• Applied Biological Chemistry
• /
• v.46 no.4
• /
• pp.361-366
• /
• 2003

Anti-aflatoxigenic studies on synthetic pyridione alkaloids were conducted. Seven derivatives using piperlongumine as a leading compound were prepared from 3,4,5-trimethoxycinnamic acid (TMCA). These derivatives were analyzed for their structural confrmation and purity by HPLC, GC, GC/MS and $1^H-NMR$. 1-piperidin-1-yl-3-(3,4,5-trimethoxyphenyl)propenone (1) reaction with piperidine; 1-morpholin-4-yl-3-(3,4,5-trimethoypenyl)propenone (2) with morpholine; 1-(3,5-dimethylpiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)propenone (3) with 3,5-dimethylpiperdine; 1-(2-methylpiperidine-1-yl)-3-(3,4,5-trimethoxyphenyl)propenone (4) with 2-methylpiperidine; 1-(3-hydroxypiperidin-1-yl)-3- (3,4,5-trimethoxyphenyl)propenone (5) with 3-hydroxypiperidine hydrochloride; 1-[3- (3,4,5-trimethoxyphenyl)acryloyl]piperidin-2-one (6) with ${\delta}-valerolactam;\; and\;ethyl\;1-[3-(3,4,5-trimethoxyphenyl)acyloyl]piperidine-4-carboxylate$ (7) with ethyl isonipectotate were synthesized respectively. All derivatives showed an inhibitory activity on aflatoxin $B_1$ production. In conclusion, we believe that they might be an agent for the control of mycotoxin in agricultural commodities.

• The Korean Journal of Pharmacology
• /
• v.31 no.3
• /
• pp.345-353
• /
• 1995

${\beta}-Carboline$ alkaloids including harmaline have been shown to inhibit enzymatically or nonenzymatically induced-lipid peroxidation of microsomes. This study was done to explore the antioxidant ability of harmaline and harmalol on the oxidative injuries of hyaluronic acid, lipid and collagen by $Fe^{2+}$ and $H_2O_2$. Their scavenging actions on reactive oxygen species were also examined. Harmaline, harmalol, superoxide dismutase, catalase and DMSO inhibited both degradation of hyaluronic acid by $Fe^{2+}$ and $H_2O_2$ and lipid peroxidation of microsomes by $Fe^{2+}$. In these reactions, DABCO inhibited degradation of hyaluronic acid but did not affect lipid peroxidation. ${\beta}-Carbolines$ inhibited degradation of cartilage collagen by $Fe^{2+}$, $H_2O_2$ and ascorbic acid. The reduction of ferricytochrome c due to autoxidation of $Fe^{2+}$, which is inhibited by superoxide dismutase, was not affected by harmaline and harmalol. They also did not have a decomposing action on $H_2O_2$. Hydroxyl radical production in the presence of $Fe^{2+}$ and $H_2O_2$ was inhibited by harmaline, harmalol and DMSO. Harmaline and harmalol may inhibit the oxidative injuries of hyaluronic acid, lipid and cartilage collagen by $Fe^{2+}$ and $H_2O_2$ through their scavenging actions on reactive oxygen species, OH and probably iron-oxygen complexes and exert antioxidant abilities.

• Korean Journal of Food Science and Technology
• /
• v.47 no.5
• /
• pp.680-685
• /
• 2015

Phytochemicals in Codonopsis lanceolata leaves were saponins, triterpenes, tannins, and flavonoids, not alkaloids. The levels of total polyphenols and flavonoids in Codonopsis lanceolata leaves were measured to evaluate the antioxidant activity. C. lanceolata leaves showed strong 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and potent reducing power. In addition, C. lanceolata leaf extracts inhibited production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. To examine active phytochemical for antioxidant activity, aglycone fraction of C. lanceolata leaves was analyzed by high performance liquid chromatography (HPLC). Luteolin was identified as a main component of aglycone fraction and showed potent antioxidant activity as determined by a DPPH radical scavenging assay and reducing power test. These results suggest that C. lanceolata leaves are a good source of antioxidants.

