Flavonoids: Broad Spectrum Agents on Chronic Inflammation.

Flavonoids are major plant constituents with numerous biological/pharmacological actions both in vitro and in vivo. Of these actions, their anti-inflammatory action is prominent. They can regulate transcription of many proinflammatory genes such as cyclooxygenase- 2/inducible nitric oxide synthase and many cytokines/chemokines. Recent studies have demonstrated that certain flavonoid derivatives can affect pathways of inflammasome activation and autophagy. Certain flavonoids can also accelerate the resolution phase of inflammation, leading to avoiding chronic inflammatory stimuli. All these pharmacological actions with newly emerging activities render flavonoids to be potential therapeutics for chronic inflammatory disorders including arthritic inflammation, meta-inflammation, and inflammaging. Recent findings of flavonoids are summarized and future perspectives are presented in this review.

Electrosprayed nanocomposites based on hyaluronic acid derivative and Soluplus for tumor-targeted drug delivery.

Nanocomposite (NC) based on hyaluronic acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.

Anti-inflammatory activity of the ethanol extract of Chungkukjang, Korean fermented bean: 5-lipoxygenase inhibition.

The anti-inflammatory activity of Chungkukjang, a Korean traditional fermented soybean food (Korean-style Natto), was examined for the first time. From the results, it was found that the ethanol extract of Chungkukjang inhibited 5-lipoxygenase from A23187-treated RBL-1 cells, reducing leukoriene production (50% inhibitory concentration = 54.1 microg/mL). However, it did not greatly affect cyclooxygenase-2-catalyzed prostaglandin E(2) and inducible nitric oxide synthase-catalyzed nitric oxide production from lipopolysaccharide-treated RAW 264.7 cells at the same concentration ranges. Since leukotrienes are intimately involved in some allergic disorders, the anti-allergic activity of Chungkukjang was further examined in animal models of passive cutaneous anaphylaxis (type I hypersensitivity) and arachidonic acid-induced ear edema, two well-known in vivo models sensitive to 5-lipoxygenase inhibitors. After oral administration for 5 consecutive days, Chungkukjang significantly reduced (27.3%) passive cutaneous anaphylaxis in rats at 400 mg/kg/day. It also showed in vivo anti-inflammatory activity against arachidonic acid-induced mouse ear edema. Therefore, it is suggested that Chungkukjang may be beneficial for several allergic conditions such as asthma and atopic dermatitis.

Antioxidant and antigenotoxic activities of Korean fermented soybean.

This study was aimed at evaluating the antioxidative and antigenotoxic activities of Korean fermented soybean (Chungkookjang) in vitro and in vivo. The 100% ethanol extract of Chungkookjang (CKJ) inhibited the generation of 1,1-diphenyl-2-picryl hydrazine (DPPH) radicals, and had an inhibitory effect on LDL oxidation. CKJ and its constituents (genistein and daidzein) also inhibited H(2)O(2)-induced DNA damage from NIH/3T3 fibroblasts. Furthermore, they showed the cytoprotective effects against H(2)O(2)-induced cell death. In vivo study also demonstrated that an oral administration of CKJ extract (800 mg/kg/day) for 2 weeks potently inhibited the formation of malondialdehyde, the damage of DNA and the formation of micronucleated reticulocytes in KBrO(3)-treated mice. The well-known antioxidants, trolox and vitamin C, also showed the potent inhibition on these parameters. All these results indicate that CKJ extract may be a useful antigenotoxic antioxidant by scavenging free radicals, inhibiting lipid peroxidation and protecting against oxidative DNA damage. The isoflavones, genistein and daidzein, may contribute to these biological effects of CKJ extract at least in part. Korean fermented soybean (Chungkookjang) is suggested to be a promising functional food witch can prevent oxidative stress.

Antioxidative constituents from Paeonia lactiflora.

The ethanol extract of the peony root (Paeonia Lactiflora Pall, Paeoniaceae) as well as its major active components including gallic acid and methyl gallate were evaluated for their protective effects against free radical generation and lipid peroxidation. In addition, the protective effects against hydrogen peroxide-induced oxidative DNA damage in a mammalian cell line were examined. The ethanol extracts of the peony root (PREs) and its active constituents, gallic acid and methyl gallate, exhibited a significant free radical scavenging effect against 1,1-diphenyl-2-picryl hydrazine (DPPH) radical generation and had an inhibitory effect on lipid peroxidation, as measured by the level of malondialdehyde (MDA) formation. The PREs did not have any pro-oxidant effect. They strongly inhibited the hydrogen peroxide-induced DNA damage from NIH/3T3 fibroblasts, as assessed by single cell gel electrophoresis. Furthermore, the oral administration of 50% PRE (50% ethanol extract of peony root), gallic acid and methyl gallate potently inhibited the formation of micronucleated reticulocytes (MNRET) in the mouse peripheral blood induced by a KBrO3 treatment in vivo. Therefore, PREs containing gallic acid and methyl gallate may be a useful antigenotoxic antioxidant by scavenging free radicals, inhibiting lipid peroxidation and protecting against oxidative DNA damage without exhibiting any pro-oxidant effect.

