Therapeutic potential of phytochemicals for cystic fibrosis.

The aim of this review was to review and discuss various phytochemicals that exhibit beneficial effects on mutated membrane channels, and hence, improve transmembrane conductance. These therapeutic phytochemicals may have the potential to decrease mortality and morbidity of CF patients. Four databases were searched using keywords. Relevant studies were identified, and related articles were separated. Google Scholar, as well as gray literature (i.e., information that is not produced by commercial publishers), were also checked for related articles to locate/identify additional studies. The relevant databases were searched a second time to ensure that recent studies were included. In conclusion, while curcumin, genistein, and resveratrol have demonstrated effectiveness in this regard, it should be emphasized that coumarins, quercetin, and other herbal medicines also have beneficial effects on transporter function, transmembrane conductivity, and overall channel activity. Additional in vitro and in vivo studies should be conducted on mutant CFTR to unequivocally define the mechanism by which phytochemicals alter transmembrane channel function/activity, since the results of the studies evaluated in this review have a high degree of heterogenicity and discrepancy. Finally, continued research be undertaken to clearly define the mechanism(s) of action and the therapeutic effects that therapeutic phytochemicals have on the symptoms observed in CF patients in an effort to reduce mortality and morbidity.

Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases.

Chemokines belong to the family of cytokines with chemoattractant properties that regulate chemotaxis and leukocyte migration, as well as the induction of angiogenesis and maintenance of hemostasis. Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Chemokines and chemokine receptors are influenced/modulated by curcumin. Thus, the current review focuses on the molecular mechanisms associated with curcumin's effects on chemoattractant cytokines, as well as putting into context the many studies that have reported curcumin-mediated regulatory effects on inflammatory conditions in the organs/systems of the body (e.g., the central nervous system, liver, and cardiovascular system). Curcumin's effects on viral and bacterial infections, cancer, and adverse pregnancy outcomes are also reviewed.

Immunomodulatory Therapeutic Effects of Curcumin on M1/M2 Macrophage Polarization in Inflammatory Diseases.

BACKGROUND: Due to their plasticity, macrophages exert critical effects on both promoting and suppressing inflammatory processes. Pathologic inflammatory conditions are frequently correlated with dynamic alterations in macrophage activation, with classically activated M1 cells associated with the promotion and maintenance of inflammation and M2 cells being linked to the resolution or smouldering of chronic inflammation. Inflammation deputes a common feature of various chronic diseases and the direct involvement in the insurgence and development of these conditions. Macrophages participate in an autoregulatory loop characterizing the inflammatory process, as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during the inflammation. Therefore, balancing the favorable ratios of M1/M2 macrophages can help ameliorate the inflammatory landscape of pathologic conditions. Curcumin is a component of turmeric with many pharmacological properties. OBJECTIVE: Recent results from both in-vivo and in-vitro studies have indicated that curcumin can affect polarization and/or functions of macrophage subsets in the context of inflammation-related diseases. There is no comprehensive review of the impact of curcumin on cytokines involved in macrophage polarization in the context of inflammatory diseases. The present review will cover some efforts to explore the underlying molecular mechanisms by which curcumin modulates the macrophage polarization in distant pathological inflammatory conditions, such as cancer, autoimmunity, renal inflammation, stroke, atherosclerosis, and macrophage-driven pathogenesis. RESULTS: The accumulation of the findings from in vitro and in vivo experimental studies suggests that curcumin beneficially influences M1 and M2 macrophages in a variety of inflammatory diseases with unfavorable macrophage activation. CONCLUSION: Curcumin not only enhances anti-tumor immunity (via shifting M polarization towards M1 phenotype and/or up-regulation of M1 markers expression) but ameliorates inflammatory diseases, including autoimmune diseases (experimental autoimmune myocarditis and Behcet's disease), nephropathy, chronic serum sickness, stroke, and atherosclerosis.

Curcumin: A dietary phytochemical for boosting exercise performance and recovery.

