Electric Stimulation Hyperthermia Relieves Inflammation via the Suppressor of Cytokine Signaling 3-Toll Like Receptor 4 Pathway in a Prostatitis Rat Model

Guan Qun Zhu,전승환,이규원,Wen Jie Tian,조혁진,하유신,홍성후,이지열,문명건,문성희,김세웅,배웅진 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.3

Purpose: Chronic prostatitis (CP), including chronic pelvic pain syndrome (CPPS), is the most commonly encountered manifestation of prostatitis. The aim of this study was to evaluate the effect of electric stimulation hyperthermia treatment (ESHT) on CP/CPPS and to explore the underlying mechanism. Materials and Methods: RWPE-2 cells with lipopolysaccharide-induced inflammation and a prostatitis rat model induced by 17β-estradiol and dihydrotestosterone underwent sham, electric stimulation, or ESHT treatment. Four weeks later, cells, supernatants, and rat prostates were collected for analysis using immunohistochemistry, Western blots, and enzyme-linked immunosorbent assays. Results: We found that ESHT improved prostatitis in vivo and attenuated inflammation in vitro. ESHT significantly induced suppressor of cytokine signaling 3 (SOCS3) expression and subsequently promoted HSP70. It attenuated inflammation through decreased expression of toll-like receptor 4 (TLR4), nuclear factor kappa B, and subsequent inflammatory cytokines. ESHT also inhibited apoptosis and released growth factor in tissue affected by prostatitis. Conclusions: ESHT improved CP/CPPS and reversed pathologic changes of prostatitis by inhibiting the SOCS3-TLR4 pathway.

Efficient Promotion of Autophagy and Angiogenesis Using Mesenchymal Stem Cell Therapy Enhanced by the Low-Energy Shock Waves in the Treatment of Erectile Dysfunction

Zhu, Guan Qun,Jeon, Seung Hwan,Bae, Woong Jin,Choi, Sae Woong,Jeong, Hyun Cheol,Kim, Kang Sup,Kim, Su Jin,Cho, Hyuk Jin,Ha, U. Syn,Hong, Sung Hoo,Lee, Ji Youl,Kwon, Eun Bi,Kim, Sae Woong Hindawi 2018 Stem cells international Vol.2018 No.-

<P><B>Background</B></P><P> Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED). However, the interactions and effects of action between MSCT and ESWT remain poorly understood. In this study, we investigated the mechanisms of combination therapy with MSCT and ESWT in a rat model of diabetic ED. </P><P><B>Materials and Methods</B></P><P> Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts. Diabetic rats induced by streptozotocin (65 mg/kg) were randomly divided into 4 groups: (1) DM control group, (2) DM + ESWT group, (3) DM + MSCT group, and (4) DM + ESWT + MSCT group. The sham group was a normal control group (without streptozotocin). MSCT and (or) ESWT were, respectively, administered to each group according to the proposal for 8 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA, and Western blotting. </P><P><B>Results</B></P><P> The ratio of ICP/MAP was significantly higher in the DM + ESWT + MSCT group than in ESWT or MSCT treated group (<I>P</I> < 0.05). Also, the treatment stimulated angiogenesis and vasodilatation in the corpus cavernosum (<I>P</I> < 0.05). ESWT increased the quantity of MSCs in the corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (<I>P</I> < 0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the corpus cavernosum. The combination approach stimulated autophagy and decreased apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the DM + ESWT + MSCT group than in the DM control group (<I>P</I> < 0.01). Furthermore, the treatment promoted the MSC recruitment by inducing penile tissues to express more PECAM and SDF-1. </P><P><B>Conclusions</B></P><P> Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future.</P>

Quisqualis indica extract for men with lower urinary tract symptoms: A randomized, double-blind, placebo-controlled trial

신동호,Guan Qun Zhu,Wen Jie Tian,안순태,전승환,조혁진,하유신,홍성후,이지열,김세웅,문두건,배웅진 대한비뇨의학회 2023 Investigative and Clinical Urology Vol.64 No.1

Purpose: To evaluate the efficacy and safety of Quisqualis indica in men with moderate lower urinary tract symptoms (LUTS). Materials and Methods: A total of 135 subjects with International Prostate Symptom Score (IPSS) of 8–19 were randomized in 2 centers from June 2018 to April 2019. Patients were assigned into one of the three groups: a low-dose group (LG, 1,000 mg Q. indica), a high-dose group (HG, 2,000 mg Q. indica) or a placebo group (PG). The primary endpoint was the change of IPSS at the end of treatment from baseline. Secondary end points included the changes of prostate specific antigen, testosterone, dihydrotestosterone, maximum urinary flow rate (Qmax), postvoid residual volume (PVR) and International Index of Erectile Function-5 (IIEF-5), with drug safety. Results: 113 patients were able to finish the study. Compared to the PG, total IPSS in the LG and the HG was significantly improved at 6 weeks and 12 weeks. For IPSS subscores, LG showed improvements in all except for urgency and quality of life at 6 weeks. HG showed improvements in incomplete emptying and frequency at 6 weeks and 12 weeks along with improvements in intermittency, straining, and quality of life at 12 weeks. For IIEF-5 subscores, orgasmic function and overall satisfaction improved in HG when compared to PG at 12 weeks. Lastly, increase of Qmax and decrease of PVR was observed at 6 weeks in LG. Conclusions: 12-week treatment with Q. indica has a therapeutic effect and is well tolerated in patients with LUTS.

