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1.
Plants and Phytomolecules for Immunomodulation: Recent Trends and Advances ; : 391-411, 2022.
Article in English | Scopus | ID: covidwho-20239826

ABSTRACT

Immunity is the major mechanism of host defence system against infectious and chronic diseases. The recent global concern of recent viral infection of SARS-CoV-19 has raised the demand of functional foods, nutraceuticals and fruits that can boost immunity. This will help in managing the overall physiological health and prevention of infectious and chronic diseases. Medicinal plants and fruits can help in boosting immunity through modulation of immune system and changing the types of immune response such as involvement of the induction, expression or amplification of the genes and proteins in inflammation and antioxidant system. The traditional medicine systems have used a wide variety of plants and fruits as supplement for immunomodulation including those for stimulation of immune system as well as immune compromisation deemed per se. Some of the plants that have been listed for immune boosting abilities included Curcuma longa, Withania somnifera, Phyllanthus emblica, Azadirachta indica, Panax ginseng, Rhododendron spiciferum, Caesalpinia bonducella, Tinospora cordifolia, Capparis zeylanica, Asparagus racemosus, Nelumbo nucifera, Arnica montana, Calendula officinalis, Echinacea purpurea and Euphorbia tirucalli. Reports indicate that a wide variety of phytochemicals like polysaccharide, alkaloids, flavonoids, terpenoids, lactones and glycoside have shown immunomodulatory properties under different pathophysiological conditions. Amongst the diverse chemical profile of plant extracts, polysaccharides are the water-soluble molecules that could activate immune responses when interacting directly with immune cells, while hydrophobic compounds like flavonoids such as quercetin and luteolin and terpenoids such as sesquiterpene lactones and curcumin showed potent immunomodulatory effects. Growing evidences suggest that phytochemicals from functional foods and fruits may be useful in maintaining the cytokine and chemokine balance, regulating oxidative status of cells, and targeting the specific cellular receptors as therapeutic targets. This chapter comprehensively enlists the plant resources with immune boosting abilities and explore their phytochemical characterization and molecular mechanism behind their protective effects. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

2.
Journal of Plant Biotechnology ; 50:27-33, 2023.
Article in English | Scopus | ID: covidwho-2322952

ABSTRACT

Zizyphus jujube is a plant in the buckthorn family (Rhamnaceae) that has been the subject of research into antibacterial, antifungal and anti-inflammatory properties of its fruit and seed. However, few studies have investigated its leaves. In this study, the anti-inflammatory activity of ZJL (an extract of Z. jujube leaf) was evaluated to verify its potential as an anti-inflammatory agent and SARS-CoV-2 medicine, using nitric oxide (NO) assay, RT-PCR, SDS-PAGE, Western blotting, and UHPLC/TOFHRMS analysis. We found that ZJL suppresed pro-inflammatory mediators such as NO, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-induced RAW264.7 cells. ZJL acted by inhibiting NF-KB and MAPK signaling pathway activity. We also confirmed that ZJL contains a phenol compound and flavonoids with anti-inflammatory activity such as trehalose, maleate, epigallocatechin, hyperoside, catechin, 3-O-coumaroylquinic acid, rhoifolin, gossypin, kaempferol 3-neohesperidoside, rutin, myricitrin, guaiaverin, quercitrin, quercetin, ursolic acid, and pheophorbide a. These findings suggest that ZJL may have great potential for the development of anti-inflammatory drugs and vaccines via inhibition of NF‐ĸB and MAPK signaling in LPS-induced RAW264.7 cells. © Korean Society for Plant Biotechnology.

