Synthetic Capsaicin Research Articles

Natural and Synthetic Capsaicin Analogues: A Comprehensive Review of Biological Effects and Synthetic Pathways.

Capsaicin analogs, whether sourced from natural origins or synthesized de novo, have garnered significant attention across diverse scientific disciplines. This comprehensive investigation explores the expansive domain of medicinal chemistry and pharmacology, focusing on capsaicin and its analogs. Notably, these analogs exhibit a wideranging pharmacological spectrum, with a particular emphasis on their potent antitumor properties. Researchers frequently explore structural modifications, particularly in region C, consistently enhancing their pharmacological activities. A highlighted finding is that analogs with alterations in both regions A and C manifest a diverse array of effects, spanning from anti-obesity to protection against ischemia. They also demonstrate anti- Alzheimer's, anti-fibrotic, anti-inflammatory, anti-diabetic, antimalarial, and anti-epileptic properties. This underscores the potential of structural adaptations in these regions, expanding the therapeutic applications of capsaicin-like compounds. Additionally, manipulations in regions B and C result in compounds that possess antioxidant and anti-obesity properties, providing valuable insights for the development of novel compounds. The therapeutic potential of capsaicin analogs opens innovative avenues for drug design and development, promising to address a broad spectrum of diseases and enhance global quality of life. Moreover, this article meticulously examines various synthetic methodologies for synthesizing capsaicin analogs, complementing the main review. These methodologies distinguish themselves through their simplicity, mild reaction conditions, and reliance on readily available commercial reagents. The accessible synthesis pathways enable researchers from diverse backgrounds to explore these compounds, fostering investigations and potential therapeutic applications.

Re-engineering and regulating molecular architecture of synthetic capsaicin for enhanced water-based degradation performance

Synthetic capsaicin, also known as pelargonic acid vanillylamide (PAVA), constitutes the primary component in riot control agents. Due to the propensity of PAVA agglomerated in aqueous environments, the interaction between the active site of PAVA molecular and catalyst was restricted, consequently reducing its degradation efficiency in water-based oxidizing agents. This study used a cationic surfactant, dodecyl trimethyl ammonium chloride (DTAC), in combination with KOH for the precise regulation and arrangement of PAVA molecules, resulting in the formation of a distinctive hydrophilic structure. This approach resolved its poor solubility in aqueous solutions while the relationship between solubility and degradation rate was obtained. The frontier orbital distribution and surface electrostatic potential distribution of PAVA molecular were predicted through first-principles calculation. The mechanism of PAVA solubilization was studied by 1H NMR techniques and infrared spectroscopy methods. The results showed that KOH substitutes the phenolic hydroxyl group “–OH” of PAVA, forming potassium phenoxide “–OK”, which enhanced the solubility of PAVA in water. Additionally, KOH might reduced the surface tension in the solution. It promotes the formation of the DTAC/PAVA complex micelle structure, which exhibited the PAVA agglomerates to exposing the catalytic activation reaction sites and accelerating the catalytic oxidation.

Arvanil induces ferroptosis of hepatocellular carcinoma by binding to MICU1.

Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate that requires research and improved treatment strategies. Chemotherapy is still one of the main methods of HCC treatment, but it may lead to drug resistance and damage to normal organs. Capsaicin, a naturally occurring active ingredient in chili peppers, has demonstrated anticancer properties in a variety of malignant tumor cell lines. However, the anti-cancer mechanism of capsaicin needs to be further explored in HCC. In this study, we utilized Arvanil, a non-stimulating synthetic capsaicin analog, in place of capsaicin. We found that Arvanil induced high mitochondrial calcium flow, which contributed to a decrease in mitochondrial membrane permeability transition pore (mPTP) opening and oxidative phosphorylation levels, ultimately triggering cellular ferroptosis by live cells in real time with a high content screening (HCS) platform and confocal microscopy. It was further confirmed by vina molecular docking and point mutation experiments that Arvanil directly binds to two amino acid sites of mitochondrial calcium uptake protein 1 (MICU1), namely Ser47 and Phe128, to trigger this process, which in turn inhibits the growth of HCC cells. In addition, it was confirmed that Arvanil enhances cisplatin chemosensitivity by inducing HCC cellular ferroptosis in vivo. In conclusion, our study suggests that Arvanil induces ferroptosis in HCC cells and is a candidate drug for the treatment of HCC.

