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1.
Phytother Res ; 38(7): 3695-3705, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761115

RESUMO

Osteoarthritis (OA) affects hundreds of millions of people worldwide. The objective was to critically appraise the efficacy and safety of topical capsaicin in reducing pain in OA. MEDLINE (PubMed) and Embase (Ebsco) were searched from inceptions until February 2023. The eligibility criteria included randomized controlled trials (RCTs), evaluating topical capsaicin in OA patients. Standard Cochrane methods were used to extract data and to appraise eligible studies. Eight double-blind RCTs involving 498 patients were included. Five trials (62.5%) were at an overall low risk of bias, and three (37.5%) were at a high risk of bias. Meta-analysis showed that, in various OA patients, compared with placebo, topical capsaicin (0.0125%-5%) may reduce pain severity measured with visual analog scale (standardized mean difference = -0.84, 95% confidence intervals [CIs] = -1.48 to -0.19, p = 0.01; eight studies). However, topical capsaicin may increase burning sensation at the application site (risk ratio = 5.56, 95% CI = 1.75-17.69, p = 0.004, numbers needed to harm = 3; five studies) when compared with placebo. Limitations include short study durations, small sample sizes, high heterogeneity, and overall low-to-very-low certainty of the evidence. Topical capsaicin may reduce OA pain at follow-ups of up to 3 months. Larger trials, potentially evaluating capsaicin in combination with phytopharmaceuticals having anti-inflammatory effects, with longer follow-ups might be needed to reduce the existing uncertainties. Topical capsaicin might be recommended for short-term management of pain in OA patients intolerant to nonsteroidal anti-inflammatory drugs.


Assuntos
Administração Tópica , Capsaicina , Osteoartrite , Capsaicina/administração & dosagem , Capsaicina/uso terapêutico , Humanos , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Drug Res (Stuttg) ; 74(5): 195-207, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729182

RESUMO

This study examines the fundamental chemical mechanisms responsible for capsaicin's advantageous impact on cancer, specifically investigating its influence on several biological processes such as inflammation in cancer metastasis, apoptosis, angiogenesis, and cellular proliferation. This entity's connections with other signaling pathways, including PI3K/AKT, NF-B, and TRPV channels, which have been linked to tumor growth, are thoroughly examined in this work. This study presents a thorough analysis of preclinical studies and clinical trials investigating the efficacy of capsaicin in treating many forms of cancer, such as breast, prostate, colorectal, pancreatic, and others. Through tests conducted in both live organisms and laboratory settings, it has been determined that capsaicin has the ability to inhibit tumor growth and induce apoptosis in cancer cells. (in vitro and in vivo). Researchers have also looked at the results of combining capsaicin with chemotherapy medications in traditional treatment. The efficacy and bioavailability of capsaicin as a viable medicinal drug are being studied, along with ways to improve its clinical value. The present investigation carefully assesses the challenges and potential options for maximizing the therapeutic benefits of capsaicin, including customized drug delivery and personalized therapeutic strategies. In finalization, this comprehensive investigation brings together the evidence currently obtainable on the anticancer properties of capsaicin, underscoring its potential as an autonomous treatment option in the struggle against cancer. Capsaicin is a compound of significant relevance for continuing research and clinical exploration in the field of cancer treatment due to its diverse mechanisms of action and ability for boosting prevailing therapy approaches.


Assuntos
Capsaicina , Neoplasias , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo
3.
Anesthesiology ; 141(2): 250-261, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38662910

