Ameliorating effects of Orostachys japonica against high-fat diet-induced obesity and gut dysbiosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonica (rock pine) has been used as a folk remedy to treat inflammation, hepatitis, and cancer in East Asia. AIM OF THE STUDY: The aim of this study was to investigate the effect of rock pine extract (RPE) on high-fat diet-induced obesity in mice and to examine its effects on gut dysbiosis. MATERIALS AND METHODS: The characteristic compound of RPE, kaempferol-3-O-rutinoside, was quantified using high-performance liquid chromatography. The prebiotic potential of RPE was evaluated by assessing the prebiotic activity score obtained using four prebiotic strains and high-fat (HF)-induced obesity C57BL/6 mice model. Analysis included examining the lipid metabolism and inflammatory proteins and evaluating the changes in gut permeability and metabolites to elucidate the potential signaling pathways involved. RESULTS: In vitro, RPE enhanced the proliferation of beneficial probiotic strains, including Lactiplantibacillus and Bifidobacterium. HF-induced model showed that the administration of 100 mg/kg/day of RPE for 8 weeks significantly (p < 0.05) reduced the body weight, serum lipid levels, and insulin resistance, which were associated with notable changes in lipid metabolism and inflammation-related markers. CONCLUSIONS: Our results demonstrate that rock pine consumption could mitigate obesity and metabolic endotoxemia in HF-fed mice through enhancing intestinal environment.

LC-QTOF/MS-Based Profiling of the Phytochemicals in Ice Plant (Mesembryanthemum crystallinum) and Their Bioactivities.

Recent assessments of the correlations between food and medicine underscore the importance of functional foods in disease prevention and management. Functional foods offer health benefits beyond basic nutrition, with fresh fruits and vegetables being particularly prominent because of their rich polyphenol content. In this study, we elucidated the phytochemicals in ice plant (Mesembryanthemum crystallinum), a globally consumed vegetable, using an LC-QTOF/MS-based untargeted detection method. The phytochemicals were clustered based on their structural similarity using molecular networking and annotated using the in silico tool for network annotation propagation. To identify the bioactive compounds, eight compounds were isolated from ice plant extracts. These compounds were identified using extensive spectroscopic methods, including 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Additionally, we evaluated the antioxidant and anti-inflammatory activities of all the isolates. Among the tested compounds, three showed antioxidant activity and all eight showed anti-inflammatory activity, demonstrating the potential of ice plant as a functional food.

Acer tegmentosum extract-mediated silver nanoparticles loaded chitosan/alginic acid scaffolds enhance healing of E. coli-infected wounds.

This work developed Acer tegmentosum extract-mediated silver nanoparticles (AgNPs) loaded chitosan (CS)/alginic acid (AL) scaffolds (CS/AL-AgNPs) to enhance the healing of E. coli-infected wounds. The SEM-EDS and XRD results revealed the successful formation of the CS/AL-AgNPs. FTIR analysis evidenced that the anionic group of AL (-COO-) and cationic amine groups of CS (-NH3+) were ionically crosslinked to form scaffold (CS/AL). The CS/AL-AgNPs exhibited significant antimicrobial activity against both Gram-positive (G+) and Gram-negative (G-) bacterial pathogens, while being non-toxic to red blood cells (RBCs), the hen's egg chorioallantoic membrane (HET-CAM), and a non-cancerous cell line (NIH3T3). Treatment with CS/AL-AgNPs significantly accelerated the healing of E. coli-infected wounds by regulating the collagen deposition and blood parameters as evidenced by in vivo experiments. Overall, these findings suggest that CS/AL-AgNPs are promising for the treatment of infected wounds.

Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes.

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.

Isobavachalcone attenuates myotube atrophy induced by TNF-α through muscle atrophy F-box signaling and the nuclear factor erythroid 2-related factor 2 cascade.

