Pinus koraiensis needle or cone extracts alleviate atopic dermatitis symptoms by regulating immunity and suppressing inflammation in HaCaT cells and Nc/Nga mice.

Pinus koraiensis needles (PKN) and cones (PKC) have been shown to protect against inflammation and pathogenic bacteria. We investigated the efficacies and action mechanisms of topical applications of 1,3-butylene glycol (BG) extracts and oral administration of their water extracts on atopic dermatitis (AD) symptoms. After exposing HaCaT cells and Nc/Nga mice dorsal skins to 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis models, they were topically applied BG (AD-control), 30% PKNX, or 30% PKCX to the skin lesions and fed water extracts (0.5%) in high-fat diets for 5 weeks. Normal-control mice had no DNCB exposure. Serum immunoglobulin E (IgE), IL-4, and TNF-α levels and gene expressions of TNF-α, IL-4, IL-6, and IFN-γ in the dorsal skin and HaCaT cells were measured. The AD-control mice elevated TNF-α and IL-6 mRNA levels in HaCaT cells. Both extracts attenuated clinical AD symptoms in AD-induced Nc/Nga mice: PKNX improved hemorrhage, erythema, and lichenification of dorsal skin better than PKCX while both similarly alleviated erythema, edema, excoriation, and itching behavior. PKCX reduced IgE contents and increased filaggrin mRNA expression better than PKNX, but PKNX reduced lipid peroxides and mRNA levels of TNF-α and IL-4 in the dorsal skin. In the histological analysis of the dorsal skin, the administration of both extracts significantly decreased mast cell numbers, immune cell infiltration, gaps between the epidermis and dermis, and abnormal cell and nucleus shapes. In conclusion, both PKCX and PKNX treatment alleviated the DNCB-induced clinical symptoms of AD by alleviating immune-related symptoms and inflammation in partially different pathways. Therefore, PKNX and PKCX may be effective for AD therapy. PRACTICAL APPLICATIONS: Atopic dermatitis (AD) is related to an overly activated immune response, and it has steadily increased last 3 decades. However, no optimal sustainable treatments are available. Pinus koraiensis needles and cones extracts have been used for anti-inflammatory and antimicrobial treatment. The present study demonstrated that their intake and topical administration onto the AD lesion alleviated clinical AD symptoms associated with reduced proinflammatory cytokines, mast cell numbers, and immune cell infiltrates to maintain dermal structure with maintaining filaggrin expression in AD-induced HaCaT cells and Nc/Nga mice. These results suggested that Pinus koraiensis needles and cones extracts can be developed and applied as beneficial alternative therapies for AD.

Protection against Neurological Symptoms by Consuming Corn Silk Water Extract in Artery-Occluded Gerbils with Reducing Oxidative Stress, Inflammation, and Post-Stroke Hyperglycemia through the Gut-Brain Axis.

Corn silk (Stigma maydis), rich in flavonoids, is traditionally used to treat edema, depression, and hyperglycemia and may alleviate ischemic stroke symptoms in Chinese medicine. This study examined whether corn silk water extract (CSW) could alleviate ischemic stroke symptoms and post-stroke hyperglycemia in Mongolian gerbils with transient cerebral ischemia and reperfusion (I/R). After being given 0.05% (I/R-LCSW) and 0.2% (I/R-HCSW), 0.02% aspirin (I/R-aspirin), and cellulose (I/R-control) in their 40 energy% fat diets for three weeks, the gerbils underwent an artery occlusion for eight minutes and reperfusion. They took the assigned diet for an additional three weeks. Sham-operated gerbils without artery occlusion had the same diet as Sham-control. CSW intake reduced neuronal cell death in gerbils with I/R and dose-dependently improved the neurological symptoms, including drooped eyes, crouched posture, flexor reflex, and walking patterns. CSW intake also alleviated the short-term memory and spontaneous alteration and grip strength compared to the I/R-control group. The protection against ischemic stroke symptoms was associated with the reduced tumor necrosis factor-α, interleukin-1ß, superoxide, and lipid peroxide levels, promoting superoxide dismutase activity in the hippocampus in the CSW groups, compared to the I/R-control. The blood flow measured by Doppler was improved with CSW compared to the I/R-control. Furthermore, CSW intake prevented the post-stroke hyperglycemia related to decreasing pancreatic ß-cell mass as much as the Sham-control, and it was related to protection against ß-cell apoptosis, restoring the ß-cell mass similar to the Sham-control. CSW intake elevated the relative abundance of Lactobacillus, Bifidobacterium, Allobaculum, and Akkermansia compared to the I/R-control. Picrust2 analysis showed that CSW increased the propionate and butyrate metabolism and the starch and glucose metabolism but reduced lipopolysaccharide biosynthesis compared to the I/R-control. In conclusion, CSW intake protects against neuronal cell death and post-hyperglycemia by reducing oxidative stress and inflammation and increasing blood flow and the ß-cell mass. The alleviation was associated with promoting the gut-brain axis by changing the gut microbiome community.

