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The activities of osteoclasts and osteoblasts are balanced to maintain normal bone density. Many pathological conditions cause osteoclastic bone resorption in excess of osteoblastic bone formation, resulting in osteoporosis. We found that oral administration of Artemisia annua ethanol extract (AaE) or major components, artemisinin and arteannuin B, to ovariectomized (OVX) mice prevented bone loss, as verified by examining three-dimensional images and bone morphometric parameters derived from microcomputed tomography analysis, as well as serum levels of bone turnover markers and proinflammatory cytokines. The administered doses were not toxic to the liver or kidney and showed promising effects that were comparable to those of 17β-estradiol treatment. At non-cytotoxic concentrations, AaE and active components, artemisinin, artemisinic acid, and arteannuin B, potently inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis and the formation of osteoclast-mediated resorption pits. Furthermore, AaE, artemisinin, and arteannuin B remarkably reduced the expression of the c-Fos and NFATc1 transcription factors, which play critical roles in RANKL-induced osteoclast differentiation. Taken together, the in vivo anti-osteoporotic activity of AaE may be derived from the anti-osteoclastic and anti-bone resorptive activities of its active components. AaE has beneficial applications for the prevention and inhibition of osteoporosis and osteoclast-mediated bone diseases.

Anti-rotaviral activities of Sophora flavescens extract (SFE) and stevioside (SV) from Stevia rebaudiana Bertoni either singly or in various combinations were examined in vitro and in vivo using a porcine rotavirus G5[P7] strain. Combination of SFE and SV inhibited in vitro virus replication more efficiently than each single treatment. In the piglet model, SV had no effect on rotavirus enteritis, whereas SFE improved but did not completely cure rotaviral enteritis. Interestingly, combination therapy of SFE and SV alleviated diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. Acute toxicity tests including the piglet lethal dose 50, and body weight, organ weight and pathological changes for the combination therapy did not show any adverse effect on the piglets. These preliminary data suggest that the combination therapy of SV and SFE is a potential curative medication for rotaviral diarrhea in pigs. Determination of the efficacy of this combination therapy in other species including humans needs to be addressed in the future., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A crude extract from Acanthopanax senticosus (AS) has drawn increased attention because of its potentially beneficial activities, including anti-fatigue, anti-stress, anti-gastric-ulcer, and immunoenhancing effects. We previously reported that AS crude extract exerts anti-inflammatory activity through blockade of monocytic adhesion to endothelial cells. However, the underlying mechanisms remained unknown, and so this study was designed to investigate the pathways involved. It was confirmed that AS extract inhibited lipopolysaccharide (LPS)-induced adhesion of monocytes to endothelial cells, and we found that whole extract was superior to eleutheroside E, a principal functional component of AS. A series of PCR experiments revealed that AS extract inhibited LPS-induced expression of genes encoding lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) in THP-1 cells. Consistently, protein levels and cell surface expression of LFA-1 and Mac-1 were noticeably reduced upon treatment with AS extract. This inhibitory effect was mediated by the suppression of LPS-induced degradation of IκB-α, a known inhibitor of nuclear factor-κB (NF-κB). In conclusion, AS extract exerts anti-inflammatory activity via the suppression of LFA-1 and Mac-1, lending itself as a potential therapeutic galenical for the prevention and treatment of various inflammatory diseases.

Panax ginseng C.A. Meyer has been traditionally used as a medicinal plant and has beneficial effects due to pharmacological properties. Although ginseng is thought to be protective under abnormal conditions, the effects of pretreatment with red ginseng (RG) extract on ischemic stroke have not been fully elucidated. We investigated the protective effects of RG extract after focal cerebral ischemia in mice. Crude RG extract (360 mg/kg) was administered intraperitoneally for 2 weeks. Mice were then subjected to occlusion of the middle cerebral artery for 1 hour, followed by reperfusion for 4 and 24 hours. Pretreatment with RG extract followed by ischemia/reperfusion (I/R) resulted in significant reduction of oxidized hydroethidine signals in ischemic areas. At 4 and 24 hours after I/R, the number of 8-hydroxyguanosine and apoptosis signal-regulating kinase 1 (ASK1)-positive cells decreased in the ischemic penumbra as seen using immunofluorescent staining. Western blotting showed that RG efficiently attenuated the protein levels of activated ASK1 in the ischemic penumbra. Consequently, DNA fragmentation and the infarct volume were reduced by RG extract pretreatment 24 hours after I/R. Also, RG extract resulted in better performance in rotarod test after I/R. Thus, RG pretreatment demonstrates a protective effect at suppressing ischemia-induced oxidative stress and apoptosis in ischemic lesions. Pretreatment with crude RG extract may be an effective strategy for preventing brain injury after an ischemic stroke.

