Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19.

The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them.

Comparison of water- and alkali-extracted polysaccharides from Fuzhuan brick tea and their immunomodulatory effects in vitro and in vivo.

In the present study, the purpose is to compare the effect of water extraction and alkali-assisted extraction on the structural characteristics and immunomodulatory activity of polysaccharides from Fuzhuan brick tea (FBTPs). The results indicated that water-extracted FBTPs (W-FBTPs) and alkali-extracted FBTPs (A-FBTPs) had similar molecular weights but different monosaccharide compositions, of which A-FBTPs had a higher yield and uronic acid groups corresponding to galacturonic acid (GalA). Moreover, A-FBTPs had stronger ability to promote phagocytic capacity, acid phosphatase activity and nitric oxide (NO) secretion in macrophages in vitro. In the in vivo study, A-FBTPs exhibited a promising effect to adjust the immune imbalance by enhancing the body features, antioxidant activities, immune response and intestinal mucosal barrier in cytoxan (CTX)-induced immunosuppressive mice. Besides, A-FBTP supplementation effectively improved CTX-induced gut microbiota dysbiosis, including promoting the abundance of beneficial bacteria (e.g., Lactobacillus) and short chain fatty acid (SCFA)-producing bacteria (e.g., Lachnospiraceae, Prevotellaceae and Ruminococcaceae), along with reducing the growth of potentially pathogenic microbes (e.g., Desulfovibrionaceae and Helicobacter). These findings suggested that alkaline extraction might be a promising way to obtain high-quality acidic polysaccharides from Fuzhuan brick tea (FBT), and A-FBTPs could be developed as novel potential prebiotics and immunomodulators for further application in food formulations.

Modulatory effects of R10 fraction of garlic (Allium sativum L.) on hormonal levels, T cell polarization, and fertility-related genes in mice model of polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is an inflammatory endocrine-metabolic disorder related to reproductive system characterized by polycystic ovarian morphology, androgen excess, and chronic anovulation. Current treatments haven't been very successful in PCOS treatment and the problem still remains as a challenge. Therefore, new approaches should be applied to overcome the disease. Previous studies demonstrated immunomodulatory effects of R10 fraction of garlic in the treatment of inflammatory conditions such as cancer. Considering previous studies suggesting immunomodulatory therapy for PCOS, therapeutic effects of R10 fraction was evaluated in a mouse model of PCOS. To do so, PCOS was developed by intramuscular injection of estradiol valerate. Treatment with R10 fraction, isolated from garlic, was performed and the alterations in hormonal levels (estradiol, progesterone, and testosterone), T cell polarization markers (IFN-γ, IL-4, and IL-17), and expression of fertility-related genes (Gpx3 and Ptx3) were evaluated. The results showed that hormonal levels were elevated in PCOS model comparing to normal animals but were markedly modulated after treatment with R10 fraction. Moreover, a severe disturbance in T cell polarization with a significant reduction of fertility-related genes expression were detected in PCOS-induced ovaries. Treatment with R10 fraction also represented modulatory effects on T cell polarization by increasing IL-4 and decreasing IL-17 and IFN-γ levels. Accordingly, fertility-related genes were also modulated following treatment with R10 fraction in PCOS. Our study elucidated that R10 fraction of garlic possess immunomodulatory effects alleviating PCOS symptoms. This approach could be adjusted to give rise the optimum therapeutic results and considered as a candidate therapeutic approach for PCOS.

The immune-enhancing effects of a mixture of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) or its active constituent nodakenin.

ETHNOPHARMACOLOGICAL RELEVANCE: A mixture (SH003) of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) has beneficial effects against several carcinomas. There have been few reports on an immune-enhancing activity of SH003 and its active constituent nodakenin. AIM OF THE STUDY: This study aimed at identifying the immune-enhancing effect of SH003 and nodakenin. MATERIALS AND METHODS: The immune-enhancing effect was evaluated using RAW264.7 macrophages, mouse primary splenocytes, and a cyclophosphamide (CP)-induced immunosuppression murine model. RESULTS: The results show that SH003 or nodakenin stimulated the production levels of granulocyte colony-stimulating factor, IL-12, IL-2, IL-6, TNF-α, and nitric oxide (NO) and the expression levels of iNOS in RAW264.7 macrophages. SH003 or nodakenin also enhanced NF-κB p65 activation in RAW264.7 macrophages. SH003 or nodakenin stimulated the production levels of IFN-γ, IL-12, IL-2, TNF-α, and NO and the expression levels of iNOS in splenocytes. SH003 or nodakenin increased the splenic lymphocyte proliferation and splenic NK cell activity. In addition, SH003 or nodakenin increased the levels of IFN-γ, IL-12, IL-2, IL-6, and TNF-α in the serum and spleen of CP-treated mice, alleviating CP-induced immunosuppression. CONCLUSION: Taken together, the results of this study show that SH003 improved immunosuppression through the activation of macrophages, splenocytes, and NK cells. These findings suggest that SH003 could be applied as a potential immunostimulatory agent for a variety of diseases caused or exacerbated by immunodeficiency.