3.
Comput Biol Chem ; 105: 107898, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2325654

ABSTRACT

Coronavirus disease is caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) known as COVID-19. COVID-19 has caused the deaths of 6,541,936 people worldwide as of September 27th, 2022. SARS-CoV-2 severity is determined by a cytokine storm condition, in which the innate immune system creates an unregulated and excessive production of pro-inflammatory such IL-1, IL-6, NF Kappa B, and TNF alpha signaling molecules known as cytokines. The patient died due to respiratory organ failure and an acute complication because of the hyper-inflammation phenomenon. Green tea, soybean, and guava bioactive substances are well-known to act as anti-inflammation, and antioxidants become prospective COVID-19 illness candidates to overcome the cytokine storm. Our research aims to discover the bioactivity, bioavailability, and protein targets of green tea, soybean, and guava bioactive compounds as anti-inflammatory agents via the TNF inhibition pathway. The experiment uses in silico methods and harnesses the accessible datasets. Samples of 3D structure and SMILE identity of bioactive compounds were retrieved from the KNApSAck and Dr Duke databases. The QSAR analysis was done by WAY2DRUG web server, while the ADME prediction was performed using SWISSADME web server, following the Lipinsky rules of drugs. The target protein and protein-protein interaction were analyzed using STRING DB and Cytoscape software. Lastly, molecular docking was performed using Autodock 4.2 and visualization with BioVia Discovery Studio 2019. The identified study showed the potential of green tea, soybean, and guava's bioactive compounds have played an important role as anti-inflammation agents through TNF inhibitor pathway.


Subject(s)
COVID-19 , Psidium , Humans , SARS-CoV-2 , Soybeans , Cytokine Release Syndrome/drug therapy , Tea , Molecular Docking Simulation , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
4.
Natural Product Communications ; 18(4), 2023.
Article in English | EMBASE | ID: covidwho-2316742

ABSTRACT

Background: Viral infections pose some of the most serious human health concerns worldwide. The infections caused by several viruses, including coronavirus, hepatitis virus, and human immunodeficiency virus, are difficult to treat. Method(s): This review details the findings of a literature search performed on the antiviral properties of luteolin. The keywords engaged in the search are "virus" along with "luteolin." Results: Luteolin possesses antiviral properties, which is the basis for the current review. It is an important natural flavonoid with numerous important biological properties, including anti-inflammatory, immune regulatory, and antitumor effects, and is found in vegetables, fruits, and several medicinal plants. Recent studies have revealed that many traditional Chinese medicines that contain luteolin inhibit the replication of coronaviruses. Conclusion(s): Luteolin effectively inhibits the replication of coronavirus, influenza virus, enterovirus, rotavirus, herpes virus, and respiratory syncytial virus, among others. In particular, it prevents viral infection by improving the body's nonspecific immunity and antioxidation capacity and inhibiting many pathways related to virus infection and replication, such as MAPK, PI3K-AKT, TLR4/8, NF-kappaB, Nrf-2/hemeoxygenase-1, and others. It also regulates the expression of some receptors and factors, including hepatocyte nuclear factor 4alpha, p53, NLRP3, TNF-alpha, and interleukins, thereby interfering with the replication of viruses in cells. Luteolin also promotes the repair of damaged cells induced by proinflammatory factors by regulating the expression of inflammatory molecules. The overall effect of these processes is the reduction in viral replication and, consequently, the viral load. This review summarizes the antiviral effect of luteolin and the mechanism underlying this property.Copyright © The Author(s) 2023.

5.
J Biomed Sci ; 30(1): 30, 2023 May 03.
Article in English | MEDLINE | ID: covidwho-2316619

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has impacted human lifestyles around the world, causing huge distress in terms of public health systems, emergency response capacity and economic development. The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with respiratory involvement, cardiovascular-related diseases, and ultimately causes multiple organ failure and death in severely affected individuals. Thus, effective prevention or early treatment of COVID-19 is critical. An effective vaccine offers a way out of the pandemic for governments, the scientific community and people worldwide, but we still lack effective drug therapies, including treatments for the prevention and treatment of COVID-19. This had led to a high global demand for many complementary and alternative medicines (CAMs). Moreover, many healthcare providers are now requesting information about CAMs that prevent, relieve, or treat the symptoms of COVID-19 and even alleviate vaccine-related side effects. Experts and scholars must therefore become familiar with the use of CAMs in COVID-19, current research directions and effectiveness of CAMs for COVID-19. This narrative review updates the current status and research worldwide on the use of CAMs for COVID-19. The review provides reliable evidence on theoretical viewpoints and therapeutic efficacies of CAM combinations, and evidence in support of the therapeutic strategy of Taiwan Chingguan Erhau (NRICM102) against moderate-to-severe novel coronavirus infectious disease in Taiwan.


