International Journal of Advanced Culture Technology
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제6권4호
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pp.109-115
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2018
Garlic is a medicinal plant used throughout the world for its anti-inflammatory, antioxidant, and antiplatelet activities. Chitosan is a natural polysaccharide obtained from chitin, and derivatives of chitosan have been shown to inhibit platelet aggregation and adhesion. We hypothesized that fermented preparations of these products may possess stronger antiplatelet effects than the non-fermented forms owing to the increased bioavailability of the bioactive compounds produced during fermentation. Therefore, we compared these compounds via in vitro and ex vivo platelet aggregation assays by using standard light transmission aggregometry and ex vivo granule secretions from rat platelets. We found that fermented preparations exerted more potent and significant inhibition of platelet aggregation both in vitro and ex vivo. Likewise, ATP release from dense granules of platelets was also significantly inhibited in fermented preparation-treated rat platelets compared to that in non-fermented preparation-treated ones. We concluded that fermented preparations exerted more potent effects on platelet function both in vitro and ex vivo, possibly as a result of the increased bioavailability of active compounds produced during fermentation. We therefore suggest that fermented products may be potent therapeutics against platelet-related CVDs and can be used as antiplatelet and antithrombotic agents.
Ahmed, Hanaa H;Abd-Rabou, Ahmed A;Hassan, Amal Z;Kotob, Soheir E
Asian Pacific Journal of Cancer Prevention
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제16권16호
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pp.7179-7188
/
2015
Cancer is a major health obstacle around the world, with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) as major causes of morbidity and mortality. Nowadays, there isgrowing interest in the therapeutic use of natural products for HCC and CRC, owing to the anticancer activity of their bioactive constituents. Boswellia serrata oleo gum resin has long been used in Ayurvedic and traditional Chinese medicine to alleviate a variety of health problems such as inflammatory and arthritic diseases. The current study aimed to identify and explore the in vitro anticancer effect of B. Serrata bioactive constituents on HepG2 and HCT 116 cell lines. Phytochemical analysis of volatile oils of B. Serrata oleo gum resin was carried out using gas chromatography-mass spectrometry (GC/MS). Oleo-gum-resin of B. Serrata was then successively extracted with petroleum ether (extract 1) and methanol (extract 2). Gas-liquid chromatography (GLC) analysis of the lipoidal matter was also performed. In addition, a methanol extract of B. Serrata oleo gum resin was phytochemically studied using column chromatography (CC) and thin layer chromatography (TLC) to obtain four fractions (I, II, III and IV). Sephadex columns were used to isolate ${\beta}$-boswellic acid and identification of the pure compound was done using UV, mass spectra, $^1H$ NMR and $^{13}C$ NMR analysis. Total extracts, fractions and volatile oils of B. Serrata oleo-gum resin were subsequently applied to HCC cells (HepG2 cell line) and CRC cells (HCT 116 cell line) to assess their cytotoxic effects. GLC analysis of the lipoidal matter resulted in identification of tricosane (75.32%) as a major compound with the presence of cholesterol, stigmasterol and ${\beta}$-sitosterol. Twenty two fatty acids were identified of which saturated fatty acids represented 25.6% and unsaturated fatty acids 74.4% of the total saponifiable fraction. GC/MS analysis of three chromatographic fractions (I,II and III) of B. Serrata oleo gum resin revealed the presence of pent-2-ene-1,4-dione, 2-methyl- levulinic acid methyl ester, 3,5- dimethyl- 1-hexane, methyl-1-methylpentadecanoate, 1,1- dimethoxy cyclohexane, 1-methoxy-4-(1-propenyl)benzene and 17a-hydroxy-17a-cyano, preg-4-en-3-one. GC/MS analysis of volatile oils of B. Serrata oleo gum resin revealed the presence of sabinene (19.11%), terpinen-4-ol (14.64%) and terpinyl acetate (13.01%) as major constituents. The anti-cancer effect of two extracts (1 and 2) and four fractions (I, II, III and IV) as well as volatile oils of B. Serrata oleo gum resin on HepG2 and HCT 116 cell lines was investigated using SRB assay. Regarding HepG2 cell line, extracts 1 and 2 elicited the most pronounced cytotoxic activity with $IC_{50}$ values equal 1.58 and $5.82{\mu}g/mL$ at 48 h, respectively which were comparable to doxorubicin with an $IC_{50}$ equal $4.68{\mu}g/mL$ at 48 h. With respect to HCT 116 cells, extracts 1 and 2 exhibited the most obvious cytotoxic effect; with $IC_{50}$ values equal 0.12 and $6.59{\mu}g/mL$ at 48 h, respectively which were comparable to 5-fluorouracil with an $IC_{50}$ equal $3.43{\mu}g/mL$ at 48 h. In conclusion, total extracts, fractions and volatile oils of B. Serrata oleo gum resin proved their usefulness as cytotoxic mediators against HepG2 and HCT 116 cell lines with different potentiality (extracts > fractions > volatile oil). In the two studied cell lines the cytotoxic acivity of each of extract 1 and 2 was comparable to doxorubicin and 5-fluorouracil, respectively. Extensive in vivo research is warranted to explore the precise molecular mechanisms of these bioactive natural products in cytotoxicity against HCC and CRC cells.
