Health functions and related molecular mechanisms of Miconia genus: A systematic review.

The Miconia genus is traditionally used in folk medicine in Brazil and other tropical American countries and is represented by 282 species in this region. It is a multifaceted genus of medicinal plants widely used to treat rheumatoid arthritis (RA), pain, inflammatory diseases, and many more therapeutic applications. In the present study, we systematically identify and discuss the literature on in vivo and in vitro studies focusing on the therapeutic potentials and related molecular mechanisms of the Miconia genus. The review also assessed phytochemicals and their pharmacological properties and considered safety concerns related to the genus. Literature searches to identify studies on the Miconia genus were carried out through four main electronic databases, namely PubMed, Embase, Scopus, and Web of Science limited to Medical Subjects Headings (MeSH) and Descriptores en Ciencias de la Salud (DCS) (Health Sciences Descriptors) to identify studies published up to December 2022. The relevant information about the genus was gathered using the keywords 'Miconia', 'biological activities', 'therapeutic mechanisms', 'animal model, 'cell-line model', 'antinociceptive', 'hyperalgesia', 'anti-inflammatory', and 'inflammation'. The therapeutic potentials and mechanisms of action of 14 species from genus Miconia were examined in 18 in vitro studies and included their anti-inflammatory, anticancer, analgesic, antibacterial, cytotoxic, mutagenic, antioxidant, anti-leishmanial, antinociceptive, schistosomicidal, and anti-osteoarthritis potentials, and in eight in vivo studies, assessing their analgesic, antioxidant, antinociceptive, and anti-osteoarthritis activities. Some of the main related molecular mechanisms identified are the modulation of cytokines such as IL-1ß, IL-6, and TNF-α, as well as the inhibition of inflammatory mediators and prostaglandin synthesis. The limited number of studies showed that commonly available species from the genus Miconia are safe for consumption. Miconia albicans Sw.Triana and Miconia rubiginosa (Bonpl.) DC was the most frequently used species and showed significant efficacy and potential for developing safe drugs to treat pain and inflammation.

Anti-inflammatory natural products modulate interleukins and their related signaling markers in inflammatory bowel disease: A systematic review.

This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease (IBD). Specifically, the objective is to examine the impact of these substances on interleukins and other key inflammatory signaling markers. Relevant articles published up to December 2022 were identified through a search of the PubMed, Scopus, Web of Science, and Embase databases. The search used keywords including "inflammatory bowel disease", "medicinal plants", "natural molecules", "anti-inflammatory", and "ulcerative colitis", and identified 1,878 potentially relevant articles, of which 89 were included in this review after completion of the selection process. This study provides preclinical data on natural products (NPs) that can potentially treat IBD, including ulcerative colitis. The main actions of these NPs relate to their effects on nuclear factor kappa B (NF-κB), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the regulation of T helper 17/regulatory T cells balance, and oxidative stress. The ability of these NPs to inhibit intestinal inflammation appears to be dependent on lowering levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and IL-17, via the Jun N-terminal kinase (JNK)1, NF-κß-p65, and STAT3 pathways. In addition, NPs were shown to reduce oxidative stress and the severity of ulcerative colitis, as well as increase the activity of antioxidant enzymes. These actions suggest that NPs represent a promising treatment for IBD, and potentially have greater efficacy and safety than current treatments.

Natural products modulating interleukins and other inflammatory mediators in tumor-bearing animals: A systematic review.

