Different Doses Of Capsaicin Research Articles

Enhanced Bone Healing Through Systemic Capsaicin Administration: An Experimental Study on Wistar Rats.

BACKGROUND The healing of bone defects is a serious challenge worldwide. One branch of dentistry deals with bone defects. Capsaicin has anti-inflammatory, anti-oxidative, and cholesterol-reducing effects. The aim of this study was to evaluate the effects of systemic capsaicin administered at different doses on bone healing. MATERIAL AND METHODS A total of 32 male wistar rats was used, their weight varying between 250 and 300 g. The rats were randomly divided into 4 groups of 8 rats each. The analyses served to evaluate the effect on healing of different doses of capsaicin and grafts. A significant increase was observed in the number of osteoblasts in the capsaicin-applied groups, compared with the control group. RESULTS The analyses served to evaluate the effect on healing of different doses of capsaicin and grafts. A significant increase was observed in the number of osteoblasts in the capsaicin-applied groups, compared with that of the control group. The inflammation scores showed a significant difference only in the control group and in the group administered with 50 mg/kg capsaicin (P=0.010). The osteoclast counts were significantly different between all groups. CONCLUSIONS As a result of the analyses, positive effects on bone healing were observed when capsaicin 0.25 mg/kg and 0.50 mg/kg was administered intraperitoneally. However, more studies are needed for more accurate information.

The Effect of Capsaicin on Growth Performance, Antioxidant Capacity, Immunity and Gut Micro-Organisms of Calves.

Capsaicin is the active ingredient of the red pepper plant of the genus Capsicum. The aim of this study was to investigate the effects of different doses of capsaicin on growth performance, antioxidant capacity, immunity, fecal fermentation parameters and gut microbial composition in nursing calves. Twenty-four newborn Holstein calves were randomly assigned to three treatment groups, which each consisted of eight calves. The milk replacer was supplemented with 0, 0.15 or 0.3 mL/d of capsaicin in each of the three treatment groups. During the 4-week experiment, intake was recorded daily, body weight and body size parameters were measured at the beginning and end of the trial and serum samples and rectal fecal samples were collected at the end of the trial to determine serum parameters, fecal fermentation parameters and fecal microbiome compartments. The results showed that both doses of capsaicin had no negative effect on the growth performance or the fecal fermentation parameters of calves, and the higher dose (0.3 mL/d) of capsaicin significantly improved the antioxidant capacity and immunity of calves. The calves in the high-dose capsaicin-treated group had lower fecal scores than those recorded in the control group. High doses of capsaicin increased glutathione antioxidant enzyme, superoxide dismutase, immunoglobulin A, immunoglobulin G, immunoglobulin M and interleukin-10 levels and decreased malondialdehyde and bound bead protein levels. In addition, capsaicin regulated the gut microbiota, reducing the abundance of diarrhea-associated bacteria, such as Eggerthella, Streptococcus, Enterococcus and Enterobacteriaceae, in the gut of calves in the treated group. Therefore, high doses of capsaicin can improve the antioxidant and immune capacity of calves without affecting growth performance, as well as improve the gut microbiological environment, which enables the healthy growth of calves.

Does capsaicin have therapeutic benefits in human colon adenocarcinoma? Selection of the most reliable dose via AgNOR

Background/aim To determine the effect of different doses of capsaicin on AgNOR protein synthesis in human colon adenocarcinoma derivate from colon cancer (Caco-2 cell).Materials and methods In this experimental study, after the cultured of Caco-2 cell line, the cells are divided into 4 groups as control and different capsaicin exposed doses (25uµ, 50uµ, and 75uµ). Mean AgNOR number and total AgNOR area/nuclear area (TAA/NA) were calculated.Results A significant differences were detected between control and capsaicin (50uµ) (P = 0.001), between control and capsaicin (75uµ) (P = 0.000), between capsaicin (25uµ) and capsaicin (50uµ) (P = 0.001) and between capsaicin (25uµ) and capsaicin (75uµ) (P = 0.000) for TAA/NA. Also, there were significant differences between control and capsaicin (50uµ) (P = 0.001), between control and capsaicin (75uµ) (P = 0.000), between capsaicin (25uµ) and capsaicin (50uµ) (P = 0.000) and between capsaicin (25uµ) and capsaicin (75uµ) (P = 0.000) for mean AgNOR number.Conclusion: A certain amount of capsaicin has a protective effect against colon adenocarcinoma and the dose concentrations are important for the most reliable treatment.

