Effect of Astaxanthin on Anti-Inflammatory and Anti-Oxidative Effects of Astaxanthin Treatment for Atopic Dermatitis-induced Mice

Park, Jin Woo,Song, Ho-Sueb Korean AcupunctureMoxibustion Medicine Society 2021 대한침구의학회지 Vol.38 No.4

Background: This study sought to determine whether the antioxidant effects of astaxanthin (AST) could have an anti-inflammatory effect to reduce inflammation caused by atopic dermatitis (AD). Methods: Using a mouse model of AD induced by phtalic acid (PA), the levels of inflammation, inflammatory agents, and evidence of antioxidant activity were examined in PA treated mice (n = 3), PA-AST treated mice (n = 3), and a control group of mice (n = 3). This included measurements of ear thickness, levels of mast cells, IgE, inflammatory cytokine, malondialdehyde (MDA), hydrogen peroxide, HO-1, and GPx-1. Results: AST treatment significantly prevented inflammation as measured by ear thickness (p < 0.05), mast cell count (p < 0.001), and IgE concentration in the blood (p < 0.001). Levels of TNF-α (p < 0.001), IL-1β (p < 0.001), IL-6 (p < 0.001), and MDA (p < 0.05) were also significantly lower. In addition, GSH levels increased significantly (p < 0.001), and the level of hydrogen peroxide significantly reduced (p < 0.01). The expression of HO-1, GPx-1 increased. Conclusion: In this small experimental study, AST acted on inflammatory mechanisms that induced AD, through anti-inflammatory and antioxidant mechanisms, and is a candidate of interest in the clinical treatment of AD.

Cell Growth Inhibition and Induction of Apoptosis by Snake Venom Toxin in Ovarian Cancer Cell via Inactivation of Nuclear Factor κB and Signal Transducer and Activator of Transcription 3

Ju Kyoung Song,Jin Tae Hong,Mi Ran Jo,Mi Hee Park,Ho Sueb Song,Byeong Jun An,Min Jong Song,Sang Bae Han 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.5

Snake venom toxin from Vipera lebetina turanica induces apoptosis in many cancer cell lines, but there is no study about the apoptotic effect of snake venom toxin on human ovarian cancer cells. In this study, we investigated the apoptotic effect of snake venom toxin in human ovarian cancer PA-1 and SK-OV3 cells. Snake venom toxin dose dependently (0~10 μg/mL) inhibited ovarian cancer cell growth with IC50 values 4.5 μg/mL in PA-1 cells, and 6.5 μg/mL in SKOV3 cells. Our results also showed that apoptotic cell death increased by snake venom toxin in a dose dependent manner (0~10 μg/mL). Consistent with increased cell death, snake venom toxin increased the expression of pro-apoptotic protein Bax and caspase-3, but down-regulated anti-apoptotic protein Bcl-2. Untreated ovarian cancer cells showed a high DNA binding activity of nuclear factor B (NF-κB), but it was inhibited by snake venom toxin accompanied by inhibition of p50 and p65 translocation into the nucleus as well as phosphorylation of inhibitory κB. Snake venom toxin also inhibited DNA binding activity of the signal transducer and activator of transcription 3 (STAT3). Moreover, the combination treatment of NF-κB (salicylic acid, 1 or 5 μM) and STAT3 (stattic, 1 μM) with snake venom toxin (1 μg/mL) further enhanced cell growth inhibitory effects of snake venom toxin. These results showed that snake venom toxin from Vipera lebetina turanica caused apoptotic cell death of ovarian cancer cells through the inhibition of NF-κB and STAT3 signal, and suggested that snake venom toxin may be applicable as an anticancer agent for ovarian cancer.

Cobrotoxin Inhibits Prostate Carcinoma PC-3 Cell Growth Through Induction or Apoptotic Cell Death Via Inactivation of NF-kB

