Effects of a Mixture of Three Extracts of Wolfberry, Chives and Graviola on the Erectile Dysfunction Induced by Bilateral Cavernous Nerve Injury in Rats

Jai Youl Ro,Gwan Ui Hong,신연호,Chung Myung-Hee 건강기능식품미래포럼 2022 건강기능식품미래포럼 학술지 Vol.2 No.4

Although some chemicals are available for erectile dysfunction (ED), efforts have been also made to seek health functional foods that can improve ED. Lycium barbarum (wolfberry) and Allium tuberosum (chives) were reported to enhance erectile function. And Annona muricata L is known to have anti-inflammatory and antioxidant actions. We assumed that if the three plants were used together, they may enhance erectile function synergistically. Hyunsung Vital Co. Ltd. prepared a mixture of water extracts of the three plants and named it Jikdaijangryeuk (JDJR). In the present study, JDJR was tested for the effect of improving ED in the rats subjected to bilateral corpus cavernous nerve injury (BCNI). BCNI decreased intra-cavernous pressure and also induced biological responses in the penile tissue that lead to ED, which were decreases in the expressions of endothelial nitric oxide (NO) synthase (eNOS) and nervous NO synthase (nNOS) that produce NO (a stimulator of 3′,5′-cyclic guanosine monophosphate [cGMP] synthesis), neurofilament-1 (a marker of nerve fibers) and an anti-apoptotic protein (Bcl2) and in the amounts of NO, cGMP (a blood vessel dilator) and smooth muscle as well as increases in the expression of inducible NO synthase (iNOS) (an inducer of microvasculature dysfunction), phosphodiesterase-5 (a cGMP destroyer), apoptotic molecules (caspase-3 and Bax) and transforming growth factor-β (a fibrosis inducer) and in the amount of asymmetric dimethylarginine (an endogenous NO synthases inhibitor). These data indicate that BCNI suppresses function of NO/cGMP axis and causes apoptosis and fibrosis of cavernous tissue. JDJR, however, reversed all these responses in a dose-dependent manner and the effects of JDJR were comparable to those of sildenafil (a positive control). The powder of Platycodon grandiflorum (a negative control) did not show the effects. These data support that JDJR has the action to enhance erectile function and thus, may be of help for ED.

Effects of Ginsenosides on the Mechanism of Histamine Release in the Guinea Pig Lung Mast Cells Activated by Specific Antigen-Antibody Reactions

Ro, Jai-Youl,Ahn, Young-Soo,Kim, Kyung-Hwan The Korean Society of Pharmacology 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.4

We previously reported that some components of ginsenosides decreased mediator releases evoked by the activation of mast cells with specific antigen-antibody reactions. This study aimed to assess the effects of ginsenosides ($Rb_2$, Re) on the mechanism of histamine release in the mast cell activation. We partially purified guinea pig lung mast cells by using enzyme digestion, the rough and the discontinuous percoll density gradient method. Mast cells were sensitized with $IgG_1$ and challenged with ovalbumin (OA). Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay. Phospholipase D (PLD) activity was assessed more directly by the production of $[^3H]phosphatidylbutanol$ (PBut) which was produced by PLD-mediated transphosphatidylation in the presence of butanol. The amount of 1,2- diacylglycerol (DAG) were measured by the $[^3H]DAG$ labeled with $[^3H]palmitic$ acid or $[^3H]myristic$ acid. Pretreatment of $Rb_2$ ($300\;{\mu}g$) significantly decreased histamine release by 60%, but Re ($300\;{\mu}g$) increased histamine release by 34%. Leukotrienes release in $Rb_2$ was decreased by 40%, Re was not affected in the leukotrienes release during mast cell activations. An increasing PLD activity during mast cell activation was decreased by the dose-dependent manner in the pretreatment of $Rb_2$, but Re pretreatment facilitated the increased PLD activity during mast cell activation. The amount of DAG produced by phospholipase C (PLC) activity was decreased by $Rb_2$ pretreatment, but Re pretreatment was not affected. The amount of mass DAG was decreased by $Rb_2$ and Re pretreatment during mast cell activation. The data suggest that $Rb_2$ purified from Korean Red Ginseng Radix inhibits the DAG which is produced by the activation of mast cells with antigen-antibody reactions via both phosphatidylinositide-PLC and phosphatidylcholine-PLD systems, and then followed by the inhibition of histamine release. However, Re increases histamine release by stimulation of DAG production, which is mediated by phosphatidylcholine-PLD system rather than by phosphatidylinositide-PLC system, but inhibits the mass DAG production. Thus, it could be inferred that other mechanisms play a role in the increase of histamine release during mast cell activation.

