Pharmacological activities of esculin and esculetin: A review.

Esculin and esculetin are 2 widely studied coumarin components of Cortex Fraxini, which is a well-known herbal medicine with a 2000-year history. In vivo and in vitro studies have demonstrated that both have a variety of pharmacological activities, including antioxidant, anti-tumor, anti-inflammatory, antibacterial, antidiabetic, immunomodulatory, anti-atherosclerotic, and so on. Their underlying mechanisms of action and biological activities include scavenging free radicals, modulating the nuclear factor erythroid 2-related factor 2 pathway, regulating the cell cycle, inhibiting tumor cell proliferation and migration, promoting mitochondrial pathway apoptosis, inhibiting the NF-κB and MAPK signaling pathways, regulating CD4+ T cells differentiation and associated cytokine release, inhibiting vascular smooth muscle cells, etc. This review aims to provide comprehensive information on pharmacological studies of esculin and esculetin, which is of noteworthy importance in exploring the therapeutic potential of both coumarin compounds.

Identification of potent target and its mechanism of action of Tripterygium wilfordii Hook F in the treatment of lupus nephritis.

AIM: The Chinese anti-rheumatic herbal remedy Tripterygium wilfordii Hook F (TWHF) has been widely shown to be effective in treating lupus nephritis (LN), but the therapeutic targets and mechanisms of action are still unclear. In this study, we aimed to combine mRNA expression profile analysis and network pharmacology analysis to screen the pathogenic genes and pathways involved in LN and to explore the potential targets of TWHF in the treatment of LN. METHODS: The mRNA expression profiles of LN patients were used to screen differentially expressed genes (DEGs) and to predict associated pathogenic pathways and networks via the Ingenuity Pathway Analysis database. Through molecular docking, we predicted the mechanism by which TWHF interacts with candidate targets. RESULTS: A total of 351 DEGs were screened from the glomeruli of LN patients and were mainly concentrated in the role of pattern recognition receptors in the recognition of bacteria and viruses and interferon signaling pathways. A total of 130 DEGs were screened from the tubulointerstitium of LN patients, which were concentrated in the interferon signaling pathway. TWHF might be effective in treating LN by hydrogen bonding to regulate the functions of 24 DEGs (including HMOX1, ALB, and CASP1), which are mainly concentrated in the B-cell signaling pathway. CONCLUSION: The mRNA expression profile of renal tissue from LN patients revealed a large number of DEGs. TWHF has been shown to interact with the DEGs (including HMOX1, ALB and CASP1) through hydrogen bonding to treat LN.

Research progress on extraction, purification, structure and biological activity of Dendrobium officinale polysaccharides.

Dendrobium officinale Kimura et Migo (D. officinale) is a traditional medicinal and food homologous plant that has been used for thousands of years in folk medicine and nutritious food. Recent studies have shown that polysaccharide is one of the main biologically active components in D. officinale. D. officinale polysaccharides possess several biological activities, such as anti-oxidant, heptatoprotective, immunomodulatory, gastrointestinal protection, hypoglycemic, and anti-tumor activities. In the past decade, polysaccharides have been isolated from D. officinale by physical and enzymatic methods and have been subjected to structural characterization and activity studies. Progress in extraction, purification, structural characterization, bioactivity, structure-activity relationship, and possible bioactivity mechanism of polysaccharides D. officinale were reviewed. In order to provide reference for the in-depth study of D. officinale polysaccharides and the application in functional food and biomedical research.

Effect of vitamin D supplementation on markers of cardiometabolic risk in children and adolescents: A meta-analysis of randomized clinical trials.

BACKGROUND AND AIMS: An increasing attention to the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents has been gained recently. However, the results are inconsistent. Therefore, we conducted a meta-analysis to examine the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents. METHODS AND RESULTS: Eligible randomized controlled trials (RCTs) were identified by searching PubMed, EMBASE and Web of Science. The results of this study are synthetized and reported in accordance with the PRISMA statement. GRADE system was used to assess the certainty of evidence. A total of 9 RCTs were identified and included in the meta-analysis. We found that vitamin D supplementation did not affect the changes of cardiometabolic risk markers including high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), body mass index (BMI), waist circumferences, systolic blood pressure (SDP) and diastolic blood pressure (DBP). However, vitamin D supplementation showed a beneficial effect on fasting glucose (MD, -1.54 mg/dl, 95% CI -2.98 to -0.10) and TG (MD, -24.76 mg/dl, 95% CI -37.66 to -11.86) in the sub-group analysis of total vitamin D supplementation ≥ 200,000 IU. CONCLUSIONS: Vitamin D supplementation appeared to have a beneficial effect on reducing fasting glucose and TG level when total vitamin D supplementation ≥200,000 IU but not HDL-C, LDL-C TC, blood pressure and waist circumferences levels in children and adolescents. Further studies are needed to address this issue.

