Anti-inflammatory effects of Mentha pulegium L. extract on human peripheral blood mononuclear cells are mediated by TLR-4 and NF-κB suppression.

There is great interest in evaluating the anti-inflammatory properties of new herbal products. Thus, the effects of Mentha pulegium L. extract on gene and protein expressions of pro-inflammatory mediators and transcription factors were determined. The hydro-ethanolic extract of Mentha pulegium L. was obtained and optimal non-cytotoxic concentrations of the extract were determined by MTT assay. Then, three different concentrations of Mentha pulegium L. (10, 30, and 90 µg/mL) were used to pre-treat the lipopolysaccharide (LPS)-stimulated and non-stimulated peripheral blood mononuclear cells (PBMCs) of 10 healthy individuals. Finally, the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, Toll-like receptor-4 (TLR-4), nuclear factor-kappa B (NF-κB) p65, activator protein-1 (AP-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) gene expressions and TNF-α, IL-1ß, IL-6, TLR-4, prostaglandin E2 (PGE2), and COX-2 protein levels were measured. MTT results showed that there is no significant difference in cell viability among 10, 20, 40, and 80 µg/mL concentrations of Mentha pulegium L. extract at 24, 48, and 72 h (P > 0.05). The IC50 values were 236.1, 147.0, and 118.0 µg/mL after 24, 48, and 72 h respectively. TNF-α, IL-1ß, IL-6, TLR-4, iNOS, and NF-κB p65 mRNA levels in the pre-treated LPS-stimulated PBMCs were concentration-dependently reduced (P < 0.01 for TNF-α, TLR-4, and NF-κB p65; P < 0.05 for IL-1ß, IL-6, and iNOS). Also, the protein levels of pro-inflammatory mediators decreased and these differences were significant for TNF-α, IL-1ß, and TLR-4 (P < 0.001, P < 0.01, and P < 0.001, respectively). Mentha pulegium L. extract decreased the expression and biosynthesis of pro-inflammatory mediators. These effects are mainly mediated by TLR-4 and NF-κB suppression. Thus, Mentha pulegium L. could be useful in treating or ameliorating chronic inflammatory diseases.

Therapeutic potency of curcumin for allergic diseases: A focus on immunomodulatory actions.

In light of increasing research evidence on the molecular mechanisms of allergic diseases, the crucial roles of innate and acquired immunity in the disease's pathogenesis have been well highlighted. In this respect, much attention has been paid to the modulation of unregulated and unabated inflammatory responses aiming to suppress pathologic immune responses in treating allergic diseases. One of the most important natural compounds with a high potency of immune modulation is curcumin, an active polyphenol compound derived from turmeric, Curcuma longa L. Curcumin's immunomodulatory action mainly arises from its interactions with an extensive collection of immune cells such as mast cells, eosinophils, epithelial cells, basophils, neutrophils, and lymphocytes. Up to now, there has been no detailed investigation of curcumin's immunomodulatory actions in allergic diseases. So, the present review study aims to prepare an overview of the immunomodulatory effects of curcumin on the pathologic innate immune responses and dysregulated functions of T helper (TH) subtypes, including TH1, TH2, TH17, and regulator T cells (Tregs) by gathering evidence from several studies of In-vitro and In-vivo. As the second aim of the present review, we also discuss some novel strategies to overcome the limitation of curcumin in clinical use. Finally, this review also assesses the therapeutic potential of curcumin regarding its immunomodulatory actions in allergic diseases.

Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases.

