Protective Effect Of Capsaicin Research Articles

Capsaicin mitigates ventilator-induced lung injury by suppressing ferroptosis and maintaining mitochondrial redox homeostasis through SIRT3-dependent mechanisms

BackgroundVentilator-induced lung injury (VILI) is one of the severe complications in the clinic concerning mechanical ventilation (MV). Capsaicin (CAP) has anti-inflammatory and inhibitory effects on oxidative stress, which is a significant element causing cellular ferroptosis. Nevertheless, the specific role and potential mechanistic pathways through which CAP modulates ferroptosis in VILI remain elusive.MethodsVILI was established in vivo, and the pulmonary epithelial cell injury model induced by circulation stretching (CS) was established in vitro. Both mice and cells were pretreated with CAP. Transmission electron microscopy, ELISA, Western blot, immunofluorescence, RT-PCR, fluorescent probes, and other experimental methods were used to clarify the relationship between iron death and VILI in alveolar epithelial cells, and whether capsaicin alleviates VILI by inhibiting iron death and its specific mechanism.ResultsFerroptosis was involved in VILI by utilizing in vivo models. CAP inhibited ferroptosis and alleviated VILI's lung damage and inflammation, and this protective effect of CAP was dependent on maintaining mitochondrial redox system through SITR3 signaling. In the CS-caused lung epithelial cell injury models, CAP reduced pathological CS-caused ferroptosis and cell injury. Knockdown SIRT3 reversed the role of CAP on the maintaining mitochondria dysfunction under pathological CS and eliminated its subsequent advantageous impacts for ferroptosis against overstretching cells.ConclusionThe outcomes showed that CAP alleviated ferroptosis in VILI via improving the activity of SITR3 to suppressing mitochondrial oxidative damage and maintaining mitochondrial redox homeostasis, illustrating its possibility as a novel therapeutic goal for VILI.Graphical

Protective Effects of Capsaicin on Experimental Testicular Torsion and Detorsion Injury

Protective Effects of Capsaicin on Experimental Testicular Torsion and Detorsion Injury

Analysis of the Ability of Capsaicin to Modulate the Human Gut Microbiota In Vitro.

Previous studies on capsaicin, the bioactive compound in chili peppers, have shown that it may have a beneficial effect in vivo when part of a regular diet. These positive health benefits, including an anti-inflammatory potential and protective effects against obesity, are often attributed to the gut microbial community response to capsaicin. However, there is no consensus on the mechanism behind the protective effect of capsaicin. In this study, we used an in vitro model of the human gut microbiota to determine how regular consumption of capsaicin impacts the gut microbiota. Using a combination of NextGen sequencing and metabolomics, we found that regular capsaicin treatment changed the structure of the gut microbial community by increasing diversity and certain SCFA abundances, particularly butanoic acid. Through this study, we determined that the addition of capsaicin to the in vitro cultures of the human gut microbiome resulted in increased diversity of the microbial community and an increase in butanoic acid. These changes may be responsible for the health benefits associated with CAP consumption.

Capsaicin Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction in Intestinal Porcine Epithelial Cell Line-J2.

Capsaicin is a spicy, highly pungent, colorless, vanilloid compound found in chili peppers with anti-inflammatory, antioxidant, anti-cancer, and analgesic properties. However, the protective effects of capsaicin on the pig intestine during inflammation are yet to be explored. This study investigated the effects of capsaicin on the gut inflammatory response, intestinal epithelial integrity, and gene expression level of nutrient transporters in a model of lipopolysaccharide (LPS)-induced inflammation in non-differentiated intestinal porcine epithelial cell line-J2 (IPEC-J2). The results showed that the pre-treatment of cells with capsaicin (100 μM) significantly decreased the gene expression and secretion of proinflammatory cytokines induced by LPS through Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. In addition, pre-treatment of cells with capsaicin also increased both gene and protein abundance of tight junction proteins. Furthermore, pre-treatment cells with capsaicin significantly increased trans-epithelial electrical resistance (TEER) and decreased permeability of fluorescein isothiocyanate-dextran (FD4) from the apical side to the basolateral side compared with the control (P < 0.05). Additionally, pre-treatment of cells with capsaicin upregulated the mRNA abundance of nutrients transporters such as Na+/glucose cotransporter 1 (SGLT1). These results suggested that capsaicin could attenuate LPS-induced inflammation response through TLR4/NF-κB pathway and improve barrier integrity and glucose absorption.

