Recent Progress in Multifunctional Stimuli-Responsive Combinational Drug Delivery Systems for the Treatment of Biofilm-Forming Bacterial Infections.

Drug-resistant infectious diseases pose a substantial challenge and threat to medical regimens. While adaptive laboratory evolution provides foresight for encountering such situations, it has inherent limitations. Novel drug delivery systems (DDSs) have garnered attention for overcoming these hurdles. Multi-stimuli responsive DDSs are particularly effective due to their reduced background leakage and targeted drug delivery to specific host sites for pathogen elimination. Bacterial infections create an acidic state in the microenvironment (pH: 5.0-5.5), which differs from normal physiological conditions (pH: 7.4). Infected areas are characterized by the overexpression of hyaluronidase, gelatinase, phospholipase, and other virulence factors. Consequently, several effective stimuli-responsive DDSs have been developed to target bacterial pathogens. Additionally, biofilms, structured communities of bacteria encased in a self-produced polymeric matrix, pose a significant challenge by conferring resistance to conventional antimicrobial treatments. Recent advancements in nano-drug delivery systems (nDDSs) show promise in enhancing antimicrobial efficacy by improving drug absorption and targeting within the biofilm matrix. nDDSs can deliver antimicrobials directly to the biofilm, facilitating more effective eradication of these resilient bacterial communities. Herein, this review examines challenges in DDS development, focusing on enhancing antibacterial activity and eradicating biofilms without adverse effects. Furthermore, advances in immune system modulation and photothermal therapy are discussed as future directions for the treatment of bacterial diseases.

Hepatoprotective Lignan Glycosides from the Leaves and Stems of Symplocos cochinchinensis (Lour.) S. Moore.

This study investigates Symplocos cochinchinensis (Lour.) S. Moore leaves and stems, commonly known as Symplocos, a plant indigenous to Asia renowned for its traditional use in holistic medicine. A comprehensive phytochemical analysis of S. cochinchinensis led to the isolation of two new lignans, namely symplolignans A and B (1 and 2) along with eleven known lignan glucosides: nortrachelogenin 4-O-ß-D-glucopyranoside (3), nortracheloside (4), matairesinol 4-O-ß-D-glucopyranoside (5), lariciresinol 4'-O-ß-D-glucopyranoside (6), balanophonin 4-O-ß-D-glucopyranoside (7), dehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside (8), dehydrodiconiferyl alcohol γ'-O-ß-D-glucopyranoside (9), 3-(ß-D-glucopyranosyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-(2R,3S)-dihydrobenzofura (10), and pinoresinol 4'-O-ß-D-glucopyranoside (11). Their chemical structures were elucidated using 1D- and 2D-NMR, mass spectrometry, and their spectroscopic data were compared with those reported in literatures. Furthermore, all compounds were evaluated for their hepatoprotective effects using the Resazurin reduction assay in HepG2 hepatocellular carcinoma cells. Compounds 1, 5, 7, and 8 exhibited notable hepatoprotective efficacy, with cell viability ranging from 105.0±2.6 to 109.2±3.3 at a concentration of 10 µM. This research highlights the therapeutic potential of these compounds and enhanced to the understanding of lignans and neolignans in liver cell proliferation.

Cytotoxic Effects of Oleanane-type Saponins from Lysimachia laxa.

Phytochemical investigation of the methanol extract of the aerial parts of Lysimachia laxa led to the isolation of four new oleanane-type saponins, lysimosides A-D (1-4) and one known compound, lysimachigenoside B (5). Their structures were elucidated using a combination of HR-ESI-MS, 1D and 2D-NMR spectral data, chemical methods, and comparison with previous literature. The cytotoxic activity of these compounds was evaluated against human lung cancer (A-549) and human breast cancer (MCF-7) cell lines. All compounds exhibited cytotoxic activity against A-549 and MCF-7 cell lines with IC50 values ranging from 6.1 to 16.0 µM, comparable to the positive control, mitoxantrone. Interestingly, oleanane-type saponins with an acetyl group (2-4) exhibited increased cytotoxic activities compared to those without an acetyl group (1).

