The Anti-Inflammatory Effect of Bee Venom Acupuncture (Apipuncture) and Its Mechanism

Lee, Jang-Hern 경희대학교 2001 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.2001 No.1

It has been reported that electrical or chemical (i.e.capsaicin) stimulation evoked nociceptive activation inhibits subsequent inflammatory reactions through either hypothalamic-pituitary-adrenal (HPA) axis or adrenal medullary activity, respectively. For these reasons, we evaluated the involvement of these systems, HPA or adrenal medullary activity, in the bee venom (BV) stimulation induced anti-inflammatory effect using zymosan induced leukocyte migration in mouse air pouch model. Subcutaneous BV injection (6mg/ kg in 20㎕ saline) into lower hind limb produced a marked reduction of leukocyte migration. The BV induced inhibitory effect of leukocyte migration was significantly suppressed in adrenalectomized mice. Corticosteroid receptor antagonist (RU486) did not affect the BV induced inhibitory effect of leukocyte migration. Consistently, serumcorticosteroid level was not changed by BV pretreatment during zymosan induced inflammation. In addition, pretreatment of β adrenoceptor antagonist, propranonol, partially but significantly reduced the BV induced inhibitory effect of leukocyte migration up to similar potency in the adrenalectomized animals. Peripheral chemical sympathectomy using 6-hydroxydopamine (6-OHDA) did not affect BV induced anti-inflammatory effect suggesting that symapathetic postganglionic nerve terminal was not involved in BV induced anti-inflammatory effect. However, central chemical sympathectomy by 6-OHDA injection dramatically reduced BV induced anti-inflammatory effect. Moreover, the BV induced inhibitory effect of leukocyte migration was totally suppressed by α2 adrenoceptor antagonist, idazoxan (s.c., i.t. and i.c.v. injection). Furthermore, the BV stimulation produced Fos expression in contralateral part of locus coeruleus (LC) in both normal and inflammatory states. Interestingly, neonatal capsaicin pretreatment did not modify the BV induced anti-inflammatory. Therefore, our results indicate that BV stimulation may activate the descending α2 adrenergic system originated from LC and modulated the adrenal medullary activity. Key words : Bee venom; Anti-inflammation; Adrenalectomy; Adrenergic; Locus coeruleus, Fos protein

Application of Cartilage Extracellular Matrix to Enhance Therapeutic Efficacy of Methotrexate

서정우,Jo Sung-Han,Kim Seon-Hwa,Choi Byeong-Hoon,Cho Hongsik,Yoo James J.,Park Sang-Hyug 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.2

BACKGROUND: Rheumatoid arthritis (RA) is characterized by chronic inflammation and joint damage. Methotrexate (MTX), a commonly used disease-modifying anti-rheumatic drug (DMARD) used in RA treatment. However, the continued use of DMARDs can cause adverse effects and result in limited therapeutic efficacy. Cartilage extracellular matrix (CECM) has anti-inflammatory and anti-vascular effects and promotes stem cell migration, adhesion, and differentiation into cartilage cells. METHODS: CECM was assessed the dsDNA, glycosaminoglycan, collagen contents and FT-IR spectrum of CECM. Furthermore, we determined the effects of CECM and MTX on cytocompatibility in the SW 982 cells and RAW 264.7 cells. The anti-inflammatory effects of CECM and MTX were assessed using macrophage cells. Finally, we examined the in vivo effects of CECM in combination with MTX on anti-inflammation control and cartilage degradation in collagen-induced arthritis model. Anti-inflammation control and cartilage degradation were assessed by measuring the serum levels of RA-related cytokines and histology. RESULTS: CECM in combination with MTX had no effect on SW 982, effectively suppressing only RAW 264.7 activity. Moreover, anti-inflammatory effects were enhanced when low-dose MTX was combined with CECM. In a collagen-induced arthritis model, low-dose MTX combined with CECM remarkably reduced RA-related and pro-inflammatory cytokine levels in the blood. Additionally, low-dose MTX combined with CECM exerted the best cartilage-preservation effects compared to those observed in the other therapy groups. CONCLUSION: Using CECM as an adjuvant in RA treatment can augment the therapeutic effects of MTX, reduce existing drug adverse effects, and promote joint tissue regeneration. BACKGROUND: Rheumatoid arthritis (RA) is characterized by chronic inflammation and joint damage. Methotrexate (MTX), a commonly used disease-modifying anti-rheumatic drug (DMARD) used in RA treatment. However, the continued use of DMARDs can cause adverse effects and result in limited therapeutic efficacy. Cartilage extracellular matrix (CECM) has anti-inflammatory and anti-vascular effects and promotes stem cell migration, adhesion, and differentiation into cartilage cells. METHODS: CECM was assessed the dsDNA, glycosaminoglycan, collagen contents and FT-IR spectrum of CECM. Furthermore, we determined the effects of CECM and MTX on cytocompatibility in the SW 982 cells and RAW 264.7 cells. The anti-inflammatory effects of CECM and MTX were assessed using macrophage cells. Finally, we examined the in vivo effects of CECM in combination with MTX on anti-inflammation control and cartilage degradation in collagen-induced arthritis model. Anti-inflammation control and cartilage degradation were assessed by measuring the serum levels of RA-related cytokines and histology. RESULTS: CECM in combination with MTX had no effect on SW 982, effectively suppressing only RAW 264.7 activity. Moreover, anti-inflammatory effects were enhanced when low-dose MTX was combined with CECM. In a collagen-induced arthritis model, low-dose MTX combined with CECM remarkably reduced RA-related and pro-inflammatory cytokine levels in the blood. Additionally, low-dose MTX combined with CECM exerted the best cartilage-preservation effects compared to those observed in the other therapy groups. CONCLUSION: Using CECM as an adjuvant in RA treatment can augment the therapeutic effects of MTX, reduce existing drug adverse effects, and promote joint tissue regeneration.

