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Xu YL, Li XJ, Cai W, Yu WY, Chen J, Lee Q, Choi YJ, Wu F, Lou YJ, Ying HZ, Yu CH, Wu QF. Diosmetin-7-O-β-D-glucopyranoside from Pogostemonis Herba alleviated SARS-CoV-2-induced pneumonia by reshaping macrophage polarization and limiting viral replication. JOURNAL OF ETHNOPHARMACOLOGY 2025; 336:118704. [PMID: 39182703 DOI: 10.1016/j.jep.2024.118704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 08/04/2024] [Accepted: 08/16/2024] [Indexed: 08/27/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS Diosmetin-7-O-β-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 μM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.
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Affiliation(s)
- Yun-Lu Xu
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xue-Jian Li
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China; Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, 310018, China
| | - Wei Cai
- College of Chinese Medicine, Zhejiang Pharmaceutical University, Ningbo, 315500, China
| | - Wen-Ying Yu
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China
| | - Jing Chen
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Qin Lee
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China; Department of Biochemistry, College of Medicine, Gachon University, Incheon, 21999, Republic of Korea
| | - Yong-Jun Choi
- Department of Biochemistry, College of Medicine, Gachon University, Incheon, 21999, Republic of Korea
| | - Fang Wu
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China
| | - Ying-Jun Lou
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China
| | - Hua-Zhong Ying
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China
| | - Chen-Huan Yu
- Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, 310018, China.
| | - Qiao-Feng Wu
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
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Huang J, Jin Y, Wu R, Xie H, Yang M, Jia J, Wang G. Identification of apigenin as a multi-target inhibitor against SARS-CoV-2 by computational exploration. FASEB J 2024; 38:e70276. [PMID: 39718442 DOI: 10.1096/fj.202401972rrr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 12/09/2024] [Accepted: 12/17/2024] [Indexed: 12/25/2024]
Abstract
Multi-target strategy can serve as a valid treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but existing drugs most focus on a single target. Thus, multi-target drugs that bind multiple sites simultaneously need to be urgently studied. Apigenin has antiviral and anti-inflammatory properties. Here, we comprehensively explored the potential effect and mechanism of apigenin in SARS-CoV-2 treatment by a network algorithm, deep learning, molecular docking, molecular dynamics (MD) simulation, and normal mode analysis (NMA). KATZ-based VDA prediction method (VDA-KATZ) indicated that apigenin may provide a latent drug therapy for SARS-CoV-2. Prediction of DTA using convolution model with self-attention (CSatDTA) showed potential binding affinity of apigenin with multiple targets of virus entry, assembly, and cytokine storms including cathepsin L (CTSL), membrane (M), envelope (E), Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cysteinyl aspartate-specific proteinase-1 (Caspase-1). Molecular docking indicated that apigenin could effectively bind these targets, and its stability was confirmed using MD simulation and NMA. Overall, apigenin is a multi-target inhibitor for the entry, assembly, and cytokine storms of SARS-CoV-2.
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Affiliation(s)
- Juanjuan Huang
- Key Laboratory of Pathobiology, Ministry of Education, China-Japan Union Hospital of Jilin University, Changchun, China
- Department of Computational Mathematics, School of Mathematics, Jilin University, Changchun, China
- College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Yixuan Jin
- Department of Computational Mathematics, School of Mathematics, Jilin University, Changchun, China
| | - Runze Wu
- Department of Probability Statistics and Data Science, School of Mathematics, Jilin University, Changchun, China
| | - Hanxi Xie
- Key Laboratory of Pathobiology, Ministry of Education, China-Japan Union Hospital of Jilin University, Changchun, China
- College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Ming Yang
- College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Jiwei Jia
- Department of Computational Mathematics, School of Mathematics, Jilin University, Changchun, China
- Jilin National Applied Mathematical Center, Jilin University, Changchun, China
| | - Guoqing Wang
- Key Laboratory of Pathobiology, Ministry of Education, China-Japan Union Hospital of Jilin University, Changchun, China
- College of Basic Medical Sciences, Jilin University, Changchun, China
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Wei MJ, Huang KL, Kang HF, Liu GT, Kuo CY, Tzeng IS, Hsieh PC, Lan CC. Jing Si Herbal Tea Modulates Macrophage Polarization and Inflammatory Signaling in LPS-Induced Inflammation. Int J Med Sci 2024; 21:3046-3057. [PMID: 39628684 PMCID: PMC11610342 DOI: 10.7150/ijms.100720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 11/05/2024] [Indexed: 12/06/2024] Open
Abstract
Background: Sepsis is a lethal disease due to uncontrolled inflammatory responses. Macrophages play an important role in sepsis-associated inflammation. Jing Si Herbal Tea (JSHT) is a plant-based regimen with anti-inflammatory properties designed to treat respiratory diseases; however, its underlying therapeutic mechanism remains unclear. This study aimed to investigate the effects of JSHT on macrophage polarization and inflammatory signaling in lipopolysaccharide (LPS)-induced inflammation to provide therapeutic approaches for inflammatory diseases. Methods: RAW264.7 cells were stimulated with LPS (1 µg/mL for 16 h) to induce inflammatory responses and treated by JSHT (0.0125% concentration for 4 h) in the experimental groups (Control, JSHT, LPS, Pre-JSHT, and Post-JSHT groups). We investigated the protein and cytokine expression levels using western blotting and enzyme-linked immunosorbent assay (ELISA). Macrophage morphology was observed using immunofluorescence staining. The polarization surface markers were detected by flow cytometry. Results: In the LPS group, the expressions of the inflammatory signaling (pERK, pJNK, and nuclear NFκB) and the pro-inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were significantly increased, with M1 polarization (CD68+/CD80+) compared to the Control group. In the Pre-JSHT and Post-JSHT groups, the expressions of the inflammatory signaling and the pro-inflammatory cytokine levels were significantly decreased, with a higher M2 polarization ratio (CD163+/CD206+) compared to the LPS group. RAW264.7 cells exhibited filopodia protruding from the cell surface in the LPS group, which were inhibited in the Pre-JSHT and Post-JSHT groups. Conclusions: LPS induced M1 polarization with elevated inflammatory signaling and cytokine levels, while JSHT not only decreased M1 polarization but also promoted M2 polarization with decreased inflammatory responses. We propose JSHT as a potential anti-inflammatory agent against LPS-induced inflammation.
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Affiliation(s)
- Meng-Jiun Wei
- Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Kuo-Liang Huang
- Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Hsiu-Fan Kang
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Guan-Ting Liu
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Chan-Yen Kuo
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - I-Shiang Tzeng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Po-Chun Hsieh
- Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
- School of Chinese Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chou-Chin Lan
- Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
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Du H, Li Z, Su L, He Z, Tan X, Hou F, He T, Pan Y, Xu S, Cao L, Dong S, Ma Y. Synthesis, characterization, and mechanistic insights into the enhanced anti-inflammatory activity of baicalin butyl ester via the PI3K-AKT pathway. Front Pharmacol 2024; 15:1417372. [PMID: 39104394 PMCID: PMC11298432 DOI: 10.3389/fphar.2024.1417372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/01/2024] [Indexed: 08/07/2024] Open
Abstract
Objective To investigate the anti-inflammatory activity and mechanism of Baicalin derivative (Baicalin butyl ester, BE). Methods BE was synthesized and identified using UV-Vis spectroscopy, FT-IR spectroscopy, mass spectrometry (MS) and high-performance liquid chromatography (HPLC) methods. Its anti-inflammatory potential was explored by an in vitro inflammation model. Network pharmacology was employed to predict the anti-inflammatory targets of BE, construct protein-protein interaction (PPI) networks, and analysis topological features and KEGG pathway enrichment. Additionally, molecular docking was conducted to evaluate the binding affinity between BE and its core targets. qRT-PCR analysis was conducted to validate the network pharmacology results. The organizational efficiency was further evaluated through octanol-water partition coefficient and transmembrane activity analysis. Results UV-Vis, FT-IR, MS, and HPLC analyses confirmed the successfully synthesis of BE with a high purity of 93.75%. In vitro anti-inflammatory research showed that BE could more effectively suppress the expression of NO, COX-2, IL-6, IL-1β, and iNOS. Network pharmacology and in vitro experiments validated that BE's anti-inflammatory effects was mediated through the suppression of SRC, HSP90AA1, PIK3CA, JAK2, AKT1, and NF-κB via PI3K-AKT pathway. Molecular docking results revealed that the binding affinities of BA to the core targets were lower than those of BE. The Log p-value of BE (1.7) was markedly higher than that of BA (-0.5). Furthermore, BE accumulated in cells at a level approximately 200 times greater than BA. Conclusion BE exhibits stronger anti-inflammatory activity relative to BA, possibly attributed to its better lipid solubility and cellular penetration capabilities. The anti-inflammatory mechanism of BE may be mediated through the PI3K-AKT pathway.