BACKGROUND: Cancer is a group of diseases characterized by abnormal cell growth and proliferation. Natural products are a potentially important source for bioactive phytochemicals in the management of cancer, which regulate a broad range of biological events via the modulation of interleukins (ILs), pro- and anti-inflammatory modulators, and other cancer hallmark-mediated signaling pathways. PURPOSE: To systematically review the literature to identify in vivo studies investigating the anticancer properties of medicinal plants and natural molecules as modulators of ILs and their related pro- and anti-inflammatory signaling markers in tumor-bearing animals. METHODS: Articles published in English were searched, without any constraint in respect of countries. The electronic databases PubMed, Embase, Scopus, and Web of Science were used for the literature search for studies published between January 2010 and January 2022. The search terms used included medicinal plants, anticancer, antineoplasic agent, ILs, cytokine, and their combinations. A manual search to detect any articles not found in the databases was also made. The identified studies were then critically reviewed and relevant data were extracted and summarized. RESULTS: Natural products were found to modulate ILs, including IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-18, IL-23, and IL-12, and interferon gamma; increase tissue inhibitor metalloprotease; decrease vascular endothelial growth factor, tumor necrosis factor alpha, granulocyte macrophage colony-stimulating factor, and nuclear factor kappa B; augment immunity by increasing the major histocompatibility complexes II and CD4+, cluster of differentiation 8 + T cell and class II trans-activator expression; and heighten the action of antioxidant enzymes, which are involved in the detoxification of free radicals and reactive oxygen species. CONCLUSION: Natural products discussed in this review show great potential to regulate ILs and weaken associated pro- and anti-inflammatory signaling markers in tumor-bearing animals. Flavonoids, polyphenols, polysaccharides, alkaloids and tannins are important phytochemicals in the modulation of ILs, especially pro-inflammatory ones. However, in terms of future research, the importance of clinical trials to investigate their beneficial properties should be warranted.

Anti-inflammatory natural products as potential therapeutic agents of rheumatoid arthritis: A systematic review.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease causing severe locomotor disability and deterioration in the quality of life. Existing treatments for RA mainly focus on the use of immunomodulators and the suppression of synovial inflammation, and many have significant side effects. Medicinal plants are regarded as important alternative sources for treating RA. PURPOSE: This review summarizes the bioactive compounds of medicinal plants, which have been shown to modulate the immune response by regulating interleukins in vitro and in vivo experimental models, and that may be promising substances for use in the treatment of RA. METHODS: Articles on natural products used for the management of arthritis were retrieved from PubMed, Embase, Scopus, and Web of Science through electronic and manual search in English. In total, 576 publications were identified, and 34 were included in this systematic review. RESULTS: Two articles presented findings on the role of natural components in the treatment of arthritis in both in vitro and in vivo studies. Nine reports defined the role of plant-derived natural molecules in the treatment of arthritis using cell lines, and 27 in vivo studies assessed the anti-arthritic efficacy and immunomodulation effects of phytoconstituents on interleukin production and inflammatory responses. CONCLUSION: This systematic review broadly reports that, in contrast to other classes of phytochemicals, flavonoids have the greatest therapeutic potential against arthritis by modulating the expression of pro-inflammatory TNF-α, IL-1ß, IL-6, IL-8, and IL-17, as well as anti-inflammatory IL-2 and IL-10 cytokines, through the suppression of dynamic inflammatory biomarkers.

Modulation of interleukin expression by medicinal plants and their secondary metabolites: A systematic review on anti-asthmatic and immunopharmacological mechanisms.

BACKGROUND: Asthma is one of the most common chronic inflammatory conditions of the lungs in modern society. Asthma is associated with airway hyperresponsiveness and remodeling of the airways, with typical symptoms of cough, wheezing, shortness of breath and chest tightness. Interleukins (IL) play an integral role in its inflammatory pathogenesis. Medicinal herbs and secondary metabolites are gaining considerable attention due to their potential therapeutic role and pharmacological mechanisms as adjunct tools to synthetic bronchodilator drugs. PURPOSE: To systematically review the literature on the use of single or mixed plants extracts therapy in vivo experimental systems for asthma, emphasizing their regulations on IL production to improve lung. METHODS: Literature searches were performed on PubMed, EMBASE, Scopus and Web of Science databases. All articles in English were extracted from 1999 up to September 2019, assessed critically for data extraction. Studies investigating the effectiveness and safety of plant extracts administered; inflammatory cell count, immunoglobulin E (IgE) production and regulation of pro-inflammatory cytokine and T helper (Th) 1 and Th2-driven cytokine expression in bronchoalveolar lavage fluid (BALF) and lung of asthmatic animals were included. RESULTS: Four hundred and eighteen publications were identified and 51 met the inclusion criteria. Twenty-six studies described bioactive compounds from plant extracts. The most frequent immunopharmacological mechanisms described included reduction in IgE and eosinophilic recruitment, decreased mucus hypersecretion and airway hyperreactivity, enhancement of the balance of Th1/Th2 cytokine ratio, suppression of matrix metallopeptidase 9 (MMP-9) and reversal of structural alterations. CONCLUSION: Plant extract therapies have potential control activities on asthma symptoms by modulating the secretion of pro-inflammatory (IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10, IL-23, IL-31, IL-33), Th1 (IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines, reducing the level of biomarkers of airway inflammation.

Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties.

BACKGROUND: Asthma, the main inflammatory chronic condition affecting the respiratory system, is characterized by hyperresponsiveness and reversible airway obstruction, recruitment of inflammatory cells and excessive production of mucus. Cytokines as biochemical messengers of immune cells, play an important role in the regulation of allergic inflammatory and infectious airway processes. Essential oils of plant origin are complex mixtures of volatile and semi volatile organic compounds that determine the specific aroma of plants and are categorized by their biological activities. PURPOSE: We reviewed whether essential oils and their bioactive compounds of plant origin could modulate cytokines' immune responses and improve asthma therapy in experimental systems in vitro and in vivo. METHODS: Electronic and manual search of articles in English available from inception up to November 2018 reporting the immunomodulatory activity of essential oils and their bioactive compounds for the management of asthma. We used PubMed, EMBASE, Scopus and Web of Science. Publications reporting preclinical experiments where cytokines were examined to evaluate the consequence of anti-asthmatic therapy were included. RESULTS: 914 publications were identified and 13 were included in the systematic review. Four articles described the role of essential oils and their bioactive compounds on bronchial asthma using cell lines; nine in vivo studies evaluated the anti-inflammatory efficacy and immunomodulating effects of essential oil and their secondary metabolites on cytokines production and inflammatory responses. The most important immunopharmacological mechanisms reported were the regulation of cytokine production, inhibition of reactive oxygen species accumulation, inactivation of eosinophil migration and remodeling of the airways and lung tissue, modulation of FOXP3 gene expression, regulation of inflammatory cells in the airways and decreasing inflammatory mediator expression levels. CONCLUSION: Plant derived essential oils and related active compounds have potential therapeutic activity for the treatment of asthma by modulating the release of pro-inflammatory (TNF-α, IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10), Th1 (IFN-γ, IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines and the suppression of inflammatory cell accumulation.

Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models.

BACKGROUND: Flavonoids are naturally occurring compounds, extensively distributed in plants. T helper (Th)1 and Th2 cytokines balance plays an essential role in the reaction of inflammatory, allergic and infectious processes and transplantation rejection. PURPOSE: This systematic review focuses on various classes of flavonoids with a view to evaluate whether Th1/Th2 cytokine-mediated pathways of immunoenhancement could reduce immune overwhelming reactions. METHODS: Articles in English published from inception to December 2017 reporting flavonoids with immunomodulatory activity for the management of immune-mediated disorders were acquired from PubMed, EMBASE, Scopus and Web of Science and a animal experiments where Th1 and Th2 cytokines were investigated to assess the outcome of immunoregulatory therapy were included. CHAPTERS: 1809 publications were identified and 26 were included in this review. Ten articles described the effect of flavonoids on allergic inflammation in an animal model of asthma; eleven in vivo studies evaluated the immunomodulating and immunosuppressive effects of flavonoids on Th1/Th2 cytokines production and five reports described the regulatory role of flavonoids for Th1/Th2 cytokine responses to experimental arthritis and myocarditis. Modulation of Th1/Th2 cytokine balance, inhibition of eosinophil accumulation and remodeling of the airways and lungs, downregulation of Notch and PI3K signaling pathways, regulation of CD4 + /CD8 + lymphocytes ratio and decreasing inflammatory mediator expressions levels are among the most important immunopharmacological mechanisms for the retrieved flavonoids. CONCLUSION: Naturally occurring flavonoids discussed in the present article have optimal immunomodulation to prevent immune-mediated disorders through management of Th1/Th2 cytokine balance.

