Extraction, purification, structure characteristics, biological activities and pharmaceutical application of Bupleuri Radix Polysaccharide: A review.

Bupleuri Radix (BR), as a well-known plant medicine of relieving exterior syndrome, has a long history of usage in China. Bupleuri Radix Polysaccharide (BRP), as the main component and an important bioactive substance of BR, has a variety of pharmacological activities, including immunoregulation, antioxidant, antitumor, anti-diabetic and anti-aging, etc. In this review, the advancements on extraction, purification, structure characteristics, biological activities and pharmaceutical application of BRP from different sources (Bupleurum chinense DC., Bupleurum scorzonerifolium Willd., Bupleurum falcatum L. and Bupleurum smithii Woiff. var. Parvifolium Shan et Y. Li.) are summarized. Meanwhile, this review makes an in-depth discussion on the shortcomings of the research on BRP, and new valuable insights for the future researches of BRP are proposed.

Association between Maternal Characteristics and Immune Factors TGF-ß1, TGF-ß2, and IgA in Colostrum: An Exploratory Study in Japan.

Colostrum is the first food for newborns and it contains various crucial immune factors. The concentrations of immune factors in breast milk may change depending on maternal characteristics such as body mass index, collection day, and age at first pregnancy. In this exploratory study, we investigated the association between TGF-ß1, TGF-ß2, and IgA in colostrum and rarely studied factors that affect breast milk components, including the use of labor-inducing medication, colostrum secretion, sex of newborns, breast or nipple problems, and nipple care. Breast milk samples were collected from 42 mothers and analyzed for TGF-ß1, TGF-ß2, and IgA. The results suggest that parity and mode of delivery may be correlated with the concentrations of immune factors in colostrum. However, we found no association between the immune factors in colostrum and the use of labor-inducing medications, colostrum secretion, sex of newborns, breast or nipple problems, and nipple care. These findings have some implications for further analysis of the effects of immune factors in breast milk on the prognosis of allergies in children.

Immunomodulatory effects of Blaps rynchopetera extract

Purpose: To explore the potential immunomodulatory effects of total extract and different polar parts from Blaps rynchopetera Fairmaire. Methods: Phagocytic activity was evaluated by neutral red assay, and the effect of the immune function was investigated by normal and immunocompromised mice models. Results: In vitro, total extract, as well as chloroform, ethyl acetate, n-butanol and water fractions could individually enhance the phagocytic ability of mouse peritoneal macrophages; in addition, chloroform and ethyl acetate fractions had an increasing tendency when combined stimulation with lipopolysaccharide (LPS). In vivo, ethyl acetate fraction (EAF) could enhance the immune organ index, increase the serum hemolysin level and peripheral blood immune cells of immunocompromised mice, while for normal mice, the effect was inconspicuous. Conclusions: Blaps rynchopetera extracts had noteworthy immunomodulatory effect, especially for individuals with immune disorders.

Bioactivity-guided isolation of immunomodulatory compounds from the fruits of Ligustrum lucidum.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Ligustrum lucidum (FLL) W.T. Aiton (Oleaceae) is included in the 2020 "Chinese Pharmacopoeia" and is widely used in traditional Chinese medicine as a tonic. In recent years, FLL has been reported to improve immune function, but the bioactive compounds and mechanisms of FLL remain poorly characterized. AIM OF THE STUDY: To identify FFL compounds with strong immune activity and explore their molecular mechanisms. MATERIALS AND METHODS: The phagocytic activity of RAW264.7 macrophages and proliferation activity of spleen lymphocytes were used to guide the isolation of bioactive compounds from FLL extracts. Lymphocyte subpopulations, Ca2+ concentrations, and surface molecule expression were analyzed using flow cytometry. Cytokine secretion was examined using ELISA. FITC-OVA uptake was observed using fluorescence microscopy. NF-κB activation was analyzed using western blotting. RESULTS: The extraction and isolation produced ten compounds, namely oleuropeinic acid, nuezhenide, isonuezhenide, salidroside, isoligustrosidic acid, ligulucidumosides A, 8(E)-nuezhenide, hydroxytyrosol, oleuropein, and p-hydroxyphenethyl 7-ß-D-glucosideelenolic acid ester were isolated and identified from FLL-Bu-30%. Immunoactivity experiments showed that hydroxytyrosol had the strongest macrophage phagocytotic and lymphocyte proliferation-promoting activities. Further studies showed that hydroxytyrosol could significantly enhance lymphocyte subsets CD3+, CD4+/CD8+, and CD3+CD4-CD8-, promote IL-4, IFN-γ, and TNF-α secretion, and increase intracellular Ca2+ concentrations. In addition, the results from RAW264.7 macrophages showed that hydroxytyrosol increased FITC-OVA uptake, induced TNF-α and IL-1ß production, upregulated MHC-II, CD80, and CD86 expression, promoted cytoplasmic IκB-α degradation, and increased nuclear NF-κB p65 levels. CONCLUSION: Our study provides substantial evidence regarding the mechanism of the immunomodulatory effects of compounds from FLL.

