The Rhizomes of Alisma orientale and Alisol Derivatives Inhibit Allergic Response and Experimental Atopic Dermatitis

The 70% ethanol extract of the rhizome of Alisma orientale (Alismatis rhizome) (AOE) was prepared and found to significantly inhibit 5-lipoxygenase (5-LOX)-catalyzed leukotriene (LT) production from rat basophilic leukemia (RBL)-1 cells and β-hexosaminidase release by antigen-stimulated RBL-2H3 cells. It also attenuated delayed-type hypersensitivity (DTH) reaction in mice. Among the three major triterpene constituents isolated (i.e., alisol B, alisol B 23-acetate, alisol C 23-acetate) as active principles, alisol B and its 23-acetate strongly and significantly inhibited LT production and β-hexosaminidase release between 1-10?μM. On the other hand, all these alisol derivatives significantly and strongly inhibited DTH response after oral administration. In addition, AOE (200?mg/kg/d) was for the first time found to considerably alleviate hapten-induced dermatitis symptoms in NC/Nga mice, an animal model of atopic dermatitis. These results indicate that alisol derivatives possess inhibitory activities on immediate-type as well as delayed-type hypersensitivity reactions and may contribute to the anti-allergic action of AOE.     

Gastroprotective activity of atractylenolide III from Atractylodes ovata on ethanol‐induced gastric ulcer in vitro and in vivo

Objectives The rhizome of Atractylodes ovata De Candolle is popularly used in traditional Chinese medicine to treat gastrointestinal diseases. However, the major gastroprotective compounds of A. ovata have not been identified. This study reports on the principal gastro‐ protective component of A. ovata. Methods Five sesquiterpenoids (atractylon, atractylenolides I, II, III and biatractylolide) were isolated from the extracts of A. ovata rhizome via silica gel column chromatography. The gastroprotective effects of these five sesquiterpenoids were measured in in‐vitro ethanol‐induced primary culture rat gastric mucosal (PRGM) cell damage and in‐vivo ethanol‐induced acute rat gastric ulcer models. Key findings Atractylon, atractylenolide I and biatractylolide were strongly toxic in PRGM cells, whilst atractylenolides II and III were not. Atractylenolide II did not show cytoprotective effects, but oral administration of atractylenolide III dose‐dependently prevented ethanol‐induced PRGM cell death and cell membrane damage. The EC50 values were 0.27 and 0.34 mm , respectively. In the in‐vivo assay, atractylenolide III 10 mg/kg significantly reduced 70% ethanol‐induced Wistar rat gastric ulcer. Atractylenolide III could inhibit matrix metalloproteinase (MMP)‐2 and MMP‐9 expression through upregulation of tissue inhibitors of metalloproteinase from the gastric ulcerated tissues. Conclusions Atractylenolide III was the major gastroprotective component of A. ovata in ethanol‐induced acute gastric ulcer. It is suggested that the gastroprotective mechanism of atractylenolide III was via inhibition of the MMP‐2 and MMP‐9 pathway.     

The Rhizomes of Acorus gramineus and the Constituents Inhibit Allergic Response In vitro and In vivo

