Solubilized curcuminoid complex prevents extensive immunosuppression through immune restoration and antioxidant activity: Therapeutic potential against SARS-CoV-2 (COVID-19).

The therapeutic benefits of curcuminoids in various diseases have been extensively reported. However, little is known regarding their preventive effects on extensive immunosuppression. We investigated the immunoregulatory effects of a curcuminoid complex (CS/M), solubilized with stevioside, using a microwave-assisted method in a cyclophosphamide (CTX)-induced immunosuppressive mouse model and identified its new pharmacological benefits. CTX-treated mice showed a decreased number of innate cells, such as dendritic cells (DCs), neutrophils, and natural killer (NK) cells, and adaptive immune cells (CD4 and CD8 T cells) in the spleen. In addition, CTX administration decreased T cell activation, especially that of Th1 and CD8 T cells, whereas it increased Th2 and regulatory T (Treg) cell activations. Pre-exposure of CS/M to CTX-induced immunosuppressed mice restored the number of innate cells (DCs, neutrophils, and NK cells) and increased their activity (including the activity of macrophages). Exposure to CS/M also led to the superior restoration of T cell numbers, including Th1, activated CD8 T cells, and multifunctional T cells, suppressed by CTX, along with a decrease in Th2 and Treg cells. Furthermore,CTX-injected mice pre-exposed to CS/M were accompanied by an increase in the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), which play an essential role against oxidative stress. Importantly, CS/M treatment significantly reduced viral loads in severe acute respiratory syndrome coronavirus2-infected hamsters and attenuated the gross pathology in the lungs. These results provide new insights into the immunological properties of CS/M in preventing extensive immunosuppression and offer new therapeutic opportunities against various cancers and infectious diseases caused by viruses and intracellular bacteria.

Preventive Effect of Garlic Oil and Its Organosulfur Component Diallyl-Disulfide on Cigarette Smoke-Induced Airway Inflammation in Mice.

Garlic (Allium sativum) has traditionally been used as a medicinal food and exhibits various beneficial activities, such as antitumor, antimicrobial, hypolipidemic, antiarthritic, and hypoglycemic activities. The aim of this study was to explore the preventive effect of garlic oil (GO) and its organosulfur component diallyl disulfide (DADS) on cigarette smoke (CS)-induced airway inflammation. Mice were exposed to CS daily for 1 h (equivalent to eight cigarettes per day) for two weeks, and intranasally instilled with lipopolysaccharide (LPS) on day 12 after the initiation of CS exposure. GO and DADS were administered to mice by oral gavage, both at rates of 20 and 40 mg/kg, for 1 h before CS exposure for two weeks. In the bronchoalveolar lavage fluid, GO and DADS inhibited the elevation in the counts of inflammatory cells, particularly neutrophils, which were induced in the CS and LPS (CS + LPS) group. This was accompanied by the lowered production (relative to the CS + LPS group) of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. Histologically, GO and DADS inhibited the CS- and LPS-induced infiltration of inflammatory cells into lung tissues. Additionally, GO and DADS inhibited the phosphorylation of extracellular signal-regulated kinase and the expression of matrix metalloproteinase-9 in the lung tissues. Taken together, these findings indicate that GO and DADS could be a potential preventive agent in CS-induced airway inflammation.

Artemisia argyi attenuates airway inflammation in ovalbumin-induced asthmatic animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi is a traditional herbal medicine in Korea and commonly called as mugwort. It is traditionally used as food source and tea to control abdominal pain, dysmenorrhea, uterine hemorrhage, and inflammation. AIM OF THE STUDY: We investigated the effects of A. argyi (TOTAL) and dehydromatricarin A (DA), its active component on ovalbumin (OVA)-induced allergic asthma. MATERIALS AND METHODS: The animals were sensitized on day 0 and 14 by intraperitoneal injection of OVA with aluminum hydroxide. On day 21, 22 and 23 after the initial sensitization, the animals received an airway challenge with OVA for 1h using an ultrasonic nebulizer. TOTAL (50 and 100mg/kg) or DA (10 and 20mg/kg) were administered to mice by oral gavage once daily from day 18-23. Airway hyperresponsiveness (AHR) was measured 24h after final OVA challenge. RESULT: TOTAL and DA treated animals reduced inflammatory cell counts, cytokines and AHR in asthmatic animals, which was accompanied with inflammatory cell accumulation and mucus hypersecretion. Furthermore, TOTAL and DA significantly declined Erk phosphorylation and the expression of MMP-9 in asthmatic animals. CONCLUSION: In conclusion, we indicate that Total and DA suppress allergic inflammatory responses caused by OVA challenge. It was considered that A. argyi has a potential for treating allergic asthma.