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. METHODS: We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. CONCLUSION: Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection.

Medicinal plants and natural molecules with in vitro and in vivo activity against rotavirus: A systematic review.

BACKGROUND: Rotaviruses can cause life-threatening health disorders, such as severe dehydrating gastroenteritis and diarrhea in children. Vaccination is the main preventive strategy to reduce rotavirus diarrhea and the severity of episodes, but vaccines are not fully effective and new episodes may occur, even in vaccinated children. The WHO recommends oral rehydration therapy and zinc supplementation for rotavirus-induced diarrhea management. There is little preclinical evidence to support the use of phytotherapeutics in the management of rotaviral infections. PURPOSE: We aim to review the use of medicinal plants and natural molecules in the management of rotavirus infections in experimental studies. METHODS: Articles, published in the English language between 1991 and 2016, were retrieved from PubMed, Scopus and Web of Science using relevant keywords. The scientific literature mainly focusing on plant natural products with therapeutic efficacies against experimental models of rotavirus, were identified and tabulated. In addition, an assessment of the reliability of animal experiments was determined under ``Risk of Bias'' criteria. CHAPTERS: After an initial search and a revision of the inclusion criteria, 41 reports satisfied the objectives of the study. 36 articles were found concerning the anti-rotaviral potential in rotavirus infected cell lines. Among the active secondary metabolites screened for rotavirus inhibition, the polyphenols of flavonoid structure had acquired the highest number of studies in our survey, compared to phenolic acids, stilbenoids, tannins, pectins, terpenoids and flavonoid glycosides. Also, many phytochemicals reduced the efficacy of viral capsid proteins foremost to their elimination and improved the tendency of host-cell inhibiting virus absorption or by prevention of viral replication. Furthermore, five in vivo studies reported that herbs, as well its components, reduced the duration and severity of diarrhea in mice and piglets. The anti-rotavirus efficacy were highlighted based on improvements in reduction on liquid stool, fecal virus shedding, small intestinal histology, levels of inflammation related cytokines and signaling receptors. However, the quality of the experiments in animal studies contained certain types of bias in terms of how they were conducted and reported. CONCLUSION: We identified and summarized studies on medicinal plants and natural molecules having anti-rotavirus activity in order to further future developments of cures for rotavirus gastroenteritis.

Polyphenols-rich Cyamopsis tetragonoloba (L.) Taub. beans show hypoglycemic and ß-cells protective effects in type 2 diabetic rats.

The aim of this study was to evaluate the antidiabetic activity of Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans in high-fat diet (HFD) fed-streptozotocin (STZ)-induced type 2 diabetic rats. Dose dependent response of oral treatment of C. tetragonoloba beans' methanol extract (CTme) (200 and 400mg/kg b wt.) was assessed by measuring fasting blood glucose, changes in body weight, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, oral glucose tolerance, intraperitoneal insulin tolerance, hepatic glycogen, marker enzymes of carbohydrate metabolism in HFD fed-STZ-induced type 2 diabetic rats. Histology and immunohistochemical analysis of pancreatic islets were also performed. High-performance liquid chromatography (HPLC) analysis of CTme showed the presence of polyphenols such as gallic acid and caffeic acid in the concentrations of 2.46% (W/W) and 0.32% (W/W). CTme significantly reverted the altered biochemical parameters to near normal levels in diabetic rats. Furthermore CTme showed the protective effect on the ß-cells of pancreatic tissues in diabetic rats. These findings indicate that C. tetragonoloba beans have therapeutic potential in HFD fed-STZ-induced hyperglycemia; therefore this can be used in the management of type 2 diabetes.

Hypoglycemic and ß-cells regenerative effects of Aegle marmelos (L.) Corr. bark extract in streptozotocin-induced diabetic rats.