Curcumin, as the main natural compound in the turmeric plant (Curcuma longa), is a yellowish polyphenol that has been used traditionally in Asian countries as a medicinal herb for various types of disease and pathological conditions caused by inflammation and oxidative stress. In the present review, we conducted a comprehensive literature search for evidence that shows the effect of curcumin on factors influencing exercise performance, including muscle damage, muscle soreness, inflammation, and oxidative stress. During exercise, reactive oxygen species and inflammation are increased. Thus, if there is no balance between endogenous and exogenous antioxidants and increases in oxidative stress and inflammation, which is important for maintaining redox homeostasis in skeletal muscle, it can lead to muscle soreness and muscle damage and ultimately result in reduced exercise performance. Due to the anti-oxidant and anti-inflammatory properties of curcumin, it can increase exercise performance and decrease exercise-induced muscle soreness and muscle damage. It appears that curcumin supplementation can have positive effects on exercise performance and recovery, muscle damage and pain, inflammation, and oxidative stress. However, there is still a need to precisely evaluate factors to more accurately assess/quantify the beneficial therapeutic effects of curcumin with regard to enhancing exercise performance and recovery.

Phytochemicals: A potential therapeutic intervention for the prevention and treatment of cachexia.

Cachexia, a multifactorial and often irreversible wasting syndrome, is often associated with the final phase of several chronic disorders. Although cachexia is characterized by skeletal muscle wasting and adipose tissue loss, it is a syndrome affecting different organs, which ultimately results in systemic complications and impaired quality of life. The pathogenesis and underlying molecular mechanisms of cachexia are not fully understood, and currently there are no effective standard treatments or approved drug therapies to completely reverse cachexia. Moreover, adequate nutritional interventions alone cannot significantly improve cachexia. Other approaches to ameliorate cachexia are urgently needed, and thus, the role of medicinal plants has received considerable importance in this respect due to their beneficial health properties. Increasing evidence indicates great potential of medicinal plants and their phytochemicals as an alternative and promising treatment strategy to reduce the symptoms of many diseases including cachexia. This article reviews the current status of cachexia, the molecular mechanisms of primary events driving cachexia, and state-of-the-art knowledge that reports the preventive and therapeutic activities of multiple families of phytochemical compounds and their pharmacological mode of action, which may hold promise as an alternative treatment modality for the management of cachexia. Based on our review of various in vitro and in vivo models of cachexia, we would conclude that phytochemicals may have therapeutic potential to attenuate cachexia, although clinical trials are required to unequivocally confirm this premise.

The beneficial therapeutic effects of plant-derived natural products for the treatment of sarcopenia.

Sarcopenia is an age-related muscle disorder typically associated with a poor quality of life. Its definition has evolved over time, and several underlying causes of sarcopenia in the elderly have been proposed. However, the exact mechanisms involved in sarcopenia, as well as effective treatments for this condition, are not fully understood. The purpose of this article was to conduct a comprehensive review of previous evidence regarding the definition, diagnosis, risk factors, and efficacy of plant-derived natural products for sarcopenia. The methodological approach for the current narrative review was performed using PubMed, Scopus, and Web of Science databases, as well as Google Scholar (up to March 2021) in order to satisfy our objectives. The substantial beneficial effects along with the safety of some plant-derived natural products including curcumin, resveratrol, catechin, soy protein, and ginseng on sarcopenia are reported in this review. Based on clinical studies, nutraceuticals and functional foods may have beneficial effects on physical performance, including handgrip and knee-extension strength, weight-lifting capacity, time or distance travelled before feeling fatigued, mitochondrial function, muscle fatigue, mean muscle fibre area, and total number of myonuclei. In preclinical studies, supplementation with herbs and natural bioactive compounds resulted in beneficial effects including increased plantaris mass, skeletal muscle mass and strength production, increased expression of anabolic factors myogenin, Myf5 and MyoD, enhanced mitochondrial capacity, and inhibition of muscle atrophy and sarcopenia. We found that several risk factors such as nutritional status, physical inactivity, inflammation, oxidative stress, endocrine system dysfunction, insulin resistance, history of chronic disease, mental health, and genetic factors are linked or associated with sarcopenia. The substantial beneficial effects of some nutraceuticals and functional foods on sarcopenia, including curcumin, resveratrol, catechin, soy protein, and ginseng, without any significant side effects, are reported in this review. Plant-derived natural products might have a beneficial effect on various components of sarcopenia. Nevertheless, due to limited human trials, the clinical benefits of plant-derived natural products remain inconclusive. It is suggested that comprehensive longitudinal clinical studies to better understand risk factors over time, as well as identifying a treatment strategy for sarcopenia that is based on its pathophysiology, be undertaken in future investigations.