Yixian Quah;Yuan Yee Lee;Seung-Jin Lee;Sung Dae Kim;Man Hee Rhee;Seung-Chun Park
Journal of Ginseng Research
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제47권2호
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pp.283-290
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2023
Hypercoagulability is frequently observed in patients with severe coronavirus disease-2019 (COVID-19). Platelets are a favorable target for effectively treating hypercoagulability in COVID-19 patients as platelet hyperactivity has also been observed. It is difficult to develop a treatment for COVID-19 that will be effective against all variants and the use of antivirals may not be fully effective against COVID-19 as activated platelets have been detected in patients with COVID-19. Therefore, patients with less severe side effects often turn toward natural remedies. Numerous phytochemicals are being investigated for their potential to treat a variety of illnesses, including cancer and bacterial and viral infections. Natural products have been used to alleviate COVID-19 symptoms. Panax ginseng has potential for managing cardiovascular diseases and could be a treatment for COVID-19 by targeting the coagulation cascade and platelet activation. Using molecular docking, we analyzed the interactions of bioactive chemicals in P. ginseng with important proteins and receptors involved in platelet activation. Furthermore, the SwissADME online tool was used to calculate the pharmacokinetics and drug-likeness properties of the lead compounds of P. ginseng. Dianthramine, deoxyharrtingtonine, and suchilactone were determined to have favorable pharmacokinetic profiles.
Lee, Seoung Rak;Choi, Jin Hee;Ryoo, Rhim;Kim, Jin-Chul;Pang, Changhyun;Kim, Seon-Hee;Kim, Ki Hyun
Journal of Microbiology and Biotechnology
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제30권11호
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pp.1769-1776
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2020
As part of our current work to discover structurally and/or biologically novel compounds from Korean wild mushrooms, we isolated five ergostane-type steroids (1-5) from the fruiting bodies of Xerula furfuracea via repeated column chromatographic separations and HPLC purification. The chemical structures of the isolated steroids were shown to be (22E,24R)-24-methylcholesta-4,22-diene-3,6-dione (1), ergosta-7,22-diene-3β,5α,6β-triol (2), ergosta-7,22-diene-3β,5α,6β,9α-tetraol (3), (22E,24R)-5α,8α-epidioxyergosta-6,22-diene-3β-ol-3-O-β-D-glucopyranoside (4), and (22E,24R)-5α,8α-epidioxyergosta-6,9,22-triene-3β-ol-3-O-β-D-glucopyranoside (5)based on comparison of the data regarding their spectroscopic and physical properties with those of previous studies. Notably, this is the first report on the presence of the identified steroids (1-5) in this mushroom. We tested compounds 1-5 to determine their effects on adipogenesis and osteogenesis in the mouse mesenchymal stem cell line C3H10T1/2 and found that compounds 4 and 5 suppressed the differentiation of stem cells into adipocytes. Notably, in addition to its suppressive effect on adipogenesis, compound 5 was also shown to promote the osteogenic differentiation of stem cells. These findings demonstrate that the bioactive compounds isolated might be effective for the treatment of menopause-associated syndromes, such as osteoporosis and obesity, as the isolated compounds were shown to suppress adipogenesis and/or promote osteogenesis of stem cells.
Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and produce excessive amounts of nitric oxide (NO) and prostaglandin E$_2$ (PGE$_2$), which play key roles in the processes of inflammation and carcinogenesis. The root of Paeonia lactiflora Pall., and the root cortex of Paeonia suffruticosa Andr., are important Chinese crude drugs used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) is a major bioactive constituent of both crude drugs. PGG has been shown to possess potent anti-oxidant, anti-mutagenic, anti-proliferative and anti-invasive effects. In this study, we examined the inhibitory effects of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) isolated from the root of Paeonia lactiflora Pall. on the COX-2 and iNOS activity in LPS-activated Raw 264.7 cells, COX-1 in HEL cells. To investigate the structure-activity relationships of gallate and gallic acid for the inhibition of iNOS and COX-2 activity, we also examined (-)-epigallocatechin gallate (EGCG), gallic acid, and gallacetophenone. The results of the present study indicated that PGG, EGCG, and gallacetophenone treatment except gallic acid significantly inhibited LPS-induced NO production in LPS-activated macrophages. All of the four compounds significantly inhibited COX-2 activity in LPS-activated macrophages. Among the four compounds examined, PGG revealed the most potent in both iNOS ($IC_{50}$ = 18 $\mu\textrm{g}/mL$) and COX-2 inhibitory activity (PGE$_2$: $IC_{50}$ = 8 $\mu\textrm{g}/mL$ and PGD$_2$: $IC_{50}$ = 12 $\mu\textrm{g}/mL$), respectively. Although further studies are needed to elucidate the molecular mechanisms and structure-activity relationship by which PGG exerts its inhibitory actions, our results suggest that PGG might be a candidate for developing anti-inflammatory and cancer chemopreventive agents.
Objectives : Ligustri Fructus has been used since ancient times as a medicinal usages in folk medicines against antitumor purpose. Many biological active constituents have been identified from this biomass such as several terpenoids and lignans. In current study, the properties of antioxidant and anti-diabetic complications using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)($ABTS^+$) radicals scavenging, and advanced glycation end products (AGEs) inhibition assays were evaluated by different extraction methods of Ligustri Fructus. Methods : In present continuing research for development of bioactive natural ingredients, antioxidant and AGEs formation inhibitory capacities of Ligustri Fructus extracts using different organic solvents were prepared and the biological potentials were investigated using in vitro bioassays. Antioxidant properties were evaluated employing radical scavenging assays using DPPH and $ABTS^+$ radicals. In addition, the anti-diabetic complications effects of Ligustri Fructus extracts were tested via AGEs formation inhibitory assay. The total phenolic contents were determined using a spectrophotometric method. Results : All the tested extracts exhibited dose-dependent radical scavenging and AGEs formation inhibitory activities. Among the tested samples, hot water extract of Ligustri Fructus was showed the most potent activity with $IC_{50}$ value of $494.8{\pm}6.7{\mu}g/m{\ell}$ against DPPH radical scavenging assay. Also, $ABTS^+$ radical scavenging activity of hot water extract was higher than those of other extracts. In addition, AGEs formation inhibitory effects of each extacts and total phenolic contents were evaluated. Conclusions : These results suggested that Ligustri Fructus can be considered as a new effective source of natural antioxidant and anti-diabetic complications resources.
Nadalian, Mehdi;Kamaruzaman, Nurkhuzaiah;Yusop, Mohd Shakir Mohamad;Babji, Abdul Salam;Yusop, Salma Mohamad
한국축산식품학회지
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제39권6호
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pp.966-979
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2019
Muscle-based by-products are often undervalued although commonly reported having a high amount of natural bioactive peptides. In this study, elastin was isolated from the protein of broiler hen skin while its hydrolysate was prepared using Elastase. Assessment of antioxidative properties of elastin-based hydrolysate (EBH) was based on three different assays; 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical, 2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical and metal chelating ability. The EBH was purified further using ultrafiltration, gel filtration and Reverse- Phase High-Performance Liquid Chromatography (RP-HPLC). The IC50 of ABTS radical activities for EBH were decreased as EBH further purified using ultrafiltration (EBH III; 0.66 mg/mL)>gel filtration (EB-II; 0.42 mg/mL)>RP-HPLC (EB-II4; 0.12 mg/mL). The sequential identification of the peptide was done by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/ TOF-MS) of the potent fractions obtained from RP-HPLC (EB-II4). The presence of hydrophobic amino acids (Val and Pro) in the peptide sequences could potentially contribute to the high antioxidant activity of EBH. The sequences GAHTGPRKPFKPR, GMPGFDVR and ADASVLPK were identified as antioxidant peptides. In conclusion, the antioxidative potential from poultry skin specifically from elastin is evident and can be explored to be used in many applications such as health and pharmaceutical purposes.