Effects of epithelium on the mechanism of mediator release from guinea pig tracheal tissues sensitized by IgG_(1) versus IgE antibody

Ro, Jai Youl,Kim, Kyung Hwan Yonsei University, College of Medicine 1995 Yonsei medical journal Vol.36 No.2

The Inhibitory Mechanism of Aloe Glycoprotein (NY945) on the Mediator Release in the Guinea Pig Lung Mast Cell Activated with Antigen-Antibody Complexes

Jai Youl Ro,Byung Chul Lee,Myung Hee Chung,Seung Ki Lee,Chung Ki Sung,Kyung Hwan Kim,Young In Park 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.1

It has been reported that the g1ycoprotein extracted from A10e has strong anti-inflammatory response,However, there has been no research report yet about the effect of A10e on allergic hypersensitivity reactivity, By using guinea pig 1ung mast cells, this study aimed to examine the effects of A10e g1ycoprotein (NY945) on the mediator re1eases caused by mast cell activation, and a1so aimed to assess the effects of NY945 on the mechanism of mediator re1eases in the mast cell activation. We partially purified mast cell from guinea pig 1ung tissues by using the enzyme digestion, the rough and the discontinuous density percoll gradient method. Mast cells were sensitized with IgG1 (anti-OA) and challenged with ova1bumin. Histamine was assayed by fluorometric ana1yzer, 1eukotrienes by radioimmunoassay. The phospholipase D activity was assessed by the production of 1abe1ed phosphatidy1alcoho1. The amount of mass 1,2-diacy1g1ycero1 (DAG) was measured by the eH]DAG produced when pre1abe1ed with eH]myristic acid. The phosph01ipid methy1ation was assessed by measuring the incorporation of the eH]methy1 moiety into phosph01ipids of cellu1ar membranes. Pretreatment of NY945 (10 μg) significant1y decreased histamine and 1eukotrienes re1eases during mast cell activation. The decrease of histamine re1ease was stronger than that of 1eukotriene during mast cell activation. The phospholipase D activity increased by the mast cell activation was decreased by the dose-dependent manner in the pretreatment of NY945. The amount of DAG produced by PLC activity was decreased by NY945 pretreatment. The amount of mass 1, 2-diacy1g1ycero1 produced by activation of mast cells was decreased in the pretreatment of NY945. NY945 pretreatment strong1y inhibited the incorporation of the eH]methy1 moiety into phosph01ipids. The data suggest that NY945 purified from A10e inhibi엄 in part an increase of 1, 2-diacy1g1ycero1 which is produced by activating mast cells with antigen-antibody reactions, which is mediated via phosphatidylcholinephospholipase D and phosphatidylinosit01-phospholipase C systems, and then followed by the inhibition of histamine re1ease. Furthermore, NY945 reduces the production of phosphatidylch01ine by inhibiting the methy1transferase 1 and II, which decreases the conversion of phosphatidylcho1ine into arachidonic acid and inhibits the production of 1eukotrienes.

Cromakalim Blocks Membrane Phosphoinositide Activated Signals in the Guinea Pig Lung Mast Cells Stimulated with Antigen-Antibody Reactions

Jai Youl Ro,Ji Young Kim,Kyung Hwan Kim 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.2

<P> Cromakalim (BRL 34915), known as an airway smooth muscle relaxant, inhibited the releases of mediators in the antigen-induced mast cell activation. It has been suggested that cromakalim, in part, inhibited mediator releases by inhibiting the initial increase of 1,2-diacylglycerol (DAG) produced by the activation of the other phospholipase system which is different from phosphatidylcholine-phospholipase D pathway. The aim of this study is to further examine the inhibitory mechanism of cromakalim on the mediator release in the mast cell activation. Guinea pig lung mast cells were purified by using enzyme digestion and percoll density gradient. In purified mast cells prelabeled with [<SUP>3</SUP>H]PIP<SUB>2</SUB>, phospholipase C (PLC) activity was assessed by the production of [<SUP>3</SUP>H]insitol phosphates. Protein kinase C (PKC) activity was assessed by measuring the protein phosphorylated from mast cells prelabeled with [γ-<SUP>32</SUP>P]ATP, and Phospholipase A<SUB>2 </SUB>(PLA<SUB>2</SUB>) activity by measuring the lyso-phosphatidylcholine produced from mast cell prelabeled with 1-palmitoyl-2-arachidonyl phosphatidyl-[<SUP>14</SUP>C]choline. Histamine was assayed by fluorometric analyzer, and leukotrienes by radioimmunoassay. The PLC activity was increased by activation of the passively sensitized mast cells. This increased PLC activity was decreased by cromakalim pretreatment. The PKC activity increased by the activation of the passively sensitized mast cells was decreased by calphostin C, staurosporine and cromakalim, respectively. The PLA<SUB>2</SUB> activity was increased in the activated mast cells. The pretreatment of cromakalim did not significantly decrease PLA<SUB>2</SUB> activity. These data show that cromakalim inhibits histamine release by continuously inhibiting signal transduction processes which is mediated via PLC pathway during mast cell activation, but that cromakalim does not affect PLA<SUB>2</SUB> activity related to leukotriene release.

