Capsaicin fails to produce changes in contractile tension in large gut of neonate rats

Objectives: Capsaicin, the most pungent constituent of chilli pepper (Capsicum annuum L.), is known to alter the physiological activity of the gut. Capsaicin mediates its action through a transient receptor potential vanilloid type 1 (TRPV1) channel. The action of capsaicin on gut smooth muscle varies from segment to segment in different species. The earlier studies were carried out in adult animals only, and its status in the neonate gut, which is in a development stage, is not known. Objective: Therefore, the present study was done to assess the effect of capsaicin on the large gut of neonates. Materials and Methods: In an organ bath preparation, isometric contractions were recorded from segments of dissected rat colon and rectum. The gut segments were exposed to cumulative concentrations of capsaicin (0.01 nM–3 µM) and a capsaicin-induced contractile response was observed. TRPV1 receptor antagonist capsazepine (1 µM) and a nitric oxide synthase inhibitor, L-NAME (100 µM), were used to assess their blocking effect on capsaicin-induced contractile response. Results: Capsaicin raised contractile tension in the colon and rectum of adult rats but not in neonate rats. In adult rats, capsazepine pre-treatment (1 µM) failed to block the capsaicin-induced response in the colon, but in the lower concentrations, it increased contractile tension in the rectum. Pre-application of L-NAME (100 µM) potentiated capsaicin-induced response in the adult rectum and neonate’s colon but had no effect in the neonate rectum and adult colon. Capsaicin with a low concentration (0.01 nM–0.01 µM) increased contractile frequency in both the colon and rectum of adult rats. However, the effect of capsaicin on frequency was abolished at higher concentrations (0.01 µM–3 µM). A capsaicin-evoked change in contractile frequency in adult rats was blocked by capsazepine and L-NAME. At lower concentrations (0.01 nM–0.01 µM), capsaicin did not show any change in frequency in the neonatal colon, while a decrease in contractile frequency was observed with the higher concentrations (0.1 µM–3 µM) of capsaicin. In neonates, capsazepine pre-treatment produced changes in frequency for both the colon and rectum. However, pre-application of L-NAME decreased frequency in the neonate rectum but not in the colon. Conclusion: Capsaicin-induced changes in contractile activity may or may not involve TRPV1 or the Nitric Oxide (NO) pathway, depending on the part of the large gut and developmental maturity.

Transient receptor potential vanilloid 1 (TRPV1) receptor stimulation by topical capsaicin for the functional assessment of diabetic neuropathy leading to diabetic foot disease

Objectives: As neuropathy predominates vasculopathy, predicting functional deterioration of autonomic neurovascular dysfunction is essential to reduce diabetic foot ulcers. The present study has evaluated the possibility of stimulating the TRPV1 receptors of the small fibres using topical capsaicin to assess diabetic neuropathy in the dorsum of the foot functionally. Materials and Methods: A prospective cross-sectional study was carried out on ten healthy volunteers and 20 diabetic patients after receiving ethical approval. The subjects underwent vascular Doppler analysis after giving written agreement followed by monofilament testing. Then, topical capsaicin was applied to measure the local autonomic neurovascular reaction. With the use of an infrared-based digital instrument that was specially created, the vasodilation and proportional increase in temperature brought on by the application of capsaicin were quantified. Results: The percentage change in the local temperature in the control group varied from 0.478 to 3.315 compared to the diabetic group, which varied from 1.862 to ?3.932. There is a statistically significant difference in the mean of the two groups (P = 0.006) at a 95% confidence interval. Conclusion: This study suggests that TRPV1 receptor stimulation using capsaicin and resultant vasodilation monitored by the increase in local temperature can be used as a quantitative predictor of the early small fibre neuropathy in Distal Symmetric Polyneuropathy before the patient ends up with diabetic foot ulcer.

