Capsaicin exerts anti-benign prostatic hyperplasia effects via inhibiting androgen receptor signaling pathway

Background:Benign prostatic hyperplasia(BPH)is a common condition in middle-aged and elderly men.Enlargement of the prostate causes lower urinary tract symptoms.Capsaicin is a phytochemical extracted from chili peppers and exerts many pharmacological actions,such as anti-tumor and anti-inflammatory effects.Methods:Our study investigated the effect of capsaicin in vitro and in a mouse model in vivo.A prostatic stromal myofibroblast cell line(WPMY-1)was co-incubated with testosterone(1µM)and different concentrations of capsaicin(10–100µM)for 24 and 48 h.Capsaicin(10–100µM)significantly inhibited testosterone-treated WPMY-1 cell growth at 48 h by MTT assay.The testosterone propionate(7.5 mg/kg)-induced BPH mouse model was used to examine the anti-proliferative effect of capsaicin.Treatment with capsaicin(10 mg/kg)for 14 days significantly attenuated prostatic hyperplasia.Finasteride was used as a positive control.Results:Capsaicin significantly decreased prostate weight and prostate index(prostate/body weight ratio)in BPH mice.The expression of 5α-reductase type II,androgen receptor(AR)and prostate specific antigen(PSA)protein expression and PSA serum were all significantly reduced in capsaicin-treated BPH mice.In addition,capsaicin also activated transient receptor potential vanilloid 1 mediated apoptosis and autophagy in BPH mice.Conclusion:These results demonstrate multiple positive effects of capsaicin in controlling prostate growth and suggest its therapeutic potential in the treatment of BPH.

Capsaicin穴位注射对穴位刺激引起的神经源性炎症反应的影响

为确定经长轴突反射和背根反射引起的皮肤循足太阳膀胱经及相关内脏的神经源性炎症反应可能是由细传入纤维内 P物质等神经递质的释放引起的 ,用 Capsaicin作为工具药 ,进行穴位注射后 ,观察两种反射条件下穴位刺激引起的神经源性炎症反应分布。结果发现 ,穴位注射 Capsaicin后 ,在长轴突反射和背根反射条件下电刺激承山穴均不能引起相应部位肉眼可见的神经源性炎症反应 ,定量分析也未发现 Evans蓝的明显渗出。结果提示 ,细纤维的长轴突反射和背根反射参与了经络活动。在经脉信息传递和经脉 -脏腑相关联系中 ,P物质等神经递质可能发挥作用。

辣椒的癌症“情结”

最近,国外杂志J Clin Invest刊载了一篇报道,说研究者发现辣椒很可能有助干预防大肠癌。此言论对于“嗜辣族”来说,无疑是个天大的好消息。辣椒是我们生活中常见的食物和调味品,但辣椒如何能够具有那么神奇的功效呢？研究人员发现,辣椒中含有的辣椒素是起着重要作用的 其实在医学中,辣椒素已有使用,

辣椒素在疾病治疗中的研究近况

辣椒素（Capsaicin ）是辣椒属（Capsicum ）植物辣椒／胡椒（chilli pepper ）中的一种活性成分，起源于美洲。在墨西哥和南美洲辣椒是烹饪中的一种调味品，后来被欧洲人引入亚洲和非洲，现已成为中国、印度、埃塞俄比亚、韩国等地区居民烹饪的一种重要食料［1］。随着对辣椒素的不断研究，辣椒素除了用作食料外，还广泛用于临床和实验室研究，并用于治疗或预防各个系统疾病。

Update on a tumor-associated NADH oxidase in gastric cancer cell growth

Gastric cancer is one of the most common human malignancies, and its prevalence has been shown to be well-correlated with cancer-related deaths worldwide. Regrettably, the poor prognosis of this disease is mainly due to its late diagnosis at advanced stages after the cancer has already metastasized. Recent research has emphasized the identification of cancer biomarkers in the hope of diagnosing cancer early and designing targeted therapies to reverse cancer progression. One member of a family of growth-related nicotinamide adenine dinucleotide(NADH or hydroquinone) oxidases is tumor-associated NADH oxidase(t NOX; ENOX2). Unlike its counterpart CNOX(ENOX1), identified in normal rat liver plasma membranes and shown to be stimulated by growth factors and hormones, t NOX activity purified from rat hepatoma cells is constitutively active. Its activity is detectable in the sera of cancer patients but not in those of healthy volunteers, suggesting its clinical relevance. Interestingly, t NOX expression was shown to be present in an array of cancer cell lines. More importantly, inhibition of t NOX was well correlated with reduced cancer cell growth and induction of apoptosis. RNA interference targeting t NOX expression in cancer cells effectively restored non-cancerous phenotypes, further supporting the vital role of t NOX in cancer cells. Here, we review the regulatory role of t NOX in gastric cancer cell growth.