Effects of Ginsenosides on the Mechanism of Histamine Release in the Guinea Pig Lung Mast Cells Activated by Specific Antigen- Antibody Reactions

Jai Youl Ro,Young Soo Ahn,Kyung Hwan Kim 대한생리학회-대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.4

<P> We previously reported that some components of ginsenosides decreased mediator releases evoked by the activation of mast cells with specific antigen-antibody reactions. This study aimed to assess the effects of ginsenosides (Rb<SUB>2</SUB>, Re) on the mechanism of histamine release in the mast cell activation. We partially purified guinea pig lung mast cells by using enzyme digestion, the rough and the discontinuous percoll density gradient method. Mast cells were sensitized with IgG<SUB>1</SUB> and challenged with ovalbumin (OA). Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay. Phospholipase D (PLD) activity was assessed more directly by the production of [<SUP>3</SUP>H]phosphatidylbutanol (PBut) which was produced by PLD-mediated transphosphatidylation in the presence of butanol. The amount of 1,2- diacylglycerol (DAG) were measured by the [<SUP>3</SUP>H]DAG labeled with [<SUP>3</SUP>H]palmitic acid or [<SUP>3</SUP>H]myristic acid. Pretreatment of Rb<SUB>2</SUB> (300 ㄍg) significantly decreased histamine release by 60%, but Re (300 ㄍg) increased histamine release by 34%. Leukotrienes release in Rb<SUB>2</SUB> was decreased by 40%, Re was not affected in the leukotrienes release during mast cell activations. An increasing PLD activity during mast cell activation was decreased by the dose-dependent manner in the pretreatment of Rb<SUB>2</SUB>, but Re pretreatment facilitated the increased PLD activity during mast cell activation. The amount of DAG produced by phospholipase C (PLC) activity was decreased by Rb<SUB>2</SUB> pretreatment, but Re pretreatment was not affected. The amount of mass DAG was decreased by Rb<SUB>2</SUB> and Re pretreatment during mast cell activation. The data suggest that Rb<SUB>2</SUB> purified from Korean Red Ginseng Radix inhibits the DAG which is produced by the activation of mast cells with antigen-antibody reactions via both phosphatidylinositide-PLC and phosphatidylcholine- PLD systems, and then followed by the inhibition of histamine release. However, Re increases histamine release by stimulation of DAG production, which is mediated by phosphatidylcholine-PLD system rather than by phosphatidylinositide-PLC system, but inhibits the mass DAG production. Thus, it could be inferred that other mechanisms play a role in the increase of histamine release during mast cell activation.

Biochemical effect of Ginsenosides on chemical mediator release from Mast cell in Type I Hypersensitivity

Jai Youl Ro 대한천식 및 알레르기학회 ( 구 대한알레르기학회 ) 1993 추계학술대회 초록집 Vol.1993 No.-

The effects of cromakalim on the mediator releases from guinea pig lung mast cell activated by specific antigen-antibody reactions

Ro, Jai Youl,Yim, Young Nae,Kim, Kyung Hwan Yonsei University, College of Medicine 1996 Yonsei medical journal Vol.37 No.5

Gα12 and Gα13 Subunits Modulate Ca(2+) - Induced Histamine Release in Human Umbilical Cord Blood - Derived Mast Cells

(Jai Youl Ro),(Ji Young Kim),(Ji Hee Ha),(Chang Ho Lee) 한국미생물생명공학회 2002 Journal of microbiology and biotechnology Vol.12 No.3