The protective effect of Capsaicin (Capsicum annum L) against the induction of Aflatoxin B1 in hepatocytes: A study of liver Histopathology in mice (Mus musculus)

The protective effect of Capsaicin (Capsicum annum L) against the induction of Aflatoxin B1 in hepatocytes: A study of liver Histopathology in mice (Mus musculus)

Protective Effect of Capsaicin against Doxorubicin Induced Cardiotoxicity in Experimental Rats

Protective Effect of Capsaicin against Doxorubicin Induced Cardiotoxicity in Experimental Rats

Capsaicin has potent anti-oxidative effects in vivo through a mechanism which is non-receptor mediated

Capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) is the active ingredient of chilli peppers and is responsible for the characteristic pungency. The ubiquitous human consumption of chilli peppers indicates their influence on human health. The effect of capsaicin through sensory neurons via TRPV1 activation has been well studied, but its non-neuronal effects are still not extensively explored. The purpose of this study was to investigate the in vivo antioxidant effect of capsaicin on erythrocytes of male Wistar rats. Markers of oxidative stress in blood were determined by assessing the plasma total antioxidant potential, activity of plasma membrane redox system, intracellular glutathione (GSH) level, ROS level, protein oxidation and lipid peroxidation. Results of this study suggest a significant protective effect of capsaicin against oxidative stress by enhancing FRAP, GSH level, PMRS activity and ameliorating ROS, MDA, PCO and AOPP.

Tsc1/Tsc2 complex: A molecular target of capsaicin for protection against testicular torsion induced injury in rats

ObjectiveThe detailed knowledge about protective effects of capsaicin (cap) and involved mechanisms against testicular torsion (TT) is still not available completely. MethodsMale Wistar rats were assigned into four major cohorts: (i) sham, (ii) TT, (iii) three subgroups subjected to TT and different doses of cap (100, 500, and 1000 µg/mL), and (iv) three subgroups of healthy animals subjected to various concentrations of cap. The animals were decapitated at 24 h after reperfusion, and the evaluation of protein expression was performed by Western blotting assay. At 72 h after reperfusion, apoptotic cell death and tissue injury were evaluated by TUNEL nuclear and H&E staining, respectively. ResultsThe results showed that cap administration following TT significantly increased the expression of tuberous sclerosis proteins 1 and 2 (Tsc1/Tsc2) in a dose-dependent manner (P < 0.05). Cap decreased cell apoptosis at highest dose. Likewise, cap contributed to the preservation of tubular morphology and decreased tissue injury at the highest tested concentration (1000 µg/mL). ConclusionCollectively, our findings demonstrate the validity of cap as a therapeutic agent against TT through targeting Tsc1/Tsc2 in a dose-dependent manner.

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.

Capsaicin ameliorates cisplatin-induced renal injury through induction of heme oxygenase-1.

Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.

Capsaicin inhibits benzo(a)pyrene-induced lung carcinogenesis in an in vivo mouse model

Lung cancer is a serious health problem in most developed countries and its incidence rate is profusely increasing. Capsaicin, a component of red chilli and red pepper has been studied widely for its chemopreventive properties. The aim of the present study is to explore the anti-tumor activity of capsaicin against benzo(a)pyrene-induced lung tumorigenesis in Swiss albino mice. Benzo(a)pyrene was administered orally (50 mg/kg body weight) to induce lung cancer in Swiss albino mice. Hematological study (hemoglobin content, RBC, WBC count and differential count), histochemical analysis of mast cells and Western blot analysis of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) were carried out. Hematological parameters and the histochemical analysis of mast cells showed abnormal changes, and the immunoblotting analysis revealed increased protein expression of TNF-α, IL-6, COX-2 and NF-κB in lung cancer-challenged mice administered with benzo(a)pyrene. Capsaicin (10 mg/kg body weight) supplementation to lung cancer bearing mice considerably prevented all the above abnormalities. The results of the present study indicate the protective effect of capsaicin against benzo(a)pyrene-induced lung carcinogenesis in mice.

Capsaicin protects mouse neuromuscular junctions from the neuroparalytic effects of botulinum neurotoxin a.

Botulinum neurotoxin A (BoNT/A), the most toxic, naturally occurring protein, cleaves synapse-associated protein of 25 kDa and inhibits acetylcholine release from motor nerve endings (MNEs). This leads to paralysis of skeletal muscles. Our study demonstrates that capsaicin protects mouse neuromuscular junctions from the neuroparalytic effects of BoNT/A. Bilateral injection of BoNT/A near the innervation of the Extensor digitorum longus (EDL) muscle of adult Swiss-Webster mice inhibited the toe spread reflex (TSR). However, when capsaicin was coinjected bilaterally, or injected 4 or 8 h before injecting BoNT/A, the TSR remained normal. In animals that were pretreated with capsazepine, capsaicin failed to protect against the neuroparalytic effects of BoNT/A. In vivo analyses demonstrated that capsaicin protected muscle functions and electromygraphic activity from the incapacitating effects of BoNT/A. The twitch response to nerve stimulation was greater for EDL preparations isolated from mice injected with capsaicin before BoNT/A. Capsaicin pretreatment also prevented the inhibitory effects of BoNT/A on end-plate currents. Furthermore, pretreatment of Neuro 2a cells with capsaicin significantly preserved labeling of synaptic vesicles by FM 1-43. This protective effect of capsaicin was observed only in the presence of extracellular Ca(2+) and was inhibited by capsazepine. Immunohistochemistry demonstrated that MNEs express transient receptor potential protein of the vanilloid subfamily, TRPV1, the capsaicin receptor. Capsaicin pretreatment, in vitro, reduced nerve stimulation or KCl-induced uptake of BoNT/A into motor nerve endings and cholinergic Neuro 2a cells. These data demonstrate that capsaicin interacts with TRPV1 receptors on MNEs to reduce BoNT/A uptake via a Ca(2+)-dependent mechanism.