Influence of capsaicin infusion on secondary peristalsis in patients with gastroesophageal reflux disease

AIM To determine whether capsaicin infusion could influence heartburn perception and secondary peristalsis in patients with gastroesophageal reflux disease(GERD). METHODS Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air in 10 patients with GERD. In a first protocol, saline and capsaicincontaining red pepper sauce infusions were randomly performed, whereas 2 consecutive sessions of capsaicin-containing red pepper sauce infusions were performed in a second protocol. Tested solutions including 5 m L of red pepper sauce diluted with 15 m L of saline and 20 m L of 0.9% saline were infused into the mid-esophagus via the manometric catheter at a rate of 10 mL /min with a randomized and doubleblind fashion. During each study protocol, perception of heartburn, threshold volumes and peristaltic parameters for secondary peristalsis were analyzed and compared between different stimuli.RESULTS Infusion of capsaicin significantly increased heartburn perception in patients with GERD(P < 0.001), whereas repeated capsaicin infusion significantly reduced heartburn perception(P = 0.003). Acute capsaicin infusion decreased threshold volume of secondary peristalsis(P = 0.001) and increased its frequency(P = 0.01) during rapid air injection. The prevalence of GERD patients with successive secondary peristalsis during slow air injection significantly increased after capsaicin infusion(P = 0.001). Repeated capsaicin infusion increased threshold volume of secondary peristalsis(P = 0.002) and reduced the frequency of secondary peristalsis(P = 0.02) during rapid air injection. CONCLUSION Acute esophageal exposure to capsaicin enhances heartburn sensation and promotes secondary peristalsis in gastroesophageal reflux disease, but repetitive capsaicin infusion reverses these effects.

Synthesis and Bacteriostatic Activity and Antifouling Capability of Benzamide Derivatives Containing Capsaicin

Five benzamide deriatives containing capsaicin were synthesized which have similar structures to capsaicin. Their yield was high. The monomers synthesized were characterized by IR, 1H NMR and MS spectroscopy. Cha-racterization data are in agreement with the proposed structures of the products. These five compounds exhibit bacterial inhibition and N-[4-hydroxy-2-methyl-5-（methylthio）benzyl]benzamide（HMMBBA）, for instance, shows that the minimal inhibitory concentrations（MIC） of HMMBBA are 0.125 and 0.25 mg/mL on Staphyloccocus aureus and Escherichia coli, respectively. A static test site was set up in the eighth harbor to investigate the antifouling effectiveness of the five new antifoulants. Five-month exposure experiments were performed on sets of panels coated with each of antifouling coatings, and the results were compared to that of the test panel without antifouling coating. Test boards with antifouling coating were covered with just a macroscopic fouling organism such as Balanus. The results of the present paper demonstrate that new antifoulants represent an alternative to the biocidal antifouling paint.

Experimental Study of the Effect of Capsaicin on the Urinary Bladder Function in Rats

In order to investigate the effect of capsaicin (CAP) on the urinary bladder function, an in vivo whole bladder study was undertaken in 25 adult healthy Wistar rats. CAP of various concentrations was instilled into the urinary bladder, and intravesical pressure, detrusor contraction and micturition status were recorded; then the trigone of the bladder was cut off and prepared for peroxidase -antiperoxidase (PAP) immunohistochemical investigation. The changes on the distribution of Sub- stance P (SP) in control and experimental groups were compared. The results showed that the intravesical application of CAP caused a significant change in the urinary bladder function. At a low concentration of CAP there was a slight increase of maximal detrusor pressure, but at a high concentration of CAP the maximal intravesical pressure was significantly decreased and associated with urinary retention and urinary incontinence. PAP sustaining had shown a depletion of SP in CAP-treated urinary bladder in rats, and this depletion was more significant at high concentrations of CAP. Because this depletion could block C-fiber transmission, detrusor function entered, from primary excitation phase, a late inhibitory phase. This suggests that a local application of CAP into urinary bladder could be used in the treatment of neurogenic bladder (detrusor hyperreflexia) to relieve frequency, urgency, incontinence and improve renal function.