Bradykinin-induced nociceptive responses are more potent than capsaicin-induced responses in rat models

Background: Peripheral blood vessels are concerned with sensing the perivascular nociceptive information and signaling it to the higher centers through ipsilateral somatic nerves, thereby regulating the cardiorespiratory parameters by means of vasosensory reflex responses. Aims and Objectives: The present study was conducted to compare the potency of nociceptive responses elicited by bradykinin (BK) with the capsaicin-induced responses. Materials and Methods: Charles-Foster rats were anesthetized with urethane and injected intraperitoneally. After tracheostomy, the right femoral artery was cannulated with a 24G, double ported cannula for administering the chemicals/saline through vertical port and to record the blood pressure (BP) through horizontal port. BP, Electrocardiogram, and respiratory movements were recorded. Results: Injection of capsaicin into a segment of femoral artery evoked instantaneous transient tachypnoeic, hyperventilatory, and hypotensive responses. BK also produced similar pattern of nociceptive responses along with a transient fall in heart rate. In addition, the vasosensory responses produced by BK are of greater magnitude as compared to the capsaicin. Conclusions: BK is more potent in eliciting reflex nociceptive responses as compared to capsaicin. Further, BK has an additional cardioprotective role by slowing the heart, in the events of acute inflammation.

Evaluation of a Protocol For Topical Application of Capsaicine Gel 0.025 % in the Management of Burning Mouth Syndrome Correlating its Impact on Quality of Life

ABSTRACT: The aim of this study is to report the results obtained with a protocol of topical application of capsaicin gel 0.025 % in the management of burning mouth syndrome (BMS) to evaluate the influence of the disease and treatment on their quality of life (QOL) using the OHIP-14 questionnaire (Oral Health Impact Profile). After clinical examination and diagnosis of BMS, 10 patients reported the intensity of the burning by means of a subjective score ranging from 0 to 10 and also answered the OHIP-14. Then, a topical application protocol of capsaicin gel 0.025 % was initiated, with weaning from medication and complete withdrawal within 180 days. At each reassessment consultation (30, 60, 90 and 180 days), the patients answered the OHIP-14 and subjective burning scores were collected again. Overall, the capsaicin gel showed gradual reduction or elimination of symptoms of BMS, as well as an improvement in the QOL of patients throughout treatment. At 180 days, after medication withdrawal, 6 patients (60 %) reported total absence of burning and in four patients (40 %) the score remained or decreased. In one patient (10 %) the score increased, although it remained below the initial score. The results showed an improvement in the QOL of all patients who completed the protocol and the impact of BMS on the QOL decreased in relation to the initial score in all patients. The topical use of 0.025 % capsaicin gel was effective in reducing or remitting symptoms of BMS. The OHIP-14 questionnaire showed the negative impact of BMS on patients' QOL and the role of treatment in its improvement.

RESUMEN: El objetivo de este estudio fue reportar los resultados obtenidos con un protocolo de aplicación tópica de gel de capsaicina al 0,025 % en el manejo del síndrome de boca ardiente (SBA), para evaluar la influencia de la enfermedad y el tratamiento en su calidad de vida (CV) mediante el cuestionario OHIP-14. Tras el examen clínico y diagnóstico de SBA, 10 pacientes refirieron la intensidad del ardor mediante una puntuación subjetiva de 0 a 10 y también respondieron la OHIP-14. Luego, se inició un protocolo de aplicación tópica de gel de capsaicina al 0,025%, con destete de la medicación y retiro completo en 180 días. En cada consulta de reevaluación (30, 60, 90 y 180 días), los pacientes respondieron el OHIP-14 y se recogieron nuevamente las puntuaciones subjetivas de quemado. En general, el gel de capsaicina mostró una reducción o eliminación gradual de los síntomas del SBA, así como una mejora en la calidad de vida de los pacientes durante todo el tratamiento. A los 180 días, después de la retirada de la medicación, 6 pacientes (60 %) informaron ausencia total de ardor y en cuatro pacientes (40%) la puntuación se mantuvo o disminuyó. En un paciente (10 %) la puntuación aumentó, aunque se mantuvo por debajo de la puntuación inicial. Los resultados mostraron una mejora en la CV de todos los pacientes que completaron el protocolo y el impacto de SBA en la CV disminuyó en relación con la puntuación inicial en todos los pacientes. El uso tópico de gel de capsaicina al 0,025 % fue efectivo para reducir o remitir los síntomas del SBA. El cuestionario OHIP-14 mostró el impacto negativo de SBA en la CV de los pacientes y el papel del tratamiento en su mejora.

