Curcumin reduces oxidative damage by increasing reduced glutathione and preventing membrane permeability transition in isolated brain mitochondria.

Mitochondria are critical regulators of energy metabolism and programmed cell death pathways. Mitochondria are also the major site for the production of reactive oxygen species which make this organelle more susceptible to oxidative damage and impairments of mitochondrial functions. Antioxidants have been of limited therapeutic success to ameliorate the toxic effects of oxidative stress in mitochondria. One reason may be the inability of mitochondria to selectively take up antioxidants. In the present study we synthesized mitochondrially targeted curcumin with an aim of delivering this polyphenolic compound to isolated mitochondria. Our observations show the strong anti-oxidative effects of curcumin and mitochondrially targeted curcumin against the lipid peroxidation, protein carbonylation and mitochondrial permeability transition induced by tert-butylhydroperoxide. Both curcumin and mitochondrially targeted curcumin significantly enhanced endogenous reduced glutathione level in the mitochondria thus preserving mitochondrial defense system against oxidative stress. We concluded that curcumin and mitochondrially targeted curcumin protected mitochondria against tert-butylhydroperoxide by lowering the oxidative damage, increasing the availability of endogenous reduced glutathione and preserving the mitochondrial integrity. Importantly, mitochondrially targeted curcumin was found most effective in ameliorating oxidative stress and preserving mitochondrial integrity than curcumin.

Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration.

Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the efficacy of UC-II (10 mg/day) in five female subjects (58-78 years) suffering from significant joint pain. Significant pain reduction including morning stiffness, stiffness following periods of rest, pain that worsens with use of the affected joint and loss of joint range of motion and function was observed. Thus, UC-II may serve as a novel therapeutic tool in joint inflammatory conditions and symptoms of OA and RA.

Benefits of resveratrol in women's health.

Resveratrol and trans-resveratrol are powerful phytoestrogens, present in the skins of grapes and other plant foods and wine, which demonstrate a broad spectrum of pharmacological and therapeutic health benefits. Phytoestrogens are naturally occurring plant-derived nonsteroidal compounds that are functionally and structurally similar to steroidal estrogens, such as estradiol, produced by the body. Various studies, reviewed herein, have demonstrated the health benefits of phytoestrogens in addressing climacteric syndrome including vasomotor symptoms and postmenopausal health risks, as well as their anticarcinogenic, neuroprotective and cardioprotective activities and prostate health and bone formation promoting properties. Conventional HRT drugs have been demonstrated to cause serious adverse effects including stroke and gallbladder disease, as well as endometrial, uterine and breast cancers. Recent research demonstrates that trans-resveratrol binds to human estrogen receptors and increases estrogenic activity in the body. We investigated the effects of protykin, a standardized extract of trans-resveratrol from Polygonum cuspidatum, on cardioprotective function, the incidence of reperfusion-induced arrhythmias and free radical production in isolated ischemic/reperfused rat hearts. The rats were orally treated with two different daily doses of protykin for 3 weeks. Coronary effluents were measured for oxygen free radical production by electron spin resonance (ESR) spectroscopy in treated and drug-free control groups. In rats treated with 50 and 100 mg/kg of protykin, the incidence of reperfusion-induced ventricular fibrillation was reduced from its control value of 83% to 75% (p < 0.05) and 33% (p < 0.05), respectively. Protykin was seen to possess cardioprotective effects against reperfusion-induced arrhythmias through its ability to reduce or remove the reactive oxygen species in ischemic/reperfused myocardium. Taken together, these data suggest that trans-resveratrol supplementation may be a potential alternative to conventional HRT for cardioprotection and osteoporosis prevention and may confer other potential health benefits in women.

Acute and long-term safety evaluation of a novel IH636 grape seed proanthocyanidin extract.

Grape seed proanthocyanidins are known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties. Previous studies in our laboratories have demonstrated the various protective abilities of a novel IH636 grape seed proanthocyanidin extract (GSPE) against various pathologic conditions. However no extensive safety studies have been conducted on grape seed proanthocyanidins to date. This study demonstrates the acute and chronic safety studies on GSPE. Acute oral toxicity, dermal toxicity, dermal irritation and eye irritation studies have been conducted. The LD50 of GSPE was found to be greater than 5000 mg/kg when administered once orally via gastric intubation to fasted male and female albino rats. The LD50 of GSPE was found to be greater than 2000 mg/kg when administered once for 24 hr to the clipped, intact skin of male and female albino rats. In addition, 2000 mg/kg was found to be the no-observed-effect level (NOEL) for systemic toxicity under the conditions of the study. In a dermal irritation study, GSPE received a descriptive rating classification of moderately irritating. Extensive chronic studies were also conducted. We have assessed the effects of chronic administration of 100 mg GSPE/kg/day for twelve months and its effect on seven vital target organs, namely, brain, heart, intestine, kidney, liver, lung and spleen, and on serum chemistry changes in male B6C3F1 mice. Furthermore, the dose-dependent chronic effects of GSPE in female B6C3F1 mice were evaluated. Mice were fed 0, 100, 250 or 500 mg GSPE/kg/day for six months and the effects of GSPE exposure were examined on brain, duodenum, heart, kidney, liver, lung, pancreas and spleen, and on serum chemistry changes in female mice. These acute studies demonstrated that GSPE is safe and did not cause any detrimental effects in vivo under the conditions investigated in this study.

Adaptation of the relaxation method for learning in bidirectional associative memory.

An iterative learning algorithm called PRLAB is described for the discrete bidirectional associative memory (BAM). Guaranteed recall of all training pairs is ensured by PRLAB. The proposed algorithm is significant in many ways. Unlike many existing iterative learning algorithms, PRLAB is not based on the gradient descent technique. It is a novel adaptation from the well-known relaxation method for solving a system of linear inequalities. The algorithm is very fast. Learning 200 random patterns in a 200-200 BAM takes only 20 epochs on the average. PRLAB is highly insensitive to learning parameters and the initial configuration of a BAM. It also offers high scalability for large applications by providing the same high performance when the number of training patterns are increased in proportion to the size of the BAM. An extensive performance analysis of the new learning algorithm is included.