Clinical therapeutic effects of acupuncture in treating patients with dysphagia after radiotherapy in nasopharyngeal carcinoma: A protocol for systematic review and meta-analysis.

BACKGROUND: Dysphagia is a commonly occurring condition in nasopharyngeal carcinoma (NPC) patients after radiotherapy. There has been an increasing number of studies focused on assessing the use of acupuncture to manage dysphagia. Moreover, the quality of the research has gradually increased. The present research will be conducted to systematically evaluate the efficiency and safety of using acupuncture to treat cases of dysphagia after radiation therapy in NPC patients. METHODS: Literature search will include all potential randomized controlled trials using MEDLINE, Cochrane Library, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, Chinese BioMedical Literature, and WanFang database from their inception to May, 2021 without language or publication status restrictions, to evaluate the efficiency and safety of using acupuncture to treat dysphagia cases following radiation therapy in NPC patients. A couple of independent authors will select related literature, extract data from studies, and estimate this risk in the bias of the selected study articles. In the instance of contrasting opinions, the outcome is mediated through discussion with a different independent author. The data synthesis and statistical analysis will be completed with the RevMan software (version 5.3). RESULTS: This study will evaluate the efficiency and safety of using acupuncture to treat dysphagia cases after radiation therapy in NPC patients. CONCLUSION: This study will determine the suitability of acupuncture as an effective and safe intervention for dysphagia in NPC patients after radiotherapy. ETHICS AND DISSEMINATION: The present study does not need ethical approval. REGISTRATION NUMBER: May 19, 2021.osf.io/f2cvt. (https://osf.io/f2cvt/).

Protective effects of citrulline supplementation in ulcerative colitis rats.

It has been reported that supplementing certain amino acids has therapeutic effects on ulcerative colitis (UC). We intend to explore whether citrulline (Cit) supplementation has protective effects on UC. Fifteen male Wistar rats were divided into normal control group (NC group), UC group and UC+Cit group, with five rats in each group. The UC model was established by TNBS/ethanol method. Rats in UC+Cit group were intragastrically administered with Cit for 7 consecutive days after modeling. All rats were sacrificed after 7 days. Blood samples were collected to detect the number of monocytes. Colon tissues were taken for HE staining. Immunohistochemistry staining for CD68 and p-STAT3 were performed to detect the infiltration of monocytes and the phosphorylation of STAT3 in colon tissues. The concentrations of MCP-1, IL-6 and IL-17A and the protein expression of p-STAT3 in colon tissues were measured by ELISA and western blot methods, respectively. The body weight of UC group rats decreased significantly after 7 days (p<0.05). However, the weight loss of UC+Cit group rats was not statistically significant (p>0.05). The number of peripheral blood monocytes in UC+Cit group was significantly lower than that in UC group (p<0.05), and the infiltration of CD68-positive monocytes in the colon tissue of UC+Cit group was significantly reduced than that in UC group. The concentrations of MCP-1, IL-6 and IL-17A and the expression of p-STAT3 in colon tissues of UC+Cit group rats were significantly lower than those in UC group (both p<0.05). Our study suggests that Cit supplementation may be a potential therapy for UC.

[Effect of hot water extract of Korean ginseng on neuroblastoma cell parthanatos].