Dolor neuropático localizado / Localized neuropathic pain

Resumen El dolor neuropático localizado (DNL) es de origen periférico y se caracteriza por áreas circunscritas de dolor con sensibilidad anormal de la piel o síntomas espontáneos característicos de dolor neuropático, por ejemplo, dolor urente. Se debe resaltar que el DNL está confinado a un área específica no mayor a una hoja de papel tamaño carta. El DNL representa 60 % de las condiciones de dolor neuropático. No existe una única etiología. El abordaje diagnóstico es similar al de otros síndromes dolorosos neuropáticos. Se utilizan herramientas diagnósticas generales para evaluar las características clínicas. En la actualidad no existen guías específicas de manejo del DNL, por lo que se utilizan las guías para dolor neuropático en general. En las guías de la Sociedad Canadiense de Dolor se incluyen los tratamientos tópicos como parte de las estrategias de segunda línea. Pese a la falta de guías, los parches de lidocaína a 5 % y los parches de capsaicina a 8 % han demostrado ser efectivos en modelos de DNL.

Abstract Localized neuropathic pain (LNP) is of peripheral origin and is characterized by circumscribed areas of pain with abnormal skin sensitivity or spontaneous symptoms that are characteristic of neuropathic pain, e.g. burning pain. It should be noted that LNP is confined to a specific area no larger than a letter size sheet of paper. LNP accounts for 60 % of neuropathic pain conditions. There is no single etiology of LNP. The diagnostic approach is similar to that for other neuropathic pain syndromes. General diagnostic tools are used to assess clinical features. So far, there are no specific guidelines for the management of LNP; for this reason, guidelines for general neuropathic pain are used. Topical treatments are included as part of second-line strategies in the Canadian Pain Society guidelines. Despite the lack of guidelines, 5 % lidocaine patches and 8 % capsaicin patches have been proven effective in LNP models.

Capsaicin Induces Apoptosis of Colon Cancer SW480 Cells Through TRPV1 / 中国实验方剂学杂志

Objective:To investigate the effects of capsaicin on colon cancer SW480 cells and the underlying molecular mechanism through the transient receptor potential vanilloid 1（TRPV1）. Method:Capsaicin groups with different concentrations and a blank group were set up. The cell viability was detected by cell counting kit-8 （CCK-8） after SW480 cells were treated with capsaicin（50，100，200，300，400，500，600，800，1 000 μmol·L^-1） for 12，24，and 48 h to select the concentration of capsaicin which can effectively inhibit proliferation. The cell cycle and apoptosis were detected by flow cytometry after SW480 cells were treated with capsaicin （200，400，800 μmol·L^-1） for 24 h. The protein expression levels of TRPV1，p53，p-p53，B-cell lymphoma-2（Bcl-2），Bcl-2-associated X protein（Bax），cleaved cysteinyl aspartate-specific protease-3（cleaved Caspase-3），cleaved Caspase-8，and cleaved poly adenosine diphosphate ribose polymerase （PARP） were detected by Western blot after SW480 cells were treated with capsaicin （200，400 μmol·L^-1） for 24 h．In addition，the apoptosis was detected after SW480 cells were treated with TRPV1 microRNA（mRNA） and capsaicin（200 μmol·L^-1）. Western blot analysis was used to detect the protein expression levels of the above proteins. Result:As compared with the blank group，capsaicin（≥200 μmol·L^-1）significantly inhibited the cell viability of SW480 cells（<italic>P</italic><0.01） in dose- and time-dependent manners. The cell cycle was arrested in G₂/M phase by 200 and 400 μmol·L^-1 capsaicin treatment，and arrested in G₁ phase by 800 μmol·L^-1 capsaicin treatment （<italic>P</italic><0.05）. Flow cytometry showed that capsaicin （200， 400， 800 μmol·L^-1） significantly promoted apoptosis of SW480 cells simultaneously（<italic>P</italic><0.05，<italic>P</italic><0.01）. Western blot showed that capsaicin （200，400 μmol·L^-1） significantly up-regulated the protein levels of apoptosis-related proteins（p53，p-p53，Bax，cleaved Caspase-3，cleaved Caspase-8，and cleaved PARP） （<italic>P</italic><0.05，<italic>P</italic><0.01），and significantly down-regulated Bcl-2（<italic>P</italic><0.01）. In addition，siRNA-mediated knockdown of TRPV1 significantly attenuated capsaicin-induced apoptosis and the protein levels of apoptosis-related proteins in SW480 cells（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Capsaicin can inhibit cell proliferation，arrest cell cycle，and induce apoptosis of SW480 cells，and the possible mechanism may be related to TRPV1 activation.