Song Kyung-chul,Song Ho-sueb 대한침구의학회 2006 대한침구의학회지 Vol.29 No.1

We previously found that cobrotoxin inhibited NF-κB activity by reacting with signal molecules of NF-κB which is critical contributor in cancer cell growthby induction of apoptotic cell death. We here investigated whether cobrotoxin inhibits cell growth of human prostate cancer cellsthrough induction of apoptotic cell death, which is related with the suppression of the NF-κB activity. Cobrotoxin (0~8 nM) inhibited prostate cancer cell growth through increased apoptosis in a dose dependent manner. Cobrotoxin inhibited DNA binding activity of NF-κB, an anti-apoptotic transcriptional factor. Consistent with the induction of apoptosis and inhibition of NF-κB, cobrotoxin increased the expression of pro-apoptotic proteins caspase 3. Cobrotoxin, a venom of Vipera lebetina turanica, is a group of basicpeptides composed of 233 amino acids with six disulfide bonds formed by twelve cysteins. NF-kB is activated by subsequent release of inhibitory IkB and translocation of p50. Since sulfhydryl group is present in kinase domain of p50 subunit of NF-kB, cobrotoxin could modify NF-kB activity by protein-protein interaction. And Cobrotoxin down regulated Akt signals. Salicylic acid as a reducing agent of Sulf-hydryl group and LY294002 as a Akt inhibitor abrogated cobrotoxin-induced cell growth and DNA binding activity of NF-κB. These findings suggest that nano to pico molar range of cobrotoxin could inhibit prostate cancer cell growth, and the effect may be related with the induction of apoptotic cell death through Akt dependent inhibition of NF-κB signal.

Cobrotoxin Inhibits Prostate Carcinoma PC-3 Cell Growth Through Induction of Apoptotic Cell Death Via Inactivation of NF-kB

Song, Kyung-Chul,Song, Ho-Sueb The Korean AcupunctureMoxibustion Medicine Society 2006 대한침구의학회지 Vol.23 No.2

We previously found that cobrotoxin inhibited $NF-{\kappa}B$ activity by reacting with signal molecules of $NF-{\kappa}B$ which is critical contributor in cancer cell growth by induction of apoptotic cell death. We here investigated whether cobrotoxin inhibits cell growth of human prostate cancer cells through induction of apoptotic cell death, which is related with the suppression of the $NF-{\kappa}B$ activity. Cobrotoxin $(0{\sim}8\;nM)$ inhibited prostate cancer cell growth through increased apoptosis in a dose dependent manner. Cobrotoxin inhibited DNA binding activity of $NF-{\kappa}B$, an anti-apoptotic transcriptional factor. Consistent with the induction of apoptosis and inhibition of $NF-{\kappa}B$, cobrotoxin increased the expression of pro-apoptotic proteins caspase 3. Cobrotoxin, a venom of Vipera lebetina turanica, is a group of basicpeptides composed of 233 amino acids with six disulfide bonds formed by twelve cysteins. NF-kB is activated by subsequent release of inhibitory IkB and translocation of p50. Since sulfhydryl group is present in kinase domain of p50 subunit of NF-kB, cobrotoxin could modify NF-kB activity by protein-protein interaction. And Cobrotoxin down regulated Akt signals. Salicylic acid as a reducing agent of Sulf-hydryl group and LY294002 as a Akt inhibitor abrogated cobrotoxin-induced cell growth and DNA binding activity of $NF-{\kappa}B$. These findings suggest that nano to pico molar range of cobrotoxin could inhibit prostate cancer cell growth, and the effect may be related with the induction of apoptotic cell death through Akt dependent inhibition of $NF-{\kappa}B$ signal.

PubMed 검색(檢索)을 이용한 전립선(前立腺) 질환(疾患)의 침치료(鍼治療)관련 연구(硏究)에 대한 고찰(考察)