Antioxidant and immunomodulatory activities in vitro of polysaccharides from bee collected pollen of Chinese wolfberry.

China is a larger apiculture producer in the world and more than 120 million kg of bee collected pollens of Chinese wolfberry (WBP) are produced per year. However, the lack of knowledge of the nutritional benefits of WBP limits the use of this natural product in food industry. In the present study, three polysaccharides (WBPPS-1, WBPPS-2 and WBPPS-3) were obtained by ion-exchange chromatography, and their preliminary structures, antioxidant and immunomodulatory activities were investigated. The results showed that WBPPS-1, WBPPS-2 and WBPPS-3 were composed of mannose, rhamnose, galacturonic acid, glucose, galactose, xylose and arabinose with different ratio and their average molecular weights were 1016.3, 878.7 and 901.6 KDa, respectively. In addition, the contents of zinc were far higher than other trace elements in the three polysaccharides, suggesting these polysaccharides probably be polysaccharides­zinc complex. Moreover, WBPPS-3 exhibited stronger scavenging activities on 2,2'-azinobis-(3-ethyl-benzothiazolin-6-sulfonic acid) and 1,1-diphenyl-2-picrylhydrazyl radicals than WBPPS-1 and WBPPS-2. Likewise, WBPPS-3 exhibited a superior enhanced effect on secretion of nitric oxide, tumor necrosis factor-α, interleukin-1ß and interleukin-6 in RAW264.7 cells than other two polysaccharides. Overall, these results suggest that WBPPS-3 has potential to be developed as antioxidant and immunomodulatory ingredients in functional foods, but further animal or clinical studies are required.

Screening and structure study of active components of Astragalus polysaccharide for injection based on different molecular weights.

As a special traditional Chinese medicine, Astragalus polysaccharides for injection (APS, batch no. Zhunzi Z20040086) includes complex polysaccharide macromolecules that may increase the risk upon application. Although fingerprints for quality control are available, the specific active ingredients are unclear. Identifying the active components is the key to reduce the risk of adverse reactions of the drug. In this work, APS was mainly separated into two components, namely, macromolecular component (APS-I) and small molecular components (APS-II). The molecular weight measurement revealed that the average molecular weight of APS-I exceeded 500 kDa, and that of APS-II was 10 kDa. Monosaccharide-composition analysis revealed that APS-I consisted of glucose, galactose, arabinose, rhamnose, and galacturonic acid, with a ratio of approximately 1.5:1:5.4:0.08:0.1. Meanwhile, APS-II consisted of glucose, galactose, arabinose, rhamnose, and galacturonic acid, with a molar ratio of 9:1:1.4:0.04:0.001. Methylation, FT-IR, and NMR analysis indicated that the APS-I monosaccharide residue was linked as follows: D-Glcp-(1→, →4)-D-Glcp-(1→, →2)-L-Rhap-(1→, D-Araf-(1→, →5)-D-Araf-(1→, →2,5)-D-Araf-(1→, →4)-D-Galp-(1 â†’ . Meanwhile, the APS-II monosaccharide residue was connected as follows: α-D-Glcp-(1→, →4)-α-D-Glcp-(1→, →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →3,4,6)-α-D-Glcp-(1→, →2)-α-L-Rhap-(1→, α-D-Araf-(1→, →5)-α-D-Araf-(1→, →4)-ß-D-Galp-(1 â†’ . Screening experiments on their in vitro immunological activity showed that APS-II had stronger effect on innate and adaptive immunities than APS-I. In vivo animal experiments showed that APS-II can increase the leukocyte level of cyclophosphamide immunosuppressed mice and improve their immunomodulatory ability. Therefore, APS-II is the main active ingredient of APS and is expected to become a new generation of APS products.