Safety assessment of the functional feed additive phenylcapsaicin in a commercial broiler diet

Introduction: Intestinal colonisation of Salmonella is a major concern in the poultry industry, and a low dose of the high-purity synthetic capsaicin analogue phenylcapsaicin (PheCap) has the potential to be a phytobiotic alternative to antibiotics in reducing floor Salmonella in commercial broiler chicken houses. In this study we present the first safety assessment of PheCap at doses relevant for the poultry industry. Methods: In a completely randomized block design, Ross 308 male broilers were offered feed containing 0, 10, 15, or 150 mg PheCap/kg. Growth rates, mortality, haematology, clinical chemistry, foot pad lesions, litter quality and gross pathological examination of organs and tissues were evaluated for signs of toxicity over a two-phase, 35-day growth period. Results: No differences in feed intake and broiler growth were found, with broilers in the control group having the highest mortality. There was a statistically significant increase in the European Production Efficiency Factor (EPEF) for the 10 (p = 0.02) and 15 mg PheCap/kg feed (p = 0.003) treatment doses. No dose dependent adverse effects were found for any of the treatment doses. The No Observed Adverse Effect Level (NOAEL) of PheCap is probably higher than that of the highest weekly averaged daily intake of 36.3 mg/kg BW/day observed in the present study. Conclusions: The inclusion of PheCap in broiler feed at doses relevant for the commercial poultry industry is assumed not have any negative effects on broiler health.

Arvanil, a synthetic capsaicin mimetic, synergizes with Irinotecan to trigger enhanced apoptosis in Cisplatin‐resistant Human Lung Cancer

Cisplatin‐based combination therapy is the first line treatment for human lung cancer patients. Initially, cisplatin shows excellent therapeutic response inducing remission in about 80% of lung cancer patients; however, the tumor inevitably relapses (within a year) and this relapsed tumor is resistant to cisplatin. Patients with platinum‐resistant or refractory disease have very limited options, as the only standard chemotherapy with an FDA‐approved drug, irinotecan has an objective response rate of approximately 3% and little or no survival benefit. Therefore, agents which improve the therapeutic response (of human lung cancers) towards irinotecan may be useful for the treatment of cisplatin‐resistant human lung cancer. Our published data show that the nutritional compound capsaicin sensitized human lung cancer cells towards the pro‐apoptotic activity of camptothecin (an analog of irinotecan) in cell culture and athymic mouse models. The administration of capsaicin causes stomach cramps, gastrointestinal irritation, gut pain and vomiting in patients. Arvanil is a non‐pungent synthetic capsaicin‐analog which displays potent growth‐suppressive activity in human lung cancer. The present study aims to investigate the combinatorial apoptotic activity of arvanil and irinotecan in cisplatin‐resistant lung cancer. Caspase‐3 activity assays reveal that the combination of irinotecan and arvanil displayed greater apoptotic activity in H69‐CPR human cisplatin‐resistant SCLC cells than the drugs used alone. These experiments were repeated in a second cisplatin‐resistant lung cancer cell line PC9‐CDDP and similar results were obtained. Chou‐Talalay isobologram analysis showed the interaction between irinotecan and arvanil is synergistic in H69‐CPR and PC9‐CDDP cells. The combination of arvanil/irinotecan showed a greater anti‐tumor activity in H69‐CPR tumors xenografted on chicken chorioallantoic membrane (CAM) and in SCID mice. In summary, the results of our studies pave the way for novel combination therapies for the management and treatment of drug resistant lung cancers in patients.

