Capsaicin alleviates the hepatic clock gene disruption and gut microbiota dysbiosis in circadian rhythm disorder mouse model

As the body’s internal clock,the circadian rhythm regulates the energy expenditure,appetite,and sleep.There exists a close relationship between the host circadian rhythm and gut microbiota.In this work,a circadian disorder mouse model induced by constant darkness(CD)was constructed to investigate the regulating effects of capsaicin(CAP)on disturbances of metabolism homeostasis and gut microbiota in the respect of circadian rhythm-related mechanisms.Our results indicated that CAP reduced weight gain induced by circadian rhythm disorder in mice by inhibiting fat accumulation in liver and adipose tissue.The rhythmic expressions of circadian clock genes and lipid-metabolism related genes in liver were also recovered by CAP.Microbial study using 16S rRNA sequencing revealed that CAP modulated the gut microbiota richness,diversity and composition,and restored diurnal oscillations of gut microbes at the phylum and family level.These results indicated that CAP could alleviate CD-induced hepatic clock gene disruption and gut microbiota dysbiosis in mice,providing theoretical basis for CAP to be used as a muti-functional ingredient with great healthpromoting effects.

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。

Nontoxic Marine Anti-fouling Coating Containing Capsaicin

This paper summarizes a nontoxic Anti-fouling coating utilizing capsaicin as an anti-fouling agent. The capsaicin constituent used in the coating has a rating from about 100 000 to about 1 500 000 Scoville Heat Units. The capsaicin is mixed with a silicon dioxide and then solubilized into a free-flowing homogeneous liquid oleoresin composition by adding a solvent to increase solubility and facilitate mixing. The oleoresin capsaicin liquid solution is mixed with a suitable corrosion resistant epoxy resin, which is then mixed with a hardening catalyst and applied to the surface to be treated.

Regulatory effect of nerve growth factor on release of substance P in cultured dorsal root ganglion neurons of rat

Objective To investigate the regulatory effects of nerve growth factor （NGF） on basal and capsaicin-induced release of neuropeptide substance P （SP） in primary cultured embryonic rat dorsal root ganglion （DRG） neurons. Methods DRGs were dissected from 15-day-old embryonic Wistar rats. DRG neurons were dissociated and cultured, and then exposed to different concentrations of NGF （10 ng/mL, 30 ng/mL, or 100 ng/mL） for 72 h. The neurons cultured in media without NGF served as control. RT-PCR were used for detecting the mRNAs of SP and vanilloid receptor 1 （VR1） in the DRG neurons. The SP basal and capsaicin （100 nmol/L）-induced release in the culture were measured by radioimmunoassay （RIA）. Results SP mRNA and VR1 mRNA expression increased in primary cultured DRG neurons in a dose-dependent manner of NGF. Both basal release and capsaicin-evoked release of SP increased in NGF-treated DRG neurons compared with in control group. The capsaicin-evoked release of SP also increased in a dose-dependent manner of NGF. Conclusion NGF may promote both basal release and capsaicin-evoked release of SP. NGF might increase the sensitivity of nociceptors by increasing the SP mRNA or VR1 mRNA.

Cloning, Expression and Analysis of pal, a Positive Gene Involved in Capsaicin Biosynthesis in Capsicum chinense Jacq

The cDNA sequence of Capal gene was cloned from Capsicum chinense Jacq by RT-PCR and sequenced. Bioinformatics analysis showed that Capal en- codes a putative polypeptide of 683 amino acids with a calculated molecular mass of 74.2 kD and a theoretical pl of 6.9. Multiple sequence alignments and phyloge- netic tree analyses showed that Capal protein of C. chinense is similar to that of Capsicum annuum var. conoides, with an overall sequence similarity of 96%. The prokaryotic expression vector pET-32a-pal was constructed and induced to express in E. coil BL21. The SDS-PAGE analysis showed that the relative molecular mass of the induced new protein is about 74 kD, which was basically identical with that predicted by DNAMAN software （74.3 kD）, Real-time PCR analysis showed that ex- ogenous jasmonic acid （JA） promoted pal expression. The accumulation of capsaicin in pepper was analyzed by high performance liquid chromatography （HPLC）, and the results indicated that exogenous jasmonic acid （JA） can promote the synthesis of capsaicin. This study will provide valuable experimental basis for the research of transcription regulation and explaining the gene function of pal.

Study on Antimicrobial Activities of Ethanol Extracts from Different Capsicum Cultivars

[Objective] This study aimed to provide basis for exploring the antimicrobial activity of capsaicin from different Capsicum cultivars and different locations in the same Capsicum fruit. [Method] Capsaicin was extracted from pericarp and seeds of three Capsicum cultivars using the alkaline ethanol extraction method. The antimicro- bial activities of capsaicin against Staphylococcus aureus, Saccharomyces cerevisiae and Asergillus niger were also studied. [Result] Capsaicin content in the ethanol ex- tracts of three Capsicum fruit followed： C. annuum L. var. conoides〉C, annuum L.〉C. annuum L. var. Iongum, and the capsaicin content in pericarp was 1.5-3.9 times that in seeds. Within the concentration range designed in this experiment （0.5-1.5 mg/ ml）, antimicrobial activities of the ethanol extracts from fruits of three Capsicum culfi- vars against the three experimental strains were obvious, with the highest antimicro- bial activity in C. annuum L., and similar antimicrobial activity in C. annuum L var. Iongum and C. annuum L, var. conoides. [Conclution] Both pericarp and seeds of three Capsicum cultivars contained capsaicinoids with high broad-spectrum antimicrobial activity.

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。

Gastroprotection induced by capsaicin in healthy human subjects

AIM： To evaluate the gastro-protective effect of capsaicin against the ethanol- and indomethacin （IND）-induced gastric mucosal damage in healthy human subjects. METHODS： The effects of small doses （1-8 μg/mL, 100 mL） of capsaicin on the gastric acid secretion basal acid output （BAO） and its electrolyte concentration, gastric transmucosal potential difference （GTPD）, ethanol- （5 mL 300 mL/L i.g.） and IND- （3×25 mg/d） induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment. RESULTS： Intragastric application of capsaicin decreased the BAO and enhanced “non-parietal” component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin, but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3×400μg i.g. CONCLUSION： Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.

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.

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.

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.