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1.
Effect of Crocus sativus (Saffron) Intake on Top of Standard Treatment, on Disease Outcomes and Comorbidities in Patients with Rheumatic Diseases: Synthesis without Meta-Analysis (SWiM) and Level of Adherence to the CONSORT Statement for Randomized Controlled Trials Delivering Herbal Medicine Interventions.
Tsiogkas, SG, Grammatikopoulou, MG, Gkiouras, K, Zafiriou, E, Papadopoulos, I, Liaskos, C, Dardiotis, E, Sakkas, LI, Bogdanos, DP
Nutrients. 2021;(12)
Abstract
Rheumatic diseases (RDs) are often complicated by chronic symptoms and frequent side-effects associated with their treatment. Saffron, a spice derived from the Crocus sativus L. flower, is a popular complementary and alternative medicine among patients with RDs. The present systematic review aimed to summarize the available evidence regarding the efficacy of supplementation with saffron on disease outcomes and comorbidities in patients with RD diagnoses. PubMed, CENTRAL, clinicaltrials.gov and the grey literature were searched until October 2021, and relevant randomized controlled trials (RCTs) were screened for eligibility using Rayyan. Risk of bias was assessed using the Cochrane's Risk of Bias-2.0 (RoB) tool. A synthesis without meta-analysis (SWiM) was performed by vote counting and an effect direction plot was created. Out of 125 reports, seven fulfilled the eligibility criteria belonging to five RCTs and were included in the SWiM. The RCTs involved patients with rheumatoid arthritis, osteoarthritis and fibromyalgia, and evaluated outcomes related to pain, disease activity, depression, immune response, inflammation, oxidative stress, health, fatigue and functional ability. The majority of trials demonstrated some concerns regarding overall bias. Moreover, the majority of trialists failed to adhere to the formula elaborations suggested by the CONSORT statement for RCTs incorporating herbal medicine interventions. Standardization of herbal medicine confirms its identity, purity and quality; however, the majority of trials failed to adhere to these guidelines. Due to the great heterogeneity and the lack of important information regarding the standardization and content of herbal interventions, it appears that the evidence is not enough to secure a direction of effect for any of the examined outcomes.
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2.
Standardized astragalus extract for attenuation of the immunosuppression induced by strenuous physical exercise: randomized controlled trial.
Latour, E, Arlet, J, Latour, EE, Juszkiewicz, A, Łuczkowska, K, Marcinkiewicz, A, Basta, P, Trzeciak, J, Machaliński, B, Skarpańska-Stejnborn, A
Journal of the International Society of Sports Nutrition. 2021;(1):57
Abstract
BACKGROUND This paper aimed to verify how a supplementation of rower's diet with Astragalus Membranaceus Root (AMR) modulated their immune system response to maximal physical exertion. METHODS The double-blind study included 18 members of the Polish Rowing Team assigned to the supplemented group (n = 10), and the placebo group (n = 8). The participants performed a 2000 m test on a rowing ergometer at the beginning and at the end of the six-week of intensive training camp during which the supplemented group received 500 mg of AMR. Blood samples were obtained prior to, 1 min after completing, and 24 h after the exertion test. The levels of interleukin 2 (IL2), interleukin 4 (IL4), interleukin 10 (IL10), interferon ɤ (IFN-ɣ), and lactic acid were determined. Subpopulations of T regulatory lymphocytes [CD4+/CD25+/CD127-] (Treg), cytotoxic lymphocytes [CD8+/TCRαβ+] (CTL), natural killer cells [CD3-/CD16+/CD56+] (NK), and TCRδγ-positive cells (Tδγ) were determined with flow cytometry. RESULTS After the camp, the initial NK and Treg levels sustained at the baseline, while Tδγ counts increased relative to the levels in the placebo group. In the supplemented subgroup, a decrease in IL2 level in reaction to maximal exertion clearly deepened while the change in IL-2/IL-10 level induced by the recovery after this exertion clearly increased, relative to the changes in the placebo group. CONCLUSIONS AMR restored the immunological balance in strenuously trained athlets through a stabilization of NK and Treg cells with a positive trend in Tδγ towards Th1 response during restitution by cytokine IL2 modulation.