N/A N/A

Cromakalim이 해명의 과민반응 매개체 유리에 미치는 영향

노재열(Jai Youl Ro),김경환(Kyung Hwan Kim) 대한약리학회 1993 대한약리학잡지 Vol.29 No.2

K⁺통로는 기도 평활근 세포에 존재하며 이들 통로가 활성화되면 평활근의 과분극의 결과 이완작용이 나타난다. K⁺통로의 이런 효과는 과민반응과 천식 치료에 응용될 수 있으므로 우리는 K⁺통로 개방제인 cromakalim (BRL34915, CK)이 IgG₁ 항체로 감작시킨 기도 및 폐조직으로 부터 유리되는 매개체 유리에 미치는 영향을 조사하였다. 피동적으로 감작된 두 조직은 2 × 10^-6 M의 CK로 30분동안 superfusion시킨 후 CK와 항원 (Ox-HSA) 0.1 mg/ml로 자극하였다. 또한 비만세포를 이용하여 CK의 효과를 조사하였다. 해명 폐조직 비만세포는 효소에 의한 digestion method (monodispersed; 미분리 정제), count current elutriation에 의한 방법(partially purified; 부분분리정제), 그리고 discontinuous Percoll방법(highly purified; 순수분리정제)에 의해 순수 분리되었다. CK로 전처치한후, 피동적으로 감작된 비만세포는 OA와 CaI의 여러 농도에 의해 자극되었다. 유리된 Hist은 spectrophotofluorometry에 의해, LT는 면역방사법에 의해 측정되었다. CK 전처치는 IgG₁ 감작후 항원에 의해 자극된 기도 조직에서 Hist 유리량을 35%까지, LT 유리량은 40%까지 감소시켰으나 기도 평활근 수축력에는 반응을 나타내지 못하였다. 항원 유도 폐조직에 있어서 CK전처치는 Hist유리량을 25%까지 감소시켰으나 LT 유리에는 미약한 감소를 나타내었다. 해명의 미분리정제, 부분분리정제, 그리고 순수 분리 정제된 비만세포로부터 Hist과 LT은 면역자극(OA)이나 비면역자극(CaI)에 의해 농도 의존적으로 유리되었다. 비만세포에서 유리된 LT는 5-lipoxygenase억제제인 A64077에 의해서 억제됨이 확인되었다. CK전처치는 OA유도 및 CaI유도 해명 폐조직 비만세포에서 Hist과 LT 유리량을 20%까지 감소시켰다. IgG₁ 감작후 Ox-HSA유도 기도 평활근 조직이나 혹은 OA유도 및 CaI유도 비만세포에서 Hist과 LT유리에 미치는 CK의 억제효과는 TEA와 GBC에 의해 완전히 봉쇄되었다. 이상의 결과에서 폐조직 비만세포는 LT를 유리할 수 있는 세포로 간주되며, 기도 평활근 이완제로 알려져 있는 CK은 특수 항원 유도 기도 평활근조직에서 매개체 유리를 부분적으로 억제하며, CK은 또한 OA유도 및 CaI로 유도된 순수분리 정제된 비만세포에서 매개체 유리를 부분적으로 억제하는 것으로 보아 비만세포가 활성화시 야기되는 여러 생화학적 현상중에서 미약하나마 K⁺통로가 관여할 것으로 사료된다. Potassium (K⁺) channels are present in airway smooth muscle cells, and their activation results in hyperpolarization and relaxation. Because these effects may have therapeutic relevance to hypersensitivity and asthma, we examined the effect of a potassium channel activator, cromakalim (BRL 34915, CK) on the release of mediators from superfused tracheal and parenchymal strips after passive sensitization with IgG₁ antibody. Both tissues were superfused with CK (2 × 10^-6 M) for 30 min and challenged with CK and antigen (Ox-HSA). Using monodispersed, partially purified, highly purified guinea pig lung mast cells, we also examined the effect of CK on mediator release from these cells after passive sensitization with IgG₁ antibody (α-OA). Guinea pig lung mast cells were purified using enzyme digestion method, count current elutriation, and discontinuous Percoll density gradient. After CK pretreatment, passively sensitized mast cells were challenged with varying concentration of antigen (OA, immunological stimuli) or with varying concentration of calcium ionophore (CaI, non-immunological stimuli). Histamine (Hist) release was determined by spectrophotofluorometry, and leukotrienes (LT) by radioimmunoassy. CK pretreatment decreased Hist by 35% and LT release by 40% in the antigen-induced tracheal tissue after IgG₁ sensitization but did not decrease the contractile response. In the antigen-induced parenchymal tissue CK decreased Hist release by 25% but poorly decreased LT. Both immunologic and non-immunologic stimuli caused a dose-dependent release of Hist and LT from monodispersed, partially purified and highly purified lung mast cells. Verification of LT release was obtained by the use of 5-lipoxygenase inhibitor, A64077 (Zileuton). CK decreased Hist and LT release by 20% respectively in the OA-induced guinea pig lung mast cells after IgG₁ sensitization. The inhibitory effects of CK on the Hist and LT release in the Ox-HSA-induced airway smooth muscle tissues or in the OA-induced and CaI-induced mast cells after IgG₁ sensitization were completely blocked by TEA and GBC. These studies show that guinea pig lung mast cells seem to be an important contributor to LT release, and that CK (which has been known as an airway smooth muscle relaxant) can in part act to inhibit mediator release in the antigen-induced airway smooth muscle, and that CK may also act to inhibit mediator release in the OA-induced and CaI-induced highly purified mast cells. These results suggest that Hist and LT release evoked by mast cell activation might in part be associated with K⁺4 channel activity.