Preparation and characterization of a novel antibacterial acrylate polymer composite modified with capsaicin

A novel antibacterial acrylate polymer composite modified with capsaicin was successfully synthesized by a two-step reaction.Capsaicin and acryloyl chloride were firstly esterified,and then applied to solution polymerization with acrylate monomers and styrene.The yield of the esterified products was about 85.3%.The polymer was characterized by Fourier transform infrared spectroscopy(FTIR),gel permeation chromatography(GPC),thermogravimetric analysis(TGA),contact angle(CA)and antibacterial ring tests.The number-average molecular weight(M_n)of the polymer was 27214,based on the capsaicin-acrylate dosage of 6.5 wt%.The TGA revealed a stable thermal property.The contact angles of the polymers films on tinplate increased from 77.5°to 86.2°with the increasing amount of capsaicin-acrylate.The antibacterial tests demonstrated excellent antimicrobial capability of the polymers.

Determination of Capsaicin and Dihydrocapsaicin in Capsicum( Capsicum annuum) Products by High Performance Liquid Chromatography-Fluorescence Detection( HPLCFLD)

[Objectives] This study was conducted to determine capsaicin and dihydrocapsaicin in capsicum products. [Methods]The sample was ultrasonically extracted with anhydrous ethanol as the extraction solvent for capsaicin and dihydrocapsaicin,followed by centrifugation. The extract was subjected to HPLC separation with methanol-water( 65∶ 35) as the mobile phase,and a fluorescence detector( Ex = 229 nm,Em = 320 nm) was used to detect capsaicinoids in the sample. [Results] Capsaicin and dihydrocapsaicin had a good linear relationship in the range of 1-200 mg/L( R_1~2= 0. 999 8,R22= 0. 999 6). The detection limits were both 0. 007 mg/kg; the quantification limits were both 0. 02 mg/kg; the precision was 0. 235% and 0. 754%,respectively; and the average recoveries were95. 94% and 95. 39%,respectively. [Conclusions]The method is simple,rapid,with good sensitivity and precision,and is suitable for detecting capsaicin substances in capsicum products.

EFFECT OF CAPSAICIN ON SUBSTANCE P IN PSORIASIS VULGARIS

Objective To the investigate the mechanism of capsaicin in psoriasis vulgaris. Methods Substance P(SP) in psoriatic lesions before and 6 weeks after the treatment with capsaicin was detedted by radioimmunoassary. Results After 3 weeks and 6 weeks treatment with capsaicin, SP in psoriatic lesions was decreased ( P <0.05), while it in the self control group was not decreased; Overall the efficient incidence in therapeutic group was 78.8% , while it in the control group was 36.8% . There was significant difference between them (χ 2 =16.30, P<0.001). Conclusion Capsaicin inhibits dermal inflammatory responses and proliferation of keratinocytes by decreasing the expression of SP in psoriasis vulgaris.

Preparation of Nonivamide and Its Insecticidal Activities

[Objective] The paper was to explore the insecticidal activities of capsaiein and nonivamlde. [Method] With nonanoic acid and vanillin as starting materials, nonivamide was prepared by reductive amination and N-acylation reaction, and the chemical structure of target compound was confirmed by 1H NMR and EI-MS. The biological activities of nonivamide and capsaicin were tested. [ Result] Both capsaicin and synthetic nonivamide had no obvious insecticidal activities against third instar larvae of diamondback moth [ Plutella xyllostella （Linnaeus） ] and 3-day-old nymphs of broad bean aphids （Aphis craccivora）. [ Conclusion] The research provided theoretical basis for further study on insecticidal activities of capsaicin.

Light Intensity Affects Pungency of Hot Pepper(Capsicum annuum L.) Fruits

This study was carried out both laboratory and field experiment to research the effects of three different light intensity on capsaicin content of hot pepper fruits during the growing stage, the varieties in the study were in different hot levels named No.4 Xiangyan(mid-hot) and No.3 Jingjianjiao(very hot). The study showed that capsaicin content increased accompanied with light intensity weakening. There was an inverse relationship between capsaicin content and peroxidase activity.