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3.
Medicinal Plants and Zinc: Impact on COVID-19 Pandemic.
Jalal, Z, Bakour, M, Lyoussi, B
TheScientificWorldJournal. 2021;:9632034
Abstract
The world is currently grappling with the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection can cause fever, a dry cough, fatigue, severe pneumonia, respiratory distress syndrome, and in some cases death. There is currently no effective antiviral SARS-CoV-2 drug. To reduce the number of infections and deaths, it is critical to focus on strengthening immunity. This review aims to conduct a comprehensive search on the previous studies using Google Scholar, ScienceDirect, Medline, PubMed, and Scopus for the collection of research papers based on the role of zinc in the immune system, the antiviral activity of zinc, the effect of zinc supplementation in respiratory infections, the therapeutic approaches against viral infections based on medicinal plants, and the role of plants' bioactive molecules in fighting viral infections. In conclusion, we highlighted the pivotal role of zinc in antiviral immunity and we suggested the bioactive molecules derived from medicinal plants as a search matrix for the development of anti-SARS-CoV-2 drugs.
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4.
Phytotherapy for treatment of cytokine storm in COVID-19.
Sapra, L, Bhardwaj, A, Azam, Z, Madhry, D, Verma, B, Rathore, S, Srivastava, RK
Frontiers in bioscience (Landmark edition). 2021;(5):51-75
Abstract
In 2020, a novel strain of coronavirus (COVID-19) has led to a significant morbidity and mortality worldwide. As of the date of this writing, a total of 116 M cases has been diagnosed worldwide leading to 2.5 M deaths. The number of mortalities is directly correlated with the rise of innate immune cells (especially macrophages) in the lungs that secrete inflammatory cytokines (IL-1β and IL-6) leading to the development of "Cytokine Storm Syndrome" (CSS), multi-organ-failure and death. Given that currently the treatment of this condition is rare and release of effective vaccine might be months away, here, we review the plants and their pharmacologically active-compounds as potential phytopharmaceuticals for the virus induced inflammatory response. Experimental validation of the effectiveness of these natural compounds to prevent or reduce the cytokine storm might be beneficial as an adjunct treatment of SARS-CoV-2.
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5.
Dietary Antiplatelets: A New Perspective on the Health Benefits of the Water-Soluble Tomato Concentrate Fruitflow®.
O'Kennedy, N, Duss, R, Duttaroy, AK
Nutrients. 2021;(7)
Abstract
Our understanding of platelet functionality has undergone a sea change in the last decade. No longer are platelets viewed simply as regulators of haemostasis; they are now acknowledged to be pivotal in coordinating the inflammatory and immune responses. This expanded role for platelets brings new opportunities for controlling a range of health conditions, targeting platelet activation and their interactions with other vascular cells. Antiplatelet drugs may be of wider utility than ever expected but often cause platelet suppression too strong to be used out of clinical settings. Dietary antiplatelets represent a nutritional approach that can be efficacious while safe for general use. In this review, we discuss potential new uses for dietary antiplatelets outside the field of cardiovascular health, with specific reference to the water-soluble tomato extract Fruitflow®. Its uses in different aspects of inflammation and immune function are discussed, highlighting exercise-induced inflammation, mediating the effects of air pollution, and controlling thrombotic aspects of the immune response. Potential future developments in women's health, erectile dysfunction, and the allergic response indicate how broad the utility of dietary antiplatelets can be.
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6.
In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion.