• The Korean Journal of Pharmacology
• /
• v.9 no.2
• /
• pp.1-6
• /
• 1973

Although numerous drugs are available for the treatment of superficial fungi infections of skin, the clinical effects of the majority of such drugs are not satisfactory. In the hope of searching the effective drugs for superficial fungi infections, authors studied whether Veratrum rhizoma extracts had any effect on fungi, with water extract (VRWE), ethanol extract (VREE) and methanol extract (VRME) from Veratrum album L. var. grandiflorum Max. In in vitro studies, the spores of fungi were inoculated on Sabouraud's glucose agar media which contained three extracts of Veratrun rhizoma in each concentration of $500\;{\mu}g/ml$, $1,000\;{\mu}g/ml$ and $5,000\;{\mu}g/ml$ respectively, and the growth of the fungi were observed for 3 weeks. The species of the fungi used in these experiments were Epidermophyton floccosum, Microsporum canis, Microsporum nanum, Microsporum gypseum, Microsporum cookei, Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Trichophyton verrucosum. The results of the studies were as follows: 1. The growth of M. canis, M. nanum, T mentagrophytes and T. tonsurans were slightly inhibited by VRWE $1,000\;{\mu}g/ml$, and with VRWE $5,000\;{\mu}g/ml$, the growth of E. floccosum, M. gypseum and T. rubrum were slightly inhibited, moderate inhibition on the growth of M. canis, M. nanum, M. cookei, T. mentagrophytes and T. tonsurans were showed by VRWE $5,000\;{\mu}g/ml$. 2. With $500\;{\mu}g/ml$ of VREE, the inhibition on growth of E. floccosum, M. nanum and M. gypseum were slight, however significant inhibition on the growth of M. canis, M. cookei, T. mentagrophytes, T. rubrum and T. tonsurans were observed. The growth of M. nanum and M. gypseum were moderately inhibited, and significant inhibition on the growth of E. floccosum, M. canis, M. cookei, T. mentagrophytes, T. rubrum and T. tonsurans were observed by VREE $1,000\;{\mu}g/ml$. By VREE $5,000\;{\mu}g/ml$, the growth of all tested fungi were significantly inhibited except T. verrucosuia being showed slight inhibition. 3. Significant inhibition on the growth of M. canis, T, mentagrophytes, T. rubrum and T. tonsurans were noted, and moderate inhibition of M. nanum, slight inhibition of E. floccosum and M. gypseum in growth were observed by VRME $500\;{\mu}g/ml$. The growth of E. floccosum, M. canis, M. nanum, M. cookei, T. mentsgrophytes, T. rubrum and T. tonsurans were significantly inhibited by VRME $1,000\;{\mu}g/ml$, and that of M. gypseum was moderate. With $5,000\;{\mu}g/ml$ of VRME, significant inhibition on the growth of E. floccosum, M. canis, M. nanum, M. gypseum, M. cookei, T mentagrophytes, T. rubrum and T. tonsurans were observed, and T. verrucosum was showed only slight inhibition. From the above results, it was found that the extracts of organic solvents from Veratrum rhizoma (VREE & VRME) exerted significant antifungal activity, and their effects were probably derived from the pharmacological action of steroidal alkaloids.

• Journal of Sericultural and Entomological Science
• /
• v.48 no.1
• /
• pp.25-27
• /
• 2006

[ ${\alpha}-Glycosidase$ ] inhibitors slows the velocity of the uptake of monosaccharides in the small intestine by retarding the speed of degradation of disaccharides to monosaccharides, which made it possible to develop ${\alpha}-glycosidase$ inhibitors as the antihyperglycemic ('antihyperglycemic' means 'blood-glucose-level-lowering') reagent for the diabetic patients such as acarbose and miglitol. Twenty kinds of ${\alpha}-glycosidase$ inhibitors have been reported to exist in mulberry, Morns alba, and some of them are also found in the silkworm, Bombyx mari, as the result of its daily feeding of mulberry leaves as the sole diet. 1-Deoxynojirimycin (DNJ), one of the most potent ${\alpha}-glycosidase$ inhibitor, is the most abundant among polyhydroxylated alkaloids with ${\alpha}-glycosidase$ inhibiting activity in both M alba and B. mari, therefore considered the antihyperglycemic criterion of the mulberry- or silkworm-based neutroceutical products. DNJ is thought to be accumulated in the body of silkworm because the its concentration in the silkworm body is two to three times as much as that in the mulberry leaves. Eighteen silkworm F1 varieties have been recommended for industrial rearing in Korea by some standards such as pathological strength. DNJ concentration in 18 recommendedwere measured at 3rd day in the 5th instar after lyophilization to determine the varieties that accumulates DNJ in its body most. GeumOk-Jam was the highest in the DNJ concentration of 5.45 mg/gDW among the recommended F1 varieties.