Helicobacter pylori is a significant human pathogen of the stomach's epithelial lining. This type of carcinogen is associated with gastric cancer, indigestion, peptic ulcers, and upper digestive diseases. Therefore, successful treatment and eradication of this bacterium are required to reduce the prevalence of these diseases, especially in high-risk individuals. Moreover, some concerns exist regarding the extensive use of elimination therapy, such as anti-microbial resistance and rising H. pylori-associated diseases. Since there is still no effective vaccine, finding alternative therapies would appear to be a worthwhile pursuit. In this regard, curcumin exhibits anti-inflammatory, anti-carcinogenic, anti-oxidant properties and is widely used as a natural product-derived medicine or nutraceutical. Furthermore, curcumin has been reported to have anti-bacterial activity. Therefore, curcumin might be an effective herbal-based medicine for preventing, managing, or treating H. pylori infection. This review discusses the anti-inflammatory, anti-cancer, and anti-bacterial properties of curcumin as it pertains to gastric cancer and H. pylori-associated diseases.

Berberine as a natural modulator of inflammatory signaling pathways in the immune system: Focus on NF-κB, JAK/STAT, and MAPK signaling pathways.

Three main inflammatory signaling pathways include nuclear factor-κB (NF-κB), Janus kinases/Signal transducer and activator of transcriptions (JAKs/STATs), and mitogen-activated protein kinases (MAPKs) play crucial roles in inducing, promoting, and regulating inflammatory responses in the immune system. Importantly, the breakdown of mechanisms that tightly regulate inflammatory signaling pathways can be the underlying cause of uncontrolled inflammatory responses and be associated with the generation and development of several inflammatory diseases. Hence, therapeutic strategies targeting inflammatory signaling pathways and their downstream components may promise to treat inflammatory diseases. Studies over the past two decades have provided important information on the polytrophic pharmacological and biochemical properties of berberine (BBR) as a naturally occurring compound, such as antioxidant, antitumor, antimicrobial, and antiinflammatory activates. Interestingly, the modulatory effects of BBR on inflammatory signaling cascades, which lead to the inhibition of inflammation, have been widely investigated in several in vitro and in vivo studies. For the first time, herein, this comprehensive review attempts to put together these studies and provide important insight into the modulatory effects of BBR on NF-κB, JAKs/STATs, and MAPKs signaling pathways in vitro in various types of immune cells and in vivo in several experimental inflammatory diseases. As the second achievement of this review, we also explore the therapeutic efficacy and antiinflammatory effects of BBR regarding its modulatory action.

An overview of the therapeutic effects of curcumin in reproductive disorders with a focus on the antiinflammatory and immunomodulatory activities.

Curcumin, the polyphenolic compound obtained from turmeric, has several pharmacological properties. These properties include antioxidant, antimicrobial, anti-angiogenic, anticarcinogenic, antiinflammatory, and immunomodulatory activities. Therefore, the clinical efficacy of this substance has been largely investigated for curing numerous disorders. Based on a growing body of literature, this review aimed to investigate curcumin's molecular and clinical effects on reproduction and related disorders. Curcumin in the female reproductive system attenuates folliculogenesis, promotes apoptosis of oocytes and blastocyst, and decreases embryo implantation and survival. Curcumin at <100 mg concentration shows protective effects against testicular injury. The concentration of >250 mg of curcumin exhibits immobilizing action on sperms, and at 500 mg concentration completely blocks pregnancy. Curcumin inhibits vaginal infections, attenuates the severity of the premenstrual syndrome, ameliorates inflammatory conditions in polycystic ovary syndrome, improves preeclampsia, and prevents ectopic endometrial lesions. Taken together, curcumin, because of the numerous biological activities, low level of toxicity, and lower adverse effects compared to the synthetic drugs, could be considered as a protective agent for preserving the semen quality parameters, a contraceptive, and chemotherapeutic or chemopreventive agent, as well as an appropriate agent for the treatment of female reproductive disorders.

Effectiveness of Curcumin on Outcomes of Hospitalized COVID-19 Patients: A Systematic Review of Clinical Trials.