Skeletal muscle atrophy is a condition characterized by damaged muscle fibers and reduced numbers of muscle cells due to various causes. Muscle atrophy is associated with chronic diseases, such as heart failure, diabetes, and aging-related diseases. Isobavachalcone (IBC) is a flavonoid found in various foods and natural products, and studies have investigated its diverse effects, including its neuroprotective and anticancer effects. However, no studies have evaluated the effects of IBC on muscle atrophy. Thus, in this study, we assessed the effects of IBC on prevention of muscle atrophy. To evaluate the preventive effects of IBC on muscle atrophy, we used C2C12 myoblasts and induced muscle atrophy by tumor necrosis factor (TNF)-α. IBC regulated the expression levels of muscle atrophy F-box and muscle RING finger-1 in response to damaged muscle cells, thereby restoring the expression of myosin heavy chain and myogenin. Moreover, IBC regulated the phosphorylation of the nuclear factor-κB and p38 and upregulated the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1, which are involved in regulating oxidative stress. Our results indicated that IBC acted to relieve TNF-α-induced skeletal muscle atrophy by regulating the factors related to inflammation and oxidative stress.

Resveratrol analog, N-(4-methoxyphenyl)-3,5-dimethoxybenzamide induces G2/M phase cell cycle arrest and apoptosis in HeLa human cervical cancer cells.

In this study, several resveratrol analogs were synthesized and evaluated in search of a more effective anti-proliferative resveratrol analog. Among the evaluated resveratrol analogs, we have identified N-(4-methoxyphenyl)-3,5-dimethoxybenamide (MPDB) as a potent anti-proliferative compound. Treatment with MPDB resulted in G2/M phase cell cycle arrest, which was accompanied by alteration of G2/M-related protein expression and phosphorylation. MPDB-induced G2/M arrest was blocked by transfection of ATM/ATR siRNAs, indicating the critical role of ATM/ATR in G2/M phase arrest. In addition, treatment with MPDB displayed the activation of caspase and decreased Bcl-xl protein expression after 20 h in HeLa cells. Moreover, MPDB increased cytosolic cytochrome c release and Fas and Fas-L protein expression, indicating intrinsic and extrinsic apoptosis pathway, respectively. These results suggest that MPDB is a new and potent compound that induces ATM/ATR-dependent G2/M phase cell cycle arrest and apoptosis, implicating it as a putative candidate in the investment of cervical cancer therapy.

Panaxydol Derived from Panax ginseng Inhibits G1 Cell Cycle Progression in Non-small Cell Lung Cancer via Upregulation of Intracellular Ca2+ Levels.

Panaxydol, a polyacetylenic compound derived from Panax ginseng has been reported to suppress the growth of cancer cells. However, the molecular mechanisms underlying cell cycle arrest by this compound in non-small cell lung cancer (NSCLC) are unknown. Our study found that panaxydol treatment induced cell cycle arrest at G1 phase in NSCLC cells. The cell cycle arrest was accompanied by down-regulation of the protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E, and decrease in the phosphorylation of retinoblastoma (Rb) protein. Furthermore, up-regulation of cyclin-dependent kinase inhibitor (CDKI) p21CIP1/WAF1 and p27KIP1 was observed in panaxydol-treated NSCLC cells. In addition, panaxydol also induced accumulation of intracellular Ca2+ ([Ca2+]i). (Acetyloxy)methyl 2-({2-[(acetyloxy)methoxy]-2-oxoethyl}[2-(2-{2-[bis({2-[(acetyloxy)methoxy]-2-oxoethyl})amino]phenoxy}ethoxy)phenyl]amino)acetate (BAPTA-AM), the Ca2+ chelator, attenuated not only panaxydol-induced accumulation of [Ca2+]i, but also G1 cell cycle arrest and decrease of CDK6 and cyclin D1 protein expression level. These results demonstrated that the anti-proliferative effects of panaxydol were caused by cell cycle arrest, which is closely linked to the up-regulation of [Ca2+]i and represents a promising approach for the treatment of lung cancer.

Compound K induced apoptosis via endoplasmic reticulum Ca2+ release through ryanodine receptor in human lung cancer cells.

