Table 1.
Potential anti-SARS-CoV-2 effects of TCM.
| Categories of TCM effect | Natural compound/herbal medicine/formula | Targets/pathway | Cell/animal model | Function | References |
|---|---|---|---|---|---|
| Diaphoretic drug | Saikosaponins (Bupleurum chinense DC.) (Chai Hu) | — | MRC-5 cells | Inhibits absorption and penetration of viral HCoV-229E | [56] |
| MXSGD | TLR signaling pathway | LPS-induced pneumonia in rats | Suppresses LPS-induced inflammatory response by inhibiting TLR signaling in LPS-induced pneumonia in rats | [127] | |
| Shen Zhu San | — | — | Network pharmacology shows that Shen Zhu San has the ability to suppress cytokine storms, protect the pulmonary alveolar-capillary barrier, regulate the immune response, and mediate cell death and survival | [133] | |
| Toujie Quwen granules | — | — | Quercetin and isoquercitrin have high affinity with the SARS-CoV-2 S protein, while astragaloside IV and rutin have high affinity with ACE2 | [134] | |
| Heat-clearing drug | Andrographolide (Andrographis paniculata (Burm. f.) Nees) (Chuan Xin Lian) | Mpro | — | Inhibits the main protease of SARS-CoV-2 | [47] |
| Baicalein (Scutellaria baicalensis Georgi) (Huang Qin) | NF-κB and Nrf2/HO-1 | LPS-induced acute lung injury in rat | Suppresses LPS-induced acute lung injury | [107] | |
| Cimicifuga foetida L. (Sheng Ma), Melia azedarach L. (Ku Lian Pi), Coptis chinensis Franch. (Huang Lian), Phellodendron chinense Schneid. (Huang Bai), and Sophora flavescens Ait. (Ku Shen) | MHV proteins | Mouse cell line—delayed brain tumor cells | Decreases MHV, VSV, and PEDV production and intracellular viral RNA and protein expression | [60] | |
| Indigo Naturalis (Polygonum tinctorium Ait.) (Qing Dai) | — | Peritoneal macrophages, IAV-induced acute lung injury in BALB/c mice | Alleviates IAV-induced ALI in mice by its anti-influenza, anti-inflammatory (TNF-α, IL-6) and antioxidation (MPO, MDA) properties | [129] | |
| β-sitosterol (Taraxacum mongolicum Hand.-Mazz., Chrysanthemum morifolium Ramat., Forsythia suspensa (Thunb.) Vahl) (Pu Gong Ying, Ju Hua, Lian Qiao) | RIG-I and IFN/STAT | Acute lung injury in mice | Ameliorates IAV-induced proinflammatory response and acute lung injury in mice | [111] | |
| LHQW | — | Vero E6 cells | Inhibits replication of SARS-CoV-2 and decreases expression of proinflammatory cytokines in Vero E6 cells | [77] | |
| — | — | Four key components (quercetin, luteolin, wogonin, and kaempferol) showed a high binding affinity with 3CLpro of SARS-CoV-2 | [130] | ||
| LHQW | — | — | Rhein, forsythoside A, forsythoside I, neochlorogenic acid, and its isomers exhibited high inhibitory effect on ACE2 | [76] | |
| — | — | Six active compounds of LHQW can enter the active pocket of Akt1 exerting potential therapeutic effects in COVID-19 | [131] | ||
| NF-κB and Raf/MEK/ERK signaling | MDCK cells, BALB/c mice | Inhibits propagation of influenza viruses and decreases expression of proinflammatory cytokines by suppressing NF-κB activation | [74] | ||
| LS | — | Vero E6 cells | Inhibits SARS-CoV-2 replication in Vero E6 cells and reduces the number of virus particles | [78] | |
| NF-κB/MAPK | Huh-7 cells | Suppresses inflammatory response by inhibiting the production of proinflammatory cytokines (TNF-α, IL-6, IL-1β, IL-8, CCL-2/MCP-1, and CXCL-10/IP-10) | [78] | ||
| Lung-toxin dispelling formula No. 1 | — | — | One hundred and eighteen constituents of respiratory detox shot (RDS) showed a high binding affinity with 3CLpro of SARS-CoV-2 | [71] | |
| PDL | — | Vero E6 cells | Suppresses replication of SARS-CoV-2 in Vero E6 cells | [81] | |
| — | SARS-CoV-2 infected hACE2 transgenic mice | Reduces replication of SARS-CoV-2 in hACE2 transgenic mice; suppresses inflammatory response by inhibiting expression of IL-10 and TNF-α | [81] | ||
| QFPD | NF-κB/MAPK | — | Inhibits expression of proinflammation factors, such as TNF-α, IL-1β, IL-8 | [4] | |
| Production of cytokines and chemokines | RAW264.7 cells | Suppresses production of proinflammatory cytokines and chemokines, such as IL-6, CCL-2, and TNF-α, and induces the expression of IL-10 | [69] | ||
| Blood-activating and stasis-dissolving drug | Curcumin (Curcuma Longa L., Curcuma phaeocaulis Val.) (Jiang Huang, E Zhu) | SARS-CoV-2 protease, spike glycoprotein-RBD, and PD-ACE2 | — | Inhibits the expression of ACE2 and viral replication | [54], [55], [128] |
| β-actin | Vero cells | Suppresses viral replication and changes the structure of the surface protein in viruses, thereby inhibiting viral entry | [54] | ||
| Differentiation of Treg cells | CLP-induced acute lung injury in mouse | Controls inflammation in CLP-induced acute lung injury | [108] | ||
