Immunomodulatory effects of vinegar-egg juice: Potential pharmacological effects of a traditional Chinese food remedy?

Thousands of years of historical practice have proven that the ancient Chinese food, vinegar-egg juice, has immune-boosting effects with the presence of many nutritional factors. However, its mechanism of action in the body remains unclear. In this research project, vinegar-egg juice was chosen to analyze its immune-enhancing effects on mice. The immune enhancing effects of egg, vinegar and vinegar egg juice on lymphocytes of mouse spleen were compared. The effects on immune function of mice were analyzed by studying the organ index, natural killer(NK) cell activity, lymphocyte transformation function and cytokine changes in immune organs after treatment with vinegar-egg juice. The mechanism of immune enhancement was speculated by analyzing the changes of total IKKα/ß/IκBα/NF-κB and its phosphorylated protein kinase by Western blot. Experiments have shown that vinegar and eggs have less immune regulation than vinegar-egg juice. Vinegar-egg juice can regulate the cellular and humoral immunity of spleen lymphocytes, increase the phosphorylated kinases of IKKα/ß, reduce the total protein expression of IκBα, and activate the signaling pathway of IKK/IκB/NF-κB. In addition, compared with the control group, vinegar-egg juice reduced the Firmicutes/Bacteroidetes ratio and increased the relative abundance of beneficial bacteria. Furthermore, vinegar-egg juice can raise phosphatidylserine (PS) and serotonin (5-HT) levels in the body. The results showed that the vinegar-egg juice had obvious immunomodulatory activity. It was speculated that the intake of vinegar-egg juice can increase the activity of NK cells, T lymphocytes and B lymphocytes by increasing 5-HT levels, ultimately enhancing the body's immune function. PRACTICAL APPLICATIONS: In this work, we evaluated the immune regulation of vinegar, egg and vinegar-egg juice in mice. In addition, we investigated the effects of vinegar-egg juice on gut microbiota. And combined with the composition of the vinegar-egg juice, it was found that the intake of vinegar-egg juice could increase the activity of NK cells, T lymphocytes and B lymphocytes by increasing 5-HT levels, ultimately enhancing the body's immune function. On the basis of the results of this study, we recommend vinegar-egg juice can be a potential health food to resist the epidemic and improve autoimmunity in special times of the novel coronavirus outbreak.

Efficacy and Safety of Novel Herbal Tablets in COVID-19 Patients in Hospital Stay Days, ICU Admission and Mortality Rate Thereof: An Ppen-Label, Single-Blind Randomized Clinical Trial

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the super-spreading virus, has claimed hundreds of thousands of lives worldwide. Objectives: This study aimed to evaluate the effectiveness of the novel suggested herbal compound, formulated as compressed tablets, in reducing the length of hospital stay(LoS), intensive care unit (ICU) admission, and mortality in confirmed COVID-19 cases. Methods: Following an open-label, single-blind randomized clinical trial design, a total of 200 patients aged 18 65 admitted to Imam Reza hospital in Tabriz, northwest of Iran, were randomized to intervention and control groups in a1:1 ratio, i.e.,100 subjects in each group. The former received standard treatment along with the compressed herbal tablets, and the latter only received the standard treatment. Adverse reactions incidence within 180 days after the beginning of the intervention was set as the primary safety endpoint. The most important and active ingredients of the tablets were Terminalia chebula, Glycyrrhiza glabra, Anacyclus pyrethrum, Senna alexandrina, Ferrula asafoetida, Pistacia lentiscus, Zizyphus jujuba, Crocus sativus, Echinacea angustifolia, and Hyssopus officinalis. This trial is registered at the Iranian Registry of Clinical Trials (code: IRCT20200522047545N1). Results: Those in the intervention arm had significantly lower rates of LoS (7.38 vs. 9.45, P = 0.030), ICU admission (6 out of 100 vs. 32 out of 100, P= 0.000), and mortality (1 vs. 19 out of 100, P= 0.000). Conclusions: Our observations suggest that adequate improvement is provided by the prepared herbal compound along with substantial savings in hospitalization hoteling costs. While further multi-center studies with a larger sample size are needed to extend our knowledge regarding the effect of this new option, these novel clinical data may well provide a new alternative for the management of COVID-19 disease.

A Comprehensive Review of Andrographis paniculata (Burm. f.) Nees and Its Constituents as Potential Lead Compounds for COVID-19 Drug Discovery.