송호섭,Song, Ho-Sueb 대한약침학회 2004 Journal of pharmacopuncture Vol.7 No.2

Objective : This study was to review on the prostate disease-related studies with Acupuncture therapy in renowned medical internet site of PubMed, and to make master plan of the study, especially, on Bee Venom Acupuncture(BVA) of Prostate disease and then to devise the idealistic therapeutic ways of it. Method : We made the internet search with the key words of bee venom(bee venom therapy, apitoxin, apitherapy, bee sting, bee sting therapy), acupuncture, prostate, prostatitis, prostrate cancer in Pubmed, from June 1st to July 1st,2004. Results : 1.25 papers were found in 19 publised jounals. of which two named'Urology'and Prostate' had three papars, two called 'JUrology' and 'Cancer Immunol Immunother' had two papers, and the others had a paper respectively. 2. In the classification by papers' types, Review papers were 8 and Original were 17 where there were 5 clinical trials, 11 experimental studies and 1 epidemiologic paper. Of 5 clinical trials, 2 belonged to Randomized Control Study, and of 11 experimental studies, 4 belonged to in vitro and 7 belonged to in vivo with in viro studies, and 1 epidemeologic belonged to meta-analysis. 3. In the classification by prostate diseases, 4 were about prostatitis, 3 were about prostate related symptoms, 16 were about prostate cancer, and two were about the others. 4. In the classification by applied treatment methods, 5 were related with Acupuncture, 10 were related with BVA(Bee Venom, Bee), and 10 were related with the others. Of 5 related with Acupuncture, 3 used general acupuncture, 1 used electrical acupuncture, and 1 used general acupuncture and electrical acupuncture at the same time. 5. In 2 RCTs of Clinical trials, Control group was set up to the group using different compatible treatment method or using meridians not related with treating prostate disease. Single or double blind methods couldn't be found. 6. In the clinical trials, IPSS, NIH, CPSI or subjective global assessment were used as the Index of Evaluation. 7. The Leg Greater Yang Bladder Meridian(B), The Leg Lesser Um Kidney Meridian(K) and Conception Vessel Meridian(CV) were used as major meridians, and B10(Taejo, Dazhu), B23(Shinsu, Shenshu), B28(Panggwangsu, Pangguangshu), B35(Hoeyang, Huiyang), B39(Wiyang, Weiyang), B40(Wijung, Weizhong), B54(chilbyon, Zhibian), K1(Yongchon, Yongquan), K10(Umgok, Yingu), CV3(Chungguk, Zhongji), CV4(Kwanwon, Guanyuan),S6(Hyopko, Jiache) were used as acupoints. Electrical acupuncture(EA) was considered to be more important and CV3(Chungguk, Zhongji), CV4(Kwanwon, Guanyuan) were mainly selected as EA applied acupoints. 8. It is mostly said that Acupuncture appeared to be a safe, effective, and durable treatment alternative in improving symptoms of patients with prostate diseases, refractory to conventional medicine. A larger controlled study was required to confirm these encouraging initial results. Conclusion : Papers about BVA of Prostate cancer or Prostatitis were not found, and low permeability of Prostate is concerned, BVA with the anti-inflammatory and anti-cancer effect can be adopted as a new alternatives of Prostate disease treatment, so it is thought that Study of how to make access to prostate, animal experiment including in vivo and in vitro and more clinical trials with using acupoints on related meridian should be followed.

봉약침액(蜂藥鍼液)이 Scopolamine으로 기억장애(記憶障碍) 유발(誘發) 시 Acetylcholine Esterase 활성에 미치는 영향(影響)

송정열,송호섭,Song, Jeong-Yeol,Song, Ho-Sueb 대한침구의학회 2006 대한침구의학회지 Vol.23 No.3

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the following 4 structural changes : Atrophy of the Cortex, Parasympathetic, and other neural cells, the existence of Neurofibrillary tangles (NFTs), and the accumulation of Senile plaques. NFTs and Senile plaques is known to be the index of this disease. Senile plaques disturbs the neutro transmission and depletes of Acetylcholine. So, Recovery of Acetylcholine is the primal objective for treating Alzheimer's disease. So, Inhibiting the activity of Acetylcholine Esterase (AChE), which causes the hydrolysus of acetylcholine into choline and acetate, can be seen as a key role for treating Alzheimer's disease. Increasing body of evidence has been demonstrated that Bee Venom Acupuncture (BV) could compete with complex protein involving in multiple step of $NF-_{\kappa}B$ activation and exert the anti-inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-_{\kappa}B$. BV dose-dependently attenuated Scopolamine-induced Acetylcholine esterase activities in cerebral cortex and hippocampus of the mice brain. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

Snake venom from Vipera lebetina turanica inhibits tumor in a PC-3 cell Xenograft model and PC-3 cell growth in vitro.