Influence of an immune-modulatory feed supplement on performance and immune function of beef cows and calves preweaning.

The ability to positively alter immune and stress response with nutritional compounds is of great interest and importance to the beef industry. There is a proprietary product (OmniGen-AF [OG]; Phibro Animal Health, Quincy, IL) reported to have performance-enhancing benefits by altering animal response to stress and immune challenges. The objective of this 2-yr research project was to study the effect of supplementing OG to beef cows and their calves on breeding and growth performance. One hundred and twelve multiparous beef cows and 48 primiparous cows were randomly assigned to treatment in year 1; control (CON, no OG; n = 56 multiparous and 24 primiparous) or treatment (OG fed at 8.8 g/100 kg body weight [BW]; n = 56 multiparous and 24 primiparous). Multiparous cows (mean ± SD = 6.4 ± 0.4 yr; BW = 589 ± 9.2 kg; body condition score [BCS] 6.2 ± 0.07) were used in both years of the experiment and primiparous cows (mean ± SD = 2.1 ± 0.04 yr of age, weighed 400 ± 7.5 kg, and BSC of 5.6 ± 0.06) were only used in the first year of the experiment. CON and OG supplements were offered over two production cycles beginning in December approximately 60 d prior to projected calving through pre-breeding in May of each year. Calves from treatment cows were offered treatments in a creep supplement limited to a daily rate of 1% as-fed of BW prorated for 3-d/wk feeding from mid-July through weaning with OG offered at 8.8 g/100 kg BW. Primiparous cow's BW, BCS, and calf performance were not affected by treatment (P ≥ 0.15) in year 1. BW of multiparous OG cows tended (P = 0.10) to be heavier at weaning in year 1 and was greater (P = 0.05) at the onset of the experiment in year 2. Body condition of OG cows was greater (P ≤ 0.02) at weaning in both years 1 and 2, as well as at the onset of the experiment in year 2. Calves fed OG from the mature cows gained more (P = 0.05) BW during the creep feeding period than CON. Core body temperatures of OG heifers measured during the late summer with intravaginal temperature data loggers tended (P ≤ 0.10) to be less at 1400 and 1700 hours and were less (P = 0.05) at 1800 hours than CON heifers. Feeding OG did not result in changes (P = 0.25) in serum titer response to the BVD virus of calves during year 2. The results of the current experiment indicate feeding OG to beef cows and calves can result in improvement in BCS of cows, enhance weight gain of calves preweaning, and reduce heat loads in heifer calves during the late summer.

In Vivo Immunomodulatory Potential of Partial Purified Lectin from the Saffron Milk Cap Mushroom, Lactarius deliciosus (Agaricomycetes), against Colloidal Carbon Particles.

Mushroom compounds and biomolecules are known for their biological beneficial effects and dietary properties. Their molecules can be used in immunology for their ability to stimulate immune cells and in biotherapy of diseases. In this study, the immunomodulatory effect using carbon clearance test in vivo of partial purified lectin of Lactarius deliciosus using DEAE-Sephacyl column, with sugar affinity against galactose, methyl-ß-D-galactopyranoside and lactose, showed a significant effect on phagocytic activity and half-life of carbon particles in mice with different concentrations (5, 10, 15, and 30 mg/kg). The results showed that the immunomodulatory effect increased in low doses and decreased in high doses compared with the control group p < 0.0001. L. deliciosus lectin exerted a dose-dependent immunostimulant activity toward the reticulo-endothelial system, and phagocytic activity toward macrophages and neutrophils in spleen and liver against the colloidal carbon.

Isolation and identification of immunomodulatory selenium-containing peptides from selenium-enriched rice protein hydrolysates.