The rhizomes of Acorus gramineus have frequently been used in traditional medicine mainly for sedation as well as enhancing brain function. In this study, the anti-allergic activity of A. gramineus was investigated. The 70% ethanol extract of the rhizomes of A. gramineus was found to inhibit the allergic response against 5-lipoxygenase (5-LOX)-catalyzed leukotriene (LT) production from rat basophilic leukemia (RBL)-1 cells and β-hexosaminidase release from RBL-2H3 cells with IC₅₀’s of 48.9 and >200 μg/ml, respectively. Among the 9 major constituents isolated, β-asarone, (2R,3R,4S,5S)-2,4-dimethyl-1,3-bis (2'',4'',5''-trimethoxyphenyl)tetrahydrofuran (AF) and 2,3-dihydro-4,5,7-trimethoxy-1-ethyl-2-methyl-3-(2,4,5-trimethoxyphenyl)indene (AI) strongly inhibited 5-LOX-catalyzed LT production in {"type":"entrez-nucleotide","attrs":{"text":"A23187","term_id":"833253","term_text":"A23187"}}A23187-treated RBL-1 cells, AI being the most potent (IC₅₀=6.7 μM). Against β-hexosaminidase release by antigen-stimulated RBL-2H3 cells, only AI exhibited strong inhibition (IC₅₀=7.3 μM) while β-asarone and AF showed 26.0% and 39.9% inhibition at 50 μM, respectively. In addition, the ethanol extract of A. gramineus showed significant inhibitory action against the hapten-induced delayed hypersensitivity reaction in mice by oral administration at 200 mg/kg. Therefore, it is suggested that A. gramineus possesses anti-allergic activity and the constituents including β-asarone and AI certainly contribute to the anti-allergic activity of the rhizomes of A. gramineus.     

Neuroprotection by herbal formula FBD and its active compounds

FBD, a Chinese herbal formula, composed of Fu Ling [the sclerotium of the fungus of Poria cocos (Schw.) Wolf (Polyporaceae)], Bai Zhu [the rhizome of Atractylodes macrocephala Koidz.(Compositae)], and Danggui [the root of Angelica sinensis (Oliv.) Diels (Umbelliferae)], has been found beneficial in treating brain ischemia-reperfusion (I/R). In this work, oral pretreatment with supercritical CO₂ extract (FBD-CO₂, 37.?5?mg/kg) twice daily for 3.5 days, significantly attenuated brain infarction (p < 0.05), blocked neuron specific enolase (NSE) efflux (p < 0.05) in mice subjected to repetitive 10?min of common carotid artery occlusion following 24?h reperfusion, whether coupled with aqueous extract (FBD-H₂O, 150?mg/kg) or not. Except atractylenolide I and pachymic acid, atractylenolide II, III, levistolid A, and ferulic acid isolated from FBD-CO₂ alone protected neuron-like PC12 cells obviously and concentration-dependently against I/R-like insults (p < 0.05 ~ 0.01) induced by sodium dithionite (10 mM), monosodium glutamate (2 mM), KCl (0.2?M), or hydrogen peroxide (0.2 mM) at 1-100 μM. Even though at sub-active concentrations (< 1 μM), the combination of the six components contained in FBD-CO₂ (10 μg/mL), protected markedly PC12 cells (p < 0.01), in a synergistic fashion. Moreover, intraperitoneal treatment with dual doses of 37.?5?mg/kg FBD-CO₂ and 1.?2?mg/kg combination reduced both infarct size (p < 0.01 and p > 0.05, respectively) and NSE efflux (p < 0.05 and p > 0.05, respectively). Therefore, neuroprotection by FBD on I/R induced neuronal injury originated partially from the synergies of its compounds atractylenolide II, atractylenolide III, levistolid A and ferulic acid.     

Interaction of gypsum and the rhizome of Anemarrhena asphodeloides plays an important role in anti-allergic effects of byakkokakeishito in mice

Gypsum is a crude mineral drug used in the formulas of Japanese kampo medicine and traditional Chinese medicine. The present study aimed to evaluate the anti-allergic effect of byakkokakeishito extract (BKT), which consists of gypsum (natural hydrous calcium sulfate), Anemarrhena Rhizome (rhizome of Anemarrhena asphodeloides), Cinnamon Bark (bark of trunk of Cinnamomum cassia), Oriza Seed (seed of Oryza sativa), and Glycyrrhiza (root and stolon of Glycyrrhiza uralensis), and to clarify the role of gypsum in the formula. We prepared BKT by boiling a mixture of various quantities of gypsum and fixed amounts of the other four crude drugs in water. We evaluated the anti-allergic activity of the formulations using three different murine models of allergy: contact dermatitis induced by painting hapten onto skin; allergic dermatitis-like symptoms induced by cutaneous injection of mite-antigen; and skin passive cutaneous anaphylaxis (PCA) reaction using ovalbumin as antigen. The calcium content in the various BKT samples was dose-dependently increased up to 60 g/day of human dosage. BKT significantly suppressed the allergic symptoms in the three different experimental models. The effect of BKT was augmented by increasing the gypsum dosage only in the PCA reaction model. The extract prepared from a mixture of Anemarrhena Rhizome and gypsum exhibited an effect comparable to that of BKT. BKT exhibits an anti-allergic effect in several animal models, which may provide experimental evidence for the clinical use of BKT in allergic diseases. Gypsum may augment the anti-allergic activity of BKT, presumably through increasing intestinal absorption of Anemarrhena Rhizome-derived active constituents.     

