Table 2.
List of plants with proven immunomodulatory and antiviral activity having potential for exploring against COVID-19 categorized for prioritization on the basis of their earlier in vitro and in vivo studies
| Botanical name (Ayurveda terminology) | Immunomodulatory effect | Antiviral effect | ||||
|---|---|---|---|---|---|---|
| Dose/model/part used | Function/mechanism | Reference | Dose/model | Function/mechanism | Reference | |
| In vitro studies | ||||||
| Adhatoda vasica Nees. (Vasa) | Aqueous extract (leaves) (in vitro) | Restores the cellular hypoxia-mediated loss of mitochondrial morphofunction | Gheware et al. (2021b) | Aqueous and methanol extract from leaves at 10mg/ml each | Methanolic extract significantly inhibited formation of plaques in Vero cells infected with 100 pfu of HSV1 and 2 by 100% and aqueous by 100% and 86%, respectively | Chavan et al. (2013) |
| Glycyrrhiza glabra L. (Yashtimadhu) | 25–100μg/ml in RAW macrophages stimulated with LPS (root) | Inhibits LPS-induced TNF-α, IL-1β, IL-6 production | Sharma et al. (2018) | Glycyrrhizin | Inhibit SARS-CoV replication | Hoever et al. (2005) |
| 50–200μg/ml in LPS-stimulated mouse endometrial epithelial cells | Glycyrrhizin inhibits LPS-induced TNF-α, IL-1β, NO and PGE2 production | Wang et al. (2017) | Inactivates HSV-1 virus irreversibly | Pompei et al. (1980) | ||
| 200, 40, 8mg/l in LPS-induced macrophage cell line of RA W264.7 | Glycyrrhizin acid supresses IL-1β, IL-3, IL-5, IL-10, IL-12, IL-13 and TNF-α (LPS stimulated) | Li et al. (2015) | Licorice and glycyrrhizin | Inhibit plaque formation in all three strains of Japanese encephalitis virus | Badam (1997) | |
| Asparagus racemosus Willd. (Shatavari) |
Human peripheral blood lymphocytes (tissue cultured extract—Shatawarin) (in vitro) |
Stimulates interleukin (IL)-12 production, inhibited production of IL-6, strong modulatory effects on Th1/Th2 cytokine profile | Pise et al. (2015) | |||
| Boerhavia diffusa L. (Punarnava) | Compound eupalitin-3-O-beta-D-galactopyranoside (Bd-I) | Inhibited production of PHA-stimulated IL-2 at the protein and mRNA transcript levels and LPS-stimulated TNF-α production in human PBMCs; it also blocked the activation of DNA binding of NF-kB and AP-1 | Pandey et al. (2005) |
Hepatoma cells Boeravinone H |
Inhibits HCV binding and entry, probably by acting directly on the viral particle | Bose et al. (2017) |
| Phyllanthus emblica L. (Aamlaki) | 500μg/ml IB3-1 cells from cystic fibrosis patient (fruit: pyrogallol) (in vitro) | Inhibits the PAO1-dependent expression of the neutrophil chemokines IL-8, GRO-α, GRO-γ, of the adhesion molecule ICAM-1 and of the pro-inflammatory cytokine IL-6 | Nicolis et al. (2008) | |||
| Phyllanthus amarus Schum. & Thonn (Bhumiamalaki) | 5–60μg/ml, LPS-activated U937 cells (phyllanthin) (in vitro) | Inhibits IL-1β, TNF-α, PGE2 and COX-2 | Harikrishnan et al. (2018) | |||
| Piper longum L. (Pippali) | 17.5μg/ml. human endothelial cells (fruit extract) | Inhibits TNF-α-induced adhesion of neutrophils to endothelium monolayer | Singh et al. (2008) | |||
| Stereospermum suaveolens DC. (Patla) | Ethanol extract, in mice | Produced significant dose-dependent analgesic effect in central and peripheral nociceptive tests and antipyretic response | Mpharm and Kumar (2010) | |||
| Methanolic extract, bark, bronchoalveolar lavage fluid (BALF) in the ova albumin-sensitized mice | Protected the mast cell disruption induced by compound 48/80 in rat model. Mast cell stabilizing activity and decreases bronchial hyperactivity by decreasing the infiltration of inflammatory cells in the airway | Bhalerao et al. (2013) | ||||
| Terminalia chebula Retz. (Haritaki) | 20–80μg/ml LPS-induced mice microglial cell (fruit) | Decreases TNF-α, IL-1β, IL-6, PGE-2, COX-2 | Aher VD (2010) | |||