BACKGROUND: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. METHODS: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. RESULTS: Compound K-induced ER stress was confirmed through increased phosphorylation of eIF2α and protein levels of GRP78/BiP, XBP-1S, and IRE1α in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular Ca2+ chelator) or dantrolene (an RyR channel antagonist). These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12) partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor) dramatically improved the compound K-induced apoptosis. CONCLUSION: Cell survival and intracellular Ca2+ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway.

Dammarane-type triterpene ginsenoside-Rg18 inhibits human non-small cell lung cancer A549 cell proliferation via G1 phase arrest.

A previous study reported that a novel dammarane-type triterpene saponin, ginsenoside-Rg18, derived from the root of Panax ginseng, displayed hydroxyl radical scavenging, anti-bacterial and cytotoxic activities. However, the underlying molecular mechanisms of its anti-proliferative effect on non-small cell lung cancer (NSCLC) A549 cells remains unclear. In the present study, it was determined that Rg18 inhibited the proliferation of A549 cells with a half-maximal inhibitory concentration of 150 µM. Flow cytometry analysis indicated that cell cycle progression was blocked by Rg18 at G1 phase in A549 cells, which was accompanied by downregulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, cyclin D2, cyclin E and phosphorylated retinoblastoma protein expression at the protein level. In addition, the CDK inhibitors (CDKNs), CDKN1A and CDKN1B, were upregulated following Rg18 treatment. Furthermore, Rg18 treatment resulted in the intracellular accumulation of reactive oxygen species (ROS), and a dose-dependent inhibition of p38 mitogen activated protein kinase (p38), c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB)/p65 phosphorylation. Taken together, Rg18-mediated G1 phase arrest was closely associated with the generation of intracellular ROS, and p38, JNK and NF-κB/p65 inhibition in A549 human NSCLC cells.

Quality and characteristics of fermented ginseng seed oil based on bacterial strain and extraction method.

BACKGROUND: In this study, the fermentation of ginseng seeds was hypothesized to produce useful physiologically-active substances, similar to that observed for fermented ginseng root. Ginseng seed was fermented using Bacillus, Pediococcus, and Lactobacillus strains to extract ginseng seed oil, and the extraction yield, color, and quantity of phenolic compounds, fatty acids, and phytosterol were then analyzed. METHODS: The ginseng seed was fermented inoculating 1% of each strain on sterilized ginseng seeds and incubating the seeds at 30°C for 24 h. Oil was extracted from the fermented ginseng seeds using compression extraction, solvent extraction, and supercritical fluid extraction. RESULTS AND CONCLUSION: The color of the fermented ginseng seed oil did not differ greatly according to the fermentation or extraction method. The highest phenolic compound content recovered with the use of supercritical fluid extraction combined with fermentation using the Bacillus subtilis Korea Food Research Institute (KFRI) 1127 strain. The fatty acid composition did not differ greatly according to fermentation strain and extraction method. The phytosterol content of ginseng seed oil fermented with Bacillus subtilis KFRI 1127 and extracted using the supercritical fluid method was highest at 983.58 mg/100 g. Therefore, our results suggested that the ginseng seed oil fermented with Bacillus subtilis KFRI 1127 and extracted using the supercritical fluid method can yield a higher content of bioactive ingredients, such as phenolics, and phytosterols, without impacting the color or fatty acid composition of the product.

Resveratrol analogue (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline induces apoptosis via Fas-mediated pathway in HL-60 human leukemia cells.