Effect of small dose capsaicin for treatment of pulmonary fibrosis in mice and its mechanism / 中国应用生理学杂志

To observe whether the mechanism of small dose capsaicin (Cap) against pulmonary fibrosis in mouse is mediated by agitating transient receptor potential vanilloid 1 (TRPV1). Methods: A total of 60 BALB/c mice were randomly divided into control (CON) group, bleomycin (BLM)group, Cap (0.5, 1,2 mg/kg) groups and Cap (2 mg/kg) plus SB-452533 (2.5 mg/kg) group. C57BL/6 mice were intratracheally injected with 3.5 mg/kg BLM to induce pulmonary fibrosis model. Animals for drugs treatment received daily drug via subcutaneous injection for 21 days. The morphological changes and collagen deposition in lung tissues were analysed by HE staining, Masson staining and immunohistochemistry. The concentration of calcitonin gene-related peptide (CGRP) in plasma was determined by ELISA. The mRNA and (or) proteins levels of α-CGRP, β-CGRP, collagen I, collagen III, E-Cadherin, zonula occludens-1 (ZO-1), vimentin, alpha smooth muscle actin (α-SMA), TRPV1, p-ERK1/2 and eukaryotic initiation factor 3a (eIF3a) were detected by qPCR and (or) Western blot. Compared with the BLM group, small dose Cap significantly reduced bleomycin-induced pulmonary fibrosis in mice and obviously reversed alveolar epithelial cells epithelial-mesenchymal transition (EMT) (the expression of E-cadherin and ZO-1 were increased(P＜0.05 or P＜0.01)and the expression of α-SMA and Vimentin were decreased (P＜0.05 or P＜0.01) after drugs treatment for 21 day, concomitantly with the increase the expressions of TRPV1 and CGRP (P＜0.05 or P＜0.01), and inhibiting ERK1/2 phosphorylation and eIF3a expression (P＜0.05 or P＜0.01). These effects of small dose Cap were abolished in the presence of TRPV1 receptor antagonist SB-452533. The results suggest that small dose Cap can reverse alveolar epithelial cells EMT and alleviate bleomycin-induced pulmonary fibrosis in mice by inhibiting ERK1/2/eIF3asignaling pathway, which is related to agitating TRPV1 receptor and releasing of CGRP.

Capsaicin: Current Understanding in Therapeutic Effects, Drug Interaction, and Bioavailability

@#Capsaicin (N-vanillyl-8-methyl-6-(E)-none amide) is a unique and significant compound from group component of capsaicinoids. This component can only be found in the plants from the Capsicum genus. It is the primary source of pungency or spiciness of chilli pepper. Traditionally, capsaicin has been used to alleviate pain. Recently, some studies showed significant therapeutic effects of capsaicin in many diseases such as diabetes, hypertension, cancer and obesity. Determination of the most effective dosage used and underlying working mechanism of capsaicin are still in progress. Currently, capsaicin research, especially in drug interaction and encapsulation technologies, has not been reviewed. We aim to report current experimental evidence of capsaicin research focusing on its pharmacological properties, interaction with drugs and ways to improve the bioavailability of capsaicin. It is essential to provide a general orientation for further investigation that can discover more potency of capsaicin usage as a medicinal supplement to treat various diseases.

Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry

The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics. Dietary supplements, especially natural products that are edible and safe for human use, are a good source of drug discovery with potential for uncovering novel applications. In this study, we tested 40 natural products of dietary supplements and identified capsaicin, a common dietary supplement abundant in chili peppers, as an inhibitor of Lassa virus (LASV) entry with EC of 6.9-10.0 μmol/L using an HIV based pseudovirus platform. Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV), showing a preferential activity against LASV. Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide (SSP)-GP2 transmembrane (GP2) region of the LASV surface glycoprotein. Mutational study revealed the key residues Ala25, Val431, Phe434 and Val435 in SSP-GP2 region in capsaicin's antiviral effect. This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV, providing detailed interaction hot spots in the unique SSP-GP2 interface of LASV glycoprotein that is crucial in fusion inhibition, and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.