Kang Jun,Song Ho-sueb 대한침구의학회 2007 대한침구의학회지 Vol.24 No.2

Objectives : We in here investigated whether snake venom toxin (SVT) from Vipera lebetina turanica inhibits cell growth of human prostate cancer cells (PC-3) Xenograft model and PC-3 cell growth in vitro through induction of apoptosis. Material and Methods : Mass and weight of he PC-3 human prostate cancer cell that was treated with SVT were evaluated on apoptosis assays, Immunofluorescence staining, confocal immonocytochemistry, electromobility shift assay and tumorigenecity study in athymic nede mice. Results :Compared with controls, Mass and weight of he PC-3 cell lessened through the above experiments . Conclusions : These in vitro findings suggest that nano molar range of SVT from Vipera lebetina turanica could inhibit prostate cancer cell growth, and the effect may be related with the NF-κB signal-mediated induction of apoptosis. In addition to the In vitro results, SVT(0.2, 0.4 mg/Kg) suppressed growth of prostate cancer in a xenograft athymic mice model, and reduced volume and weight of the cancer. Key words :Key words: snake venom toxin, Vipera lebetina turanica, prostate cancer, apoptosis, NF-κB, p53, caspase-3, caspase-9, Bcl-2, Bax, Xenograft, PC-3 연구목적 : 이 연구는 Vipera lebetina turanica의 蛇毒藥鍼液(Snake venom toxin, SVT)이 in vitro에서 NF-κB의 활성억제와 apoptosis 관련 단백질의 발현 조절을 통하여 세포자멸사(Apoptosis)를 유도하는지 in vivo에서 또한 전립선 암세포주인 PC-3 세포의 성장을 억제하는지 살펴보고자 하였다. 실험방법 : SVT를 처리한 후 PC-3의 성장억제를 관찰하기 위해 WST-1 assay, CCK-8 assay를 시행하였고, Apoptosis evaluation에는 DAPI, TUNEL staining assay를 시행하였으며, Apoptosis regulatory proteins의 변화 관찰에는 western blot analysis를 시행하였고, apoptosis와 연관된 NF-κB의 활성 변화를 관찰하기 위해 EMSA시행하였으며, SVT의 핵내이동을 관찰하기 위해 Immunofluorescence Staining, Confocal immunocytochemistry를 시행하였으며, 전립암세포의 종양형성에는 흉선을 제거한 쥐에 Tumorigenecity study를 시행하였다. 결 과: PC-3 세포에 SVT를 처리한후, 전립선암세포의 성장, Apoptosis의 유발, Apoptosis관련 단백질의 발현, NF-κB의 활성, SVT의 PC-3세포 핵내 이동여부 및 흉선제거 후 PC-3 세포를 이식한 쥐의 종양형성과정에 미치는 영향을 관찰하여 다음과 같은 결과를 얻었다. 1. PC-3 세포에서 SVT를 처리한 후 세포성장이 억제되고, 세포자멸사가 유도되며, 조절인자인 p53, caspase-3, -9는 증가되었고, Bcl-2는 감소되었다. 2. PC-3 세포에서 SVT를 처리한 후 NF-κB의 활성이 유의하게 감소되었다. 3. DAPI로 염색된 상태에서 SVT가 PC-3 세포의 핵내로 이동되는 것이 관찰되었다. 4. 흉선 제거 후 전립선 암세포주를 이식한 쥐에서 SVT를 피내로 주입한 결과 전립선암의 크기와 무게가 유의하게 감소하였다. 결 론 : 이상의 결과는 SVT가 NF-κB의 활성 억제를 통하여 인간 전립선암세포주인 PC-3의 세포자멸사를 유발함으로써 증식억제 효과가 있음을 입증한 것이며, 이를 재확인한 생체 연구에서의 긍정적인 결과는 향후 SVT의 전립선암의 예방과 치료에 대한 효과적인 치료제 개발에 초석이 될 것으로 기대된다.

Scutellaria baicalensis Extract Alleviates Pain and Inflammation in Animal Models

Haeni Seo,Ho-Sueb Song 대한침구의학회 2023 대한침구의학회지 Vol.40 No.1

Background: This study aimed to examine the effect of Scutellaria baicalensis extract (SBE) on ameliorating pain response and inflammation in an animal model. Methods: The effects of SBE on joint inflammation-induced rats and pain writhing response were measured. In rats with monosodium iodoacetate (MIA)-induced knee osteoarthritis (OA), the weight-bearing distribution of the hind legs was measured, the actual joint condition was visually confirmed, and serum cytokines were extracted from whole blood and measured. In addition, the acetic acid-induced pain was measured by the number of abdominal wall contractions and writhing responses. Results: 1. The weight-bearing distribution of the hind limbs of the SBE group was remarkably improved compared with that of the control group 7 days after MIA treatment, and the SBE 300 group was improved similarly to that of the indomethacin group. 2. Cartilage erosion was significantly recovered in the SBE and indomethacin groups, and the degree of healing of cartilage erosion by SBE was similar to that by indomethacin. 3. The serum levels of cytokines interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly decreased in the SBE group compared with that in the control group, and the SBE 300 group had reduced levels of cytokines similar to the indomethacin group. 4. As regards acetic acid-induced writhing response, the number of writhes was significantly reduced in the SBE and ibuprofen groups, and the SBE 600 group had fewer writhes than the ibuprofen group. Conclusion: SBE significantly improves knee OA and pain and is expected to show similar therapeutic effects to indomethacin and ibuprofen.