The RAW264.7 cell model was employed to screen immunomodulatory selenium-containing peptides from selenium-enriched rice protein hydrolysates (SPHs). Moreover, the selenium-containing peptides of high-activity protein hydrolysates were purified by Sephadex G-25, and identified by reversed phase ultra performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry. The results showed that 25 peptide sequences containing selenomethionine (SeMet) information above 90% of probability confidence were found in a fraction of alcalase hydrolysates. SeMDPGQQ and TSeMMM of 100% probability confidence were speculated as two novel selenium-containing peptide sequences. The artificially synthesized peptide TSeMMM was subsequently verified by an excellent immunomodulatory activity at a concentration of 80 µg/mL. In conclusion, the immunomodulatory activity of SPHs was correlated to SeMet sequence in the structure of selenium-containing peptides, and TSeMMM with a stronger immunomodulatory activity demonstrated potential as functional food additives for improving human health.

Catechin rich butanol fraction extracted from Acacia catechu L. (a thirst quencher) exhibits immunostimulatory potential.

Acacia catechu L., (Fabaceae) named as "catechu" is a plant, the decoction of heartwood of which is daily consumed as thirst quencher by a good percentage of the population in South India. The plant is mainly distributed in India and other Asian countries. It has been used in Indian traditional medicine for the treatment of asthma, bronchitis, colic, diarrhea, boils, skin afflictions, sores and stomatitis. The present investigation was aimed to study the immunomodulatory effects of different fractions of ethanol extract of A. catechu heartwood and HPLC analysis of the active fraction. Three fractions namely, butanol, chloroform and ethyl acetate were prepared from ethanol extract of A. catechu heartwood. Each of these fractions was assessed for its immunomodulatory activity. In vivo immunomodulatory activity was analyzed by sheep red blood cells (SRBC) specific hemagglutinating antibody titer, plaque-forming cell assay and delayed type hypersensitivity (DTH) reaction in Swiss albino mice. In vitro immunomodulating potential of the fractions was studied using murine peritoneal macrophages and splenocytes. Non-specific immune functions such as phagocytosis (nitroblue tetrazolium reduction assay and cellular lysosomal enzyme assay), nitric oxide (NO) production and cytokine release (TNF-α and IL-10) were studied in macrophages. In addition, splenocyte proliferation was also studied. In the in vivo experiments, butanol and chloroform fractions showed an increase in antibody titer dose-dependently. At higher dose (400 mg/kg b. w.) treatment the butanol fraction produced an enhancement in the number of plaque-forming cells (antibody producing cells) in the spleen. SRBC induced DTH reaction was significantly increased with butanol fraction in a dose-dependent manner. Peritoneal macrophages showed an increased phagocytic response on treatment with butanol fraction (100 µg/mL) as evidenced by its effect on nitroblue tetrazolium reduction and cellular lysosomal enzyme activity. All three fractions inhibited the production of NO and the release of TNF-α. Interleukin-10 production was significantly increased after treatment with butanol fraction. High-performance liquid chromatography analysis of the butanol fraction showed the presence of high concentration of catechin. The results suggested that butanol fraction of ethanol extract of A. catechu heartwood had immunomodulatory effects on non-specific, humoral, and cell-mediated immune functions. This study may be useful in validating the rationality of daily consumption of decoction of A. catechu and also its use in traditional medicine system. The study also suggests the possible use of A. catechu in the immunostimulatory herbal preparations.

An integrated metabolomic strategy for the characterization of the effects of Chinese yam and its three active components on septic cardiomyopathy.

Chinese yam (CY), used as both a traditional Chinese medicine and a nutritious food, is an excellent candidate for treating septic cardiomyopathy (SCM). Adenosine, arbutin and allantoin are the major active components in the aqueous extract of CY. The aim of the present study was to interpret the roles of CY, adenosine, arbutin and allantoin in SCM treatment. Firstly, significant physiological indexes were examined to assess the model and treatment effects of CY, adenosine, arbutin and allantoin. Then, a metabolomic approach was utilized to reveal the metabolic disorders in SCM concerning the intervention of CY/adenosine/arbutin/allantoin. The integrated results demonstrated that adenosine, arbutin and allantoin are responsible for the efficacy of CY on SCM treatment by regulating amino acid, arachidonic acid, sphingolipid, glycerophospholipid and glycol metabolism. Moreover, adenosine and/or arbutin could be used as a substitute for CY in treating SCM, and allantoin efficacy was slightly weaker. This integrated metabolomic approach performed excellently in understanding the herbal function and the roles of its components.

Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development.

BACKGROUND & AIMS: Exposure to biologic and immunosuppressant agents during breastfeeding is controversial, and there are limited data on safety. We investigated whether biologics are detectable in breast milk from women receiving treatment for inflammatory bowel diseases (IBDs) and whether breastfeeding while receiving treatment is associated with infections or developmental delays. METHODS: We performed a multicenter prospective study of women with IBD and their infants, collecting breast milk samples (n = 72) from patients receiving biologic therapy from October 2013 to November 2015. Drug concentrations were measured in all breast milk samples at several time points within 48 hours of collection and within 168 hours for some samples. Child development was assessed using the Ages and Stages Questionnaire 3, completed by 824 women with IBD (treated or untreated) during pregnancy (620 breastfed, and 204 did not). Data on children's health and development were obtained from mothers and pediatricians, along with information on mothers' medication exposure, IBD history, activity, pregnancy, and postpartum complications. We used chi-squared method or Fisher exact test to determine associations between categorical values and compared differences in continuous outcomes between groups using analysis of variance models. The primary outcome was drug concentration of biologic agents in breast milk (from 72 women) at 1, 12, 24, and 48 hours after dosing and also at 72, 96, 120, and 168 hours for available samples. Secondary outcomes were a range of infant infections and Ages and Stages Questionnaire 3-defined developmental delays among all breastfed infants. RESULTS: We detected infliximab in breast milk samples from 19 of 29 treated women (maximum, 0.74 µg/mL), adalimumab in 2 of 21 treated women (maximum, 0.71 µg/mL), certolizumab in 3 of 13 treated women (maximum, 0.29 µg/mL), natalizumab in 1 of 2 treated women (maximum, 0.46 µg/mL), and ustekinumab in 4 of 6 treated women (maximum, 1.57 µg/mL); we did not detect golimumab in breast milk from the 1 woman receiving this drug. Rates of infection and developmental milestones at 12 months were similar in breastfed vs non-breastfed infants: any infection, 39% vs 39% in control individuals (P > .99) and milestone score, 87 vs 86 in control individuals (P = .9992). Rates of infection and developmental milestones did not differ among infants whose mothers received treatment with biologics, immunomodulators, or combination therapy compared with unexposed infants (whose mothers received treatment with mesalamines or steroids or no medication). CONCLUSIONS: In a study of women receiving treatment for IBD and their infants, we detected low concentrations of infliximab, adalimumab, certolizumab, natalizumab, and ustekinumab in breast milk samples. We found breastfed infants of mothers on biologics, immunomodulators, or combination therapies to have similar risks of infection and rates of milestone achievement compared with non-breastfed infants or infants unexposed to these drugs. Maternal use of biologic therapy appears compatible with breastfeeding. Clinicaltrials.gov no.: NCT00904878.

Immunomodulatory effects of Tinospora crispa extract and its major compounds on the immune functions of RAW 264.7 macrophages.

The in vivo immunomodulatory activities of Tinospora crispa have been reported but its molecular mechanisms underlying its immunomodulatory properties remains obscure and the active constituents contributing to the activities have not been identified. The present study was aimed to investigate the immunomodulatory effects of T. crispa extract (TCE) and its chemical constituents on RAW 264.7 macrophages. Six known compounds including magnoflorine and syringin were isolated by various chromatographic techniques from TCE and their structures were determined spectroscopically. A validated HPLC method was used to quantify magnoflorine and syringin in the extract. The immunomodulatory effects of TCE and its isolated compounds on chemotaxis, phagocytosis, production of inflammatory mediators including reactive oxygen species (ROS), nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines which include tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 and monocyte chemoattractant protein-1 (MCP-1) on macrophages were assessed. TCE increased the chemotaxis and phagocytic activity of macrophages and significantly enhanced the production of ROS, NO and pro-inflammatory cytokines. All alkaloids isolated, specifically magnoflorine showed remarkable inducing effects on the chemotaxis, phagocytic activity, ROS and NO productions and the secretions of IL-1ß, TNF-α, IL6, PGE2 and MCP-1. In contrast, syringin potently reduced the chemotaxis, phagocytic activity, ROS and NO productions and secretions of IL-1ß, TNF-α, IL6, PGE2 and MCP-1. TCE showed strong immunostimulant effects on various components of the immune system and these activities were possibly contributed mainly by the alkaloids specifically magnoflorine. TCE has potential to be developed as an effective natural immunostimulant for improvement of immune-related disorders.