Capsaicin topical cream (8%) for the treatment of myofascial pain syndrome / Creme tópico de capsaicina (8%) para o tratamento da síndrome da dor miofascial

Abstract Background: Myofascial pain syndrome is a common cause of musculoskeletal pain. The objective of this study was to evaluate the potential analgesic action of 8% capsaicin cream for topical use in patients with myofascial pain syndrome. Methods: Initially, cream formulations of PLA (Placebo) and CPS (Capsaicin 8%) were developed and approved according to the current requirements of the health authority agency. The 40 participating patients were randomly assigned to the PLA and CPS groups in a double-blind fashion. Before the creams were topically administered, according to the allocation group, the local anesthetic was used for a period of 50 minutes directly in the area of interest. The cream was applied to the area of the skin over the trigger point, represented by the area with pain at palpation, in an amount of 10 g for 30 minutes in a circular area of 24 mm diameter. Subsequently, the cream was removed and the skin tolerability parameters were evaluated. The pain was measured before and during the formulation application, as well as at 1 hour, 7 days, 30 days, and 60 days after the procedure, evaluated using a verbal numerical scale (from 0 to 10: with 0 = no pain and 10 = worst pain imaginable). Results: No patient in PLA Group had hyperemia or burning sensation at the site of application, while 85% of patients in CPS Group had hyperemia or burning sensation at 15 minutes. These complaints disappeared 24 hours after the cream was removed. The pain score in CPS Group decreased steadily up to the 60th day of evaluation (p < 0.0001). Conclusion: Application of the formulations did not cause macroscopic acute or chronic skin lesions in patients, and the 8% capsaicin formulation was beneficial and well tolerated.

Resumo Justificativa: A síndrome da dor miofascial é uma causa comum de dor musculoesquelética. O objetivo deste estudo foi avaliar a potencial ação analgésica de 8% do creme de capsaicina para uso tópico em pacientes com síndrome da dor miofascial. Métodos: Inicialmente, as formulações de creme de PLA (Placebo) e CPS (Capsaicina 8%) foram desenvolvidas e aprovadas de acordo com os requisitos atuais da agência de autoridade de saúde. Os 40 pacientes participantes foram distribuídos aleatoriamente e de forma duplo-cega para os grupos PLA e CPS. Antes dos cremes serem administrados topicamente, de acordo com o grupo de alocação, o anestésico local foi usado por um período de 50 minutos diretamente na área de interesse. A administração ocorreu na área da pele sobre o ponto-gatilho, o qual apresentou a área dolorida à palpação, em uma quantidade de 10 g por 30 minutos em área circular com diâmetro de 24 mm. Posteriormente, o creme foi removido e os parâmetros de tolerabilidade à pele foram avaliados. A dor foi medida antes e durante a aplicação da formulação, bem como 1 hora, 7 dias, 30 dias e 60 dias após o procedimento avaliado pela escala numérica verbal (0 a 10, com zero sem dor e dez a pior dor imaginável). Resultados: Nenhum paciente no grupo PLA experimentou hiperemia ou sensação de queimação no local de aplicação do creme, enquanto 85% dos que experimentaram no grupo CPS apresentaram hiperemia ou sensação de queimação 15 minutos. Essas queixas desapareceram 24 horas após a remoção do creme. O escore de dor no grupo CPS diminui de forma sustentada até o 60° dia de avaliação (p < 0,0001). Conclusão: A administração das formulações não causou lesões cutâneas agudas ou crônicas macroscópicas nos pacientes e a formulação de 8% de capsaicina foi benéfica e bem tolerada.

Targeting the hTRPV6 with capsaicinoid inhibitors

Capsaicin is a substance produced by Capsicum peppers with extensive biological activity reported in the literature. Among these studies, it was suggested that the anti-tumor activity is related to modulation of the Transient Potential Receptor Vanilloid (TRPV) channels. Capsaicin is known to bind with very high affinity to TRPV1 (IC50 ≈ 7 nM), triggering the burning sensation followed by analgesia. However, recent studies have suggested that the pro-apoptotic effects of capsaicin are TRPV6-mediated. Herein we report the development of a novel inhibitor of the TRPV6 using two different strategies for compounds design. We generated a series of direct and chimeric capsaicinoids based on the literature compounds, capsaicin, and cis-22a. These analogs were probed against HEK-hTRPV6 and the hits were further optimized. Based on the previous SAR and chemical optimization, we found 56h, named MRC-130, a derivative that remarkably inhibited TRPV6 in the nanomolar range (IC50 = 83 ± 4 nM), possess high selectivity and stability in vitro, and lesser hERG inhibition compared to the reference compound, cis-22a. It is expected that these new molecules would contribute significantly to the study on the TRPV6 function and its role in tumor pathophysiology

