Traditional Herbal Medicine for the Prevention and Treatment of Cold and Flu in the Autumn of 2020,Overlapped With COVID-19

Abstract

Many herbs and plants included in several traditional systems have promising bioactive compounds for modern drug therapy. The second round of COVID-19 cases will be accompanied by the spread of seasonal influenza in the fall. The combination of the influenza season and the second wave of COVID-19 may lead to more confusion and put more pressure on public health systems. A literature survey was accomplished using multiple databases including PubMed, Science Direct, ISI web of knowledge, and Google Scholar. The most important antiviral herbs for cold and flu are Thymus vulgaris, honeysuckle flowers, Andrographis, yarrow, peppermint leaf and oil, and Calendula. The most important expectorant herbs for flu and cold are tulsi, snake root, licorice root, clove, slippery elm root, marshmallow osha root, and sage leaf. Immunostimulant herbs for these 2 diseases are Echinacea root, Eucalyptus, garlic, ginseng, marshmallow, slippery elm, Isatisroot, Usnea lichen, myrrh resin, and ginger root. In this mini-review, we mention the key role of some of the most important herbal plants and prescriptions against influenza and cold on the basis of traditional Asian medicine.

Introduction

Seasonal influenza has caused morbidity and mortality every year and is a major public health concern. ^1,2 Due to increased comorbidities and reduction of the immune system, adults more than 65 years old are more at risk of influenza-related deaths and hospitalization. ^3,4 Pregnant women and their infants are also at high risk of seasonal influenza. ^5,6 There are 4 types of influenza viruses: types, A, B, C, and D, of which A, B, and C infect humans. ^7,8 Type A is categorized into subtypes based on 2 surface antigens: hemagglutinin and neuraminidase. Type A viruses have caused pandemic impacts, influenza B causes seasonal epidemics, and influenza C causes mild human infection with little public health impact. On the basis of traditional Chinese medicine (TCM), influenza is differentiated into 2 types, namely, wind-cold syndrome and wind-heat syndrome. Influenza is a contagious respiratory infection, but the common cold is a viral infectious disease of the upper respiratory system caused primarily by rhinoviruses and corona viruses. Site infection of the common cold and influenza are the upper respiratory tract and the entire respiratory system, respectively. In the years to come, influenza will overlap with COVID-19, and both these viruses present a global health threat, associated with a high risk of severe complications; both viruses are transmitted mainly through coughing, sneezing and close bodily contact.

Traditional Herbal Plants and Prescriptions for Treatment and Prevention of Cold and Influenza