Subject(s)
COVID-19 , Humans , COVID-19/therapy , SARS-CoV-2 , Taiwan
6.
J Biomed Mater Res A ; 110(5): 1101-1108, 2022 05.
Article in English | MEDLINE | ID: covidwho-2320830

ABSTRACT

Lipid nanoparticles (LNPs) play a crucial role in delivering messenger RNA (mRNA) therapeutics for clinical applications, including COVID-19 mRNA vaccines. While mRNA can be chemically modified to become immune-silent and increase protein expression, LNPs can still trigger innate immune responses and cause inflammation-related adverse effects. Inflammation can in turn suppress mRNA translation and reduce the therapeutic effect. Dexamethasone (Dex) is a widely used anti-inflammatory corticosteroid medication that is structurally similar to cholesterol, a key component of LNPs. Here, we developed LNP formulations with anti-inflammatory properties by partially substituting cholesterol with Dex as a means to reduce inflammation. We demonstrated that Dex-incorporated LNPs effectively abrogated the induction of tumor necrosis factor alpha (TNF-ɑ) in vitro and significantly reduced its expression in vivo. Reduction of inflammation using this strategy improved in vivo mRNA expression in mice by 1.5-fold. Thus, we envision that our Dex-incorporated LNPs could potentially be used to broadly to reduce the inflammatory responses of LNPs and enhance protein expression of a range of mRNA therapeutics.


Subject(s)
COVID-19 , Nanoparticles , Animals , Anti-Inflammatory Agents/pharmacology , Liposomes , Mice , Nanoparticles/chemistry , RNA, Messenger/genetics , RNA, Messenger/metabolism
7.
Cosmetics ; 10(2):43, 2023.
Article in English | ProQuest Central | ID: covidwho-2302826

ABSTRACT

Dendrobium sulcatum Lindl or "Ueang Jampa-Nan” (Orchidaceae family) is widely dis-tributed in Thailand and Laos. It is classified in the genus Dendrobium, which is used in both traditional Chinese medicine and Ayurvedic medicine for health enhancement and anti-aging. The purpose of this study was to investigate the phytochemical constituents and bioefficacy of stems, leaves and flowers from D. sulcatum for cosmetic and cosmeceutical applications. Phenolic and flavonoid contents were tested for the phytochemical evaluation. The antioxidant (DPPH, FRAP and ABTS assays), anti-lipid peroxidation, antiglycation, anti-inflammatory and anti-tyrosinase properties were assessed for their bioefficacy. The results showed that the extracts of stem and leaf had higher total phenolic content than that of the flower, and the leaf extract had the highest flavonoid content. The antioxidant, anti-lipid peroxidation and anti-inflammatory activities of the extracts were greater in those from the stem and leaf compared with that of the flower. The leaf extract exhibited the greatest antiglycation property. The results of anti-tyrosinase analysis of the extracts showed that the leaf and flower exhibited potent activities with a percentage inhibition greater than 70% (at a concentration of 50 µg/mL). In conclusion, these findings suggest that the ethanolic extracts from different parts of D. sulcatum are promising sources of natural active ingredients for further cosmetic and cosmeceutical products.

