Macrophage immunomodulatory activity of Acanthopanax senticousus polysaccharide nanoemulsion via activation of P65/JNK/ikkαsignaling pathway and regulation of Th1/Th2 Cytokines

Nanoemulsions (NE) are used widely in pharmaceutical drug formulations and vaccine preparation, and Acanthopanax senticousus polysaccharide (ASPS) is a natural bioactive compound with immunostimulatory activity. Therefore, NE-loaded ASPS is expected to provide immunological enhancement for effective treatment. In the present study, Acanthopanax senticousus polysaccharide (ASPS was encapsulated into nanoemulsions, the resultant ASPS–NE were coated with a negative charge, and the immune enhancement mechanism of these ASPS-NE formulations was analyzed. The immunosuppressive animal models (70 ICR mice, male) for the study were established using cyclophosphamide. In addition, the activation of splenocyte proliferation, phagocytosis of the macrophages, the ratio of CD4+ to CD8+, the concentrations of the cytokines in serum, Western blot analysis was used for the analysis of the P65/JNK/ikk α signaling pathway in the peritoneal macrophage s. The results revealed that the ASPS-NE could stimulated the proliferation of splenocytes and enhance immunity. The ASPS-NE induced the expression of different cytokines (TNF-α, IFN-γ, IL-2, and IL-6), could activate the expressions of P65, JNK, and ikkα, and regulated the Th1/Th2 cytokines. These findings demonstrated the potential of ASPS-NE formulations for drug delivery and to induce potent and sustained immune responses.

Curcumin Extraction, Isolation, Quantification and Its Application in Functional Foods: A Review With a Focus on Immune Enhancement Activities and COVID-19

An entirely unknown species of coronavirus (COVID-19) outbreak occurred in December 2019. COVID-19 has already affected more than 180 million people causing ~3.91 million deaths globally till the end of June 2021. During this emergency, the food nutraceuticals can be a potential therapeutic candidate. Curcumin is the natural and safe bioactive compound of the turmeric (Curcuma longa L.) plant and is known to possess potent anti-microbial and immuno-modulatory properties. This review paper covers the various extraction and quantification techniques of curcumin and its usage to produce functional food. The potential of curcumin in boosting the immune system has also been explored. The review will help develop insight and new knowledge about curcumin's role as an immune-booster and therapeutic agent against COVID-19. The manuscript will also encourage and assist the scientists and researchers who have an association with drug development, pharmacology, functional foods, and nutraceuticals to develop curcumin-based formulations.

Immune enhancement to prevent infected pancreatic necrosis: A double-blind randomized controlled trial

BACKGROUND&AIMS Infected pancreatic necrosis (IPN) is a highly morbid complication of acute pancreatitis(AP). Since there is evidence of immunosuppression in the early phase of AP, immune enhancement using Thymosin alpha 1 (Tα1), which stimulates both innate and adaptive immunity, may be a therapeutic strategy to prevent IPN. Our aim was to assess the efficacy of early Tα1 treatment on the development of IPN. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial in patients with predicted severe acute necrotizing pancreatitis (ANP). ANP patients with an APACHE II score≥8 admitted within seven days of the advent of symptoms were considered eligible. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg, every 12 hours for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebo (normal saline). The primary outcome was the development of IPN during the index admission. RESULTS From Mar 2017 through Dec 2020, 508 patients were randomized at 16 hospitals, of whom 254 were assigned to receive Tα1 and 254 placebo. During the index admission, 40/254 (15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95%CI -7.4% to 5.0%]; p=0.47). The results were similar in four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15.0%; p=0.15), bleeding (6.3% vs. 3.5%; p=0.15), and gastrointestinal fistula (2.0% vs. 2.4%; p=0.75) during the index admission. CONCLUSIONS The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.

Immune and metabolic beneficial effects of Beta 1,3-1,6 glucans produced by two novel strains of Aureobasidium pullulans in healthy middle-aged Japanese men: An exploratory study

Background: Imbalances in glucose and lipid metabolism in the background of a declining immune system, along with aging, make one prone to glucolipotoxicity-related diseases such as hepatic steatosis and to high risk of infection-related mortality, as with COVID-19, warranting a safe prophylactic measure to help regulate both metabolism and the immune system. Based on the beneficial effects of the AFO-202 strain of black yeast Aureobasidium pullulans-produced beta 1,3-1,6 glucan in balancing of blood glucose and immune enhancement, and that of the N-163 strain of the same species in lipid metabolism and immune modulation, in this pilot study, we have evaluated their specific benefits in healthy human subjects. Methods: Sixteen healthy Japanese male volunteers (aged 40 to 60 years) took part in this clinical trial. They were divided into four groups (n = 4 each): Group I consumed AFO-202 beta glucan (2 sachets of 1 g each per day), IA for 35 days and IB for 21 days; Group II consumed a combination of AFO-202 beta glucan (2 sachets of 1 g each) and N-163 beta glucan (1 sachet of 15 g gel each per day), IIA for 35 days and IIB for 21 days. Investigations for immune stimulation, anti-glycaemic, and anti-cholesterolemia biomarkers were undertaken in all four groups. Results: In terms of metabolic control of glucose, the decrease in HbA1C and glycated albumin (GA) was significantly better in Group I compared with the other groups. Immune enhancement in terms of a significant increase of eosinophils and monocytes and marginal decrease in D-dimer levels, decrease in neutrophil-to-lymphocyte ratio (NLR), with an increase in the lymphocyte-to-CRP ratio (LCR) and leukocyte-to-CRP ratio (LeCR) was observed in Group I. Regulation of lipids by decrease in total and LDL cholesterol was better in Group II, and immunomodulation of coagulation-associated and anti-inflammatory markers by a decrease of CD11b, serum ferritin, galectin-3, fibrinogen was profound in Group II. Conclusion: A. pullulans, a polythermotolerant black yeast - produced AFO-202 beta glucan has balanced blood glucose with marginal immune enhancement in healthy individuals, which when combined with N-163 beta glucan, balanced the lipid profile and immunomodulation. This outcome warrants larger clinical trials to understand the mechanisms and explore the potentials of these safe food supplements in prevention and prophylaxis of diseases due to dysregulated glucose and lipid metabolism, such as fatty liver disease, and infections such as COVID-19 in which a balanced immune activation and immunomodulation are of utmost importance, besides their administration as an adjunct to existing therapeutic approaches of both communicable and non-communicable diseases.