The COVID-19 pandemic has intensively disrupted global health, economics, and well-being. Andrographis paniculata (Burm. f.) Nees has been used as a complementary treatment for COVID-19 in several Asian countries. This review aimed to summarize the information available regarding A. paniculata and its constituents, to provide critical points relating to its pharmacological properties, safety, and efficacy, revealing its potential to serve as a source of lead compounds for COVID-19 drug discovery. A. paniculata and its active compounds possess favorable antiviral, anti-inflammatory, immunomodulatory, and antipyretic activities that could be beneficial for COVID-19 treatment. Interestingly, recent in silico and in vitro studies have revealed that the active ingredients in A. paniculata showed promising activities against 3CLpro and its virus-specific target protein, human hACE2 protein; they also inhibit infectious virion production. Moreover, existing publications regarding randomized controlled trials demonstrated that the use of A. paniculata alone or in combination was superior to the placebo in reducing the severity of upper respiratory tract infection (URTI) manifestations, especially as part of early treatment, without serious side effects. Taken together, its chemical and biological properties, especially its antiviral activities against SARS-CoV-2, clinical trials on URTI, and the safety of A. paniculata, as discussed in this review, support the argument that A. paniculata is a promising natural source for drug discovery regarding COVID-19 post-infectious treatment, rather than prophylaxis.

Herbal Drugs as Immune Booster Against Viral Infections

The immune system involves both active and passive immunization. The antibodies are developed against the antigens during active immunization and are permanently stored. But, in the case of passive immunization, the antibodies are exposed to the same antigens in every person who is already infected. In order to enhance the immune systems i.e. innate and adaptive immune responses, herbal plants are used as an immune booster. Some of the herbal plants have been proven clinically to enhance immunity that includes Morniga oleifera (Drumstick), Azadirachta indica (Neem), Ocimum sanctum (Tulsi), Withania somnifera (Aswagandha), Zingiber officinale (Ginger), Allium sativum (Garlic), Curcuma longa (Turmeric), Emblica officinalis (Amla) etc. Compared to synthetic drugs, herbal drugs have fewer side effects and stimulate the immune system to defend against various foreign pathogens. Even though herbal medicines are usually considered as safe and effective therapy, it is clinically proven that if a drug is effective, it would have some side effects. But, sometimes, the antioxidant property of herbal medicines is helpful in reducing the toxicities produced by any toxic substances or any drugs. This review aims to encourage the study of various herbal constituents and their role in the treatment of different types of viral infections.

Herbal medicine is the way of potential therapeutic option for the treatment of COVID-19: Recent updates

COVID-19 is an acute and progressive respiratory illness, which is highly contagious. In 2020, COVID-19 has become a major health issue;its prevalence has been increasing at an alarming rate across the world. Less availability of COVID-19 drugs, high treatment cost, and side effects affect the quality of life of a person infected with COVID-19 in countries with poorly developed health systems. Through infection, patients can die due to acute respiratory distress syndrome (ARDS) initiated by systemic inflammatory reactions due to the undue emancipation of chemokines and pro-inflammatory cytokines by the immune effector cells. The aim of this review is to summarize and evaluate the evidence of traditional medicine, which can facilitate the treatment options according to the clinical manifestations of COVID-19 patients and has proven effectiveness in prevention and control of disease. The systemic search for medicinal plants for the therapeutics of COVID-19 was performed considering the articles published through the different scientific databases. The results suggested that some important medicinal plants reported for antiviral and anti-allergic/anti-inflammatory activities are Withania somnifera "Ashwagandha", Asparagus racemosus "Shatavari", Ocimum sanctum "Basil", Foeniculum vulgare "Fennel", Allium Sativum "Garlic", Tinospora cordifolia "Giloy", Glycyrrhiza glabra "licorice", Organum vulgare "Oregano", Rosmarinus Officinalis "Rosemary", Salvia "Sage", Zinger officinale "Ginger", Torreya nucifera"Japenese torreya", Isatis indigotica "Ban-Lan-Gen" Echinacea, Panax ginseng, Houttuynia cordata, Cannabinoid (CBD). The traditional medicines against COVID-19, currently under clinical trials (NCT04494204, NCT04387643, NCT04395976, NCT04621903, NCT04621903, NCT04544605) and clinical application of traditional Indian and Chinese medicine for the treatment of COVID-19 are also found. This review highlights the major goal of herbal remedies and their significant role to cure antiviral diseases like COVID-19. It is suggested that promising polyherbal formulations and traditional plants must be investigated on the priority basis to solve current crisis.

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides.