Curcumin-based nanotechnology approaches and therapeutics in restoration of autoimmune diseases.

Autoimmune diseases usually arise as a result of an aberrant immune system attack on normal tissues of the body, which leads to a cascade of inflammatory reactions. The immune system employs different types of protective and anti-inflammatory cells for the regulation of this process. Curcumin is a known natural anti-inflammatory agent that inhibits pathological autoimmune processes by regulating inflammatory cytokines and their associated signaling pathways in immune cells. Due to the unstable nature of curcumin and its susceptibility to either degradation, or metabolism into other chemical entities (i.e., metabolites), encapsulation of this agent into various nanocarriers would appear to be an appropriate strategy for attaining greater beneficial effects from curcumin as it pertains to immunomodulation. Many studies have focused on the design and development of curcumin nanodelivery systems (micelles, dendrimers, and diverse nanocarriers) and are summarized in this review in order to obtain greater insight into novel drug delivery systems for curcumin and their suitability for the management of autoimmune 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.

Immunomodulatory effects of curcumin in systemic autoimmune diseases.

Systemic autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus represent various autoimmune conditions identified by immune system dysregulation. The activation of immune cells, auto-antigen outbreak, inflammation, and multi-organ impairment is observed in these disorders. The immune system is an essential complex network of cells and chemical mediators which defends the organism's integrity against foreign microorganisms, and its precise operation and stability are compulsory to avoid a wide range of medical complications. Curcumin is a phenolic ingredient extracted from turmeric and belongs to the Zingiberaceae, or ginger family. Curcumin has multiple functions, such as inhibiting inflammation, oxidative stress, tumor cell proliferation, cell death, and infection. Nevertheless, the immunomodulatory influence of curcumin on immunological reactions/processes remains mostly unknown. In the present narrative review, we sought to provide current information concerning the preclinical and clinical uses of curcumin in systemic autoimmune diseases.

Therapeutic Effects of Polyphenols on the Treatment of Colorectal Cancer by Regulating Wnt ß-Catenin Signaling Pathway.

Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide in terms of both its rates of incidence and mortality. Due to serious side effects associated with conventional chemotherapeutic treatments, many natural products with fewer adverse side effects have been considered as potential treatment options. In fact, many natural products have widely been used in various phases of clinical trials for CRC, as well as in in vitro and in vivo preclinical studies. Curcumin (CUR) and resveratrol (RES) are classified as natural polyphenolic compounds that have been demonstrated to have anticancer activity against CRC and are associated with minimal side effects. By regulating select target genes involved in several key signaling pathways in CRC, in particular, the Wnt ß-catenin signaling cascade, the course of CRC may be positively altered. In the current review, we focused on the therapeutic effects of CUR and RES in CRC as they pertain to modulation of the Wnt ß-catenin signaling pathway.

The clinical use of curcumin on neurological disorders: An updated systematic review of clinical trials.

Neuroprotective effects of curcumin have been shown in previous studies. This updated systematic review of clinical trials aimed to investigate the effect of curcumin on neurological disorders. Databases including PubMed, Scopus, Web of Science, and Google Scholar were systematically searched to identify clinical trials investigating the effects of curcumin/turmeric supplements alone, or in combination with other ingredients, on neurological diseases. Nineteen studies comprising 1,130 patients met the inclusion criteria. Generally, intervention and study outcomes were heterogeneous. In most of the studies, curcumin had a favorable effect on oxidative stress and inflammation. However, with the exception of AD, curcumin supplementation either alone, or in combination with other ingredients, had beneficial effects on clinical outcomes for the other aforementioned neurodegenerative diseases. For example, the frequency, severity, and duration of migraine attacks, scores on the revised ALS functional rating scale, and the occurrence of motor complications in PD were all significantly improved with curcumin supplementation either alone or in combination with other ingredients. However, in three studies, several adverse side effects (mostly gastrointestinal in nature) were reported. Curcumin supplementation may have favorable effects on inflammatory status and clinical outcomes of patients with neurological disease, although the results were not consistent.

Paving the Road Toward Exploiting the Therapeutic Effects of Ginsenosides: An Emphasis on Autophagy and Endoplasmic Reticulum Stress.

