Table 1.
Effects and mechanisms of single Chinese medicine and its components on antiviral pneumonia.
| Name of Herb | Components contained/product | Model/Strains | Dosage/Duration | IC50, EC50, TCID50, TC50, TC0, LD50, CD50 * | Control | Actions and mechanisms | References |
|---|---|---|---|---|---|---|---|
| Rhus chinensis Mill. (Wubeizi) | Ethyl acetate extract: acyl pentagalic acid glucose, ellagic acid and gallic acid | In vitro: influenza virus neuraminidase (NA) | 10, 25, 50, 75, 100 mg/L | 62.81 mg/L (IC50) | Oseltamivir | Inhibits neuraminidase activity, restrain influenza virus A/PR/8/34 (H1N1), inhibits the activation of TLR4 and the downstream MyD88 dependent transduction pathway, reduces the transcription of inflammatory factors, and alleviates lung inflammation and slow down the process of acute lung injury. | Yang et al., 2017; Zhang et al., 2018 |
| Ethanol extract: acyl pentagalic acid glucose, ellagic acid and gallic acid | 58.31 mg/L (IC50) | ||||||
| Gallic acid | In vitro: A/California/07/2009 (H1N1) in MDCK | 2.5 μg/ml | 2.6 ± 0.07 μg/ml (EC50) | Amantadine | |||
| Osmunda japonica Thunb. (Ziqiguanzhong) | Isoginkgetin | In vitro: A/Califomia/04/2009 (H1N1) | 50 mg/L | 42.54 ± 2.85 μmol/L (IC50) | Oseltamivir | Inhibits neuraminidase activity, and plays an anti-inflammatory role through IκB and c-JUN pathway. | Lang et al., 2019; Li et al., 2019 |
| Nepeta tenuifolia Benth. (Jingjie) | Volatile oil of Nepeta tenuifolia | In vitro: A/PR/8/34 (H1N1) in MDCK | 3.1×10-3-0.10 mg/ml | 3.1×10-3 mg/ml (IC50); 0.20 mg/ml (TC50); 0.10 mg/ml (TC0) | Ribavirin | Inhibits and kills influenza virus, increases the content of IFN-α, TLR7, IFN-β and IL-2 and inhibits the secretion of IL-6 and TNF-α in the serum of mice, and restrains the protein expression of Myd88 and TRAF6. | Xie X. H. et al., 2007; He et al., 2012; Gou et al., 2013; He et al., 2013 |
| Pulegone | 1.3×10-2-0.10 mg/ml | 7.2×10-3 mg/ml (IC50); 0.36 mg/ml (TC50); 0.10 mg/ml (TC0) | |||||
| Menthone | 7.8×10-3-0.10 mg/ml | 1.9×10-3 mg/ml (IC50); 0.43 mg/ml (TC50); 0.25 mg/ml (TC0) | |||||
| Arctium lappa L. (Niubangzi) | Arctigenin | In vitro: A/FM1/1/47 (H1N1) in MDCK | 500, 125, 31.25, 7.81 mg/ml | 31.25 mg/ml (IC50) | Ribavirin | Inhibits the release of progeny viruses from the host cells and induces interferon in vivo; and improves the protein expression of IFN to regulate human immune function. | Tsou, 2007; Fu et al., 2008; Hayashi et al., 2010 |
| Ilex asprella (Hook. et Arn.) Champ. ex Benth. (Gangmei) | Water extraction of Ilex asprella root | In vitro: A/FM1/1/47 (H1N1) in MDCK | 50, 12.5, 3.12, 0.78 mg/ml | 23.04 mg/ml (TC50) | Ribavirin | Inhibits influenza virus type A FM1 strain, RSV and parainfluenza virus type 3, increases the percentage of CD3+ in peripheral blood T lymphocyte subsets, and regulates the ratio of CD4/CD8 to enhance the immune function of mice. | Chen et al., 2016 |
| Water extraction of Ilex asprella stem | 10.82 mg/ml (TC50) | ||||||
| Reynoutria japonica Houtt. (Huzhang) | Resveratrol | In vitro: A/PR/8/34 (H1N1) in MDCK | 31.25–1,000 mg/L | 129.8 μmol/L (IC50); 5.9 μmol/L (EC50) | Zanamivir | Inhibits neuraminidase activity, reduces lung index, alleviates pulmonary edema, reduces inflammatory factors TNF-α, IL-1β, increases PI3K protein expression, and reduces the protein expression of p-Akt, caspase-3 and NF-κB. | Chen et al., 2012; Li M. et al., 2020 |