Olwenyi, OA, Asingura, B, Naluyima, P, Anywar, GU, Nalunga, J, Nakabuye, M, Semwogerere, M, Bagaya, B, Cham, F, Tindikahwa, A, et al
BMC complementary medicine and therapies. 2021;(1):114
Abstract
BACKGROUND In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation. METHODS Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load < 1000 copies per mL (n = 10) and viral load > 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated. RESULTS Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p < 0.0001) and both HIV infected groups (P = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative ((p = 0.0001 and p = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups. CONCLUSION A. indica exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm A. indica as a source of natural products for targeting persistent immune activation and inflammation during ART.
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7.
Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review.
Wieland, LS, Piechotta, V, Feinberg, T, Ludeman, E, Hutton, B, Kanji, S, Seely, D, Garritty, C
BMC complementary medicine and therapies. 2021;(1):112
Abstract
BACKGROUND Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of 'cytokine storm'. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines. METHODS We conducted a systematic review and searched six databases, four research registers, and two preprint sites for studies. Two reviewers independently assessed studies for inclusion, extracted data from studies, assessed risk of bias using Cochrane tools, and evaluated certainty of estimates using GRADE. Outcomes included new illnesses and the severity and duration of illness. RESULTS We screened 1187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. We did not find any studies linking elderberry to clinical inflammatory outcomes. However, we found three studies measuring production of cytokines ex vivo after ingestion of elderberry. Elderberry may not reduce the risk of developing the common cold; it may reduce the duration and severity of colds, but the evidence is uncertain. Elderberry may reduce the duration of influenza but the evidence is uncertain. Compared to oseltamivir, an elderberry-containing product may be associated with a lower risk of influenza complications and adverse events. We did not find evidence on elderberry and clinical outcomes related to inflammation. However, we found evidence that elderberry has some effect on inflammatory markers, although this effect may decline with ongoing supplementation. One small study compared elderberry to diclofenac (a nonsteroidal anti-inflammatory drug) and provided some evidence that elderberry is as effective or less effective than diclofenac in cytokine reduction over time. CONCLUSIONS Elderberry may be a safe option for treating viral respiratory illness, and there is no evidence that it overstimulates the immune system. However, the evidence on both benefits and harms is uncertain and information from recent and ongoing studies is necessary to make firm conclusions.
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8.
Anti-Inflammatory Activity of Extracts and Pure Compounds Derived from Plants via Modulation of Signaling Pathways, Especially PI3K/AKT in Macrophages.
Merecz-Sadowska, A, Sitarek, P, Śliwiński, T, Zajdel, R
International journal of molecular sciences. 2020;(24)
Abstract
The plant kingdom is a source of important therapeutic agents. Therefore, in this review, we focus on natural compounds that exhibit efficient anti-inflammatory activity via modulation signaling transduction pathways in macrophage cells. Both extracts and pure chemicals from different species and parts of plants such as leaves, roots, flowers, barks, rhizomes, and seeds rich in secondary metabolites from various groups such as terpenes or polyphenols were included. Selected extracts and phytochemicals control macrophages biology via modulation signaling molecules including NF-κB, MAPKs, AP-1, STAT1, STAT6, IRF-4, IRF-5, PPARγ, KLF4 and especially PI3K/AKT. Macrophages are important immune effector cells that take part in antigen presentation, phagocytosis, and immunomodulation. The M1 and M2 phenotypes are related to the production of pro- and anti-inflammatory agents, respectively. The successful resolution of inflammation mediated by M2, or failed resolution mediated by M1, may lead to tissue repair or chronic inflammation. Chronic inflammation is strictly related to several disorders. Thus, compounds of plant origin targeting inflammatory response may constitute promising therapeutic strategies.
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9.
Effect of Immunomodulatory Supplements Based on Echinacea Angustifolia and Echinacea Purpurea on the Posttreatment Relapse Incidence of Genital Condylomatosis: A Prospective Randomized Study.