Natural products from herbal medicines, especially traditional Chinese and Persian medicines, have been found to exert effects against influenza virus. Traditional herbal remedies have been gaining more attention in recent years due to accessibility, affordability, their safety, promising efficacy, and being eco-friendly. ^{9 -12} Their important roles in public health and wellness have led many people of different nationalities to rely on traditional herbal remedies, including TCM and traditional Persian medicine. ^{13 -17} Asia, especially China and Iran, are reservoirs of various high-valued medicinal plants, which have been used in the cosmetic, nutraceutical, and pharmaceutical industries. ^{18 -22} Chinese and other Asian herbal medicines focus on prevention more than treatment. Herbal medicines are the most important field for new antimicrobial drug discovery for combating pathogenic infectious diseases like the common cold and influenza. ^23,24 Tang et al ²⁵ introduced 126 Chinese patent medicine recipes for influenza, and 55 drugs with a higher use frequency for treatment of influenza were Frutctus Forsythiae, Flos Lonicerae, Radix Glycyrrhizae, Radix Platycodi, Radix Scutellariae, Fructus Arctii, Radix Isatidis, Herba Schizonepetae, Herba Menthae, Herba Lophatheri, Semen Armeniaceae, Semen Sojae Fermentatum, Folium Isatidis, Flos Chrysanthemi, Chrysanthemi Indici, Rhizoma Phragmitis, Folium Mori, Radix Puerariae, Gypsum Fibrosum, Fructus Gardeniae, Bupleuri, Cornu Saigae Tatricae, Radix Ledebouriellae, Radix Angelicae Dahuricae, Calculus Bovic, Rhizomaseu Radix Notopterygii, Caulis Lonicerae, Borneolum, Radix Rehmanniae, Cornu Bubali, Rhizoma Anemarrhenae, Radix Ophiopogonis, Radix Peucedani, Herba Artemisiae, Radix Scrophulariae, Folium Perillae, Herba Ephedrae, Radix Trichisanthis, Herba Houttuyniae, Radix Paeoniae Rubra, Bulbus Fritillariae Cirrhosae, Cortex Mori Radicis, Fructus Perillae, Rhizoma Chuanxiong, Fructus Aurantii, Periostracum Cicadae, Pericarpium Citri Reticulatae, Herba Andrographitis, Radix et Rhizoma Rhei, Bombyx Batryticatus, Folium Eriobotryae, Rhizoma Bistortae, and Caulis Bambusae. Mehrbod et al ²⁶ found that methanol extracts of Rapaneamelanophloeos leaf, and methanol and ethanol extracts of Pittosporumviridiflorum leaf had significant effects against influenza A virus. Mousa ²⁷ suggested maoto, licorice roots, antiwei berries, Echinacea, North American ginseng, pomegranate, guava tea, carnosic acid, and Bai Shao for prevention and treatment of viral respiratory illnesses. The root of Paeonialactiflora Pall. (Bai Shai) has been used in TCM to treat viral infections. Rajasekaran et al ²⁸ showed the importance of Santiriaapiculata (Burseraceae) and Trivalvariamacrophylla (Annonaceae) for treatment of influenza H1N1 and H3N1. Traditional herbal medicines and natural prescriptions for treatment and prevention of cold and influenza are shown in Table 1. TCM treatments for different COVID-19 cases are presented in Table 2.

Table 1

Traditional Medicines and Herbal Compound Prescriptions for Treatment and Prevention of Cold and Influenza.