OBJECTIVE: To explore the effect of pretreatment of neuroblastoma cells with hot water extract of Korean ginseng on MNNG-induced parthanatos and its mechanism. METHODS: Neuroblastoma SH-SY5Y cells were pretreated with 1 mg/L hot water extract of Korean ginseng before induction with 250 µmol/L MNNG for 1 h or 4 h. CCK-8 and cell flow cytometry were used to detect cell survival rate. Western blotting was used to detect the changes in poly(ADP-ribose) (PAR) expression in the treated cells. Immunofluorescence assay was used to detect nuclear distribution of apoptosis-inducing factor (AIF), and flow cytometry was used to detect the level of reactive oxygen species (ROS) in the cells. RESULTS: Compared with the blank control cells, MNNG-treated SH-SY5Y cells showed significantly decreased survival rate as the concentration of MNNG and the stimulation time increased (P < 0.05). Stimulation with MNNG also resulted in significantly increased expression of PAR protein in the cells (P < 0.05). Pretreatment of the cells with hot water extract of Korean ginseng obviously inhibited MNNG-induced cell death and significantly reduced AIF expression and nucleation in the cells (P < 0.05). MNNG stimulation significantly increased ROS level in the cells, which was decreased significantly by pretreatment of the cells with the extract (P < 0.05). CONCLUSIONS: Pretreatment with hot water extract of Korean ginseng reduces MNNG-induced parthanatos and ROS production in SH-SY5Y cells.

Yangjing Capsule Can Improve the Function of the Testicular Angiogenesis through Activating VEGFA/eNOS Signaling Pathway.

BACKGROUND: The testicular microcirculation was an important aspect of testicular physiology and it offered a stable environment for the transport of nutrients and secretary products in the testis. Yangjing capsule (YC), a traditional Chinese compound herbal prescription, has been proved as an effective drug to ameliorate spermatogenesis, promote testosterone synthesis in vivo, and cure spermatogenesis in clinical practice. OBJECTIVE: This study was aimed at understanding the potential mechanisms of YC exerting angiogenic effects in the mouse spermatogenesis dysfunction model induced by cyclophosphamide (CP) and MLTC-1 cells. MATERIALS AND METHODS: Balb/c mice were randomly divided into five groups: control, CP, CP plus YC (630 mg/kg), CP plus YC (1260 mg/kg), and CP plus YC (2520 mg/kg). After 30 days, mice were sacrificed and the expressions of endothelial marker CD34+, angiogenic marker VEGFA, VEGFR1, VEGFR2, and eNOS in the testes of the mice were examined; moreover, Leydig cell line MLTC-1 cells were cultured and treated with different concentrations of YC extracts (YCE), and the expressions of VEGFA, VEGFR1, VEGFR2, and eNOS, as well as the secretion of NO, were evaluated. RESULTS: We observed that YC significantly increased the expressions of VEGFA, VEGFR1, VEGFR2, and eNOS in testes of CP-treated mice; moreover, YCE has led to increased expressions of VEGFA, VEGFR1, VEGFR2, and eNOS and secretion of NO in MLTC-1 in vitro. These data suggested that the YC might be an alternative treatment for the dysfunction of testicular microcirculation by promoting the angiogenesis in the testis.

Identification of a Kavain Analog with Efficient Anti-inflammatory Effects.

Kavain, a compound derived from Piper methysticum, has demonstrated anti-inflammatory properties. To optimize its drug properties, identification and development of new kavain-derived compounds was undertaken. A focused library of analogs was synthesized and their effects on Porphyromonas gingivalis (P. gingivalis) elicited inflammation were evaluated in vitro and in vivo. The library contained cyclohexenones (5,5-dimethyl substituted cyclohexenones) substituted with a benzoate derivative at the 3-position of the cyclohexanone. The most promising analog identifed was a methylated derivative of kavain, Kava-205Me (5,5-dimethyl-3-oxocyclohex-1-en-1-yl 4-methylbenzoate.) In an in vitro assay of anti-inflammatory effects, murine macrophages (BMM) and THP-1 cells were infected with P. gingivalis (MOI = 20:1) and a panel of cytokines were measured. Both cell types treated with Kava-205Me (10 to 200 µg/ml) showed significantly and dose-dependently reduced TNF-α secretion induced by P. gingivalis. In BMM, Kava-205Me also reduced secretion of other cytokines involved in the early phase of inflammation, including IL-12, eotaxin, RANTES, IL-10 and interferon-γ (p < 0.05). In vivo, in an acute model of P. gingivalis-induced calvarial destruction, administration of Kava-205Me significantly improved the rate of healing associated with reduced soft tissue inflammation and osteoclast activation. In an infective arthritis murine model induced by injection of collagen-antibody (ArthriomAb) + P. gingivalis, administration of Kava-205Me was able to reduce efficiently paw swelling and joint destruction. These results highlight the strong anti-inflammatory properties of Kava-205Me and strengthen the interest of testing such compounds in the management of P. gingivalis elicited inflammation, especially in the management of periodontitis.