| 50–62.5 mg/kg/d for 5 weeks bovine type II collagen-induced arthritis DBA/1J mice (fruit) (in vitro) | Suppresses the production of TNF-α, IL-6 and IL-1β in a dose-dependent manner | Narayana Moorthy et al. (2013) | ||||
| Tinospora cordifolia (Thunb.) Miers. (Guduchi) | The macrophage cells J774A.1 were treated with guduchi | NADH oxidase, NADPH oxidase and myeloperoxidase activities via macrophage activation | More and Pai (2012) | Berberine, mice model (in vivo) | Inhibitory effects on cytopathogenic effects and neuraminidase activity of virus. In vivo, decreased mice mortality from 90 to 55%, reduced virus titres in the lungs on day 2 post-infection | Wu et al. (2011) |
|
Withania somnifera (L.) Dunal (Ashwagandha) |
Withania somnifera (L.) Dunal (Ashwagandha) |
Significant increase in total count of WBC, ALC and Platelets. | (Ali et al. 2015) | Antiviral activity against infectious bursal disease virus replication, hydroalcoholic root extract, in chicken embryo fibroblast | Inhibition of virus at maximum 99.9 % in its highest nontoxic concentration, 25μg/ml in cytopathic effect reduction assay | Pant et al. (2012) |
| In vivo studies | ||||||
| Adhatoda vasica Nees. (Vasa) | 400mg/kg p.o. for 8 days in male Wistar rats (methanolic, chloroform and diethyl ether extracts of leaves) | Increase adhesion of neutrophils to nylon fibres | Vinothapooshan and Sundar (2011) | |||
| 130mg/kg for 21 days in male C57BL/6 mice (aqueous extract) | Increases TGF-β1, IL-6, HIF-1α in pulmonary fibrosis and sepsis, rescues the siRNA-induced inflammation. Alters cellular hypoxic response, modulates thrombosis | Gheware et al. (2021a) | ||||
| Asparagus racemosus | Root aqueous extract (100mg/(kg b.w.p.o.) Balb/c mice | Significant increase of CD3(+) and CD4/CD8(+) percentages, significant upregulation of Th1 (IL-2, IFN-γ) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity also showed higher antibody titres and DTH responses | Gautam et al. (2009) | |||
| Phyllanthus amarus Schum. & Thonn (Bhumiamalaki) | 2 μg–2 mg (w/v) i.p. Oreochromis mossambicus fish of either sex (aqueous leaf extract) | Enhances neutrophil activation | Muthulakshmi et al. (2016) | |||
| Piper longum L. (Pippali) |
10–100mg/kg p.o. in C57BL/6 mice with cerulein-induced acute pancreatitis (piperine) |
Piperine reduces production of TNF-α, IL-1β and IL-6; reduces acute pancreatitis-induced neutrophil infiltration | Bae et al. (2011) | |||
| Stereospermum suaveolens DC. (Patla) | Methanolic extract, bark, bronchoalveolar lavage fluid (BALF) in the ova albumin-sensitized mice | Protected the mast cell disruption induced by compound 48/80 in rat model. Mast cell stabilizing activity and decreases bronchial hyperactivity by decreasing the infiltration of inflammatory cells in the airway | Bhalerao et al. (2013) | |||
| Tinospora cordifolia (Thunb.) Miers. (Guduchi) | 50 to 100mg/kg p.o. for 11 days in male BALB/c mice (glycyrrhizin) | Inhibits airway inflammation by inhibiting inflammatory cytokines TNF-α, IL-17A, IL-6, COX-2 | Kim et al. (2020b) | |||
| Migration in response to LPS 1g/kg in 2ml volume p.o. from day 9 to 19 in male Lewis rats adjuvant induced arthritis model (methanolic stem extract) | Reduces pro-inflammatory mediators IL-1β, IL-6, IL-23, TNF-α and MIP-1 | Sannegowda et al. (2015) | ||||
| Withania somnifera (L.) Dunal (Ashwagandha) | Aqueous extract ashwagandha (300mg/kg b.w.) | Significant increase in total count of WBC, ALC and platelets. | Ali et al. (2015) | |||
| Ethanolic extract administered orally as 0.1% suspension of carboxymethylcellulose at a dose of 100 mg kg−1 of body weight of male Swiss albino mice (in vivo) | Enhanced neutrophil counts and humoral antibody response | Siddiqui et al. (2012) | ||||