In vitro antioxidant, anti-hyperglycemic, anti-cholinesterase, and inhibition of nitric oxide production activities of methanol and hot water extracts of Russula rosacea mushroom

Ki Nam Yoon,Tae Soo Lee 한국버섯학회 2015 한국버섯학회지 Vol.13 No.1

Russula rosacea, a mycorrhizal fungus, has been used for edible and medicinal purposes. This study was conducted to evaluate the in vitro antioxidant, anti-hyperglycemic, anti-cholinesterase, and nitric oxide inhibitory effects of the fruiting bodies from R. rosacea extracted with methanol, and hot water. The 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activities of the methanol and hot water extracts (2.0 mg/ml) of R. rosacea were comparable with BHT, the positive control. The chelating effects of the mushroom and hot water extracts were significantly higher than that of BHT. The reducing power of methanol and hot water extract (6 mg/ml) were significantly lower than that of BHT. Seven phenolic compounds were detected from acetonitrile and hydrochloric acid solvent extract of the mushroom. alpha-amylase and alpha-glucosidase inhibitory activities of methanol and hot water extracts were lower than that of acarbose, the positive control. The acetylcholinesterase and butyrylcholinesterase inhibitory effects were moderate compared with galanthamine, the standard drug. Nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW 264.7 cells were inhibited significantly by the mushroom extracts in a concentration dependent manner. Therefore, we demonstrated that fruiting bodies of R. rosacea possess in vitro antioxidant, anti-hyperglycemic, anti-cholinesterase, and NO production inhibitory activities. The experimental results suggest that the fruiting bodies of R. rosacea are good natural antioxidant, anti-hyperglycemic, anti-cholinesterase, and anti-inflammatory sources.

Active Molecular Chitosan alleviate Bleomycin-induced Acute Pulmonary Inflammation in Mice

( Seong-bo Yun ),( Dong-hun Kang ),( Ji-sun Choi ),( Dae-young Kim ) 한국키틴키토산학회 2019 한국키틴키토산학회지 Vol.24 No.3

Generally acute pulmonary inflammation is triggered by damage to alveolar epithelial cells due to the pollutants, viral infection, allergens and toxic substances. The active molecular chitosan (AMC, 5~8 kDa) is known to have non-toxic, bio-degradable, and biological activities including anti-tumor, anti-viral, and anti-inflammatory activities. The purpose of this study was to observe AMC’s preclinical efficacy to acute pulmonary inflammation and evaluate the therapeutic effect of a bleomycin (BLM) induced mouse model using AMC, a final product made by the hydrolysis of chitosan. Our experiments were conducted using male C57BL/6 mouse and BLM (5 mg/kg) was injected once with the intratracheal instillation (IT) method to induce pulmonary inflammation. Each group was conducted with prednisolone (PDS, 6.5 mg/kg) or AMC (100 mg/kg and 200 mg/kg, respectively) for 10 days with oral gavage. The relative lung weight measurements, histological findings in lung tissue specimens and cell counts through bronchoalveolar lavage fluid (BALF) were performed to determine the anti-inflammatory effects of AMC. The AMC treated groups with BLM induction had a decreased tendency of inflammation on our experiments. A dose of 100 mg/kg AMC induce group showed that similar aspect with control group on histological results. In addition, the lymphocyte rate appeared a noticeable on this group. The degree of lymphocyte was remarkably lower. It was inferred that inflammatory improvement in the AMC treated group. We confirmed that the BLM-induced lung disease model that progressed inflammation was inhibited by AMC. Furthermore, AMC performs an anti-inflammation function and has the possibility of use for the treatment of inflammatory disease.