Oleanane-type saponins from Lysimachia laxa Baudo and their antibacterial activities.

Seven new oleanane-type triterpene saponins, lysimaponins A-G, were isolated from aerial parts of Lysimachia laxa Baudo. Their chemical structures have been elucidated by analysis of spectroscopic and chemical methods. All compounds were evaluated for their antibacterial effects against Microcystis aeruginosa, Vibrio parahaemolyticus, V. harveyi, V. vulinificus, V. cholerae, and V. alginolyticus. All compounds showed potent antibacterial activities against the cyanobacteria M. aeruginosa with IC50 values ranging from 14.4 ± 1.2 to 35.3 ± 2.2 µg/mL. Compounds 1, 2, 4-7 inhibited V. parahaemolyticus with MIC values ranging from 64 to 256 µg/mL. The results suggested that saponins from L. laxa could be potential anti-cyanobacteria agents.

Symplosaponins A-D: New acylated oleanane-type triterpene saponins from Symplocos cochinchinensis and their hepatoprotective effect.

Four new acylated oleanane-type triterpene saponins, symplosaponins A-D (1-4) were successfully isolated from the leaves of Symplocos cochinchinensis (Lour.) S. Moore, alongside with five known compounds (5-9), 2-methoxy-4-prop-1-enylphenyl-1-O-ß-D-apiofuranosyl-(1 â†’ 6)-ß-D-glucopyranoside (5), and 1-[O-ß-d-xylopyranosyl-(1 â†’ 6)-O-ß-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6), 6-O-p-coumaroylsucrose (7), arillatose B (8), and (-)-secoisolariciresinol-O-ß-D-glucopyranoside (9). The structures of these compounds were elucidated through spectroscopic methods, comparison with existing data, and chemical methods. Furthermore, all compounds were assessed for their impact on hepatocellular viability using the Resazurin reduction assay. These investigations aimed to explore the potential hepatoprotective properties of isolated compounds. As a result, 1-[O-ß-d-xylopyranosyl-(1 â†’ 6)-O-ß-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6) and (-)-secoisolariciresinol-O-ß-D-glucopyranoside (9) demonstrated statistically significant hepatoprotective activity in a concentration-dependent manner.

Bithiophene and coumestan derivatives from Eclipta prostrata (L.) L. and their hepatoprotective activity.

One new bithiophene derivative, 5-(but-3-en-1-yn-1-yl)-5'-(methoxymethyl)-2,2'-bithiophene (1), along with twelve known compounds, senecioester (2), tiglinsaureester (3), 5-acetoxymethyl-2'-(but-3-en-1-yn-1-yl)-2,5'-bithiophene (4), 5-(4-isovaleroyloxybut-1-ynyl)-2,2'-bithiophene (5), 5-hydroxymethyl-(2,5':2',5'')-terthienyl tiglate (6), 5-hydroxymethyl-(2,5':2',5'')-terthienyl agelate (7), 5- hydroxymethyl-2,5':2',5''-terthiophene dimethylacrylate (8), 5-methoxymethyl-2,2':5',2''-terthiophene (9), α-terthiophene (10), 1,3,8,9-tetrahydroxycoumestan 3-sulfate (11), demethylwedelolactone (12), and wedelolactone (13) were isolated from the methanol extract of aerial parts of Eclipta prostrata (L.) L. All isolated compounds were evaluated for the protective ability on the HepG2 cells. At the concentration of 100 µM, compounds 11-13 showed the highest hepatoprotective effects, with HepG2 cell viability ranging from 38.68% to 48.54%. Bithiophenes showed higher hepatoprotective cell viability than terthiophenes.

Discovery of a novel natural compound, vitekwangin B, with ANO1 protein reduction properties and anticancer potential.

