Gerobiotics: probiotics targeting fundamental aging processes.

Aging is recognized as a common risk factor for many chronic diseases and functional decline. The newly emerging field of geroscience is an interdisciplinary field that aims to understand the molecular and cellular mechanisms of aging. Several fundamental biological processes have been proposed as hallmarks of aging. The proposition of the geroscience hypothesis is that targeting holistically these highly integrated hallmarks could be an effective approach to preventing the pathogenesis of age-related diseases jointly, thereby improving the health span of most individuals. There is a growing awareness concerning the benefits of the prophylactic use of probiotics in maintaining health and improving quality of life in the elderly population. In view of the rapid progress in geroscience research, a new emphasis on geroscience-based probiotics is in high demand, and such probiotics require extensive preclinical and clinical research to support their functional efficacy. Here we propose a new term, "gerobiotics", to define those probiotic strains and their derived postbiotics and para-probiotics that are able to beneficially attenuate the fundamental mechanisms of aging, reduce physiological aging processes, and thereby expand the health span of the host. We provide a thorough discussion of why the coining of a new term is warranted instead of just referring to these probiotics as anti-aging probiotics or with other similar terms. In this review, we highlight the needs and importance of the new field of gerobiotics, past and currently on-going research and development in the field, biomarkers for potential targets, and recommended steps for the development of gerobiotic products. Use of gerobiotics could be a promising intervention strategy to improve health span and longevity of humans in the future.

Calophyllolide content in Calophyllum inophyllum at different stages of maturity and its osteogenic activity.

Calophyllum inophyllum is a coastal plant rich in natural substances. Its ingredients have been used for the development of an anti-human immunodeficiency virus (HIV) drug. In this study, we collected C. inophyllum fruit, and the ethanol extract of the fruit was chromatographically separated using silica gel and Sephadex LH-20 columns to obtain the major compound, calophyllolide. The fruits were harvested from September to December in 2011; a quantitative analysis of the calophyllolide content was conducted using HPLC to explore the differences between the different parts of the fruit during the growing season. The results showed that in fruits of C. inophyllum, calophyllolide exists only in the nuts, and dried nuts contain approximately 2 mg·g-1 of calophyllolide. The calophyllolide levels in the nuts decreased during maturity. In addition, calophyllolide dose-dependently enhanced alkaline phosphatase (ALP) activity in murine osteoblastic MC3T3-E1 cells, without significant cytotoxicity. The expression of osteoblastic genes, ALP and osteocalcin (OCN), were increased by calophyllolide. Calophyllolide induced osteoblasts differentiation also evidenced by increasing mineralization and ALP staining.

A Special Ingredient (VtR) Containing Oligostilbenes Isolated from Vitis thunbergii Prevents Bone Loss in Ovariectomized Mice: In Vitro and In Vivo Study.

Vitis thunbergii is used in Taiwan as a botanical supplement for inflammatory bone diseases. This study aims to examine its direct effect on bone metabolism. Three-month-old female mice were randomly divided into ovariectomized control (OVX), sham operated (SHAM), and ovariectomy treated with either 17 ß -estradiol or a special ingredient (VtR) fractionated from an ethanol extract of V. thunbergii started two weeks after ovariectomy. VtR treatment for 8 weeks significantly ameliorated the deterioration of bone mineral density and reversed all the ovariectomy-induced changes in µ -CT parameters. The antiosteoporotic effect of VtR accompanied decrease in serum levels of C-terminal telopeptides of type I collagen (CTx), interleukin-7, and ration of RANKL/osteoprotegerin (OPG) but rise in osteocalcin concentration. Sparse calcified microarchitecture and less alkaline-phosphatase- (ALP-) positive cells were observed at the femur and vertebral sites in OVX mice while VtR remarkably restored such variation. HPLC analysis showed (+)-vitisin-A, (-)-vitisin-B, and ampelopsin C predominated in VtR. Both (-)-vitisin B and ampelopsin C increased ALP activity and bone nodule formation in cultured osteoblasts. Instead of stimulating osteoblastogenesis, (+)-vitisin A dramatically repressed osteoclasts differentiation and bone resorption. The results suggested VtR composed of diverse components to reciprocally drive osteoblastogenesis and interdict osteoclastogenesis may serve as a potential botanic drug for osteoporosis therapy.

Immunomodulatory Activity of Lactococcus lactis A17 from Taiwan Fermented Cabbage in OVA-Sensitized BALB/c Mice.