5-Lipoxygenase Inhibition of the Fructus of Foeniculum vulgare and Its Constituents

The fruits of Foeniculum vulgare (Foeniculi Fructus) have been widely used in Chinese medicine as an antiemetic, ameliorating stomach ailments and as an analgesic. In order to establish its potential for antiallergic use, inhibitory actions of the fruiton 5-lipoxgenase (5-LOX) and β-hexosaminidase release were evaluated. The 70% ethanol extract of this plant material (FR) considerably inhibited 5-LOX-catalyzed leukotriene production from {"type":"entrez-nucleotide","attrs":{"text":"A23187","term_id":"833253"}}A23187-induced rat basophilic leukemia (RBL)-1 cells. The IC₅₀ was 3.2 μg/ml. From this extract, 12 major compounds including sabinene, fenchone, γ-terpinene, α-pinene, limonene, p-anisylacetone, p-anisylaldehyde, estragole (4-allylanisole), trans-anethole, scopoletin, bergapten and umbelliferone were isolated. And it was found that several terpene derivatives including γ-terpinene and fenchone as well as phenylpropanoid, trans-anethole, showed considerable inhibitory action of 5-LOX. In particular, the IC₅₀ of trans-anethole was 51.6 μ M. In contrast, FR and the isolated compounds did not show considerable inhibitory activity on the degranulation reaction of β-hexosaminidase release from antigen-treated RBL-2H3 cells. Against arachidonic acid-induced ear edema in mice, FR and trans-anethole showed significant inhibition by oral administration at doses of 100-400 mg/kg. In conclusion, FR and several major constituents are 5-LOX inhibitors and they may have potential for treating 5-LOX-related disorders.     

Neuroprotective effects of Eriobotrya japonica against β-amyloid-induced oxidative stress and memory impairment

The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of neurodegenerative disorders. Eriobotrya japonica has been used to treat several diseases in East Asia. In this study, we investigated the protective effect of an E. japonica extract against Aβ peptide-induced oxidative stress. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay demonstrated that the E. japonica extract scavenged approximately 40% of DPPH radicals. Also, treatment of the E. japonica extract inhibited Aβ_1-42-mediated neuronal cell death. Furthermore, treatment of E. japonica extract efficiently suppressed the increase in intracellular ROS triggered by the Aβ_1-42 peptide. Importantly, mice pre-treated with the E. japonica extract showed restoration of alternation behavior and reversal of Aβ_1-42-induced memory impairment.Consequently, the E. japonica extract substantially inhibited the increase in lipid peroxidation and restored superoxide dismutase activity. These results suggest that E. japonica protects from oxidative stress and cognitive deficits induced by the Aβ peptide.     

Elucidation of the molecular mechanism and the efficacy in vivo of a novel 1,4-benzoquinone that inhibits 5-lipoxygenase

Background and Purpose

1,4-Benzoquinones are well-known inhibitors of 5-lipoxygenase (5-LOX, the key enzyme in leukotriene biosynthesis), but the molecular mechanisms of 5-LOX inhibition are not completely understood. Here we investigated the molecular mode of action and the pharmacological profile of the novel 1,4-benzoquinone derivative 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id) in vitro and its effectiveness in vivo.

