Alteration of Gut Microbes in Benign Prostatic Hyperplasia Model and Finasteride Treatment Model.

Gut microbes are closely associated with disease onset and improvement. However, the effects of gut microbes on the occurrence, prevention, and treatment of benign prostatic hyperplasia (BPH) are still unclear. We investigated the alteration of gut microbiota with implications for the diagnosis, prevention, and treatment of BPH and identified correlations among various indicators, including hormone indicators, apoptosis markers in BPH, and finasteride treatment models. BPH induction altered the abundance of Lactobacillus, Flavonifractor, Acetatifactor, Oscillibacter, Pseudoflavonifractor, Intestinimonas, and Butyricimonas genera, which are related to BPH indicators. Among these, the altered abundance of Lactobacillus and Acetatifactor was associated with the promotion and inhibition of prostate apoptosis, respectively. Finasteride treatment altered the abundance of Barnesiella, Acetatifactor, Butyricimonas, Desulfovibrio, Anaerobacterium, and Robinsoniella genera, which are related to BPH indicators. Among these, altered abundances of Desulfovibrio and Acetatifactor were associated with the promotion and inhibition of prostate apoptosis, respectively. In addition, the abundances of Lactobacillus and Acetatifactor were normalized after finasteride treatment. In conclusion, the association between apoptosis and altered abundances of Lactobacillus and Acetatifactor, among other gut microbes, suggests their potential utility in the diagnosis, prevention, and treatment of BPH.

Comparative application of testosterone undecanoate and/or testosterone propionate in induction of benign prostatic hyperplasia in Wistar rats.

Testosterone undecanoate is a hormone agent with long-acting potential and is used for testosterone replacement therapy for hypogonadism. This study was designed to investigate application of testosterone undecanoate in maintaining high androgen levels for inducing benign prostatic hyperplasia more conveniently than that for testosterone propionate. We conducted two-part studies to determine the optimal dosage and dosing cycle for efficient and stable induction of benign prostatic hyperplasia using testosterone undecanoate. In the injection dosage substudy, single testosterone undecanoate dose (125, 250, 500, 750, or 1000 mg/kg body weight) was administered, and the optimal concentration was determined for 8weeks by measuring changes in testosterone, dihydrotestosterone, and 5-alpha reductase levels. And then, testosterone undecanoate was administered at the optimal dose at intervals of 1, 2, 3, or 4 weeks for 12weeks to induce benign prostatic hyperplasia. The injection dosage substudy showed dose-dependently higher and more stable levels of testosterone in groups administrated testosterone undecanoate than in groups administered testosterone propionate. In the injection cycle substudy, testosterone undecanoate-administered group stably maintained high levels of testosterone, dihydrotestosterone, and 5-alpha reductase compared with testosterone propionate-administered group for the same injection cycle; moreover, the prostate measurements, an important sign of benign prostatic hyperplasia, were significantly increased. Based on these two substudies, we determined the optimal conditions for inducing benign prostatic hyperplasia stably and more conveniently than that for testosterone propionate. This study suggests an extended application of testosterone undecanoate for inducing benign prostatic hyperplasia that can improve research reliability considering the half-life of testosterone as well as injection dosage and concentration.

Effects of Saussurea costus on apoptosis imbalance and inflammation in benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea costus (synonym: Aucklandia lappa Decne) is a medicinal plant distributed in Yunnan, Guangxi, and Sichuan in China. In traditional Korean medicine, the plant parts (especially the root-"radix aucklandiae") is widely used to treat vomiting, diarrhea, and inflammation. However, little has been reported on its effect on benign prostatic hyperplasia (BPH), which is common in middle-aged men. AIM OF THE STUDY: BPH is caused by apoptosis imbalance and inflammation due to aging of the prostate. Therefore, the aim of this was to prove the efficacy of S. costus by analyzing its effect on the biological mechanisms leading to BPH progression. MATERIALS AND METHODS: Wistar rats were injected subcutaneously with a single dose of testosterone (125 mg/kg) to induce BPH, and were later administered with S. costus (20, 40 mg/kg). After 12 weeks, histological changes in the prostate and hormone regulation factors were assessed in all animals. Furthermore, apoptotic protein and apoptotic body values were analyzed to confirm the improvement of apoptosis imbalance, and inflammatory cytokines were analyzed to confirm the anti-inflammatory efficacy of S. costus. RESULTS: In the serum and tissue of S. costus-treated BPH rats, a significant reduction in prostate weight, prostate index, and hormone regulation factors was observed. S. costus also increased the levels of apoptosis marker proteins and reduced the levels of inflammatory cytokines. It also decreased the expression of B-cell lymphoma 2 (BCL-2) and increased the expression of BCL-2 associated X protein (BAX) in the prostate. Histological changes such as epithelial thickness significantly increased in BPH induced group but significantly decreased in the S. costus-treated groups (p < 0.001). CONCLUSIONS: S. costus may prevent and treat BPH occurrence by modulating inflammation and apoptosis imbalance.

Amelioration of Benign Prostatic Hyperplasia by Costunolide and Dehydrocostus Lactone in Wistar Rats.