RESUMO

BACKGROUND: Nonopioid management of postsurgical pain remains a major unmet need. Few studies have evaluated transient receptor potential vanilloid subfamily member 1 agonists for analgesia after surgery. This study examines intraoperative vocacapsaicin, a novel prodrug of the transient receptor potential vanilloid subfamily member 1 agonist capsaicin, in a validated model of postsurgical pain. METHODS: This was a triple-blinded, randomized, placebo-controlled, dose-ranging trial in patients undergoing bunionectomy. Patients were randomized 1:1:1:1 to surgical site administration of 14 ml of placebo or one of three vocacapsaicin concentrations: 0.30, 0.15, or 0.05 mg/ml. The prespecified primary endpoint was the area-under-the-curve of the numerical rating scale pain score at rest through 96 h for the 0.30 mg/ml group. Prespecified ordered, secondary endpoints for the 0.30 mg/ml group included the percentage of patients who did not require opioids from 0 to 96 h, total opioid consumption through 96 h, and the area-under-the-curve of the numerical rating scale pain score for the first week. RESULTS: The 147 patients were randomized. During the first 96 h, vocacapsaicin (0.30 mg/ml) reduced pain at rest by 33% versus placebo (primary endpoint, 95% CI [10%, 52%], effect size [Cohen's d] = 0.61, P = 0.005). Of patients receiving vocacapsaicin (0.30 mg/ml), 26% did not require postoperative opioids for analgesia (P = 0.025) versus 5% of patients receiving placebo. Vocacapsaicin (0.30 mg/ml) reduced opioid consumption over the first 96 h by 50% versus placebo (95% CI [26%, 67%], effect size = 0.76, P = 0.002). Vocacapsaicin (0.30 mg/ml) reduced pain over the first week by 37% versus placebo (95% CI [12%, 57%], effect size = 0.62, P = 0.004). The treatment effect persisted for at least 2 weeks. All study endpoints showed an administered concentration-versus-response relationship. Vocacapsaicin was well tolerated with no differences between groups in any safety parameter. CONCLUSIONS: A single, local administration of vocacapsaicin during surgery reduced pain and opioid consumption for at least 96 h after surgery compared to control.


Assuntos
Capsaicina , Medição da Dor , Dor Pós-Operatória , Humanos , Dor Pós-Operatória/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Capsaicina/administração & dosagem , Capsaicina/uso terapêutico , Medição da Dor/métodos , Medição da Dor/efeitos dos fármacos , Resultado do Tratamento , Método Duplo-Cego , Relação Dose-Resposta a Droga , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Hallux Valgus/cirurgia , Pró-Fármacos/administração & dosagem , Canais de Cátion TRPV
4.
Am Fam Physician ; 109(3): 226-232, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38574212

RESUMO

Diabetic peripheral neuropathy occurs in up to 50% of patients with diabetes mellitus and increases the risk of diabetic foot ulcers and infections. Consistent screening and clear communication are essential to decrease disparities in assessment of neuropathic symptoms and diagnosis. Physicians should address underlying risk factors such as poor glycemic control, vitamin B12 deficiency, elevated blood pressure, and obesity to reduce the likelihood of developing neuropathy. First-line drug therapy for painful diabetic peripheral neuropathy includes duloxetine, gabapentin, amitriptyline, and pregabalin; however, these medications do not restore sensation to affected extremities. Evidence for long-term benefit and safety of first-line treatment options is lacking. Second-line drug therapy includes nortriptyline, imipramine, venlafaxine, carbamazepine, oxcarbazepine, topical lidocaine, and topical capsaicin. Periodic, objective monitoring of medication response is critical because patients may not obtain desired pain reduction, adverse effects are common, and serious adverse effects can occur. Opioids should generally be avoided. Nondrug therapies with low- to moderate-quality evidence include exercise and neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation. Peripheral transcutaneous electrical nerve stimulation is well tolerated and inexpensive, but benefits are modest. Other treatments, such as acupuncture, alpha-lipoic acid, acetyl-L-carnitine, cannabidiol, and onabotulinumtoxinA need further study in patients with diabetic peripheral neuropathy.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/prevenção & controle , Cloridrato de Duloxetina/uso terapêutico , Capsaicina/uso terapêutico , Gabapentina/uso terapêutico , Pregabalina/uso terapêutico , Dor/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico
5.
J Integr Neurosci ; 23(3): 64, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38538230