• Korean Journal of Clinical Pharmacy
• /
• v.22 no.4
• /
• pp.356-366
• /
• 2012

Background: Chemotherapy-induced peripheral neuropathy (CIPN) involving sensory and motor nerve damage or dysfunction is a common and serious clinical problem that affects many patients receiving cancer treatment. This condition may pose challenges for the clinician to diagnose and manage, particularly in patients with coexisting conditions or disorders that involve the peripheral nervous system. Many chemotherapeutic agents used today are associated with the development of serious and dose-limiting CIPN that can adversely affect the administration of planned therapy and can impair quality of life by interference with the patients' activities of daily living. The most important clinical objective in the evaluation of patients with CIPN is to determine their level of functional impairment involving activities of daily living. These findings are used to make medical decisions to continue, modify, delay, or stop treatment. The most commonly reported drugs to cause CIPN include taxanes, platinum agents, vinca alkaloids, thalidomide, and bortezomib. We aimed to determine PN incidence during cisplatin, carboplatin and oxaliplatin administration. Methods: We collected data from 125 patients who received at least one cycle of cisplatin, carboplatin or oxaliplatin. They completed a self-reported questionnaire and items related to their disease and peripheral neuropathy. The investigators filled in part of items about disease and treatment. Patient Neurotoxicity Qeustionnaire developed by Bionumerik company were applied for PN assessment. Results: The incidences of sensory neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 23%, 56% and 50%. The incidences of motor neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 18%, 42% and 19%. The incidences of severe neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 13%, 28% and 14%. The incidences of PN were associated with cumulative dose but not age, gender and concurrent illness. 19.2% of the patients (24/125) were prescribed with gabapentin, nortriptyline or gabapentin plus nortriptyline to reduce these peripheral symptoms and 75% of the patients answered the drug were effective. Conclusion: Incidence of PN after cisplatin or oxaliplatin administration is cumulative dose-related. Physician-based assessments under-reported the incidence and severity of CIPN. To overcome this limitation, diagnostic tools specifically designed to assess peripheral neuropathy severity associated with chemotherapy must be developed.

• Journal of Plant Biotechnology
• /
• v.42 no.3
• /
• pp.186-195
• /
• 2015

Anthranilate synthase (AS) is a key enzyme in the biosynthesis of tryptophan (Trp), which is the precursor of bioactive metabolites like indole-3-acetic acid and other indole alkaloids. Alpha anthranilate synthase 2 (OsASA2) plays a critical role in the feedback inhibition of tryptophan biosynthesis. In this study, two vectors with single (F124V) and double (S126F/L530D) point mutations of the OsASA2 gene for feedback-insensitive ${\alpha}$ subunit of rice anthranilate synthase were constructed and transformed into wildtype Dongjinbyeo by Agrobacterium-mediated transformation. Transgenic single and double mutant lines were selected as a single copy using TaqMan PCR utilized nos gene probe. To select intergenic lines, the flanking sequence of RB or LB was digested with a BfaI enzyme. Four intergenic lines were selected using a flanking sequence tagged (FST) analysis. Expression in rice (Oryza sativa L.) of the transgenes resulted in the accumulation of tryptophan (Trp), indole-3-acetonitrile (IAN), and indole-3-acetic acid (IAA) in leaves and tryptophan content as a free amino acid in seeds also increased up to 30 times relative to the wildtype. Two homozygous event lines, S-TG1 and D-TG1, were selected for characterization of agronomic traits and metabolite profiling of seeds. Differentially expressed genes (DEGs), related to ion transfer and nutrient supply, were upregulated and DEGs related to co-enzymes that work as functional genes were down regulated. These results suggest that two homozygous event lines may prove effective for the breeding of crops with an increased level of free tryptophan content.