Programmed cell death processes such as apoptosis and autophagy strongly contribute to the onset and progression of cancer. Along with these lines, modulation of cell death mechanisms to combat cancer cells and elimination of resistance to apoptosis is of great interest. It appears that modulation of autophagy and endoplasmic reticulum (ER) stress with specific agents would be beneficial in the treatment of several disorders. Interestingly, it has been suggested that herbal natural products may be suitable candidates for the modulation of these processes due to few side effects and significant therapeutic potential. Ginsenosides are derivatives of ginseng and exert modulatory effects on the molecular mechanisms associated with autophagy and ER stress. Ginsenosides act as smart phytochemicals that confer their effects by up-regulating ATG proteins and converting LC3-I to -II, which results in maturation of autophagosomes. Not only do ginsenosides promote autophagy but they also possess protective and therapeutic properties due to their capacity to modulate ER stress and up- and down-regulate and/or dephosphorylate UPR transducers such as IRE1, PERK, and ATF6. Thus, it would appear that ginsenosides are promising agents to potentially restore tissue malfunction and possibly eliminate cancer.

Medicinal plants and bioactive natural products as inhibitors of NLRP3 inflammasome.

The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that induces caspase-1 activation and the downstream substrates involved with the processing and secretion of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 and tumor necrosis factor-α (TNF- α). The NLRP3 inflammasome is activated by a wide range of danger signals that derive from metabolic dysregulation. Activation of this complex often involves the adaptor ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. It has been shown that nutraceuticals and medicinal plants have antiinflammatory properties and could be used as complementary therapy in the treatment of several chronic diseases that are related to inflammation, for example, cardiovascular diseases and diabetes mellitus. Herb-based medicine has demonstrated protective effects against NLRP3 inflammasome activation. Therefore, this review focuses on the effects of nutraceuticals and bioactive compounds derived from medicinal plants on NLRP3 inflammasome activation and the possible mechanisms of action of these natural products. Thus, herb-based, natural products/compounds can be considered novel, practical, and accessible agents in chronic inflammatory diseases by inhibiting NLRP3 inflammasome activation.

Targeting the PD-1/PD-L1 pathway in glioblastoma multiforme: Preclinical evidence and clinical interventions.

Glioblastoma multiforme (GBM), as one of the immunosuppressive and common intrinsic brain tumors in adults, remains an intractable malignancy to manage. Since the standard of care for treatment, which includes surgery and chemoradiation, has not provided a sustainable and durable response in affected patients, seeking novel therapeutic approaches to treat GBM seems imperative. Immunotherapy, a breakthrough for cancer treatment, has become an attractive tool for combating cancer with the potential to access the blood-brain-barrier (BBB). In this regard, programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), as major immunological checkpoints, have drawn considerable interest due to their effectiveness in a spectrum of highly-aggressive neoplasms through negative regulation of the T-cell-mediated immune response. Nevertheless, due to the immunosuppressive microenvironment of GBM, the efficacy of these immune checkpoint inhibitors (ICIs), when used as monotherapy, has been unfavorable and lacks sufficient beneficial outcomes for GBM patients. A variety of clinical studies are attempting to evaluate the combination of ICIs (neoadjuvant/adjuvant) and existing treatment guidelines to strengthen their effectiveness; however, the exact mechanism of this signaling axis affects the consequences of immune therapy remains elusive. This review provides an overview of the PD-1/PD-L1 pathway, currently approved ICIs for clinical use, preclinical and clinical trials of PD-1/PD-L1 as monotherapy, and when used concomitantly with other GBM treatments.

The effect of oral curcumin supplementation on health-related quality of life: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: With an aging society, a multitude of physical, mental, and emotional challenges are being faced both in the general population and by those with chronic disorders. An enhanced understanding of 'quality of life' could be considered a major criterion for improved clinical care. We performed a meta-analysis to examine the effect of oral curcumin on improving the health-related quality of life (HRQOL). METHODS: A systematic search was performed through PubMed, Clarivate Web of Science, Scopus, and Embase up to February 2020 using relevant keywords. Trials that met the inclusion criteria were included in this study. We applied the standardized mean difference (SMD) in a random-effects model to analyze the impact of combined trials. Additionally, we used the Cochrane Risk Bias Tool to evaluate any potential risks of bias. RESULTS: A total of 10 studies were considered eligible and included in the meta-analysis. We found an overall significant effect of oral curcumin supplementation on improved HRQOL (SMD: 2.46, 95% CI: 1.30, 3.63; I2=97.4). In the subgroup analysis, curcumin showed significantly favorable effects on HRQOL in trials with a short duration of curcumin intervention (<5 months) and those that used curcumin formulations with high bioavailability. CONCLUSION: Oral curcumin has a strong positive impact on HRQOL. Our analysis supports the use of an improved-bioavailability formulation of curcumin to improve HRQOL. However, given the heterogeneity among the studies included in this review, additional evidence from well-designed, large, and long-term trials is still required.