RESUMO

BACKGROUND: Pannexin1 (Panx1) is a membrane channel expressed in different cells of the nervous system and is involved in several pathological conditions, including pain and inflammation. At the central nervous system, the role of Panx1 is already well-established. However, in the periphery, there is a lack of information regarding the participation of Panx1 in neuronal sensitization. The dorsal root ganglion (DRG) is a critical structure for pain processing and modulation. For this reason, understanding the molecular mechanism in the DRG associated with neuronal hypersensitivity has become highly relevant to discovering new possibilities for pain treatment. Here, we aimed to investigate the role of Panx1 in acute nociception and peripheral inflammatory and neuropathic pain by using two different approaches. METHODS: Rats were treated with a selective Panx1 blocker peptide (10Panx) into L5-DRG, followed by ipsilateral intraplantar injection of carrageenan, formalin, or capsaicin. DRG neuronal cells were pre-treated with 10Panx and stimulated by capsaicin to evaluate calcium influx. Panx1 knockout mice (Panx1-KO) received carrageenan or capsaicin into the paw and paclitaxel intraperitoneally. The von Frey test was performed to measure the mechanical threshold of rats' and mice's paws before and after each treatment. RESULTS: Pharmacological blockade of Panx1 in the DRG of rats resulted in a dose-dependent decrease of mechanical allodynia triggered by carrageenan, and nociception decreased in the second phase of formalin. Nociceptive behavior response induced by capsaicin was significantly lower in rats treated with Panx1 blockade into DRG. Neuronal cells with Panx1 blockage showed lower intracellular calcium response than untreated cells after capsaicin administration. Accordingly, Panx1-KO mice showed a robust reduction in mechanical allodynia after carrageenan and a lower nociceptive response to capsaicin. A single dose of paclitaxel promoted acute mechanical pain in wildtype (WT) but not in Panx1-KO mice. Four doses of chemotherapy promoted chronic mechanical allodynia in both genotypes, although Panx1-KO mice had significant ablation in the first eight days. CONCLUSION: Our findings suggest that Panx1 is critical for developing peripheral inflammatory pain and acute nociception involving transient receptor potential vanilloid subtype 1 (TRPV1) but is not essential for neuropathic pain chronicity.


Assuntos
Hiperalgesia , Neuralgia , Ratos , Camundongos , Animais , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/patologia , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Paclitaxel/efeitos adversos , Carragenina/efeitos adversos , Cálcio , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Formaldeído/efeitos adversos , Gânglios Espinais , Proteínas do Tecido Nervoso , Conexinas/genética , Conexinas/uso terapêutico
6.
Math Biosci Eng ; 21(3): 4104-4116, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38549320

RESUMO

In this paper, Gompertz type models are proposed to understand the temporal tumor volume behavior of prostate cancer when a periodical treatment is provided. Existence, uniqueness, and stability of periodic solutions are established. The models are used to fit the data and to forecast the tumor growth behavior based on prostate cancer treatments using capsaicin and docetaxel anticancer drugs. Numerical simulations show that the combination of capsaicin and docetaxel is the most efficient treatment of prostate cancer.


Assuntos
Antineoplásicos , Neoplasias da Próstata , Masculino , Humanos , Docetaxel/uso terapêutico , Capsaicina/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
8.
J Integr Med ; 22(1): 39-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38311541

RESUMO

BACKGROUND: As one of the most common musculoskeletal ailments, chronic nonspecific low-back pain (CNLBP) causes persistent disability and substantial medical expenses. Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising. Recent guidelines indicate a reduced role for medicines in the management of CNLBP. OBJECTIVE: The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm, compared to nonsteroidal anti-inflammatory drug (NSAID) with a capsaicin plaster, in the treatment of CNLBP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a prospective multicenter randomized clinical trial enrolling patients from January 1, 2022 to December 31, 2022. A total of 156 patients with CNLBP were randomized into two parallel groups. Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally. Patients in the test group were treated with cupping and scraping using a medical device and medicated balm. MAIN OUTCOME MEASURES: Primary outcome was pain recorded using the visual analogue scale (VAS). Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale (JOA) and the traditional Chinese medicine (TCM) syndrome integral scale (TCMS) as assessment tools. RESULTS: Between baseline and postintervention, all changes in outcome metric scales were statistically significant (P < 0.001). Compared to the control group, patients in the test group had a significantly greater treatment effect in all outcome variables, as indicated by lower VAS and TCMS scores and higher JOA scores, after the one-week intervention period (P < 0.001). Further, according to the findings of multivariate linear regression analysis, the participants' pain (VAS score) was related to their marital status, age, smoking habits and body mass index. No adverse reactions were reported for any participants in this trial. CONCLUSION: The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters, regarding to pain intensity, TCM symptoms and quality of life. The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ChiCTR2200055655). Please cite this article as: He JY, Tu XY, Yin ZF, Mu H, Luo MJ, Chen XY, Cai WB, Zhao X, Peng C, Fang FF, Lü C, Li B. Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial. J Integr Med. 2024; 22(1): 39-45.