In vitro antioxidant, anti-hyperglycemic, anti-cholinesterase, and inhibition of nitric oxide production activities of methanol and hot water extracts of Russula rosacea mushroom

Yoon, Ki Nam,Lee, Tae Soo 한국버섯학회 2015 한국버섯학회지 Vol.13 No.1

Russula rosacea, a mycorrhizal fungus, has been used for edible and medicinal purposes. This study was conducted to evaluate the in vitro antioxidant, anti-hyperglycemic, anti-cholinesterase, and nitric oxide inhibitory effects of the fruiting bodies from R. rosacea extracted with methanol, and hot water. The 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activities of the methanol and hot water extracts (2.0 mg/ml) of R. rosacea were comparable with BHT, the positive control. The chelating effects of the mushroom and hot water extracts were significantly higher than that of BHT. The reducing power of methanol and hot water extract (6 mg/ml) were significantly lower than that of BHT. Seven phenolic compounds were detected from acetonitrile and hydrochloric acid solvent extract of the mushroom. alpha-amylase and alpha-glucosidase inhibitory activities of methanol and hot water extracts were lower than that of acarbose, the positive control. The acetylcholinesterase and butyrylcholinesterase inhibitory effects were moderate compared with galanthamine, the standard drug. Nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW 264.7 cells were inhibited significantly by the mushroom extracts in a concentration dependent manner. Therefore, we demonstrated that fruiting bodies of R. rosacea possess in vitro antioxidant, anti-hyperglycemic, anti-cholinesterase, and NO production inhibitory activities. The experimental results suggest that the fruiting bodies of R. rosacea are good natural antioxidant, anti-hyperglycemic, anti-cholinesterase, and anti-inflammatory sources.

고마리 추출물의 항산화, 항균, 항염, 항알레르기 효과

곽정심 ( Jung-sim Gwak ),김춘득 ( Chun-dug Kim ) 한국미용학회 2018 한국미용학회지 Vol.24 No.5

This study was examin the potential of Persicaria thunbergii extracts as physiologically active cosmetic ingredients. Ethanol and hot-water extracts of P. thunbergii were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method for antioxidant activity, MTT assay for cell viability in RBL-2H3 and RAW 264.7 cells, paper diffusion assay for anti-microbial activity against Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes, inhibition of nitric oxide (NO) production for anti-inflammatory effect and inhibition of β-hexosaminidase for anti-allergy effect. The polyphenol contents of P. thunbergii ethanol and hot-water extracts were 132.00 and 89.46 μg/mL, respectively. And total flavonoid contents of P. thunbergii ethanol and hot-water extracts were 115.27, 84.94 μg/mL, respectively. The anti-oxidative activity of the two P. thunbergii extracts was compared, and the anti-oxidative activity of the ethanol extract was found to be superior to that of the hot-water extract. The DPPH radical scavenging activity was found to be 79.80% for the ethanol extract and 70.33% for the hot-water extract at a concentration of 500 μg/mL. No significant cytotoxicity was observed in RAW 264.7 and RBL-2H3 cells. In addition, the concentration dependent antimicrobial activities of two extracts were demonstrated in 3 microbial strains, such as those of S. aureus, S. epidermidis, and P. acnes. The anti-inflammatory activity of two extracts was examined in RAW 264.7 cells, and nitric oxide (NO) production was suppressed in a concentration-dependent manner. Both ethanol and hot-water extracts also inhibited secretion of β- hexosaminidase in a concentration-dependent manner. Based on the findings from this study, P. thunbergii extracts could be used as functional cosmetic ingredients that possess anti-oxidative, anti-microbial, anti-inflammatory, and anti-allergy properties. In order to determine their applicability, further research should be systematically conducted to verify their efficacy through clinical studies in humans.