The Efficacy of Anti-inflammatory Agents in the Prevention of Atrial Fibrillation Recurrences.

Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF.

Regulation of Apolipoprotein B by Natural Products and Nutraceuticals: A Comprehensive Review.

Cardiovascular Disease (CVD) is the most important and the number one cause of mortality in both developing and industrialized nations. The co-morbidities associated with CVD are observed from infancy to old age. Apolipoprotein B100 (Apo B) is the primary apolipoprotein and structural protein of all major atherogenic particles derived from the liver including Very-Low- Density Lipoproteins (VLDL), Intermediate-density Lipoprotein (IDL), and Low-density Lipoprotein (LDL) particles. It has been suggested that measurement of the Apo B concentration is a superior and more reliable index for the prediction of CVD risk than is the measurement of LDL-C. Nutraceuticals and medicinal plants have attracted significant attention as it pertains to the treatment of non-communicable diseases, particularly CVD, diabetes mellitus, hypertension, and Nonalcoholic Fatty Liver Disease (NAFLD). The effect of nutraceuticals and herbal products on CVD, as well as some of its risk factors such as dyslipidemia, have been investigated previously. However, to the best of our knowledge, the effect of these natural products, including herbal supplements and functional foods (e.g. fruits and vegetables as either dry materials, or their extracts) on Apo B has not yet been investigated. Therefore, the primary objective of this paper was to review the effect of bioactive natural compounds on plasma Apo B concentrations. It is concluded that, in general, medicinal plants and nutraceuticals can be used as complementary medicine to reduce plasma Apo B levels in a safe, accessible, and inexpensive manner in an attempt to prevent and treat CVD.

Protective Effects of Curcumin on Pulmonary Arterial Hypertension.

Pulmonary hypertension is one of the most common diseases among older people. This disease is usually associated with complications such as vascular changes, vascular remodeling, vasoconstriction, endothelial dysfunction, right ventricular failure, and reduction in nitric oxide availability. Many chemical drugs have been used to treat pulmonary hypertension, but result in limited efficacy and several side effects, and these medications are not always available worldwide. Various studies in traditional medicine have shown that changes in lifestyle and nutritional habits can be extremely effective in both the prevention and treatment of various diseases. One treatment method related to changing nutritional habits is the use of curcumin as a nutritional supplement. Curcumin plays an important role in treating pulmonary hypertension and positively alters the aforementioned complications.

A Review on the Phytochemistry, Pharmacology, and Therapeutic Effects of Rheum ribes.

Herbal medications are typically used for the treatment of diverse diseases without significant adverse effects. The Rheum ribes (R. ribes), commonly called rhubarb, is a hardy perennial herb and is consumed all over the world. There is growing evidence of the therapeutic benefits of R. ribes. Extensive in vitro and in vivo investigations have shown that R. ribes reveals beneficial properties via different mechanisms. In the current article, various pharmacological and therapeutic effects of R. ribes have been reviewed. For this purpose, different online databases using keywords such as R. ribes, therapeutic effects, and pharmacological effects were searched until the end of December 2020. R. ribes has been suggested to be effective in the treatment of a wide range of disorders including stomachache, nausea and vomiting, hemorrhoids, and measles. Additionally, different studies have demonstrated that R. ribes possesses numerous pharmacological properties including anti-inflammatory, anticancer, antibacterial, and antiviral, and may also function as an expectorant. The present narrative review provides a detailed survey of scientific investigations regarding the pharmacological properties and therapeutic effects of R. ribes.

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective.

Sepsis and septic shock are still a leading cause of mortality and morbidity in intensive care units worldwide. Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper-production of pro-inflammatory mediators such as interleukin (IL)-1ß, IL-6, tumor-necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro-inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well-known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti-inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life-threatening complications, such as multi-organ failure.