• 제목/요약/키워드: nuclear factor (NF)-${\kappa}B$

검색결과 813건 처리시간 0.036초

The Preventive Effects of Colon Cancer and Imflammatory Bowel Disease of Supercritical Heat-Treated Radish Extracts

  • Kim, Hyun-Kyoung
    • International Journal of Internet, Broadcasting and Communication
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    • 제12권2호
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    • pp.98-112
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    • 2020
  • There is a strong connection between the diet rich in antioxidants and the decreased incidence of inflammatory bowel disease and cancerous diseases. Diets that are rich in anti-oxidants particularly include fruits and vegetables containing the high amounts of vitamin A-E, carotenoids, and minerals. The supercritical heat-treated radish extracts of the research result had an inhibitory effect on the development of aberrant crypt foci (ACF), namely, preneoplastic lesions having a potential to become cancer cells and reduced the number of the aberrant crypt foci (ACF) consisting of four or more aberrant crypts (AC) having high risk to become tumors by about half. The supercritical heat-treated radish extracts can reduce the incidence of preneoplastic lesions having a high risk of developing cancer by about 28 %. DSS-treated mice developed symptoms similar to those of human UC, such as severe bloody diarrhea and weight loss. Supercritical heat-treated radish extracts, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, supercritical heat-treated radish extracts treatment significantly reduced the expression of pro-inflammatory signaling molecules through suppression both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-kB) signaling pathways, and prevented the apoptosis of colon. Moreover, supercritical heat-treated radish extracts administration significantly led to the up-regulation of anti-oxidant enzyme including SOD and Catalase.

Effects of Acupuncture at SP6 on Reflux Esophagitis in Rats

  • Lee, Yun Kyu;Rho, Sung Soo;Kim, Jae Soo
    • Journal of Acupuncture Research
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    • 제32권3호
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    • pp.83-93
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    • 2015
  • Objectives : The purpose of this study was to evaluate whether acupuncture at $SP_6$ attenuates esophageal inflammation on refluxed-induced esophagitis. Methods : Acupuncture at $SP_6$ was stimulated by acupuncture torsion technique for 30 seconds four times every hour after an operation induced reflux esophagitis(RE), and its effects were assessed in comparison with RE rats without acupuncture, and normal rats. Results : $SP_6$ acupuncture stimulation markedly ameliorated mucosal damage in the histological evaluation. Reflux-induced esophagitis rats exhibited the down-regulation of antioxidant-related protein expression levels such as heme oxygenase-1(HO-1) in the esophagitis; however, the associated levels with $SP_6$ acupuncture stimulation were significantly higher than those in RE rats without acupuncture stimulation. Moreover, $SP_6$ acupuncture stimulation significantly reduced the expression of inflammatory proteins through mitogen-activated protein kinase(MAPK)-related signaling pathways. The increased protein expressions of inflammatory mediators, cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS), by nuclear factor-kappa B(NF-kB) activation were significantly suppressed through $SP_6$ acupuncture stimulation. Conclusions : Our findings support the therapeutic evidence for $SP_6$ acupuncture stimulation alleviating the development of esophagitis via regulating inflammation through the activation of the antioxidant pathway.

이삭물수세미(Myriophyllum spicatum L.) 에탄올 추출물의 항산화와 항염증 효과 (Evaluation Antioxidant and Anti-inflammatory Activity of Ethanolic Extracts of Myriophyllum spicatum L. in Lipopolysaccharide-stimulated RAW 264.7 Cells )