Development of an Oriental Medicine Discrimination Method through Analysis of Steroidal Saponins in Dioscorea nipponica Makino and Their Anti-Osteosarcoma Effects.

To prevent confusing Dioscorea nipponica (DN), an Oriental medicine, with Dioscorea quinquelobata (DQ) and Dioscorea septemloba (DS), a simple and accurate quantitative analysis method using HPLC combined with ultraviolet (UV) detection was developed and verified with UPLC-QTOF/MS through identification of five saponin glycosides: protodioscin (1), protogracillin (2), pseudoprotodioscin (3), dioscin (4), and gracillin (5). The newly developed analysis method showed sufficient reproducibility (<1.91%) and accuracy (92.1%-102.6%) and was able to identify DN based on the presence of compound 3 (13.821 ± 0.037 mg/mL) and the absence of 5. Compound 1, which is present in DN at a relatively high level (159.983 ± 0.064 mg/mL), was also an important marker for identification. Among the three species, DN showed the strongest activation of apoptotic signaling in osteosarcoma cells, while the four compounds detected in DN showed IC50 values of 6.43 (1), 10.61 (2), 10.48 (3), and 6.90 (4). In conclusion, the strong inhibitory effect of DN against osteosarcoma was confirmed to be associated with 1 and 4, which is also related to the quantitative results. Therefore, the results of this study might provide important information for quality control related to Oriental medicine.

Correction to: Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1.

Following publication of the original article [1], the authors have re-evaluated the authorship for this article. The updated author group is.

Ameliorating effects of Cuscuta chinensis Lamak extract on hind­limb ischemia, and angiogenic­ or inflammatory associated factors in ovariectomized mice.

Cuscuta chinensis Lamak (CCL) has traditionally been used in Korea to treat sexual disorders and skin problems. The aim of the present study was to investigate the effects of CCL extract on surgical injury­induced ischemia in the hind limbs of mice. Specifically, female C57BL/6 mice were ovariectomized, and their hind­limb vessels were ligated with surgical silk (6­0) and excised. CCL (150 or 450 mg/kg/BW) was then administered to the mice for 3 weeks, and the blood flow rate was evaluated using a laser Doppler system at ­7, 0, 7, 14 and 21 days following hind­limb ischemia. The serum expression profiles of angiogenic and inflammatory mediators were measured using an antibody array, and the transcript levels were reverse transcription­quantitative polymerase chain reaction. The rate of hind limb blood flow was normalized to non­ischemic lesions and revealed to be markedly elevated at 14 and 21 days following ischemia when compared with the vehicle group. The density of capillaries in the hind limbs was also significantly increased following treatment with CCL in a dose­dependent manner. In addition, the transcriptional expression of angiogenetic factors were upregulated, whereas that of inflammatory cytokines were downregulated. Finally, vascular endothelial cell migration and tube formation were evaluated in vitro using human umbilical vein endothelial cells (HUVECs) and identified to be significantly increased following treatment with CCL. Overall, the results of the present study indicate that CCL extract exhibits therapeutic potential for the treatment of hind­limb ischemia as it promotes peripheral angiogenic and anti­inflammatory effects in mice.