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Affiliation(s)
- Hongxu Du
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
- Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, China
| | - Zhangxun Li
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Lijuan Su
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Zhengke He
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Xiaoyan Tan
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Fengzhi Hou
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Tanjie He
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Yu Pan
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Shuang Xu
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Liting Cao
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
- Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, China
| | - Shiqi Dong
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
| | - Yue Ma
- Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China
- Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, China
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Wang J, Zeng X, Gou J, Zhu X, Yin D, Yin L, Shen X, Dai Y, Pan X. Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro. BMC Vet Res 2024; 20:288. [PMID: 38961481 PMCID: PMC11221151 DOI: 10.1186/s12917-024-04053-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 05/02/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses. RESULTS We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10. CONCLUSIONS Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.
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Affiliation(s)
- Jieru Wang
- Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Sciences, Anhui Academy of Agricultural Sciences, Hefei, Anhui, 230031, China
| | - Xiaoyu Zeng
- Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Sciences, Anhui Academy of Agricultural Sciences, Hefei, Anhui, 230031, China
| | - Jiaojiao Gou
- Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Sciences, Anhui Academy of Agricultural Sciences, Hefei, Anhui, 230031, China
| | - Xiaojie Zhu
- China Institute of Veterinary Drug Control, Beijing, 100000, China
| | - Dongdong Yin
- Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Sciences, Anhui Academy of Agricultural Sciences, Hefei, Anhui, 230031, China
| | - Lei Yin
- Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Sciences, Anhui Academy of Agricultural Sciences, Hefei, Anhui, 230031, China
| | - Xuehuai Shen
- Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Sciences, Anhui Academy of Agricultural Sciences, Hefei, Anhui, 230031, China
| | - Yin Dai
- Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Sciences, Anhui Academy of Agricultural Sciences, Hefei, Anhui, 230031, China.
| | - Xiaocheng Pan
- Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Sciences, Anhui Academy of Agricultural Sciences, Hefei, Anhui, 230031, China.
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Jantan I, Norahmad NA, Yuandani, Haque MA, Mohamed-Hussein ZA, Mohd Abd Razak MR, Syed Mohamed AF, Lam KW, Ibrahim S. Inhibitory effect of food-functioned phytochemicals on dysregulated inflammatory pathways triggered by SARS-CoV-2: a mechanistic review. Crit Rev Food Sci Nutr 2024; 65:2405-2430. [PMID: 38619217 DOI: 10.1080/10408398.2024.2341266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2024]
Abstract
Inflammatory cascades of the dysregulated inflammatory pathways in COVID-19 can cause excessive production of pro-inflammatory cytokines and chemokines leading to cytokine storm syndrome (CSS). The molecular cascades involved in the pathways may be targeted for discovery of new anti-inflammatory agents. Many plant extracts have been used clinically in the management of COVID-19, however, their immunosuppressive activities were mainly investigated based on in silico activity. Dietary flavonoids of the extracts such as quercetin, luteolin, kaempferol, naringenin, isorhamnetin, baicalein, wogonin, and rutin were commonly identified as responsible for their inhibitory effects. The present review critically analyzes the anti-inflammatory effects and mechanisms of phytochemicals, including dietary compounds against cytokine storm (CS) and hyperinflammation via inhibition of the altered inflammatory pathways triggered by SARS-CoV-2, published since the emergence of COVID-19 in December 2019. Only a few phytochemicals, mainly dietary compounds such as nanocurcumin, melatonin, quercetin, 6-shagoal, kaempferol, resveratrol, andrographolide, and colchicine have been investigated either in in silico or preliminary clinical studies to evaluate their anti-inflammatory effects against COVID-19. Sufficient pre-clinical studies on safety and efficacy of anti-inflammatory effects of the phytochemicals must be performed prior to proper clinical studies to develop them into therapeutic adjuvants in the prevention and treatmemt of COVID-19 symptoms.
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Affiliation(s)
- Ibrahim Jantan
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
- Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Indonesia
| | - Nor Azrina Norahmad
- Herbal Medicine Research Centre, Institute for Medical Research, Shah Alam, Malaysia
| | - Yuandani
- Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Indonesia
| | - Md Areeful Haque
- Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Zeti-Azura Mohamed-Hussein
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
- Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
| | | | | | - Kok Wai Lam
- Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Sarah Ibrahim
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Malaysia
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Wang CH, Yang JS, Chen CJ, Su SH, Yu HY, Juan YN, Chiu YJ, Ho TJ. Protective effects of Jing-Si-herbal-tea in inflammatory cytokines-induced cell injury on normal human lung fibroblast via multiomic platform analysis. Tzu Chi Med J 2024; 36:152-165. [PMID: 38645788 PMCID: PMC11025590 DOI: 10.4103/tcmj.tcmj_267_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/03/2023] [Accepted: 11/23/2023] [Indexed: 04/23/2024] Open
Abstract
OBJECTIVES The protective effects and related mechanisms of Jing-Si herbal tea (JSHT) were investigated in cellular damage mediated by pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, on normal human lung fibroblast by multiomic platform analysis. MATERIALS AND METHODS The in silico high-throughput target was analyzed using pharmacophore models by BIOVIA Discovery Studio 2022 with ingenuity pathway analysis software. To assess cell viability, the study utilized the MTT assay technique. In addition, the IncuCyte S3 ZOOM System was implemented for the continuous monitoring of cell confluence of JSHT-treated cytokine-injured HEL 299 cells. Cytokine concentrations were determined using a Quantibody Human Inflammation Array. Gene expression and signaling pathways were determined using next-generation sequencing. RESULTS In silico high-throughput target analysis of JSHT revealed ingenuity in canonical pathways and their networks. Glucocorticoid receptor signaling is a potential signaling of JSHT. The results revealed protective effects against the inflammatory cytokines on JSHT-treated HEL 299 cells. Transcriptome and network analyses revealed that induction of helper T lymphocytes, TNFSF12, NFKB1-mediated relaxin signaling, and G-protein coupled receptor signaling play important roles in immune regulatory on JSHT-treated cytokine-injured HEL 299 cells. CONCLUSION The findings from our research indicate that JSHT holds promise as a therapeutic agent, potentially offering advantageous outcomes in treating virus infections through various mechanisms. Furthermore, the primary bioactive components in JSHT justify extended research in antiviral drug development, especially in the context of addressing coronavirus.
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Affiliation(s)
- Chien-Hao Wang
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Jai-Sing Yang
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Chao-Jung Chen
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Research, Proteomics Core Laboratory, China Medical University Hospital, Taichung, Taiwan
| | - San-Hua Su
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Hsin-Yuan Yu
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Yu-Ning Juan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Yu-Jen Chiu
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tsung-Jung Ho
- Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
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Pan E, Xin Y, Li X, Ping K, Li X, Sun Y, Xu X, Dong J. Immunoprotective effect of silybin through blocking p53-driven caspase-9-Apaf-1-Cyt c complex formation and immune dysfunction after difenoconazole exposure in carp spleen. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2024; 31:19396-19408. [PMID: 38358624 DOI: 10.1007/s11356-024-32392-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 02/05/2024] [Indexed: 02/16/2024]
Abstract
As a broad-spectrum and efficient triazole fungicide, difenoconazole is widely used, which not only pollutes the environment but also exerts toxic effects on non-target organisms. The spleen plays an important role in immune protection as an important secondary lymphoid organ in carp. In this study, we assessed the protective impact of silybin as a dietary additive on spleen tissues of carp during exposure to difenoconazole. Sixty carp were separated into four groups for this investigation including control group, difenoconazole group, silybin group, and silybin and difenoconazole group. By hematoxylin-eosin staining, dihydroethidium staining, immunohistochemical staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, quantitative real-time PCR assay, Western blot analysis, biochemical assays, and immune function indicator assays, we found that silybin could prevent difenoconazole-induced spleen tissue damage, oxidative stress, and immune dysfunction, and inhibited apoptosis of carp spleen tissue cells by suppressing the formation of p53-driven caspase-9-apoptotic protease activating factor-1-cytochrome C complex. The results suggested that silybin as a dietary additive could improve spleen tissue damage and immune dysfunction induced by difenoconazole in aquaculture carp.