  • 김철환;이영경;김민진;최지수;황병수;조표연;김영준;정용태
    • 한국자원식물학회지
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    • 제36권1호
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    • pp.15-25
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    • 2023
  • 이삭물수세미는 민간에서는 전초를 고름, 염증 등에 약용으로 사용하였으나, 염증에 대한 연구가 미비한 상황이다. 이에 본 연구에서는 이삭물수세미 추출물(EMS)의 항산화 효능과 항염증 효능을 분석하였다. 항산화 효능은 DPPH 라디칼 소거능과 환원력을 통해 산화적 스트레스를 통해 염증을 유발시킬 수 있는 ROS (Hong et al., 2020; Snezhkina et al., 2019)를 억제하는지 확인하였고, 항염증 효능은 염증 발현 인자인 LPS를 이용하여 RAW 264.7 대식세포에 염증을 유도한 뒤 pro-inflammatory cytokine (TNF-α, IL-1β)과 염증 매개체(NO, PGE2)의 억제 및 TLR4/Myd88/NF-κB signaling pathway 발현 억제를 통해 확인하였다. 연구 결과, 항산화 효능에 있어서는 DPPH 라디칼 소거능과 Fe3+를 Fe2+로 환원시키는 환원력이 농도 의존적으로 증가함을 확인하였다. 무독성 상태에서 실험하기 위해 LPS와 EMS를 처리한 RAW 264.7 대식세포에서 90% 이상의 생존율을 나타내는 조건에서 실험을 진행하였다. LPS로 염증이 유도된 RAW 264.7 세포에서 EMS는 염증 매개 인자의 발현 및 생성 억제(iNOS에 의한 NO 생성 및 COX-2에 의한 PGE2 생성억제)와 pro-inflammatory cytokine (TNF-α 및 IL-1β)의 생성 또한 억제하였다. 특이적으로 COX-2에 의한 PGE2 생성 억제에서는 고농도에서 작용함을 확인하였고, IL-1β에서는 약한 억제력을 보였다. 이후 signaling pathway에서 염증 전사인자 경로를 확인하기 위하여 TLR4/MyD88의 활성을 확인하였고, EMS 처리에 따라 농도 의존적으로 억제되는 것을 확인하였다. 이에 따라 염증 초기 단계에서 NF-κB p65가 nuclear로 들어가는 것을 억제하는지 확인하기 위해 early time (LPS 처리 후 30, 60 min) 조건으로 nuclear에서 p65 인산화를 확인하였다. 그 결과, LPS 자극으로 인해 증가된 p65 인산화가 EMS에 의해 부분적으로 억제됨을 확인하였다. 이상의 결과를 통해 LPS로 염증이 유도된 RAW 264.7 대식세포에서 EMS가 COX-2에 의한 PGE2 생성 억제와 IL-1β의 생성에 있어 낮은 억제력을 가진 반면, iNOS에 의한 NO과 TNF-α 생성 및 TLR4/MyD88 singnaling pathway에 있어 강한 억제력을 가짐을 확인하였다. 결론적으로 EMS가 ROS를 제거하고 TLR4/MyD88/NF-κB signaling pathway를 억제함으로써 염증 인자들의 전사를 억제하고, 염증 인자 부분에서는 iNOS에 의한 NO 생성과 TNF-α 생성을 강하게 억제하여 RAW 264.7 대식세포에서 LPS로 자극된 염증을 억제하는 것으로 판단된다. 또한 TLR4/Myd88/NF-κB signaling pathway를 통한 pro-inflammatory cytokine과 염증 매개체와의 연관성에 대한 기초자료로 활용할 수 있는 근거 자료가 될 수 있을 것으로 생각된다.

Neuroprotective effects of hesperetin on H2O2-induced damage in neuroblastoma SH-SY5Y cells

  • Ha-Rin Moon;Jung-Mi Yun
    • Nutrition Research and Practice
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    • 제17권5호
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    • pp.899-916
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    • 2023
  • BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H2O2)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H2O2 (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H2O2-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H2O2-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H2O2-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H2O2-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

Folic acid supplementation regulates key immunity-associated genes and pathways during the periparturient period in dairy cows

  • Khan, Muhammad Zahoor;Zhang, Zhichao;Liu, Lei;Wang, Di;Mi, Siyuan;Liu, Xueqin;Liu, Gang;Guo, Gang;Li, Xizhi;Wang, Yachun;Yu, Ying
    • Asian-Australasian Journal of Animal Sciences
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    • 제33권9호
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    • pp.1507-1519
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    • 2020
  • Objective: The current research was aimed to profile the transcriptomic picture of the peripheral blood lymphocytes (PBLs) associated with immunity in Chinese Holsteins supplemented orally with coated folic acid during the periparturient period. Methods: The total of 123 perinatal cows were selected for this study and divided into three groups; group A (n = 41, 240 mg/500 kg cow/d), group B (n = 40, 120 mg/500 kg cow/d) and group C (n = 42, 0 mg/cow/d) based on the quantity of folic acid fed. Three samples of PBLs were selected from each folic acid treated group (high, low, and control) and RNA sequencing method was carried out for transcriptomic analysis. Results: The analysis revealed that a higher number of genes and pathways were regulated in response to high and low folic acid supplementation compared to the controls. We reported the novel pathways tumor necrosis factor (TNF) signaling, antigen processing and presentation, Staphylococcus aureus infection and nuclear factor (NF)-kappa B signaling pathways) and the key genes (e.g. C-X-C motif chemokine ligand 10, TNF receptor superfamily member 1A, cluster difference 4, major histocompatibility complex, class II, DQ beta, NF-kappa-B inhibitor alpha, and TNF superfamily 13) having great importance in immunity and anti-inflammation in the periparturient cows in response to coated folic acid treatment. Conclusion: Collectively, our study profiled first-time transcriptomic analysis of bovine lymphocytes and compared the involved cytokines, genes, and pathways between high vs control and low vs control. Our data suggest that the low folic acid supplementation (120 mg/500 kg) could be a good choice to boost appropriate immunity and anti-inflammation as well as might being applied to the health improvement of perinatal dairy cows.