Prenylated flavonoids as tyrosinase inhibitors.

In order to find new tyrosinase inhibitors and the effects of prenyl residue on flavonoid molecules, eight prenylated and three synthetic vinylated flavonoids were examined on their inhibitory effect against tyrosinase activity. From the results, kuwanon C, papyriflavonol A, sanggenon D and sophoflavescenol were found to possess the considerable inhibitory activity. Especially, sanggenon D is revealed as a potent inhibitor (IC50 = 7.3 microM), compared to the reference compound, kojic acid (IC50 = 24.8 microM). However, the prenylation with isoprenyl group or the vinylation to flavonoid molecules did not enhance tyrosinase inhibitory activity.

Inhibitory effects of Ramulus mori extracts on melanogenesis.

To develop an active agent for skin whitening, the inhibitory effects of 285 plant extracts on tyrosinase activity were examined, and one plant extract having tyrosinase inhibition activity was chosen. Ramulus mori (young twigs of Morus alba L.) extracts showed inhibition activity in tyrosinase and melanin synthesis in B-16 melanoma cells. To clarify the mechanism of its inhibition on melanogenesis, the effect of R. mori extracts on tyrosinase activity, synthesis, and gene expression was evaluated. R. mori extracts showed tyrosinase inhibition activity by competitive method, and there was no suppression of tyrosinase synthesis and gene expression. Further, to evaluate the inhibitory activity of R. mori in vivo, its effect on melanin production in UV-induced brown guinea pigs was examined, where a decrease of melanin production in the guinea pig model was observed. Also, R. mori extracts showed no toxicity in animal tests such as the acute toxicity test, the skin irritation test, the eye irritation test, the skin sensitization test, and the acute oral toxicity test, and no toxicity in the human skin irritation test. A single compound from R. mori extracts was purified using various column chromatography and recrystallization, and its chemical structure was identified using mass chromatography, IR spectroscopy, and NMR analysis. The chemical structure was that of 2,3',4,5'-tetrahydroxystilbene(2-oxyresveratrol) and showed inhibition activity on tyrosinase (IC(50) = 0.23 microg/ml). Also, R. mori extracts inhibited tyrosinase activity in a competitive manner (Ki = 1.5 x 10(-6) M) when L-tyrosine was used as a substrate.

Effects of the chestnut inner shell extract on the expression of adhesion molecules, fibronectin and vitronectin, of skin fibroblasts in culture.

The inner shell of the chestnut (Castanea crenata S. et Z., Fagaceae) has been used as an anti-wrinkle/skin firming agent in East Asia, and preliminary experiments have found that a 70% ethanol extract from this plant material can prevent cell detachment of skin fibroblasts from culture plates. In order to examine the molecular mechanisms underlying this phenomenon, its effects on the expression of adhesion molecules, such as fibronectin and vitronectin, were investigated using the mouse skin fibroblast cell line, NIH/3T3. Using fixed-cell ELISA, Western blotting and immunofluorescence cell staining, it was clearly demonstrated that the chestnut inner shell extract enhanced the expression of the cell-associated fibronectin and vitronectin. Scoparone (6,7-dimethoxycoumarin), isolated from the extract, also possessed similar properties. These findings suggest that the enhanced expression of the adhesion molecules may be one of the molecular mechanisms for how the chestnut inner shell extract preventing cell detachment and may be also responsible for its anti-wrinkle/skin firming effect.

The extract of the flowers of Prunus persica, a new cosmetic ingredient, protects against solar ultraviolet-induced skin damage in vivo.

The flowers of Prunus persica Batsch have been used for skin disorders in East Asia from ancient times. In this investigation, the ethanol extract from this plant material was prepared and several major constituents were isolated. In addition, the protective effects of the extract were evaluated against solar ultraviolet (UV)-induced skin damage using in vivo animal models of UVB-induced erythema in guinea pigs and ear edema in ICR mice. From the extract, four kaempferol glycoside derivatives were successfully isolated and their contents were measured with HPLC. Among the derivatives isolated, the content of multiflorin B was highest (3.3%, w/w). The P. persica extract clearly inhibited UVB-induced erythema formation dose dependently when topically applied (IC(50) = 0.5 mg/cm(2)). It also inhibited UVB-induced ear edema (49% inhibition at 3.0 mg/ear). Moreover, multiflorin B inhibited UVB-induced erythema formation (80% inhibition at 0.3 mg/cm(2)), indicating that this compound is one of the active principles of the extract. All these results suggest that P. persica extract may be useful for protection against UVB-induced skin damage when topically applied.