Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.
The effect of saffron supplementation on subclinical inflammation remains inconclusive. We performed a systematic review and meta-analysis to summarize available findings on the effect of saffron supplementation on inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) in adults. We searched PubMed/Medline, Scopus, Web of Science, and Google Scholar databases up to November 2019 using relevant keywords to identify eligible trials. All randomized controlled trials (RCTs) that examined the effect of oral saffron supplementation on plasma concentrations of CRP, TNF-α, and IL-6 were included. For each outcome, mean differences and SDs were pooled using a random-effects model. Overall, eight RCTs were included in this meta-analysis. The pooled results showed that saffron supplementation did not result in significant changes in serum CRP (weighted mean difference [WMD]: -0.43 mg/L; 95% confidence interval [CI]: -1.04 to 0.17; p = .16), serum TNF-α (WMD: -1.29 pg/mL; 95% CI: -4.13 to 1.55; p = .37), and IL-6 concentrations (WMD: 0.11 pg/mL; 95% CI: -0.79 to 1.00; p = .81). Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin. Similarly, saffron was found to decrease TNF-α in studies that recruited non-diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day. We also found a significant non-linear effect of saffron dosage on serum CRP concentrations (pnon-linearity = .03). The overall results indicated that saffron supplementation did not affect inflammatory cytokines. Further high-quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers.
Inflammation is a common complication in hemodialysis (HD) patients with no valid treatment strategy. In addition, carnitine deficiency occurs frequently in HD patients because of intradialytic loss of carnitine, impaired de novo carnitine renal synthesis, and reduced dietary intake. It appears that carnitine deficiency is related to inflammation in HD patients. A few clinical trials have investigated the effect of L-carnitine supplement on inflammatory markers in HD patients. All studies in this field, except one, showed that L-carnitine could significantly reduce C-reactive protein and serum amyloid A, as two systemic inflammation markers, in HD patients. Therefore, considering high prevalence of inflammation and carnitine deficiency in HD patients, L-carnitine therapy is a reasonable approach for reducing systemic inflammation and its complications in these patients.
The fruit pulp extract of Tamarindus indica has been reported for its antioxidant and hypolipidemic properties. In this study, the methanol extract of T. indica fruit pulp was investigated for its effects on the abundance of HepG2 cell lysate proteins. Cell lysate was extracted from HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp. Approximately 2500 spots were resolved using two-dimensional gel electrophoresis and the abundance of 20 cellular proteins was found to be significantly reduced. Among the proteins of reduced abundance, fourteen, including six proteins involved in metabolism (including ethanolamine phosphate cytidylyltransferase), four mitochondrial proteins (including prohibitin and respiratory chain proteins), and four proteins involved in translation and splicing, were positively identified by mass spectrometry and database search. The identified HepG2 altered abundance proteins, when taken together and analyzed by Ingenuity Pathways Analysis (IPA) software, are suggestive of the effects of T. indica fruit pulp extract on metabolism and inflammation, which are modulated by LXR/RXR. In conclusion, the methanol fruit pulp extract of T. indica was shown to cause reduced abundance of HepG2 mitochondrial, metabolic, and regulatory proteins involved in oxidative phosphorylation, protein synthesis, and cellular metabolism.
Topical application of honey to burn and wounds has been found to be effective in controlling infection and producing a clean granulating bed. It is suggested that the wound healing effect of honey may in part be related to the release of inflammatory cytokines from surrounding tissue cells, mainly monocytes and macrophages. It has been reported that honey hastens wound healing by accelerating wound contractions. Microscopic evaluation demonstrated that there was a significant acceleration of dermal repair in wound treated with honey. Macroscopic and microscopic observations under in vivo assessment suggested that the topical application of honey might have favourable influences on the various phases of burn and wound healing hence accelerating the healing process. The regulatory effects of honey are related to components other than the sugars. However, the mechanisms by which honey affects the release of anti inflammatory agents and growth factors from monocytic cells are as yet unclear. Whether honey affects other cell types, particularly endothelial cells and fibroblasts, involved in wound healing also needs to be clarified. The present article is a short review of recent patents on the healing effect of honey in wound and burn management.
We investigated the effects of honey and its methanol and ethyl acetate extracts on inflammation in animal models. Rats' paws were induced with carrageenan in the non-immune inflammatory and nociceptive model, and lipopolysaccharide (LPS) in the immune inflammatory model. Honey and its extracts were able to inhibit edema and pain in inflammatory tissues as well as showing potent inhibitory activities against NO and PGE(2) in both models. The decrease in edema and pain correlates with the inhibition of NO and PGE(2). Phenolic compounds have been implicated in the inhibitory activities. Honey is potentially useful in the treatment of inflammatory conditions.