| In vitro: A/Guangdong/243/72 (H3N2) in MDCK | 144.7 μmol/L (IC50) | ||||||
| Catechin-3-O-gallate | In vitro: A/PR/8/34 (H1N1) in MDCK | 21.3 μmol/L (IC50); 0.9 μmol/L (EC50) | |||||
| In vitro: A/Guangdong/243/72 (H3N2) in MDCK | 21.5 μmol/L (IC50) | ||||||
| Isatis tinctoria L. (Banlangen) | Isatis root polysaccharide (IRP) | In vitro: A/Califomia/04/2009 (H1N1), A/Anhui/1/2005 (H5N1) in Fluorescein-n-acetylneuraminic acid solution | 0.5-35 mg/ml | H1N1: 24.13 mg/ml (IC50); H5N1: 22.91 mg/ml (IC50) | Oseltamivir, apigenin | Inhibits neuraminidase activity in influenza virus H1N1 and H5N1, and decrease the protein expression of IFN-β by downregulating the expression of TLR3, TBK1 and p-IRF3 in RAW264.7 cells infected by respiratory syncytial virus (RSV), attenuates inflammation, and decreases H1N1 viral replications in lungs, reduces the protein expression of mitofusin-2 (MFN2) to reduce the susceptibility to influenza virus via mitochondrial antiviral signaling. | Li et al., 2009; Li J, 2013; Hou et al., 2017; Luo et al., 2019 |
| Acid Isatis root polysaccharide (IRPA) | H1N1: 5.88 mg/ml (IC50); H5N1: 4.12 mg/ml (IC50) | ||||||
| Neutral Isatis root polysaccharide (IRPN) | H1N1: 52.34 mg/ml (IC50); H5N1: 49.39 mg/ml (IC50) | ||||||
| Isatis root polysaccharide (IRP) | In vitro: A/Califomia/04/2009 (H1N1), A/Anhui/1/2005 (H5N1) in Fluorescein-4,7-dimethoxy-n-acetylneuraminic acid solution | H1N1: 25.66 mg/ml (IC50); H5N1: 23.10 mg/ml (IC50) | |||||
| Acid Isatis root polysaccharide (IRPA) | H1N1: 6.09 mg/ml (IC50); H5N1: 5.08 mg/ml (IC50) | ||||||
| Neutral Isatis root polysaccharide (IRPN) | H1N1: 55.19 mg/ml (IC50); H5N1: 52.16 mg/ml (IC50) | ||||||
| Gardenia jasminoides J. Ellis (Zhizi) | Geniposide, Gardenia extract ZG | In vitro: A3/Guifang/81/23 (H3N2) in A549 | 6.25–1,600 μg/ml | 50-60 μg/ml (IC50) | Ribavirin | Decreases the protein expression of IL-6, TNFα, TLR3 and NF-κB and mRNA expression of TLR7/MyD88 and TRIF in lung tissue of H3N2-infected mice, and improve cell membrane fluidity. | Guo et al., 2007; Zhang and Yu, 2010; Wang Y. F. et al., 2020 |
| Hypericum perforatum L. (Guanyelianqiao) | Hypericin, hyperoside | In vitro: 2337/A/Gansuchengguan/1771/2006 (H1N1) in MDCK | 100, 50, 25, 12.5 μg/ml | 10-4.90/0.1 ml (TCID50); 200 μg/ml (TC0) | Oseltamivir | Increases the function of T and B lymphocyte conversion, phagocytic function of macrophages and NK killing activity of influenza virus-infected mice, decreases the content of IL-6 and TNF-α and increases the protein expression of IFN-γ and IL-10 in lung tissue and serum of mice. | Wang et al., 2009; Xu et al., 2016 |
| Andrographis paniculata (Burm.f.) Nees (Chuanxinlian) | Water extraction of Andrographis paniculata | In vitro: A/FM1/1/47 (H1N1) in MDCK | 250, 62.5, 15.63, 3.9, 0.98, 0.24 mg/ml | 10-3.50/0.1 ml (TCID50); 250 mg/ml (TC0) | Ribavirin | Increases the percentage of CD3+ in peripheral blood T lymphocyte subsets, regulates the ratio of CD4/CD8, enhances the immune function of mice, and shows antiviral activity against H5N1 virus. | Sornpet et al., 2017; Wang et al., 2019 |
| Ethanol extraction of Andrographis paniculata | In vitro: influenza virus A/Chicken/Thailand/CUK2/04 (H5N1) in MDCK | 8.2 g/ml | 8.2 μg/ml (CD50) | – | |||
| Water extraction of Andrographis paniculata | 380.3 μg/ml (CD50) | ||||||