창상을 유발한 흰쥐에서 금은화(金銀花) 추출물의 치료 효과 (The Effect of Lonicera japonica Extract in Wound-induced Rats)

  • 원제훈;우창훈
    • 한방재활의학과학회지
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    • 제30권1호
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    • pp.47-61
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    • 2020
  • Objectives This study is carried out to investigate the effects of Lonicera japonica in wound-induced rats. Methods Rats were divided into 5 groups; normal (Nor), control (Veh), positive comparison (PC), Lonicera japonica 100 mg/kg (LL), Lonicera japonica 200 mg/kg (LH), each n=8. Total polyphenol and flavonoid were quantified. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3 ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging activation were measured. Reactive oxygen species (ROS) was measured in serum. Antioxidant factors and inflammatory factors were measured in skin tissue, and also hydroxyproline content. Skin tissue was analyzed by Hematoxylin & Eosin and Masson's trichrome staining method. Results Total polyphenol and flavonoid were 32.86±0.14 mg/g and 67.17±0.57 mg/g. The IC50 values of DPPH and ABTS free radical scavenging activation were 26.69±1.50 ㎍/mL and 49.33±4.52 ㎍/mL. ROS was significantly lower in LL and LH groups. Nuclear factor-erythroid 2-related factor 2 (Nrf2) was significantly higher in LH group and higher in LL group but not significant. Superoxide dismutase 1 (SOD-1), catalase, and heme oxygenase 1 (HO-1) were significantly higher in LL and LH groups. Nuclear factor kappa-B p65 (NF-κBp65), phosphorylated iκBα (p-iκBα), cyclooxygenase 2 (COX-2), and tumor necrosis factor alpha (TNF-α) were significantly lower in LL and LH groups. Hydroxyproline was significantly higher in LL and LH groups. The histopathologic analysis showed that skin tissue had recovered further more in LL and LH groups than in Veh group. Conclusions These results suggest that Lonicera japonica has the anti-oxidant, anti-inflammatory and healing effects in wound-induced rats.

미니돼지에서 허혈성 신장 손상의 조기진단 (Initial Diagnosis of Acute Renal Failure Induced by Ischemia in Miniature Pig)

  • 김세은;고아라;배춘식;박수현;한호재;심경미;강성수
    • 한국임상수의학회지
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    • 제28권1호
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    • pp.52-56
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    • 2011
  • Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

백출에서 분리된 Atractylenolide II의 RAW264.7 대식세포와 BV2 미세아교세포에서의 항염증 효과 (Atractylenoide II Isolated from Atractylodes macrocephala Inhibited Inflammatory Responses in Lipopolysaccharide-induced RAW264.7 Macrophages and BV2 Microglial Cells)

  • 김홍광;김관우;이정;임혜리;이대영;윤다혜;정진태;김금숙;오현철;안인파;김윤철
    • 생약학회지
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    • 제51권4호
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    • pp.244-254
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    • 2020
  • Atractylodes macrocephala is a perennial herb and is a member of the Compositae family. This plant is known to contain various bioactive constituents indicating anti-inflammatory, neuroprotective, anti-oxidant, immunological enhancement, and gastroprotective effects. In this investigation, we isolated four compounds with similar chemical structures from A. macrocephala, and evaluated their anti-inflammatory effects. Among the four compounds, compound 2(atractylenolide II) showed the second-best inhibitory effect on the lipopolysaccharide(LPS)-induced production of nitric oxide in RAW264.7 macrophages and BV2 microglial cells. Compound 2 also inhibited the LPS-induced the production of prostaglandin E2(PGE2), and the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 proteins in both cells. In addition, compound 2 suppressed the production of pro-inflammatory cytokines including interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by treatment with compound 2. This compound did not induce the expression of heme oxygenase(HO)-1 protein indicating that the anti-inflammatory effect of compound 2 was independent with HO-1 protein. Taken together, these results suggested that atractylenolide II can be a candidate material to treat inflammatory diseases.