Altered capsaicin levels in domesticated chili pepper varieties affect the interaction between a generalist herbivore and its ectoparasitoid

Plant domestication has commonly reduced levels of secondary metabolites known to confer resistance against insects. Chili pepper is a special case because the fruits of different varieties have been selected for lower and higher levels of capsaicin, the main compound associated with defence. This may have important consequences for insect herbivores and their natural enemies. Despite the widespread consumption of chili peppers worldwide, the effects of capsaicin on insects are poorly understood. Here, we investigated the effect of capsaicin on a generalist herbivore, Spodoptera latifascia (Lepidoptera: Noctuidae) and its ectoparasitoid, Euplectrus platyhypenae (Hymenoptera: Eulophidae). Using chili varieties with three pungency levels: non-pungent (Padron), mild (Cayenne) and highly pungent (Habanero), as well as artificial diets spiked with three different levels of synthetic capsaicin, we determined whether higher capsaicin levels negatively affect the performance of these insects. Overall, capsaicin had a negative effect on both herbivore and parasitoid performance, particularly at high concentrations. Caterpillars reared on highly pungent fruits and high-capsaicin diet had longer development time, reduced pupation success, lower adult emergence, but also lower parasitism rates than caterpillars reared on mild or non-capsaicin treatments. In addition, we found that the caterpillars were capable of sequestering capsaicinoids in their haemolymph when fed on the high pungent variety with consequences for parasitoids’ performance and oviposition decisions. These results increase our understanding of the role of capsaicin as a chemical defence against insects and its potential implications for pest management.

Real-world clinical efficacy assessment of Kapsikam a combined topical medication based on nonivamide synthetic capsaicin analog in patients with acute nonspecific musculoskeletal back pain: LOCUS observational study outcomes

Evaluation of the effect of local therapy with Kapsikam on the dynamics of clinical symptoms and indices of the disability scale, as well as on reducing the doses of systemic non-steroidal anti-inflammatory drugs (NSAIDs) used in patients with acute back pain (LOCUS study). An observational study included 120 patients with nonspecific pain in the lower back and a verified diagnosis of Lumbodynia M54.5; «Lumbodynia with sciatica» M54.4, of which 78 received in addition to the basic treatment with systemic NSAIDs topical drug Kapsikam and 42 - only basic treatment.

OP0187 DETERMINING OPTIMAL COOLING AND ADMINISTRATION METHODS FOR CNTX-4975 INTRA-ARTICULAR INJECTION IN SUBJECTS WITH MODERATE TO SEVERE OSTEOARTHRITIS KNEE PAIN