Background: Prostate cancer and non-small cell lung cancer (NSCLC) present significant challenges in the development of effective therapeutic strategies. Hormone therapies for prostate cancer target androgen receptors and prostate-specific antigen markers. However, treatment options for prostatic small-cell neuroendocrine carcinoma are limited. NSCLC, on the other hand, is primarily treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors but exhibits resistance. This study explored a novel therapeutic approach by investigating the potential anticancer properties of vitekwangin B, a natural compound derived from Vitex trifolia. Methods: Vitekwangin B was chromatographically isolated from the fruits of V. trifolia. ANO1 protein levels in prostate cancer and NSCLC cells were verified and evaluated again after vitekwangin B treatment. Results: Vitekwangin B did not inhibit anoctamin1 (ANO1) channel function but significantly reduced ANO1 protein levels. These results demonstrate that vitekwangin B effectively inhibited cancer cell viability and induced apoptosis in prostate cancer and NSCLC cells. Moreover, it exhibited minimal toxicity to liver cells and did not affect hERG channel activity, making it a promising candidate for further development as an anticancer drug. Conclusion: Vitekwangin B may offer a new direction for cancer therapy by targeting ANO1 protein, potentially improving treatment outcomes in patients with prostate cancer and NSCLC. Further research is needed to explore its full potential and overcome existing drug resistance challenges.

Rheological properties, biochemical changes, and potential health benefits of dehulled and defatted industrial hempseeds after fermentation.

Dehulled hempseed (DHS), fermented dehulled hempseed (FDHS), hempseed cake (HSC), and fermented HSC (FHSC) were examined for their phytochemical composition, health benefits, and rheological characteristics. At 500 µg/mL concentration, DHS, FDHS, HSC, and FHSC extracts exhibited the ability to inhibit DPPH radicals, with 32.46 %, 47.35 %, 33.85 %, and 47.41 %, respectively. Similarly, they demonstrated potential to scavenge ABTS radicals by 13.7 %, 27.87 %, 14.40 % and 25.70 %, respectively. For lipase inhibition activity, FDHS (72.92 %) and FDHS (85.89 %) outperformed DHS (52.94 %) and HSC (43.08 %). Furthermore, FHSC enhanced the survival and reduced fat accumulation in glucose-supplemented Caenorhabditis elegans. We used HPLC and UHPLC-ESI-QTOF-MS for metabolite analysis, quantifying eight polyphenols using HPLC and identifying thirty-four metabolites with UHPLC-ESI-QTOF-MS. Generally, metabolomics indicated an improved metabolite profile after fermentation. Fermentation also showed impact on rheological characteristics, modifying viscosity, loss modulus, and storage modulus. These findings collectively demonstrate the ability of fermentation in enhancing overall value of hempseed.

Cellular metabolism and health impacts of dichlorvos: Occurrence, detection, prevention, and remedial strategies-A review.

Dichlorvos (2,2-Dichlorovinyl dimethyl phosphate, [DDVP]) belongs to the class of organophosphates and is widely used as an insecticide in agriculture farming and post-harvest storage units. Extensive research has been conducted to assess the factors responsible for the presence of DDVP in terrestrial and aquatic ecosystems, as well as the entire food chain. Numerous studies have demonstrated the presence of DDVP metabolites in the food chain and their toxicity to mammals. These studies emphasize that both immediate and chronic exposure to DDVP can disrupt the host's homeostasis, leading to multi-organ damage. Furthermore, as a potent carcinogen, DDVP can harm aquatic systems. Therefore, understanding the contamination of DDVP and its toxicological effects on both plants and mammals is vital for minimizing potential risks and enhancing safety in the future. This review aimed to comprehensively consolidate information about the distribution, ecological effects, and health impacts of DDVP, as well as its metabolism, detection, prevention, and remediation strategies. In summary, this study observes the distribution of DDVP contaminations in vegetables and fruits, resulting in significant toxicity to humans. Although several detection and bioremediation strategies are emerging, the improper application of DDVP and the alarming level of DDVP contamination in foods lead to human toxicity that requires attention.

Aloe-Emodin Isolated from Rheum Undulatum L. Regulates Cell Cycle Distribution and Cellular Senescence in Human Prostate Cancer LNCaP Cells.