Ojayeonjonghwan, an oriental medicine composed of five seeds, protects against vasomotor and neurological disorders in estrogen-deficient rats.

IMPACT STATEMENT: Menopausal symptoms impair the quality of life of many women, and although conventional treatments are often effective, their use is limited by adverse effects. Ojayeonjonghwan, OJa, is a traditional Oriental medicine that is used for both male and female reproductive health and has a long history of safe use. We evaluated the effectiveness of two variations of OJa (OJa1 and OJa2) for treating menopausal symptoms in ovariectomized (OVX) rats. Both OJa preparations were effective for relieving indicators of hot flashes and depression, and for preventing loss of bone mineral density and lean body mass. Only OJa 2 prevented memory dysfunction. These results show that the traditional Oriental medicine, Ojayeonjonghwan, has the potential to relieve menopausal symptoms in women and should be further evaluated in human clinical trials as an alternative to convention therapies in women for whom conventional therapies are not indicated or found to be ineffective.

Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model.

Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo. Human adrenocortical NCI-H295R cells were used to assess the effects of TTK extract on production of dehydroepiandrosterone and testosterone, as well as the protein expression of steroidogenic enzymes. Further, a letrozole-induced PCOS rat model was used in vivo to assess whether dietary administration of TTK extract restores normal hormones and reduces PCOS symptoms. TTK extract significantly inhibited forskolin (FOR)-induced androgen production in NCI-H295R cells and serum luteinizing hormone, testosterone, and follicular cysts, but not estradiol, were reduced in letrozole-induced PCOS rats orally administered the TTK extract. In addition, TTK extract inhibits androgen biosynthesis through the ERK-CREB signaling pathway, which regulates CYP17A1 or HSD3B2 expression. TTK extract could be utilized for the prevention and treatment of hyperandrogenism and other types of PCOS.

Tetragonia tetragonioides (Pall.) Kuntze protects estrogen-deficient rats against disturbances of energy and glucose metabolism and decreases proinflammatory cytokines.

Tetragonia tetragonioides (Pall.) Kuntze (TTK) and JakYakGamCho-Tang (JGT) have been used for improving women's health and treating inflammatory diseases. We determined that the long-term consumption of these herbal extracts alleviates the progression of postmenopausal symptoms in high-fat-diet fed ovariectomized (OVX) rats, and further explored the mechanisms involved. Five groups of OVX rats were fed high fat diets that were supplemented with either 2% dextrin (control), 2% TTK (70% ethanol extract), 2% JGT (water extract), 1% JGT + 1% TTK (JGTT), or 30 µg/kg body weight/day of 17ß-estradiol (positive control). After eight weeks of dietary intervention, the herbal treatments did not change the serum concentrations of 17ß-estradiol or uterine weight in control rats, but they were higher in the positive-control group. TTK rats exhibited higher daily energy expenditure, particularly fat oxidation, without modifying the energy intake than the controls. TTK lowered the fat mass but lean body mass of the abdomen and leg were increased. JGT decreased periuterine fat mass and lean body mass more than the control but the decrease was not as much as TTK. TTK resulted in substantially lower serum concentrations of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1, than the control and JGT had lesser effect than TTK. Insulin resistance, determined by homeostasis model assessment estimate for assessing insulin resistance (HOMA-IR) and insulin tolerance test, was reduced in the decreasing order of control, JGT, JGTT, and TTK and the HOMA-IR of TTK was similar to the positive control. TTK, but not JGT, enhanced glucose tolerance compared with the control, although the serum insulin levels in TTK were lower compared to the control. Interestingly, the ß-cell masses were much greater in the TTK and JGTT groups than in the control, and they were comparable to the positive control. The increases in ß-cell masses in TTK and JGTT groups were associated with enhanced ß-cell proliferation and suppressed apoptosis, which was related to the decreased TNF-α and interleukin-1ß expressions. In conclusion, JGTT did not improve menopausal symptoms better than TTK itself. TTK itself prevented the OVX-induced impairments in energy, lipid, and glucose metabolism, similar to the positive control, without changing serum 17ß-estradiol levels and potentiating insulin signaling and decreasing proinflammatory cytokines. TTK may be a useful intervention to alleviate some menopausal symptoms similar to selective estrogen receptor modulators and should be investigated with further human study. Impact statement Menopause decreases the quality of life in middle-aged women and herbal remedies are sometimes used as alternatives for hormone replacement therapy, which may have detrimental side effects. Although several herbal extracts have been studied, no remedies improve all the menopausal symptoms. In this study, the 70% ethanol extract of Tetragonia tetragonioides (Pall.) Kuntze (TTK) reduced the symptoms of hot flushes and improved energy, glucose, and lipid metabolism in estrogen-deficient animals without increasing serum 17ß-estradiol levels. This extract acts like a selective estrogen receptor modulator and it may be a useful intervention for alleviating menopausal symptoms. This is the first study to show that the 70% ethanol extract of TTK has the potential to treat menopause-associated symptoms and metabolic disturbances. It may be a useful intervention for alleviating the symptoms of menopause in women if its efficacy can be confirmed in human studies.

