Flavonoids are known to exert anti-inflammatory effects. Their pharmacological activities have been proved using various in vitro and in vivo models. Although their action spectrum and potencies are not adequate to alleviate acute inflammatory disorders, they have the potential to treat chronic inflammatory diseases. Recent investigations have revealed that inflammatory processes are involved in many disease processes and conditions. Some examples are skin disorders, cartilage diseases, metabolic inflammatory diseases, and aging. The effects of flavonoids on these disorders have been examined. Several possible application areas for flavonoids have been studied. Local treatment of these disorders with flavonoids is favorable to avoid systemic transformation. In this review, the findings based on the experimental results from my laboratory are summarized and the future possibility of using flavonoids clinically is discussed.
Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.
Kristina Lama;Hyehyun Hong;Tae-Jin Park;Jin-Soo Park;Won-Jae Chi;Seung-Young Kim
Journal of Applied Biological Chemistry
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v.66
/
pp.29-38
/
2023
Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E2, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.
Kim, Kyung-Ae;Yi, Hyo-Seung;Yun, Hyun-Jeong;Park, Sun-Dong
Journal of Physiology & Pathology in Korean Medicine
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v.23
no.6
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pp.1320-1331
/
2009
Oxidative stress and inflammation are important events in the development of chronic inflammatory diseases including arthritis, atherosclerosis, diabetes, hypertension. Cynomorium songaricum (CS) has been used as a traditional Korean herbal medicine, and it is currently used in traditional clinics to treat frequent urination, spermatorrhea, weakness of the sinews and constipation in the folk medicine. The aim of this study was to determine whether fractionated extracts of CS inhibit free radical generation such as DPPH radical, superoxide radical, nitric oxide and peroxynitrite, production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Cytotoxic activity of extracts on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. Our results indicated that the most superior extract which scavenged DPPH radical, reactive oxygen species (ROS) and RNS was CS ethyl acetate extract (CSEA). Moreover, CSEA significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-$\alpha$, IL-$1{\beta}$ and IL-6 formation in macrophages. Furthermore, CSEA treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$. These findings indicate that CSEA inhibits the production of pro-inflammatory mediators and cytokines via the suppression of ROS production and NF-${\kappa}B$ activation. Take together, these results indicate that CSEA has the potential for use as an natural anti-oxidant and an agent of anti-chronic inflammatory diseases.
Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin $(IL)-1{\beta}$ and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and $Sj{\ddot{o}}gren^{\prime}s$ syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.
Gentisic acid (GA), a benzoic acid derivative present in various food ingredients, has been shown to have diverse pharmaceutical activities such as anti-carcinogenic, antioxidant, and hepatoprotective effects. In this study, we used a co-culture system to investigate the mechanisms of the anti-inflammatory and anti-adipogenic effects of GA on macrophages and adipocytes, respectively, as well as its effect on obesity-related chronic inflammation. We found that GA effectively suppressed lipopolysaccharide-stimulated inflammatory responses by controlling the production of nitric oxide and pro-inflammatory cytokines and modulating inflammation-related protein pathways. GA treatment also inhibited lipid accumulation in adipocytes by modulating the expression of major adipogenic transcription factors and their upstream protein pathways. Furthermore, in the macrophage-adipocyte co-culture system, GA decreased the production of obesity-related cytokines. These results indicate that GA possesses effective anti-inflammatory and anti-adipogenic activities and may be used in developing treatments for the management of obesity-related chronic inflammatory diseases.
Objective: There is increasing evidence that chronic non-bacterial prostatitis is recognized to be a local inflammatory disease, and there is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and clinical value in the evaluation of therapeutic efficacy. Prunella vulgaris has been traditionally used in treatment of inflammatory diseases, including of scrofula, goiter, and allergy diseases. In this study, we investigated the effects of Prunella vulgaris on inflammatory cytokines and cytopathological alternation in the rat model of non-bacterial prostatitis induced by castration and $17{\beta}-estradiol$ treatment. Methods: Two-month-old rats were treated with $17{\beta}-estradiol$ after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histopathological profiles. Prunella vulgaris as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathological parameters including the epithelial score and epithelial-stromal ratio for glandular damage, and the expression of inflammatory cytokine genes including the interleukin $(IL)-1{\beta}$, IL-5, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$. Results: While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Prunella vulgaris showed a diminished range of tissue damage. Epithelial score was improved in Prunella vulgaris over that of the control (P<0.05). The epithelial-stromal ratio was lower with Prunella vulgaris when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytokine genes, Prunella vulgaris inhibited the expression of $IL-1{\beta}$ and $TNF-{\alpha}$ genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions: These findings suggest that Prunella vulgaris may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and promotion of anti-inflammatory cytokine. From theses results, we suggest that Prunella vulgaris could be a useful remedy agent for treating chronic non-bacterial prostatitis.