With the growing problem of the emergence of antibiotic-resistant bacteria, the search for alternative ways to combat bacterial infections is extremely urgent. While analyzing the effect of antimicrobial peptides (AMPs) on immunocompetent cells, their effect on all parts of the immune system, and on humoral and cellular immunity, is revealed. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes, and mast cells, participating in innate immunity. They act on B-lymphocytes indirectly, enhancing the induction of antigen-specific immunity, which ultimately leads to the activation of adaptive immunity. The adjuvant activity of AMPs in relation to bacterial and viral antigens was the reason for their inclusion in vaccines and made it possible to formulate the concept of a "defensin vaccine" as an innovative basis for constructing vaccines. The immunomodulatory function of AMPs involves their influence on cells in the nearest microenvironment, recruitment and activation of other cells, supporting the response to pathogenic microorganisms and completing the inflammatory process, thus exhibiting a systemic effect. For the successful use of AMPs in medical practice, it is necessary to study their immunomodulatory activity in detail, taking into account their pleiotropy. The degree of maturity of the immune system and microenvironment can contribute to the prevention of complications and increase the effectiveness of therapy, since AMPs can suppress inflammation in some circumstances, but aggravate the response and damage of organism in others. It should also be taken into account that the real functions of one or another AMP depend on the types of total regulatory effects on the target cell, and not only on properties of an individual peptide. A wide spectrum of biological activity, including direct effects on pathogens, inactivation of bacterial toxins and influence on immunocompetent cells, has attracted the attention of researchers, however, the cytostatic activity of AMPs against normal cells, as well as their allergenic properties and low stability to host proteases, are serious limitations for the medical use of AMPs. In this connection, the tasks of searching for compounds that selectively affect the target and development of an appropriate method of application become critically important. The scope of this review is to summarize the current concepts and newest advances in research of the immunomodulatory activity of natural and synthetic AMPs, and to examine the prospects and limitations of their medical use.

Efficacy of Integrative Siddha Medicine, Kabasura Kudineer with Vitamin C, Zinc Supplementation for the Management of Asymptomatic COVID 19 Cases in Tertiary Hospital: A Randomized Controlled Trial

Introduction: Non-tested asymptomatic COVID-19 cases poses threat of transmitting the disease silently. The Siddha polyherbal formulation, hnology Kabasurakudineer, (KSK) was found to be effective in preventing viral replication of SARS-CoV-2 by in-silico studies. A pilot study was conducted to test the antiviral activity of KSK in asymptomatic individuals tested positive for COVID-19. Methods: A single centre, open labelled, randomized controlled study was carried out during June-August 2020, in Tertiary Medical College Hospital, after approval from the institutional ethics committee and registered in CTRI. RTPCR confirmed COVID-19 asymptomatic cases, aged 18-65 years, consented to participate were . included and those with co-morbidities like diabetes, hypertension, severe respiratory disease, malignancies, pregnant and lactating mothers were excluded. Hospitals of Semnan Uniiessi y 60 participants were randomly assigned to study and control group. Study group received KSK (60 ml) along with vitamin C in the morning and zinc in the night, while the control group (CZ) received vitamin C and zinc for 10 days. The primary outcome was the reduction in the SARS-CoV-2 load (ct value), prevention of progression to symptomatic state. Results: In the study group, there was faster reduction in the viral load in terms of ct value as all the 30 participants turned negative for SARS-Co-V2, while 4 remain positive in the control group on the 10th day. The inflammatory markers and serum cytokine findings were inconclusive. No one progressed to the symptomatic state and no adverse event was reported in either groups. Conclusion: This study demonstrated the potential of Kabasurakudineer in reducing the viral load. Further clinical studies are warranted with larger sample size.

Therapeutic and Industrial Applications of Curdlan With Overview on Its Recent Patents.