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Affiliation(s)
- Enzhuang Pan
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Yue Xin
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Xueqing Li
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Kaixin Ping
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Xing Li
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Ying Sun
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Xuhui Xu
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China
| | - Jingquan Dong
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
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9
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Singh Dagur H, Behmard E, Rajakumara E, Barzegari E. Identifying potent inhibitory phytocompounds from Lagerstroemia speciosa against SARS-Coronavirus-2: structure-based virtual screening. J Biomol Struct Dyn 2024; 42:806-818. [PMID: 37170794 DOI: 10.1080/07391102.2023.2205942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 03/20/2023] [Indexed: 05/13/2023]
Abstract
The ongoing spillover of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) calls for expedited countermeasure through developing therapeutics from natural reservoirs and/or the use of less time-consuming drug discovery methodologies. This study aims to apply these approaches to identify potential blockers of the virus from the longstanding medicinal herb, Lagerstroemia speciosa, through comprehensive computational-based screening. Nineteen out of 22 L. speciosa phytochemicals were selected on the basis of their pharmacokinetic properties. SARS-CoV-2 Main protease (Mpro), RNA-directed RNA polymerase (RdRp), Envelope viroporin protein (Evp) and receptor-binding domain of Spike glycoprotein (S-RBD), as well as the human receptor Angiotensin-converting enzyme-2 (hACE2) were chosen as targets. The screening was performed by molecular docking, followed by 100-ns molecular dynamic simulations and free energy calculations. 24-Methylene cycloartanol acetate (24MCA) was found as the best inhibitor for both Evp and RdRp, and sitosterol acetate (SA) as the best hit for Mpro, S-RBD and hACE2. Dynamic simulations, binding mode analyses, free energy terms and share of key amino acids in protein-drug interactions confirmed the stable binding of these phytocompounds to the hotspot sites on the target proteins. With their possible multi-targeting capability, the introduced phytoligands might offer promising lead compounds for persistent fight with the rapidly evolving coronavirus. Therefore, experimental verification of their safety and efficacy is recommended.
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Affiliation(s)
- Hanuman Singh Dagur
- Macromolecular Structural Biology Lab, Department of Biotechnology, Indian Institute of Technology Hyderabad, Sangareddy, Telangana, India
| | - Esmaeil Behmard
- School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Eerappa Rajakumara
- Macromolecular Structural Biology Lab, Department of Biotechnology, Indian Institute of Technology Hyderabad, Sangareddy, Telangana, India
| | - Ebrahim Barzegari
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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10
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Barrera-Vázquez OS, Escobar-Ramírez JL, Santiago-Mejía J, Carrasco-Ortega OF, Magos-Guerrero GA. Discovering Potential Compounds for Venous Disease Treatment through Virtual Screening and Network Pharmacology Approach. Molecules 2023; 28:7937. [PMID: 38138427 PMCID: PMC10745828 DOI: 10.3390/molecules28247937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/28/2023] [Accepted: 11/30/2023] [Indexed: 12/24/2023] Open
Abstract
Peripheral venous hypertension has emerged as a prominent characteristic of venous disease (VD). This disease causes lower limb edema due to impaired blood transport in the veins. The phlebotonic drugs in use showed moderate evidence for reducing edema slightly in the lower legs and little or no difference in the quality of life. To enhance the probability of favorable experimental results, a virtual screening procedure was employed to identify molecules with potential therapeutic activity in VD. Compounds obtained from multiple databases, namely AC Discovery, NuBBE, BIOFACQUIM, and InflamNat, were compared with reference compounds. The examination of structural similarity, targets, and signaling pathways in venous diseases allows for the identification of compounds with potential usefulness in VD. The computational tools employed were rcdk and chemminer from R-Studio and Cytoscape. An extended fingerprint analysis allowed us to obtain 1846 from 41,655 compounds compiled. Only 229 compounds showed pharmacological targets in the PubChem server, of which 84 molecules interacted with the VD network. Because of their descriptors and multi-target capacity, only 18 molecules of 84 were identified as potential candidates for experimental evaluation. We opted to evaluate the berberine compound because of its affordability, and extensive literature support. The experiment showed the proposed activity in an acute venous hypertension model.
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Affiliation(s)
| | | | | | | | - Gil Alfonso Magos-Guerrero
- Department of Pharmacology, Faculty of Medicine, University National Autonomous of Mexico (UNAM), Mexico City 04510, Mexico; (O.S.B.-V.); (J.L.E.-R.); (J.S.-M.); (O.F.C.-O.)
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11
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Gour A, Dogra A, Verma MK, Bhardwaj M, Kour D, Jamwal A, Gorain B, Kumar M, Vij B, Kumar A, Nandi U. Ayurveda-based phytochemical composition attenuates lung inflammation and precipitates pharmacokinetic interaction with favipiravir: an in vivo investigation using disease-state of acute lung injury. Nat Prod Res 2023; 37:3758-3765. [PMID: 36469694 DOI: 10.1080/14786419.2022.2150620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 10/26/2022] [Accepted: 11/13/2022] [Indexed: 12/12/2022]
Abstract
Acute respiratory distress syndrome (ARDS) is a critical form of acute lung injury (ALI). Here, we investigated the effect of a defined combination of ten pure phytochemicals in equal proportions of weight (NPM) from plants, recommended by Ayurveda for any protective action against lipopolysaccharide (LPS)-induced ALI. Results indicate that NPM markedly improved protein and neutrophil contents, myeloperoxidase and hydroxyproline levels, oxidative stress markers (glutathione and malonaldehyde), inflammatory cytokines, and genes (IL-6, TNF-α, TGF-β, and NF-κB/IκBα) in BALF/lung tissue. The histopathological examination of the lung revealed the shielding effect of NPM against ALI. NPM exhibited a protective effect on the lung by reducing oxidative stress and inhibiting inflammation. A substantial drop in favipiravir's oral exposure was observed in ALI-state compared to normal-state, but oral exposure upon NPM treatment in ALI-state followed similar behaviour of favipiravir alike normal-state without NPM treatment. Overall, results offer potential insight into Ayurvedic recommendations for immunity boosting during ALI situations.
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Affiliation(s)
- Abhishek Gour
- PK-PD Toxicology (PPT) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
| | - Ashish Dogra
- PK-PD Toxicology (PPT) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
| | - Mahendra K Verma
- Natural Products and Medicinal Chemistry (NPMC) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
| | - Mahir Bhardwaj
- PK-PD Toxicology (PPT) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
| | - Dilpreet Kour
- PK-PD Toxicology (PPT) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
| | - Ashiya Jamwal
- PK-PD Toxicology (PPT) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
| | - Bapi Gorain
- Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Ranchi-835215, India
| | - Mukesh Kumar
- Natural Products and Medicinal Chemistry (NPMC) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
| | - Bhavna Vij
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
| | - Ajay Kumar
- PK-PD Toxicology (PPT) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
| | - Utpal Nandi
- PK-PD Toxicology (PPT) Division, CSIR-Indian Institute of Integrative Medicine, Jammu-180001, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
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12
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Müller L, Di Benedetto S. Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions. Immun Ageing 2023; 20:17. [PMID: 37046272 PMCID: PMC10090758 DOI: 10.1186/s12979-023-00341-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 04/03/2023] [Indexed: 04/14/2023]
Abstract
Advanced age is one of the significant risk determinants for coronavirus disease 2019 (COVID-19)-related mortality and for long COVID complications. The contributing factors may include the age-related dynamical remodeling of the immune system, known as immunosenescence and chronic low-grade systemic inflammation. Both of these factors may induce an inflammatory milieu in the aged brain and drive the changes in the microenvironment of neurons and microglia, which are characterized by a general condition of chronic inflammation, so-called neuroinflammation. Emerging evidence reveals that the immune privilege in the aging brain may be compromised. Resident brain cells, such as astrocytes, neurons, oligodendrocytes and microglia, but also infiltrating immune cells, such as monocytes, T cells and macrophages participate in the complex intercellular networks and multiple reciprocal interactions. Especially changes in microglia playing a regulatory role in inflammation, contribute to disturbing of the brain homeostasis and to impairments of the neuroimmune responses. Neuroinflammation may trigger structural damage, diminish regeneration, induce neuronal cell death, modulate synaptic remodeling and in this manner negatively interfere with the brain functions.In this review article, we give insights into neuroimmune interactions in the aged brain and highlight the impact of COVID-19 on the functional systems already modulated by immunosenescence and neuroinflammation. We discuss the potential ways of these interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and review proposed neuroimmune mechanisms and biological factors that may contribute to the development of persisting long COVID conditions. We summarize the potential mechanisms responsible for long COVID, including inflammation, autoimmunity, direct virus-mediated cytotoxicity, hypercoagulation, mitochondrial failure, dysbiosis, and the reactivation of other persisting viruses, such as the Cytomegalovirus (CMV). Finally, we discuss the effects of various interventional options that can decrease the propagation of biological, physiological, and psychosocial stressors that are responsible for neuroimmune activation and which may inhibit the triggering of unbalanced inflammatory responses. We highlight the modulatory effects of bioactive nutritional compounds along with the multimodal benefits of behavioral interventions and moderate exercise, which can be applied as postinfectious interventions in order to improve brain health.