| Lonicera japonica Thunb. (Jinyinhua) | Chlorogenic acid, caffeic acid | In vitro: influenza A (H3N2) in MDCK | 5 mg/ml | 236.28 ± 15.37 μg/ml (IC50) | Ribavirin | Inhibits the influenza virus proliferation and neuraminidase activity, increases the content of IFN-γ in serum, and decrease the lung index. | Shen et al., 2012; Zhu et al., 2018; Zhao et al., 2020 |
| In vitro: Influenza A (H1N1) in MDCK | 290.50 ± 34.82 μg/ml (IC50) | ||||||
| Scutellaria baicalensis Georgi (Huangqin) | Baicalin | In vitro: A/FM1/1/47 (H1N1) in MDCK/A549 | 20, 30, 40, 60, 80 μg/ml (in MDCK); 5, 10, 20, 30, 40 μg/ml (in A549) | 43.3/40.3 μg/ml (EC50) | Ribavirin | Inhibits neuraminidase activity, reduces virus replication, and decreases the protein expression of TLR3 and NF-κB and mRNA expression of TRIF, the protein and gene expression of proinflammatory cytokines TNF-α, IL-1 and IL-6 in lung tissue, and increases the protein and gene expression of anti-inflammatory cytokine IL-10 and antiviral factor IFN-γ in lung tissue after infection. | Ding et al., 2014; Wang et al., 2014; Zhang and Yu, 2010; Xu et al., 2019 |
| In vitro: A/Beijing/32/92 (H3N2) in MDCK or A549 | 104.9/100.1 μg/ml (EC50) | ||||||
| In vivo: A/FM1/1/47 (H1N1) in mice | 50, 100, 200 mg/kg/day | 52.3 μmol/L (IC50) | |||||
| In vivo: A/Beijing/32/92 (H3N2) in mice | 85.8 μmol/L (IC50) | ||||||
| Coptis chinensis Franch. (Huanglian) and Magnolia officinalis Rehder & E.H.Wilson (Houpo) | Berberine | In vitro: influenza virus neuraminidase (NA) | 32, 16, 8.0, 4.0, 2.0, 1.0, 0.5 mg/ml | 21.10 mg/ml (IC50) | Oseltamivir | Inhibits neuraminidase activity, restrain influenza A (H1N1) virus, reduce the lung index of infected mice and ameliorates the lung pathological changes, suppresses the viral infection‐induced up‐regulation of TLR7 signaling pathway, such as TLR7, MyD88, and NF-κB (p65), at both the mRNA and protein levels, and inhibits the viral infection‐induced increase in Th1/Th2 and Th17/Treg ratios as well as the production of inflammatory cytokines. | Wu et al., 2014; Chen et al., 2017; Enkhtaivan et al., 2018; Yan et al., 2018 |
| Berberine: magnolol (1:5) | 19.09 mg/ml (IC50) | ||||||
| Berberine: magnolol (2:5) | 15.39 mg/ml (IC50) | ||||||
| Berberine: magnolol (2:3) | 3.80 mg/ml (IC50) | ||||||
| Berberine: magnolol (1:1) | 3.53 mg/ml (IC50) | ||||||
| Berberine: magnolol (3:2) | 13.66 mg/ml (IC50) | ||||||
| Berberine: magnolol (5:2) | 8.90 mg/ml (IC50) | ||||||
| Berberine: magnolol (5:1) | 19.04 mg/ml (IC50) | ||||||
| Magnolol | 19.37 mg/ml (IC50) | ||||||
| Berberine: magnolol (1:1) | In vivo: A/PR/8/34 (H1N1) in mice | 8 g/kg | 10-2.5/100 μl (LD50) | Ribavirin | |||
| Ephedra sinica Stapf (Mahuang) | (+) - Catechin | In vitro: A/California/07/2009 (H1N1) in MDCK | 25 μg/ml | 18.4 ± 0.7 μg/ml (EC50) | Amantadine | Suppresses the proliferation of influenza virus H1N1 and neuraminidase activity, and inhibits the adsorption and penetration of respiratory syncytial virus. | Mantani et al., 2001; You et al., 2018; Zhu, 2008 |
| Water extract of Ephedra sinica | In vitro: respiratory syncytial virus (RSV) in Hela | 5.00, 4.00, 3.20, 2.56 mg/ml | 3.74 mg/ml (EC50) | Ribavirin | |||