Capsaicina é uma substância produzida por pimentas do gênero Capsicum com extensa atividade biológica relatada na literatura. Entre esses estudos, sugeriu-se que a atividade antitumoral esteja relacionada à modulação dos canais TRPV (do inglês, Transient Potential Receptor Vanilloid). Sabe-se que a capsaicina se liga com altíssima afinidade ao TRPV1 (IC50 ≈ 7 nM), desencadeando a sensação de queimação seguida de analgesia. No entanto, estudos recentes sugeriram que os efeitos pró-apoptóticos da capsaicina são mediados pelo TRPV6. Visando o exposto, este trabalho relata o desenvolvimento de um novo inibidor do TRPV6 usando duas estratégias diferentes para o planejamento dos compostos. Geramos séries de capsaicinoides diretos e quiméricos com base nos compostos da literatura, capsaicina e cis-22a. Esses análogos foram analisados contra HEK-hTRPV6 e os análogos mais promissores foram otimizados. Com base na REA e em otimizações químicas anteriores, encontramos 56h, chamado MRC-130, um derivado que inibiu notavelmente o TRPV6 na faixa nanomolar (IC50 = 83 ± 4 nM), possui alta seletividade e estabilidade in vitro e menor inibição de hERG em comparação com o composto de referência, cis-22a. Espera-se que essas novas moléculas contribuam significativamente para o estudo da função do TRPV6 e seu papel na fisiopatologia tumoral

Clinical application of capsaicin cough challenge test / 中国基层医药

The capsaicin cough provocation test is the most commonly used test to objectively evaluate cough sensitivity.The mechanism is simple and the test can be accepted by a lot of patients, which could evaluate the degree of cough, guide medicine, promote new drug development, seek for the cause.This article mainly reviews the clinical application of capsaicin cough test to assess degree of cough and guide treatment.

Anti-tumor Molecular Mechanism of Capsaicin / 中国实验方剂学杂志

Malignant tumors are major chronic diseases that threaten human health worldwide and one of the most serious public health problems in China and even in the world in the 21st century. How to effectively control and even cure tumors is also one of the most essential problems in the medical field today. Currently, although surgery, chemotherapy and radiotherapy remain the main therapies, the accompanying adverse events of chemotherapy and radiotherapy cannot be ignored. Therefore, it is of great significance to find new anti-tumor targeted drugs with a low toxicity and strong effects. Capsaicin is a plant base of fat-soluble vanillin amide isolated from Solanaceae. Its chemical structure is trans-8-methyl-N-vanillyl-6-nonenamide (C18H27NO3), a type of monoclinic rectangular flake of colorless crystals, which is the main biologically active ingredient in peppers. Capsaicin has a wide range of pharmacological effects, including anti-oxidation, prevention of cardiovascular disease, protection of gastrointestinal mucosa, analgesia, anti-inflammation, itching relief and even anti-tumor. Numerous studies indicated that capsaicin has significant anti-tumor effects in vivo and in vitro. Capsaicin can play a chemopreventive role by regulating the metabolism of carcinogens and the interaction of carcinogens with DNA. As well, capsaicin was proven to play an anti-tumor effect by inhibiting tumor cell proliferation, inducing tumor cell cycle arrest, promoting tumor cell apoptosis, inhibiting tumor cell migration, invasion and metastasis, inhibiting tumor angiogenesis, regulating tumor cell autophagy and mediating of tumor immunity. In this paper, we searched, analyzed, and summarized domestic and foreign literatures relating to capsaicin in recent years. We reviewed the effect of capsaicin on inhibiting tumor cell proliferation, inducing tumor cell cycle arrest, promoting tumor cell apoptosis, inhibiting tumor cell migration, invasion and metastasis, inhibiting tumor angiogenesis, regulating tumor cell autophagy and mediating of tumor immunity, as well as the underlying main molecular mechanisms, so as to provide scientific and theoretical basis for further research, development and utilization of capsaicin.