Protective effects of Δ 9-tetrahydrocannabinol against N-methyl- d-aspartate-induced AF5 cell death

The neuroprotective effects of Δ 9-tetrahydrocannabinol (THC) were examined using an in vitro model in which the AF5 CNS cell line was exposed to toxic levels of N-methyl- d-aspartate (NMDA), an agonist of the NMDA glutamate receptor. NMDA toxicity was reduced by THC, but not by the more specific cannabinoid receptor agonist, WIN55,212-2. Addition of dibutyryl cAMP (dbcAMP) to the culture medium did not alter the neuroprotective effect of THC and did not unmask a neuroprotective effect of WIN55,212-2. The cannabinoid antagonist SR141716A did not inhibit the neuroprotection induced by THC or alter the response to WIN55,212-2, even in the presence of dbcAMP, indicating that the neuroprotective effect of THC was cannabinoid receptor-independent. On the other hand, both THC and WIN55,212-2 produced cellular toxicology at higher dosages, an effect which was blocked in part by SR141716A. Capsaicin, an antioxidant and vanilloid receptor agonist, also produced a protective effect against NMDA toxicology. The protective effect of capsaicin was blocked by co-application of ruthenium red, but was not blocked by the specific vanilloid receptor antagonist capsazepine, and the transient receptor potential vanilloid type 1 (TRPV1) and ANKTM1 transcripts were not detected in AF5 cells. Thus, the neuroprotective effects of THC and capsaicin did not appear to be mediated by TRP ion channel family receptors. The antioxidant α-tocopherol prevented neurotoxicity in a dose-dependent manner. Therefore, THC may function as an antioxidant to increase cell survival in NMDA-induced neurotoxicity in the AF5 cell model, while higher dosages produce toxicity mediated by CB1 receptor stimulation.

Protective Effects of Capsaicin against Cisplatin-Induced Nephrotoxicity in Rats

Cisplatin-induced nephrotoxicity is related to an increase in lipid peroxidation and oxygen free radicals in a kidney. In the present study, we investigated the effect of the dietary antioxidants, capsaicin (Cap), against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. Nephrotoxicity induced by treatment with a single dose of cisplatin (5 mg/kg body weight i.p.). The animals were divided into 4 groups. Cap (10 mg/kg/d) was given by gavage from the same day of cisplatin injection. Cisplatin administration resulted in significant increases in the kidney weight as a percentage of the total body weight, urine volume, serum creatinine, and blood urea nitrogen by about 132, 315, 797, and 556% in comparison with the control rats, respectively (p < 0.05). Also, the renal tissue from the cisplatin-treated rats showed significant decreases in the kidney glutathione (GSH) content and superoxide dismustase (SOD) activity and a significant increase in malondialdehyde (MDA) production in comparison to the values at 0 h (p < 0.05). Seven days after Cap plus cisplatin treatments, the renal damage induced by cisplatin recovered to a significant statistically level. In addition, Cap prevented the rise of MDA and the reduction of SOD activities. These results suggest that Cap has protective effects against cisplatin-induced nephrotoxicity and lipid peroxidation in rats.

Expression of vanilloid receptors in rat gastric epithelial cells: role in cellular protection

Vanilloid receptors subtype 1 (VR1), a nonselective cation channel responsive to capsaicin, protons, and noxious heat, has been recently identified in not only neural but also non-neural cells. In the present study, we demonstrated the peripheral expression of VR1 in gastric mucosal epithelial cells and investigated the role of the receptor in cellular protection. The rat gastric mucosal epithelial cell line was used. The expression of VR1 was examined by Western blotting and RT–PCR. Cell damage was induced by immersion in 10% ethanol or acid (pH 4.0) for 30 min, and cell viability was determined by MTT assay. Capsaicin or resiniferatoxin was added 30 min before the challenge with ethanol or acid, while capsazepine or ruthenium red (a VR1 antagonist) was added simultaneously with capsaicin. The distinct expression of VR1 protein and mRNA was detected in rat gastric mucosal epithelial cell line as well as in the rat stomach and spinal cord by Western blotting and RT–PCR, respectively. The cDNA sequence of the PCR product was found to be almost identical to that of the authentic VR1 (99.8%) when the product was subcloned and sequenced. On the other hand, the cell damage induced by ethanol or acid was dose-dependently prevented by pretreatment with capsaicin. The protective effect of capsaicin was mimicked by resiniferatoxin and almost totally abolished by co-addition of capsazepine or ruthenium red. These findings suggest that VR1 is expressed peripherally in gastric mucosal epithelial cells and plays a cellular protective role.