Senescence can promote hyperplastic pathologies, such as cancer. Prostate cancer is the second most common type of cancer in men. The p21-mediate cellular senescence, facilitated through the tumor suppressor p53-dependent pathway, is considered the primary mechanism for cancer treatment. Aloe-emodin, has been reported to exert anticancer effects in various types of cancers. This study aimed to investigate the bioactivity of aloe-emodin in LNCaP cells via the activation of p21-mediated cellular senescence. Aloe-emodin treatment increased the percentage of cells in the G1 phase while decreasing the percentage in the S phase. This effect was reflected in the expression levels of proteins associated with cell cycle progression, such as p21CIP, retinoblastoma protein, and cyclin-dependent kinase2/4 in LNCaP cells. However, aloe-emodin-treated LNCaP cells did not induce cell cycle arrest at G2/M checkpoint. Moreover, increased senescence-associated-galactosidase activity was observed in a dose-dependent manner following treatment with aloe-emodin. Aloe-emodin also induced DNA damage by modulating the expression of histone H2AX and lamin B1. Furthermore, aloe-emodin inhibited the proliferation of LNCaP cells, contrasting with the exponential growth observed in the nontreated cells. Importantly, this inhibition did not impact the immune system, as evidenced by the increased proliferation of splenocytes isolated from mice. These findings provide preliminary evidence of the anticancer effect of aloe-emodin in LNCaP cells, necessitating further investigations into the underlying mechanisms in vivo and human subjects.

Fucoidan-coated cotton dressing functionalized with biomolecules capped silver nanoparticles (LB-Ag NPs-FN-OCG) for rapid healing therapy of infected wounds.

The colonization of pathogenic microbes poses a significant clinical barrier that hinders the physiological wound-healing process. Addressing this challenge, we developed a novel wound dressing using a modified cotton gauze dressing coated with fucoidan and functionalized with silver nanoparticles (LB-Ag NPs-FN-OCG) for the rapid treatment of infected wounds. Firstly, phytochemical-capped LB-Ag NPs were synthesized and characterized using high performance liquid chromatography (HPLC), transmission electron microscopy (TEM), and zeta potential analysis. Secondly, different concentrations of LB-Ag NPs (0.1%-1%) were functionalized into FN-OCG to identify appropriate concentrations that were non-toxic with superior antibacterial activities. Screening assays, including antibacterial, hemolysis, chick chorioallantoic membrane (CAM) assay, and cytotoxicity assay, revealed that LB-Ag NPs (0.5%)-FN-OCG were non-toxic and demonstrated greater efficiency in inhibiting bacterial pathogens (Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Listeria monocytogenes) and promoting fibroblast cell (NIH3T3) migration. In vivo assays revealed that LB-Ag NPs (0.5%)-FN-OCG treatment exhibited excellent wound healing activity (99.73 ± 0.01%) compared to other treatments by inhibiting bacterial colonization, maintaining the blood parameters, developing granulation tissue, new blood vessels, and collagen deposition. Overall, this study highlights that LB-Ag NPs (0.5%)-FN-OCG serve as a antibacterial wound dressing for infected wound healing applications.

Moracin E and M isolated from Morus alba Linné induced the skeletal muscle cell proliferation via PI3K-Akt-mTOR signaling pathway.

Twigs of Morus alba have been used in traditional medicine to treat muscle-related symptoms such as aches, numbness, and stiffness. Despite its clinical use in traditional medicine, its active compounds and mode of action have not yet been investigated. Therefore, we aimed to isolate the compounds from the twigs of M. alba and deduce active compounds, key gene targets, and mechanism of action against sarcopenia using network pharmacology analysis. Using various isolation techniques and spectroscopic methods, 43 phytochemicals, including 3 new flavonoids, were isolated and performed network pharmacology analysis. According to the computational-assistant analysis, 28 compounds, 9 genes, and the PI3K-Akt-mTOR signaling pathway were deduced as expected active compounds (EAC), key targets, and the main signaling pathway. To verify the predicted results, the cell proliferation activities of the EAC were evaluated. Especially, moracin E and M significantly increased by 130% (p < 0.001) and 57% (p < 0.05), respectively, which have more than 2- and 1.5-fold stronger effects compared to the control. Furthermore, both increased the expression level of proteins involved in the PI3K-Akt-mTOR signaling pathway and myogenic proteins, including myogenin and MyoD. This study demonstrated that moracin E and M exhibit cell proliferative effects on skeletal muscle cells through the PI3K-Akt-mTOR signaling pathway.