Imiquimod is a chemotherapeutic agent for many skin-associated diseases, but it has also been associated with inflammatory side effects. The aim of this study was to prevent the inflammatory effect of commercial imiquimod (Aldara(®)) by controlled release of imiquimod through a hydrogel/oleogel colloidal mixture (CA bigel) containing fish oil as an anti-inflammatory agent. Imiquimod permeability from Aldara® cream and bigel through mice skin was evaluated, and the drug content residing in the skin via the tape stripping technique was quantified. The fish oil fatty acid content in skin along with its lipophilic environment was also determined. An inflammation study was conducted using animal models, and Aldara(®) cream was found to potentially cause psoriasis-like inflammation, which could be owing to prolonged application and excessive drug permeation. Controlled release of imiquimod along with fish oil through CA bigel may have caused reduced imiquimod inflammation. NMR studies and computerized molecular modeling were also conducted to observe whether the fish oil and imiquimod formed a complex that was responsible for improving imiquimod transport and reducing its side effects. NMR spectra showed dose-dependent chemical shifts and molecular modeling revealed π-σ interaction between EPA and imiquimod, which could help reduce imiquimod inflammation.
A 49 year-old Indian housewife was diagnosed with Hodgkin's disease in 1995. She was given combination chemotherapy comprising Chlorambucil, Vincristine, Procarbazine and Prednisolone. Unfortunately she defaulted after two courses of chemotherapy. One year later, she developed progressive right knee swelling and pain, associated with loss of appetite, loss of weight, intermittent fever, night sweats and pruritus. The right knee swelling measured 15 cm x 20 cm and was warm and tender. A plain radiograph of the right knee revealed osteolytic lesions at the distal end of the right femur and the proximal ends of the right tibia and fibula, associated with gross periosteal reaction and soft tissue swelling. Apart from left cervical lymphoadenopathy, examination of other systems was unremarkable. Pelvic bone marrow biopsy was inconclusive. An open biopsy of the lower end of the right femur was consistent with Hodgkin's disease. She was given salvage combination therapy comprising Chlorambucil, Vincristine, Procarbazine, Prednisolone, Doxorubicin, Bleomycin and Vinblastine. She tolerated the treatment well and responded with significant reduction in the swelling and pain of the right knee. Unfortunately, she again defaulted treatment after 2 courses of chemotherapy. This case illustrates an unusual presentation of Hodgkin's disease in relapse.
Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.
Colon-specific drug delivery has found important applications in the wide array of diseases affecting the lower intestinal tract. Recent developments and advancements in the polymer-based colonic delivery ensure targeted therapeutics with reduced systemic adverse effects. Latest progress in the understanding of polymer science has decorated a polymer-based formulation with a number of special features, which may prove effective in the localized drug targeting at specific sites of the intestine. Upon oral administration, polymeric vehicles or polymer-coated formulations serve to protect the drug from premature release and degradation in the upper gastrointestinal tract. Moreover, it also facilitates the selective accumulation and controlled release of the drug at inflamed sites of the colon. This review article focuses on a wide coverage of major polymers, their modifications, pros and cons, mechanism of colon targeting and applications as a vehicle system for colonic drug delivery, with a special emphasis on the inflammatory bowel disease.
Hyaluronic acid (HA) plays multifaceted role in regulating various biological processes and maintaining homeostasis into the body. Numerous researches evidenced the biomedical implications of HA in skin repairmen, cancer prognosis, wound healing, tissue regeneration, anti-inflammatory, immunomodulation. The present review was aimed to summarize and critically appraise the recent developments and efficacy of HA for treatment of inflammatory skin and joint diseases. A thorough analysis of the literature revealed that HA based formulations (i.e., gels, creams, autologous graft, thin sheets, soaked gauze, gauze pad, tincture, injection) have shown remarkable efficacy in treating a wide range of inflammatory skin diseases. The safety, tolerability, and efficacy of HA (as intra-articular injection) have also been well-documented for treatment of various types of joint disease including knee osteoarthritic, joint osteoarthritis, canine osteoarthritis, and meniscal swelling. Intra-articular injection of HA produces remarkable reduction in joint pain, synovial inflammation, and articular swelling. A remarkable improvement in chondrocyte density, territorial matrix appearance, reconstitution of superficial amorphous layer of the cartilage, collagen remodelling, and regeneration of meniscus have also been evident in patients treated with HA. Conclusively, we validate that the application/administration of HA is a promising pharmacotherapeutic regimen for treatment of inflammatory skin and joint diseases.
The causal and functional connection between inflammation and cancer has become a subject of much research interest. Modulation of cell signaling pathways, such as those involving mitogen activated protein kinases (MAPKs), nuclear factor kappa β (NF-κB), phosphatidylinositol 3-kinase and protein kinase B (PI3K/Akt), and Wnt, and their outcomes play a fundamental role in inflammation and cancer. Activation of these cell signaling pathways can lead to various aspects of cancer-related inflammation. Hence, compounds able to modulate inflammation-related molecular targets are sought after in anticancer drug development programs. In recent years, plant extracts and their metabolites have been documented with potential in the prevention and treatment of cancer and inflammatory ailments. Plants possessing anticancer and anti-inflammatory properties due to their bioactive constituents have been reported to modulate the molecular and cellular pathways which are related to inflammation and cancer. In this review we focus on the flavonoids (astragalin, kaempferol, quercetin, rutin), lignans (phyllanthin, hypophyllanthin, and niranthin), tannins (corilagin, geraniin, ellagic acid, gallic acid), and triterpenes (lupeol, oleanolic acid, ursolic acid) of Phyllanthus amarus, which exert various anticancer and anti-inflammatory activities via perturbation of the NF-κB, MAPKs, PI3K/Akt, and Wnt signaling networks. Understanding the underlying mechanisms involved may help future research to develop drug candidates for prevention and new treatment for cancer and inflammatory diseases.
Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and lung cancer. Currently, there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics. Berberine, an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases. Nevertheless, the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited. In this review, we have attempted to discuss the reported anti-inflammatory properties of berberine that function through several pathways such as, the NF-κB, ERK1/2 and p38 MAPK pathways which affect several pro-inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases. This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases.
Inflammatory gastrointestinal (GI) diseases and malignancies are associated with growing morbidity and cancer-related mortality worldwide. GI tumor and inflammatory cells contain activated sphingolipid-metabolizing enzymes, including sphingosine kinase 1 (SphK1) and SphK2, that generate sphingosine-1-phosphate (S1P), a highly bioactive compound. Many inflammatory responses, including lymphocyte trafficking, are directed by circulatory S1P, present in high concentrations in both the plasma and the lymph of cancer patients. High fat and sugar diet, disbalanced intestinal flora, and obesity have recently been linked to activation of inflammation and SphK/S1P/S1P receptor (S1PR) signaling in various GI pathologies, including cancer. SphK1 overexpression and activation facilitate and enhance the development and progression of esophageal, gastric, and colon cancers. SphK/S1P axis, a mediator of inflammation in the tumor microenvironment, has recently been defined as a target for the treatment of GI disease states, including inflammatory bowel disease and colitis. Several SphK1 inhibitors and S1PR antagonists have been developed as novel anti-inflammatory and anticancer agents. In this review, we analyze the mechanisms of SphK/S1P signaling in GI tissues and critically appraise recent studies on the role of SphK/S1P/S1PR in inflammatory GI disorders and cancers. The potential role of SphK/S1PR inhibitors in the prevention and treatment of inflammation-mediated GI diseases, including GI cancer, is also evaluated.
For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents.
Oxidative stress and inflammation are two interlinked events that exist simultaneously in metabolic syndrome (MetS) and its related complications. These pathophysiological processes can be easily triggered by each other. This review summarizes the current evidence from animal and human studies on the effects of vitamin C in managing MetS. In vivo studies showed promising effects of vitamin C, but most of the interventions used were in combination with other compounds. The direct effects of vitamin C remain to be elucidated. In humans, the current state of evidence revealed that lower vitamin C intake and circulating concentration were found in MetS subjects. A negative relationship was observed between vitamin C intake / concentration and the risk of MetS. Oral supplementation of vitamin C also improved MetS conditions. It has been postulated that the positive outcomes of vitamin C may be in part mediated through its anti-oxidative and anti-inflammatory properties. These observations suggest the importance of MetS patients to have an adequate intake of vitamin C through food, beverages or supplements in order to maintain its concentration in the systemic circulation and potentially reverse MetS.
We evaluated the efficacy of a 12-week oral treatment with azithromycin in adult patients with bronchiectasis. The objectives were to demonstrate that this treatment reduces sputum volume, improves quality of life and to assess the lengths of effects after cessation of therapy.
Till to date, the advancement of medical science and technology is still unable to provide inclusive treatment to liver inflammation caused by neither microbial invasion nor antibiotics nor environmental toxins. Therefore, this article provides the basic knowledge of liver inflammation up to the cellular level and its current medical treatment for inflammatory symptom suppression. Because of the adverse effects of drug treatment, people start looking for comprehensive alternative nowadays. Herbal medicine is believed to be the best of choice because it is being practiced until now for centuries. Although numerous herbal plants have been reported for their efficacies in liver protection, Andrographis paniculata is the most widely used herb for hepatoprotection, particularly in Ayurveda and traditional Chinese medicine. This review covers the significant observation on the biochemical responses due to the experimental induction of liver damage in vitro and in vivo using the marker compound of the herb, namely andrographolide and its derivatives. The standardized extract of A. paniculata with the right phytochemical composition of diterpenic labdanes is likely to have tremendous potential for the development of hepatoprotective medicine. This standardized herbal medicine may not provide immediate remedy, but it can be considered as a comprehensive therapy for liver inflammation.
Chalcones (1, 3-Diphenyl-2-propen-1-one) are constituted by a three carbon α, β-unsaturated carbonyl system. The biosynthesis of flavonoids and isoflavonoids is initiated by chalcones. Notable pharmacological activities of chalcones and its derivatives include anti-inflammatory, antifungal, antibacterial, antimalarial, antituberculosis, antitumor, antimicrobial and antiviral effects respectively. Owing to simplicity of the chemical structures and a huge variety of pharmacological actions exhibited, the entities derived from chalcones are subjected to extensive consideration. This review article is an effort to sum up the anti-inflammatory activities of chalcone derived chemical entities. Effect of chalcones on lipid peroxidation, heme oxygenase 1(HO-1), cyclooxygenase (COX), interleukin 5 (IL-5), nitric oxide (NO) and expression of cell adhesion molecules (CAM) is summarized stepwise.