Experimental Approach

Mechanistic investigations in cell-free assays using 5-LOX and other enzymes associated with eicosanoid biosynthesis were conducted, along with cell-based studies in human leukocytes and whole blood. Molecular docking of RF-Id into the 5-LOX structure was performed to illustrate molecular interference with 5-LOX. The effectiveness of RF-Id in vivo was also evaluated in two murine models of inflammation.

Key Results

RF-Id consistently suppressed 5-LOX product synthesis in human leukocytes and human whole blood. RF-Id also blocked COX-2 activity but did not significantly inhibit COX-1, microsomal PGE₂ synthase-1, cytosolic PLA₂ or 12- and 15-LOX. Although RF-Id lacked radical scavenging activity, reducing conditions facilitated its inhibitory effect on 5-LOX whereas cell stress impaired its efficacy. The reduced hydroquinone form of RF-Id (RED-RF-Id) was a more potent inhibitor of 5-LOX as it had more bidirectional hydrogen bonds within the 5-LOX substrate binding site. Finally, RF-Id had marked anti-inflammatory effects in mice in vivo.

Conclusions and Implications

RF-Id represents a novel anti-inflammatory 1,4-benzoquinone that potently suppresses LT biosynthesis by direct inhibition of 5-LOX with effectiveness in vivo. Mechanistically, RF-Id inhibits 5-LOX in a non-redox manner by forming discrete molecular interactions within the active site of 5-LOX.     

Inhibition of 5-lipoxygenase and skin inflammation by the aerial parts of Artemisia capillaris and its constituents

The aerial parts of Artemisia capillaris Thunberg (Compositae) have been used in Chinese medicine as a liver protective agent, diuretic, and for amelioration of skin inflammatory conditions. This study was conducted to establish the scientific rationale for treating skin inflammation and to find active principles from A. capillaris. To accomplish these goals, the 70% ethanol extract of the aerial parts of A. capillaris (AR) was prepared and its 5-lipoxygenase (5-LOX) inhibitory action was studied since 5-LOX products are known to be involved in several allergic and skin inflammatory disorders. AR showed potent inhibitory activity against 5-LOX-catalyzed leukotriene production by ionophore-induced rat basophilic leukemia-1 cells, with an IC₅₀ of < 1.0 μg/mL. Nine major compounds, scopoletin, scopolin, scoparone, esculetin, quercetin, capillarisin, isorhamnetin, 3-O-robinobioside, isorhamnetin 3-O-galactoside and chlorogenic acid, were isolated from A. capillaris, and their effects were examined to identify the active principle(s). Several coumarin and flavonoid derivatives were found to be 5-LOX inhibitors. In particular, esculetin and quercetin were potent inhibitors, with IC₅₀ values of 6.6 and 0.7 μM, respectively. Against arachidonic acid-induced ear edema in mice, AR, and esculetin strongly inhibited edematic response. AR and esculetin also inhibited delayed-type hypersensitivity response in mice. In conclusion, AR and some of their major constituents are 5-LOX inhibitors, and these in vitro and in vivo activities may contribute to the therapeutic potential of AR in skin inflammatory disorders in traditional medicine.     

细茎银莲花的化学成分

目的 对细茎银莲花（Anemone rossii Moore）根茎的化学成分进行初步研究。方法 细茎银莲花根茎以体积分数为75%的乙醇提取,提取物经系统溶剂萃取,对其氯仿萃取部分进行反复柱色谱分离,利用理化性质和波谱分析进行结构鉴定。 结果 从细茎银莲花根茎中分离得到7个已知化合物,分别为桦皮醇（1）、桦皮酸 （2）、齐墩果酸（3）、β-谷甾醇（4）、香豆素 （5）、4,7-二甲氧基-5-甲基香豆素 （6）、齐墩果酸-3-O-α-L-吡喃阿拉伯糖苷（7）。结论 所有化合物均为首次从细茎银莲花中分离得到。     

A pirinixic acid derivative (LP105) inhibits murine 5-lipoxygenase activity and attenuates vascular remodelling in a murine model of aortic aneurysm

BACKGROUND AND PURPOSE

Arachidonic acid derivatives play a central role in inflammation processes. Arachidonic acid is metabolized by several enzymes, particularly cyclooxygenases (COX), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E-synthase-1 (mPGES-1) to pro-inflammatory mediators.