Despite the ongoing vaccination efforts, there is still an urgent need for safe and effective treatments to help curb the debilitating effects of COVID-19 disease. This systematic review aimed to investigate the efficacy of supplemental curcumin treatment on clinical outcomes and inflammation-related biomarker profiles in COVID-19 patients. We searched PubMed, Scopus, Web of Science, EMBASE, ProQuest, and Ovid databases up to 30 June 2021 to find studies that assessed the effects of curcumin-related compounds in mild to severe COVID-19 patients. Six studies were identified which showed that curcumin supplementation led to a significant decrease in common symptoms, duration of hospitalization and deaths. In addition, all of these studies showed that the intervention led to amelioration of cytokine storm effects thought to be a driving force in severe COVID-19 cases. This was seen as a significant (p < 0.05) decrease in proinflammatory cytokines such as IL1ß and IL6, with a concomitant significant (p < 0.05) increase in anti-inflammatory cytokines, including IL-10, IL-35 and TGF-α. Taken together, these findings suggested that curcumin exerts its beneficial effects through at least partial restoration of pro-inflammatory/anti-inflammatory balance. In conclusion, curcumin supplementation may offer an efficacious and safe option for improving COVID-19 disease outcomes. We highlight the point that future clinical studies of COVID-19 disease should employ larger cohorts of patients in different clinical settings with standardized preparations of curcumin-related compounds.

Nanomicellar Curcumin Supplementation Improves the Clinical Manifestations of HAM/TSP Patients.

BACKGROUND: HTLV-1 infection causes a chronic, progressive, demyelinating, neuroinflammatory disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Treatment of HAM/TSP patients which have high levels of proviral load and pro-inflammatory markers is a challenge for clinicians. Therefore, we aimed to investigate the immunomodulatory, anti-inflammatory, and antiviral effects of curcumin in HAM/TSP patients. METHODS: In this study, 20 newly diagnosed HAM/TSP patients (2 men and 18 women) were enrolled and evaluated for clinical symptoms, HTLV-1 proviral load, Tax and HBZ expression, neopterin serum concentration, and complete blood count (CBC) before and 12 weeks after treatment with nanomicellar curcumin (80 mg/day, orally). RESULTS: Clinical symptoms such as the mean Osame Motor Disability Score and Ashworth Spasticity Scale Score were significantly improved after the treatment (P = 0.001 and P = 0.001). Sensory symptoms such as pain and paresthesia were significantly decreased in all of the patients (P = 0.001). Furthermore, urinary disorders, including urinary frequency, incontinence, and the feeling of incomplete bladder emptying, were significantly improved (P = 0.001, P = 0.003, and P = 0.03). However, the mean HTLV-1 proviral load (P = 0.97) and CBC were similar, whereas Tax, HBZ, and neopterin levels tend to increase after the treatment (P = 0.004, P = 0.08, and P = 0.04). CONCLUSION: Results suggest that curcumin can safely improve the clinical symptoms of HAM/TSP patients but has no observable positive effects on the HTLV-1 proviral load, Tax, and HBZ expression. Therefore, prolonged use or the use of curcumin with antiviral agents in addition to clinical signs and symptoms can reduce the HTLV-1 proviral load and the expression of functional viral factors such as Tax and HBZ.

Obstacles against the Marketing of Curcumin as a Drug.

Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb Curcuma longa, has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it's interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug.

Curcumin: a modulator of inflammatory signaling pathways in the immune system.

Curcumin is a natural compound derived from the spice, turmeric, that has been extensively reported for its efficacy in controlling or treatment of several inflammatory diseases. There is a growing body of literature that recognizes the anti-inflammatory effects of curcumin in the immune system. On the other hand, the role of inflammatory signaling pathways has been highlighted in the pathogenesis of several inflammatory diseases, and signaling molecules involved in these pathways are considered as valuable targets for new treatment approaches. We aimed to provide a comprehensive overview of the modulatory effects of curcumin on inflammatory signaling pathways which leads to inhibition of inflammation in different types of immune cells and animal models. In this comprehensive review, we elaborate on how curcumin can effectively inhibit multiple signaling molecules involved in inflammation including NF-κB, JAKs/STATs, MAPKs, ß-catenin, and Notch-1.