Capsaicin protects against testicular torsion injury through mTOR-dependent mechanism

ScopeTesticular torsion and subsequent release of reactive oxygen species (ROS) can cause infertility in adults. Oxidative stress following testicular torsion plays an important role in the ýonset and development of apoptotic cell death through dysregulation of the cellular signaling pathways. Anti-inflammatory and antioxidant properties of capsaicin, a bioactive composition present in red peppers, has already been exploited for treatment of the cancer and pain relief. In present work, we evaluated the role of the mammalian target of rapamycin (mTOR) in antioxidant effect of capsaicin against reperfusion injury following testicular torsion. MethodsMale Wistar rats weighing 200–220 g were randomly assigned into four major groups: (i) a sham operated group, (ii) a testicular torsion (TT) group, (iii) three groups treated with different doses of capsaicin (TT + 100, 500 and 1000 μg/ml Cap), and (iv) three groups of healthy rats treated with different doses of capsaicin (100, 500 and 1000 μg/ml). Western blotting assay was used to examine the anti-apoptotic effects of capsaicin in testicular cells following torsion. H&E and TUNEL methods were used to evaluate testicular morphology and apoptosis activity. ResultsCompared to control group, phosphorylation of mTOR was significantly increased in the TT groups. Capsaicin administration remarkably decreased the phosphorylation of mTOR at the highest dose (P < 0.05). Capsaicin decreased apoptosis and preserved tubular morphology in testes. ConclusionOur results showed that antioxidant properties of capsaicin minimizes cell death and reperfusion injury following testicular torsion.

Effects of capsaicin on ovarian granulosa cell proliferation and apoptosis.

Capsaicin is the pungent ingredient in red peppers. Due to the effects on the sensory nerve fibers, capsaicin has been used to treat pain and inflammation associated with a variety of diseases including rheumatoid arthritis and diabetic neuropathy, obesity, and cardiovascular and gastrointestinal conditions. Despite the extensive publications on different systems, the studies of the effects on the ovary are very limited. The present study was conducted to examine the possible proliferative and/or apoptotic effects of various doses of capsaicin on primarily derived granulosa cells. In accordance with this purpose, ovarian granulosa cells were exposed to different doses of capsaicin for 24 and 48h. The proliferative effects of capsaicin were examined by immunocytochemistry, immunofluorescence, and western blot using an antibody against proliferating cell nuclear antigen (PCNA) and cell viability assay (MTT). The effects on apoptosis were determined by immunocytochemistry and immunofluorescence using antibodies against cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). We showed that the number of apoptotic cells increased in a capsaicin dose and time-dependent manners. We found that a low dose of CAP in 24h administration was more effective on granulosa cell proliferation. Our results suggest that low-dose and short-term administration of CAP may have a positive effect on ovarian folliculogenesis.

FOXO1 targeting by capsaicin reduces tissue damage after testicular torsion.

Testicular torsion-related oxidative stress causes a sequential chain of DNA damage, lipid peroxidation and cell death that leads to the derangement in the sperm functions and infertility. Capsaicin that has been applied for pain relief and cancer prevention possesses antioxidant properties which can be exploited to confer cell survival under ischaemic testis damage. Wistar male rats weighing 150-200g were randomly divided into four groups: (i) sham group (all procedures except torsion of testis), (ii) ischaemia group (TT group), (iii) three TT groups treated with different dose of capsaicin (TT + different doses of Cap) and (iv) three control groups treated with different doses of capsaicin (100, 500 and 1000 ug/ml). Capsaicin administration significantly decreased the expression of pro-apoptotic factors and increased the expression of anti-apoptotic factors. Likewise, the expression of FOXO1 is significantly increased by higher doses of the capsaicin. Histological assessment by H&E and TUNEL method also exhibited an improved testicular morphology and decreased apoptosis in testes. These results suggested clinical potential for capsaicin in treatment of testicular torsion by targeting FOXO1 and apoptotic pathways.

Protective effect of capsaicin against methyl methanesulphonate induced toxicity in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the main component in hot peppers, including red chili peppers, jalapenos, and habanero, belonging to the genus Capsicum. Capsaicin is a potent antioxidant that interferes with free radical activities. In the present study, the possible protective effect of capsaicin was studied against methyl methanesulphonate (MMS) induced toxicity in third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9. The third instar was allowed to feed on the diet having different doses of capsaicin and MMS separately and in combination. The results suggested that the exposure of third instar larvae to the diet having MMS alone showed significant hsp70 expression as well as tissue DNA and oxidative damage, whereas the larvae feed on the diet having MMS and capsaicin showed a decrease in the toxic effects for 48-h of exposure. In conclusion, capsaicin showed a dose-dependent decrease in the toxic effects induced by MMS in the third instar larvae of transgenic Drosophila melanogaster.