자외선에 의한 피부손상 및 염증반응에서 크랜베리 에탄올 추출물의 억제효과

정민지 ( Min-ji Jung ),김배환 ( Bae-hwan Kim ) 한국동물실험대체법학회 2021 동물실험대체법학회지 Vol.15 No.1

This research was conducted to examine the usability of Cranberry Ethanol Extract (CEE) as an anti-inflmmatory ingredient. The total content of polyphenol and flavonoid as well as DPPH electron-donation and ABTS+ radical scavenging abilities were measured to check anti-oxidation activity. To verify anti-inflammatory effect, the nitric oxide (NO) inhibition assay in Raw 264.7 cell were conducted. The anti-inflammatory effect of CEE in UVB (160 mJ/cm²) irradiated HaCaT cell was evaluated by checking tumor necrosis factor (TNF)-α expression. The cell migration assay was peformed to confirm the wound healing effect of test material. In addition, the safety related to irritation was verified by Bovine Corneal Opacity and Permeability (BCOP) assay. The antioxidant abilities increased in concentration dependent manner in all tests, which confirmed CEE had a good anti-oxidation activity. In anti-inflammatory test, LPS-induced NO secretion was inhibited by CEE treatment, confirming anti-inflammatory effect of CEE. In UVB irradiated HaCaT cell, TNF-α expression, main cytokine in inflammation induced by UVB, also decreased in CEE treatment group in western blot assay. In migration assay of HaCaT cells, the remaining area of wound decreased significantly in CEE treated group, indicating CEE showed the wound healing effect. As for BCOP assay, CEE was classified as a non-irritant according to the OECD guideline 437. In conclusion, the results of this study showed that CEE has high anti-oxidation and anti-inflammation effects, and inhibits irritation from an external irritant such as UVB, which indicated it can be used as an anti-inflmmatory ingredient.

우슬 다당 추출물의 항염 효과에 관한 연구

이대우 ( Dae-woo Lee ),김영진 ( Young-jin Kim ),김영실 ( Young-sil Kim ),엄상용 ( Sang-yong Eom ),김종헌 ( Jong-heon Kim ) 대한화장품학회 2008 대한화장품학회지 Vol.34 No.1

우슬(Acyranthes bidentata)은 항관절염(anti-arrthritic), 최음(aphrodisiac), 항바이러스(anti-viral), 항경련(anti-spasmodic), 항고혈압(anti-hypertensive), 항응고(anti-coagulant) 그리고 항암(anti-tumor)효과에 사용되어 왔다. 본 연구는 우슬 추출물로부터 분리한 다당 추출물의 화장품 원료로서의 특성을 알아보기 위하여 항염 효과와 관련된 다양한 실험을 실시하였다. 우슬 다당 추출물을 대상으로 실험한 결과 항염(IL-1α, IL-6, COX-2 그리고 total NO 생성 억제) 효과를 나타내었다. Acyranthes bidentata has been used as anti-arrthritic, aphrodisiac, anti-viral, anti-spasmodic, anti-hypertensive, anti-coagulant and anti-tumor agent. In this study, we evaluated anti-inflammatory effect of polysaccharide extract from Acyranthes bidentata. Acyranthes bidentata polysaccaride decreased IL-1α, IL-6, COX-2, and total NO synthesis. Our results point to the potential use of Acyranthes bidentata polysaccaride as a cosmeceutical agent for inflammatory cutaneous symptoms.