Cynanchum auriculatum Royle ex Wight., Cynanchum bungei Decne. and Cynanchum wilfordii (Maxim.) Hemsl.: Current Research and Prospects.

Cynanchum auriculatum Royle ex Wight. (CA), Cynanchum bungei Decne. (CB) and Cynanchum wilfordii (Maxim.) Hemsl. (CW) are three close species belonging to the Asclepiadaceous family, and their dry roots as the bioactive part have been revealed to exhibit anti-tumor, neuroprotection, organ protection, reducing liver lipid and blood lipid, immunomodulatory, anti-inflammatory, and other activities. Until 2021, phytochemistry investigations have uncovered 232 compounds isolated from three species, which could be classified into C21-steroids, acetophenones, terpenoids, and alkaloids. In this review, the morphology characteristics, species identification, and the relationship of botany, extraction, and the separation of chemical constituents, along with the molecular mechanism and pharmacokinetics of bioactive constituents of three species, are summarized for the first time, and their phytochemistry, pharmacology, and clinical safety are also updated. Moreover, the direction and limitation of current research on three species is also discussed.

Gelsemium elegans Benth: Chemical Components, Pharmacological Effects, and Toxicity Mechanisms.

Gelsemium elegans Benth (GEB), also known as heartbreak grass, is a highly poisonous plant belonging to the family Loganiaceae and genus Gelsemium that has broad application prospects in medicine. This article reviews its chemical components, pharmacological effects, toxicity mechanisms, and research progress in clinical applications in recent years. Indole alkaloids are the main active components of GEB and have a variety of pharmacological and biological functions. They have anti-tumor, anti-inflammatory, analgesic, and immunomodulation properties, with the therapeutic dose being close to the toxic dose. Application of small-dose indole alkaloids fails to work effectively, while high-dose usage is prone to poisoning, aggravating the patient's conditions. Special caution is needed, especially to observe the changes in the disease condition of the patients in clinical practice. In-depth research on the chemical components and mechanisms of GEB is essential to the development of promising lead compounds and lays the foundation for extensive clinical application and safe usage of GEB in the future.

Chemical Characterization, Antitumor, and Immune-Enhancing Activities of Polysaccharide from Sargassum pallidum.

Searching for natural products with antitumor and immune-enhancing activities is an important aspect of cancer research. Sargassum pallidum is an edible brown alga that has been used in Chinese traditional medicine for the treatment of tumors. However, the purification and application of its active components are still insufficient. In the present study, the polysaccharides from S. pallidum (SPPs) with antitumor and immune-enhancing activities were isolated and purified, and five polysaccharide fractions (SPP-0.3, SPP-0.5, SPP-0.7, SPP-1, and SPP-2) were obtained. The ratio of total saccharides, monosaccharide composition, and sulfated contents was determined, and their structures were analyzed by Fourier transform infrared spectroscopy. Moreover, bioactivity analysis showed that all five fractions had significant antitumor activity against three types of cancer cells (A549, HepG2, and B16), and can induce cancer cell apoptosis. In addition, the results indicated that SPPs can enhance the proliferation of immune cells and improve the expression levels of serum cytokines (IL-6, IL-1ß, iNOS, and TNF-α). SPP-0.7 was identified as the most active fraction and selected for further purification, and its physicochemical properties and antitumor mechanism were further analyzed. Transcriptome sequencing result showed that SPP-0.7 can significantly induce the cell apoptosis, cytokine secretion, and cellular stress response process, and inhibit the normal physiological processes of cancer cells. Overall, SPPs and SPP-0.7 may be suitable for use as potential candidate agents for cancer therapy.

Evaluating nitric oxide produced by rat inflamed microglial cell Lline, CHME-5, under the effect of IMOD.

Nitric oxide (NO), as a free radical, is produced by inflamed microglia cells and is one of the destructive factors of the immune system and a factor in myelin degradation. Therefore, inhibition of microglia activity is a chief strategy in reducing neurotoxic damage to the central nervous system. In this study, an herbal Immunomodulatory Drug (IMOD) was used to evaluate the effects of this drug in controlling the amount of nitric oxide. Nitric oxide induction was performed by bacterial lipopolysaccharide (LPS) in rat inflamed microglial cell line, CHME-5. ELISA test was used to measure the produced nitric oxide at 24, 48, and 72 hours. The results showed that the high concentrations of IMOD (1.2, and 4% V/V) had anti-inflammatory effects on microglial cells and were able to reduce the amount of nitric oxide in these cells but the effective dose of IMOD was in the range of 1.2% V/V. Therefore, the safest dose and the best time for the effect of IMOD on inflammatory cell groups are 1.2% V/V and 72h, respectively. Hence, with further studies, IMOD can be considered as an herbal anti-inflammatory drug that is effective in controlling neurodegenerative diseases.

Lipoic acid. Kinetics and pluripotent biological properties and derivatives.

