Yooheon Park

Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses.

The new age of nutraceuticals is now embracing the centuries old herbal extract of Ginkgo biloba (Mantissa Plantarum Altera, 1771, Ginkgoceae). The standardized preparation of the Ginkgo leaf extract (EGb 761) contained 2 main bioactive constituents, flavonoid glycosides (24%) and terpene lactones (6%), along with less than 5 ppm of the allergenic component, ginkgolic acid. The Ginkgo leaf extract has been reported to have neuroprotective, anticancer, cardioprotective, stress alleviating, and memory enhancing effects and possible effects on tinnitus, geriatric complaints, and psychiatric disorders. The therapeutic mechanisms of action of the Ginkgo leaf extract are suggested to be through its antioxidant, antiplatelet, antihypoxic, antiedemic, hemorrheologic, and microcirculatory actions, where the flavonoid and the terpenoid constituents may act in a complementary manner. Toxicity studies show that the Ginkgo leaf extract is relatively safe for consumption, although a few side effects have been reported, that is, intracerebral hemorrhage, gastrointestinal disturbances, headaches, dizziness, and allergic skin reactions. The use of Ginkgo leaf extract may be promising for treatment of certain conditions, although its long-term use still needs to be evaluated.

Droplet size and composition of nutraceutical nanoemulsions influences bioavailability of long chain fatty acids and Coenzyme Q10.

The influence of droplet size (d32=0.21, 0.70 or 2.2μm) and oil digestibility (corn oil versus mineral oil) on the bioavailability of a model long chain fatty acid (heptadecanoic acid) and lipophilic nutraceutical (Coenzyme Q10) was investigated using a rat feeding study. Initially, we showed that small droplets were digested more rapidly than large droplets using a simulated small intestinal model (pH stat), which was attributed to the greater surface area of lipid exposed to intestinal juices. The pH stat model also confirmed that emulsified corn oil was digestible, whereas emulsified mineral oil was indigestible. A rat feeding study showed that the bioavailability of the fatty acid and lipophilic nutraceutical in small intestinal tissues was highest when they were encapsulated within digestible oil droplets with the smallest size. This study provides important information for development of nanoemulsion-based delivery systems that increase oral bioavailability of lipophilic nutraceuticals.

Fermenting Red Ginseng Enhances Its Safety and Efficacy as a Novel Skin Care Anti-Aging Ingredient: In Vitro and Animal Study

The objective of this study was to evaluate the anti-aging potential and skin safety of red ginseng (RG) and fermented red ginseng (FRG) using Lactobacillus brevis for use as cosmetic ingredients. Concentrations of uronic acid, polyphenols, and flavonoids, and antioxidant activities were greater in FRG compared to RG. The contents of total ginsenosides were not significantly different. However, the ginsenoside metabolite content was higher in FRG (14,914.3 μg/mL) compared to RG (5697.9 μg/mL). The tyrosinase inhibitory activity (IC(50)) of FRG was 27.63 μg/mL, and more potent compared with RG (34.14 μg/mL), (P<.05). The elastase inhibitory activity (IC(50)) of FRG was 117.07 μg/mL also higher compared with RG (157.90 μg/mL). In a primary skin irritation test, 10% RG and 10% FRG were classified as practically nonirritating materials. In a skin sensitization test, the RG group showed a sensitization rate of 100% and its mean evaluation score of irritation was 1.4, whereas the FRG group showed 20% and 0.2%, respectively. By fermentation of RG, FRG has increased contents of ginsenoside metabolites, such as Rg3, Rg5, Rk1, compound K, Rh1, F2, Rg2, and flavonoids content. Therefore, FRG offers increased anti-wrinkle efficacy, whitening efficacy, and reduced toxicological potency compared to RG.