Obovatol extracted from Magnolia Obovata inhibits inflammation mediator generation and prostate carcinoma PC-3, LNCap cell growth through induction of apoptotic cell death via inactivation of NF-κB

KimGoon-Joong,Song Ho-sueb 대한침구의학회 2007 대한침구의학회지 Vol.26 No.2

Objectives : To evaluate effect of obovatol extracted from Magnolia Obovata inhibits inflammation mediator generation and prostate carcinoma PC-3, LNCap cell growth through induction of apoptotic cell death via inactivation of NF-κB.Methods : We conducted an in vitro analysis to evaluate RAW264.7 cell and the prostate cell response to obovatol in order to determine the ability and related mechanism of this therapeutic agent from natural herb to inhibit inflammation and to suppress prostate cell growth by affecting inflammation-related gene expression, cell proliferation and apoptosis via inactivation of NF-κB and other cell survival signals.Results : We found that obovatol inhibited a pronounced down- regulation of nuclear localized protein levels of nuclear factor-κB family members. Down regulated NF-κB signals by obovatol is consistent with inflammation and cell growth inhibition. These data suggest that NF-κB signal may be significant contributor in obovatol-induced anti-inflammatory effect and human prostate cancer cell PC-3, LNCap cell death. 연구목적 : 厚朴(Magnolia Obovata)에서 추출한 낮은 농도의 Obovatol 약침액의 RAW264.7 세포에서 LPS로 유발된 염증, TNF-α로 유발된 human Prostate carcinoma PC-3 및 LNCap 세포의 세포증식에 대한 영향과 그 기전을 살펴보고자 하였다. 실험방법 : RAW264.7 세포에서 LPS로 염증을 유발하고 낮은 농도의 Obovatol 약침액을 처리한 후 cell viability, NO 생성량, iNOS와 COX-2의 발현, NF-κB활성, 전사능력을 관찰하기 위해 MTT assay, NO determination assay, western blot analysis, EMSA, luciferase activity assay를 시행하였고, LNCap, PC-3 세포에 TNF-α로 증식을 유도하고 낮은 농도의 Obovatol 약침액을 처리한 후 cell growth, apoptosis 및 apoptosis와 연관된 NF-κB의 활성 변화를 관찰하기 위해 WST-1, Cell morphogy test, DAPI staining and TUNEL assay, EMSA, luciferase activity assay를 시행하였다. 결 과: 1. RAW264.7 세포에서 낮은 농도의 Obovatol 약침액 처리는 NF-κB의 활성 및 전사능력을 낮추고 iNOS와 COX-2의 발현과 NO 생성을 감소시켜 LPS로 유발된 염증을 억제하였다. 2. LNCap, PC-3 세포에서 낮은 농도의 Obovatol 약침액 처리는 NF-κB의 활성을 낮추어 세포자멸사을 촉진함으로써 TNF-α로 유발된 암세포의 성장을 억제하였다. 결 론 : 이상의 결과는 낮은 농도의 Obovatol 약침액이 항염 및 인간 전립선암세포주인 PC-3, LNCap에 대한 증식억제 효과가 있음을 입증한 것이며, 향후 이를 바탕으로 한 생체 연구에서의 긍정적인 결과는 Obovatol 약침액이 만성염증성 질환 및 전립선암의 예방과 치료에 대한 효과적인 치료제 개발에 초석이 될 것으로 기대된다.

Effects of Scutellaria baicalensis Extract on Gout-Induced Rats

Eunchang Lee,Ho-Sueb Song 대한침구의학회 2023 대한침구의학회지 Vol.40 No.2

Background: This study aimed to investigate hyperuricemia, renal inflammation, and xanthine oxidase (XO) activity improvement in a rat model treated with Scutellaria baicalensis extract (SBE). Methods: The rats were divided into 4 groups (n = 5 each), including sham, potassium oxonate (PO) injected hyperuricemia (control group), PO + 10 mg/kg allopurinol administrated (allopurinol group), and a PO + 50 mg/kg SBE administrated (SBE group), to investigate the effectiveness and molecular mechanisms of SBE. The effects of SBE on PO-induced hyperuricemia rats, renal inflammation, and XO activity were measured. Body weight and organ index of the kidney and liver were measured in PO-induced hyperuricemia rats, and serum uric acid level was extracted from whole blood and was measured. Renal inflammation was observed under a microscope after sections. XO activity was measured by liver tissue and serum XO levels. Results: Organ indexes of the kidney and liver in rats were significantly decreased in the allopurinol group than in the control group and with no significant difference in the SBE group. A PO injection for 5 days significantly increased serum uric acid levels in the control group compared to the sham group. Meanwhile, the SBE and allopurinol groups have significantly decreased serum uric acid levels compared to the control group. The SBE group revealed effectively improved renal histopathological changes compared to the control group. The XO inhibitor, allopurinol, significantly decreased XO activity. Additionally, SBE significantly lowered XO activity in rats. Conclusion: SBE can be used as an effective treatment for gout in the future.