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Affiliation(s)
- Ludmila Müller
- Center for Lifespan Psychology, Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany
| | - Svetlana Di Benedetto
- Center for Lifespan Psychology, Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany
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13
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Chen TH, Tsai MJ, Chang CS, Xu L, Fu YS, Weng CF. The exploration of phytocompounds theoretically combats SARS-CoV-2 pandemic against virus entry, viral replication and immune evasion. J Infect Public Health 2023; 16:42-54. [PMID: 36470006 PMCID: PMC9675089 DOI: 10.1016/j.jiph.2022.11.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/12/2022] [Accepted: 11/16/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND The novel coronavirus disease-2019 (COVID-19) that emerged in China, is an extremely contagious and pathogenic viral infection caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that has sparked a global pandemic. The few and limited availability of approved therapeutic agents or vaccines is of great concern. Urgently, Remdesivir, Nirmatrelvir, Molnupiravir, and some phytochemicals including polyphenol, flavonoid, alkaloid, and triterpenoid are applied to develop as repurposing drugs against the SARS-CoV-2 invasion. METHODS This study was conducted to perform molecular docking and absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis of the potential phytocompounds and repurposing drugs against three targets of SARS-CoV-2 proteins (RNA dependent RNA polymerase, RdRp, Endoribonclease, S-protein of ACE2-RBD). RESULTS The docking data illustrated Arachidonic acid, Rutin, Quercetin, and Curcumin were highly bound with coronavirus polyprotein replicase and Ebolavirus envelope protein. Furthermore, anti- Ebolavirus molecule Remedesivir, anti-HIV molecule Chloroquine, and Darunavir were repurposed with coronavirus polyprotein replicase as well as Ebolavirus envelope protein. The strongest binding interaction of each targets are Rutin with RdRp, Endoribonclease with Amentoflavone, and ACE2-RBD with Epigallocatechin gallate. CONCLUSIONS Taken altogether, these results shed a light on that phytocompounds have a therapeutic potential for the treatment of anti-SARS-CoV-2 may base on multi-target effects or cocktail formulation for blocking viral infection through invasion/activation, transcription/reproduction, and posttranslational cleavage to battle COVID-19 pandemic.
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Affiliation(s)
- Ting-Hsu Chen
- Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China
| | - May-Jywan Tsai
- Department of Neurosurgery, Neurological Institute, Neurological Institute, Taipei 11217, Taiwan
| | - Chun-Sheng Chang
- Department of biotechnology and food technology, Southern Taiwan University of Science and Technology, Yungkang City 701, Taiwan
| | - Linxi Xu
- Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China
| | - Yaw-Syan Fu
- Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China,Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China,Corresponding author
| | - Ching-Feng Weng
- Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China,Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China,Corresponding author
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14
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Ruiz-Iglesias P, Estruel-Amades S, Massot-Cladera M, Franch À, Pérez-Cano FJ, Castell M. Rat Mucosal Immunity following an Intensive Chronic Training and an Exhausting Exercise: Effect of Hesperidin Supplementation. Nutrients 2022; 15:nu15010133. [PMID: 36615791 PMCID: PMC9824398 DOI: 10.3390/nu15010133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022] Open
Abstract
Stressful situations such as a high-intensity exercise or exhausting training programs can act as immune disruptors leading to transitory immunodepression status, which can be accompanied by alterations of the gastrointestinal functions. Hesperidin intake has demonstrated ergogenic activity and is able to influence the intestinal ecosystem and immunity. We aimed to investigate the effect of hesperidin consumption in rats submitted to an intense training and a final exhaustion test, focusing on the functionality of the intestinal immune system and on the cecal microbiota. Rats, supplemented or not with hesperidin, were intensively trained on a treadmill for 5 weeks. Samples were obtained 24 h after a regular training session, and immediately and 24 h after a final exhaustion test. Cecal microbiota and composition and function of mesenteric lymph node (MLN) lymphocytes and mucosal immunoglobulin A (IgA) were determined. Results showed that chronic intense exercise followed by an exhausting test induced changes in the intestinal immune compartment such as the distribution and function of MLN lymphocytes. Although the hesperidin supplementation did not prevent these alterations, it was able to enhance IgA synthesis in the intestinal compartment. This could be important in enhancing the immune intestinal barrier in this stressful situation.
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Affiliation(s)
- Patricia Ruiz-Iglesias
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), UB, 08921 Santa Coloma de Gramenet, Spain
| | - Sheila Estruel-Amades
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), UB, 08921 Santa Coloma de Gramenet, Spain
| | - Malén Massot-Cladera
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), UB, 08921 Santa Coloma de Gramenet, Spain
| | - Àngels Franch
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), UB, 08921 Santa Coloma de Gramenet, Spain
| | - Francisco J. Pérez-Cano
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), UB, 08921 Santa Coloma de Gramenet, Spain
- Correspondence: (F.J.P.-C.); (M.C.); Tel.: +34-934-024-505 (F.J.P.-C. & M.C.)
| | - Margarida Castell
- Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), 08028 Barcelona, Spain
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), UB, 08921 Santa Coloma de Gramenet, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (F.J.P.-C.); (M.C.); Tel.: +34-934-024-505 (F.J.P.-C. & M.C.)
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15
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Li Y, Wu Y, Li S, Li Y, Zhang X, Shou Z, Gu S, Zhou C, Xu D, Zhao K, Tan S, Qiu J, Pan X, Li L. Identification of phytochemicals in Qingfei Paidu decoction for the treatment of coronavirus disease 2019 by targeting the virus-host interactome. Biomed Pharmacother 2022; 156:113946. [PMID: 36411632 PMCID: PMC9618446 DOI: 10.1016/j.biopha.2022.113946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 10/25/2022] [Accepted: 10/28/2022] [Indexed: 01/11/2023] Open
Abstract
Qingfei Paidu decoction (QFPDD) has been clinically proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). However, the bioactive components and therapeutic mechanisms remain unclear. This study aimed to explore the effective components and underlying mechanisms of QFPDD in the treatment of COVID-19 by targeting the virus-host interactome and verifying the antiviral activities of its active components in vitro. Key active components and targets were identified by analysing the topological features of a compound-target-pathway-disease regulatory network of QFPDD for the treatment of COVID-19. The antiviral activity of the active components was determined by a live virus infection assay, and possible mechanisms were analysed by pseudotyped virus infection and molecular docking assays. The inhibitory effects of the components tested on the virus-induced release of IL-6, IL-1β and CXCL-10 were detected by ELISA. Three components of QFPDD, oroxylin A, hesperetin and scutellarin, exhibited potent antiviral activities against live SARS-CoV-2 virus and HCoV-OC43 virus with IC50 values ranging from 18.68 to 63.27 μM. Oroxylin A inhibited the entry of SARS-CoV-2 pseudovirus into target cells and inhibited SARS-CoV-2 S protein-mediated cell-cell fusion by binding with the ACE2 receptor. The active components of QFPDD obviously inhibited the IL-6, IL-1β and CXCL-10 release induced by the SARS-CoV-2 S protein. This study supports the clinical application of QFPDD and provides an effective analysis method for the in-depth study of the mechanisms of traditional Chinese medicine (TCM) in the prevention and treatment of COVID-19.
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Affiliation(s)
- Yuyun Li
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China,Key Laboratory of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan 523808, China
| | - Yan Wu
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
| | - Siyan Li
- School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Yibin Li
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xin Zhang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Zeren Shou
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Shuyin Gu
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Chenliang Zhou
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Daohua Xu
- Key Laboratory of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan 523808, China
| | - Kangni Zhao
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Suiyi Tan
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jiayin Qiu
- School of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China,Corresponding authors
| | - Xiaoyan Pan
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China,Corresponding authors
| | - Lin Li
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China,Corresponding authors
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16
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Valipour M. Recruitment of chalcone's potential in drug discovery of anti-SARS-CoV-2 agents. Phytother Res 2022; 36:4477-4490. [PMID: 36208000 PMCID: PMC9874432 DOI: 10.1002/ptr.7651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/09/2022] [Accepted: 09/22/2022] [Indexed: 01/27/2023]
Abstract
Chalcone is an interesting scaffold found in the structure of many naturally occurring molecules. Medicinal chemists are commonly interested in designing new chalcone-based structures because of having the α, β-unsaturated ketone functional group, which allows these compounds to participate in Michael's reaction and create strong covalent bonds at the active sites of the targets. Some studies have identified several natural chalcone-based compounds with the ability to inhibit the severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus proteases. A few years after the advent of the coronavirus disease 2019 pandemic and the publication of many findings in this regard, there is some evidence that suggests chalcone scaffolding has great potential for use in the design and development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibitors. Artificial placement of this scaffold in the structure of optimized anti-SARS-CoV-2 compounds can potentially provide irreversible inhibition of the viral cysteine proteases 3-chymotrypsin-like protease and papain-like protease by creating Michael interaction. Despite having remarkable capabilities, the use of chalcone scaffold in drug design and discovery of SARS-CoV-2 inhibitors seems to have been largely neglected. This review addresses issues that could lead to further consideration of chalcone scaffolding in the structure of SARS-CoV-2 protease inhibitors in the future.
