Flavonoids: Potential Antiinflammatory Agents

Kim, Hyun-Pyo,Son, Kun-Ho,Chang, Hyun-Wook,Kang, Sam-Sik The Korean Society of Pharmacognosy 1996 Natural Product Sciences Vol.2 No.1

Flavonoids are widely distributed polyphenol compounds in plant kingdom and known to possess varieties of biological/pharmacological activities in vitro and in vivo. A search for antiinflammatory/immunoregulatory flavonoids as potential therapeutic agents has been continued, since serious side effects of currently used nonsteroidal and steroidal antiinflammatory drugs limit their long term uses for the inflammatory disorders. In this reserch, various flavonids were isolated and tested for their in vivo antiinflammatory activity and in vitro inhibitory activity of lymphocyte proliferation. Using a mouse ear edema assay, it was found that certain flavones/flavonols possess mild antiinflammatory activity and a C-2,3-double bond might be essential. Isoflavones were less active. These flavonoids inhibited in vitro lymphocyte proliferation, relatively specific for T-cell proliferation $(IC_{50}=1-10\;{\mu}M)$ and the inhibition was reversible. We have also tested several biflavonoid derivatives, since we recently found that biflavones were phospholipase $A_2$ inhibitors. It was demonstrated that biflavones such as ochnaflavone and ginkgetin inhibited lymphocyte proliferation induced by both concanavaline A and lipopolysaccharide. The inhibition was irreversible in contrast to that of flavones/flavonols. And antiinflammatory activity of biflavonoids are discussed.

Potential Antiinflammatory Agents

Kim, Hyun Pyo,Son, Kun Ho,Chang, Hyeun Wook,Kang, Sam Sik 영남대학교 약품개발연구소 1996 영남대학교 약품개발연구소 연구업적집 Vol.6 No.-

Flavonoids are widely distributed polyphenol compounds in plant kingdom and known to possess varieties of biological/pharmacological activities in vitro and in vivo. A search for antiinflammatory/immunoregulatory flavonoids as potential therapeutic agents has been continued, since serious side effects of currently used nonsteroidal and steroidal antiinflammatory drugs limit their long term uses for the inflammatory disorders. In this reserch, various flavonids were isolated and tested for their in vivo antiinflammatory activity and in vitro inhibitory activity of lymphocyte proliferation. Using a mouse ear edema assay, it was found theat certain flavones/flavonols possess mild antiinflammatory activity and a C-2-3-double bond might be essential. Isoflavones were leass active. These flavonoids inhibited in vitro lymphocyte proliferation, relatively specific for T-cell proliferation (IC_(50)-1-10μM) and the inhibition was reversible. We have also tested several biflavonoid derivatives, since we recently found that biflavones were phospholipase A₂ inhibitors. It was demonstrated that biflavones such as ochnaflavone and ginkgetin inhibited lymphocyte proliferation induced by both concanavaline A and lipopolysaccharide. The inhibition was irreversible in contrast to that of flavones/flavonols. And antiinflammatory activity of biflavonoids are discussed.

Monovalent와 bivalent aminoantipyrine 유도체의 합성과 항염 진통활성

김승재(Seung Jae Kim),권오혁(Oh Hyeok Kwon),전상철(Sang Chul Jun),박상민(Sang Min Park),임채욱(Chae Uk Im),임철부(Chul Bu Yim) 대한약학회 2002 약학회지 Vol.46 No.3

Six novel 4-aminoantipyrine derivatives as potential nonsteroidal antiinflammatory and analgesic compounds were prepared and their antiiflammatory-analgesic activity were compared with antipyrine. Succinyl chloride and Ac20 were reacted with glycine, respectively to give glycine compounds (3-4, 9-10), which were treated with hydroxysuccinimide and dicyclohexyl carbodiimide to yield active esters (5-6,11-12), and then reacted with 4-aminoantipyrine to prepare 4-aminoantipyrine derivatives (7-8, 13-14). 4-Aminoantipyrine reacted with succinyl chloride and Ac20, respectively to give succinyl leis aminoantipyrine (15) and acetyl aminoantipyrine (16). Compounds (7), (8) and (13) gave comparable antiinflammatory activity to antipyrine.

Cinmetacin의 amide유도체 합성과 항염진통촬성

임채욱(Chaeuk Im),홍용기(Yong Ki Hong),임철부(Chul Bu Yim) 대한약학회 2001 약학회지 Vol.45 No.6

Five novel cinmetacin amide derivatives as potential nonsteroidal antiinflammatory and analgesic compounds were prepared and their antiinflammatory-analgesic activity was compared with cinmetacin. Cinmetacin and hydroxysuccinimide were reacted with dicyclohexyl carbodiimide to give cinmetacin active ester (4), which was treated with amines to yield cinmetacin amides (5-9). Compounds (5) and (9) gave stronger analgesic activity than cinmetacin and compounds (5), (6), (9) showed comparable antiin1ammatory activity to cinmetacin.

