• Journal of Photoscience
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• v.9 no.3
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• pp.33-36
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• 2002

This study describes RT-PCR and in situ hybridisation protocols, and the immunohistochemical detection method that we have developed to detect and localise cells that express HO-1 in the skin. We found that HO-1 mRNA was absent in normal mouse skin, but after UVA irradiation HO-1 mRNA was expressed in the dermal fibroblasts, and strongly in basal epidermal cells. HO-1 protein was also induced strongly in dermal fibroblasts, and also in epidermal cells. In addition, the HO substrate heme was reduced in skin microsome at 72 hrs post UVA (when HO activity is high). At the same time, the HO products bilirubin and iron levels were elevated in the cutaneous tissue. Thus in addition to a dermal response, there appears to be an epidermal HO response to UVA in vivo that may be relevant for immune modulation by UVA radiation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.11
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• pp.1507-1511
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• 2011

This study investigated the anti-inflammatory effect of Erigeron annuus L. flower (EAF) methanol extract. We examined the involvement of heme oxygenase-1 (HO-1) in the inhibitory activities of EAF methanol extract on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Cell viability and NO assays were performed. In addition, inducible nitric oxide synthase (iNOS) and HO-1 expressions were detected by Western blotting and blocking HO-1 activity on NO production. EAF methanol extract (25, 50, 100, 200 ${\mu}g$/mL) significantly inhibited LPS-stimulated NO production (p<0.05; 12.82, 9.61, 6.83, 2.52 ${\mu}m$) in a concentration-dependent manner. EAF methanol extract also reduced the expression of iNOS protein. The EAF methanol extract induced the expression of HO-1 in a dose-dependent manner. Blockage of HO-1 activity by zinc protoporphyrin suppressed EAF methanol extract-induced reductions in the production of NO. The present results suggest that EAF methanol extract has a potent anti-inflammatory effect in RAW264.7 macrophages through the induction of HO-1.

• Journal of Life Science
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• v.28 no.1
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• pp.43-49
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• 2018

Chrysoeriol is a widespread flavone, and it is usually found in alfalfa, which has been used as a traditional medicine to treat dyspepsia, asthma, and urinary system disorders. Recently, analysis has been conducted on the anti-inflammatory activity of chrysoeriol, but information on its antioxidative capacity is limited. In this study, the antioxidative potential of chrysoeriol against oxidative damage and its molecular mechanisms were evaluated by analysis of the cell viability, reactive oxygen species (ROS) formation, and Western blots in the RAW 264.7 cell line. Chrysoeriol significantly scavenged lipopolysaccharide (LPS)-induced intracellular ROS formation in a dose-dependent manner, without any cytotoxicity. Heme oxygenase-1 (HO-1), a phase II enzyme that exerts antioxidative activity, was also potently induced by chrysoeriol treatment, which corresponded to the translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) into the nucleus. Moreover, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) were analyzed due to their important role in maintaining cellular redox homeostasis against oxidative stress. As a result, chrysoeriol-induced HO-1 upregulation was mediated by extracellular signal - regulated kinase (ERK), c-Jun $NH_2$-terminal kinase (JNK), and p38 phosphorylation. To identify the antioxidative potential exerted by HO-1, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was applied and mitigated by chrysoeriol treatment, which was confirmed by the HO-1 selective inhibitor and inducer, respectively. Consequently, chrysoeriol strongly strengthened the HO-1-mediated antioxidative potential through the regulation of the Nrf2/MAPK signaling pathways.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.615-621
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• 2023

Korean Red Ginseng (KRG) plays a key role in heme oxygenase (HO)-1 induction under physical and moderate oxidative stress conditions. The transient and mild induction of HO-1 is beneficial for cell protection, mitochondrial function, regeneration, and intercellular communication. However, chronic HO-1 overexpression is detrimental in severely injured regions. Thus, in a chronic pathological state, diminishing HO-1-mediated ferroptosis is beneficial for a therapeutic approach. The molecular mechanisms by which KRG protects various cell types in the central nervous system have not yet been established, especially in terms of HO-1-mediated mitochondrial functions. Therefore, in this review, we discuss the multiple roles of KRG in the regulation of astrocytic HO-1 under pathophysiological conditions. More specifically, we discuss the role of the KRG-mediated astrocytic HO-1 pathway in regulating mitochondrial functions in acute and chronic neurodegenerative diseases as well as physiological conditions.

• Korean Journal of Pharmacognosy
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• v.6 no.1
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• pp.1-4
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• 1975

Polygonum cuspidatum $S_{IEB}$. et $Z_{UCC}$. ('Ho-Jang'), P. sachalinense $F_R$. $S_{CHM}$. ('Wang Ho-Jang') and P. ellipticum $M_{IGO} ('Dung Geun Ib Ho-Jang') are the three species growing in Korea. Their rhizomes can be classified into two types: horizontal rhizome type ('Ho-Jang') and erect type ('Wang Ho-Jang' and 'Dung Geun Ib Ho-Jang'). The most of 'Ho-Jang' on Korean markets are the rhizome of 'Wang Ho-Jang' and only limited quantity of the rhizome of 'Ho-Jang' is used. 'Dung Geun Ib Ho-Jang' is a species transplanted from the China continent and is not collected for medicinal use. It is suggested that the name 'Ho-Jang Geun' (Reynoutriae Radix) should be corrected to 'Ho-Jang' (Reynoutriae Rhizoma=Polygoni Rhizoma).