Previously, we reported that (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline (8-ADEQ), a synthetic analogue of resveratrol had anti-inflammatory and G2/M cell cycle arrest activities, but the underlying molecular mechanism of cytotoxic effects of this compound was not determined. In this study, 8-ADEQ displayed potent cytotoxicity and triggered apoptosis in HL-60 cells as evidenced by DNA fragmentation, DNA ladder formation, and the externalization of Annexin V-targeted phosphatidylserine residues in HL-60 cells. In addition, 8-ADEQ triggered activation of caspases-8, -9, -6 and -3 and cleavage of their substrates such as poly(ADP-ribose) polymerase (PARP). Moreover, 8-ADEQ induced loss of mitochondrial membrane potential (MMP) and release of cytochrome c to the cytosol. Caspase-3 inhibitor (z-DEVD-fmk), caspase-8 inhibitor (z-IETD-fmk), caspase-9 inhibitor (z-LEHD), and broad caspase inhibitor (z-VAD­fmk) significantly suppressed the 8-ADEQ-induced DNA fragmentation. Interestingly, pretreatment with z-IETD-fmk, a caspase-8 inhibitor, completely abolished 8-ADEQ-induced caspase-3 and -9 activation, and subsequent DNA fragmentation. 8-ADEQ also increased the expression of Fas, Fas-associated death domain (FADD) and FasL, and formation of death-inducing signaling complex (DISC). Further analysis revealed that 8-ADEQ-induced apoptosis was mediated by upregulation of reactive oxidative species (ROS) generation. Taken together, our data indicated that 8-ADEQ-stimulated apoptosis in HL-60 leukemia cells is due to a Fas-mediated caspase-8-dependent pathway via ROS generation, but also, to a lesser extent cytochrome c release and caspase-9 activation.

Neochlorogenic Acid Inhibits Lipopolysaccharide-Induced Activation and Pro-inflammatory Responses in BV2 Microglial Cells.

Microglia is the resident innate immune cells that sense pathogens and tissue injury in the central nervous system. Microglia becomes activated in response to injury, infection, and other stimuli that threaten neuronal survival. Microglia activation plays an important role in neurodegenerative diseases. Neochlorogenic acid (NCA) is a natural polyphenolic compound found in dried fruits and other plants. Although previous studies have shown that phenolic acids including NCA have outstanding antioxidant, antibacterial, antiviral, and antipyretic activities, there has not yet been investigated for anti-inflammatory effects. Therefore, for the first time we have examined the potential of NCA to inhibit microglial activation and pro-inflammatory responses in the brain. We found that lipopolysaccharide-induced inducible nitric oxide synthase, and cyclooxygenase-2 expression, and nitric oxide formation was suppressed by NCA in a dose-dependent manner in BV2 microglia. NCA also inhibited the production of pro-inflammatory mediators, tumor necrosis factor-α and interleukin-1 beta. Furthermore, phosphorylated nuclear factor-kappa B p65 and p38 mitogen-activated protein kinase activation were blocked by NCA. Taken together, these results suggest that NCA exerts neuroprotective effects through the inhibition of pro-inflammatory pathways in activated microglia.

Quality and characteristics of ginseng seed oil treated using different extraction methods.

Ginseng seed oil was prepared using compressed, solvent, and supercritical fluid extraction methods of ginseng seeds, and the extraction yield, color, phenolic compounds, fatty acid contents, and phytosterol contents of the ginseng seed oil were analyzed. Yields were different depending on the roasting pretreatment and extraction method. Among the extraction methods, the yield of ginseng seed oil from supercritical fluid extraction under the conditions of 500 bar and 65℃ was the highest, at 17.48%. Color was not different based on the extraction method, but the b-value increased as the roasting time for compression extraction was increased. The b-values of ginseng seed oil following supercritical fluid extraction were 3.54 to 15.6 and those following compression extraction after roasting treatment at 200℃ for 30 min, were 20.49, which was the highest value. The result of the phenolic compounds composition showed the presence of gentisic acid, vanillic acid, ferulic acid, and cinnamic acid in the ginseng seed oil. No differences were detected in phenolic acid levels in ginseng seed oil extracted by compression extraction or solvent extraction, but vanillic acid tended to decrease as extraction pressure and temperature were increased for seed oil extracted by a supercritical fluid extraction method. The fatty acid composition of ginseng seed oil was not different based on the extraction method, and unsaturated fatty acids were >90% of all fatty acids, among which, oleic acid was the highest at 80%. Phytosterol analysis showed that ß-sitosterol and stigmasterol were detected. The phytosterol content of ginseng seed oil following supercritical fluid extraction was 100.4 to 135.5 mg/100 g, and the phytosterol content following compression extraction and solvent extraction was 71.8 to 80.9 mg/100 g.