Background:CNTX-4975 is a highly purified, synthetic capsaicin being developed to provide long-term analgesia after a single intra-articular (IA) injection for patients with moderate to severe osteoarthritis (OA) knee pain. CNTX-4975 IA administration is associated with short-term post-procedural pain that can be attenuated with preemptive joint cooling.Objectives:To evaluate cooling and administration procedures for CNTX-4975 IA injection, with goals of balancing patient comfort and ease of use and assessing clinical response 8 weeks after injection.Methods:This phase 3, open-label, 8-week study (NCT03661996) enrolled subjects aged 40–95 y with Kellgren-Lawrence grade 1–4, BMI ≤45 kg/m2, and stable, moderate to severe OA knee pain and who failed ≥2 therapies. Subjects were assigned to unilateral/bilateral CNTX-4975 1 mg IA injections as determined by OA pain/joint replacement status, then randomized by study site to 1 of 5 treatment regimens (Figure). The primary outcome measure assessed Breg cooling control vs other cooling regimens on day 1 using a combined sum of 1) pain (0, none; 4, severe) 30 minutes after CNTX-4975 injection; 2) subject satisfaction (SS) with cooling/injection procedures; and 3) investigator satisfaction (IS) with procedures. SS and IS were measured on a 1–7 scale (1, completely dissatisfied; 7, completely satisfied); pain was reverse scored and normalized (1, severe; 7, none) for equal weighting. Geometric mean ratios (GMR) with 95% CIs were constructed for each regimen vs Breg control (ANCOVA); lower 95% CI >0.7 was considered clinically acceptable. Secondary endpoints included percentage of subjects by subject type meeting criteria for Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders 8 weeks after injection. Safety assessments included TEAEs.Results:The intent-to-treat population included 848 subjects. The primary combined outcome showed that all cooling and administration regimens were clinically acceptable, with the evaluated cold gel wraps being at least as effective as the Breg circulating ice-water wrap (Table). For subjects with unilateral OA, OMERACT-OARSI response rates were 67% in those with no/mild nonindex knee pain and 81% in those with nonindex knee single joint replacement. For subjects with bilateral knee OA receiving bilateral injections, response rates for index and nonindex knees were 73% and 79%. TEAEs were reported in 22% of subjects; <1% were serious. TEAEs occurring in >2% of subjects were procedural pain (2.9%), arthralgia (2.2%), and nausea (2.1%), with no meaningful differences across groups.Conclusion:All cooling regimens for CNTX-4975 IA administration were clinically acceptable and well tolerated, offering feasible options for use in routine practice. Importantly, high levels of clinical response were observed 8 weeks after unilateral or bilateral knee injections for moderate to severe OA knee pain.Primary Combined Endpoint Outcome in the Index Knee, Normalized Scale, by Cooling and Administration Procedure (ANCOVA Model)Breg Cooling ControlN=162Gel Pack CoolingN=179Shortened Gel Pack CoolingN=175Single Needle Injection,Gel Pack Cooling,2% LidocaineN=160Single Needle Injection,Gel Pack Cooling,1% LidocaineN=172Mean (SD)17.23 (2.660)18.23 (2.023)16.81 (2.891)17.57 (3.049)16.43 (3.138)Geometric LS Mean (SE)17.18 (1.016)18.26 (1.015)16.48 (1.016)17.40 (1.016)16.00 (1.015)95% CI16.66, 17.7217.74, 18.8015.99, 16.9916.87, 17.9515.53, 16.49Comparison vs Breg CoolingGMR (SE)1.06 (1.022)0.96 (1.022)1.01 (1.022)0.93 (1.022)95% CI1.02, 1.110.92, 1.000.97, 1.060.89, 0.97Clinically Acceptable?YesYesYesYesLS, least squares; SD, standard deviation; SE, standard error.GMR lower 95% CI >0.7 considered clinically equivalent.Disclosure of Interests:Randall Stevens Shareholder of: Centrexion Therapeutics Corp, Employee of: Centrexion Therapeutics Corp, Peter Hanson Shareholder of: Centrexion Therapeutics Corp, Employee of: Centrexion Therapeutics Corp, Paul Tiseo Employee of: Centrexion Therapeutics Corp, Kimberly Guedes Shareholder of: Centrexion Therapeutics Corp, Employee of: Centrexion Therapeutics Corp, James Campbell Shareholder of: Centrexion Therapeutics Corp, Employee of: Centrexion Therapeutics Corp, James Connolly Employee of: Centrexion Therapeutics Corp, Stephanie Ruggiero Employee of: Centrexion Therapeutics Corp, Meg Corliss Employee of: Centrexion Therapeutics Corp, Valerie Smith Consultant of: Centrexion Therapeutics Corp, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer

Effect of intra-articular injection of CNTX-4975 on pain relief of knee osteoarthritis

Purpose: The main clinical symptoms of knee osteoarthritis are knee pain and limited joint movement, especially when walking or walking up and down stairs. CNTX-4975 is a synthetic capsaicin that blocks pain signals from the central nervous system. It has a half-life of only four hours, but damaged pain fibers only gradually regrown after three months. So it has a longer pain relief period. In this study, CNTX-4975 was injected into the knee cavity to relieve the pain of moderate and severe knee arthritis.

Capsaicin 8% Dermal Patch: A Review in Peripheral Neuropathic Pain.

