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Background: The cholinergic neuronal loss in the basal forebrain and increasing brain oxidative stress are one of the main features of the brain suffering from Alzheimer's disease. Marrubium vulgare (M. vulgare), commonly known as 'white horehound,' possesses a variety of valuable properties, such as antioxidative, anti-inflammatory, and antidiabetic activities. Moreover, it possesses neuromodulatory properties that could potentially impact short-term memory functions., Objective: The present study was undertaken to investigate the preventive effects of water M. vulgare extract on working memory, cholinergic neurotransmission, and oxidative stress in rats with scopolamine (Sco)-induced dementia., Methods: Male Wistar rats (200-250 g) were divided into four experimental groups. The plant extract was administered orally for 21 days, and Sco (2 mg/kg) was administered intraperitoneally for 11 consecutive days. The behavioral performance of the animals was evaluated by the T-maze test. The effect of the extract on acetylcholinesterase (AChE) activity and antioxidant status in cortex and hippocampus were also monitored., Results: Our experimental data revealed that treatment with M. vulgare significantly increased the percentage of correct choices of rats with Sco-induced dementia in the T maze test (by 38%, p < 0.05). Additionally, it reduced AChE activity in the hippocampus (by 20%, p < 0.05) and alleviated oxidative stress induced by Sco, particularly in the cortex., Conclusions: M. vulgare water extract demonstrated working memory preserving effect in rats with Sco-induced dementia, AChE inhibitory activity and in vivo antioxidant potential, and deserve further attention.

Background: The neurodegenerative process in Alzheimer's disease, one of the most common types of dementia worldwide, mostly affects the cholinergic neurotransmitter system and, to a lesser extent, the monoaminergic one. The antioxidant acetylcholinesterase (AChE) and triple monoamine reuptake inhibitory activity of Sideritis scardica (S. scardica) and other Sideritis species has already been reported., Objective: To investigate the effects of S. scardica water extracts on the learning and memory processes, anxiety-like behavior, and locomotor activities in scopolamine (Sco)-induced dementia in mice., Methods: Male Albino IRC mice were used. The plant extract was administered for 11 consecutive days in the presence or absence of Sco (1 mg/kg, i.p). The behavioural performance of the animals was evaluated by passive avoidance, T-maze, and hole-board tests. The effects of extract on AChE activity, brain noradrenalin (NA), and serotonin (Sero) content, and antioxidant status were also monitored., Results: Our experimental data revealed that the S. scardica water extract caused a reduction in degree of memory impairment and anxiety-like behaviour in mice with scopolamine-induced dementia. The extract did not affect changed by the Sco AChE activity but impact reduced brain NA and Sero levels and demonstrated moderate antioxidant activity. In healthy mice we did not confirm the presence of anxiolytic-like and AChE inhibitory effects of the S. scardica water extract. The extract did not change the control Sero brain levels and reduce those of NA., Conclusion: S. scardica water extract demonstrated memory preserving effect in mice with scopolamine-induced dementia and deserve further attention.

Macrolepiota procera (MP) is an edible mushroom used in the treatment of diabetes, hypertension and inflammation. However, the structure and biological effects of its polysaccharides (PSs) are unclear. This study investigates the structural features of a PS complex from MP (MP-PSC), its immunomodulatory activities and effects on probiotic and pathogenic bacteria. MP-PSC was obtained by boiling water, and PSs were characterized by 2D NMR spectroscopy. The immunomodulatory effects on blood and derived neutrophils, other leukocytes, and murine macrophages were studied by flow cytometry, chemiluminescence, spectrophotometry, and ELISA. The total carbohydrate content of MP-PSC was 74.2%, with glycogen occupying 36.7%, followed by β -D-glucan, α -L-fuco-2-(1,6)-D-galactan, and β -D-glucomannan. MP-PSC (200 μg/mL) increased the number of CD14+ monocyte cells in the blood, after ex vivo incubation for 24 h. It dose-dependently (50-200 μg/mL) activated the spontaneous oxidative burst of whole blood phagocytes, NO, and interleukin 6 productions in RAW264.7 cells. MP-PSC exhibited a low antioxidant activity and failed to suppress the oxidative burst and NO generation, induced by inflammatory agents. It (2.0%, w / v ) stimulated probiotic co-cultures and hindered the growth and biofilm development of Escherichia coli , Streptococcus mutans and Salmonella enterica . MP PSs can be included in synbiotics to test their immunostimulating effects on compromised immune systems and gut health.