Effects of three different formulae of Gamisoyosan on lipid accumulation induced by oleic acid in HepG2 cells.

BACKGROUND: Gamisoyosan (GSS) is an herbal formula which has been used to treat women's diseases for several hundred years in Korea. GSS is one of the three most common prescriptions among women and is used to treat menopausal symptoms. Fatty liver disease is also common in postmenopausal women and can precede more severe diseases, such as steatohepatitis. The present study compared the effects of GSS on fatty liver using three different formulae, Dongui-Bogam (KIOM A), Korean Pharmacopeia (KIOM B) and Korean National Health Insurance (KIOM C). METHODS: In oleic acid-induced HepG2 fatty liver cells, cellular lipid accumulation, triglycerides and total cholesterol were measured after treatment with three GSS formulae and simvastatin as a positive control. To investigate the phytoestrogen activity of GSS, MCF-7 cells were treated with GSS, and hormone levels were quantified. Also, qualitative analysis was performed with UPLC. RESULTS: All types of GSS decreased cellular lipid accumulation. KIOM A was slightly less effective than the other two GSS formulae. KIOM B and KIOM C decreased cellular triglycerides more effective than simvastatin, but KIOM A did not affect cellular triglycerides. Cellular total cholesterol was decreased by all GSS and simvastatin. GSS showed phytoestrogen activity in MCF-7 cells. From the UPLC analysis data, geniposide, paeoniflorin and glycyrrhizin were detected form three GSS formulae. CONCLUSION: These results suggest that all GSS formulae have a beneficial effect on fatty liver disease during menopause and that differences of formula have no effect on the efficacy of the prescription.

Palmiwon attenuates hepatic lipid accumulation and hyperlipidemia in a menopausal rat model.

OBJECTIVE: We examined the phytoestrogenic effects of palmiwon on breast carcinoma, lipid accumulation in methyl-ß-cyclodextrin-induced HepG2 cells, and lipid-related diseases in a rat model of menopausal hyperlipidemia. METHODS: E-Screen assay was used to screen for phytoestrogens, especially those with antiestrogenic activity, in MCF-7 cells. Oil Red O staining and intracellular cholesterol analyses were used to quantify cellular cholesterol levels. 3-Hydroxy-3-methyl glutaryl coenzyme A reductase assay was used to measure enzyme activity. The levels of phosphorylated adenosine monophosphate-activated protein kinases and products of genes involved in cholesterol synthesis were measured by Western blot analysis. Thirty rats were either ovariectomized or sham-operated and randomly assigned to four groups (n = 5)-Sham, OVX, OVX-SV, or OVX-PMW (50, 150, or 450 mg/kg) group-for 8 weeks. A number of targets associated with lipid-related diseases were examined to confirm the estrogenic effects of palmiwon. RESULTS: Palmiwon showed antiestrogenic activity in MCF-7 cells. Palmiwon decreased lipid accumulation, total cholesterol levels, and low-density lipoprotein/very-low-density lipoprotein levels in HepG2 cells. Moreover, palmiwon reversed the effects of methyl-ß-cyclodextrin on cholesterol synthesis regulators and inhibited the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase. Phosphorylation of adenosine monophosphate-activated protein kinase was stimulated by palmiwon. In ovariectomized rats, palmiwon reduced retroperitoneal and perirenal fat accumulation, serum lipids, atherogenic index, cardiac risk factor score, intima-media thickness, and nonalcoholic steatohepatitis scores. CONCLUSIONS: These results indicate that palmiwon inhibits lipid accumulation without estrogenic activity in the breast. Therefore, palmiwon may have potential as a therapeutic agent for the treatment of hyperlipidemia in postmenopausal women.