Background: Since rotavirus is one of the leading pathogens that cause severe gastroenteritis and represents a serious threat to human and animal health, researchers have been searching for cheap, safe, and effective anti-rotaviral drugs. There is a widespread of interest in using natural products as antiviral agents, and among them, licorice derived from Glycyrrhiza spp. has exerted antiviral properties against several viruses. In this study, anti-rotaviral efficacy of Glycyrrhiza uralensis extract (GUE) as an effective and cheaper remedy without side-effects was evaluated in colostrums-deprived piglets after induction of rotavirus diarrhea., Methods: Colostrums-deprived piglets were inoculated with porcine rotavirus K85 (G5P[7]) strain. On the onset of diarrhea, piglets were treated with different concentration of GUE. To evaluate the antiviral efficacy of GUE, fecal consistency score, fecal virus shedding and histological changes of the small intestine, mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were determined., Results: Among the dosages (100-400 mg/ml) administrated to animals, 400 mg/ml of GUE cured diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were markedly increased in animals with RVA-induced diarrhea, but dose- dependently decreased in GUE treated animals after RVA-induced diarrhea., Conclusions: GUE cures rotaviral enteritis by coordinating antiviral and anti-inflammatory effects. Therapy of this herbal medicine can be a viable medication for curing rotaviral enteritis in animals and humans.

Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoporosis occurs when osteoclast activity surpasses osteoblast activity. Pro-inflammatory cytokines stimulate osteoclast differentiation and activity by increasing production of macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). In this study, we investigated whether Magnoliae Flos (MF), one of the most commonly used Chinese medicinal herbs for managing rhinitis, sinusitis and headache, could effectively inhibit osteoporosis. In ovariectomized (OVX) mice compared to sham mice, the body weight increased and serum levels of alkaline phosphatase (ALP), tartrate resistant acid phosphatase 5b, calcium, and osteocalcin were significantly elevated. However, orally administrated MF extract substantially inhibited the increased body weight and serum levels of bone turnover markers, without any evidence of tissue toxicity. MF extract treatment significantly reversed the morphometric parameters of ovariectomy-induced bone loss, including trabecular bone volume, thickness, number, separation, and bone density, to almost the same levels of the sham mice. Furthermore, MF extract reduced the RANKL-mediated osteoclast differentiation and bone resorption by inhibiting the activities of matrix metalloproteinases (MMPs) and cathepsin K in mouse bone marrow macrophages. MF extract appeared to increase ALP activity in murine osteoblastic cells. Taken together, MF extract may be a beneficial supplement for the blockade of osteoporosis progression, particularly for the management of postmenopausal osteoporosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We determined the phenolic, anthocyanin, and proanthocyanidin content of three brown, purple, and red rice brans isolated from different rice varieties using HPLC-PDA with the aid of 27 standards of known structure and matching unknown peaks to a spectral library of known compounds. Antioxidative capacities were determined by DPPH and ORAC and cell-inhibiting effects using an MTT assay. Based on the calculated IC(50) values, the light-brown bran had no effect, the purple bran exhibited a minor effect on leukemia and cervical cancer cells, and the red bran exhibited strong inhibitory effects on leukemia, cervical, and stomach cancer cells. High concentrations of protocatechuic acid and anthocyanins in purple bran and proanthocyanidins in red bran were identified. The red bran was further fractionated on a Sephadex column. Fraction 3 rich in proanthocyanidin oligomers and polymers had the greatest activity. Red bran has the potential to serve as a functional food supplement for human consumption.