Three Undescribed Iridoid Derivatives Isolated from the Fruits of Vitex trifolia with Their Cytotoxic and Antimicrobial Activities.

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).

Impacts of germination and lactic acid bacteria fermentation on anti-nutrients, bioactive compounds, and selected functional properties of industrial hempseed (Cannabis sativa L.).

The impact of fermentation and germination on the metabolite profile and bioactive of 'Cheongsam' hempseed was investigated. The seeds were germinated for 3 days at 26 °C and fermented for 48 h at 37 °C using Pediococcus acidilactici (SRCM201591). The raw (R), fermented seed (RF), sprouts (S), and fermented sprouts (SF) extracts were assessed for anti-nutrients, metabolite profile, and selected bioactivities. Germination and fermentation significantly altered anti-nutrient levels (tannins, saponins, phytic acid, and trypsin inhibitors). They increased total polyphenols, flavonoid contents, and individual polyphenols and cannabinoids. SF demonstrated the highest ABTS (IC50, 291.65 µg/mL) and DPPH (IC50, 345.30 µg/mL) scavenging capacities. However, S (IC50, 73.295 µg/mL) was the most potent anti-inflammatory ingredient. SF (IC50, 74.07 µg/mL) exhibited the most potent alpha-glucosidase inhibition for enzyme inhibitions, while RF (IC50, 63.31 µg/mL) showed the best lipase inhibition potential. The findings demonstrate that germination and fermentation could improve the functional properties of hempseed.

ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers.

Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from Schisandra sphenanthera, known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent.

Phytochemical profiling, in vitro antioxidants, and antidiabetic efficacy of ethyl acetate fraction of Lespedeza cuneata on streptozotocin-induced diabetic rats.

In the recent past, phytomolecules are exponentially applied in discovering the antidiabetic drug due to less adverse effects. This work screened the active solvent fraction of Lespedeza cuneata based on the phytochemical, enzyme inhibition, and antioxidant properties. The antioxidant efficacy of the different fractions of the L. cuneata was assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing power, hydrogen peroxide, and hydroxyl radical scavenging assays. The digestive enzyme (α-amylase and α-glucosidase) inhibitory activity was also evaluated. The phytochemical composition of ethyl acetate fraction of L. cuneata (Lc-EAF) was studied by UHPLC-QTOF-MS/MS. The effect of Lc-EAF treatments on glucose uptake was studied in insulin resistance HepG2 cells (IR-HepG2). Further, the antidiabetic effect of Lc-EAF in streptozotocin (STZ)-induced diabetic mice were demonstrated. Ethyl acetate, hexane, and methanol fractions of the L. cuneata showed notable antioxidant, α-amylase, and α-glucosidase inhibitory properties. Among the fractions, Lc-EAF was found to be the most potent. The Lc-EAF exhibited an IC50 of 205.32 ± 23.47 µg/mL and 105.32 ± 13.93 µg/mL for α-amylase and α-glucosidase inhibition, respectively. In addition, 75 µg/mL of Lc-EAF exposure enhanced glucose uptake (68.23%) in IR-HepG2 cells. In vivo study indicated that treatment of Lc-EAF (100 mg/kg b.wt) maintained the blood glucose level through reduced insulin level while improving the lipid profile, hepatic, and renal markers. These findings suggest that Lc-EAF could be considered a prominent source for antidiabetic, anti-hyperlipidemic, and anti-ROS potentials.

Dermal Papilla Cell Proliferation of Phytochemicals Isolated from Chestnut Shells (Castanea crenata).

Castanea crenata (Fagaceae) is a species of chestnut tree that is endemic to the Republic of Korea and Japan. While its kernels are consumed, chestnut by-products such as shells and burs, which account for 10-15% of the total weight, are discarded as waste. Phytochemical and biological studies have been carried out to eliminate this waste and develop high-value products from its by-products. In this study, five new compounds (1-2, 6-8) along with seven known compounds were isolated from the shell of C. crenata. This is the first study to report diterpenes from the shell of C. crenata. Comprehensive spectroscopic data including 1D, 2D NMR, and CD spectroscopy were used to determine the compound structures. All isolated compounds were examined for their ability to stimulate dermal papilla cell proliferation using a CCK-8 assay. In particular, 6ß,7ß,16α,17-Tetrahydroxy-ent-kauranoic acid, isopentyl-α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranoside, and ellagic acid exhibited the most potent proliferation activity of all.