Evidence for the direct gastric protective effect of capsaicin in human healthy subjects

Evidence for the direct gastric protective effect of capsaicin in human healthy subjects

Endotoxin-Mediated Intestinal Damage: Protective Effect of Capsaicin in the Rat

Background: Endotoxin provokes the disruption of intestinal mucosal architecture. To investigate whether afferent fibers of the enteric nervous system are involved in this damage, we have used capsaicin to induce a selective, long-lasting degeneration of these fibers in the rat. Methods: The rats were divided in two groups, receiving subcutaneously either capsaicin or its vehicle. After 10 days the rats from each group were injected with nonlethal doses of endotoxin or with saline. The next day all the animals were killed, and the jejunum and ascending colon were collected for light and scanning electron microscopy analysis; morphometric analysis of jejunal villus height was also performed. Results: The rats receiving endotoxin but not pretreated with capsaicin had severe morphologic alterations and a significant reduction in villus height. In contrast, the rats pretreated with capsaicin and then with endotoxin showed a preserved mucosa with normal mean villus height. Conclusions: Capsaicin pretreatment is able to prevent endotoxin-induced damage of intestinal mucosa; this result seems to indicate that afferent fibers of the enteric nervous system are involved in the pathogenesis of this damage.

The indomethacin-induced gastric mucosal damage in rats. Effect of gastric acid, acid inhibition, capsaicin-type agents and prostacyclin

In pylorus-ligated rats subcutaneous (sc) pentagastrin (325.5 nmol/kg) or histamine (54.3 μmol/kg), but not the cholinergic linergic agent bethanechol (7.6 or 15.2 μmol/kg), increased gastric mucosal injury by sc indomethacin (55.8 μmol/kg). Intragastric (ig) administration of 0.15 or 0.3 N HCl greatly potentiated injury by sc indomethacin with widespread ulceration, intragastric bleeding and even perforation. The gastric mucosal damage produced by indomethacin plus 0.3 N HCl was reduced by ig capsaicin (3.1–25.1 μM), ig resiniferatoxin (0.38-6.1 μM), by sc atropine (0.15-1.2 μmol/kg) and to a lesser extent by ig prostacyclin (40–267 μM) or sc cimetidine (198.2 μmol/kg). The protective effect of capsaicin or resiniferatoxin was not prevented by atropine or cimetidine treatment. Capsaicin (6.5 mM) enhanced gastric injury by sc or ig indomethacin. Results indicate the importance of early vascular events in the pathogenesis of mucosal injury induced by indomethacin in the stomach and suggest a role for gastric acid in potentiation of such injury. Results further strengthen the idea of a protective role for capsaicin-sensitive sensory nerves in the stomach.

A monoclonal antibody to calcitonin gene-related peptide abolishes capsaicin-induced gastroprotection

Calcitonin gene-related peptide (CGRP) released from vasodilator nerves is implicated in the gastroprotective action of capsaicin. This experimental paradigm was used to prove the effectiveness of a monoclonal anti-CGRP antibody. The experiments were performed in anaesthetized rats in which intragastric capsaicin (0.5 mg/kg) reduced gastric injury due to ethanol (50%) by 72%. The protective effect of capsaicin was abolished by close arterial administration of the anti-CGRP antibody #4901 (5 mg) to the stomach. A monoclonal antibody to keyhole limpet haemocyanin was without effect. These data establish anti-CGRP antibody #4901 as a tool to neutralize endogenously released CGRP and show that CGRP is indispensable for the gastroprotective action of capsaicin.

The Role of Capsaicin-Sensitive Afferent Nerves in Protective Effect of Capsaicin against Absolute Ethanol-Induced Gastric Lesions in Rats

The role of capsaicin-sensitive afferent nerves in gastroprotection by capsaicin was investigated in the absolute ethanol-induced gastric lesion model in rats. Capsaicin (0.1 and 0.5 mg/kg, p.o.) inhibited the lesion formation dose-dependently. The protective effect of capsaicin was attenuated by indomethacin-pretreatment and disappeared in capsaicin-sensitive nerve degenerated rats. Capsaicin did not induce the distension of gastric mucosal folds. These results suggested that stimulation of capsaicin-sensitive afferent nerves by capsaicin would enhance the prostaglandin formation, leading to an inhibition of gastric lesions.