| Isoforskolin (Sparganium stoloniferum Buch.-Ham.) (San Leng) | — | LPS-induced acute lung injury in mice and rats | Suppresses LPS-induced acute lung injury and decreases the expression of TNF-α, IL-6, IL-8 and IL-1β | [99] | |
| Tanshinone IIA (Salvia miltiorrhiza Bge.) (Dan Shen) | MIF and NF-κB | LPS-induced lung injury in mice | Protects against LPS-induced lung injury in mice | [112] | |
| XBJ | — | — | The active ingredients of XBJ regulate different genes, act on different pathways, and synergistically produce anti-inflammatory and immune regulatory effects | [132] | |
| Crocin (Crocus sativus L.) (Zang Hong Hua), Digitoxigenin (Nerium oleander L.) (Jia Zhu Tao), and β-eudesmol (Laurus nobilis, Commiphora myrrha Engl.) (Yue Gui, Mo Yao) | — | — | Suppresses the replication of SARS-CoV-2 by inhibiting the main protease of SARS-CoV-2 | [51] | |
| Purging drug | Emodin (Rheum officinale Baill.) (Da Huang) | SARS-CoV-2 S protein | Vero E6 cells infected with protein-pseudotyped retrovirus | Blocks the S protein and ACE2 interaction and the infectivity of S-protein-pseudotyped retrovirus to Vero E6 cells in a dose-dependent manner | [58] |
| Emodin (Rheum officinale Baill., Polygonum cuspidatum Sieb. et Zucc.) (Da Huang, Hu Zhang) | mTOR/HIF-1α/VEGF | LPS-induced acute lung injury in rat | Improves the pathological conditions and decreases the number of infiltrated inflammatory cells in LPS-induced ALI | [104] | |
| Nrf2/HO-1 | Rat with acute pancreatitis | Protects rats against acute pancreatitis-associated lung injury by inhibiting NLRP3 inflammasome activation | [105] | ||
| p38 MAPK | Rat with sepsis | Protects lung injury in septic rats by suppressing inflammatory response | [106] | ||
| Tonify deficiency medicine | Polygonum multiflorum Thunb. (He Shou Wu) and Caulis Polygoni multiflora (Shou Wu Teng) | SARS-CoV-2 S protein | Vero E6 cells infected with protein-pseudotyped retrovirus | Blocks the S protein and ACE2 interaction and the infectivity of S-protein-pseudotyped retrovirus to Vero E6 cells in a dose-dependent manner | [58] |
| Ruscogenin (Ophiopogon japonicus (L.f) Ker-Gawl) (Mai Dong) | — | LPS-induced acute lung injury in rats | Suppresses LPS-induced acute lung injury | [100] | |
| Glycyrrhizic acid (Glycyrrhiza uralensis Fisch.) (Gan Cao) | — | HEK293 cells | Inhibits the SARS-CoV-2 RBD interaction with ACE2 | [124] | |
| Arenaria kansuensis Maxim. (Xue Ling Zhi) | Nrf2 pathway and NF-κB/TGF-β1/Smad2/3 pathway | Paraquat-induced pulmonary fibrosis animal model | Protects pulmonary fibrosis though activation of the Nrf2 pathway and inhibition of the NF-κB/TGF-β1/Smad2/3 pathway | [102] | |
| Liquiritin (Glycyrrhiza uralensis Fisch.) (Gan Cao) | NF-κB, TRPV1, and TRPA1 | LPS-induced acute lung injury in mice | Alleviates lung injury and suppresses inflammation | [103] | |
| Cordyceps sinensis extract (Cordyceps sinensis (Berk.) Sacc.) (DCXC) | NF-κB, COX-2, and iNOS | LPS-induced acute lung injury in mice | Alleviates LPS-induced ALI | [113] | |
| Shenfu decoction | — | — | The effective ingredients showed a high docking affinity with Mpro, RdRP, and S proteins | [80] | |
| Dampness-resolving drug | Honokiol (Magnolia officinalis Rehd. et Wils.) (Hou Po) | NF-κB | Sepsis in mice | Alleviates sepsis-associated acute lung injury and lethality via the inhibition of oxidative stress in mice | [96] |
| Paclitaxel (Taxus cuspidata Sieb. et Zucc.) (Zi Shan) | MUC1 and TLR-4/NF-κB | CLP-induced sepsis in mice | Alleviates acute lung injury in CLP-induced septic mice | [110] | |
| Peels of Citrus sinensis (Citrus reticulata Blanco.) (Chen Pi) | TRPA1, TRPC4, TRPM6, TRPM7, TRPM8, and TRPV4 | HeLa-CEACAM1a cells | Decreases the virus load in HeLa-CEACAM1a cells inoculated with MHV-A59 | [58] | |
| Qi-regulating drug | Diosmetin (Citrus aurantium L.) (Zhi Shi) | Nrf2 | RAW264.7, A549 cells LPS-induced ALI in mice | Inhibits LPS-induced ALI via activation of Nrf2 and inhibition of NLRP3 inflammasome | [109] |
| Cold-dispelling drug | Caffeic acid phenethyl ester (Cinnamomum cassia Presl.) (Rou Gui) | TNF, iNOS, and NF-κB p65 | LPS-induced acute lung injury in mice | Suppresses LPS-induced acute lung injury | [98] |
MRC-5: human fetal lung fibroblasts; MDA: malondialdehyde; Akt1: V-akt murine thymoma viral oncogene homologue 1; Raf: serine/threonine kinase; MEK: mitogen-activated protein kinase kinase; ERK: extracellular signal-regulated kinase; MDCK: Madin–Darby canine kidney; MIF: macrophage migration inhibitory factor; TRPA: transient receptor potential ankyrin; TRPM: transient receptor potential melastatin; TNF: tumour necrosis factor.