Partial acid hydrolysis of the tetrasaccharide (lycotetraose) side chain of the tomato glycoalkaloid α-tomatine resulted in the formation of four products with three, two, one, and zero carbohydrate side chains, which were separated by high-performance liquid chromatography (HPLC) and identified by thin-layer chromatography (TLC) and liquid chromatography ion-trap time-of-flight mass spectrometry (LCMS-IT-TOF). The inhibitory activities in terms of IC(50) values (concentration that inhibits 50% of the cells under the test conditions) of the parent compound and the hydrolysates, isolated by preparative HPLC, against normal human liver and lung cells and human breast, gastric, and prostate cancer cells indicate that (a) the removal of sugars significantly reduced the concentration-dependent cell-inhibiting effects of the test compounds, (b) PC3 prostate cancer cells were about 10 times more susceptible to inhibition by α-tomatine than the breast and gastric cancer cells or the normal cells, (c) the activity of α-tomatine against the prostate cancer cells was 200 times greater than that of the aglycone tomatidine, and (d) the activity increased as the number of sugars on the aglycone increased, but this was only statistically significant at p < 0.05 for the normal lung Hel299 cell line. The effect of the alkaloids on tumor necrosis factor α (TNF-α) was measured in RAW264.7 macrophage cells. There was a statistically significant negative correlation between the dosage of γ- and α-tomatine and the level of TNF-α. α-Tomatine was the most effective compound at reducing TNF-α. The dietary significance of the results and future research needs are discussed.

Tomato ( Solanum lycopersicum ) plants synthesize nutrients, pigments, and secondary metabolites that benefit nutrition and human health. The concentrations of these compounds are strongly influenced by the maturity of the tomato fruit on the vine. Widely consumed Korean tomatoes of the variety Doturakworld were analyzed for changes in the content of free amino acids, phenolic compounds, chlorophylls, carotenoids, and glycoalkaloids at 11 stages (S1-S11) of ripeness. The results show that (a) the total content (in mg/100 g of FW) of the free amino acids and other nitrogen-containing compounds in the extracts ranged from about 41 to 85 in the green tomato extracts S1-S7 and then increased to 251 (S9) in the red extracts, followed by a decrease to 124 in S11 red extracts; (b) the total initial concentration and composition of up to 12 phenolic compounds of approximately 2000 microg/100 g of FW varied throughout the ripening process, with the quantity decreasing and the number of individual compounds increasing in the red tomato; (c) chlorophyll a and b content of tomatoes harvested during S1 was 5.73 mg/100 g of fresh pericarp and then decreased continuously to 1.14 mg/100 g for S11; (d) the concentration (in mg/100 g of FW) of lycopene in the S8 red extract of 0.32 increased to 1.27 in S11; and (e) tomatoes harvested during S1 contained 48.2 mg of dehydrotomatine/100 g of FW, and this value continually decreased to 1.5 in S7, with no detectable levels in S8-S11. The corresponding alpha-tomatine content decreased from S1 (361) to S8 (13.8). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell assay IC(50) values showed that Hel299 lung cells, A549 lung cancer cells, and HeLa cervical carcinoma cells were highly susceptible to inactivation by glycoalkaloid-rich green tomato extracts. Chang normal liver cells and U937 lymphoma cells were less susceptible. The possible significance of the results for plant physiology and the diet is discussed.

The purpose of the current study was to determine the effect of the Artemisia capillaris ethyl acetate (ACE) fraction on diet-induced obesity and to elucidate the underlying mechanism. The ACE fraction treatment decreased the leptin level and fat accumulation in cultured 3T3-L1 adipocytes through the free fatty acids released in the medium. The ACE fraction significantly suppressed the expression of peroxisome proliferator-activated receptor-gamma in cultured 3T3-L1 adipocytes. To determine the effect of the ACE fraction on C57BL/6J male mice, the mice were separated into six groups: normal control (N), N plus 0.1 g/kg body weight ACE (NB), high fat control group (HF), HF plus 0.05 g/kg of body weight ACE (HFA), HF plus 0.1 g/kg of body weight ACE (HFB), and HF plus 0.03 g/kg of body weight rosiglitazone (RG) groups. We speculate that the HFB group exhibits a lipid-lowering effect via increased mitochondrial beta-oxidation, of which the rate-limiting enzyme is carnitine palmitoyl transferase I, the activity of which was significantly increased. Also, the activity of fatty acid synthase, a key enzyme of fatty acid synthesis, was markedly suppressed (19%) in the HFB group, as compared to the HF group, and glycerol-3-phosphate dehydrogenase activity, which is very useful in studying adipogenic differentiation in vitro, was markedly suppressed (30%) in the HFB group compared with the HF group. Furthermore, the HFB group showed lowered hepatic lipid droplet accumulation and adipose tissue weight and size. We suggest that 0.1 g of the ACE fraction/kg of body weight may exert an anti-obesity effect in C57BL/6J mice by enhancing lipid metabolism.