Assuntos
Dor Crônica , Dor Lombar , Humanos , Anti-Inflamatórios não Esteroides/uso terapêutico , Capsaicina/uso terapêutico , Dor Crônica/terapia , Dor Lombar/terapia , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
9.
ACS Nano ; 18(7): 5632-5646, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38344992

RESUMO

Physical stimulation with mild heat possesses the notable ability to induce immunomodulation within the tumor microenvironment (TME). It transforms the immunosuppressive TME into an immune-active state, making tumors more receptive to immune checkpoint inhibitor (ICI) therapy. Transient receptor potential vanilloid 1 (TRPV1), which can be activated by mild heat, holds the potential to induce these alterations in the TME. However, achieving precise temperature control within tumors while protecting neighboring tissues remains a significant challenge when using external heat sources. Taking inspiration from the heat sensation elicited by capsaicin-containing products activating TRPV1, this study employs capsaicin to chemically stimulate TRPV1, imitating immunomodulatory benefits akin to those induced by mild heat. This involves developing a glutathione (GSH)-responsive immunomodulatory prodrug micelle system to deliver capsaicin and an ICI (BMS202) concurrently. Following intravenous administration, the prodrug micelles accumulate at the tumor site through the enhanced permeability and retention effect. Within the GSH-rich TME, the micelles disintegrate and release capsaicin and BMS202. The released capsaicin activates TRPV1 expressed in the TME, enhancing programmed death ligand 1 expression on tumor cell surfaces and promoting T cell recruitment into the TME, rendering it more immunologically active. Meanwhile, the liberated BMS202 blocks immune checkpoints on tumor cells and T cells, activating the recruited T cells and ultimately eradicating the tumors. This innovative strategy represents a comprehensive approach to fine-tune the TME, significantly amplifying the effectiveness of cancer immunotherapy by exploiting the TRPV1 pathway and enabling in situ control of immunomodulation within the TME.


Assuntos
Acetamidas , Neoplasias , Pró-Fármacos , Piridinas , Humanos , Micelas , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Temperatura Alta , Microambiente Tumoral , Imunoterapia , Imunomodulação , Neoplasias/tratamento farmacológico
10.
Recent Adv Food Nutr Agric ; 15(1): 33-45, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38258782

RESUMO

Osteoarthritis (OA) is a progressive degenerative joint disease. It basically impairs the structural integrity of articulate cartilage and imbalances the catabolic and anabolic signals in the joint. A degenerative disease is characterized by swelling, pain, and joint stiffness. The treatment and management of osteoarthritis are based on analgesic and anti-inflammatory agents, whereas the exact cause of OA is not known yet. The negative effects of synthetic medications have led to a daily rise in the usage of nutraceuticals and dietary supplements. Clinicians are aware of these treatments, and they also recommend nutraceuticals in addition to the currently preferred therapy. Many in-vitro and in-vivo experiments have been performed in past years to evaluate the function of these on osteoarthritis. The collection of articles was published on search engines like PubMed, Scopus, Google Scholar, ResearchGate, and ScienceDirect. The evaluation covers every potential nutraceutical utilized in osteoarthritis, together with its supporting data and mode of action. The present review discusses nutraceuticals, including devil's claw, vitamin D, boswellic acid, capsaicin, ginger, curcumin, krill oil, ginger, and avocado/soybean unsaponifiable.