Quantitative analysis of phenolic metabolites from different parts of Angelica keiskei by HPLC-ESI MS/MS and their xanthine oxidase inhibition.

Angelica keiskei is used as popular functional food stuff. However, quantitative analysis of this plant's metabolites has not yet been disclosed. The principal phenolic compounds (1-16) within A. keiskei were isolated, enabling us to quantify the metabolites within different parts of the plant. The specific quantification of metabolites (1-16) was accomplished by multiple reaction monitoring (MRM) using a quadruple tandem mass spectrometer. The limit of detection and limit of quantitation were calculated as 0.4-44 µg/kg and 1.5-148 µg/kg, respectively. Abundance and composition of these metabolites varied significantly across different parts of plant. For example, the abundance of chalcones (12-16) decreased as follows: root bark (10.51 mg/g)>stems (8.52 mg/g)>leaves (2.63 mg/g)>root cores (1.44 mg/g). The chalcones were found to be responsible for the xanthine oxidase (XO) inhibition shown by this plant. The most potent inhibitor, xanthoangelol inhibited XO with an IC50 of 8.5 µM. Chalcones (12-16) exhibited mixed-type inhibition characteristics.

Effect of high vs standard early parenteral amino acid supplementation on the growth outcomes in very low birth weight infants.

BACKGROUND: The goal of this study was to evaluate the effect of 2 different strategies for parenteral amino acid (AA) supplementation in the range of standard doses (>1.0-1.5 g/kg/d) on growth outcomes in very low birth weight (VLBW) infants. MATERIALS AND METHODS: The unit policy of AA doses on the first day of life changed from 1.5 g/kg/d (n = 56; standard protein group, SP, in 2008) to 3.0 g/kg/d (n = 53; high protein group, HP, in 2009) with a daily advance to a target dose of 3.5-4.0 g/kg/d. Daily nutritive and laboratory profiles were collected for the initial 14 days, and patient weight, height, and head circumference on postnatal day 14 and again at 36 weeks, 6 months, and 12 months of corrected age were evaluated. RESULTS: During the first 14 days, AA intake was greater in the HP group than in the SP group (2.9 ± 0.4 vs 2.6 ± 0.4 g/kg/d, P < .001). The HP group demonstrated a lower peak plasma glucose level during the first 3 days (116 ± 24 vs 137 ± 39 mg/dL) and a higher serum urea nitrogen level for the first 14 postnatal days than the SP group (19.2 ± 7.0 vs 14.8 ± 6.7 mg/dL) (both P < .01). From birth to postnatal 14 days and to 36 weeks, 6 months, and 12 months of corrected age, the z score changes in all growth parameters did not differ between the 2 groups. CONCLUSION: In the range of the standard AA protocol, there was no dose-response relationship between the early AA doses and the growth outcomes in VLBW infants.

Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition.

Pterocarpans (1-3) and flavanones (4-10) were isolated from Sophora flavescens and screened for their ability to inhibit neuraminidase (an enzyme crucial in the proliferation of the influenza virus). The majority of inhibitors were shown to have IC(50) values of 20 microM or below. Interestingly, pterocarpan 1 emerged as the best inhibitor with an IC(50) of 1.4 microM. We were thus able to prove that the pterocarpan skeleton is a new class of lead structure for neuraminidase inhibitors. Our studies reveal that the IC(50) has a marked dependence upon structure in the case of the pterocarpans but much less so for the flavanones. Kinetic analysis disclosed that all inhibitors are noncompetitive. Our molecular docking experiment resulted that the most potent pterocarpan-derived inhibitor 1 may bind to another binding pocket adjacent to the active site.