The adhesive capsaicin dermal patch (Qutenza®) delivers a high concentration (8% w/w) of synthetic capsaicin, a highly selective agonist of transient receptor potential vanilloid-1 (TRPV-1), directly to the site of pain. The capsaicin 8% dermal patch is indicated in the EU for the treatment of peripheral neuropathic pain (PNP) in adults, either alone or in combination with other medicinal products for pain. In patients with painful diabetic peripheral neuropathy, a single 30-min application of the capsaicin 8% dermal patch provided 12weeks of pain relief and improved sleep quality compared with placebo. Repeat treatment with the capsaicin 8% dermal patch plus standard of care over 52weeks provided sustained pain relief, with no negative neurological effects compared with standard of care alone. The capsaicin 8% dermal patch was non-inferior to oral pregabalin in relieving pain in patients with non-diabetic PNP, with a faster onset of action and greater treatment satisfaction. A single 60-min application of the capsaicin 8% dermal patch provided rapid and sustained pain relief in patients with postherpetic neuralgia. Results in patients with HIV-associated neuropathy were equivocal, with a significant improvement in pain intensity observed in one trial, but not in the other. The capsaicin 8% dermal patch was generally well tolerated; transient application-site reactions were the most common adverse events. In conclusion, the capsaicin 8% dermal patch is a useful addition to the treatment options currently available for patients with PNP.

A 90-day toxicity and genotoxicity study with high-purity phenylcapsaicin

To evaluate the safety of the synthetic capsaicin analogue phenylcapsaicin (PheCap; 7-phenylhept-6-yne-acid-hydroxy-3-mathoxylbenzylamide, CAS no 848127-67-3), a 90-day repeated dose oral gavage of 0, 30, 100 or 250 mg/kg body weight (bw)/day toxicity study with a 28-day recovery period was conducted using Wistar rats. Examinations of clinical signs, body and organ weight, haematology, urinalysis, clinical chemistry, food consumption and macroscopic, as well as histopathological tissue examinations were carried out for signs of toxicity. Degenerative, but reversible changes in the liver at 250 mg/kg bw/day, and local irritating effects in the stomach at 100 and 250 mg/kg bw/day were found. These findings were associated with test item-related clinical symptoms, that is, diarrhoea, salivation and moving of bedding material. PheCap did neither cause gene mutations by base pair changes or frame shifts in the genome of the tester stains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 or TA 102 nor induce structural and/or numerical chromosomal damage in human lymphocytes. Therefore, it can be concluded that PheCap is not genotoxic. The No Observed Adverse Effect Level (NOAEL) of PheCap for systemic toxicity is considered to be at 100 mg/kg bw/day which is based on degenerative changes in the liver. Due to irritating effects in the stomach, the NOAEL for local effects was established at 30 mg/kg bw/day.

Anticancer Activity of Natural and Synthetic Capsaicin Analogs.

The nutritional compound capsaicin is the major spicy ingredient of chili peppers. Although traditionally associated with analgesic activity, recent studies have shown that capsaicin has profound antineoplastic effects in several types of human cancers. However, the applications of capsaicin as a clinically viable drug are limited by its unpleasant side effects, such as gastric irritation, stomach cramps, and burning sensation. This has led to extensive research focused on the identification and rational design of second-generation capsaicin analogs, which possess greater bioactivity than capsaicin. A majority of these natural capsaicinoids and synthetic capsaicin analogs have been studied for their pain-relieving activity. Only a few of these capsaicin analogs have been investigated for their anticancer activity in cell culture and animal models. The present review summarizes the current knowledge of the growth-inhibitory activity of natural capsaicinoids and synthetic capsaicin analogs. Future studies that examine the anticancer activity of a greater number of capsaicin analogs represent novel strategies in the treatment of human cancers.

Antimicrobial Effect of Capsaicin against Aggregatibacter actinomycetemcomitans

This study aimed to evaluate the in vitro antimicrobial activity of synthetic capsaicin and in natura capsaicin against Aggregatibacter actinomycetemcomitans,and compare them with each other. The in natura and synthetic extracts of capsaicin at the concentrations of 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5% and 3.0% were diluted in 1mL of dimethylsulfoxide (DMSO). The positive control was chlorhexidine 0.12% and the negative control was DMSO. The diameter of the zone of bacterial inhibition was measured after 72 hours. The main effect of capsaicin (natural vs. synthetic) origin against Aggregatibacter actinomycetemcomitans was not significant; No effect of interaction between capsaicin origin and concentration on bacterial growth was observed. Capsaicin presented in vitro antibacterial activity against Aggregatibacter actinomycetemcomitans, with no difference between in natura and synthetic type, but its effect at the concentrations tested was lower than that of chlorhexidine 0.12%. It was concluded that capsaicin presented antimicrobial activity on Aggregatibacter actinomycetemcomitans, irrespective of origin.