Assuntos
Suplementos Nutricionais , Osteoartrite , Osteoartrite/dietoterapia , Osteoartrite/tratamento farmacológico , Osteoartrite/terapia , Humanos , Capsaicina/uso terapêutico , Animais , Curcumina/uso terapêutico , Zingiber officinale/química , Vitamina D/uso terapêutico , Vitamina D/administração & dosagem , Persea/química , Triterpenos
11.
Int J Mol Sci ; 25(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38255865

RESUMO

Capsaicin, the organic compound which attributes the spicy flavor and taste of red peppers and chili peppers, has been extensively studied for centuries as a potential natural remedy for the treatment of several illnesses. Indeed, this compound exerts well-known systemic pleiotropic effects and may thus bring important benefits against various pathological conditions like neuropathic pain, rhinitis, itching, or chronic inflammation. Yet, little is known about the possible biological activity of capsaicin at the kidney level, as this aspect has only been addressed by sparse experimental investigations. In this paper, we aimed to review the available evidence focusing specifically on the effects of capsaicin on renal physiology, as well as its potential benefits for the treatment of various kidney disorders. Capsaicin may indeed modulate various aspects of renal function and renal nervous activity. On the other hand, the observed experimental benefits in preventing acute kidney injury, slowing down the progression of diabetic and chronic kidney disease, ameliorating hypertension, and even delaying renal cancer growth may set the stage for future human trials of capsaicin administration as an adjuvant or preventive therapy for different, difficult-to-treat renal diseases.


Assuntos
Injúria Renal Aguda , Neoplasias Renais , Insuficiência Renal Crônica , Humanos , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Rim , Insuficiência Renal Crônica/tratamento farmacológico
12.
Mol Med Rep ; 29(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38240083

RESUMO

Capsaicin, which is abundant in chili peppers, exerts antioxidative, antitumor, antiulcer and analgesic effects and it has demonstrated potential as a treatment for cardiovascular, gastrointestinal, oncological and dermatological conditions. Unique among natural irritants, capsaicin initially excites neurons but then 'calms' them into long­lasting non­responsiveness. Capsaicin can also promote weight loss, making it potentially useful for treating obesity. Several mechanisms have been proposed to explain the therapeutic effects of capsaicin, including antioxidation, analgesia and promotion of apoptosis. Some of the mechanisms are proposed to be mediated by the capsaicin receptor (transient receptor potential cation channel subfamily V member 1), but some are proposed to be independent of that receptor. The clinical usefulness of capsaicin is limited by its short half­life. The present review provided an overview of what is known about the therapeutic effects of capsaicin and the mechanisms involved and certain studies arguing against its clinical use were mentioned.


Assuntos
Capsaicina , Dor , Humanos , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Dor/tratamento farmacológico , Canais de Cátion TRPV , Obesidade/tratamento farmacológico , Trato Gastrointestinal
14.
Behav Brain Res ; 459: 114789, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38036264

RESUMO

Descending control of nociception (DCN), a measure of efficiency of descending pain inhibition, can be assessed in animals by the combined application of test and conditioning noxious stimuli. Evidence from pre-clinical and clinical studies indicates that this mechanism of pain control may differ between sexes and might be impaired in many chronic pain states. However, little is known about sex differences in DCN efficiency in models of acute and chronic orofacial pain. Herein, we first evaluated DCN responses in male and female rats by the applying formalin into the upper lip or capsaicin into the forepaw as the conditioning stimulus, followed by mechanical stimulation (Randall-Selitto) of the hind paw as the test stimulus. The same protocol (i.e., capsaicin in the forepaw followed by mechanical stimulation of the hind paw) was evaluated in male and female rats on day 3 after intraoral incision and on day 15 and 30 after chronic constriction injury of the infraorbital nerve (CCI-ION). Additionally, we assessed the effect of the kappa opioid receptor (KOR) antagonist Norbinaltorphimine (nor-BNI) on DCN responses of female nerve-injured rats. This study shows that naïve female rats exhibit less efficient DCN compared to males. Postoperative pain did not alter DCN responses in female and male rats, but CCI-ION induced loss of DCN responses in females but not in males. Systemic pretreatment with nor-BNI prevented the loss of DCN induced by CCI-ION in female rats. The results reveal sex differences in DCN responses and female-specific impairment of DCN following chronic orofacial pain. Moreover, the findings suggest that, at least for females, blocking KOR could be a promising therapeutic approach to prevent maladaptive changes in chronic orofacial pain.