EXPERIMENTAL APPROACH

We determined the effect of LP105, a pirinixic acid derivative which acts as inhibitor of 5-LOX, COX and mPGES-1, on aortic aneurysm development in mice and on 5-LOX activity in murine monocytes.

KEY RESULTS

In a monocyte cell line (RAW264.7), LP105 inhibited 5-LOX in whole cells (IC₅₀: 1–3 µM) and in supernatants (IC₅₀: ∼10 µM). Oral administration of LP105 to mice resulted in therapeutic tissue and plasma levels. Aortic aneurysms were induced in ApoE^−/− mice by angiotensin II (AngII) and LP105 (5 mg·day⁻¹ per animal) was co-administered to a subgroup. Compared with animals receiving AngII alone, the LP105+AngII group showed a lower heart rate, a trend towards reduced heart to body weight ratio but similar hypertensive responses. AngII alone significantly increased aortic weight and diameter but co-treatment with LP105+AngII prevented these changes. LC/MS-MS studies revealed increased 15-hydroxytetraenoic acid (15-HETE) and 14,15-epoxyeicosatrienoic acid (14,15-EET) plasma levels in LP105-treated animals. In the murine kidney, mRNAs of EET-generating or metabolizing enzymes and of 5-LOX and 15-LOX were unaffected by LP105. LP105 also did not inhibit the EET-metabolizing soluble epoxide hydrolase.

CONCLUSIONS AND IMPLICATIONS

LP105 was a potent inhibitor of monocyte 5-LOX and reduced AngII-induced vascular remodelling in mice. A shift of arachidonic acid metabolism to the protective EET pathway may contribute to the beneficial effects of LP105.     

Inhibitory effect of Psidium guajava water extract in the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice

Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disease associated with eczematous symptoms and IgE hyperproduction. Psidium guajava is an important food crop and medicinal plant with anti-oxidant, anti-inflammatory, and anti-allergic activities, supporting its traditional uses. Our previous studies have shown that P. guajava extract inhibits Th2 chemokine expression by suppressing the activation of NF-κB and STAT1 co-stimulated with TNF-α and INF-γ. In this study, we investigated the inhibitory effect of P. guajava water extract (PGW) on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in NC/Nga mice. Treatment of cream containing PGW onto DNCB-induced AD-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, levels of IgE, thymus and activation-regulated chemokine (TARC), TNF-α, and IL-4 in serum and ears. In contrast, PGW increased level of the immunosuppressive cytokine IL-10. Histological analyses demonstrated decreased thickening of the epidermis/dermis as well as dermal infiltration by inflammatory cells. These results suggest that cream containing PGW may be a potential therapeutic modality for AD and adjunctive agent to control pruritus in AD.     

A Comparison between Extract Products of Magnolia officinalis on Memory Impairment and Amyloidogenesis in a Transgenic Mouse Model of Alzheimer’s Disease