8.
Smart Mater Med ; 4: 514-521, 2023.
Article in English | MEDLINE | ID: covidwho-2298947

ABSTRACT

Alleviating excessive inflammation while accelerating chronic wound healing to prevent wound infection has remained challenging, especially during the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 when patients experienced difficulties with receive appropriate healthcare. We addressed this issue by developing handheld electrospun aloe-nanofiber membranes (ANFMs) with convenient, environmentally friendly properties and a therapeutic capacity for wound closure. Our results showed that ANFMs fabricated with high molecular weight polyvinyl alcohol (PVA) to form fibers during electrospinning had uniform fibrous architecture and a porous structure. Given the value of aloe gel in accelerating wound healing, liquid extracts from ANFMs significantly downregulated the expression of the pro-inflammatory genes, interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), and markedly suppress the generation of reactive oxygen species (ROS) induced by lipopolysaccharide in RAW264.7 macrophages. These results indicated the excellent antioxidant and anti-inflammatory effects of ANFMs. After implantation into a mouse diabetic wound model for 12 days in situ, ANFMs notably expedited chronic wound healing via promoting angiogenesis and enhancing cell viability. Our ANFMs generated by handheld electrospinning in situ healed chronic wounds offer a convenient and promising alternative for patients to heal their own wounds under variable conditions.

9.
Proc Natl Acad Sci U S A ; 120(18): e2301775120, 2023 05 02.
Article in English | MEDLINE | ID: covidwho-2305928

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.


Subject(s)
COVID-19 , Humans , Antiviral Agents/pharmacology , SARS-CoV-2 , Quercetin/pharmacology , Anti-Inflammatory Agents/pharmacology , Molecular Docking Simulation
10.
Advances in Traditional Medicine ; 23(1):85-96, 2023.
Article in English | EMBASE | ID: covidwho-2275040

ABSTRACT

The search for a potent anti-coronavirus therapy for severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) remains an overwhelming task since the outbreak of COVID-19. It is more evident that most of the existing antiviral and immune-boosting drugs are non-promising and ineffective for the treatment of coronavirus infected patients while the safety of a few drugs/vaccines that have demonstrated high potential remains unclear. With daily records of confirmed infectious cases across the world, it is crucial to emphasize the need for repurposed therapies with a validated ethnomedicinal base focused on well-known active medicines with traceable biochemical, pharmacological and safety profiles for viral infection management. In the present study, recent literature on Artemisia and Artemisia-based products for the management of COVID-19 are reviewed. Artemisia-based products have demonstrated a broad spectrum of biological ability including antiviral properties. Besides its antiviral activity, Artemisia annua have shown to contain appreciable amounts of minerals such as zinc, gallium and selenium among others. Graphic abstract: [Figure not available: see fulltext.].Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.

11.
Pharmacological Research - Modern Chinese Medicine ; 2 (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2269814

ABSTRACT

Background: SARS-CoV-2 has led to a sharp increase in the number of hospitalizations and deaths from pneumonia and multiorgan disease worldwide;therefore, SARS-CoV-2 has become a global health problem. Supportive therapies remain the mainstay treatments against COVID-19, such as oxygen inhalation, antiviral drugs, and antibiotics. Traditional Chinese medicine (TCM) has been shown clinically to relieve the symptoms of COVID-19 infection, and TCMs can affect the pathogenesis of SARS-CoV-2 infection in vitro. Jing Si Herbal Drink (JSHD), an eight herb formula jointly developed by Tzu Chi University and Tzu Chi Hospital, has shown potential as an adjuvant treatment for COVID-19 infection. A randomized controlled trial (RCT) of JSHD as an adjuvant treatment in patients with COVID-19 infection is underway Objectives: This article aims to explore the efficacy of the herbs in JSHD against COVID-19 infection from a mechanistic standpoint and provide a reference for the rational utilization of JSHD in the treatment of COVID-19. Method(s): We compiled evidence of the herbs in JSHD to treat COVID-19 in vivo and in vitro. Result(s): We described the efficacy and mechanism of action of the active ingredients in JSHD to treat COVID-19 based on experimental evidence. JSHD includes 5 antiviral herbs, 7 antioxidant herbs, and 7 anti-inflammatory herbs. In addition, 2 herbs inhibit the overactive immune system, 1 herb reduces cell apoptosis, and 1 herb possesses antithrombotic ability. Conclusion(s): Although experimental data have confirmed that the ingredients in JSHD are effective against COVID-19, more rigorously designed studies are required to confirm the efficacy and safety of JSHD as a COVID-19 treatment.Copyright © 2021