Assuntos
Dor Crônica , Neuralgia , Feminino , Ratos , Masculino , Animais , Dor Crônica/tratamento farmacológico , Receptores Opioides kappa , Neuralgia/tratamento farmacológico , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Hiperalgesia/tratamento farmacológico , Caracteres Sexuais , Nociceptividade , Ratos Sprague-Dawley , Dor Facial/tratamento farmacológico , Antagonistas de Entorpecentes/farmacologia , Antagonistas de Entorpecentes/uso terapêutico
15.
Bioorg Chem ; 143: 107026, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103330

RESUMO

A series of novel hybrid compounds were designed, synthesized, and utilized as multi-target drugs to treat Alzheimer's disease (AD) by connecting capsaicin and tacrine moieties. The biological assays indicated that most of these compounds demonstrated strong inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities with IC50 values in the nanomolar, as well as good blood-brain barrier permeability. Among the synthesized hybrids, compound 5s displayed the most balanced inhibitory effect on hAChE (IC50 = 69.8 nM) and hBuChE (IC50 = 68.0 nM), and exhibited promising inhibitory activity against ß-secretase-1 (BACE-1) (IC50 = 3.6 µM). Combining inhibition kinetics and molecular model analysis, compound 5s was shown to be a mixed inhibitor affecting both the catalytic active site (CAS) and peripheral anionic site (PAS) of hAChE. Additionally, compound 5s showed low toxicity in PC12 and BV2 cell assays. Moreover, compound 5s demonstrated good tolerance at the dose of up to 2500 mg/kg and exhibited no hepatotoxicity at the dose of 3 mg/kg in mice, and it could effectively improve memory ability in mice. Taken together, these findings suggest that compound 5s is a promising and effective multi-target agent for the potential treatment of AD.


Assuntos
Doença de Alzheimer , Tacrina , Camundongos , Animais , Tacrina/química , Doença de Alzheimer/tratamento farmacológico , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides , Simulação de Acoplamento Molecular , Desenho de Fármacos , Relação Estrutura-Atividade
16.
Mol Pain ; 19: 17448069231210423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37845039

RESUMO

Traumatic neuropathic pain (TNP) is caused by traumatic damage to the somatosensory system and induces the presentation of allodynia and hyperalgesia. Mitochondrial dysfunction, neuroinflammation, and apoptosis are hallmarks in the pathogenesis of TNP. Recently, mitochondria-based therapy has emerged as a potential therapeutic intervention for diseases related to mitochondrial dysfunction. However, the therapeutic effectiveness of mitochondrial transplantation (MT) on TNP has rarely been investigated. Here, we validated the efficacy of MT in treating TNP. Both in vivo and in vitro TNP models by conducting an L5 spinal nerve ligation in rats and exposing the primary dorsal root ganglion (DRG) neurons to capsaicin, respectively, were applied in this study. The MT was operated by administrating 100 µg of soleus-derived allogeneic mitochondria into the ipsilateral L5 DRG in vivo and the culture medium in vitro. Results showed that the viable transplanted mitochondria migrated into the rats' spinal cord and sciatic nerve. MT alleviated the nerve ligation-induced mechanical and thermal pain hypersensitivity. The nerve ligation-induced glial activation and the expression of pro-inflammatory cytokines and apoptotic markers in the spinal cord were also repressed by MT. Consistently, exogenous mitochondria reversed the capsaicin-induced reduction of mitochondrial membrane potential and expression of pro-inflammatory cytokines and apoptotic markers in the primary DRG neurons in vitro. Our findings suggest that MT mitigates the spinal nerve ligation-induced apoptosis and neuroinflammation, potentially playing a role in providing neuroprotection against TNP.


Assuntos
Capsaicina , Neuralgia , Ratos , Animais , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Doenças Neuroinflamatórias , Ratos Sprague-Dawley , Neuralgia/metabolismo , Nervos Espinhais/metabolismo , Hiperalgesia/metabolismo , Gânglios Espinais/metabolismo , Ligadura/efeitos adversos , Citocinas/metabolismo , Apoptose
17.
Nutrients ; 15(20)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37892544

RESUMO

Capsaicin, a lipophilic, volatile compound, is responsible for the pungent properties of chili peppers. In recent years, a significant increase in investigations into its properties has allowed the production of new formulations and the development of tools with biotechnological, diagnostic, and potential therapeutic applications. Most of these studies show beneficial effects, improving antioxidant and anti-inflammatory status, inducing thermogenesis, and reducing white adipose tissue. Other mechanisms, including reducing food intake and improving intestinal dysbiosis, are also described. In this way, the possible clinical application of such compound is expanding every year. This opinion article aims to provide a synthesis of recent findings regarding the mechanisms by which capsaicin participates in the control of non-communicable diseases such as obesity, diabetes, and dyslipidemia.