Electroacupuncture Delays Cartilage Degeneration by Modulating Nuclear Factor-κB Signaling Pathway.

OBJECTIVE: To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture (EA) on knee osteoarthritis (OA). METHODS: Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group (no surgery-induced OA; without treatment), model group (surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi (ST 35) and Neixiyan (EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin's score principles, the synovial fluid concentration of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1ß, IL-6, TNF-α, MMP-3, IκB kinase-ß (IKK-ß), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α (IκB-α) and nuclear factor-κB (NF-κB) p65 were quantified by Western blot analysis. RESULTS: EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1ß, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group (all P<0.01). Compared with the model group, the IL-1ß, IL-6, TNF-α, MMP-3, IKK-ß and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased (all P<0.01), whereas IκB-α expression was significantly up-regulated (P<0.01). CONCLUSION: EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.

Electroacupuncture Delays Cartilage Degeneration by Modulating Nuclear Factor-κB Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture (EA) on knee osteoarthritis (OA).@*METHODS@#Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group (no surgery-induced OA; without treatment), model group (surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi (ST 35) and Neixiyan (EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin's score principles, the synovial fluid concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1β, IL-6, TNF-α, MMP-3, IκB kinase-β (IKK-β), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α (IκB-α) and nuclear factor-κB (NF-κB) p65 were quantified by Western blot analysis.@*RESULTS@#EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1β, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group (all P<0.01). Compared with the model group, the IL-1β, IL-6, TNF-α, MMP-3, IKK-β and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased (all P<0.01), whereas IκB-α expression was significantly up-regulated (P<0.01).@*CONCLUSION@#EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.

Mechanisms of Yangjing Capsule in Leydig Cell Apoptosis and Testosterone Synthesis via Promoting StAR Expression.

The present study aims to investigate the roles of steroidogenic acute regulatory protein (StAR) in Yangjing Capsule (YC) induced anti-apoptotic effects on Leydig cells and the related mechanism. Leydig tumor cells (MLTC-1) were cultured and treated with YC, and immunofluorescence assay was performed to examine the expression of StAR; furthermore, luciferase reporter assay was conducted to evaluate the impact of YC on StAR promoter; next, MLTC-1 cells were treated with StAR small interfering RNA (siRNA), and flow cytometry was carried out to examine the effect of StAR siRNA on the apoptosis of the cells; furthermore, quantitative (q)RT-PCR and Western blot methods was used to determine the expression of StAR and apoptosis related molecules Bcl-2, Bax and Caspase-3 on both mRNA and protein levels in different groups; finally the secretion of testosterone in different groups was examined by radioimmunoassay. We observed that the YC can increase the expression of StAR in a dose-dependent manner, and YC can activate the promoter of StAR; moreover, transfection of StAR siRNA can block YC induced anti-apoptotic effects and increased production of testosterone. In conclusion, our results suggested that YC might suppress the apoptosis of MLTC-1 cells and enhance the production of testosterone through regulating the expression of StAR.

Reduction of Articular and Systemic Inflammation by Kava-241 in a Porphyromonas gingivalis-Induced Arthritis Murine Model.

Rheumatoid arthritis (RA) is an inflammatory disease that has been linked to several risk factors, including periodontitis. Identification of new anti-inflammatory compounds to treat arthritis is needed. We had previously demonstrated the beneficial effect of Kava-241, a kavain-derived compound, in the management of Porphyromonas gingivalis-induced periodontitis. The present study evaluated systemic and articular effects of Kava-241 in an infective arthritis murine model triggered by P. gingivalis bacterial inoculation and primed with a collagen antibody cocktail (CIA) to induce joint inflammation and tissular destruction. Clinical inflammation score and radiological analyses of the paws were performed continuously, while histological assessment was obtained at sacrifice. Mice exposed to P. gingivalis and a CIA cocktail and treated concomitantly with Kava-241 exhibited a reduced clinical inflammatory score and a decreased number of inflammatory cells and osteoclasts within joint. Kava-241 treatment also decreased significantly tumor necrosis factor alpha (TNF-α) in serum from mice injected with a Toll-like receptor 2 or 4 (TLR-2/4) ligand, P. gingivalis-lipopolysaccharide (LPS). Finally, bone marrow-derived macrophages infected with P. gingivalis and exposed to Kava-241 displayed reduced TLR-2/4, reduced mitogen-activated protein kinase (MAPK)-related signal elements, and reduced LPS-induced TNF-α factor (LITAF), all explaining the observed reduction of TNF-α secretion. Taken together, these results emphasized the novel properties of Kava-241 in the management of inflammatory conditions, especially TNF-α-related diseases such as infective RA.