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Affiliation(s)
- Mehdi Valipour
- Razi Drug Research Center, Iran University of Medical SciencesTehranIran
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17
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Vilas-Boas AA, Magalhães D, Campos DA, Porretta S, Dellapina G, Poli G, Istanbullu Y, Demir S, San Martín ÁM, García-Gómez P, Mohammed RS, Ibrahim FM, El Habbasha ES, Pintado M. Innovative Processing Technologies to Develop a New Segment of Functional Citrus-Based Beverages: Current and Future Trends. Foods 2022; 11:foods11233859. [PMID: 36496667 PMCID: PMC9735808 DOI: 10.3390/foods11233859] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/23/2022] [Accepted: 11/25/2022] [Indexed: 12/03/2022] Open
Abstract
The food industries are interested in developing functional products due to their popularity within nutritional and healthy circles. Functional fruit-based beverages represent one of the fast-growing markets due to the high concentrations of bioactive compounds (BCs), which can be health promoters. Hence, functional beverages based on citrus fruits are a potential way to take advantage of their nutritional and bioactive properties that could attract the interest of consumers. In order to ensure microbial and quality stability, the beverages are subjected to preservation treatment; however, the application of high temperatures leads to the loss of thermolabile BCs. Nowadays, innovative processing technologies (IPT) such as pulsed electric field (PEF), high-pressure processing (HPP), ultrasound processing (US), ohmic heating (OH), and microwave (MW) are a promising alternative due to their efficiency and low impact on juice BCs. The available literature concerning the effects of these technologies in functional fruit-based beverages is scarce; thus, this review gathers the most relevant information about the main positive and negative aspects of the IPT in functional properties, safety, and consumer acceptance of functional citrus-based beverages, as well as the use of citrus by-products to promote the circular economy in citrus processing.
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Affiliation(s)
- Ana A. Vilas-Boas
- Universidade Católica Portuguesa, CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Rua Arquiteto Lobão Vital 172, 4200-374 Porto, Portugal
| | - Daniela Magalhães
- Universidade Católica Portuguesa, CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Rua Arquiteto Lobão Vital 172, 4200-374 Porto, Portugal
| | - Débora A. Campos
- Universidade Católica Portuguesa, CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Rua Arquiteto Lobão Vital 172, 4200-374 Porto, Portugal
| | - Sebastiano Porretta
- Experimental Station for the Food Preserving Industry, Department of Consumer Science, Viale Tanara 31/a, I-43121 Parma, Italy
| | - Giovanna Dellapina
- Experimental Station for the Food Preserving Industry, Department of Consumer Science, Viale Tanara 31/a, I-43121 Parma, Italy
| | - Giovanna Poli
- Experimental Station for the Food Preserving Industry, Department of Consumer Science, Viale Tanara 31/a, I-43121 Parma, Italy
| | - Yildiray Istanbullu
- Central Research Institute of Food and Feed Control, Adalet M, 1. Hürriyet Cd. No:128, 16160 Osmangazi, Bursa, Turkey
| | - Sema Demir
- Central Research Institute of Food and Feed Control, Adalet M, 1. Hürriyet Cd. No:128, 16160 Osmangazi, Bursa, Turkey
| | - Ángel Martínez San Martín
- National Technological Centre for the Food and Canning Industry (CTNC), C. Concordia, s/n, 30500 Molina de Segura, Murcia, Spain
| | - Presentación García-Gómez
- National Technological Centre for the Food and Canning Industry (CTNC), C. Concordia, s/n, 30500 Molina de Segura, Murcia, Spain
| | - Reda S. Mohammed
- Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo P.O. Box 12622, Egypt
| | - Faten M. Ibrahim
- Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo P.O. Box 12622, Egypt
| | - El Sayed El Habbasha
- Field Crops Research Department, National Research Centre, Cairo P.O. Box 12622, Egypt
| | - Manuela Pintado
- Universidade Católica Portuguesa, CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Rua Arquiteto Lobão Vital 172, 4200-374 Porto, Portugal
- Correspondence:
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18
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Theoharides TC, Antonopoulou S, Demopoulos CA. Platelet activating factor: Have we been missing the forest for the trees? Biofactors 2022; 48:1184-1188. [PMID: 36300767 DOI: 10.1002/biof.1908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 01/19/2023]
Affiliation(s)
- Theoharis C Theoharides
- Institute of Neuro-Immune Medicine, Nova Southeastern University, Clearwater, Florida, USA
- Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Smaragdi Antonopoulou
- Laboratory of Biology, Biochemistry and Microbiology, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - Constantinos A Demopoulos
- Laboratory of Biochemistry, Faculty of Chemistry, National & Kapodistrian University, Athens, Greece
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19
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Al‐kuraishy HM, Al‐Gareeb AI, Kaushik A, Kujawska M, Batiha GE. Ginkgo biloba in the management of the COVID-19 severity. Arch Pharm (Weinheim) 2022; 355:e2200188. [PMID: 35672257 PMCID: PMC9348126 DOI: 10.1002/ardp.202200188] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 05/04/2022] [Accepted: 05/09/2022] [Indexed: 12/18/2022]
Abstract
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is linked with inflammatory disorders and the development of oxidative stress in extreme cases. Therefore, anti-inflammatory and antioxidant drugs may alleviate these complications. Ginkgo biloba L. folium extract (EGb) is a herbal medicine containing various active constituents. This review aims to provide a critical discussion on the potential role of EGb in the management of coronavirus disease 2019 (COVID-19). The antiviral effect of EGb is mediated by different mechanisms, including blocking SARS-CoV-2 3-chymotrypsin-like protease that provides trans-variant effectiveness. Moreover, EGb impedes the development of pulmonary inflammatory disorders through the diminution of neutrophil elastase activity, the release of proinflammatory cytokines, platelet aggregation, and thrombosis. Thus, EGb can attenuate the acute lung injury and acute respiratory distress syndrome in COVID-19. In conclusion, EGb offers the potential of being used as adjuvant antiviral and symptomatic therapy. Nanosystems enabling targeted delivery, personalization, and booster of effects provide the opportunity for the use of EGb in modern phytotherapy.
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Affiliation(s)
- Hayder M. Al‐kuraishy
- Department of Clinical Pharmacology and Medicine, College of MedicineALmustansiriyia UniversityBaghdadIraq
| | - Ali I. Al‐Gareeb
- Department of Clinical Pharmacology and Medicine, College of MedicineALmustansiriyia UniversityBaghdadIraq
| | - Ajeet Kaushik
- NanoBioTech Laboratory, Health System Engineering, Department of Environmental EngineeringFlorida Polytechnic UniversityLakelandFloridaUSA
| | | | - Gaber El‐Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary MedicineDamanhour UniversityDamanhourAlBeheiraEgypt
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20
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Zalpoor H, Bakhtiyari M, Shapourian H, Rostampour P, Tavakol C, Nabi-Afjadi M. Hesperetin as an anti-SARS-CoV-2 agent can inhibit COVID-19-associated cancer progression by suppressing intracellular signaling pathways. Inflammopharmacology 2022; 30:1533-1539. [PMID: 35994216 PMCID: PMC9393098 DOI: 10.1007/s10787-022-01054-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 08/06/2022] [Indexed: 12/23/2022]
Abstract
Hesperetin, an aglycone metabolite of hesperidin with high bioavailability, recently gained attention due to its anti-COVID-19 and anti-cancer properties. Multiple studies revealed that cancer patients are prone to experience a severe form of COVID-19 and higher mortality risk. In addition, studies suggested that COVID-19 can potentially lead to cancer progression through multiple mechanisms. This study proposes that hesperetin not only can be used as an anti-COVID-19 agent but also can reduce the risk of multiple cancer progression by suppressing several intracellular signaling pathways in cancer patients with COVID-19. Therefore, in this review, we attempted to provide evidence demonstrating anti-COVID-19/cancer properties of hesperetin with several mechanisms.