De Rosa, N, Giampaolino, P, Lavitola, G, Morra, I, Formisano, C, Nappi, C, Bifulco, G
BioMed research international. 2019;:3548396
Abstract
Introduction. HPV infection is a highly infectious disease; about 65% of partners of individuals with genital warts will develop genital condylomatosis. Only in 20-30% it regresses spontaneously and relapse rates range deeply (9-80%). Echinacea extracts possess antiviral and immunomodulator activities. The aim of this study was to evaluate the efficacy of the therapy, using a formulation based on HPVADL18® (on dry extracts of 200 mg Echinacea Purpurea (EP) roots plus E. Angustifolia (EA)), on the posttreatment relapse incidence of genital condylomatosis. Materials and Methods. It is a prospective single-arm study. Patients with a satisfactory and positive vulvoscopy, colposcopy, or peniscopy for genital condylomatosis were divided into two random groups and subjected to destructive therapy with Co2 Laser. Group A (N=64) immediately after the laser therapy started a 4-month treatment with oral HPVADL18®; Group B (N=61) did not undergo any additional therapy. Patients were subjected to a follow-up after 1, 6, and 12 months. Differences in relapse incidence between the two groups during follow-up controls were evaluated by χ2-test; the groups were stratified by age, gender, and condylomatosis extension degree. Results and Discussion. Gender, age, and condyloma lesions' extension degree showed no statistically significant differences between the two trial groups. The relapse incidence differs statistically between the two studied groups and progressively decreases during the 12 months after treatment in both groups. Statistically significant reduction of relapse rates has been shown in Group A in patients over 25 years old. This difference is significant for both men and women. The relapse incidence is superior in case of extended condylomatosis. Conclusions. In conclusion, the presence of a latent infection causes condylomatosis relapse; in order to reduce the relapse risk an induction of a protective immune response seems to be essential to allow rapid viral clearance from genital areas surrounding lesion and treatment zones. Echinacea promotes this process. EP and EA dry root extracts seem to be a valid adjuvant therapy in reducing relapse incidence of lesions in patients treated for genital condylomatosis.
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10.
An attempt to induce an immunomodulatory effect in rowers with spirulina extract.
Juszkiewicz, A, Basta, P, Petriczko, E, Machaliński, B, Trzeciak, J, Łuczkowska, K, Skarpańska-Stejnborn, A
Journal of the International Society of Sports Nutrition. 2018;:9
Abstract
BACKGROUND The aim of this study was to analyze the response of selected components of the immune system in rowers to maximal physical exercise, and to verify if this response can be modulated by supplementation with spirulina (cyanobacterium Spirulina platensis). METHOD The double-blind study included 19 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group (n = 10), receiving 1500 mg of spirulina extract for 6 weeks, or to the placebo group (n = 9). The participants performed a 2000-m test on a rowing ergometer at the beginning (1st examination) and at the end of the supplementation period (2nd examination). Blood samples were obtained from the antecubital vein prior to each exercise test, 1 min after completing the test, and after a 24-h recovery period. Subpopulations of T regulatory lymphocytes (Tregs) [CD4+/CD25+/CD127-], cytotoxic lymphocytes (CTLs) [CD8+/TCRαβ+], natural killer (NK) cells [CD3-/CD16+/CD56+] and TCRδγ-positive (Tδγ) cells were determined by means of flow cytometry. RESULTS On the 2nd examination, athletes from the supplemented group showed neither a post-exercise increase in Treg count nor a post-recovery decrease in Tδγ cell count (both observed in the placebo group), and presented with significantly lower values of Treg/CTL prior to and after the exercise. During the same examination, rowers from the placebo group showed a significant post-recovery increase in Treg/(NK + Tδγ + CTL) ratio, which was absent in the supplemented group. CONCLUSION The results of this study imply that supplementation with spirulina extract may protect athletes against a deficit in immune function (especially, anti-infectious function) associated with strenuous exercise, and may cause a beneficial shift in "overtraining threshold" preventing a radical deterioration of immunity.