Dammarane-type triterpene oligoglycosides from the leaves and stems of Panax notoginseng and their antiinflammatory activities

Li, Juan,Wang, Ru-Feng,Zhou, Yue,Hu, Hai-Jun,Yang, Ying-Bo,Yang, Li,Wang, Zheng-Tao The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.3

Background: Inflammation is widespread in the clinical pathology and closely associated to the progress of many diseases. Triterpenoid saponins as a key group of active ingredients in Panax notoginseng (Burk.) F.H. Chen were demonstrated to show antiinflammatory effects. However, the chemical structures of saponins in the leaves and stems of Panax notoginseng (PNLS) are still not fully clear. Herein, the isolation, purification and further evaluation of the antiinflammatory activity of dammarane-type triterpenoid saponins from PNLS were conducted. Methods: Silica gel and reversed-phase C8 column chromatography were used. Furthermore, preparative HPLC was used as a final purification technique to obtain minor saponins with high purities. MS, NMR experiments, and chemical methods were used in the structural identifications. The antiinflammatory activities of the isolated saponins were assessed by measuring the nitric oxide production in RAW 264.7 cells stimulated by lipopolysaccharides. Real-time reverse transcription polymerase chain reaction was used to measure the gene expressions of inflammation-related gene. Results: Eight new minor dammarane-type triterpene oligoglycosides, namely notoginsenosides LK1-LK8 (1-8) were obtained from PNLS, along with seven known ones. Among the isolated saponins, gypenoside IX significantly suppressed the nitric oxide production and inflammatory cytokines including tumor necrosis $factor-{\alpha}$, interleukin 10, interferon-inducible protein 10 and $interleukin-1{\beta}$. Conclusion: The eight saponins may enrich and expand the chemical library of saponins in Panax genus. Moreover, it is reported for the first time that gypenoside IX showed moderate antiinflammatory activity.

Antinociceptive and antiinflammatory activities of pine (Pinus densiflora) pollen extract

Heyden & Son 2007 Phytotherapy research Vol.21 No.5

<P>The study aimed to evaluate the antinociceptive and antiinflammatory activity of pine (Pinus densiflora) pollen in mice. The antinociceptive activity was determined using acetic acid-induced abdominal constriction and formalin-induced licking, and the hot plate test. Antiinflammatory effects were evaluated using carrageenan- and formalin-induced paw edema, and arachidonic acid-induced ear edema in mice. The ethanol extract of pine pollen (100 and 200 mg/kg, p.o.) produced a significant inhibition of both phases of the formalin pain test in mice, a reduction in mouse writhing induced by acetic acid and an elevation of the pain threshold in the hot plate test in mice. The pine pollen extract also produced a significant inhibition of carrageenan- and formalin-induced paw edema as well as arachidonic acid-induced ear edema in mice. The inhibitions were similar to those produced by aminopyrine and indomethacin, p.o. The different polyphenols found in pine pollen could account for the antinociceptive and antiinflammatory actions. The results obtained indicate that the extract possesses analgesic and antiinflammatory effects. Copyright © 2007 John Wiley & Sons, Ltd.</P>

Analgesic and Antiinflammatory Activities of Some New Mannich Bases of 5-Nitro- 2-Benzoxazolinones

Meri?K?sal,Nesrin G?han,Esra K?eli,Erdem Yesilada,Hakki Erdogan 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.4

In this study, the synthesis of a novel series Mannich bases of 5-nitro-3-substituted piperazinomethyl- 2-benzoxazolinones are described. The structures attributed to compounds 3a-3k were elucidated using IR, 1H-NMR spectroscopic techniques besides elemental analysis. The compounds were examined for their in vivo antiinflammatory and analgesic activities in two different bioassays, namely, carrageenan-induced hind paw edema and p-benzoquinone-induced abdominal constriction tests in mice, respectively. In addition, the ulcerogenic effects of the compounds were determined. Among the tested derivatives most promising results were obtained for the compounds bearing electron-withdrawing substituents (F, Cl, COCH3) in the ortho/para position of the phenyl nucleus on the piperazine ring at 3 position of benzoxazolinone moiety (3a, 3b, 3c, 3d, 3h). The analgesic activities of all compounds are higher than their antiinflammatory activities. Antiinflammatory inhibitory ratios for all compounds were above 30% for the last two measurements. Because of this compounds 3a, 3b, 3c, 3d deserve attention and may be considered for further evaluation.