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Affiliation(s)
- Hamidreza Zalpoor
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran.
| | - Maryam Bakhtiyari
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Hooriyeh Shapourian
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Puria Rostampour
- Department of Medical Biotechnology, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Chanour Tavakol
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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21
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Karakkadparambil Sankaran S, Nair AS. Molecular dynamics and docking studies on potentially active natural phytochemicals for targeting SARS-CoV-2 main protease. J Biomol Struct Dyn 2022:1-17. [PMID: 35930306 DOI: 10.1080/07391102.2022.2107573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
In the present study, we screened eighty seven novel phytochemical compounds from four popular herbs, such as, Aegle Marmelos, Coleus Amboinicus, Aerva Lanata and Biophytum Sensitivum and identified the best three for targeting the main protease (Mpro) receptor of SARS-CoV-2. After categorizing all the phytochemicals based upon LibDock scores and hydrogen bonding interactions, the top ranked 26 compounds were further subjected for detailed Molecular dynamics (MD) study. From these screening we identified that Aegelinosides B leads the list with a high LibDock value of 142.50 (binding energy: -8.54 kcal/mol), which is better than several popular reference compounds namely, Tipranavir (LibDock score, 141.50), Saquinavir (125.34), Zopicole (122.9), Pirenepine (122.70), (115.37), Metixene (109.18), Oxiconazole Pimozide (138.00) and Rimonabant (91.88). Detailed analysis for structural stability (RMSD), Cα fluctuations (RMSF), intermolecular hydrogen bond interactions, effect of solvent accessibility (SASA) and compactness (Rg) factors were performed for the best six compounds and it is found that they are very stable and exhibit folding behavior. Apart from the docking and MD tests, through further drug-likeness and toxicity tests, three compounds, such as, Aegelinosides B, Epicatechin, and Feruloyltyramine (LibDock scores, respectively, 142.50, 124.33 and 129.06) can be suggested for fighting SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
| | - Achuthsankar S Nair
- Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala, India
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22
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Hamdy R, Mostafa A, Abo Shama NM, Soliman SSM, Fayed B. Comparative evaluation of flavonoids reveals the superiority and promising inhibition activity of silibinin against SARS-CoV-2. Phytother Res 2022; 36:2921-2939. [PMID: 35596627 PMCID: PMC9347486 DOI: 10.1002/ptr.7486] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/19/2022] [Accepted: 04/22/2022] [Indexed: 01/08/2023]
Abstract
Flavonoids are phenolic compounds naturally found in plants and commonly consumed in diets. Herein, flavonoids were sequentially evaluated by a comparative in silico study associated with systematic literature search. This was followed by an in vitro study and enzyme inhibition assays against vital SARS-CoV-2 proteins including spike (S) protein, main protease (Mpro ), RNA-dependent RNA-polymerase (RdRp), and human transmembrane serine protease (TMPRSS2). The results obtained revealed 10 flavonoids with potential antiviral activity. Out of them, silibinin showed promising selectivity index against SARS-CoV-2 in vitro. Screening against S protein discloses the highest inhibition activity of silibinin. Mapping the activity of silibinin indicated its excellent binding inhibition activity against SARS-CoV-2 S protein, Mpro and RdRP at IC50 0.029, 0.021, and 0.042 μM, respectively, while it showed no inhibition activity against TMPRSS2 at its IC50(SARS-CoV-2) . Silibinin was tested safe on human mammalian cells at >7-fold its IC50(SARS-CoV-2) . Additionally, silibinin exhibited >90% virucidal activity at 0.031 μM. Comparative molecular docking (MD) showed that silibinin possesses the highest binding affinity to S protein and RdRP at -7.78 and -7.15 kcal/mol, respectively. MDs showed that silibinin exhibited stable interaction with key amino acids of SARS-CoV-2 targets. Collectively, silibinin, an FDA-approved drug, can significantly interfere with SARS-CoV-2 entry and replication through multi-targeting activity.
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Affiliation(s)
- Rania Hamdy
- Research Institute for Medical and Health SciencesUniversity of SharjahSharjahUnited Arab Emirates
- Faculty of PharmacyZagazig UniversityZagazigEgypt
| | - Ahmed Mostafa
- Center of Scientific Excellence for Influenza VirusesNational Research CentreGizaEgypt
| | - Noura M. Abo Shama
- Center of Scientific Excellence for Influenza VirusesNational Research CentreGizaEgypt
| | - Sameh S. M. Soliman
- Research Institute for Medical and Health SciencesUniversity of SharjahSharjahUnited Arab Emirates
- College of PharmacyUniversity of SharjahSharjahUnited Arab Emirates
| | - Bahgat Fayed
- Research Institute for Medical and Health SciencesUniversity of SharjahSharjahUnited Arab Emirates
- Chemistry of Natural and Microbial Product DepartmentNational Research CentreCairoEgypt
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23
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Al-Rajhi AMH, Yahya R, Abdelghany TM, Fareid MA, Mohamed AM, Amin BH, Masrahi AS. Anticancer, Anticoagulant, Antioxidant and Antimicrobial Activities of Thevetia peruviana Latex with Molecular Docking of Antimicrobial and Anticancer Activities. Molecules 2022; 27:molecules27103165. [PMID: 35630642 PMCID: PMC9145871 DOI: 10.3390/molecules27103165] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/07/2022] [Accepted: 05/09/2022] [Indexed: 12/13/2022] Open
Abstract
Natural origin molecules represent reliable and excellent sources to overcome some medicinal problems. The study of anticancer, anticoagulant, and antimicrobial activities of Thevetia peruviana latex were the aim of the current research. An investigation using high-performance liquid chromatography (HPLC) revealed that the major content of the flavonoids are rutin (11.45 µg/mL), quersestin (7.15 µg/mL), naringin (5.25 µg/mL), and hisperdin (6.07 µg/mL), while phenolic had chlorogenic (12.39 µg/mL), syringenic (7.45 µg/mL), and ferulic (5.07 µg/mL) acids in latex of T. peruviana. Via 1,1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging, the experiment demonstrated that latex had a potent antioxidant activity with the IC50 43.9 µg/mL for scavenging DPPH. Hemolysis inhibition was 58.5% at 1000 µg/mL of latex compared with 91.0% at 200 µg/mL of indomethacin as positive control. Negligible anticoagulant properties of latex were reported where the recorded time was 11.9 s of prothrombin time (PT) and 29.2 s of the activated partial thromboplastin time (APTT) at 25 µg/mL, compared with the same concentration of heparin (PT 94.6 s and APPT 117.7 s). The anticancer potential of latex was recorded against PC-3 (97.11% toxicity) and MCF-7 (96.23% toxicity) at 1000 μg/mL with IC50 48.26 μg/mL and 40.31 µg/mL, respectively. Disc diffusion assessment for antimicrobial activity recorded that the most sensitive tested microorganisms to latex were Bacillus subtilis followed by Escherichia coli, with an inhibition zone (IZ) of 31 mm with minimum inhibitory concentration (MIC) (10.2 μg/mL) and 30 mm (MIC, 12.51 μg/mL), respectively. Moreover, Candida albicans was sensitive (IZ, 28 mm) to latex, unlike black fungus (Mucor circinelloides). TEM examination exhibited ultrastructure changes in cell walls and cell membranes of Staphylococcus aureus and Pseudomonas aeruginosa treated with latex. Energy scores of the molecular docking of chlorogenic acid with E. coli DNA (7C7N), and Rutin with human prostate-specific antigen (3QUM) and breast cancer-associated protein (1JNX), result in excellent harmony with the experimental results. The outcome of research recommended that the latex is rich in constituents and considered a promising source that contributes to fighting cancer and pathogenic microorganisms.
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Affiliation(s)
- Aisha M. H. Al-Rajhi
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia;
| | - Reham Yahya
- Medical Microbiology, College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia;
- King Abduallah International Medical Research Center, Riyadh 11671, Saudi Arabia
| | - Tarek M. Abdelghany
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo 11751, Egypt;
- Correspondence:
| | - Mohamed A. Fareid
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo 11751, Egypt;
- Basic Science Department, Prep Year Deanship, University of Ha’il, Ha’il 2440, Saudi Arabia
| | - Alawlaqi M. Mohamed
- Biology Department, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia; (A.M.M.); (A.S.M.)
| | - Basma H. Amin
- The Regional Centre for Mycology and Biotechnology (RCMB), Al-Azhar University, Cairo 11751, Egypt;
| | - Abdurrahman S. Masrahi
- Biology Department, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia; (A.M.M.); (A.S.M.)
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24
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Md S, Alhakamy NA, Sharma P, Ansari MS, Gorain B. Nanocarrier-based co-delivery approaches of chemotherapeutics with natural P-glycoprotein inhibitors in the improvement of multidrug resistance cancer therapy. J Drug Target 2022; 30:801-818. [DOI: 10.1080/1061186x.2022.2069782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Shadab Md
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Nabil A. Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Priyanka Sharma
- Center for Innovation in Personalized Medicine, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | | | - Bapi Gorain
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India
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25
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Bardelčíková A, Miroššay A, Šoltýs J, Mojžiš J. Therapeutic and prophylactic effect of flavonoids in post-COVID-19 therapy. Phytother Res 2022; 36:2042-2060. [PMID: 35302260 PMCID: PMC9111001 DOI: 10.1002/ptr.7436] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/16/2022] [Accepted: 02/21/2022] [Indexed: 12/17/2022]
Abstract
The high incidence of post-covid symptoms in humans confirms the need for effective treatment. Due to long-term complications across several disciplines, special treatment programs emerge for affected patients, emphasizing multidisciplinary care. For these reasons, we decided to look at current knowledge about possible long-term complications of COVID-19 disease and then present the effect of flavonoids, which could help alleviate or eliminate complications in humans after overcoming the COVID-19 infection. Based on articles published from 2003 to 2021, we summarize the flavonoids-based molecular mechanisms associated with the post-COVID-19 syndrome and simultaneously provide a complex view regarding their prophylactic and therapeutic potential. Review clearly sorts out the outcome of post-COVID-19 syndrome according particular body systems. The conclusion is that flavonoids play an important role in prevention of many diseases. We suggest that flavonoids as critical nutritional supplements, are suitable for the alleviation and shortening of the period associated with the post-COVID-19 syndrome. The most promising flavonoid with noteworthy therapeutic and prophylactic effect appears to be quercetin.