Resveratrol analog 4-[2-(3,5-dimethoxyphenyl)vinyl]pyridine reduces differentiation of the 3T3-L1 adipocyte.

CONTEXT: Resveratrol (3,5,4'-trihydroxystilbene) is a phytoalexin synthesized by plants, most notably grapes, against microbial invasion or ultraviolet stimulation, and is known to exert antioxidant, anticancer, and antiobesity effects. OBJECTIVE: This study was conducted to find resveratrol derivatives with higher anti-obesity activity compared to resveratrol and to verify their mechanism of action. MATERIALS AND METHODS: The inhibitory effect of resveratrol and its derivatives on adipocyte differentiation in 3T3-L1 cells was studied using Oil Red O staining, and the effects on the intracellular expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured via Western blot analysis. RESULTS: A derivative of resveratrol, 4-[2-(3,5-dimethoxyphenyl)vinyl]pyridine (DPVP), exerted inhibitory effects against 3T3-L1 adipocyte differentiation (IC(50) = 13.5 µM) and FAS expression. Notably, it displayed higher activity at concentrations lower than 25 µM compared to resveratrol. DISCUSSION AND CONCLUSION: DPVP is considered to have greater potential as an anti-obesity substance, as it exhibits excellent activity at low concentrations compared to resveratrol.

3-[2-(3,5-Dimethoxyphenyl)vinyl]furan protects hippocampal neurons against ischemic damage.

Resveratrol, an ingredient in grapes, has been reported to exhibit anti-cancer activity, anti-inflammatory activity, and cardiovascular protection property. Interestingly, resveratrol has been recently reported to have neuroprotective effect. This study reports the neuroprotective effect of a resveratrol derivative, 3-[2-(3,5-dimethoxyphenyl)vinyl]furan (DPVF). This synthetic DPVF conferred more protection than resveratrol against neuronal cell damage induced by oxygen and glucose deprivation in a rat hippocampal slice culture. In addition, DPVF inhibited ATP depletion following oxygen and glucose deprivation in the adult hippocampal slice. Moreover, we found that DPVF is neuroprotective against ischemic damage in rats. DPVF showed potent neuroprotection on a 4-velssel-occusion model and inhibited iron-induced malondialdehyde (MDA) formation in the rat brain tissue. These results demonstrate that DPVF might be a useful agent in reducing ischemic neuronal damage.

Isolation and anti-inflammatory activity of Bakuchiol from Ulmus davidiana var. japonica.

The bark of the root and stem of Ulmus davidiana var. japonica has been used as a traditional Korean medicine to treat inflammatory disorders. This plant reportedly exhibits antioxidant, anticancer, and anti-inflammatory effects. A search for biologically active compounds in U. davidiana var. japonica extracts yielded bakuchiol, which we structurally identified on the basis of spectral data, including two-dimensional nuclear magnetic resonance spectroscopy and distortionless enhancement by polarization transfer. In our study, bakuchiol (50 microM) inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production in RAW 264.7 macrophages by 53.7% and 84.2%, respectively. These results suggested that bakuchiol is one of the potent anti-inflammatory components of U. davidiana var. japonica.

Virulence attenuation of Streptococcus pneumoniae clpP mutant by sensitivity to oxidative stress in macrophages via an NO-mediated pathway.

ClpP protease is essential for virulence and survival under stress conditions in several pathogenic bacteria. The clpP mutation in a murine infection model has demonstrated both attenuation of virulence and a sensitivity to hydrogen peroxide. However, the underlying mechanisms for these changes have not been resolved. Because macrophages play a major role in immune response and activated macrophages can kill microbes via oxygen-dependant mechanisms, we investigated the effect of the clpP mutation on its sensitivity to macrophage-mediated oxygen-dependant mechanisms. The clpP mutant derived from D39 (serotype 2) exhibited a higher sensitivity to oxidative stresses such as reactive oxygen intermediates, reactive nitrogen intermediates, and H(2)O(2), but no sensitivity to osmotic stress (NaCl) and pH. Moreover, viability of the clpP mutant was significantly increased in murine macrophage cells by treatment with S-methylisothiourea sulfate, which inhibits inducible nitric oxide synthase (iNOS) activity and subsequently elicits lower level secretions of nitric oxide (NO). However, viability of wild type was unchanged. Taken together, these results indicate that ClpP is involved in the resistance to oxidative stresses after entrapment by macrophages and subsequently contributes to virulence via NO mediated pathway.