12.
Coronaviruses ; 3(1):3-8, 2022.
Article in English | EMBASE | ID: covidwho-2254497

ABSTRACT

Coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new coronavirus isolated from Wuhan, China. It is a global health emergency, and there is no effective antiviral therapeutics available to date. Continuous structural genomic insights of SARS-CoV-2 proteins provide a warranty for the development of ra-tional-based antivirals. Nevertheless, a structure-based drug candidate with multiple therapeutic actions would be a practical choice of medication in the treatment of severe COVID-19 patients. Cordycepin from medicinal fungi (Cordyceps spp.) and its nucleoside analogs targeting viral RNA-dependent RNA polymerase and human RNase L have potent antiviral activity against various human viruses with additional immunomodulatory and anti-inflammatory effects. Anti-inflammation treatment is of pivotal importance and should be timely tailored to the individual patient along with antivirals. Our perspective on the combined antiviral and anti-inflammatory effects of cordycepin and its analogs suggests them as new therapeutics in the treatment of systemic COVID-19 infec-tion.Copyright © 2022 Bentham Science Publishers.

13.
Acta Neuropsychiatr ; 33(4): 165-177, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-2281783

ABSTRACT

Neuropsychiatric sequalae to coronavirus disease 2019 (COVID-19) infection are beginning to emerge, like previous Spanish influenza and severe acute respiratory syndrome episodes. Streptococcal infection in paediatric patients causing obsessive compulsive disorder (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, widespread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long-term-specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favourable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease-modifying therapies are increasingly being applied to neuropsychiatric diseases characterised by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.


Subject(s)
Autoimmune Diseases/psychology , COVID-19/psychology , Obsessive-Compulsive Disorder/psychology , Streptococcal Infections/psychology , Anti-Inflammatory Agents/therapeutic use , Autoimmune Diseases/epidemiology , Autoimmune Diseases/immunology , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Cyclooxygenase 2 Inhibitors/therapeutic use , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Female , Humans , Inflammation/complications , Inflammation/immunology , Inflammation/psychology , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/etiology , Obsessive-Compulsive Disorder/immunology , SARS-CoV-2/genetics , Streptococcal Infections/complications , Streptococcal Infections/epidemiology , Streptococcal Infections/immunology
14.
Engineering (Beijing) ; 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-2268751

ABSTRACT

Traditional Chinese medicine (TCM) has been successfully applied worldwide in the treatment of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacological mechanisms underlying this success remain unclear. Hence, the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways, targets, active compounds, and formulas of herbs that are involved in the TCM treatment of COVID-19, which exhibits combatting viral infections, immune regulation, and amelioration of lung injury and fibrosis. Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data. The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19. Therefore, more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.

15.
Scientia Pharmaceutica ; 91(1), 2023.
Article in English | Scopus | ID: covidwho-2263991

ABSTRACT

Essential oils are potential therapeutics for coronavirus disease 2019 (COVID-19), in which some of the volatile compounds of essential oils have been well known for their broad antiviral activities. These therapeutic candidates have been shown to regulate the excessive secretion of pro-inflammatory cytokines, which underlies the pathogenesis of severe COVID-19. We aimed to identify molecular targets of essential oils in disrupting the cell entry and replication of SARS-CoV-2, hence being active as antivirals. Literature searches were performed on PubMed, Scopus, Scillit, and CaPlus/SciFinder (7 December 2022) with a truncated title implying the anti-SARS-CoV-2 activity of essential oil. Data were collected from the eligible studies and described narratively. Quality appraisal was performed on the included studies. A total of eight studies were included in this review;four of which used enzyme inhibition assay, one—pseudo-SARS-CoV-2 culture;two—whole SARS-CoV-2 culture;and one—ACE2-expressing cancer cells. Essential oils may prevent the SARS-CoV-2 infection by targeting its receptors on the cells (ACE2 and TMPRSS2). Menthol, 1,8-cineole, and camphor are among the volatile compounds which serve as potential ACE2 blockers. β-caryophyllene may selectively target the SARS-CoV-2 spike protein and inhibit viral entry. Other interactions with SARS-CoV-2 proteases and RdRp are observed based on molecular docking. In conclusion, essential oils could target proteins related to the SARS-CoV-2 entry and replication. Further studies with improved and uniform study designs should be carried out to optimize essential oils as COVID-19 therapies. © 2023 by the authors.