Curdlan is an exopolysaccharide, which is composed of glucose linked with ß-(1,3)-glycosidic bond and is produced by bacteria, such as Alcaligenes spp., Agrobacterium spp., Paenibacillus spp., Rhizobium spp., Saccharomyces cerevisiae, Candida spp., and fungal sources like Aureobasidium pullulan, Poria cocos, etc. Curdlan has been utilized in the food and pharmaceutical industries for its prebiotic, viscosifying, and water-holding properties for decades. Recently, the usefulness of curdlan has been further explored by the pharmaceutical industry for its potential therapeutic applications. Curdlan has exhibited immunoregulatory and antitumor activity in preclinical settings. It was observed that curdlan can prevent the proliferation of malarial merozoites in vivo; therefore, it may be considered as a promising therapy for the treatment of end-stage malaria. In addition, curdlan has demonstrated potent antiviral effects against human immunodeficiency virus (HIV) and Aedes aegypti virus. It has been suggested that the virucidal properties of curdlans should be extended further for other deadly viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19). The prebiotic property of curdlan would confer beneficial effects on the host by promoting the growth of healthy microbiota in the gut and consequently help to reduce gastrointestinal disorders. Therefore, curdlan can be employed in the manufacture of prebiotics for the management of various gastrointestinal dysbiosis problems. Studies on the mechanism of action of curdlan-induced suppression in microbial and tumor cells at the cellular and molecular levels would not only enhance our understanding regarding the therapeutic effectiveness of curdlan but also help in the discovery of new drugs and dietary supplements. The primary focus of this review is to highlight the therapeutic interventions of curdlan as an anticancer, anti-malaria, antiviral, and antibacterial agent in humans. In addition, our review provides the latest information about the chemistry and biosynthesis of curdlan and its applications for making novel dairy products, functional foods, and nutraceuticals and also details about the recent patents of curdlan and its derivatives.

SARS-CoV-2 and helminth co-infections, and environmental pollution exposure: An epidemiological and immunological perspective.

Soil-transmitted helminths infect billions of people globally, particularly those residing in low- and middle-income regions with poor environmental sanitation and high levels of air and water pollution. Helminths display potent immunomodulatory activity by activating T helper type 2 (Th2) anti-inflammatory and Th3 regulatory immune responses. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes Coronavirus disease 2019 (COVID-19), can exacerbate Th1/Th17 pro-inflammatory cytokine production in humans, leading to a cytokine storm. Air pollutants (particulate matter, oxygen radicals, hydrocarbons and volatile organic compounds) and water pollutants (metals and organic chemicals) can also intensify Th1/Th17 immune response and could exacerbate SARS-CoV-2 related respiratory distress and failure. The present review focused on the epidemiology of SARS-CoV-2, helminths and fine particulate matter 2.5 µm or less in diameter (PM2.5) air pollution exposure in helminth endemic regions, the possible immunomodulatory activity of helminths against SARS-CoV-2 hyper-inflammatory immune response, and whether air and water pollutants can further exacerbate SARS-CoV-2 related cytokine storm and in the process hinder helminths immunomodulatory functionality. Helminth Th2/Th3 immune response is associated with reductions in lung inflammation and damage, and decreased expression levels of angiotensin-converting enzyme 2 (ACE2) receptors (SARS-CoV-2 uses the ACE2 receptors to infect cells and associated with extensive lung damage). However, air pollutants are associated with overexpression of ACE2 receptors in the epithelial cell surface of the respiratory tract and exhaustion of Th2 immune response. Helminth-induced immunosuppression activity reduces vaccination efficacy, and diminishes vital Th1 cytokine production immune responses that are crucial for combating early stage infections. This could be reversed by continuous air pollution exposure which is known to intensify Th1 pro-inflammatory cytokine production to a point where the immunosuppressive activities of helminths could be hindered. Again, suppressed activities of helminths can also be disadvantageous against SARS-CoV-2 inflammatory response. This "yin and yang" approach seems complex and requires more understanding. Further studies are warranted in a cohort of SARS-CoV-2 infected individuals residing in helminths and air pollution endemic regions to offer more insights, and to impact mass periodic deworming programmes and environmental health policies.

Is Ferroptosis a Future Direction in Exploring Cryptococcal Meningitis?

Cryptococcal meningitis (CM) is the leading cause of mortality among patients infected with human immunodeficiency virus (HIV). Although treatment strategies for CM are continually being developed, the mortality rate is still high. Therefore, we need to explore more therapeutic strategies that are aimed at hindering its pathogenic mechanism. In the field of CM, several studies have observed rapid iron accumulation and lipid peroxidation within the brain, all of which are hallmarks of ferroptosis, which is a type of programmed cell death that is characterized by iron dependence and lipid peroxidation. In recent years, many studies have confirmed the involvement of ferroptosis in many diseases, including infectious diseases such as Mycobacterium tuberculosis infection and coronavirus disease-2019 (COVID-19). Furthermore, ferroptosis is considered as immunogenic and pro-inflammatory as the ferroptotic cells release damage-associated molecular pattern molecules (DAMPs) and alarmin, both of which regulate immunity and pro-inflammatory activity. Hence, we hypothesize that there might be a relationship between this unique cell death modality and CM. Herein, we review the evidence of ferroptosis in CM and consider the hypothesis that ferroptotic cell death may be involved in the cell death of CM.