Ethnopharmacological Relevance: Geranium sanguineum L. is used for treatment of inflammations, anemia, malignant diseases of the blood-forming organs, diarrhea, respiratory infections, etc. Only flavonoids in root extracts have been elucidated as immunostimulating and anti-inflammatory compounds, and polysaccharides in the herb have not been examined., Aim of the Study: to compare the chemical features of polysaccharide complexes (PSCs) from leaves (GSL-PSC) and roots (GSR-PSC) of G. sanguineum, as well as their immunomodulatory activities on leukocytes after inflammation, and effects on the growth of different bacteria., Materials and Methods: The samples were isolated by water extraction and their structural features were studied by 2D NMR spectroscopy. The stimulatory effects of both PSCs on human leukocytes were analyzed with flow cytometry. Their suppressive activities on the oxidative burst in blood and derived neutrophils against opsonized zymosan and phorbol myristate acetate were investigated. The effects of the samples on viability, NO and interleukin 6 (IL-6) syntheses in RAW264.7 cells after inflammation with lipopolysaccharides (LPS) were tested. The prebiotic and anti-biofilm activities of the PSCs were evaluated., Results: The total carbohydrate content in the samples was significant (73.6-76.8%). GSL-PSC contained pectins, which were rich in homogalacturonan (HG), and smaller amounts of rhamnogalacturonan (RG) type I, decorated by 1,5-α-L-Araf, 1,4- and 1,6-β-D-Galp chains. GSR-PSC contained starch, followed by pectins with lower HG content and more RG-I regions, substituted by 1 → 3,5-α-L-arabinans and 1 → 3,6-β-D-galactans. GSL-PSC and GSR-PSC (200 μg/mL) increased monocyte and granulocyte cell counts, but GSR-PSC also elevated T helper and B cell levels in a normal and activated state. GSR-PSC triggered a dose-dependent (50-200 μg/mL) oxidative burst in blood, but alleviated it after inflammation even in blood-derived neutrophils. It was free of LPS, and activated NO and IL-6 productions in RAW264.7 cells better than GSL-PSC, without affecting their viability. Both PSCs (2.0%, w/v) stimulated probiotic co-cultures between Clostridium beijerinckii strains and Lactobacillus sp. ZK9, and inhibited the growth and biofilm formation of Escherichia coli, Streptococcus mutans and Salmonella enterica., Conclusions: The PSs in G. sanguineum could be involved in the stimulatory effects on blood-forming organs and anti-inflammatory action of aqueous root extracts in case of infections. These PSs should be included in synbiotic foods to support the treatment of inflammations and infections in the gut., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Haberlea rhodopensis (HR) use dates back to the Thracian and Roman periods. Bulgarians call it Orpheus flower and exploit its leaves for making tea and extracts with detoxifying, tonic, restorative and rejuvenating effects. HR was traditionally applied in wound healing and treatment of cattle diseases., Aim of the Study: The general aim of the review was to analyze the progress of phytochemical and pharmacological studies on HR, focusing on its radioprotective and immunomodulating effects., Materials and Methods: The main source material for the review was collected using several global search engines with the phrase: Haberlea rhodopensis, as well as Bulgarian books and dissertations., Results: HR metabolite profile includes large amounts of free sugars, polyols, polysaccharides (PS), flavonoids, phenolic acids and carotenoids. The radioprotective effect of 70% ethanolic leaf extract (70HREE) is explained by preservation of lymphocytes, other blood cells and testicular tissue from aberration under γ-radiation via stimulation of antioxidant enzymes and neutralization of free radicals. The extract immunomodulating activity results from raised antibody response, stem and neutrophil cell count, complement system activation, anti-tumour and anti-inflammatory effects. The detoxifying, restorative, rejuvenating and wound healing plant properties known to ethnomedicine were supported by radioprotective and immunomodulating studies., Conclusions: Metabolites of phenolic origin involved in HR resurrection are supposed to contribute to its radioprotective, immunomodulatory, anti-mutagenic and anti-aging effects. However, there is no chemical characterization of 70HREE in the investigations with humans and animals. Structure-activity relationship studies on HR immunomodulating and radioprotective compounds, and on their mode of action are required. They should include not only phenols but PS and other unexplored molecules. The metabolic activity of phagocytes, platelets and lymphocytes triggered by HR extracts has to be examined to elucidate their immunostimulatory potential. HR formulations can be tested in cosmetic, food and medical products as adjuvants to treat infectious, chronic inflammatory and tumour diseases, and especially in patients undergoing radiotherapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Three polysaccharide complexes (PSCs) were isolated from the aerial parts of common purslane (Portulaca oleracea L.), and the flowers of common lavender (Lavandula angustifolia Mill.) and silver linden (Tilia tomentosa