The pikromycin biosynthetic system in Streptomyces venezuleae is unique for its ability to produce two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolides narbomycin and pikromycin. The metabolic pathway also contains two post polyketide-modification enzymes, a glycosyltransferase and P450 hydroxylase that have unusually broad substrate specificities. In order to explore further the substrate flexibility of these enzymes a series of hybrid polyketide synthases were constructed and their metabolic products characterized. The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products. The polyketide backbone of rifamycin B is assembled through successive condensation and ${\beta}$-carbonyl processing of the extender units by the modular rifamycin PKS. The eighth module, in the RifD protein, contains nonfunctional DH domain and functional KR domain, which specify the reduction of the ${\beta}$-carbonyl group resulting in the C-21 bydroxyl of rifamycin B. A four amino acid substitution and one amino acid deletion were introduced in the putative NADPH binding motif in the proposed KR domain encoded by rifD. This strategy of mutation was based on the amino acid sequences of the corresponding motif of the KR domain of module 3 in the RifA protein, which is believed dysfunctional, so as to introduce a minimum alteration and retain the reading frame intact, yet ensure loss of function. The resulting strain produces linear polyketides, from tetraketide to octaketide, which are also produced by a rifD disrupted mutant as a consequence of premature termination of polyketide assembly. Much of the structural diversity within the polyketide superfamily of natural products is due to the ability of PKSs to vary the reduction level of every other alternate carbon atom in the backbone. Thus, the ability to introduce heterologous reductive segments such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) into modules that naturally lack these activities would increase the power of the combinatorial biosynthetic toolbox. The dehydratase domain of module 7 of the rifamycin PKS, which is predicted to be nonfunctional in view of the sequence of the apparent active site, was replaced with its functional homolog from module 7 of rapamycin-producing polyketide synthase. The resulting mutant strain behaved like a rifC disrupted mutant, i.e., it accumulated the heptaketide intermediate and its precursors. This result points out a major difficulty we have encountered with all the Amycolatopsis mediterranei strain containing hybrid polyketide synthases: all the engineered strains prepared so far accumulate a plethora of products derived from the polyketide chain assembly intermediates as major products instead of just analogs of rifamycin B or its ansamycin precursors.
Efficiency of a far-infrared radiation (FIR) dryer for drying of citrus by-products (CBPs) was evaluated through their antioxidant activities. The CBPs dried through FIR were enzymatically digested by six carbohydrases (AMG, Celluclast, Pectinase, Termamyl, Ultraflo and Viscozyme) to prepare digests for evaluation of the activities. The total polyphenolic and total flavonoid contents of the digests were determined by colorimetric assays. The AMG digest was selected for the further experiments. The antioxidant potential of the digests were evaluated by DPPH, superoxide, hydroxyl and alkyl radical scavenging activities, $H_2O_2$ scavenging activity, metal chelating, lipid peroxidation inhibition and the reduction of DNA damage. The AMG digest from CBPs dried through FIR at $50^{\circ}C$ showed strong antioxidant activities in DPPH, superoxide, hydrogen peroxide, alkyl and metal chelating assays while all the digests showed strong lipid peroxidation activities. Further, enzymatic digests showed remarkable inhibitory activities against $H_2O_2$-induced DNA damage. Hence, the data obtained using different in vitro models clearly established the antioxidant potential of enzymatic digests from CBPs dried through FIR. Furthermore, they can be used as a source of natural antioxidants; hence, far-infrared radiation drying is a viable method for transforming wet CBPs into a dried form without destroying the bioactive components.
Bui, Trung Hieu;Le, Thi Thuy;Vu, Thu Thuy;Hoang, Xuan Tien;Luu, Van Chinh;Vu, Dinh Hoang;Tran, Khac Vu
Bulletin of the Korean Chemical Society
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제33권5호
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pp.1586-1592
/
2012
A series of Novel Mannich bases has been synthesized and evaluated $in$$vitro$ cytotoxic activity against the human hepatocellular carcinoma (HepG2), human lung carcinoma (SK-LU-1), and human breast cancer (MCF-7). Compound $\mathbf{9f}$ was found to be most potent against three cell lines with $IC_{50}$ values of 1.57, 1.16 and 1.21 ${\mu}g$/mL, respectively. In addition, compounds $\mathbf{9g}$, $\mathbf{10f}$ exhibited very significant activity against MCF-7 cell line with $IC_{50}$ values of 2.0 ${\mu}g$/mL.
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