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Affiliation(s)
- Annamária Bardelčíková
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
| | - Andrej Miroššay
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
| | - Jindřich Šoltýs
- Institute of Parasitology, Slovak Academy of Science, Košice, Slovak Republic
| | - Ján Mojžiš
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
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Fazio S, Affuso F, Bellavite P. A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19. Med Sci Monit 2022; 28:e936292. [PMID: 35256581 PMCID: PMC8917781 DOI: 10.12659/msm.936292] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 02/22/2022] [Indexed: 01/11/2023] Open
Abstract
In the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has driven investigational studies and controlled clinical trials on antiviral treatments and vaccines that have undergone regulatory approval. Now that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants may become endemic over time, there remains a need to identify drugs that treat the symptoms of COVID-19 and prevent progression toward severe cases, hospitalization, and death. Understanding the molecular mechanisms of SARS-CoV-2 infection is extremely important for the development of effective therapies against COVID-19. This review outlines the key pathways involved in the host response to SARS-CoV-2 infection and discusses the potential role of antioxidant and anti-inflammatory pharmacological approaches for the management of early mild-to-moderate COVID-19, using the examples of combined indomethacin, low-dose aspirin, omeprazole, hesperidin, quercetin, and vitamin C. The pharmacological targets of these substances are described here for their possible synergism in counteracting SARS-CoV-2 replication and progression of the infection from the upper respiratory airways to the blood, avoiding vascular complications and cytokine and bradykinin storms.
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Affiliation(s)
- Serafino Fazio
- Department of Internal Medicine (retired professor), Medical School University Federico II, Naples, Italy
| | | | - Paolo Bellavite
- Physiopathology Chair, Homeopathic Medical School of Verona, Verona, Italy
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Jing Si Herbal Drink as a prospective adjunctive therapy for COVID-19 treatment: Molecular evidence and mechanisms. PHARMACOLOGICAL RESEARCH - MODERN CHINESE MEDICINE 2022. [PMCID: PMC8654706 DOI: 10.1016/j.prmcm.2021.100024] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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 We compiled evidence of the herbs in JSHD to treat COVID-19 in vivo and in vitro. Results 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 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.
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Hou Y, Liang Z, Qi L, Tang C, Liu X, Tang J, Zhao Y, Zhang Y, Fang T, Luo Q, Wang S, Wang F. Baicalin Targets HSP70/90 to Regulate PKR/PI3K/AKT/eNOS Signaling Pathways. Molecules 2022; 27:1432. [PMID: 35209223 PMCID: PMC8874410 DOI: 10.3390/molecules27041432] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 02/04/2023] Open
Abstract
Baicalin is a major active ingredient of traditional Chinese medicine Scutellaria baicalensis, and has been shown to have antiviral, anti-inflammatory, and antitumor activities. However, the protein targets of baicalin have remained unclear. Herein, a chemical proteomics strategy was developed by combining baicalin-functionalized magnetic nanoparticles (BCL-N3@MNPs) and quantitative mass spectrometry to identify the target proteins of baicalin. Bioinformatics analysis with the use of Gene Ontology, STRING and Ingenuity Pathway Analysis, was performed to annotate the biological functions and the associated signaling pathways of the baicalin targeting proteins. Fourteen proteins in human embryonic kidney cells were identified to interact with baicalin with various binding affinities. Bioinformatics analysis revealed these proteins are mainly ATP-binding and/or ATPase activity proteins, such as CKB, HSP86, HSP70-1, HSP90, ATPSF1β and ACTG1, and highly associated with the regulation of the role of PKR in interferon induction and the antiviral response signaling pathway (P = 10-6), PI3K/AKT signaling pathway (P = 10-5) and eNOS signaling pathway (P = 10-4). The results show that baicalin exerts multiply pharmacological functions, such as antiviral, anti-inflammatory, antitumor, and antioxidant functions, through regulating the PKR and PI3K/AKT/eNOS signaling pathways by targeting ATP-binding and ATPase activity proteins. These findings provide a fundamental insight into further studies on the mechanism of action of baicalin.
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Affiliation(s)
- Yinzhu Hou
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
- College of Chemical Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zuqing Liang
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
- College of Chemical Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Luyu Qi
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
- College of Chemical Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chao Tang
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
| | - Xingkai Liu
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
- College of Chemical Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jilin Tang
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
- College of Chemical Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yao Zhao
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
| | - Yanyan Zhang
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
| | - Tiantian Fang
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
| | - Qun Luo
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
- College of Chemical Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Shijun Wang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Fuyi Wang
- Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; (Y.H.); (Z.L.); (L.Q.); (C.T.); (X.L.); (J.T.); (Y.Z.); (Y.Z.); (T.F.)
- College of Chemical Science, University of Chinese Academy of Sciences, Beijing 100049, China
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
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Pagano E. Phytocompounds and COVID-19: Two years of knowledge. Phytother Res 2022; 36:2267-2271. [PMID: 35170093 PMCID: PMC9111037 DOI: 10.1002/ptr.7420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 01/30/2022] [Indexed: 11/07/2022]
Affiliation(s)
- Ester Pagano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
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30
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Yao J, Zhang Y, Wang XZ, Zhao J, Yang ZJ, Lin YP, Sun L, Lu QY, Fan GJ. Flavonoids for Treating Viral Acute Respiratory Tract Infections: A Systematic Review and Meta-Analysis of 30 Randomized Controlled Trials. Front Public Health 2022; 10:814669. [PMID: 35252093 PMCID: PMC8888526 DOI: 10.3389/fpubh.2022.814669] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 01/14/2022] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND This meta-analysis aimed to investigate the efficacy and safety of flavonoids in treating viral acute respiratory tract infections (ARTIs). METHODS Randomized controlled trials (RCTs) were entered into meta-analyses performed separately for each indication. Efficacy analyses were based on changes in disease-specific symptom scores. Safety was analyzed based on the pooled data from all eligible trials, by comparing the incidence of adverse events between flavonoids and the control. RESULTS In this study, thirty RCTs (n = 5,166) were included. In common cold, results showed that the flavonoids group decreased total cold intensity score (CIS), the sum of sum of symptom intensity differences (SSID) of CIS, and duration of inability to work vs. the control group. In influenza, the flavonoids group improved the visual analog scores for symptoms. In COVID-19, the flavonoids group decreased the time taken for alleviation of symptoms, time taken for SARS-CoV-2 RT-PCR clearance, the RT-PCR positive subjects at day 7, time to achievement of the normal status of symptoms, patients needed oxygen, patients hospitalized and requiring mechanical ventilation, patients in ICU, days of hospitalization, and mortality vs. the control group. In acute non-streptococcal tonsillopharyngitis, the flavonoids group decreased the tonsillitis severity score (TSS) on day 7. In acute rhinosinusitis, the flavonoids group decreased the sinusitis severity score (SSS) on day 7, days off work, and duration of illness. In acute bronchitis, the flavonoids group decreased the bronchitis severity score (BSS) on day 7, days off work, and duration of illness. In bronchial pneumonia, the flavonoids group decreased the time to symptoms disappearance, the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). In upper respiratory tract infections, the flavonoids group decreased total CIS on day 7 and increased the improvement rate of symptoms. Furthermore, the results of the incidence of adverse reactions did not differ between the flavonoids and the control group. CONCLUSION Results from this systematic review and meta-analysis suggested that flavonoids were efficacious and safe in treating viral ARTIs including the common cold, influenza, COVID-19, acute non-streptococcal tonsillopharyngitis, acute rhinosinusitis, acute bronchitis, bronchial pneumonia, and upper respiratory tract infections. However, uncertainty remains because there were few RCTs per type of ARTI and many of the RCTs were small and of low quality with a substantial risk of bias. Given the limitations, we suggest that the conclusions need to be confirmed on a larger scale with more detailed instructions in future studies.Systematic Review Registration: inplasy.com/inplasy-2021-8-0107/, identifier: INPLASY20218010.