Synergistic effects of extracorporeal shockwave therapy and modified Ojayeonjonghwan on erectile dysfunction in an animal model of diabetes

정현철,배웅진,Guan Qun Zhu,전승환,최세웅,김수진,조혁진,홍성후,이지열,황성연,김세웅 대한비뇨의학회 2019 Investigative and Clinical Urology Vol.60 No.4

Purpose: We investigated the synergy effect of extracorporeal shock wave therapy (ESWT) with modified Ojayeonjonghwan (Korean herbal formula, KH-204) in an animal model of diabetes mellitus (DM)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male Sprague-Dawley rats were used in this study. DM was induced by an intraperitoneal injection of streptozotocin. DM rats were divided into 5 groups (n=10 per group): group 1, control; group 2, DM; group 3, DM+ESWT; group 4, DM+KH-204; and group 5, DM+ESWT+KH-204. In ESWT groups, rats were treated with ESWT at the penis 3 times a week for 2 weeks under anesthesia. The KH-204 groups were treated with a daily oral dose of KH-204 for 12 weeks. After all treatments, intracavernosal pressure (ICP) was measured, and the cavernous tissues were evaluated by Masson's trichrome, immunohistochemistry and western blot analysis. Results: ICP was evaluated as a measurement of erectile function. The DM+ESWT, DM+KH-204, and DM+ESWT+KH-204 groups showed significantly restored erectile function compared with the DM group (p<0.05). Among these groups, the DM+ESWT+KH-204 group showed the highest ICP. Moreover, ESWT and KH-204 treatment restored smooth muscle contents and many parameters related to potency (vascular endothelial growth factor, neuronal nitric oxide synthase (NOS), endothelial [NOS] and platelet endothelial cell adhesion molecule-1) compared with the DM group (p<0.05). Conclusions: We confirmed the potential efficacy of ESWT and KH-204 in the treatment of ED patients using an animal model. The combination treatment of KH-204 and ESWT is expected to have good potential clinical results in the future treatment of refractory ED.

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

정현철,전승환,Zhu Guan Qun,김강섭,최세웅,Fahad Bashraheel,배웅진,김수진,조혁진,하유신,홍성후,이지열,문두건,김세웅 대한남성과학회 2017 The World Journal of Men's Health Vol.35 No.3

Purpose: Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED.Materials and Methods: Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated.Results: In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p<0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p<0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson’s trichrome staining (p<0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p<0.05).Conclusions: Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

Antioxidant and Antifibrotic Effect of a Herbal Formulation <i>In Vitro</i> and in the Experimental Andropause via Nrf2/HO-1 Signaling Pathway

Bae, Woong Jin,Zhu, Guan Qun,Choi, Sae Woong,Jeong, Hyun Cheol,Bashraheel, Fahad,Kim, Kang Sup,Kim, Su Jin,Cho, Hyuk Jin,Ha, U Syn,Hong, Sung Hoo,Lee, Ji Youl,Oh, Hyun-A,Koo, Hye Cheong,Kim, Do Ram,Hw Hindawi 2017 Oxidative medicine and cellular longevity Vol.2017 No.-

<P>The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH) symptoms such as erectile dysfunction (ED). A previous research suggested that a modified Ojayeonjonghwan (KH-204) could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1) preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1); (2) lowered the expression of transforming growth factor-beta (TGF-<I>β</I>) 1/SMAD; (3) increased the average of serum testosterone in androgen-deprived male rats; (4) kept the activation of spermatogenesis; (5) upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG) and degraded the contents of superoxide dismutase (SOD); and (6) reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.</P>

Effect of Korean Herbal Formula (Modified Ojayeonjonghwan) on Androgen Receptor Expression in an Aging Rat Model of Late Onset Hypogonadism

Sae Woong Choi,Seung Hwan Jeon,Eun Bi Kwon,Guan Qun Zhu,Kyu Won Lee,Jin Bong Choi,Hyun Cheol Jeong,Kang Sup Kim,Sang Rak Bae,Woong Jin Bae,Su Jin Kim,Hyuk Jin Cho,U-Syn Ha,Sung Hoo Hong,Sung Yeoun Hwa 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.1

Purpose: Testosterone replacement therapy is an effective treatment for late-onset hypogonadism (LOH) despite a few con-traindications and side-effects. The aim of this study was to determine whether modified Ojayeonjonghwan (KH-204, Korean herbal formula) improved LOH. KH-204 is a strong antioxidant herbal formula. We evaluated the effect of Korean herbal pre-scription on androgen receptor (AR) expression in an aged rat model of LOH. Materials and Methods: Eighteen-month-old rats were used as aged LOH rat models. Eighteen Sprague-Dawley rats were ran-domly divided into three equal groups of six animals each and treated with one of the following: 1) normal control group (oral administration with distilled water, n=6), 2) KH-204 200 group (oral administration with 200 mg/kg of KH-204, n=6), and 3) KH-204 400 group (oral administration with 400 mg/kg of KH-204, n=6). After four weeks of treatment (once daily, distilled water or KH-204), serum testosterone levels, changes in testicular and epididymal weight, Western blotting analysis of AR ex-pression and measurement of oxidative stress were examined. Results: Treatment with the herbal formulation KH-204 200 mg/kg and 400 mg/kg (1) increased the weights of testis and epi-didymis; (2) increased the level of serum testosterone; (3) increased the level of superoxide dismutase and reduced the level of 8-hydroxy-20-deoxyguanosine; and (4) upregulated AR expression in testicular tissue. Conclusions: KH-204 might be an effective alternative for LOH. It improves antioxidant mechanisms and increases testicular AR expression without side-effects.