The effects of intrathecal injecting capsaicin on the analgesia effects of enflurane and sevoflurane

Objective The present research was designed to explore the role of transient receptor potential vanilloid 1(TRPV1) in analgesia induced by enflurane(Enf) and sevoflurane(Sev). Methods Two hundred and forty mice were completely randomly divided into intraperitoneally (ip) (hot-plate test) or subcutaneously (SC) (acetic acid-induced writhing test) saline and Enf, Sev groups and each group according to intrathecal injection solvent and capsaicin (2.5, 5, 10 ng) was divided into four subgroups. After established the mice model of analgesia by intraperitoneal or subcutaneous injection of appropriate doses of Enf or Sev, we injected different doses of capsaicin intrathecally and observed effects on the pain threshold using the hot-plate and acetic acid-induced writhing test. Results The results showed that intrathecal injection of capsaicin(2.5, 5, 10 ng) did not affect the pain threshold in hot-plate test(HPPT) or the writhing numbers in conscious mice(P>0.05). In contrast, capsaicin (2.5, 5, 10 ng intrathecally) was signiflcantly decreased the HPPT and increased the writhing nubmers [Enf group: (22±7), (24±5), (29±6) vs (16±6), Sev group: (21±6), (23±7), (28±4) vs (13±5)]in mice treated with Enf or Sev(P<0.05). Conclusions These results suggest that spinal TRPV1 may mediate the analgesic effects of Enf and Sev. Key words: Enflurane; Sevoflurane; Analgesia; Intrathecal injection; Transient receptor potential vanilloid 1

Inhibiting ROS-STAT3-dependent autophagy enhanced capsaicin–induced apoptosis in human hepatocellular carcinoma cells

Capsaicin, which is the pungent ingredient of red hot chili peppers, has been reported to possess anticancer activity, including that against hepatocellular carcinoma. However, the precise molecular mechanisms by which capsaicin exerts its anticancer effects remain poorly understood. Herein, we have tested the involvement of autophagy in the capsaicin mechanism of action in human hepatocellular carcinoma. HepG2 cancer cells were treated with different doses of capsaicin (50, 100 and 200μmol/L) for 6, 12, and 24 h. Flow cytometry and Caspase-3 activity assay were performed to determine cell apoptosis. Immunofluorescence was performed to visualize LC3-positive puncta. Western blotting was used to detect the expression of the hallmarks of apoptosis and autophagy. Capsaicin can induce apoptosis in HepG2 cells. The expression levels of CL-PARP and Bcl-2 were significantly increased. In line with the apoptosis, capsaicin can trigger autophagy in HepG2 cells. Capsaicin increased LC3-II and beclin-1 expression and GFP-LC3-positive autophagosomes. Pharmacological or genetic inhibition of autophagy further sensitized HepG2 cells to capsaicin-induced apoptosis. Mechanistically, capsaicin upregulated the Stat3 activity which contributed to autophagy. Importantly, we found that capsaicin triggered reactive oxygen species (ROS) generation in hepatoma cells and that the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Moreover, NAC abrogated the effects of capsaicin on Stat3-dependent autophagy. In this study, we demonstrated that capsaicin increased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3)-dependent autophagy through the generation of ROS signaling pathways in human hepatoma. Inhibiting autophagy could enhance capsaicin-induced apoptosis in human hepatocellular carcinoma.

Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination)

Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.

Orally Given Capsaicinoids do not Modify the Absorption, Metabolism, and Excretion of Aspirin and its Platelet Aggregation in Human Male Healthy Subjects (Human Clinical Pharmacological Phase. I. Examinations)