The Prospective Antiobesity Effect of Capsaicin Synthetic Analogs: A Matter of Weight

Capsaicin, the major component of chili peppers, has shown potential therapeutic effect against metabolic disease inducing weight loss. Its effect is exerted by a particular molecular mechanism and pharmacodynamics, distinct to current obesity treatments. However, its high irritating taste or pungency has limited its use to some clinical trials. Capsaicin-like molecules, known as capsaicin synthetic analogs, contain the majority of capsaicin domains but without those of pungency. Recently, they have received much attention by their potent antiobesity effect. The study of their structure-activity relationship would unravel the mechanisms responsible of this effect. This review summarizes much of the current experimental evidence of the potential effect in metabolism regulation of natural and synthetic capsaicin analogs discovered to date.

Capsaicin 8 % Patch: A Review in Peripheral Neuropathic Pain.

The capsaicin 8 % patch (QUTENZA®) is an adhesive patch containing a high concentration (8 % w/w) of synthetic capsaicin, a selective agonist of transient receptor potential vanilloid 1 channel. It is approved for treatment of peripheral neuropathic pain in adults either alone or in combination with other medicinal products for pain in the EU; it is only approved to treat postherpetic neuralgia (PHN) in the USA. In patients with painful diabetic peripheral neuropathy (PDPN), a single 30-min application of the capsaicin 8 % patch significantly improved pain relief and sleep quality compared with placebo in a 12-week double-blind trial. In a 52-week, randomized trial, up to seven consecutive 30-min treatments with the capsaicin 8 % patch (≤7 treatments each at least 8 weeks apart) plus standard of care therapy was associated with sustained pain relief and no negative neurological safety consequences compared with standard of care. In two randomized trials, a single 60-min application of the capsaicin 8 % patch reduced pain scores significantly more than a low-concentration (0.04 %) capsaicin control patch in patients with PHN. Capsaicin 8 % patch treatment was noninferior to pregabalin (optimized dosage) in a randomized trial in patients with nondiabetic peripheral neuropathic pain. Results in two trials in patients with HIV-AN were equivocal, with a significant improvement in pain intensity observed in one trial, but not in the other. The capsaicin 8 % patch was associated with expected, transient, capsaicin-related application-site adverse events such as erythema and pain.

Discovery of non-electrophilic capsaicinoid-type TRPA1 ligands.

Replacement of the benzylamide motif of synthetic capsaicin (nonivamide, 1c) with a tetrazole moiety was detrimental for TRPV1 binding, but unexpectedly generated a potent and non-electrophilic TRPA1 agonist (4a). Spurred by this observation and by the relatively small number of non-covalent TRPA1 ligands reported so far, the benzylamide-to-tetrazole swap was investigated in the more lipophilic and powerful vanilloids olvanil (1d), rinvanil (1e), and phenylacetylrinvanil (1f). In all cases, the replacement was detrimental for TRPV1 binding, but a clear modulation of TRPA1 activity was observed. These observations show that the capsaicinoid pharmacophore displays orthogonal structure-activity relationships for TRPV1 and TRPA1 binding, and suggest the possibility of obtaining compounds with dual TRPV1/TRPA1 modulatory properties by exploration of the chemical space around the capsaicin motif.

THU0347 Clinical Effectiveness of 8 % Capsaicin Dermal Patch in the Treatment of Carpal Tunnel Syndrome

BackgroundThe name of carpal tunnel syndrome (CTS) refers to a complex of symptoms resulting from the pressure exerted on the median nerve in the carpal tunnel area. CTS is the...