Imidacloprid, a Neonicotinoid Insecticide, Potentiates Adipogenesis in 3T3-L1 Adipocytes

There is emerging evidence that organochlorine and organophosphorus insecticide exposure may be linked to excessive weight gain and symptoms of diabetes. However, there is a lack of knowledge for other types of insecticides with potential influence on obesity and diabetes. Thus, the purpose of this investigation was to determine the role of imidacloprid, a neonicotinoid insecticide, in lipid metabolism by use of 3T3-L1 adipocytes. Imidacloprid treatment potentiated lipid accumulation in 3T3-L1 adipocytes and significantly increased expression of a key regulator of adipocyte differentiation and key regulators of lipogenesis. These results imply the involvement of imidacloprid in altered adipogenesis, resulting in increased fat accumulation. This finding is the first report of a potential link between neonicotinoid insecticide exposure and lipid accumulation in adipocytes. Further in vivo as well as epidemiological studies will be required before we can extrapolate these findings to a potential contribution of imidacloprid in human obesity.

Permethrin Alters Adipogenesis in 3T3-L1 Adipocytes and Causes Insulin Resistance in C2C12 Myotubes

Pyrethroids are a class of insecticides structurally derived from the naturally occurring insecticides called pyrethrins. Along with emerging evidence that exposure to insecticides is linked to altered weight gain and glucose homeostasis, exposure to pyrethroids has been linked to altered blood glucose levels in humans. Thus, the purpose of this study was to determine the role of permethrin on lipid and glucose metabolisms. Permethrin was treated to 3T3‐L1 adipocytes and C2C12 myoblasts to determine its role in lipid and glucose metabolisms, respectively. Permethrin treatment resulted in increased expression of key markers of adipogenesis and lipogenesis in adipocytes. Permethrin significantly reduced insulin‐stimulated glucose uptake in myotubes. This is the first report on the role of permethrin in altered lipid metabolism in adipocytes and impaired glucose homeostasis in myotubes. These results may help elucidate fundamental underlying mechanisms between insecticide exposure, particularly permethrin, and potential risk of developing obesity and its comorbidities.

The bioavailability of red ginseng extract fermented by Phellinus linteus.

For the improvement of ginsenoside bioavailability, the ginsenosides of fermented red ginseng by Phellinus linteus (FRG) were examined with respect to bioavailability and physiological activity. The polyphenol content of FRG (19.14±0.50 mg/g) was significantly higher (p<0.05) compared with that of non-fermented red ginseng (NFRG, 11.31±1.15 mg/g). The antioxidant activities in FRG, such as 2,2’-diphenyl-1-picrylhydrazyl, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, and ferric reducing antioxidant power, were significantly higher (p<0.05) than those in NFRG. The HPLC analysis results showed that the FRG had a high level of ginsenoside metabolites. The total ginsenoside contents in NFRG and FRG were 41.65±1.53 mg/g and 50.12±1.43 mg/g, respectively. However, FRG had a significantly higher content (33.90±0.97 mg/g) of ginsenoside metabolites (Rg3, Rg5, Rk1, compound K, Rh1, F2, and Rg2) compared with NFRG (14.75±0.46 mg/g). The skin permeability of FRG was higher than that of NFRG using Franz diffusion cell models. In particular, after 3 h, the skin permeability of FRG was significantly higher (p<0.05) than that of NFRG. Using a rat everted intestinal sac model, FRG showed a high transport level compared with NFRG after 1 h. FRG had dramatically improved bioavailability compared with NFRG as indicated by skin permeation and intestinal permeability. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

Conjugated nonadecadienoic acid is more potent than conjugated linoleic acid on body fat reduction

Conjugated linoleic acid (CLA) has shown a number of health benefits, particularly on controlling body fat while improving lean mass. As one of CLA cognates, conjugated nonadecadienoic acid (CNA, 19-carbon conjugated fatty acid) has been previously reported to have greater efficacy on body fat control. In this report, we compared the efficacy of dietary CLA and CNA on body fat regulation and also compared the mechanism of body fat control using a mouse model. Effects of 0.1% dietary CNA on body fat reduction were comparable to that of 0.5% dietary CLA. The mechanisms of dietary CNA on body fat control were similar to those of CLA: increased energy expenditure and increased fatty acid beta-oxidation. Dietary CNA, but not CLA, also improved expression of hormone-sensitive lipase from white adipose tissue, and this may help explain how CNA has better efficacy on body fat control than CLA. Dietary CNA had similar effects as CLA on liver weights; however, unlike CLA, CNA improved glucose tolerance. Thus, CNA has potential to be used as a pharmacological agent to assist current efforts to reduce obesity with less adverse effects than CLA.