The aim of this study was to examine the antidiabetic potential of Aegle marmelos (L.) Corr. (Rutaceae) bark in a diabetic rat model. Dose dependent effects of methanol extract of Aegle marmelos bark (AM) (200 and 400 mg/kg) on blood glucose, plasma insulin, glycated haemoglobin (HbA1c), total protein, hepatic glycogen, marker enzymes of hepatic function and carbohydrate metabolism were evaluated in (streptozotocin) STZ-induced diabetic rats by oral administration for 30 days. Structural integrity of pancreatic islets was assessed by routine histology while, their functional status was assessed by immunolocalization for insulin. High-performance liquid chromatography (HPLC) study established that AM contained antihyperglycemic constituents, aegelin (1.27% w/w) and lupeol (0.29% w/w). AM at 200 and 400 mg/kg showed significant reduction in blood glucose level by 19.14% and 47.32%, respectively in diabetic rats. AM treatment significantly increased insulin level, and produced similar effects on other biochemical parameters. Histological studies showed the regenerative effect of AM on the ß-cells of diabetic rats. Immunohistochemical observations in the extract treated diabetic rats showed increased insulin-immunoreactive ß-cells. These findings suggest that A. marmelos bark extract has the therapeutic potential in STZ-induced hyperglycemia; hence it can be used in the treatment of diabetes mellitus.

Antihyperglycemic activity and antidiabetic effect of methyl caffeate isolated from Solanum torvum Swartz. fruit in streptozotocin induced diabetic rats.

Natural remedies from medicinal plants are considered to be effective and safe alternatives to treat diabetes mellitus. Solanum torvum Swartz. fruit is widely used in the traditional system of medicine to treat diabetes. In the present study methyl caffeate, isolated from S. torvum fruit, was screened for its efficacy in controlling diabetes in animal models. Antihyperglycemic effect of methyl caffeate was studied in normal glucose-fed rats. The effects of oral administration of methyl caffeate (10, 20 and 40 mg/kg) for 28 days on body weight, fasting blood glucose, plasma insulin, hemoglobin, glycated hemoglobin, total protein, hepatic glycogen and carbohydrate metabolism enzymes in streptozotocin induced diabetic rats were investigated. Histological observations in the pancreas and GLUT4 expression in skeletal muscles were also studied. Methyl caffeate at 40 mg/kg significantly prevented the increase in blood glucose level after glucose administration at 60 min in comparison to the hyperglycemic control group. In streptozotocin induced diabetic rats, methyl caffeate produced significant reduction in blood glucose and increased body weight. The levels and/or activities of other biochemical parameters were near normal due to treatment with methyl caffeate. Methyl caffeate treated diabetic rats showed upregulation of GLUT4 and regeneration of ß-cells in the pancreas. These results substantiated that methyl caffeate possessed hypoglycemic effect, and it could be developed into a potent oral antidiabetic drug.

Solanum torvum Swartz. fruit containing phenolic compounds shows antidiabetic and antioxidant effects in streptozotocin induced diabetic rats.

In this study, quantification of phenolic compounds and the investigation of antidiabetic and antioxidant activities of the fruit of Solanum torvum Swartz. are described. S. torvum fruit methanol extract (STMe) was administered orally at a dose of 200 and 400mg/kg/day to streptozotocin induced diabetic rats for 30days. The levels of glucose, insulin, total protein, hemoglobin, glycated hemoglobin, liver glycogen and marker enzymes of carbohydrate metabolism, hepatic function and antioxidants were analyzed. High-performance liquid chromatography (HPLC) analysis revealed that STMe contained high levels of phenolic compounds, mainly rutin (1.36%w/w), caffeic acid (12.03%w/w), gallic acid (4.78%w/w) and catechin (0.46%w/w). STMe at 200 and 400mg/kg reduced blood glucose level by 17.04% and 42.10%, respectively in diabetic rats. The levels and/or activities of other biochemical parameters were restored significantly compared to diabetic control rats due to treatment with fruit extract. Histology of liver and pancreas in STMe treated groups substantiated the cytoprotective action of the drug. Immunohistochemical observation of islets in extract treated diabetic rats showed apparent ß-cells regeneration. These findings suggest that S. torvum fruit containing phenolic compounds has great potential as a natural source of antidiabetic and antioxidant drug.