Tomato plants ( Lycopersicon esculentum ) synthesize the glycoalkaloids dehydrotomatine and alpha-tomatine, possibly as a defense against bacteria, fungi, viruses, and insects. Six green and three red tomato extracts were investigated for their ability to induce cell death in human cancer and normal cells using a microculture tetrazolium (MTT) assay. Compared to untreated controls, the high-tomatine green tomato extracts strongly inhibited the following human cancer cell lines: breast (MCF-7), colon (HT-29), gastric (AGS), and hepatoma (liver) (HepG2), as well as normal human liver cells (Chang). There was little inhibition of the cells by the three low-tomatine red tomato extracts. Cell death induced by the pure glycoalkaloids dehydrotomatine and alpha-tomatine isolated from green tomatoes and characterized by HPLC, GC, and GC-MS, as well as their respective aglycones tomatidenol and tomatidine, was also evaluated. alpha-Tomatine was highly effective in inhibiting all of the cell lines. Dehydrotomatine, tomatidenol, and tomatidine had little, if any, effect on cell inhibition. The results show that the susceptibility to destruction varies with the nature of the alkaloid and plant extract and the type of cancer cell. These findings extend related observations on the anticarcinogenic potential of glycoalkaloids and suggest that consumers may benefit by eating not only high-lycopene red tomatoes but also green tomatoes containing glycoalkaloids. Possible mechanisms of the anticarcinogenic and other beneficial effects and the significance of the cited observations for breeding improved tomatoes and for the human diet are discussed.

This study was carried out to investigate the chemopreventive effects of immature plum extracts. The methanol extract of immature plums (plum 1), that are picked at 20-40 days before final harvest, has remarkably inhibited the growth of hepatoma HepG2 cells. The effects of immature plum extracts on hepatotoxicity in benzo(alpha)pyrene (B(alpha)P, carcinogen)-treated mice were investigated. Male ICR mice were pretreated with immature plum extracts (2.5 or 5 g/kg bw/day, for 5 days, i.p.) before treatment with B(alpha)P(0.5 mg/kg bw, i.p., single dose). The activities of serum aminotransferase, cytochrome P450 (CYPs) and the hepatic content of lipid peroxide were increased on B(alpha)P-treatment group than control, but those levels were significantly decreased by the pretreatment of immature plum extracts. The primary CYPs involved in the metabolism and bioactivation of B(alpha)P are CYP1A1. The pretreatment of immature plum extracts inhibited the induction of CYP1A1 expression. The activities of glutathione peroxidase, superoxide dismutase and catalase were decreased by the pretreatment of immature plum extracts more than with B(alpha)P alone. Whereas, the hepatic content of glutathione and glutathione S-transferase activity depleted by B(alpha)P was significantly increased (p > 0.05). These results suggest that immature plum extracts may counteract toxic effects of carcinogens, such as B(alpha)P, and therefore possess the chemopreventive efficacy.