Effect of Capsaicin in Inhibiting Migration and Invasion of Breast Cancer MCF-7 Cells by Down-regulating SIRT1 / 中国实验方剂学杂志

Objective: To investigate the effect of capsaicin on the migration and invasion of human breast cancer MCF-7 cells and the underlying molecular mechanism. Method: Three capsaicin intervention groups of different concentrations (25, 50, 75 μmol·L-1) and a blank group were set up. After MCF-7 cells were treated with different concentrations of capsaicin (25, 50, 75 μmol·L-1) for 24 h, the cell migration and invasion abilities were assessed by Transwell migration and invasion assay, respectively. Meanwhile, the mRNA level of silent information regulator 2 homolog 1 (SIRT1) and DNA polymerase δ catalytic subunit p125 encoding gene POLD1 (POLD1) were detected by Real-time polymerase chain reaction (Real-time PCR). The protein levels of SIRT1 and DNA polymerase δ catalytic subunit p125 (p125) were detected by Western blot. Result: Compared with the blank group, the number of transmembrane cells was significantly reduced, and the mobility was significantly decreased (P-1) in MCF-7 cells for 24 h. Capsaicin (25, 50, 75 μmol·L-1) significantly down-regulated the mRNA and protein expressions of SIRT1 (P-1) in MCF-7 cells for 24 h. Furthermore, capsaicin (25, 50, 75 μmol·L-1) also significantly down-regulated the mRNA expression of POLD1 and the protein expression of p125 (P-1) in MCF-7 cells for 24 h. Conclusion: Capsaicin remarkably inhibits the cell migration and invasion of breast cancer MCF-7 cells, and the possible mechanism may be related to the down-regulation of SIRT1 and POLD1 mRNA expression levels and SIRT1 and p125 protein expression levels.

Effect of Capsaicin on Proliferation and HMGB1 and IL-6 Expressions in Hepatoma SMMC-7721 Cells / 中国实验方剂学杂志

Objective: To investigate the effect of capsaicin on proliferation in human hepatoma SMMC-7721 cells and its possible molecular mechanism. Method: Capsaicin (50,100,150,200,250,300 μmol·L-1) groups and blank group were set up. The cell viability was detected by cell counting kit-8 (CCK-8) assay after SMMC-7721 cells were treated with capsaicin (50,100,150,200,250,300 μmol·L-1) for 24, 48, 72 h. The morphological changes were observed under an inverted microscope after SMMC-7721 cells were treated with capsaicin (150,200,250 μmol·L-1) for 24 h. The mRNA expression levels of high mobility group box 1 (HMGB1) and interleukin-6(IL-6) were measured by Real-time PCR after SMMC-7721 cells were treated with capsaicin (150,200,250 μmol·L-1) for 24 h. The levels of HMGB1 and IL-6 in cell culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA) after SMMC-7721 cells were treated with capsaicin (150,200,250 μmol·L-1) for 24 h. Result: Compared with the blank group, there was no significant difference between 50 and 100 μmol·L-1 capsaicin groups treated for 24, 48, 72 h; after treated with the other concentrations of capsaicin (150, 200, 250, 300 μmo·L-1) at different time points, the proliferation inhibition rate was statistically significant (P-1) groups showed different degrees of morphological changes in SMMC-7721 cells, which became round and wrinkled, with a poor attachment and more exfoliation; compared with the blank group, the mRNA expressions of HMGB1 and IL-6 in SMMC-7721 cells of capsaicin (150, 200, 250 μmol·L-1) groups were significantly down-regulated (PPConclusion: Capsaicin inhibits cell proliferation of SMMC-7721 cells, and the possible mechanism may be related to the down-regulation of HMGB1 and IL-6 at the mRNA and protein levels.

Inhibitory Effect of Capsaicin on Growth of Breast Cancer MDA-MB-231 Cells Transplanted Tumor in Nude Mice / 中国实验方剂学杂志

Objective: To investigate the inhibitory effect of capsaicin on the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice and its possible molecular mechanism. Method: Transplanted tumor model of breast cancer MDA-MB-231 cells in nude mice were established. Then the tumor-bearing mice were randomly divided into 4 groups:model group, and low, medium and high-dose capsaicin groups (5, 10, 20 mg·kg-1). Mice of low, medium and high-dose capsaicin groups (5, 10, 20 mg·kg-1) were intraperitoneally injected with the corresponding dose of capsaicin, and the model group was injected with the same volume of phosphate buffer saline (PBS), once every 3 days, for a total of 8 times in succession. Body weight of mice and transplantation tumor volume were measured before each injection of capsaicin. Mice of each group were put to death 24 h after the last administration, and then the tumor volume, mass and the tumor inhibitory rate were calculated. The protein expression levels of high mobility group box 1 (HMGB1) and Toll-like receptors 4(TLR4) were measured by immunohistochemistry and Western blot. Result: No significant difference was observed between each group in body weight. However, compared with the model group, capsaicin (5, 10, 20 mg·kg-1) remarkably inhibited the tumor volume and mass (PPP-1) also markedly inhibited the protein expression levels of HMGB1 and TLR4 (PConclusion: Capsaicin remarkably inhibits the growth of breast cancer MDA-MB-231 cells transplanted tumour in nude mice, and the possible mechanism may be related to the down-regulation of HMGB1 and TLR4 at the protein level.