Ginsenoside rb1 and rg3 attenuate glucocorticoid-induced neurotoxicity.

Glucocorticoid (GC) hormones, increased in response to stress, can cause neuronal loss. We tested the effect of GC hormone on cell viability of neural SHSY-5Y cells and protective effects of ginsenoside Rb1 and Rg3 on the action of GC. We treated SHSY-5Y cells with increasing concentrations of synthetic GC dexamethasone (DEX; 10, 25, 50, and 100 nM) for 24 and 48 h, and then determined cell viability by using MTT assay. We then treated SHSY-5Y cells with DEX (100 nM) with or without the ginsenosides to examine their preventive effects on the cytotoxicity. To explore the underlying molecular mechanisms, we measured mRNA expression of bax and bcl-2 by using reverse transcriptase real-time PCR. SHSY-5Y cells treated with DEX significantly reduced cell viability as compared with control cells. In the presence of Rb1 or Rg3, DEX-induced cytotoxicity was effectively blocked. DEX considerably increased pro-apoptotic bax mRNA expression as compared with control cells. However, Rb1 and Rg3 completely blocked DEX-mediated up-regulation of bax expression. DEX significantly increased neuronal death in organotypic hippocampal slice cultures of rat brain with enhanced generation of ROS, which was effectively inhibited by ginsenoside Rb1 and Rg3. This suggests a potential role of the ginsenosides to target GC action in the brain.

Inhibitory effect of (E)-1,2-di(3,5-dimethoxyphenyl)ethene on 3T3-L1 adiopocyte differentiation.

Resveratrol (trans-3,5,4'-trihydroxystilbene) is a phytoalexin found in diverse plant species, including grapes and peanuts. The antioxidant, anticancer, and cardioprotective properties of resveratrol have been well-characterized. The anti-obesity effect of resveratrol has also been demonstrated in previous studies. In this study, we evaluated the effects of a resveratrol analogue, (E)-1,2-di(3,5-dimethoxyphenyl)ethene, on adipocyte differentiation using 3T3-L1 cells. According to our results, the tested analogue potently inhibits the differentiation of 3T3-L1 adipocyte to a greater degree than resveratrol. Moreover, (E)-1,2-di(3,5-dimethoxyphenyl)ethene strongly downregulated the expression of fatty acid metabolism-related proteins such as fatty acid synthase and acetyl-CoA carboxylase. These results point to the potential of (E)-1,2-di(3,5-dimethoxyphenyl)ethene as an obesity prevention agent.

Inhibitory effects of cinnamic acid on melanin biosynthesis in skin.

Cinnamic acid is a wildly distributed phenylpropanoid component naturally occurring in plants, and is mainly found in Cinnamomum cassia BLUME and Panax ginseng. Cinnamic acid was recently reported to exert a tyrosinase inhibitory effect. However, research on melanocytes and animal bodies was not reported until now. In this study, we examined the effects of cinnamic acid on melanin biosynthesis within the melanocytes and brown guinea pigs. Melan-a cells were used to examine the effects of cinnamic acid in the melanocytes. Treatment with 100 ppm of cinnamic acid resulted in a significant reduction of melanin production in the melan-a cells at 29.0%. This compound also exhibited a potent inhibitory effect on tyrosinase activity and reduced tyrosinase expression in the melan-a cells. Moreover, cinnamic acid exhibited depigmenting activity on the UV-B-induced hyperpigmentation of brown guinea pig skin. Our results suggest that cinnamic acid might act as a skin whitening agent via inhibition of tyrosinase activity and expression within melanocytes.