PURPOSE: Sesquiterpene lactones, which are found in plants of the Asteraceae family, contain costunolide (CO) and dehydrocostus lactone (DCL) as indicator material. CO, in particular, has been reported to possess varied pharmacological activity, including anti-inflammatory, antibacterial, and antioxidant effects. This study was designed to characterize the effects of CO and DCL on benign prostate hyperplasia (BPH). MATERIALS AND METHODS: Rats were injected subcutaneously daily for 8 weeks with 5 mg/kg testosterone to induce prostatic hyperplasia. Wistar rats were randomly divided into 5 groups of 10 animals each and received the following treatment: I. Normal control group; II. BPH-induced group; III. CO group (0.075 mg/kg); IV. DCL group (0.075 mg/kg); and V. Finasteride group (0.8 mg/kg). After treatment, changes in prostate weight and serum biochemical indices, serum dihydrotestosterone level, and mRNA levels of BCL2 were measured and histological examinations performed. RESULTS: Absolute and relative prostate weight in the indicator material treated groups, as well as prostate volume, decreased compared to those in the disease-induced group. Epithelial cell thickness increased significantly in the disease-induced group, with a significant decrease being observed in the CO group. The level of the anti-apoptotic protein BCL2 (B-cell lymphoma 2) tended to decrease to a greater extent in the DCL group than in the disease-induced group. CONCLUSIONS: In this study, we confirmed that the indicator materials (CO and DCL) can help suppress the development of BPH.

Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice.

The gut microbiota is a contributing factor in obesity-related metabolic disorders. The effect of metformin on the gut microbiota has been reported; however, the relationship between the gut microbiota and the mechanism of action of metformin in elderly individuals is unclear. In this study, the effect of metformin on the gut microbiota was investigated in aged obese mice. The abundance of the genera Akkermansia, Bacteroides, Butyricimonas, and Parabacteroides was significantly increased by metformin in mice fed a high-fat diet. Metformin treatment decreased the expression of IL-1ß and IL-6 in epididymal fat, which was correlated with the abundance of various bacterial genera. In addition, both fecal microbiota transplantation from metformin-treated mice and extracellular vesicles of Akkermansia muciniphila improved the body weight and lipid profiles of the mice. Our findings suggest that modulation of the gut microbiota by metformin results in metabolic improvements in aged mice, and that these effects are associated with inflammatory immune responses.

Restoration of Declined Immune Responses and Hyperlipidemia by Rubus occidenalis in Diet-Induced Obese Mice.

Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.

Aloe QDM complex enhances specific cytotoxic T lymphocyte killing in vivo in metabolic disease mice.

We developed spontaneous diet-induced metabolic disease in mice by feeding them a high-fat diet for 23 weeks and administered Aloe QDM complex for 16 weeks to examine its restorative effect on immune disorders and metabolic syndrome. A series of immune functional assays indicated Aloe QDM complex enhanced lymphocyte proliferation and antigen-specific immunity as determined by the restored functions of cytotoxic T lymphocytes (CTL) and IgG production. The elevated serum TNF-α level was also regulated by Aloe QDM complex treatment, which suggested its complex therapeutic potential. As for metabolic phenotypes, oral administration of Aloe QDM complex significantly improved diabetic symptoms, including high fasting glucose levels and glucose tolerance, and distinctly alleviated lipid accumulation in adipose and hepatic tissue. The simultaneous restoration of Aloe QDM complex on metabolic syndrome and host immune dysfunction, especially on the specific CTL killing was first elucidated in our study.

Atorvastatin and rosuvastatin improve physiological parameters and alleviate immune dysfunction in metabolic disorders.

This study was designed to characterize the potential therapeutic effects of two statin drugs commonly used to treat dyslipidemia in inflammation-linked metabolic disorders related to type 2 diabetes. Atorvastatin (10 mg/kg/day) and rosuvastatin (3 mg/kg/day) were administered to mice with diet-induced obesity (DIO). The statins lowered serum total and LDL cholesterol levels, and improved the atherogenic index and cardiac risk index. Furthermore, the drugs decreased fasting glucose levels, improved glucose tolerance, and decreased fat tissue weight and adipocyte size; this was accompanied by an overall body weight loss tendency. The statins also improved antigen-specific immunity. The killing activity of cytotoxic T cells and exacerbation of IgG secretion levels were considerably normalized. Most importantly, serum tumor necrosis factor-α and interleukin 6 levels decreased, while their RNA expression levels in fat tissue were regulated by the statins as well. This study is the first to indicate that low doses of atorvastatin and rosuvastatin, the dosing regimen for which has been controversial, could significantly improve diabetes-related metabolic disorders, and could modulate pro-inflammatory cytokines, alleviating inflammation and simultaneously restoring overall humoral and cell-mediated immunity.

Site-specific deposition of Au nanoparticles in CNT films by chemical bonding.

There has been no attempt to date to specifically modify the nodes in carbon nanotube (CNT) networks. If the nodes can be modified in favorable ways, the electrical and/or thermal and/or mechanical properties of the CNT networks could be improved. In an attempt to influence the performance as a transparent conductive film, gold nanoparticles capped with the amino acid cysteine (Au-CysNP) have been selectively attached at the nodes of multiwalled carbon nanotubes (MWCNTs) networks. These nanoparticles have an average diameter of 5 nm as observed by TEM. FTIR and XPS were used to characterize each step of the MWCNT chemical functionalization process. The chemical process was designed to favor selective attachment at the nodes and not the segments in the CNT networks. The chemical processing was designed to direct formation of nodes where the gold nanoparticles are. The nanoparticles which were loosely held in the CNT network could be easily washed away by solvents, while those bound chemically remained. TEM results show that the Cys-AuNPs are preferentially located at the nodes of the CNT networks when compared to the segments. These nanoparticles at the nodes were also characterized by a novel technique called diffraction scanning transmission electron microscopy (D-STEM) confirming their identity. Four-probe measurements found that the sheet resistance of the modified CNT networks was half that of similarly transparent pristine multiwalled CNT networks.