Formulation Optimization of Capsaicin Solid Dispersion and Its Characterization / 中国药房

OBJECTIVE： To prepare Capsaicin solid dispersion， to optimize its formulation and characterize the dispersion. METHODS： Capsaicin solid dispersion was prepared by melting method using P188 or PEG4000 as carrier. Using 60 min accumulative dissolution rate in vitro as index， orthogonal test was used to optimize type of carrier， drug ratio and stirring time. Validation test was conducted. The stability of Capsaicin solid dispersion within 0， 30， 180 d was investigated at 40 ℃ under the relative humidity of 75％， and X-ray diffraction （XRD） was used to analyze whether there were peaks. Capsaicin solid dispersion was characterized by differential scanning calorimetry （DSC） and XRD. RESULTS： The optimized formula included P188-PEG4000 as carrier， capsaicin-P188-PEG 4000 mass ratio of 1 ∶ 5 ∶ 3， stirring for 20 min. Accumulative dissolution rate in vitro of Capsaicin solid dispersion was 84.6％ within 60 min （n＝3）， and the preparation kept stable within 180 d [RSD of content was 3％ （n＝3）； XRD showed that there was no peak]. The phase characteristics showed that capsaicin was highly dispersed in the amorphous or molecular state in carrier. CONCLUSIONS： The optimized technology can be used to prepare Capsaicin solid dispersion， and improves more than 80％ dissolution rate in vitro at 60 min. It is stable， simple and feasible.

Effects of Capsaicin on Fat Accumulation in Rats with High Fat Diet and Alcohol / 日本補完代替医療学会誌

Objectives: We studied the effects of capsaicin (CP) with high fat diets and alcohol (Alc）on the weight of accumulated fat and oxidative stress in rats. Methods: The Sprague-Dawley rats of 4weeks male were fed for 4 weeks with the experimental diets using high fat diet. The rats were divided Control group, CP group, Alc group and CP+Alc group. Alcohol was used as a drinking solution instead of water. The control group was fed without capsaicin. It was measured fat accumulation and oxidative stress in rats. Results: There was no different between each group with respect to the body weigt gain and total foods intake. The posterior abdominal wall fat weight, concentration of liver triglyceride and oxidative stress degree of the CP group and the CP+Alc group were lower significantly than those of the Control group, and those of the CP+Alc group was lower significantly than thoes of the Alc group. Conclusion: These results suggested that the high fat diets and alcohol diets containing the capsaicin appear to effectively decrease the fat accumulation and oxidative stress. The capsaicin were expected to prevent dyslipidemia.

Clinical application of capsaicin cough challenge test / 中国基层医药

The capsaicin cough provocation test is the most commonly used test to objectively evaluate cough sensitivity.The mechanism is simple and the test can be accepted by a lot of patients,which could evaluate the degree of cough,guide medicine,promote new drug development,seek for the cause.This article mainly reviews the clinical application of capsaicin cough test to assess degree of cough and guide treatment.

Combination of a Rapidly Penetrating Agonist and a Slowly Penetrating Antagonist Affords Agonist Action of Limited Duration at the Cellular Level

The capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) has been an object of intense interest for pharmacological development on account of its critical role in nociception. In the course of structure activity analysis, it has become apparent that TRPV1 ligands may vary dramatically in the rates at which they interact with TRPV1, presumably reflecting differences in their abilities to penetrate into the cell. Using a fast penetrating agonist together with an excess of a slower penetrating antagonist, we find that we can induce an agonist response of limited duration and, moreover, the duration of the agonist response remains largely independent of the absolute dose of agonist, as long as the ratio of antagonist to agonist is held constant. This general approach for limiting agonist duration under conditions in which absolute agonist dose is variable should have more general applicability.