Two new triterpenoid saponins derived from the leaves of Panax ginseng and their antiinflammatory activity

Li, Fu,Cao, Yufeng,Luo, Yanyan,Liu, Tingwu,Yan, Guilong,Chen, Liang,Ji, Lilian,Wang, Lun,Chen, Bin,Yaseen, Aftab,Khan, Ashfaq A.,Zhang, Guolin,Jiang, Yunyao,Liu, Jianxun,Wang, Gongcheng,Wang, Ming-Kui The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

Background: The leaves and roots of Panax ginseng are rich in ginsenosides. However, the chemical compositions of the leaves and roots of P. ginseng differ, resulting in different medicinal functions. In recent years, the aerial parts of members of the Panax genus have received great attention from natural product chemists as producers of bioactive ginsenosides. The aim of this study was the isolation and structural elucidation of novel, minor ginsenosides in the leaves of P. ginseng and evaluation of their antiinflammatory activity in vitro. Methods: Various chromatographic techniques were applied to obtain pure individual compounds, and their structures were determined by nuclear magnetic resonance and high-resolution mass spectrometry, as well as chemical methods. The antiinflammatory effect of the new compounds was evaluated on lipopolysaccharide-stimulated RAW 264.7 cells. Results and conclusions: Two novel, minor triterpenoid saponins, ginsenoside $LS_1$ (1) and 5,6-didehydroginsenoside $Rg_3$ (2), were isolated from the leaves of P. ginseng. The isolated compounds 1 and 2 were assayed for their inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 cells, and Compound 2 showed a significant inhibitory effect with $IC_{50}$ of $37.38{\mu}M$ compared with that of NG-monomethyl-L-arginine ($IC_{50}=90.76{\mu}M$). Moreover, Compound 2 significantly decreased secretion of cytokines such as prostaglandin $E_2$ and tumor necrosis factor-${\alpha}$. In addition, Compound 2 significantly suppressed protein expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggested that Compound 2 could be used as a valuable candidate for medicinal use or functional food, and the mechanism is warranted for further exploration.

Identification of a novel triterpene saponin from Panax ginseng seeds, pseudoginsenoside RT<SUB>8</SUB>, and its antiinflammatory activity

Taewoong Rho,Hyun Woo Jeong,Yong Deog Hong,Keejung Yoon,Jae Youl Cho,Kee Dong Yoon 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.1

Background: Panax ginseng Meyer (Araliaceae) is a highly valued medicinal plant in Asian regions, especially in Korea, China, and Japan. Chemical and biological studies on P. ginseng have focused primarily on its roots, whereas the seeds remain poorly understood. This study explores the phytochemical and biological properties of compounds from P. ginseng seeds. Methods: P. ginseng seeds were extracted with methanol, and 16 compounds were isolated using various chromatographic methods. The chemical structures of the isolates were determined by spectroscopic data. Antiinflammatory activities were evaluated for triterpene and steroidal saponins using lipopolysaccharide-stimulated RAW264.7 macrophages and THP-1 monocyte leukemia cells. Results: Phytochemical investigation of P. ginseng seeds led to the isolation of a novel triterpene saponin, pseudoginsenoside RT8, along with 15 known compounds. Pseudoginsenoside RT8 exhibited more potent antiinflammatory activity than the other saponins, attenuating lipopolysaccharide-mediated induction of proinflammatory genes such as interleukin-1β, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-9, and suppressed reactive oxygen species and nitric oxide generation in a dose-dependent manner. Conclusion: These findings indicate that pseudoginsenoside RT8 has a pharmaceutical potential as an antiinflammatory agent and that P. ginseng seeds are a good natural source for discovering novel bioactive molecules.

빈용 한약재의 진통 소염활성

박종은,최혁재,정석희,김동현,김남재,Park, Jong-Eun,Choi, Hyuk-Jae,Jung, Suk-Hee,Kim, Dong-Hyun,Kim, Nam-Jae 한국생약학회 2001 생약학회지 Vol.32 No.4

Analgesic and antiinflammatory activities of several herbal medicines were investigated in order to develop the antiinflammatory drugs from oriental herbal medicines. 80% Ethanol extracts of Ephedra sinica, Chaenoleles sinensis, Asiasarum siboldi, Nelumbo nucifera, Scolopendra subspinipes mutians, Evodia officinalis, Aremarrhenae asphodeloides, Bufo bufo gargarizans, Gardenia jasminoides, Piper longum, Carthamus tinctorius, Piperus nigrum, Magnolia officinalis and Siegesbeckia glabrescens showed significant inhibitory effects on hyaluronidase, trypsin, and albumin denaturation in vitro. They also decreased the acetic acid-induced pain and vascular permeability induced by histamine in mice.