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Affiliation(s)
- Jia Yao
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Yuan Zhang
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Xian-Zhe Wang
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jia Zhao
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhao-Jun Yang
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yu-Ping Lin
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Lu Sun
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Qi-Yun Lu
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Guan-Jie Fan
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
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31
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Liu X, Lou L, Zhou L. Molecular Mechanisms of Cardiac Injury Associated With Myocardial SARS-CoV-2 Infection. Front Cardiovasc Med 2022; 8:643958. [PMID: 35127841 PMCID: PMC8812276 DOI: 10.3389/fcvm.2021.643958] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 11/29/2021] [Indexed: 01/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world. The development of cardiac injury is a common condition in patients with COVID-19, but the pathogenesis remains unclear. The RNA-Seq dataset (GSE150392) comparing expression profiling of mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-CoV-2-infected hiPSC-CMs was obtained from Gene Expression Omnibus (GEO). We identified 1,554 differentially expressed genes (DEGs) based on GSE150392. Gene set enrichment analysis (GSEA), Gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that immune-inflammatory responses were activated by SARS-CoV-2, while muscle contraction, cellular respiration, and cell cycle of hiPSC-CMs were inhibited. A total of 15 hub genes were identified according to protein-protein interaction (PPI), among which 11 upregulated genes were mainly involved in cytokine activation related to the excessive inflammatory response. Moreover, we identified potential drugs based on these hub genes. In conclusion, SARS-CoV-2 infection of cardiomyocytes caused a strong defensive response, leading to excessive immune inflammation, cell hypoxia, functional contractility reduction, and apoptosis, ultimately resulting in myocardial injury.
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Affiliation(s)
- Xianfang Liu
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Longquan Lou
- Department of General Surgery, The Third People's Hospital of Hangzhou, Hangzhou, China
| | - Lei Zhou
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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32
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Theoharides TC. Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome? Mol Neurobiol 2022; 59:1850-1861. [PMID: 35028901 PMCID: PMC8757925 DOI: 10.1007/s12035-021-02696-0] [Citation(s) in RCA: 92] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023]
Abstract
SARS-CoV-2 infects cells via its spike protein binding to its surface receptor on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that many patients develop a chronic condition characterized by fatigue and neuropsychiatric symptoms, termed long-COVID. Most of the vaccines produced so far for COVID-19 direct mammalian cells via either mRNA or an adenovirus vector to express the spike protein, or administer recombinant spike protein, which is recognized by the immune system leading to the production of neutralizing antibodies. Recent publications provide new findings that may help decipher the pathogenesis of long-COVID. One paper reported perivascular inflammation in brains of deceased patients with COVID-19, while others showed that the spike protein could damage the endothelium in an animal model, that it could disrupt an in vitro model of the blood-brain barrier (BBB), and that it can cross the BBB resulting in perivascular inflammation. Moreover, the spike protein appears to share antigenic epitopes with human molecular chaperons resulting in autoimmunity and can activate toll-like receptors (TLRs), leading to release of inflammatory cytokines. Moreover, some antibodies produced against the spike protein may not be neutralizing, but may change its conformation rendering it more likely to bind to its receptor. As a result, one wonders whether the spike protein entering the brain or being expressed by brain cells could activate microglia, alone or together with inflammatory cytokines, since protective antibodies could not cross the BBB, leading to neuro-inflammation and contributing to long-COVID. Hence, there is urgent need to better understand the neurotoxic effects of the spike protein and to consider possible interventions to mitigate spike protein-related detrimental effects to the brain, possibly via use of small natural molecules, especially the flavonoids luteolin and quercetin.
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Affiliation(s)
- Theoharis C Theoharides
- Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, 136 Harrison Avenue, Suite 304, Boston, MA, 02111, USA.
- School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, 02111, USA.
- Departments of Internal Medicine and Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, 02111, USA.
- Institute of Neuro-Immune Medicine, Nova Southeastern University, Clearwater, FL, 33759, USA.
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Ribeiro TDS, Stechi G, Castro PCD, Viana AL. Comunicação em saúde sobre COVID-19 e Diabetes Mellitus em mídias sociais: verdadeiro e falso. ESCOLA ANNA NERY 2022. [DOI: 10.1590/2177-9465-ean-2021-0358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Resumo Objetivos Identificar em canais de veiculação midiática, os assuntos verdadeiros e falsos relacionados à COVID-19 e às pessoas com diabetes mellitus. Método Pesquisa documental realizada em postagens no Twitter e nos sites da Sociedade Brasileira de Diabetes e do Ministério da Saúde e submetidas à análise temática e discutidas à luz das evidências científicas sobre o tema. Resultados Das 110 postagens, 71 eram do Twitter, 31 do Ministério da Saúde e 8 da Sociedade Brasileira de Diabetes. As fake news correspondiam a 88 postagens; sete divulgavam informações sobre estudos não concluídos; seis eram notícias equivocadas; e nove verdadeiras. Os assuntos foram agrupados em alimentos e substâncias, condições de vida (socioeconômica e hábitos), medicações, COVID-19 e diabetes mellitus, gravidade e fatores de risco. Há excesso de desinformação com a finalidade de enganar e negar a realidade, dadas as disputas de saberes e poderes políticos, econômicos e ideológicos. Conclusão e implicações para a prática A maior parte das postagens eram fake news. Em sendo as mídias sociais um lugar para a fácil disseminação de informações verdadeiras ou falsas, os cientistas e profissionais de saúde precisam se aproximar das comunidades virtuais dessas mídias e usá-las como ferramentas aliadas da comunicação em saúde.
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Nanotechnology Applications of Flavonoids for Viral Diseases. Pharmaceutics 2021; 13:pharmaceutics13111895. [PMID: 34834309 PMCID: PMC8625292 DOI: 10.3390/pharmaceutics13111895] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/14/2021] [Accepted: 11/01/2021] [Indexed: 12/14/2022] Open
Abstract
Recent years have witnessed the emergence of several viral diseases, including various zoonotic diseases such as the current pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Other viruses, which possess pandemic-causing potential include avian flu, Ebola, dengue, Zika, and Nipah virus, as well as the re-emergence of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) coronaviruses. Notably, effective drugs or vaccines against these viruses are still to be discovered. All the newly approved vaccines against the SARS-CoV-2-induced disease COVID-19 possess real-time possibility of becoming obsolete because of the development of ‘variants of concern’. Flavonoids are being increasingly recognized as prophylactic and therapeutic agents against emerging and old viral diseases. Around 10,000 natural flavonoid compounds have been identified, being phytochemicals, all plant-based. Flavonoids have been reported to have lesser side effects than conventional anti-viral agents and are effective against more viral diseases than currently used anti-virals. Despite their abundance in plants, which are a part of human diet, flavonoids have the problem of low bioavailability. Various attempts are in progress to increase the bioavailability of flavonoids, one of the promising fields being nanotechnology. This review is a narrative of some anti-viral dietary flavonoids, their bioavailability, and various means with an emphasis on the nanotechnology system(s) being experimented with to deliver anti-viral flavonoids, whose systems show potential in the efficient delivery of flavonoids, resulting in increased bioavailability.
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Khazeei Tabari MA, Iranpanah A, Bahramsoltani R, Rahimi R. Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review. Molecules 2021; 26:3900. [PMID: 34202374 PMCID: PMC8271800 DOI: 10.3390/molecules26133900] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 01/03/2023] Open
Abstract
A newly diagnosed coronavirus in 2019 (COVID-19) has affected all human activities since its discovery. Flavonoids commonly found in the human diet have attracted a lot of attention due to their remarkable biological activities. This paper provides a comprehensive review of the benefits of flavonoids in COVID-19 disease. Previously-reported effects of flavonoids on five RNA viruses with similar clinical manifestations and/or pharmacological treatments, including influenza, human immunodeficiency virus (HIV), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, were considered. Flavonoids act via direct antiviral properties, where they inhibit different stages of the virus infective cycle and indirect effects when they modulate host responses to viral infection and subsequent complications. Flavonoids have shown antiviral activity via inhibition of viral protease, RNA polymerase, and mRNA, virus replication, and infectivity. The compounds were also effective for the regulation of interferons, pro-inflammatory cytokines, and sub-cellular inflammatory pathways such as nuclear factor-κB and Jun N-terminal kinases. Baicalin, quercetin and its derivatives, hesperidin, and catechins are the most studied flavonoids in this regard. In conclusion, dietary flavonoids are promising treatment options against COVID-19 infection; however, future investigations are recommended to assess the antiviral properties of these compounds on this disease.
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Affiliation(s)
- Mohammad Amin Khazeei Tabari
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran;
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Amin Iranpanah
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran;
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Kermanshah USERN Office, Universal Scientific Education and Research Network (USERN), Kermanshah, Iran
| | - Roodabeh Bahramsoltani
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran P.O. Box 1417653761, Iran;
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Roja Rahimi
- Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran P.O. Box 1417653761, Iran;
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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