Kava analogues as agents for treatment of periodontal diseases: Synthesis and initial biological evaluation.

Six kava analogues of the structural type 3-oxocyclohex-1-en-1-yl benzoates (and corresponding benzamides) were synthesized and evaluated for their affect on periodontal deconstruction in collagen anti-body primed oral gavage model of periodontitis. The compounds were prepared through an acylation or amidation of the enolizable cyclic 1,3-diketone. We have learned that three of the analogues are responsible for the reduction of inflammatory cell counts within soft tissue. These novel kava-like molecules where the lactone is replaced by an α,ß-unsaturated ketone show promise in the prevention and treatment of inflammation and alveolar bone loss associated with periodontitis.

Kava-241 reduced periodontal destruction in a collagen antibody primed Porphyromonas gingivalis model of periodontitis.

AIM: The aim of this study was to evaluate the effect of Kava-241, an optimized Piper methysticum Kava compound, on periodontal destruction in a collagen antibody primed oral gavage model of periodontitis. METHODS: Experimental periodontitis was induced by oral gavage of Porphyromonas gingivalis (P. gingivalis) + type II collagen antibody (AB) in mice during 15 days. Mice were treated with Kava-241 concomitantly or prior to P. gingivalis gavage and compared to untreated mice. Comprehensive histomorphometric analyses were performed. RESULTS: Oral gavage with P. gingivalis induced mild epithelial down-growth and alveolar bone loss, while oral gavage with additional AB priming had greater tissular destruction in comparison with gavage alone (p < .05). Kava-241 treatment significantly (p < .05) reduced epithelial down-growth (72%) and alveolar bone loss (36%) in P. gingivalis+AB group. This Kava-241 effect was associated to a reduction in inflammatory cell counts within soft tissues and an increase in fibroblasts (p < .05). CONCLUSION: Priming with type II collagen antibody with oral gavage is a fast and reproducible model of periodontal destruction adequate for the evaluation of novel therapeutics. The effect of Kava-241 shows promise in the prevention and treatment of inflammation and alveolar bone loss associated with periodontitis. Further experiments are required to determine molecular pathways targeted by this therapeutic agent.

Yangjing Capsule extract promotes proliferation of GC-1 spg cells via up-regulated POU3F1 pathway.

As is similar to glial cell line-derived neurotrophic factor (GDNF), the Yangjing Capsule (YC) extract could also lead to proliferation of spermatogonial stem cells (SSCs) by stimulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway; however, the regulatory effect of YC extract on the expression of POU3F1 still remains unknown. The objective of this study is to determine whether the transcription factor POU3F1 is up-regulated by YC extract through the PI3K/AKT signaling pathway to regulate SSCs survival and proliferation. Cultured GC-1 spermatogonial (spg) cells were treated with 0.01, 0.1, and 1 mg/mL YC extract for 48 h. Cell viability was analyzed using MTT assay, while POU3F1 expression was quantitatively detected using real time-polymerase chain reaction and Western blot analysis. POU3F1, GDNF family receptor alpha1 (GFRα1) short interfering ribonucleic acid (siRNA), and LY294002 (PI3K inhibitor) were applied as blockers to explore the underlying pathway. After 48 h treatment with YC extract, GC-1 spg cells proliferated and POU3F1 expression was significantly increased in a dose-dependent manner. POU3F1 siRNA partially blocked those effects of YC extract. Both GFRα1 siRNA and LY294002, as upstream blockers, reduced POU3F1 expression induced by YC extract. The conclusion is that YC extract promotes proliferation of GC-1 spg cells via up-regulation of POU3F1. The potential mechanism is that YC extract triggers the activation of the PI3K/AKT pathway and then up-regulates POU3F1 expression.

[Bushen Daozhuo Granules for type â ¢ prostatitis: A multicenter randomized controlled clinical trial].