Fractionated Coptis chinensis Extract and Its Bioactive Component Suppress Propionibacterium acnes-Stimulated Inflammation in Human Keratinocytes.

Coptis chinensis (CC) is widely used in Asian countries to treat inflammatory diseases. We investigated the anti-inflammatory activity of the aqueous fraction separated from CC extract and of berberine, its key bioactive component, in human keratinocytes and the possible molecular mechanisms underlying this. Treating HaCaT keratinocytic cells with heat-killed Propionibacterium acnes induced nitric oxide and proinflammatory cytokine (e.g., tumor necrosis factor-α, interleukin (IL)-1ß, and IL-8) production and their mRNA expression; these effects were suppressed by pretreatment with the aqueous fraction or berberine, which also suppressed the phosphorylation of ERK, JNK, and p38 kinases and the nuclear expression of nuclear factor (NF)-κB p65 in P. acnes-stimulated cells. Thus, the aqueous fraction and berberine effectively exerted anti-inflammatory activities by suppressing mitogen-activated protein kinase and NF-κB signaling pathways in human keratinocytes and may be used for treating P. acnes-induced inflammatory skin diseases.

Suppressive effects of Vochysia divergens aqueous leaf extract and its 5-methoxyflavone on murine macrophages and lymphocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Vochysia divergens Pohl (Vochysiaceae), popularly known as "Cambará", is a tree that is resistant to the seasonal floods in the Pantanal, and usually found in monodominant stands called "Cambarazal". The inhabitants of the Pantanal exploit this tree for medicinal uses. Infusions and decoctions of its leaves are taken as teas, particularly for the treatment of asthma, flu and diarrhea, according to the local tradition transmitted empirically through the generations. AIM OF THE STUDY: To evaluate the beneficial health effects related to the ethnomedicinal uses of V. divergens (Vd) by using biomonitored fractionation of an aqueous leaf extract. MATERIALS AND METHODS: The aqueous leaf extract was obtained by decoction, and then the extract was fractionated by a combination of separation techniques including precipitation, organic partition and chromatography. Chromatographic analyses of the active samples were carried out using HPLC-DAD-MS. Flavonoid 1 was isolated from the n-BuOH fraction through classic chromatographic techniques. The inhibitory effects and cytotoxicity of the Vd extract, fractions and flavonoid 1 on NO and TNF-α production were assessed in LPS-stimulated RAW 264.7 macrophage cultures. Additionally, suppression on the proliferation of BALB/c lymphocytes was estimated by [3H] thymidine incorporation. The antioxidant activity of the samples was verified by SNP and DPPH assays and the suppression of the iNOS protein expression was evaluated through Western blotting. RESULTS: The HPLC-DAD-MS analysis of the Vd extract led to the identification of 5-methoxyluteolin-7-O-ß-glucopyranoside (2), rutin (4) and the tannin galloyl-HHDP-glucopyranoside (3), besides the main flavonoid 3',5-dimethoxyluteolin-7-O-ß-glucopyranoside (1), which was biologically evaluated in comparison with luteolin aglycone. The Vd extract, n-BuOH fraction and flavonoid 1 inhibited NO and TNF-α production by LPS-stimulated macrophages. The reduction of NO levels was mediated mainly by suppression of the iNOS expression. In addition, both the Vd extract (IC50 13.6 µg/mL) and flavonoid 1 (IC50 19.8 µg/mL; 41.6 µM) strongly inhibited stimulated lymphocyte proliferation when compared to the immunosuppressive agent cyclosporin A (IC50 43.8 µg/mL; 36.4 µM). The Vd extract also showed a scavenging activity toward DPPH and NO free radicals. This is the first report describing the immunomodulatory potential of V. divergens and its major flavonoid (1). CONCLUSION: Our findings showed that the aqueous leaf extract of V. divergens and its flavonoid reduced the production of excessive pro-inflammatory markers, collaborating with the Pantanal folk medicinal tradition that recommends the tea of cambará leaves for both asthma and flu. In addition, this study contributes to the knowledge of the pharmacological properties of 5-methoxy flavones, a poorly investigated subclass of flavonoids.