Hemopoietic effect of extracts from constituent herbal medicines of Samul-tang on phenylhydrazine-induced hemolytic anemia in rats.

Samul-tang (Si-Wu-Tang, SMT), a kind of herbal medicines, has been used for the hemato-deficient disease for hundreds of years. In this work, investigate the anti-anemia activity of the H2O extracts from constituent herbal medicines of Samul-tang in an anemia model induced by intravenous infection of phenylhydrazine-HCL (PHZ) at 10 mg/kg for 4 days. After PHZ injection, female Sparague-Dawley rats were administrated extracts from constituent herbal medicines of SMT (300 mg/kg/day, p.o.) daily for 1 week. Results showed that sever hemolysis was induced by PHZ. For Paeonia lactiflora (PL2) H2O extract treated groups, the concentration of hemoglobin, hematocrit and red blood cells number increased much more significantly than PHZ-treated group. Moreover, Angelica gigas (AG), Angelica. acutiloba (AA), Paeonia lactiflora (PL2) and Rehmannia glutinosa (RG) extract administration significantly improved serum erythropoietin concentration. The activity of aminolevulinic acid dehydrates (ALDL) in liver homegenate was increased in Angelica gigas(AA), Paeonia lactiflora (PL2) and Rehmannia glutinosa (RG) treated group.

Supplementing with Opuntia ficus-indica Mill and Dioscorea nipponica Makino extracts synergistically attenuates menopausal symptoms in estrogen-deficient rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Prickly pear cactus grown in Korea (Opuntia ficus-indica Mill, KC) and Buchema (Dioscorea nipponica Makino, B) have been traditionally used in East Asia and South America to treat various metabolic diseases. The aim of the present study was to determine whether the extracts of KC, B, and KC+B can prevent the impairments of energy, glucose, lipid and bone homeostasis in estrogen-deficient ovariectomized (OVX) rats and to explore their mechanisms. MATERIALS AND METHODS: OVX rats were divided into 4 groups and fed high fat diets supplemented with either 3% dextrin (control), 3% KC, 3% B or 1.5% KC+1.5% B. Sham rats were fed 3% dextrin. After 12 weeks of diet consumption, energy, lipid, glucose and bone metabolisms were analyzed and Wnt signaling in the femur and hepatic signaling were determined. RESULTS: OVX impaired energy, glucose and lipid metabolism and decreased uterine and bone masses. B and KC+B prevented the decrease in energy expenditure, especially from fat oxidation, in OVX rats, but did not affect food intake. KC+B and B reduced body weight and visceral fat levels, as compared to the OVX-control, by decreasing fat synthesis and inhibiting FAS and SREBP-1c expression. KC+B and B prevented the increases in serum lipid levels and insulin resistance by improving hepatic insulin signaling (pIRS→pAkt→pGSK-3ß). KC and KC+B also prevented decreases in bone mineral density (BMD) in the femur and lumbar spine in OVX rats. This was related to decreased expressions of bone turnover markers such as serum osteocalcin, alkaline phosphatase (ALP) and bone-specific ALP levels, and increased serum P levels. KC and KC+B upregulated low-density lipoprotein receptor-related protein 5 and ß-catenin in OVX rats, but suppressed the expression of dickkopf-related protein 1. B alone improved energy, lipid and glucose homeostasis, but not bone loss, whereas KC alone enhanced BMD, but not energy, lipid or glucose homeostasis. CONCLUSION: KC+B synergistically attenuated impairments of bone, energy, lipid and glucose metabolism by OVX, suggesting potential efficacy of the combination for alleviating menopausal symptoms.

