering.

Natural products as alternative treatments for metabolic bone disorders and for maintenance of bone health

Bone metabolism involves a complex balance between the deposition of matrix and mineralization and resorption. There is now good evidence that dietary components and herbal products can influence these processes, particularly by inhibiting bone resorption, thus having beneficial effects on the skeleton. For example, it has been reported that a number of common vegetables, including onion, garlic and parsley, can inhibit bone resorption in ovariectomized rats. Essential oils derived from sage, rosemary, thyme and other herbs inhibit osteoclast activity in vitro and in vitro and leading to an increase in bone mineral density. Soya, a rich source of isoflavones, has shown promising results and epidemiological evidence to support a use in maintaining bone health, and various traditional herbal formulae in Chinese and Ayurvedic medicine also have demonstrable effects in pharmacological models of osteoporosis. Recently, cannabinoids have been described as having positive effects on osteoblast differentiation, and the presence of cannabinoid receptors in bone tissue indicates a more complex role in bone metabolism than previously thought. The first part of this review briefly discusses normal bone metabolism and disorders caused by its disruption, with particular reference to osteoporosis and current pharmacological treatments. The effects of natural products on bone and connective tissue are then discussed, to include items of diet, herbal extracts and food supplements, with evidence for their efficacy outlined. Copyright (c) 2006 John Wiley & Sons, Ltd.

Diallyl disulfide-induced apoptosis in a breast-cancer cell line (MCF-7) may be caused by inhibition of histone de-acetylation

The health benefits of garlic have been proven by epidemiological and experimental studies. Diallyl disulphide (DADS), the major organosulfur compound found in garlic oil, is known to lower the incidence of breast cancer both in vitro and in vivo. The studies reported here demonstrate that DADS induces apoptosis in the MCF-7 breast-cancer cell line through interfering with cell-cycle growth phases in a way that increases the sub-G0 population and substantially halts DNA synthesis. DADS also induces phosphatidylserine (PS) translocation from the inner to the outer leaflet of the plasma membrane and activates caspase-3. Further studies revealed that DADS modulates the cellular levels of Bax, Bcl-2, Bcl-xL and Bcl-w in a dose-dependent manner, suggesting the involvement of Bcl-2 family proteins in DADS induced apoptosis. Histone deacetylation inhibitors (HDACi) are known to suppress cancer growth and induce apoptosis in cancer cells. Here it is shown that DADS has HDACi properties in MCF-7 cells as it lowers the removal of an acetyl group from an acetylated substrate and induces histone-4 (H4) hyper-acetylation. The data thus indicate that the HDACi properties of DADS may be responsible for the induction of apoptosis in breast cancer cells.