The silymarin composition and why does it matter???

The extract from milk thistle (Silybum marianum (L.) Gaertn. (Asteraceae)), known as silymarin, contains a variety of flavonolignans and displays antioxidant, anti-inflammatory, immunomodulatory and hepatoprotective properties. As silybin is the main component of silymarin, the literature mainly focuses on this compound, ignoring all other components. This leads to problems in reproducibility of scientific results, as the exact composition of silymarin is often unknown and can vary to a certain degree depending on the processing, chemo-variety of the plant used and climatic conditions during the plant growth. There are studies dealing with the analytical separation and quantification of silymarin components as well as studies focused on silymarin content in clinically used drugs, in various plant parts, seasons, geographic locations etc. However, no comparison of detail flavonolignan profiles in various silymarin preparations is available to date. Also, as a result of the focus on the flavonolignans; the oil fraction, which contains linoleic, oleic and palmitic acids, sterols, tocopherol (vitamin E) and phospholipids, has been neglected. Due to all these factors, the whole plant is used e.g. as animal feed, the leaves can be eaten in salads and seed oil, besides culinary uses, can be also utilized for biodiesel or polymer production. Various HPLC separation techniques for the determination of the content of the flavonolignans have been vastly summarized in the present review.

In vitro characterization and in vivo toxicity, antioxidant and immunomodulatory effect of fermented foods; Xeniji™.

BACKGROUND: Xeniji, produced by fermenting various types of foods with lactic acid bacteria and yeast, has been commonly consumed as functional food. However, nutrition value, bioactivities and safety of different fermented products maybe varies. METHODS: Organic acid and antioxidant profiles of Xeniji fermented foods were evaluated. Moreover, oral acute (5 g/kg body weight) and subchronic toxicity (0.1, 1 and 2 g/kg body weight) of Xeniji were tested on mice for 14 days and 30 days, respectively. Mortality, changes of body weight, organ weight and serum liver enzyme level were measured. Liver and spleen of mice from subchronic toxicity study were subjected to antioxidant and immunomodulation quantification. RESULTS: Xeniji was rich in ß-carotene, phytonadione, polyphenol, citric acid and essential amino acids. No mortality and significant changes of body weight and serum liver enzyme level were recorded for both oral acute and subchronic toxicity studies. Antioxidant level in the liver and immunity of Xeniji treated mice were significantly upregulated in dosage dependent manner. CONCLUSION: Xeniji is a fermented functional food that rich in nutrients that enhanced antioxidant and immunity of mice. Xeniji that rich in ß-carotene, phytonadione, polyphenol, citric acid and essential amino acids promote antioxidant and immunity in mice without causing toxic effect.

Bioactive Immune Components of Anti-Diarrheagenic Enterotoxigenic Escherichia coli Hyperimmune Bovine Colostrum Products.

Diarrhea is a common illness among travelers to resource-limited countries, the most prevalent attributable agent being enterotoxigenic Escherichia coli (ETEC). At this time, there are no vaccines licensed specifically for the prevention of ETEC-induced traveler's diarrhea (TD), and this has propelled investigation of alternative preventive methods. Colostrum, the first milk expressed after birthing, is rich in immunoglobulins and innate immune components for protection of newborns against infectious agents. Hyperimmune bovine colostrum (HBC) produced by immunization of cows during gestation (and containing high levels of specific antibodies) is a practical and effective prophylactic tool against gastrointestinal illnesses. A commercial HBC product, Travelan, is available for prevention of ETEC-induced diarrhea. Despite its demonstrated clinical efficacy, the underlying immune components and antimicrobial activity that contribute to protection remain undefined. We investigated innate and adaptive immune components of several commercial HBC products formulated to reduce the risk of ETEC-induced diarrhea, including Travelan and IMM-124E, a newer product that has broader gastrointestinal health benefits. The immune components measured included total and ETEC-specific IgG, total IgA, cytokines, growth factors, and lactoferrin. HBC products contained high levels of IgG specific for multiple ETEC antigens, including O-polysaccharide 78 and colonization factor antigen I (CFA/I) present in the administered vaccines. Antimicrobial activity was measured in vitro using novel functional assays. HBC greatly reduced ETEC motility in soft agar and exhibited bactericidal activity in the presence of complement. We have identified immune components and antimicrobial activity potentially involved in the prevention of ETEC infection by HBC in vivo.