| Forsythia suspensa (Thunb.) Vahl (Lianqiao) | Ethanol extract: Forsyshiyanins A-B, Forsythiaside (Phillyrin) | In vitro: A/PR/8/34 (H1N1) in MDCK | 10 μM | 18.4-26.2 μM (IC50) | Ginkgolide B | Forsyshiyanins A-B inhibit NP gene expression of influenza A virus after transfection. Forsythoside A reduces the viral titers of different influenza virus subtypes in cell cultures and increases the survival rate of the mice in an in vivo influenza virus infection model, and reduces the influenza M1 protein, which in turn intervenes the budding process of the newly formed virions. | Duan et al., 2012; Law et al., 2017; Zhao et al., 2020 |
| In vitro: respiratory syncytial virus (RSV) Long in Hep-2 | 10.5-14.4 μM (EC50) | ||||||
| Morus alba L. (Sangbaipi) | Cortex mori polysaccharide, total flavonoids of Cortex mori | In vitro: respiratory syncytial virus (RSV) Long in Hep-2 | – | 10-2.25/100 μl (TCID50) | Ribavirin | Inhibits respiratory syncytial virus, reduces the infiltration of inflammatory cells in alveolar wall to ameliorate the inflammatory status of lung tissue, promotes cell immune adjustment in mice infected by respiratory syncytial virus, decreases the protein expression of PI3K, Akt1/2 and NF-κBp65 in lung tissue of mice as well as the IL-4 and INF-γ in serum. | Dong et al., 2016a; Dong et al., 2016b; Liu, 2016 |
| Cortex mori polysaccharide | In vivo: respiratory syncytial virus (RSV) Long in mice | 91 mg/kg/day | 10-1.92/100 μl (LD50) | ||||
| Total flavonoids of Cortex mori | 114 mg/kg/day | ||||||
| Houttuynia cordata Thunb. (Yuxingcao) | Quercetin, isoquercetin | In vitro: Influenza A (H3N2) in MDCK | 5 mg/ml | 428.97 ± 38.54 μg/ml (IC50) | Ribavirin | Houttuynia cordata Thunb. extract, quercetin and cinanserin inhibit the activity of murine coronavirus and the protein expression of NF-κB, and restrains the replication of influenza A virus in vitro. Quercitrin inhibites both viral replication and TLR signaling in cells. Flavonoids from Houttuynia cordata attenuate H1N1-induced acute lung injury in mice via inhibition of influenza virus and Toll-like receptor signaling. | Chiow et al., 2016; Zhu et al., 2018; Ling et al., 2020 |
| In vitro: Influenza A (H1N1) in MDCK | 522.28 ± 36.48 μg/ml (IC50) | ||||||
| Ethyl acetate (EA) fraction of Houttuynia cordata Thunb. | In vitro: Murine coronavirus | 0.24-3.91 mg/ml | 0.98 μg/ml (IC50) | Rutin | |||
| Quercetin | 15.63-500.00 mg/ml | 125.00 μg/ml (IC50) | |||||
| Cinanserin (1 dpi)Cinanserin (2 dpi) | 3.91-125.00 mg/ml | 31.25 μg/ml (IC50)62.50 μg/ml (IC50) | |||||
| Cinnamomum cassia (L.) J.Presl (Guizhi) | Cinnamic aldehyde | In vitro: A/PR/8/34 (H1N1) in MDCK | 0.132, 0.264 mg/kg | 5.31×10-5 mg/ml (IC50) | Ribavirin | Inhibits the proliferation of influenza A virus (H1N1) in MDCK cells, restrains the infection by interfering with endocytosis, kills influenza virus, and increases the content of IFN-α and IFN-β in the serum of H1N1-infected mice. | Liu et al., 2012; Gou et al., 2013; Liu et al., 2013; Zhuang et al., 2009 |
| Volatile oil of Cassia twig | 0.174, 0.348 mg/kg | 5.80×10-5 mg/ml (IC50) | |||||
| Cinnamomi Cortex extract | In vitro: wild-type SARS-CoV in Vero E6 cells | 0.1, 0.2, 0.3 mg/ml | 43.1± 2.8 μg/ml (IC50) | – | |||
| Ethanol extract of Cinnamomi Cortex | 10.7± 0.4 μg/ml (IC50) | ||||||
| Butanol fraction of Cinnamomi Cortex | 7.8± 0.3 μg/ml (IC50) | ||||||
| Aqueous fraction of Cinnamomi Cortex | 39.7± 2.1 μg/ml (IC50) | ||||||