From fermented Taiwan foods, we have isolated numerous lactic acid bacteria (LAB) of plant origin and investigated their biological activities. This study aimed to investigate the immunomodulatory effect and mechanism of Lactococcus lactis A17 (A17), isolated from Taiwan fermented cabbage, on ovalbumin (OVA)-sensitized mice. Human peripheral blood mononuclear cells were used to verify immune responses of A17 by IFN-γ production. Live (A17-A) and heat-killed A17 (A17-H) were orally administered to OVA-sensitized BALB/c mice to investigate their effects on immunoglobulin (Ig) and cytokine production. The mRNA expression of Toll-like receptors (TLR) and nucleotide binding oligomerization domain (NOD)-like protein receptors in spleen cells was analyzed by real-time RT-PCR. Both live and heat-killed A17 modulate OVA-induced allergic effects. B-cell response was modulated by diminishing IgE production and raising OVA-specific IgG2a production, while T-cell response was modulated by increasing IFN-γ production and decreasing IL-4 production. The mRNA expression of NOD-1, NOD-2, and TLR-4 was down-regulated by A17 as well. This is the first report to describe a naïve Lactococcus lactis A17 strain as a promising candidate for prophylactic and therapeutic treatments of allergic diseases via oral administration. Our results suggest the ameliorative effects of A17 may be caused by modulating NOD-1 NOD-2, and TLR-4 expression.

Biological activities and applications of dioscorins, the major tuber storage proteins of yam.

Yam tubers, a common tuber crop and an important traditional Chinese medicine in Taiwan, have many bioactive substances, including phenolic compounds, mucilage polysaccharides, steroidal saponins and proteins. Among the total soluble proteins, 80% of them are dioscorins. In the past two decades, many studies showed that dioscorins exhibited biological activities both in vitro and in vivo, including the enzymatic, antioxidant, antihypertensive, immunomodulatory, lectin activities and the protecting role on airway epithelial cells against allergens in vitro. Some of these activities are survived after chemical, heating process or enzymatic digestion. Despite of lacking the intact structural information and the detail action mechanisms in the cells, yam dioscorins are potential resources for developing as functional foods and interesting targets for food protein researchers.

Protective effects of Antrodia cinnamomea against liver injury.

Chinese herbal medicine () attracts much attention in the treatment of liver injuries. Numerous studies have revealed various biological activities of medicinal mushrooms such as Antrodia Cinnamomea (). Although A. cinnamomea is rare in the wild, recent developments in fermentation and cultivation technologies make the mycelia and fruiting bodies of this valuable medicinal mushroom readily available. Liver diseases such as fatty liver, hepatitis, hepatic fibrosis, and liver cancer are complicated processes of liver injuries that have tremendous impact on human society. In this article, we reviewed studies about the hepatoprotective effects of the fruiting bodies and mycelia of A. cinnamomea performed in different experimental models. The results of those studies suggest the potential application of A. cinnamomea in preventing and treating liver diseases and its potential to be developed into health foods or new drugs.

Pectin hydroxamic acids exhibit antioxidant activities in vitro.

Commercial pectins with different degrees of esterification (DE) were reacted with equal volumes of 2 M alkaline hydroxylamine (pH 12.0) at room temperature for 4 h to prepare pectin hydroxamic acids (PHAs; DE94T4, DE65T4, and DE25T4) according to a previously reported method (Hou et al., J. Agric. Food Chem. 2003, 51, 6362-6366) and were used to test the antioxidant and antiradical activities in comparison with those of DE94, DE65, and DE25 pectins. The half-inhibition concentrations, IC(50), of scavenging activity against DPPH were 1.51, 5.43, and 5.63 mg/mL for DE94T4, DE65T4, and DE25T4, respectively, and were much lower than those of corresponding DE pectins under the same concentrations. The scavenging activities of PHAs for DPPH radicals were positively correlated with original DE values of pectin. The optimal pH of DE94T4 for scavenging DPPH radicals was 7.9 or 8.0. Using electron spin resonance (ESR) for scavenging hydroxyl radicals, under the same concentrations of 125 microg/mL, DE94T4, DE65T4, and DE25T4, respectively, exhibited 73.53, 69.01, and 55.17% antiradical activities. PHAs also exhibited protection against hydroxyl radical-mediated DNA damage and anti-human low-density lipoprotein peroxidation tests.

Patatin, the tuber storage protein of potato (Solanum tuberosum L.), exhibits antioxidant activity in vitro.

The potato (Solanum tuberosum L.) tuber storage protein, patatin, was purified to homogeneity with a molecular mass of 45 kDa. The purified patatin showed antioxidant or antiradical activity by a series of in vitro tests, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (half-inhibition concentration, IC(50), was 0.582 mg/mL) scavenging activity assays, anti-human low-density lipoprotein peroxidation tests, and protections against hydroxyl radical-mediated DNA damages and peroxynitrite-mediated dihydrorhodamine 123 oxidations. Using electron paramagnetic resonance (EPR) spectrometry for hydroxyl radical detections, it was found that the intensities of the EPR signal were decreased by the increased amounts of patatin added (IC(50) was 0.775 mg/mL). Through modifications of patatin by iodoacetamide or N-bromosuccinimide, it was found that the antiradical activities of modified patatin against DPPH or hydroxyl radicals were decreased. It was suggested that cysteine and tryptophan residues in patatin might contribute to its antioxidant activities against radicals.