Wnt-signaling-mediated antiosteoporotic activity of porcine placenta hydrolysates in ovariectomized rats.

Anti-osteoporotic effects of two types of porcine placenta hydrolysates (PPH) were evaluated in ovariectomized (OVX) rats orally administered PPH without (WPPH) or with (NPPH) ovarian hormones (1 g/kg bw/day). PPH groups were compared with OVX rats with estrogen replacement (0.1 mg/kg bw conjugated estrogen; EST), or dextrose (placebo; OVX-control) All rats received high-fat/calcium-deficient diets for 12 weeks. NPPH contained less estrogen and progesterone, but more essential amino acids, whereas the opposite was true for WPPH. NPPH decreased body weight and peri-uterine fat pads, and maintained uterus weight. NPPH rats had higher femur and lumbar spine bone mass density compared to controls; but less than those of EST rats. Serum phosphorus and urinary calcium and phosphorus levels were reduced in NPPH rats compared to OVX-controls. Serum bone-specific alkaline phosphatase, osteocalcin, and bone turnover marker levels were reduced NPPH rats compared to OVX-controls. WPPH produced results similar to those of NPPH, but less significant. Both NPPH and estrogen upregulated low-density lipoprotein receptor-related protein 5 and ß-catenin in OVX rats, while the expression of dickkopf-related protein 1 was suppressed. In conclusion, NPPH exerted anti-osteoporotic effects by activating osteogenesis and stimulating Wnt signaling, possibly mediated by the various amino acids and not ovarian hormones.

Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells.

AIM: To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells. METHODS: Cinnamon extract was used to treat murine macrophage cell line (Raw 264.7), mouse primary antigen-presenting cells (APCs, MHCII(+)) and CD11c(+) dendritic cells to analyze the effects of cinnamon extract on APC function. The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production, and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry. In addition, the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H(3)]-thymidine incorporation and cytokine analysis, respectively. To confirm the anti-inflammatory effects of cinnamon extract in vivo, cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid. The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms, histological analysis and cytokine expression profiles in inflamed tissue. RESULTS: Treatment with cinnamon extract inhibited maturation of MHCII(+) APCs or CD11c(+) dendritic cells (DCs) by suppressing expression of co-stimulatory molecules (B7.1, B7.2, ICOS-L), MHCII and cyclooxygenase (COX)-2. Cinnamon extract induced regulatory DCs (rDCs) that produce low levels of pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] while expressing high levels of immunoregulatory cytokines (IL-10 and transforming growth factor-ß). In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation, and converted CD4(+) T cells into IL-10(high) CD4(+) T cells. Furthermore, oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines (IL-1ß, IFN-γ and TNF-α), while enhancing IL-10 levels. CONCLUSION: Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10(+) regulatory T cells.

Cinnamon extract induces tumor cell death through inhibition of NFkappaB and AP1.