Backgrounds : 1. The acetylsalicylic acid (ASA, Aspirin) is very frequently used in the every day medical practice as platelet aggregation, analgetic, antipyretic agent in patients with myocardial infarction, prevention of stroke, different thrombophylic events and in different groups of patients and healthy subjects, however, it produces frequently serious gastrointestinal mucosal damage (bleeding, ulceration and perforation); 2. The gastrointestinal mucosal protection was proved by capsaicin(oids), when it (those) was (were) orally given in the doses, which are able to stimulate the capsaicin-sensitive afferent nerve fibers in animal experiments and human observations. Aims of this study were: 1. To evaluate the different pharmacokinetic parameters of capsaicin(oids) (given in doses in stimulatory doses of capsaicin-sensitive afferent nerves) in healthy male volunteers; 2. To study the action of capsaicin(oids) on the co-administration of ASA pharmacokinetic parameters and some pharmacological effect of ASA on the epinephrine-induced platelet aggregation, and 3. To follow strictly the internationally and the human clinical pharmacologically accepted pathway of the pharmaceutical production of a new drug combination [ASA + capsaicin(oids)] for the human medical therapy. Materials and Methods . 1. Fifteen human healthy male subjects were included into this human classical clinical pharmacological phase I., 2. The observations were carried out according to the “Protocol of Study” (protocol number: 1.4.1; EudraCT number: 2000-007048-32), which was permitted by the Hungarian Institute of Pharmacy (dated by June 4, 2009) and by the Hungarian Ethics of Committee for Clinical Pharmacology, Hungarian Medical Research Council (dated by March 1, 2009); 3. The criteria of inclusion and exclusion of healthy male subjects for this study were very strictly identified, 4. The screening and collection of the healthy males were maximally 2 weeks before the starting of study. 5. The phase I. examination covers 5 different sequences (7 days in each), and one week was the post study period, 6. The time-table of examinations (including a short hospitalization time, 3 days for washout, post-study examinations, food and fluid intakes, etc.) were determined, 7. The schedule of the administration of drugs [ASA alone, ASA + capsaicin(oids) – given orally in doses of 400 and 800µg, or placebo] was fixed by the protocol, 8. The human healthy male subjects were randomly treated, 9. The blood samples were obtained from the brachial vena (pre-dose, 0.10, 0.20, 0.40 1.00, 1.30, 2, 4, 6, 10, 12, 16 and 24 hours post dose), 10. The capsaicin and dihydrocapsaicin measured by HPLC, ASA and salicylic acid by HPLC from the plasma of healthy volunteers (during the first 24 hours period) and 11. The effects of capsaicinoids alone, ASA alone, and their combinations were studied on the epinephrine-induced platelet aggregation, 12. Different pharmacokinetic parameters ( C max , T max , AUC 0-tlast , AUC 0- ∞ , mean residence time, MRT ) of ASA and salicylic acid were calculated and these results and were compared in treated groups [ASA alone vs . ASA plus capsaicin(oids) 400 µg vs . ASA plus capsaicin(oids) 800 µg], 12. The extents of platelet aggregation produced by ASA alone and in different combination with capsaicin(oids) on the epinephrine-induced platelet aggregation. Results : 1. The healthy male volunteers tolerated well the different drug candidate combinations, and their applications were safe, 2. Neither capsaicin nor dihydrocapsaicin could be detected in any samples of plasma volunteers after oral application of capsaicin(oids) (given orally in doses of 400 µg and 800 µg) in time period of 0 to 24 hours; 3. The pharmacokinetic parameters of ASA and salicylic acid did not differ in groups treated with ASA alone vs . ASA plus 400 µg capsaicin(oids) vs . ASA plus 800 µg capsaicin(oids), 4. The capsaicin(oids) does (do) not modify the epinephrine-induced platelet aggregation induced by ASA, meanwhile the different doses of capsaicin(oids) alone have no direct effect of the epinephrine-induce platelet aggregation. Conclusions : 1. The capsaicin(oids) acts(act) locally in the gastrointestinal tract (indicating that we used a good selection of bioadhesive compounds for pharmaceutical preparation of ASA + capsaicin(iods) combination, 2. The results of these phase I. examinations offer us a further possibility to carry out forthcoming phase II. and III. examinations in patients.

The orofacial capsaicin test in rats: effects of different capsaicin concentrations and morphine

The aim of this study was to develop a rat model of capsaicin-induced pain in the orofacial region. We examined the effects of subcutaneous injection of different doses of capsaicin (0.25, 0.4, 0.8, 1.5, 2.5, 25, 50, 100, 500 μg) on the face-grooming response. Injection of capsaicin into the vibrissa pad produced an immediate grooming of the injected area with ipsilateral fore- or hindpaw. A positive relationship between the amplitude of the grooming response and the capsaicin dose was observed until 1.5 μg, but with the highest concentrations (ranging from 25 to 500 μg) the amplitude of the response decreased. Morphine administered either systemically (in the neck, 0.5–4.0 mg/kg) or locally (0.25–1.0 mg/kg) reduced in a dose-dependent fashion the face grooming provoked by subcutaneous capsaicin (1.5 μg). The systemic and local morphine effects could be reversed by systemic (0.1 mg/kg) and local (0.05 mg/kg) administration of naloxone, respectively. The local administration of morphine (ED 50: 0.65 mg/kg) was more potent than systemic injection (ED 50: 2.54 mg/kg) in reducing the grooming behavior. In conclusion, the orofacial capsaicin test appears to be a valid and reliable method for studying trigeminal pain mechanisms and testing analgesic drugs. The results of the present study also support the clinical use of peripheral opioid administration for the treatment of orofacial painful conditions.

Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin

Psychophysical measurements of pain and mechanical hyperalgesia were obtained following different doses of capsaicin injected intradermally into the forearms of human subjects. Each subject received a 10 μ1 injection of the vehicle and capsaicin doses of 0.01, 0.1, 1, 10 and 100μg. The relationship between capsaicin dose and the magnitude and duration of pain was determined using the method of magnitude estimation. In addition to pain, capsaicin produced a flare and mechanical hyperalgesia. The area of flare and the area and time course of mechanical hyperalgesia were measured as a function of the dose of capsaicin. The magnitude and duration of pain, based on averaged responses of all subjects, increased as a negatively accelerating function of dose. The lowest dose of capsaicin to produce more pain than the vehicle was 0.1 μg. The area and duration of mechanical hyperalgesia also increased as a negatively accelerating function of dose. The lowest dose of capsaicin to produce an area of mechanical hyperalgesia was 0.1μg. An area of hyperalgesia was present within seconds following injection. For doses of 10 and 100 μg, the area of hyperalgesia grew to reach a maximum within 5 and 7 min following the injection and gradually decreased, disappearing within 15 and 137 min, respectively. Capsaicin doses of 1, 10 and 100μg produced successively greater areas of flare. The results demonstrate that humans can scale the magnitude of pain produced by capsaicin in a dose-dependent fashion. Further, the duration of pain, the area and duration of mechanical hyperalgesia, and the area of flare are dose-dependent. It is concluded that intradermal injection of capsaicin will provide a useful method of carrying out parallel psychophysical and neurophysiological studies of pain and hyperalgesia.

Desensitization and capsaicin-induced release of substance P-like immunoreactivity from guinea-pig ureter in vitro

Substance P-like immunoreactivity was assayed in superfusates of guinea-pig ureters following stimulation of afferent fibres with capsaicin, potassium chloride and the calcium channel agonist Bay K 8644. Capsaicin-evoked release of substance P-like immunoreactivity was calcium-dependent but unaffected by cobalt. Under appropriate conditions release was dose-related (ED 50 = 610nM) and reproducible. Selective desensitization to capsaicin could be demonstrated following prolonged exposure to different doses of capsaicin. No desensitization to capsaicin was observed following afferent fibre stimulation with a combination of Bay K 8644 and K +, which released a similar amount of substance P-like immunoreactivity as a desensitizing capsaicin stimulus. These data suggest that depletion of releasable substance P-like reactivity is unlikely to account for selective desensitization of ureteric primary afferent fibres to capsaicin.

Dose-response relationships in the thermoregulatory effects of capsaicin.

The hypothermic effect of capsaicin, the reduced responsiveness towards the hypothermic effect of the drug as well as the impairment of thermoregulation in the warm environment subsequent to the administration of different doses of capsaicin have been studies in rats. The mortality after capsaicin treatment has also been established. 1. Capsaicin given subcutaneously in doses of 1-10 mg/kg induced a dose-dependent fall in body temperature lasting for 2-5 h. A single dose of 10 mg/kg caused the most pronounced hypothermic effect reaching its maximum (3,4 degrees C) after 107 min. After higher doses (20-50 mg/kg) the fall in body temperature was less, being similar to that observed after the administration of 1-2 mg/kg. 2. A decreased sensitivity towards the hypothermic effect of a test dose of 2 mg/kg capsaicin, as well as an impaired tolerance to high ambient temperature have been found in rats 2 weeks after the pretreatment either with a single dose of 20-50 mg/kg or fractionated administration of 50 mg/kg capsaicin. The fractionated administration of a dose of 50 mg/kg capsaicin proved to be beneficial in decreasing mortality without affecting the desensitizing effect of capsaicin pretreatment. 3. After single doses of capsaicin the hypothermic period was followed by a dose-dependent hyperthermia which lasted for at least 2 days. A close correlation between the prolonged hyperthermic action and the desensitizing effect of capsaicin administration has also been established. The possible relationship between the desensitizing and hyperthermia inducing effect of capsaicin is briefly discussed.