• Journal of Plant Biotechnology
• /
• v.42 no.3
• /
• pp.135-153
• /
• 2015

The aromatic amino acids, which are composed of $\small{L}$-phenylalanine, $\small{L}$-tyrosine and $\small{L}$-tryptophan, are general components of protein synthesis as well as precursors for a wide range of secondary metabolites. These aromatic amino acids-derived compounds play important roles as ingredients of diverse phenolics including pigments and cell walls, and hormones like auxin and salicylic acid in plants. Moreover, they also serve as the natural products of alkaloids and glucosinolates, which have a high potential to promote human health and nutrition. The biosynthetic pathways of aromatic amino acids share a chorismate, the common intermediate, which is originated from shikimate pathway. Then, tryptophan is synthesized via anthranilate and the other phenylalanine and tyrosine are synthesized via prephenate, as intermediates. This review reports recent studies about all the enzymatic steps involved in aromatic amino acid biosynthetic pathways and their gene regulation on transcriptional/post-transcriptional levels. Furthermore, results of metabolic engineering are introduced as efforts to improve the production of the aromatic amino acids-derived secondary metabolites in plants.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.7
• /
• pp.3335-3340
• /
• 2016

Background: Oral submucous fibrosis (OSF) is a precancerous condition with a 4 to13% malignant transformation rate. Related to the habit of areca nut chewing it is mainly prevalent in South-east Asian countries where the habit of betel quid chewing is frequently practised. On chewing, alkaloids and polyphenols are released which undergo nitrosation and give rise to N-nitrosamines which are cytotoxic agents. CYP450 is a microsomal enzyme group which metabolizes various endogenous and exogenous chemicals including those released by areca nut chewing. CYP1A1 plays a central role in metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes nitrosamines and tannins. Polymorphisms in genes that code for these enzymes may alter their expression or function and may therefore affect an individuals susceptibility regarding OSF and oral cancer. The present study was therefore undertaken to investigate the association of polymorphisms in CYP1A1 m2 and CYP2E1 (RsaI/PstI) sites with risk of OSF among areca nut chewers in the Northern India population. A total of 95 histopathologically confirmed cases of OSF with history of areca nut chewing not less than 1 year and 80, age and sex matched controls without any clinical signs and symptoms of OSF with areca nut chewing habit not less than 1 year were enrolled. DNA was extracted from peripheral blood samples and polymorphisms were analyzed by PCR-RFLP method. Gene polymorphism of CYP1A1 at NcoI site was observed to be significantly higher (p = 0.016) in cases of OSF when compared to controls. Association of CYP1A1 gene polymorphism at NcoI site and the risk of OSF (Odd's Ratio = 2.275) was also observed to be significant. However, no such association was observed for the CYP2E1 gene polymorphism (Odd's Ratio = 0.815). Our results suggest that the CYP1A1 gene polymorphism at the NcoI site confers an increased risk for OSF.

• Biomolecules & Therapeutics
• /
• v.17 no.1
• /
• pp.47-56
• /
• 2009

Schizandra chinensis (S. chinensis) exhibits a harmless, 'adaptogen-type' effect leading to improvements in mental performance and learning efficacy in brain. Activated microglia contributes to neuronal injury by releasing neurotoxic products, which make it important to regulate microglial activation to prevent further cytological as well as functional brain damage. However, the effect of S. chinensis on microglial activation has not been examined yet. We have investigated the effects of four compounds (Gomisin A, Gomisin N, Schizandrin and Schizandrol A) from S. chinensis on lipopolysaccharide (LPS)-induced microglial activation. In this study, BV2 microglial cells were activated with LPS and the microglial activation was assessed by up-regulation of activation markers such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinase-9 (MMP-9). The results showed that all four compounds significantly reduced the intracellular level of ROS, the release of NO and MMP-9 as well as LPS-induced phosphorylation of ERK1/2. These results strongly suggested that S. chinensis may be useful to modulate inflammation-mediated brain damage by regulating microglial activation.