PLASMA EXTRAVASATION IN THE VISCERAL ORGANS CAUSED BY ELECTRICAL STIMULATION OF ACUPOINT "ZUSANLI" IN RATS

Objective To investigate the plasma extravasation of visceral organs caused by electrical stimulation of acupoint under the dorsal root reflex and axon reflex conditions. Methods By the means of measuring the content of Evans blue, this study investigated the plasma extravasation of visceral organs induced by electrical stimulation of acupoint 'Zusanli'(ST 36).Results The Evans blue content in the visceral organs such as liver, spleen, pancreas and the whole gastrointestinal tract in rats increased significantly after electrical stimulation of acupoint 'Zusanli' compared with that of the control group (P<0.01). The Evans blue extravasation in the above visceral organs was blocked by pre-treatment of capsaicin (66 mmol·L -1, 50 μL) into the acupoint. Conclusion The neurogenic inflammation of the visceral organs evoked by electrical stimulation of acupoint was mediated by the capsaicin-sensitive afferent fibers through the dorsal root reflex and axon reflex. It is a new method to study the correlation of meridian-viscera.

Synthesis of Capsaicin Oligosaccharides and Their Anti-Allergic Activity<br>——Synthesis of Capsaicin Oligosaccharides as Anti-Allergic Food-Additives

The production of β-maltooligosaccharides of capsaicin was investigated using Lactobacillus delbrueckii and cyclodextrin glucanotransferase (CGTase) as biocatalysts. The cells of L. delbrueckii glucosylated capsaicin to give its β-glucoside. The β-glucoside of capsaicin was converted into the corresponding β-maltoside and β-maltotrioside by CGTase. On the other hand, β-melibioside and β-isomaltoside of capsaicin, which were two new compounds, were synthesized by chemical glycosylation. The β-glucoside, β-maltoside, β-melibioside, and β-isomaltoside of capsaicin showed inhibitory effects on IgE antibody production.

Combined Effects of Capsaicin and HA14-1 in Inducing Apoptosis in Melanoma Cells

Abnormal regulation of apoptosis is an important aspect of tumour development. Capsaicin, an extract of red chilli peppers, has been shown to inhibit growth of melanoma and other malignant cell lines and HA14-1 is an organic compound that directly induces apoptosis by binding to Bcl-2 protein. The aim of this work was to investigate whether combination therapy with capsaicin and HA14-1 might hold any promise for the treatment of melanoma. Three melanoma cell lines of a range of aggressive potential, melanocytes and fibroblasts were examined, looking at the effects of both drugs singly and in combination on cell viability and induction of apoptosis. This comparative study showed that melanoma cells and melanocytes have a similar sensitivity to capsaicin while fibroblasts are more resistant to it. HA14-1, as expected, induced apoptosis in all cells at relatively low concentrations. A combination of the two agents produced the expected results of an additive effect for 2 (HBL and A375SM) out of 3 melanoma cell lines in inducing apoptosis, but encouragingly for the most metastatically aggressive cancer cell line (C8161), a combination of the two showed a synergistic induction of apoptosis.

Hippocampal plasticity after a vagus nerve injury in the rat

Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine （BrdU） incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus, leading to alteration of neurogenesis.

Neurotransmitter systems in mouse airways

OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways.METHODS Murine precision cut lung slices(PCLS)and trachea were prepared,placed into perfusion chambers equipped with platinum electrodes and stimulated transmurally(1.0 ms,50 V,0.1-30 Hz).To measure PCLS constriction,changes in airway luminal area in response to electric field stimulation(EFS)were captured as video images quantified using Image J software.For trachea,changes in isometric tension were recorded using Grass force transducers.Frequency response curves were generated in the absence and the presence of the inhibitors magnesium,atropine and capsaicin and responses analyzed and compared using a student's t-test(P<0.05).RESULTS EFS caused airway constriction in a frequency-dependent manner that was best fit by a biphasic curve.Neuron-specific stimulation was verified by Mg^(2+) blockade.Maximum airway constriction to 30 Hz EFS in PCLS was(51.8±3.0)%while tracheal constriction averaged(551±80)mg.Interestingly,in PCLS the muscarinic receptor antagonist atropine(10μmol·L^(-1))blocked(99.5±7.2)%of EFS induced constriction at 1 Hz,but only blocked(23.3±3.8)%of EFS induced constriction at 30 Hz and eliminated the first phase but not the second phase of the biphasic EFS response.Treatment with capsaicin to deplete sensory neurotransmitters significantly increased EFS constriction supporting the presence of sensory neurotransmitter systems in airways.CONCLUSION These data are consistent with parasympathetic constriction of airways by acetylcholine at lower EFS frequencies while higher frequencies release sensory dilator neurotransmitters.These data provide evidence for multiple nerve types innervating airways which may provide novel targets for treatment of lung disease.

Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury

The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.