This study was performed to investigate the effect of ethanol extract from Saururus chinensis (Lour.) Baill on liver function, plasma lipid composition and antioxidant system with high-fat diet for 4 weeks. Rats were divided into the following five groups; untreated control group (normal), treated with 0.5% SE (normal + 0.5% SE), high-fat group (high-fat), high-fat group treated with 0.1% SE (high-fat + 0.1% SE), or 0.5% SE (high-fat + 0.5% SE). Weight gains showed a tendency to decrease in rat with high-fat + SE. Plasma total cholesterol showed a tendency to decrease with ethanol extract from S. chinensis (Lour.) Baill. LDL-cholesterol contents were lower in ethanol extract group than that of control group. Aspartate amino transferase and alanine amino transferase activities were increased by high-fat diet, and were decreased by 0.5% SE. Lipid peroxide level showed a tendency to increase in high-fat diet group than that of normal group. In ethanol extract from S. chinensis (Lour.) Baill groups, lipid peroxide level decreased significantly and SOD activity was also decreased progressively. These results demonstrated that the ethanol extract of S. chinensis (Lour.) Baill lowered serum cholesterol levels, tissue lipid contents and accumulation of cholesterol in the rat.

In this study, we found that alpha-pinene (α-pinene) exhibits anti-inflammatory activity through the suppression of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) pathway in mouse peritoneal macrophages. α-Pinene is found in the oils of many coniferous trees and rosemary. We investigated the inhibitory effects of α-Pinene on inflammatory responses induced by lipopolysaccharide (LPS) using mouse peritoneal macrophages. α-Pinene significantly decreased the LPS-induced production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). α-Pinene also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-stimulated macrophages. Additionally, the activations of MAPKs and NF-κB were attenuated by means of α-pinene treatment. These results indicate that α-pinene has an anti-inflammatory effect and that it is a potential candidate as a new drug to treat various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Cynanchum paniculatum (Bunge) Kitag. ex H. Hara (Asclepiadaceae) have been traditionally used in East Asia as analgesic or antiviral agents. Interestingly, some Chinese and Korean traditional medicinal books reported that the use of C. paniculatum in the treatment of psychotic symptoms, such as hallucinations and delusions. In this study, we aimed to investigate whether C. paniculatum could improve sensorimotor gating disruption in mice with MK-801-induced schizophrenia-like behaviors. We also aimed to identify the active component of C. paniculatum that could potentially serve as a treatment for schizophrenia and found that paeonol, the major constituent compound of C. paniculatum , showed potential as a treatment for schizophrenia. To assess the effect of paeonol on mice with MK-801-induced schizophrenia-like behaviors, we carried out a series of behavioral tests related with symptoms of schizophrenia. In addition, we utilized Western blotting and ELISA techniques to investigate the antipsychotic actions of paeonol. C. paniculatum extract (100 or 300 mg/kg) and paenol (10 or 30 mg/kg) significantly reversed MK-801-induced prepulse deficits in acoustic startle response test. In addition, paeonol (10 or 30 mg/kg) attenuated social novelty preference and novel object recognition memory on MK-801-induced schizophrenia-like behaviour in mice. Furthermore, the phosphorylation levels of PI3K, Akt, GSK3β and NF-κB, as well as related pro-inflammatory cytokine, such as IL-1β and TNF-α, were significantly reversed by the administration of paeonol (10 or 30 mg/kg) in the prefrontal cortex of MK-801-treated mice. Collectively, these data show that paeonol can potentially be used as an agent for treating sensorimotor gating deficits, negative symptoms, and cognitive deficits, such as those observed in schizophrenia with few adverse effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The present study investigated the effects of azuki bean (Vigna angularis) extract (VAE) on the progress of atopic dermatitis (AD)-like skin lesions in NC/Nga mice induced by 1-chloro-2,4-dinitrobenzene. The efficacy of VAE in NC/Nga mice was determined by measuring gross and histological skin lesions, serum IgE levels, eosinophil ratio in peripheral leucocytes, and mRNA expression levels of interleukin (IL)-4, tumour necrosis factor (TNF)-α and interferon (IFN)-γ in splenocytes. Continuous ingestion of VAE inhibited the development of the AD-like skin lesions in a dose-dependent manner. In the VAE-treated mice, the numbers of mast cells in the skin, eosinophil ratio in peripheral leucocytes, relative mRNA expression of inflammatory cytokines in the spleen, and serum IgE levels were significantly reduced. Results suggest that VAE can inhibit the development of AD-like skin lesions in NC/Nga mice by regulating immune mediators and cells, and may be an effective alternative therapy for AD. [Copyright &y& Elsevier]