Isolation, Characterization, Antioxidant, and Wound Healing Activities of Extracellular Polysaccharide from Endophytic Fungus Talaromyces purpureogenus.

In this study, two extracellular polysaccharides (TEPS1 and TEPS2) were isolated from the endophytic fungus (Talaromyces purpureogenus) and purified by DEAE-Sepharose Fast Flow column using NaCl as gradient eluent. The HPLC analysis displayed that TEPS1 was composed of mannose (38.70%), ribose (25.02%), glucose (19.34%), and galactose (16.94%) while the TEPS2 composed by mannose (100%). The NMR results indicated that TEPS1 exhibited α-glycosidic configurations. The both polysaccharides, TEPS1 and TEPS2 were exhibited a good antioxidant activity in terms of DPPH, ABTS, and •OH scavenging. However, TEPS1 showed a higher antioxidant activity than TEPS2. The IC50 of TEPS1 were 32.16, 192.57, and 54.67 µg·mL-1, for DPPH, ABTS, and •OH radical scavenging, respectively. Furthermore, TEPS1 showed the high cellular antioxidant and wound healing activity in the human embryonic kidney (HEK293) cell line. Overall, these two polysaccharides were promising in antioxidant activity.

Anti-inflammatory activity of Echinosophora koreensis nakai root extract in lipopolysaccharides-stimulated RAW 264.7 cells and carrageenan-induced mouse paw edema model.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinosophora koreensis Nakai is an endemic plant species distributed in a limited area within the Korean province of Gangwon, including the Yanggu-gun, Inje-gun, Cheorwon-gun, Chuncheon-si, and Hongcheon-gun counties. It is used in traditional medicine to treat various disorders, such as fever, skin diseases, diuresis, and neuralgia. MATERIALS AND METHODS: This study demonstrated the effects of E. koreensis Nakai root extract (EKRE) on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Cell viability was assessed through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Nitric oxide (NO) production was measured using Griess reagent. Interleukin (IL)-6 and tumor necrosis factor (TNF) levels were assessed using enzyme-linked immunosorbent assays. Inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinase (MAPK) expression were assessed using Western blot analysis. To examine the effects of EKRE in vivo, it was administered orally at doses of 50 or 200 mg/kg for 3 days in mice. Edema in the paws was induced through λ-carrageenan injection and measured hourly for up to 5 h using calipers. RESULTS: EKRE markedly suppressed LPS-generated NO, IL-6, and iNOS production in RAW 264.7 cells. Moreover, it suppressed the activation of the NF-κB and MAPK in LPS-stimulated cells. Furthermore, EKRE significantly inhibited carrageenan-induced edema in mouse paws. There were no significant differences in IL-6 and TNF production in paw tissue harvested from mice, but levels decreased at high EKRE concentrations (200 mg/kg). CONCLUSION: The results of this study provided validation for EKRE-induced inhibition of inflammatory responses in vitro and in vivo. This research suggested that EKRE is a promising treatment for inflammatory disorders.

The chemical constituents from twigs of Hamamelis japonica and their antiviral activities.

Three new monoterpenoid glycosides (1-3) and one new flavanol (4) along with 15 known compounds were isolated from the twig of Hamamelis japonica Sieb. et Zucc. The chemical constituent study of the twig of H. japonica has performed for the first time in the present investigation. Their structures were determined based on extensive spectroscopic methods including 1 D and 2 D NMR and CD spectra data. All isolated compounds were tested for their antiviral activities against HRV1B-, EV71-, PR8- and CVB3-infected Vero cells. Among the tested compounds, (-)-epigallocatechin 3-O-gallate exhibited the most consistent and effective antiviral activities against EV71 and PR8 infections.