화장품 소재로서 고마리 추출물의 생리활성

곽정심,김춘득 한국피부과학연구원 2018 아시안뷰티화장품학술지 Vol.16 No.3

Purpose: The purpose of this study was to investigate the potential of Persicaria thunbergii (P. thunbergii) extracts as physiologically active cosmetic ingredients. Methods: To elucidate the anti-oxidative, anti-inflammatory, and anti-microbial properties of P. thunbergii , its ethanol and hot-water extracts were examined for 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, nitric oxide (NO) production, protective effects against oxidative stress in HaCaT cells, anti-inflammatory activity, anti-microbial activity, and inhibition of β-hexosaminidase expression, an allergy factor. Results: The anti-oxidative activity of the two P.thunbergii extracts was compared, and the anti-oxidative activity of the ethanol extract was found to be superior to that of the hot-water extract. The polyphenol contents of P. thunbergii ethanol and hot-water extracts were 132.00 and 89.46 μg/ mL, respectively. And total flavonoid contents of P. thunbergii ethanol and hot-water extracts were 115.27, 84.94 μg/mL, respectively. The DPPH radical scavenging activity was found to be 79.80% for the ethanol extract and 70.33% for the hot-water extract at a concentration of 500 μg/mL. No significant cytotoxicity was observed in HaCaT, RAW 264.7 and RBL-2H3 cells. The protective effect of the extracts on HaCaT cell against oxidative stress induced by hydrogen peroxide (H 2 O 2 ) was confirmed by 23% for ethanol extract and 18% for hot water extract. The anti-inflammatory activity of the extracts was examined in RAW 264.7 cells, and nitric oxide (NO) production was suppressed in a concentration-dependent manner. Both ethanol and hotwater extracts also inhibited the degranulation of immune cells in a concentration-dependent manner, as assessed by the secretion of β-hexosaminidase. In addition, the concentration dependent anti-microbial activities of the extracts were demonstrated in several bacterial strains, such as those of Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), and Propionibacterium acnes (P. acnes). Conclusion: Based on the findings from this study, P. thunbergii extracts could be used as functional cosmetic ingredients that possess anti-oxidative, anti-inflammatory, and anti-microbial properties. In order to determine their applicability, further research should be systematically conducted to verify their efficacy through clinical studies in animals and humans. 목적: 고마리 추출물에 대한 생리활성 및 그에 따른 화장품 소재로서의 응용 가능성을 알아보고자 하였다. 방법: 고마리 에탄올및 열수 추출물의 항산화, 항염, 항균 효능을 확인하기 위하여 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical 소거능, nitric oxide (NO) 생성량 측정, 산화적 스트레스에 대한 HaCaT 세포 보호 효과, 항염, 항균, 알러지인자인 β-hexosaminidase 발현량 억제를 측정하였다. 결과: 고마리 추출물의 항산화 효능을 비교한 결과, 에탄올 추출물이 열수 추출물보다 우수하였으며, 고마리 에탄올, 열수 추출물의 폴리페놀 함량은 각각 132.00, 89.46 μg/mL이고, 총 플라보노이드 함량은 각각 115.27, 84.94 μg/mL으로 확인되 었다. 그리고 DPPH radical 소거능 측정결과, 고마리 에탄올, 열수 추출물의 농도가 500 μg/mL 일 때 각각 79.80, 70.33%로 확인 되었으며, 세포 독성 실험결과, HaCaT, RAW 264.7, RBL-2H3 세포에서 유의한 세포독성은 나타나지 않았다. Hydrogen peroxide (H 2 O 2 )에 의해 유발되는 산화적 스트레스에 대한 HaCaT 세포 보호 효과 확인결과, 고마리 에탄올, 열수 추출물은 23%, 18%로 세포 보호 효과가 확인되었다. RAW 264.7 세포에 대한 고마리 추출물의 항염 효과를 확인한 결과, 농도 의존적으로 nitric oxide (NO) 생성이 억제되었다. β-Hexosaminidase의 분비를 측정한 결과, 고마리 에탄올과 열수 추출물은 농도 의존적으로 면역세포의 탈과 립을 억제하였다. 고마리 추출물의 항균효능을 측정한 결과, Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), Propionibacterium acnes (P. acnes)에서도 농도 의존적으로 항균 활성이 확인되었다. 결론: 이상의 연구결과를 통해 고마리 추출물은 항산화, 항염증 및 항균 효과를 가지는 기능성 화장품 소재로서의 효능이 확인되었다. 앞으로 기능성 화장품 소재 로서의 활용 가능성을 판단하기 위하여 임상적으로 동물, 인체실험을 통한 고마리 추출물의 효능 검증 연구가 체계적으로 진행되어야 할 것이다.

Effects of Egg Shell Membrane Hydrolysates on Anti-Inflammatory, Anti-Wrinkle, Anti-Microbial Activity and Moisture-Protection

Yoo, Jinhee,Park, Kimoon,Yoo, Youngji,Kim, Jongkeun,Yang, Heejin,Shin, Youngjae Korean Society for Food Science of Animal Resource 2014 한국축산식품학회지 Vol.34 No.1

This study was conducted to examine the effects of eggshell membrane hydrolysates (ESMH) on the anti-inflammatory, anti-wrinkle, anti-microbial activity, and moisture-protection for cosmetic use. Whole ESMH (before fractionation), and fraction I (>10 kDa), fraction II (3-10 kDa), and fraction III (<3 kDa) of the hydrolysates were assessed in this experiment. As lipopolysaccharide (LPS) and IFN-${\gamma}$ caused the inflammation on Raw264.7 cell, whole ESMH and fraction I showed to be effective in inhibiting the induction of cell inflammation depending on the concentration, and also showed outstanding effect to suppress the skin inflammation. Fraction I inhibited collagenase and elastase activities to a greater extent than the other fractions, while all fractions had antibiotic effects at concentrations of 10 mg/disc and 20 mg/disc. In addition, it showed the moisture protection effects of skin on the holding amount and losing amount of moisture in upper-inner arm of the human body with a relatively low loss rate in skin, which confirmed that the hydrolyzed fractions of ESM helps to form the superior protective layer of moisture. It was concluded that ESMH fractions with different molecular weights, especially the 10 kDa fraction, have anti-lipopolysaccharide, anti-IFN-${\gamma}$-induced inflammation, anti-collagenase and elastase activities, and thus can be used as a cosmetic agent to protect skin.