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.278-290
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• 2020

The purpose of this study is to investigate the hangover relieving effect of HO-series. HO-S1 is an herbal mixture, which consists of extracts from Flower of Pueraria lobata Ohwi, Glycyrrhiza glabra Linné, Fruit of Lycium chinense Miller, Poria cocos Wolf, Acanthopanax sessiliflorum Seeman, Scutellaria baicalensis Georgi, Atractylodes lancea De Candlle and Zingiber officinale Roscoe. HO-S2 is a candidate that has been performed to ultra filtration based on HO-S1. HO-S3 is a mixture of amino acids and vitamins based on HO-S2. HO-01 is the final beverage base produced based on HO-S3. The antioxidant activity of HO-series was similar to that of vitamin C or trolox. The production of t-BHP induced reactive oxygen species(ROS) was significantly blocked in the presence of HO-series. In vivo study, AUC of alcohol and acetaldehyde concentrations in HO-S2 and HO-S3 treated groups significantly decreased. Hepatic alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase(ALDH) activity were significantly higher in HO-S2 and HO-S3 treated groups. And 2E1 activity and glutathione were significantly elevated, while the malondialdehyde level was not significantly in liver tissue. After alcohol exposure, the sensitivity scores of blood alcohol and acetaldehyde concentration and hangover symptoms were significantly decreased in the HO-01 intake group compared with the non-intake group. ALDH activity was significantly increased in the HO-01 intake group. HO-series have antioxidant activity and a protective effect from ROS. HO-S2, HO-S3 and HO-01 are potentially highly beneficial in relieving hangover, as it scavenges reactive free radicals and boosts the endogenous antioxidant system.

• Journal of Life Science
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• v.33 no.10
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• pp.776-782
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• 2023

Silymarin, which is derived from dried Silybum marianum (milk thistle) seeds and fruits, possesses various beneficial properties, such as hepatoprotective, antioxidative, anti-inflammatory, and anticancer activity. This research aimed to explore the antioxidative activity of silymarin against oxidative stress and understand its molecular mechanism in RAW 264.7 cells. The study employed cell viability and reactive oxygen species (ROS) formation assays and western blot analysis. The results demonstrated that silymarin effectively reduced intracellular ROS levels induced by lipopolysaccharide (LPS) in a dose-dependent manner without causing any cytotoxic effects. Moreover, silymarin treatment significantly upregulated the expression of heme oxygenase (HO)-1, a phase II enzyme known for its potent antioxidative activity. Additionally, silymarin treatment significantly induced the expression of nuclear factor-erythroid 2 p45-related factor (Nrf) 2, a transcription factor responsible for regulating antioxidative enzymes, which was consistent with the upregulated HO-1 expression. To investigate the involvement of key signaling pathways in maintaining cellular redox homeostasis against oxidative stress, the phosphorylation status of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) was estimated by western blot analysis. The results showed that silymarin potently induced HO-1 expression, which was mediated by the phosphorylation of p38 MAPK. To further validate the antioxidative potential of silymarin-induced HO-1 expression, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was employed and attenuated by silymarin treatment, as identified by a selective inhibitor for each signaling molecule. In conclusion, silymarin robustly enhanced antioxidative activity by inducing HO-1 via the Nrf2/p38 MAPK signaling pathway in RAW 264.7 cells.

• Journal of the Korean Applied Science and Technology
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• v.37 no.5
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• pp.1306-1313
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• 2020

The aims of this study were to determine the effects of Sapindus mukorossi fruit extracts (SME) on the anti-oxidant activity in LPS-stimulated RAW264.7 macrophages. The results showed that SME significantly reduced the production of ROS in LPS-stimulated RAW264.7 cells. The expression of pro-inflammatory proteins including COX-2 and iNOS were also obviously inhibited by SME in LPS-stimulated RAW264.7 cells. Further studies revealed that SME up-regulated HO-1 and Nrf2 expression. Additionally, SME increased phosphorylation of Akt and GSK-3β. These results suggest that SME could attenuate oxidative stress by activating the Nrf2/HO-1 signaling pathway.

• Journal of Nutrition and Health
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• v.55 no.3
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• pp.348-358
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• 2022

Purpose: Hyperglycemia accelerates the formation of advanced glycation end products (AGEs), a group of compounds formed via non-enzymatic glycation/glycoxidation. Type 2 diabetes mellitus (T2DM) is related to oxidative stress, resulting in some overgeneration of AGEs. The accumulation of AGEs in T2DM patients leads to increased inflammation, DNA damage, tissue damage, progression of diabetic microvascular disease, and nephropathy. Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme. Expression of HO-1 in the endothelium and in muscle monocytes/macrophages was upregulated upon exposure to reactive oxygen species or oxidized low-density lipoprotein. Cells activated by oxidative stress are reported to release HO-1 in the serum. In the current study, we discuss the oxidative status according to the level of AGEs and the association of HO-1 with AGEs or urinary DNA damage marker in type 2 diabetic Korean patients. Methods: This study enrolled 36 diabetic patients. Subjects were classified into two groups by serum AGEs level (Low AGEs group: < 0.85 ng/mL serum AGEs; High AGEs group: ≥ 0.85 ng/mL serum AGEs). Body composition was measured using bioelectrical impedance analysis. Blood and urinary parameters were measured using commercial kits. Results: No significant differences were observed in the general characteristics and body composition between the two groups. Serum HO-1 concentration was significantly higher in the High AGEs group than in the Low AGEs group. After adjustment of age and gender, a correlation was performed to assess the association between serum HO-1 and serum AGEs or urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Our results indicate that serum HO-1 is positively correlated with serum AGEs and urinary 8-OHdG. Conclusion: Taken together, our results indicate that in diabetes patients, a high level of HO-1 is associated with a high concentration of AGEs and 8-OHdG, probably reflecting a protective response against oxidative stress.

• IMMUNE NETWORK
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• v.9 no.1
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• pp.12-19
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• 2009

Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the first and rate-limiting step in the oxidative degradation of free heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV), the latter being subsequently converted into bilirubin (BR). HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation. The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1. This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.