Jo, Suk-Yong;Kang, Min-Seo;Kim, Yong-Min;Kim, Hee-Taek
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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v.29
no.3
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pp.95-105
/
2016
Objectives : Allergic diseases have a various symptoms of hyperresponsiveness and recently hyperresponsive reaction in the chronic phase is reported as the important mechanisms. Cheonggisan(CGS) is used in oriental clinics for curing various skin diseases due to effect of controlling of pruritus. There have been studies on the anti-allergic effect and anti-inflammatory effect of CGS, but there had no study of anti-allergic effects in allergic late inflammation of CGS, so we aimed to find out the effects of CGS in allergic late inflammation in our study.Methods : To investigate the anti-allergy effect and anti-inflammatory effect of CGS, RAW 264.7 macrophage cells and CSG water-extracts were used. Cytotoxic effect of CSG was examined by MTT assay, an oxidative product of NO was measured in the culture medium by the Griess reagent assay. The level of prostaglandin E2(PGE2) was measured by competitive enzyme-linked immunoassay. Cytokine(PGE2, IL-1β, IL-6, TNF-α) was measured by Bio-Plex suspension assay system and quantitative multiplexed cytokine/chemokine assay.Results : We investigated that there was no cytotoxic effect of CGS water-extract at any levels of concentration on RAW 264.7 macrophage cells by MTT assay. CGS water-extracts significantly suppressed the levels of the inflammatory mediators such as NO and PGE2, cytokine of IL-1β, TNF-α at the level of 400 ㎍/㎖ CGS concentration. But there was no significant effect on IL-6 production suppression.Conclusions : These results suggest that CSG water-extract has and anti-inflammatory effects in allergic reaction. These properties may contribute to the allergic diseases and inflammatory related disease care.
Yu, Shin-Hye;Kim, Soomin;Kim, Yujin;Lee, Seo-Eun;Park, Jong Hyeok;Cho, Gayoung;Ha, Jong-Cheon;Jung, Hahnsun;Lim, Sang-Min;Han, Kyuboem;Lee, Hong Kyu;Kang, Young Cheol;Kim, Chun-Hyung
BMB Reports
/
v.55
no.3
/
pp.136-141
/
2022
Inflammation is one of the body's natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases and multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases by inducing an abnormal inflammatory response. Therefore, treating inflammatory diseases by recovering mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation has been proven to be beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to PN-101. We found that PN-101 could significantly reduce LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated LPS-induced increase production of pro-inflammatory cytokines. Furthermore, the anti-inflammatory effect of PN-101 was mediated by blockade of phosphorylation, nuclear translocation, and trans-activity of NFκB. Taken together, our results demonstrate that PN-101 has therapeutic potential to attenuate pathological inflammatory responses.
Chattopadhyay, Debprasad;Das, Sonali;Mandal, Asit Baran;Arunachalam, G;Bhattacharya, SK
Advances in Traditional Medicine
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v.7
no.4
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pp.395-408
/
2007
This study reports the analgesic, anti-inflammatory and membrane-stabilizing property of alcoholic extract of Ophiorrhiza nicobarica (ON), a wild herb, used as an anti-infective ethnomedicine of Nicobarese and Shompen tribes of Great Nicobar Island, India. We for the first time investigated the analgesic and antiinflammatory potential of this herb in acute, subacute and chronic model of inflammation in Swiss albino mice and Wistar albino rats, along with sheep RBC-induced sensitivity and membrane stabilization. The acetic acid induced writhing, tail flick and tail immersion tests are used as a model for evaluating analgesic activity; while the carrageenin-induced paw oedema was used as the model for acute inflammation, dextran-induced oedema as sub-acute and cotton-pellateinduced granuloma as chronic inflammatory model. The probable mode by which ON mediate its effect on inflammatory conditions was studied on sheep RBC-induced sensitivity and membrane stabilization. The in vitro results revealed that the ON extract possesses significant (P < 0.05) dose dependent analgesic and antiinflammatory activity at 200 and 300 mg/kg and its fractions at 50 mg/kg, p.o. respectively, compared to the control groups. However, the extract failed to exhibit membrane-stabilizing property as it unable to reduce the level of haemolysis of RBC exposed to hypotonic solution. The acute toxicity studies of ON extract in rats and mice revealed that the extract was nontoxic even up to 3.0 g/kg body weight of the animals, with a high safety profile. We have isolated ursolic acid, ${\beta}$-sitosterol and harmaline respectively, from the bioactive part of the extract. The results indicated that the O. nicobarica is indeed beneficial in primary health care, and suggest that its anti-inflammatory activity may not be related to membrane-stabilization.
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