16.
Cell Mol Immunol ; 20(4): 351-364, 2023 04.
Article in English | MEDLINE | ID: covidwho-2287148

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.


Subject(s)
COVID-19 , Receptors, Chimeric Antigen , Humans , SARS-CoV-2/metabolism , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Caspofungin , Felodipine , Cytokine Release Syndrome/drug therapy , Inflammation , Cytokines/metabolism
17.
Front Pharmacol ; 13: 928106, 2022.
Article in English | MEDLINE | ID: covidwho-2282768

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. As at June 2022, increasing numbers of newly diagnosed COVID-19-associated pneumonia cases worldwide have attracted close attention from the international community. The present review analyzes and summarizes the treatment of COVID-19 with traditional Chinese medicine (TCM). A systematic analysis of the efficacies and benefits of TCM for the treatment of COVID-19 was performed, and the mechanisms underlying such treatment are summarized. This analysis of the literature highlights the potential of TCM to prevent and treat COVID-19 via antiviral, anti-inflammatory and immunomodulatory activities, with evidence showing that many TCM components act upon multiple targets and pathways. Famous TCM formulas include Qing-Fei-Pai-Du-Tang (QFPDT), Lianhuaqingwen Capsule (LHC), Taiwan Chingguan Yihau (NRICM101), and Jing Si herbal drink (JSHD). In particular, the botanical preparation NRICM101 was developed in 2020 for use in viral respiratory tract infections and is recommended for treating non-severe and mild COVID-19 infections. NRICM101 has been adopted for use in Taiwan for the clinical treatment of COVID-19. The common components and active ingredients of 10 TCM preparations have been analyzed for the most promising substances. This review aims to provide reliable evidence demonstrating the therapeutic efficacy of TCM substances in support of their further development against novel coronavirus infectious diseases in Taiwan.

18.
Pharmacol Res ; 180: 106246, 2022 06.
Article in English | MEDLINE | ID: covidwho-2258937

ABSTRACT

Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic strategies aimed at controlling excessive inflammation are effective in some cases, though they may be accompanied by severe side effects, such as immunosuppression. Phytochemicals as a therapeutic alternative can have a fundamental impact on the different stages of inflammation and its resolution. Biochanin A (BCA) is an isoflavone known for its wide range of pharmacological properties, especially its marked anti-inflammatory effects. Recent studies have provided evidence of BCA's abilities to activate events essential for resolving inflammation. In this review, we summarize the most recent findings from pre-clinical studies of the pharmacological effects of BCA on the complex signaling network associated with the onset and resolution of inflammation and BCA's potential protective functionality in several models of inflammatory diseases, such as arthritis, pulmonary disease, neuroinflammation, and metabolic disease.


Subject(s)
Genistein , Isoflavones , Genistein/pharmacology , Genistein/therapeutic use , Humans , Inflammation/drug therapy , Phytochemicals/pharmacology , Phytotherapy
19.
Cureus ; 15(1): e33265, 2023 Jan.
Article in English | MEDLINE | ID: covidwho-2237830