Moench) by boiling water extraction and ethanol precipitation. The chemical composition and immunomodulating effects of isolated PSCs were characterized. The chemical characterization revealed that the three samples contain mainly pectic polysaccharides. They exhibited ex vivo intestinal immunomodulating activity through the murine Peyer's patch-mediated bone marrow cell proliferation test at 100μg/ml concentration. At the same time, they stimulated ex vivo human blood T-cell populations (CD4 + /CD25 + and CD8 + /CD25 + ), phagocytic leukocytes (CD14 + and CD64 + cells) and induced IL-6 production from human white blood cells and Peyer's patch cells. The herbal PSCs stimulated ex vivo ROS production from whole blood phagocytes and showed unspecific in vitro anti-proliferative activity against normal and A549, HeLa and LS180 tumor cells. This is the first report on immunomodulating studies of linden flower pectins and chemical and biological activity characterization of lavender polysaccharides. Our study demonstrates that similarly to purslane, lavender and silver linden herbal materials contain immunomodulating polysaccharides that could be useful for support of compromised immune system., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Silver linden flowers contain different pectins (PSI-PSIII) with immunomodulating properties. PSI is a low-esterified pectic polysaccharide with predominant homogalacturonan region, followed by rhamnogalacturonan I (RGI) with arabinogalactan II and RGII (traces) domains. PSII and PSIII are unusual glucuronidated RGI polymers. PSIII is a unique high molecular weight RGI, having almost completely O-3 glucuronidated GalA units with >30% O-3 acetylation at the Rha units. Linden pectins induced reactive oxygen species (ROS) and NO generation from non-stimulated whole blood phagocytes and macrophages, resp., but suppressed OZP-(opsonized zymosan particles)-activated ROS generation, LPS-induced iNOS expression and NO production. This dual mode of action suggests their anti-inflammatory activity, which is known for silver linden extracts. PSI expressed the highest complement fixation and macrophage-stimulating activities and was active on intestinal Peyer's patch cells. PSIII was active on non-stimulated neutrophils, as it induced ß 2 -integrin expression, revealing that acetylated and highly glucuronidated RGI exhibits immunomodulating properties via phagocytes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Two pectic (chPS-L1, chPS-L2) and one polyphenolic (chPP-L) fractions were obtained from lavender flowers after boiling water extraction, exhaustive removing of alcohol-soluble molecules and SEC. chPS-L1 (52.4kDa) contains mainly low-acetylated and high-methoxylated homogalacturonans (HG), and smaller rhamnogalacturonan (RG) I backbone fragments rich in 1,3,5-branched arabinan and arabinogalactan (AG) II side chains. chPS-L2 (21.8kDa) contains predominantly similarly esterified HG, followed by RGI with AGII structures and RGII. The prevalence of catechin and epicatechin in chPP-L indicates that they form weak interactions with pectins. chPS-L1 and chPS-L2 enhanced ß 2 -integrin expression on neutrophils, inducing ROS generation and macrophage NO production. Both the effects on ß 2 -integrin and high complement fixation activity of chPS-L1 were proposed for its inhibitory action against PMA- and OZP-activated ROS formation. This, together with suppression of NO generation after co-stimulation with chPS-L1 and LPS, suggested anti-inflammatory activity of studied pectins. Lavender polysaccharides expressed intestinal Peyer's patch immunomodulating activity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Betalains are water-soluble plant pigments that are widely used as food colorants, and have a wide range of desirable biological activities, including antioxidant, anti-inflammatory, hepatoprotective, anti-cancer properties. They can be produced from various plants, notably beetroot, but betalain products obtained in this way also have some undesirable properties and are difficult to standardize. A potentially attractive alternative is to use hairy root cultures. In the study reported here, we found that betalain extracts obtained from hairy root cultures of the red beetroot B. vulgaris cv. Detroit Dark Red also had higher antioxidant activity than extracts obtained from mature beetroots: six-fold higher 2,2-dyphenyl-1-picrylhydrazyl radical scavenging ability (90.7% inhibition, EC(50) = 0.11 mg, vs 14.2% inhibition, EC(50) = 0.70 mg) and 3.28-fold higher oxygen radical absorbance capacity (4,100 microM TE/g dry extract, vs 1,250 microM TE/g dry extract). The high antioxidant activity of the hairy root extracts was associated with increased concentrations (more than 20-fold) of total phenolic concomitant compounds, which may have synergistic effects with betalains. The presence of 4-hydroxybenzoic acid, caffeic acid, catechin hydrate, and epicatechin were detected in both types of extract, but at different concentrations. Rutin was only present at high concentration (1.096 mg.g(-1) dry extract) in betalain extracts from the hairy root cultures, whereas chlorogenic acid was only detected at measurable concentrations in extracts from intact plants.