BACKGROUND: Cinnamomum cassia bark is the outer skin of an evergreen tall tree belonging to the family Lauraceae containing several active components such as essential oils (cinnamic aldehyde and cinnamyl aldehyde), tannin, mucus and carbohydrate. They have various biological functions including anti-oxidant, anti-microbial, anti-inflammation, anti-diabetic and anti-tumor activity. Previously, we have reported that anti-cancer effect of cinnamon extracts is associated with modulation of angiogenesis and effector function of CD8+ T cells. In this study, we further identified that anti-tumor effect of cinnamon extracts is also link with enhanced pro-apoptotic activity by inhibiting the activities NFkappaB and AP1 in mouse melanoma model. METHODS: Water soluble cinnamon extract was obtained and quality of cinnamon extract was evaluated by HPLC (High Performance Liquid Chromatography) analysis. In this study, we tested anti-tumor activity and elucidated action mechanism of cinnamon extract using various types of tumor cell lines including lymphoma, melanoma, cervix cancer and colorectal cancer in vitro and in vivo mouse melanoma model. RESULTS: Cinnamon extract strongly inhibited tumor cell proliferation in vitro and induced active cell death of tumor cells by up-regulating pro-apoptotic molecules while inhibiting NFkappaB and AP1 activity and their target genes such as Bcl-2, BcL-xL and survivin. Oral administration of cinnamon extract in melanoma transplantation model significantly inhibited tumor growth with the same mechanism of action observed in vitro. CONCLUSION: Our study suggests that anti-tumor effect of cinnamon extracts is directly linked with enhanced pro-apoptotic activity and inhibition of NFkappaB and AP1 activities and their target genes in vitro and in vivo mouse melanoma model. Hence, further elucidation of active components of cinnamon extract could lead to development of potent anti-tumor agent or complementary and alternative medicine for the treatment of diverse cancers.

Cinnamon extract suppresses tumor progression by modulating angiogenesis and the effector function of CD8+ T cells.

Cinnamon is one of the most widely used herbal medicines with diverse bioactive effects. However, little evidence has been reported about the potential anti-tumor effects of cinnamon. In vitro and in vivo system, cinnamon treatment strongly inhibited the expression of pro-angiogenic factors and master regulators of tumor progression not only in melanoma cell lines but also in experimental melanoma model. In addition, cinnamon treatment increased the anti-tumor activities of CD8(+) T cells by increasing the levels of cytolytic molecules and their cytotoxic activity. In conclusion, cinnamon extract has the potential to be an alternative medicine for tumor treatment.

Ginsenosides Rb1 and Rg1 suppress triglyceride accumulation in 3T3-L1 adipocytes and enhance beta-cell insulin secretion and viability in Min6 cells via PKA-dependent pathways.

Ginseng root is known to induce anti-diabetic activity, but the key components involved are unknown. We investigated which major ginsenosides in ginseng enhanced glucose homeostasis by in vitro studies. Rb1 and Rg1 reduced the triglyceride accumulation in 3T3-L1 adipocytes by activating PKA with increased intracellular cAMP. However, the insulin-stimulated glucose uptake was enhanced by Rb1 and Rg1 via activation of phosphatidylinositol-3 kinase. Rb1 and Rg1 promoted glucose-stimulated insulin secretion and cell viability in Min6 cells through PKA which augmented IRS2 expression to enhance insulin/IGF-1 signaling. These results suggest that Rb1 and Rg1 improved glucose homeostasis through the activation of a PKA like glucagon-like peptide-1 receptor agonist.

Anti-platelet effects of bioactive compounds isolated from the bark of Rhus verniciflua Stokes.

It has previously been shown that EtOAc extracts of Rhus verniciflua Stokes (RVS) inhibit the platelet aggregation response. In this report, bioassay-guided fractionation using ADP-, arachidonic acid-, and collagen-induced human platelet aggregation by a whole blood aggregometer yielded the bioactive compounds isomaltol and pentagalloyl glucose from different highly effective fractions. In addition, column chromatography of fractions from RVS yielded another five compounds: butin, fisetin, sulfuretin, butein and 3,4',7,8-tetrahydroxyflavone. We investigated the effects of bioactive compounds from RVS fractions on several markers of platelet activation using receptor expression on platelet membranes, including glycoprotein IIb/IIIa (CD41), GPIIb/IIIa-like expression (PAC-1) and P-selectin (CD62), and intracelluar calcium mobilization responses by flow cytometry in healthy subjects. Dose-dependent inhibition of platelet aggregation and significantly decreased platelet activation were observed for the isomaltol- and pentagalloyl glucose-treated platelets, respectively. These results show that isomaltol and pentagalloyl glucose from the bark of Rhus verniciflua Stokes have potent anti-platelet activity and emphasize the need to further examine the mechanism of these active compounds for platelet modulation.