OBJECTIVE: To study the safety and efficacy of Bushen Daozhuo Granules (BDG) in the treatment of type Ⅲ prostatitis. METHODS: This multicenter randomized controlled clinical trial included 478 patients with type Ⅲ prostatitis, 290 in the trial group and 188 as controls, the former treated with BDG at 200 ml bid and the latter with tamsulosin hydrochloride sustainedrelease capsules at 0.2 mg qd, both for 4 weeks. Before treatment, after 4 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the NIH Chronic Prostatitis Symptom Index (NIHCPSI) scores and compared the safety and effectiveness rate between the two groups of patients. RESULTS: Compared with the baseline, the NIHCPSI score was markedly decreased in the control group after 4 weeks of medication (21.42 ± 4.02 vs 15.67 ± 3.65, P < 0.05) but showed no statistically significant difference from that at 4 weeks after drug withdrawal (19.03 ± 3.86) (P>0.05), while the NIHCPSI score in the trial group was remarkably lower than the baseline both after 4 weeks of medication and at 4 weeks after drug withdrawal (10.92 ± 2.06 and 12.91 ± 2.64 vs 21.58 ± 3.67, P < 0.05). The trial group exhibited both a higher rate of total effectiveness and safety than the control (P < 0.05). CONCLUSIONS: BDG is safe and effective for the treatment of type Ⅲ prostatitis.

Mechanism of uncoupling protein 2­mediated myocardial injury in hypothermic preserved rat hearts.

In the present study, the alterations in uncoupling protein 2 (UCP2) expression following hypothermic preservation in rat hearts were investigated. Isolated rat hearts were preserved in Celsior solution for 3­12 h followed by 60 min of reperfusion. The cardiac function was evaluated using the Langendorff perfusion system. UCP2 and silent mating type information regulation 2 homolog 1 (SIRT1) proteins were detected by western blot analysis. The ATP production and mitochondrial reactive oxygen species (ROS) levels were assessed. Subsequent to preservation in ice­cold Celsior solution for 3­12 h, the UCP2 protein expression in rat hearts was observed to increase in a time­dependent manner. The UCP2 inhibitor genipin inhibited the hypothermic preservation­induced cardiac dysfunction, prevented a decline in ATP production induced by 9 h of preservation, however had no effect on the hypothermic preservation­induced increase in mitochondrial ROS levels. Compared with the control group, the SIRT1 protein expression in rat hearts reduced following hypothermic preservation. Compared with the 9­h preservation group, Celsior solution supplemented with the SIRT1 activator resveratrol (20 or 40 µmol/l) inhibited UCP2 protein overexpression, prevented the decline in ATP production and resulted in an improvement cardiac function. The SIRT1 inhibitor EX­527 abolished the resveratrol­induced inhibition of UCP2 overexpression and cardiac protection in the hypothermic preserved rat heart. These observations suggest that downregulation of UCP2 expression in the hypothermic preserved rat heart in part initiated the protective mechanism via the SIRT1 pathway.

Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

Citrulline (Cit) supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg) concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP) model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1ß were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

The Stimulative Effect of Yangjing Capsule on Testosterone Synthesis through Nur77 Pathway in Leydig Cells.

Yangjing Capsule (YC), an innovative Chinese medicine based on traditional prescription, promotes testosterone synthesis by upregulating the expression of steroidogenic enzymes. Nur77 as a nuclear receptor is known to regulate the expression of many steroid synthetases. This study aimed to explore the potential mechanisms by which YC regulates testosterone synthesis in Leydig cells. Real-time PCR and Western blot analysis were employed to assess the expressions of steroidogenic enzymes and Nur77 after treating MLTC-1 cells with YC. The luciferase reporter gene assay was performed to detect the activity of Nur77 gene promoter. Also, the expressions of steroid synthases were detected after Nur77 gene was knocked down. YC significantly stimulated Nur77 production and upregulated StAR and HSD3B expression, and this agrees with the activity of Nur77 gene promoter that was significantly enhanced by YC. Interestingly, knockdown of Nur77 blocked the above YC's effects and consequently inhibited testosterone synthesis in MLTC-1 cells. YC promotes StAR and HSD3B expression and upregulates testosterone synthesis in Leydig cells, which is mediated by Nur77 pathway.