trans-10,cis-12 Conjugated linoleic acid promotes bone formation by inhibiting adipogenesis by peroxisome proliferator activated receptor-γ-dependent mechanisms and by directly enhancing osteoblastogenesis from bone marrow mesenchymal stem cells

The bone undergoes continuous remodeling of osteoblastic bone formation and osteoclastic bone resorption to maintain proper bone mass. It is also reported that bone marrow adiposity has a reciprocal role in osteoblasts due to their same origin from mesenchymal stem cells. In addition, one of the key mediators of adipogenesis, peroxisome-proliferator activated receptor-γ (PPARγ), plays a significant role in osteoblastogenesis in bone marrow mesenchymal stem cells. One dietary component that is known to have significant impact on adiposity and bone mass is conjugated linoleic acid (CLA). However, the link between controlling adiposity to improving bone mass by CLA has not been studied intensively. Thus, the purpose of this study is to determine the role of CLA on bone marrow adiposity and bone formation using murine mesenchymal stem cells. The results confirmed that the trans-10,cis-12 CLA, but not the cis-9,trans-11 CLA isomer, significantly inhibited adipogenesis and promoted osteoblastogenesis from mesenchymal stem cells. The inhibition of adipogenesis by the trans-10,cis-12 CLA was mediated by PPARγ; however, the trans-10,cis-12 CLA had a direct effect on osteoblastogenesis which was independent to PPARγ in this model. The trans-10,cis-12 CLA also had significant effects on osteoclastogenesis inhibitory factor, which suggests potential influence of CLA on osteoclastogenesis. Overall, the results suggest that the trans-10,cis-12, but not the cis-9,trans-11 CLA isomer, has a positive impact on bone health by both PPARγ mediated and independent mechanisms in mesenchymal stem cells.

Conjugated linoleic acid and calcium co-supplementation improves bone health in ovariectomised mice

Osteoporosis is a significant health concern for the elderly; conjugated linoleic acid (CLA) has been shown to improve overall bone mass when calcium is included as a co-supplement. However, potential effects of CLA and calcium on bone mass during a period of bone loss have not been reported. The purpose of this study was to determine how dietary calcium modulates the effects of conjugated linoleic acid (CLA) in preventing bone loss, using an ovariectomised mouse model. CLA supplementation significantly prevented ovariectomy-associated weight and fat mass gain, compared to non-supplemented controls. CLA significantly increased bone markers without major changes in bone mineral composition in the femur compared to respective controls. CLA treatment increased serum parathyroid hormone (PTH) significantly (p=0.0172), while serum 1,25-dihydroxyvitamin D3 concentration was not changed by CLA. Meanwhile, CLA significantly reduced femur tartrate resistant acid phosphatase (TRAP) activity, suggesting potential reduction of osteoclastogenesis. The data suggest that CLA, along with dietary calcium, has great potential to be used to prevent bone loss and weight gain associated with menopause.

Enzymatic Improvement in the Polyphenol Extractability and Antioxidant Activity of Green Tea Extracts

This study describes increases in extraction efficiency and the bioconversion of catechins after treatment with several commercial enzymes. Tannase was also used to improve the anti-radical activities of green tea extracts. Enzymatic treatment with various commercial enzymes was introduced to improve the extraction efficiency of polyphenols. The total polyphenol, flavonoid, and catechin contents and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of the green tea extract treated with Viscozyme (VG) were significantly higher than those treated with other commercial enzymatic extractions (p<0.05). More than 95% of the epigallocatechingallate (EGCG) and of the epicatechingallate (ECG) was hydrolyzed to epigallocatechin (EGC) and to epicatechin (EC) in successive 20 min treatments with Viscozyme and tannase (TG). Due to its hydrolytic activity, treatment involving tannase resulted in a significant release of gallic acid (GA), EGC, and EC, leading to greater radical scavenging activities. Regarding the IC(50) values of the DPPH and 2,2-azino-di-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, the green tea extract treated with TG showed values of 131.23 and 28.83 µg/mL, VG showed values of 224.70 and 32.54 µg/mL, and normal green tea extract (NG) showed values of 241.11 and 66.27 µg/mL, respectively. These results indicate that successive treatment with Viscozyme and tannase improves the extraction efficiency of polyphenols and increases radical scavenging activities.