The components of Magnolia officinalis have well known to act anti-inflammatory, anti-oxidative and neuroprotective activities. These efficacies have been sold many products as nutritional supplement extracted from bark of Magnolia officinalis. Thus, to assess and compare neuroprotective effect in the nutritional supplement (Magnolia Extract^TM, Health Freedom Nutrition LLC, USA) and our ethanol extract of Magnolia officinalis (BioLand LTD, Korea), we investigated memorial improving and anti-Alzheimer’s disease effects of extract products of Magnolia officinalis in a transgenic AD mice model. Oral pretreatment of two extract products of Magnolia officinalis (10 mg/kg/day in 0.05% ethanol) into drinking water for 3 months ameliorated memorial dysfunction and prevented Aβ accumulation in the brain of Tg2576 mice. In addition, extract products of Magnolia officinalis also decreased expression of β-site APP cleaving enzyme 1 (BACE1), amyloid precursor protein (APP) and its product, C99. Although both two extract products of Magnolia officinalis could show preventive effect of memorial dysfunction and Aβ accumulation, our ethanol extract of Magnolia officinalis (BioLand LTD, Korea) could be more effective than Magnolia Extract^TM (Health Freedom Nutrition LLC, USA). Therefore, our results showed that extract products of Magnolia officinalis were effective for prevention and treatment of AD through memorial improving and anti-amyloidogenic effects via down-regulating β-secretase activity, and neuroprotective efficacy of Magnolia extracts could be differed by cultivating area and manufacturing methods.     

Two new compounds from Atractylodes macrocephala with neuroprotective activity

In the present study, two new compounds, together with six known compounds, were isolated from rhizome of Atractylodes macrocephala Koidz by a series of silica gel, ODS column chromatography, and preparative HPLC. Their structures were characterized as atractylenolide II (1), atractylenolide I (2), biepiasterolid (3), isoatractylenolide I (4), atractylenolide III (5), 3β-acetoxyl atractylenolide I (6), (4E,6E,12E)-tetradeca-4,6,12-triene-8,10-diyne-13,14-triol (7), (3S,4E,6E,12E)-1-acetoxy-tetradeca-4,6,12-triene-8,10-diyne-3,14-diol (8) on the basis of 1D, 2D NMR, and circular dichroism analyses. Among them, compounds 6 and 8 were novel compounds. In addition, their neuroprotective activity against MPP⁺-induced SH-SY5Y cells was evaluated by MTT colorimetry. The results showed that all these compounds have definite protective effect on MPP⁺-induced SH-SY5Y cells.     

DA-9601 suppresses 2, 4-dinitrochlorobenzene and dust mite extract-induced atopic dermatitis-like skin lesions

DA-9601 (Stillen?) is a novel anti-peptic formulation prepared from the ethanol extracts of Artemisia asiatica possessing anti-oxidative, anti-allergic and anti-inflammatory activities. However, their effect on atopic dermatitis (AD) has not been studied yet. In this study, we report that topical application of DA-9601 suppressed house dust mite extract (Dermatophagoides farinae extract, DFE) and 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in BALB/c mice model. We established atopic dermatitis model in BALB/c mice by repeated local exposure of DFE/DNCB to the ears. Repeated alternative treatment of DFE/DNCB caused AD-like lesions. DA-9601 reduced AD-like skin lesions based on ear thickness and histopathological analysis, and serum IgE levels. DA-9601 inhibited mast cell infiltration into the ear and elevation of serum histamine in AD model. In addition, DA-9601 suppressed DFE/DNCB-induced expression of IL-4, IL-13, IL-31, and TNF-α in the ears. Taken together, our results showed that topical application of DA-9601 exerts beneficial effects in animal model of AD, suggesting that DA-9601 might be a candidate for the treatment of AD.     

Inhibitory effect of chaga mushroom extract on compound 48/80-induced anaphylactic shock and IgE production in mice

Chaga mushrooms (Inonotus obliquus) are hypothesised to exhibit general immune-potentiating, anti-inflammatory, and antitumor properties, but their anti-allergic activities are not fully understood. Therefore, this study investigated whether a chaga mushroom extract (C-HE) might have anti-allergic activity. This activity was assessed through the levels of the IgE Ab produced in response to an allergen (OVA). The administration of C-HE prophylactically inhibited the systemic anaphylactic shock induced by compound 48/80 in mice. The oral administration of C-HE significantly reduced the total IgE levels in mice and slightly affected the production of IgG1. Furthermore, spleen cell cultures harvested from OVA-sensitised mice that had received C-HE orally showed a significant increase in Th1-derived responses (IFN-γ production). Therefore, our results suggest that the chaga mushroom extract may be used as an anti-allergic functional food.     