Assuntos
Capsicum , Neuralgia , Capsaicina/uso terapêutico , Capsaicina/farmacologia , Neuralgia/tratamento farmacológico , Obesidade/tratamento farmacológico
18.
Diabetes Metab J ; 47(6): 743-756, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37670573

RESUMO

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of patients with diabetes experience neuropathic pain, referred to as "painful DPN." Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Neuralgia , Estados Unidos , Humanos , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/tratamento farmacológico , Capsaicina/uso terapêutico , Qualidade de Vida , Cloridrato de Duloxetina/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Diabetes Mellitus/tratamento farmacológico
19.
J Complement Integr Med ; 20(4): 714-720, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37712769

RESUMO

OBJECTIVES: To investigate the effects of solid lipid microparticle (SLM) creams containing a long pepper extract (LPE) or piperine on neuropathy-related pain and the expression of glial fibrillary acidic protein (GFAP) as a measure of astrogliosis. METHODS: Neuropathic pain in male Spraque Dawley rats was induced by sciatic nerve ligation (SNL) and followed by treatment with LPE-SLM, piperine-SLM, capsaicin or vehicle creams. The pain score was assessed by thermal hyperalgesia test. The GFAP expression in the spinal cord was determined by immunohistochemistry. RESULTS: Pain scores were significantly increased after SNL and decreased when treated by LPE-SLM. The number of GFAP immunopositive cells was significantly increased in the SNL rats. Treated by LPE-SLM and capsaicin creams resulted in a significant reduction of the number of GFAP immunopositive cells. The LPE-SLM treated rats showed greater effects than the piperine and capsaicin preparations. CONCLUSIONS: The LPE-SLM cream has a potential effect on pain attenuation via a decrease of spinal astrocyte activation-related mechanism. The LPE in SLM preparation could provide an alternative therapeutic strategy for treating neuropathic pain.


Assuntos
Astrócitos , Neuralgia , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Astrócitos/metabolismo , Capsaicina/farmacologia , Capsaicina/metabolismo , Capsaicina/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Medula Espinal/metabolismo , Hiperalgesia/tratamento farmacológico
20.
Pain Manag ; 13(10): 613-626, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37750226

RESUMO

Prescription-strength (8%) capsaicin topical system is a US FDA-approved treatment for painful diabetic peripheral neuropathy of the feet. A 30 min application of the capsaicin 8% topical system can provide sustained (up to 3 months) local pain relief by desensitizing and reducing TRPV1-expressing cutaneous fibers. Capsaicin is not absorbed systemically; despite associated application-site discomfort, capsaicin 8% topical system is well tolerated, with no known drug interactions or contraindications, and could offer clinical advantages over oral options. Capsaicin 8% topical system are not for patient self-administration and require incorporation into office procedures, with the added benefit of treatment compliance. This article reviews existing literature and provides comprehensive, practical information regarding the integration of capsaicin 8% topical systems into office procedures.


Capsaicin 8% topical system is used to treat diabetic nerve pain of the feet. This in-office 30 min application can provide lasting relief of pain (for up to 3 months) by targeting the nerves damaged by diabetes. Since capsaicin acts at the site of diabetic nerve pain without being absorbed into the bloodstream, it is unlikely to interfere with other treatments and has few undesirable effects. Discomfort at the application site is the most commonly reported adverse event. Capsaicin 8% topical system must be applied by a healthcare professional and up to four topical systems can be used per treatment. Incorporating the use of capsaicin 8% topical systems into office procedures can help provide relief for patients living with diabetic nerve pain of the feet and may improve treatment compliance.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Capsaicina/uso terapêutico , Capsaicina/efeitos adversos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/induzido quimicamente , Administração Tópica , Dor/tratamento farmacológico , Administração Cutânea , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico
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