A Systems Pharmacology Approach to Determine Active Compounds and Action Mechanisms of Xipayi KuiJie'an enema for Treatment of Ulcerative colitis.

Xipayi Kui Jie'an (KJA), a type of traditional Uygur medicine (TUM), has shown promising therapeutic effects in Ulcerative colitis (UC). Owing to the complexity of TUM, the pharmacological mechanism of KJA remains vague. Therefore, the identification of complex molecular mechanisms is a major challenge and a new method is urgently needed to address this problem. In this study, we established a feasible pharmacological model based on systems pharmacology to identify potential compounds and targets. We also applied compound-target and target-diseases network analysis to evaluate the action mechanisms. According to the predicted results, 12 active compounds were selected and these compounds were also identified by HPLC-ESI-MS/MS analysis. The main components were tannins, this result is consistent with the prediction. The active compounds interacted with 22 targets. Two targets including PTGS2 and PPARG were demonstrated to be the main targets associated with UC. Systematic analysis of the constructed networks revealed that these targets were mainly involved in NF-κB signaling pathway. Furthermore, KJA could also regulate the CD4 + CD25 + Foxp3 + Treg cells. In conclusion, this systems pharmacology-based approach not only explained that KJA could alleviate the UC by regulating its candidate targets, but also gave new insights into the potential novel therapeutic strategies for UC.

Enhanced Release of Immunostimulating ß-1,3- Glucan by Autodigestion of the Lingzhi Medicinal Mushroom, Ganoderma lingzhi (Agaricomycetes).

Ganoderma lingzhi is a widely used medicinal mushroom that has antioxidative effects, ameliorates insulin resistance, and improves quality of life in patients with metabolic syndrome. Potentiation of immunity is also a major function of G. lingzhi, and this has been applied in patients with cancer. Supplementing G. lingzhi into foods reduced the metastasis of cancer cells. ß-l,3-glucan is an important bioactive component of G. lingzhi. In this study we enhanced the solubilization ofimmunostimulating ß-l,3-glucan by autodigestion of G. lingzhi. Fruiting bodies of G. lingzhi were disrupted and suspended in distilled water, then autodigested at 37°C for 24 hours. The resulting suspension was dried by spray drying. To assess the solubilization of ß-l,3-glucan by autodigestion, cold and hot water extracts and sodium hydroxide extracts of G. lingzhi were prepared with and without autodigestion. Sodium hydroxide extracts were neutralized and dialyzed against distilled water. The resulting soluble and precipitated fractions were collected. Chemical, biochemical, and immunochemical characteristics of the extracts were compared. The yields of cold water extracts of autodigested and native G. lingzhi were significantly lower than the other extracts. Glucose was the major sugar component of the hot water extract, cold alkali extract (CAS), and the cold hydroxide extract insoluble in neutral aqueous condition (CASP) of the autodigested and native G. lingzhi. Nuclear magnetic resonance analysis revealed branched ß-glucans in the hot water extract and CAS of the autodigested and native G. lingzhi. By contrast, the CASP of the autodigested and native G. lingzhi comprised mainly mixtures of linear α-l,3-glucans and linear ß-l,3-glucans. Immunostimulation by ß-l,3-glucan was examined by limulus factor G activation, dectin-1 binding, and anti-ß-glucan antibody binding. Comparing relative activity, immunostimulating ß-l,3-glucan was detected in the hot water extract, rather than the CAS, of autodigested and native G. lingzhi. Immunostimulating of ß-glucan was also detected in the cold water extract of the autodigested G. lingzhi. These findings demonstrate that autodigestion is a useful processing protocol for enhancing the usefulness of G. lingzhi as a functional food.