Mutagenetic and anti-allergic studies for evaluation of extracts of Coptis Rhizome produced by an artificial hydroponic system

As a part of the investigation of the safety and efficacy of the cultivated Coptis japonica rhizome extracts using an artificial hydroponic cultivation system, the mutagenetic and anti-allergic activities were evaluated. Some extracts of commercial crude drugs of Coptis sp. were also evaluated for the comparison. None of the extracts showed a significant mutagenicity in Salmonella typhimurium TA102 by the Ames tests, but all the extracts showed in S. typhimurium TA98. The extracts of the hydroponically cultivated rhizomes showed anti-allergic activities against contact hypersensitivity as well as those of commercial crude drugs of Coptis sp. These results suggested the potential of the hydroponically cultivated rhizomes as one of the alternative sources for the medicinal usage.

     

The Leaves of Broussonetia kazinoki Siebold Inhibit Atopic Dermatitis-Like Response on Mite Allergen-Treated Nc/Nga Mice

Broussonetia kazinoki Siebold. (B. kazinoki) has long been used in the manufacture of paper in Asian countries. Although B. kazinoki leaves (BK) have been employed in dermatological therapy, use of BK has not been tested in patients with atopic dermatitis (AD). Using Nc/Nga mice, which are genetically predisposed to develop AD-like skin lesions, we confirmed the efficacy of BK in AD treatment. BK extract was applied topically to Dermatophagoides farinae-induced AD-like lesions in Nc/Nga mice, and the effects were assessed both clinically and by measuring skin thickness on the back and ears. We measured the effects of BK extract on plasma levels of IgE and IL-4. We also measured the ability of BK extract to inhibit the secretion of hTARC in HaCaT cells after stimulation by TNF-α and IFN-γ. We found that BK extract significantly reduced ear and dorsal skin thickness and the clinical signs of AD, as well as significantly down-regulating the plasma levels of IgE and IL-4 (p<0.01 for each comparison). Moreover, 500 μg/mL of BK extract inhibited hTARC secretion in HaCaT cells by activated TNF-α/IFN-γ by about 87%. These findings suggest that topical application of BK extract has excellent potential in the treatment of AD.     

Taiwanese and Japanese yam (Dioscorea spp.) extracts attenuate doxorubicin-induced cardiotoxicity in mice

The present study was designed to explore whether yam could protect the heart from doxorubicin (DOX)-induced oxidative stress leading to cardiotoxicity in vivo. In this study, the protective effects of water and ethanol extracts of three varieties of yam, including water extracts of Dioscorea japonica Thunb., ethanol extracts of D. japonica Thunb., water extracts of Dioscorea alata, ethanol extracts of D. alata, water extracts of Dioscorea purpurea, and ethanol extracts of D. purpurea, against DOX-induced cardiotoxicity in experimental mice were evaluated. DOX treatment led to significant decreases in the ratio of heart weight to body weight and heart rate, and increases in blood pressure and the serum level of lactate dehydrogenase, a marker of cardiotoxicity, were recovered by yam extracts, especially in water extracts of D. alata. Yam extracts also decreased the cardiac levels of thiobarbituric acid relative substances, reactive oxygen species, and inflammatory factors, as well as the expression of nuclear factor kappa B, while ethanol extracts of D. japonica Thunb. and D. purpurea were shown to be more potent. Moreover, yam extracts had a role in increasing the activities of glutathione peroxidase and superoxide dismutase, thus improving the DOX-induced alterations in oxidative status in the heart tissue of DOX-treated mice. All ethanol extracts of yam exhibited their antiapoptotic abilities on caspase-3 activation and mitochondrial dysfunction, and ethanol extracts of D. alata still exerted a superior effect. Based on these findings, it can be concluded that yam has significant cardioprotective properties against DOX-induced damage via its multiple effects on antioxidant, anti-inflammatory, or antiapoptotic activities.