| Syzygium aromaticum (L.) Merr. & L.M.Perry (Dingxiang) | Methanol extraction of Clove | In vitro: A/PR/8/34 (H1N1) in MDCK | 30, 10, 10/3, 10/9, 10/27, 10/81 μg/ml | 9.1 μg/ml (IC50) | Zanamivir, ribavirin | Inhibits neuraminidase activity, restrains the infection by interfering with endocytosis, increases the levels of IFN-γ and IL-10 in serum, decreases the levels of TNF-α and IL-6, alleviates the pathological changes of lung tissue and decreases the lung index of mice infected by A/swine/Tianjing/14/2009(H1N1). | Zhuang et al., 2009; Li et al., 2013; Liu et al., 2018 |
| Eugeniin | 7.85 μg/ml (IC50) | ||||||
| CFE (Caryophylli Flos extract) | In vitro: wild-type SARS-CoV in Vero E6 cells | 0.1, 0.2, 0.3 mg/ml | 50.1± 3.5 μg/ml (IC50) | – | |||
| Cibotium barometz (L.) J.Sm. (Gouji) | Ethanol extraction of Cibotium barometz | In vitro: SARS-CoV in Vero E6 cells | 200, 100, 50, 25 μg/ml | 8.42 μg/ml (EC50) | Valinomycin | Inhibits viral replication and the enzymatic activity of SARS-CoV 3CL protease, and inhibit respiratory syncytial virus induced cytopathic effect in vitro. | Li et al., 2008; Wen et al., 2011 |
| Methanol extraction of Cibotium barometz | >10 μg/ml (EC50) | ||||||
| Taxillus chinensis (DC.) Danser (Sangjisheng) | N-hexane extraction of Taxillus chinensis | 5.39 μg/ml (EC50) | |||||
| Dioscorea oppositifolia L. (Shanyao) | Methanol extraction of Dioscorea batatas | 8.06 μg/ml (EC50) | |||||
| Senna tora (L.) Roxb. (Juemingzi) | N-hexane extraction of Cassia tora | 8.43 μg/ml (EC50) | |||||
| Gentiana scabra Bunge (Longdan) | N-hexane extraction of Gentiana scabra | 8.70 μg/ml (EC50) | |||||
| Active compound RG2-1 from Gentiana scabra | In vitro: respiratory syncytial virus (RSV) Long in Hela cells | 50, 25, 12.5, 6.25 mg/ml | 11.07 mg/ml (TC50); 0.42 mg/ml (EC50) | Ribavirin | |||
| Glycyrrhiza uralensis Fisch. ex DC. (Gancao) | Glycyrrhizic acid | In vitro: SARS-associated coronavirus in Vero cells | 1,000, 4,000 mg/ml | After virus adsorption: 600 mg/L (EC50); during and after virus adsorption: 300 mg/L (EC50); during virus adsorption: 2,400 mg/L (EC50) | Mycophenolic acid, pyrazofurin and ribavirin | Inhibits virus replication, adsorption and membrane penetration, up-regulates the mRNA expression of IFN-γ and its immunomodulatory function against influenza virus infection, down-regulates the mRNA expression of TNF-α, and decreases the inflammatory reaction induced by TNF-α to reduce the host immune damage. | Cinatl et al., 2003; Xie Z. P. et al., 2007; Liu et al., 2006; Fu X. L. et al., 2020 |
| Active compound (GC3-1-4) | In vitro: Parainfluenza virus (type III) in Hela | 25, 20, 16,12.8, 10.2 μg/ml | 12.82 μg/ml (EC50); 144.17 μg/ml (TC50) | Ribavirin | |||
| In vitro: respiratory syncytial virus (RSV) in Hela | 100, 75, 56, 42, 32, 24 μg/ml | 41.32 μg/ml (EC50); 0.45 mg/ml (TC50) | |||||
| Rheum officinale Baill. (Dahuang) | Emodin (1,3,8-trihydroxy-6-methylanthraquinone), aqueous extract of Radixet Rhizoma Rhei | In vitro: SARS-CoV in Vero E6 cells | 0.1, 0.5, 1, 5, 10, 50, 100 μg/ml | 200 μM (IC50) | Promazine | Blocks the S protein and ACE2 interaction in a dose-dependent manner and also inhibits the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. | Ho et al., 2007 |
*IC50, 50% inhibiting concentration; EC50, 50% maximal effective concentration; TCID50, 50% tissue culture infectious dose; TC50, median toxic concentration. TCO, Maximum nontoxic concentration; LD50, median lethal dose; CD50, 50% cytotoxicity dose.