OLIGONOL PREVENTED THE RELAPSE OF DEXTRAN SULFATE SODIUM-ULCERATIVE COLITIS THROUGH ENHANCING NRF2-MEDIATED ANTIOXIDATIVE DEFENSE MECHANISM

  • K.-J. KIM;J.-M. PARK;J.-S. LEE;Y.S. KIM;N. KANGWAN;Y.-M. HAN;E.A. KANG;J.M. AN;Y.K. PARK;K.-B. HAHM
    • The Korean Journal of Physiology and Pharmacology
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    • 제69권3호
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    • pp.359-371
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    • 2018
  • Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P < 0.05). Oligonol pretreatment significantly decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) as well as nuclear factor-κB (NF-κB), c-Fos, and c-Jun in affected colon tissues, but the expression of heme oxygenase-1 (HO-1) and NADH: quinone oxidoreductase-1(NQO-1) as well as total antioxidant concentration (P < 0.005) was significantly increased with oligonol. A relapse model established with repeated DSS administration led to high mortality. However, oligonol significantly ameliorated exacerbations of colitis, while sulfasalazine did not (P < 0.01). Significantly decreased expressions of cyclooxygenase-2 (COX-2), TNF-α, and macrophages inhibition were relapse preventing actions of oligonal, but significant action of oligonol relevant to relapse prevention was either significantly increased expressions of NQO-1 or significantly preserved mucin (P < 0.05). Concerted anti-inflammatory, antioxidative, and host defense enhancing actions of oligonol can be applied during maintenance therapy of IBD to prevent relapse of IBD.

RAW 264.7 대식세포에서 lipopolysaccharide 자극에 의한 염증성 및 산화적 스트레스에 미치는 5-aminolevulinic acid phosphate의 영향 (Attenuation of Lipopolysaccharide-induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid Phosphate in RAW 264.7 Macrophages)

  • 지선영;김민영;황보현;이혜숙;홍수현;차희재;김희수;김석만;최영현
    • 생명과학회지
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    • 제31권9호
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    • pp.818-826
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    • 2021
  • 5-ALA-p는 천연 아미노산인 5-ALA를 암모니아수로 용출하고 인산과 아세톤을 첨가하여 광역학 요법에 적합한 특성을 갖도록 개발된 물질이다. 그러나 항산화 및 항염증에 대한 잠재적인 기전을 포함한 약리학적 효능은 아직 명확하지 않다. 본 연구에서는 LPS로 자극된 RAW 264.7 세포에서 산화적 및 염증성 반응에 대한 5-ALA-p의 효과를 평가하였다. 본 연구의 결과에 의하면, 5-ALA-p는 LPS에 의한 RAW 264.7 세포의 과도한 식균 활성을 유의하게 억제하였고 산화적 스트레스를 약화시켰다. 5-ALA-p는 또한 LPS에 의해 감소된 미토콘드리아 생물 발생을 개선하였으며, 이는 5-ALA-p가 LPS로 인한 미토콘드리아 손상을 복원시켰음을 시사한다. 아울러 5-ALA-p는 NO와 TNF-α, IL-1β 및 IL-6과 같은 염증성 사이토카인의 생성을 현저히 억제하였으며, 이는 iNOS 및 각 사이토카인의 발현 감소와 연관성이 있었다. 나아가 5-ALA-p는 NF-κB의 핵 전이를 감소시키고 MAPKs의 인산화를 억제하여 5-ALA-p의 항염증 효과가 이들 신호전달 경로의 활성 억제와 매개되었음을 보여주었다. 이러한 결과들은 5-ALA-p가 산화적 및 염증성 스트레스를 줄이는 잠재적인 후보 약물로 적용될 수 있음을 의미한다.