Lipoic acid (LA) is globally known and its supplements are widely used. Despite its importance for the organism it is not considered a vitamin any more. The multiple metabolic forms and the differences in kinetics (absorption, distribution and excretion), as well as the actions of its enantiomers are analysed in the present article together with its biosynthetic path. The proteins involved in the transfer, biotransformation and activity of LA are mentioned. Furthermore, the safety and the toxicological profile of the compound are commented, together with its stability issues. Mechanisms of lipoic acid intervention in the human body are analysed considering the antioxidant and non-antioxidant characteristics of the compound. The chelating properties, the regenerative ability of other antioxidants, the co-enzyme activity and the signal transduction by the implication in various pathways will be discussed in order to be elucidated the pleiotropic effects of LA. Finally, lipoic acid integrating analogues are mentioned under the scope of the multiple pharmacological actions they acquire towards degenerative conditions.

Differential effects of Huaier aqueous extract on human CD4+T lymphocytes from patients with primary immune thrombocytopenia.

Huaier, a traditional Chinese medicine, is currently used to treat certain types of cancer in the clinic and is also regarded as an immune-modulating and immune-enhancing agent that regulates immune cells. Emerging evidence indicates that an imbalance of immune cells, such as CD4+ T helper (Th) lymphocytes, contributes to the progression of immune thrombocytopenia (ITP), but the effects of Huaier on the regulation of CD4+ T cells are not yet fully elucidated. In the present study, Jurkat cells and peripheral blood mononuclear cells (PBMCs) from patients with ITP and healthy volunteers were treated with Huaier aqueous extract (HR). The CCK-8 assay revealed that HR suppressed the proliferation of Jurkat cells in a dose-dependent manner, whereas 3 mg/mL could decrease cell viability by 50%. At the latter concentration, the activation of CD4+ T cells from patients with ITP was partially attenuated. In addition, HR could correct the unbalanced Th1/Th2 polarization and inhibit the secretion of pro-inflammatory factors interleukin (IL)-2, tumor necrosis factor-α, and interferon-γ. It also suppressed Treg and facilitated Th17 differentiation, but did not change the levels of IL-10 and transforming growth factor-ß. Thus, this study provides more information on how Huaier regulates cellular immunity and improves our understanding of the use of Huaier in ITP.

Role of taraxerone isolated from Leucas lavandulifolia, as an immunomodulator.

ETHNOPHARMACOLOGICAL RELEVANCE: The Indian tradition system of medicine enlists a large number of plants for basic health care. Leucas lavandulifolia is mentioned in the ayurvedic medicinal system and also used among the folklores. The plant is used for the treatment of fever, asthma, psoriasis, dermatitis and healing snake bites. The scientific validation of the plant for their traditional use in different immune related disorders are yet to be explored. AIM OF THE STUDY: The study aims to isolate immunomodulatory active compound from Leucas lavandulifolia and evaluating its efficiency in immune related disorders. MATERIALS AND METHODS: The immunomodulatory activity of the phytocompound is evaluated through in vitro and in vivo studies. The compound purification and identification were done by chromatography and LC/Q-TOF respectively. Its immunomodulatory activity was evaluated in cells like PBMC, neutrophils and macrophages by MTT assay and cell cycle analysis. Animal studies were performed on Swiss albino mice. The levels of IL-4 and IL-6 cytokines were also evaluated in both in vitro and in vivo models. RESULTS: Leucas lavandulifolia stem portion was found to have good modulatory property. An active immunomodulator was isolated from the methanol extract of the plant. LC/Q-TOF data revealed the isolated compound to be taraxerone. In PBMC, the compound was capable of suppressing the proliferation rate of the compound indicated by a decrease in cell numbers. The activated IL-4 and IL-6 production was also suppressed actively at 25 µg/ml of taraxerone. Similar inhibitory effects were seen in RAW 264.7 and THP-1 macrophage cell lines. An IC50 value of 17.5 µg/ml was obtained for taraxerone in LPS stimulated RAW 264.7 macrophage cell lines. The NO level, IL-4, IL-6 and phagocytosis in the LPS stimulated macrophage was effectively lowered by 25 µg/ml of taraxerone. In PMA stimulated THP-1 Macrophage Cell Lines, taraxerone was capable of suppressing the cell number and IL-6. The compound didn't show any effect on IL-4 levels. The compound exhibited an immunosuppressive activity in PHA induced PMN cells by suppressing the respiratory burst and interleukins IL-4 and IL-6. TX could also suppress the proliferation of DNCB induced monocyte cells and IL-4. The haematological parameters exhibited a significant suppression for the high dose group of taraxerone. The antibody titre and phagocytic index was suppressed by the high dose group, whereas the low dose group did not have any effect. So taraxerone at 50 mg/kg body weight is capable of modulating the B-lymphocytes and macrophages. But the compound has exhibited insignificant effect on the DTH hypersensitivity response and organ index. CONCLUSION: Taraxerone at high concentration was capable of suppressing stimulated PBMC, macrophage and PMN. The activated nitric oxide, IL-4, IL-6 production and phagocytosis was also suppressed. The haematological parameters, antibody titre and phagocytic index was also lowered in antigenically challenged mice. The terpenoid taraxerone exhibits a good modulatory effect on the immune system and proves to be a potent drug for the treatment of many allergic disorders.