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.

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.

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.

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.

Capsaicin-induced cell death in a human gastric adenocarcinoma cell line

AIM Capsaicin, a pungent ingredient found in red pepper, has long been used in spices, food additives, and drugs. Cell death induced by the binding of capsaidn was examined in a human gastric adenocarcinoma cell line （AGS cells）. METHODS： By using XTT-based cytotoxicity assay, flow cytometry using the TUNEL method, and quantitation of DNA fragmentation, both cell death and DNA fragmentaUon were detected in AGS cells treated with capsaicin. By using Western blotting methods, capsaicin reduced the expression of Bcl-2, the antiapoptotic protein, in AGS cells in a concentration-dependent manner. RESULTS- After incubation of AGS cells with capsaicin for 24 h, cell viability decreased significantly in a dose-dependent manner. After incubation of AGS cells with capsaicin for 24 h, apoptotic bodies also significantly increased, and were again correlated with the dose of capsaicin. When the concentration of capsaicin was 1 mmol/L, the amount of DNA fragments also increased. Similar results were also in the lower traces. CONCLUSION： These results suggest that capsaicin- induced cell death might be via a Bcl-2 sensitive apoptotic pathway. Therefore, capsaicin might induce protection from gastric cancer.

Capsaicin对NAFLD小鼠肝脏脂肪变性、炎症与坏死的改善作用研究

目的研究辣椒素(Capsaicin)对非酒精性脂肪性肝病(NAFLD)小鼠肝脏脂肪变性、炎症与坏死的改善作用。方法取24只C57/B6小鼠,通过高脂饮食诱导建立NAFLD小鼠模型,随机分为对照组(给予常规饲料喂养)、模型组(给予高脂饮食诱导NAFLD动物模型)、实验组(给予高脂饮食诱导NAFLD动物模型+capsaicin干预),三组各8只。对三组小鼠肝脏行苏木精-伊红染色,观察小鼠肝脏病理形态学变化;比较三组小鼠血糖水平、血脂四项和肝功能指标的差异。结果相比对照组,模型组小鼠肝脏可见脂肪体积增大,明显脂肪变性,核被挤向一侧,气球样变性和坏死,并且肝小叶中心出现大量炎性细胞浸润和明显坏死。相比模型组,实验组小鼠肝脏脂肪细胞排列相对完整,脂肪体积明显缩小,脂肪变性、炎症程度和坏死明显减轻。相比对照组,模型组小鼠血清空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白-胆固醇(LDL-C)含量明显增高,高密度脂蛋白-胆固醇(HDL-C)显著下降(P<0.05);相比模型组,实验组小鼠血清FBG、TC、TG及LDL-C含量显著降低,HDL-C含量明显升高(P<0.05)。相比对照组,模型组小鼠天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)及谷胱甘肽转移酶(GST)活性明显升高(P<0.05);相比模型组,实验组小鼠AST、ALT及GST活性明显下降(P<0.05)。经苏木精-伊红染色可知,实验组小鼠肝脏脂肪变性、炎症程度和坏死明显减轻。结论Capsaicin可有效改善高脂饮食诱导NAFLD小鼠肝脏脂肪变性、炎症与坏死,具有保护小鼠肝脏功能的作用。

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.

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.

Effects of Jasmonic Acid on the Expression of Capsaicin Biosynthesis Related Genes in Chili Pepper(Capsicum annuum)

To explore the regulatory effects of jasmonic acid （JA） on the expression of the genes involved in capsaicin biosynthesis pathway, the mRNA expression of the genes was determined by fluorescence-based quantitative PCR 0, 4, 12, 24 and 48 h after chili peppers （Capsicum annuum var. conoides） were treated with 100 μmol/L JA, and the content of capsaicin was measured by high performance liquid chromatography （HPLC） 0, 1, 3, 6, 10 and 15 d after JA treatment. The results showed that JA upregulated the mRNA levels of pal, C4h, Comt, 4Cl, Hct, Paint, Bcat, FatA and pun1 in chili pepper, thus promoting the synthesis of capsaicin to different extents.

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.

Study on vasoactive intestinal polypeptide receptor 1 gene translation in psoriatic epidermis with the topical treatment of capsaicin ointment

Objective To investigate the mechanism of capsaicin in treating active psoriasis vulgaris.Methods A total of 42 patients with active psoriasis vulgaris diagnosed by histology and clinical features were given either placebo or 0.025% capsaicin ointment four times daily for 30 days randomly by double-blind method.Vasoactive intestinal polypeptide receptor 1(VIPR1)gene translation in active psoriatic lesions before and after treatment with capsaicin ointment was detected by in situ hybridization.Results There was positive staining of VIPR1 gene in all the layers of psoriatic epidermis(95.5%)before the treatment with capsaicin ointment,but nearly no dyeing in epidermis(18.2%)after the treatment for 30 days.There was nearly no brown staining before and after treatment in control group.Conclusion VIPR1 gene translation in psoriatic epidermis is down-regulated after capsaicin treatment for 30 days.

Cold exposure and capsaicin promote 1,2-dimethylhyrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling

BACKGROUND Extracellular matrix(ECM)remodeling and stiffening,which are correlated with tumor malignancy,drives tumor development.However,the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine(DMH)-induced colorectal cancer(CRC)imposed by cold and capsaicin exposure remains unclear.AIM To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.METHODS For histopathological analysis,the sections of colon tissues were stained with hematoxylin and eosin,Masson’s trichrome,Picrosirius red,and Weigert’s Resorcin-Fuchsin to observe the remodeling of collagen and elastin.Additionally,the protein expression level of type I collagen(COL I),type 3 collagen(COL III0,elastin,matrix metalloproteinase(MMP)1,MMP2,MMP9,and tissue-specific matrix metalloproteinase 1(TIMP1)was assessed by immunohistochemistry.The messenger RNA(mRNA)levels of COL I,COL III,elastin,and lysyl oxidase-like-2(LOXL2)in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.RESULTS Although no differences were observed in the proportion of adenomas,a trend towards the increase of invasive tumors was observed in the cold and capsaicin group.The cold exposure group had a metastasis rate compared with the other groups.Additionally,abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group.Specifically,collagen quantitative analysis showed increased length,width,angle,and straightness compared with the DMH group.Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group.Cold exposure and capsaicin significantly increased the protein levels of COL I,elastin,and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group,while COL III did not show a significant difference.Furthermore,in immunohistochemical evaluations,MMP1,MMP2,MMP9,and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.CONCLUSION These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue.Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue.The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.