Determination of capsaicinoids and eugenol in waste-edible-oil by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry

A method was developed for the determination of capsaicinoids (capsaicin, dihydrocapsaicin and synthetic capsaicin) and eugenol in waste-edible-oil extracted by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The capsaicinoids and eugenol in waste-edible-oil were extracted by methanol, and then separated by a SUPEL COSIL ABZ + Plus dC18 column (150 mm x4.6 mm, 5 microm). The analysis was performed by MS/MS with electrospray ionization in positive and negative ion modes with multiple reaction monitoring (MRM). The limits of detection for capsaicin, dihydrocapsaicin, synthetic capsaicin and eugenol were 0.02, 0.03, 0.03 and 0.6 microg/L, respectively. The good linear relationships were obtained in certain concentration ranges of capsaicinoids and eugenol. The relative standard deviations (RSDs, n=5) of same-worker and different-worker were less than 5%. The method is exclusive, sensitive and accurate, and can be used in waste-edible-oil determination.

Capsaicin-induced metabolic and cardiovascular autonomic improvement in an animal model of the metabolic syndrome

The metabolic syndrome (MetS) is associated with an increased risk of cardiac mortality, as it is characterised by the clustering of multiple cardiovascular risk factors. Studies have shown that capsaicin (red pepper) may be useful as a nutraceutical, ameliorating metabolic profile and cardiovascular function. The aim of the present study was to investigate the cardiovascular and metabolic effects of orally administered capsaicin in rats with the MetS. Neonate spontaneously hypertensive rats were injected with monosodium glutamate and subjected to one of the following three treatments by oral administration for 14d, between 27 and 30 weeks: low-dose capsaicin (CAP05, n 18, synthetic capsaicin powder diluted in a vehicle (10% ethyl alcohol) plus 0·5mg/kg body weight (BW) of capsaicin); high-dose capsaicin (CAP1, n 19, synthetic capsaicin powder diluted in a vehicle (10% ethyl alcohol) plus 1mg/kg BW of capsaicin); control (C, n 18, vehicle). Lee's index, lipid/metabolic profile, and cardiovascular parameters with the rats being conscious, including arterial pressure (AP) and heart rate (HR) variability, as well as aortic wall thickness (haematoxylin and eosin staining) and CD68 (cluster of differentiation 68) antibody levels (monocyte/macrophage immunostaining) were evaluated. Weight, Lee's index, and lipid and metabolic parameters, as well as AP and HR and aortic wall thickness, were similar between the groups. Capsaicin determined HR variability improvement (16·0 (sem 9·0), 31·0 (sem 28·2) and 31·3 (sem 19·0)ms2 for the C, CAP05 and CAP1 groups, respectively, P=0·003), increased vascular sympathetic drive (low-frequency component of systolic AP variability: 3·3 (sem 2·8), 8·2 (sem 7·7) and 12·1 (sem 8·8)mmHg2 for the C, CAP05 and CAP1 groups, respectively, P<0·001) and increased α-index (spontaneous baroreflex sensitivity). The present data show that capsaicin did not improve lipid and glucose abnormalities in rats with the MetS. However, beneficial cardiovascular effects were observed with this nutraceutical.

Capsaicin Dermal Patch

Capsaicin dermal patch is an adhesive patch containing a high concentration (8% w/w) of synthetic capsaicin. It is indicated in the EU for the treatment of peripheral neuropathic pain in non-diabetic adults using a single 30- or 60-minute application repeated every 90 days, as required, and in the US for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN). In pivotal, randomized, double-blind, multicentre trials in adults with PHN, a single 60-minute application of capsaicin dermal patch reduced the mean Numeric Pain Rating Scale (NPRS) scores from baseline to a significantly greater extent than a low-concentration (0.04% w/w capsaicin) control patch during weeks 2-8. In randomized, double-blind, multicentre trials in patients with HIV-associated neuropathy, capsaicin dermal patch reduced the mean NPRS scores from baseline significantly more than control in one study for the 30- and 90-minute, but not the 60-minute, application during weeks 2-12. In another study, the differences between capsaicin (30- and 60-minute applications) and control did not reach statistical significance. An integrated analysis of both studies showed that the 30-minute application of capsaicin dermal patch was significantly better than control for the reduction from baseline in mean NPRS scores during weeks 2-12. The efficacy of capsaicin dermal patch was maintained for up to 1 year in extension studies in which patients could receive up to three or four repeat treatments. Capsaicin dermal patch was generally well tolerated in clinical trials. The most common adverse events were transient, mostly mild to moderate, application-site reactions.