ABSTRACT

This study was conducted to test the hypothesis that platelet-rich plasma (PRP) therapy in chronic respiratory disease patients will cause lung regeneration, thereby slowing the progression of the disease. We performed a search to obtain pertinent articles on the following electronic databases: Google Scholar, PubMed, NCBI, Medscape, and clinicaltrials.gov. Keywords used during in search included "Platelet Rich Plasma" AND "Chronic Respiratory Disease" AND/OR "Chronic Obstructive Pulmonary Disease". A total of 15 articles were chosen for this paper, published from 2011 to 2021, and included case series, lab studies, animal studies, cohort studies, and clinical trials. All statistical data were considered significant if the p-value was less than 5%, or 0.05. Our findings confirmed that PRP therapy successfully caused anti-inflammatory effects and acceleration of tissue regeneration, resulting in improved lung function. This, in turn, slowed the progression of the disease and led to an improved quality of life. Not all chronic respiratory disease patients present in the same manner, but the connecting link is the damaged tissue of the lungs, causing issues with the functionality of the lungs. By adjunctively treating patients with PRP, the high concentration of platelets and their secreted growth factors can help induce an acceleration of healing and regeneration of pulmonary tissue. This, in turn, can slow the progression of the disease, which could lower the overall mortality rate in chronic respiratory disease patients. More studies should be conducted on this topic, specifically large, double-blinded, randomized human trials with controls, to further assess the efficacy and beneficial effects of PRP treatment on the lungs.

20.
Front Med (Lausanne) ; 9: 1072056, 2022.
Article in English | MEDLINE | ID: covidwho-2229520

ABSTRACT

Objective: The multi-systemic inflammation as a result of COVID-19 can persevere long after the initial symptoms of the illness have subsided. These effects are referred to as Long-COVID. Our research focused on the contribution of the Spike protein S1 subunit of SARS-CoV-2 (Spike S1) on the lung inflammation mediated by NLRP3 inflammasome machinery and the cytokine releases, interleukin 6 (IL-6), IL-1beta, and IL-18, in lung epithelial cells. This study has attempted to identify the naturally- occurring agents that act against inflammation-related long-COVID. The seed meal of Perilla frutescens (P. frutescens), which contains two major dietary polyphenols (rosmarinic acid and luteolin), has been reported to exhibit anti-inflammation activities. Therefore, we have established the ethyl acetate fraction of P. frutescens seed meal (PFEA) and determined its anti-inflammatory effects on Spike S1 exposure in A549 lung cells. Methods: PFEA was established using solvent-partitioned extraction. Rosmarinic acid (Ra) and luteolin (Lu) in PFEA were identified using the HPLC technique. The inhibitory effects of PFEA and its active compounds against Spike S1-induced inflammatory response in A549 cells were determined by RT-PCR and ELISA. The mechanistic study of anti-inflammatory properties of PFEA and Lu were determined using western blot technique. Results: PFEA was found to contain Ra (388.70 ± 11.12 mg/g extract) and Lu (248.82 ± 12.34 mg/g extract) as its major polyphenols. Accordingly, A549 lung cells were pre-treated with PFEA (12.5-100 µg/mL) and its two major compounds (2.5-20 µg/mL) prior to the Spike S1 exposure at 100 ng/mL. PFEA dose-dependently exhibited anti-inflammatory properties upon Spike S1-exposed A549 cells through IL-6, IL-1ß, IL-18, and NLRP3 gene suppressions, as well as IL-6, IL-1ß, and IL-18 cytokine releases with statistical significance (p < 0.05). Importantly, Lu possesses superior anti-inflammatory properties when compared with Ra (p < 0.01). Mechanistically, PFEA and Lu effectively attenuated a Spike S1-induced inflammatory response through downregulation of the JAK1/STAT3-inflammasome-dependent inflammatory pathway as evidenced by the downregulation of NLRP3, ASC, and cleaved-caspase-1 of the NLRP3 inflammasome components and by modulating the phosphorylation of JAK1 and STAT3 proteins (p < 0.05). Conclusion: The findings suggested that luteolin and PFEA can modulate the signaling cascades that regulate Spike S1-induced lung inflammation during the incidence of Long-COVID. Consequently, luteolin and P. frutescens may be introduced as potential candidates in the preventive therapeutic strategy for inflammation-related post-acute sequelae of COVID-19.

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