Plant	Plant family	Mechanism and impacts	References
Aloe barbadensis Mill. (Aloevera)	Asphodelaceae	a. Most important chemical components: aloin, emodin, aloe-emodin, barbaloin, isobarbaloin, and chrysophanic acid b. Rich source of quinone components; aloe anthraquinones have been reported to be active against human influenza virus	29,30
Andrographis paniculata (Burm.f.) Nees	Acanthaceae	Andrographolide has the potential to inhibit neuraminidase activity of H1N1 and can be used as an alternative medicinal therapy for swine flu-positive patients	31
Berberis vulgaris L.	Berberidaceae	Used for colds, flu, fever, and respiratory tract infections	32
Clinacanthus siamensis Bremek	Acanthaceae	Leaf extract has shown activity on influenza virus	33
Echinacea	Asteraceae	Extract has profound activity against several viruses such as human and avian influenza viruses, H3N2-type IV, H1N1-type IV, and reversed virus-induced proinflammatory responses	28,34 -37
Epimedium koreanum Nakai	Berberidaceae	Is part of both traditional Chinese and Korean medicine against different influenza A subtypes by significant reduction in viral replication	38
Flos ionicerae; Radix scutellariae	Caprifoliaceae Lamiaceae	Used against influenza	39 -45
Fructus forsythiae	Oleaceae	Used against influenza	46 -49
Glechoma hederacea L.	Lamiaceae	Used for treatment of flu, fever, and respiratory tract infections	32
Glycyrrhiza glabra L. (Licorice)	Fabaceae	Glycyrrhetinic acid, its major component, can be used as a lead compound for the development of potential anti-influenza virus agents	50
Camellia sinensis L. Kuntze (Green tea)	Theaceae	a. Most widely consumed daily beverages in Asia b. Contains high concentrations of catechins such as epigallocatechin gallate, which inhibit influenza A virus (IAV) c. Green tea catechins on the pharyngeal mucosa is important for the anti-IAV activity of green tea extract	51 -53
Hippophae rhamnoides L.	Elaeagnaceae	Fruits used for treatment of flu, colds, and infections	32
Hypericum perforatum L.	Hypericaceae	Can reduce the influenza H1N1 viral titer of infected mice by modulation of inflammatory cytokines	54
Isatidis radix	Brassicaceae	a. Used again influenza viruses with different strains and subtypes. In TCM, it has been prescribed for treating fever, pestilence, sore throat, seasonal toxin, and papule b. Antiviral potency of the components is in the order of progoitrin > goitrin > epigoitrin > epiprogoitrin	55 -61
Isatis indigotica Fort.	Brassicaceae	a. Used in the treatment of colds, fever and sore throats in TCM. b.Its alkaloids, for example clemastanin B, and lariciresino-4-β-D-glucopyranoside, have anti-influenza activities	62 -66
Lepidium meyenii Walp. (Maca)	Brassicaceae	Methanol extracts have antiviral impacts on influenza similar to amantadine. Has inhibitory effects on Flu-A and Flu-B	67
Linum usitatissimum L.	Linaceae	Seeds used for treatment of cold, flu, fever, and infections	32
Panax ginseng C. A. Meyer (Ginseng)	Araliaceae	a. Treatment with ginseng is effective in alleviating the symptoms of influenza viral infection b. Ginseng modulates both T-helper type 1 and 2 (Th1) and (Th2) immune responses via antibody production, inhibiting the invasion and replication of influenza virus and aiding the detachment of the virus from mucosa c. Korean red ginseng is a popular influenza-like illness medication in Korea	68 -70
Petasites hybridus L.	Asteraceae	Leaf used against flu, colds, and fever	32
Phoenix sylvestris Roxb	Arecaceae	Known as Indian date. Fresh sap rich in vitamin C and useful in treatment of colds, fever, and sore throats	71
Pimpinella major (L.) Hudson	Apiaceae	Root use for colds, flu, and fever	32
Pithecellobium clypearia (Jack) Benth.	Fabaceae	Flavan derivatives isolated from its leaves have activity against respiratory syncytial virus and Flu-1 (H1N1)	72
Psidium guajava Linn (guava tea)	Myrtaceae	Inhibits viral hemagglutination and sialidase activity and inhibits the growth of clinical influenza A (H1N1)	73
Punica granatum L. (pomegranate)	Punicaceae	Shown anti-influenza properties by replication suppression of influenza A virus in cell culture	74
Radix bupleuri	Apiaceae	Used against influenza and upper respiratory infection	75,76
Sambucus nigra L.	Adoxaceae	Fruits and flowers used for treatment of viral infections, fever, flu, and colds	32
Scutellaria baicalensis Gorgi (Baicalin)	Lamiaceae	a. Inhibits influenza H1N1 by exerting cytotoxic activity against infected cells b. May act as a neuraminidase inhibitor, with distinct inhibitory activities, which were effective against different strains of influenza A virus	77,78
Sesbania grandiflora L. Poiret	Fabaceae	a. Leaves are rich source of amino acids, minerals, and vitamins A, C, thiamine, riboflavin, and nicotinic acid b. Can be used as a good antimicrobial agent for cold and influenza	23,79,80
Sorbus aucuparia L.	Rosaceae	Fruits used for treatment of fever, colds, and flu	32
Prunella vulgaris L. Morus alba L. (Folium mori) Toonasinensis (Juss.) M. Roem	Lamiaceae; Moraceae Meliaceae	Used against influenza Used against influenza a. Extracts from its leaves shown to have a variety of effects, including glycemic control, inhibition of lipid accumulation, and antimicrobial activity b. The leaves extract has been verified to inhibit attachment activity toward pandemic influenza A (H1N1) through downregulation of adhesion molecules to prevent virus infection	81 -84
Trachyspermum ammi L. (Ajwain)	Apiaceae	a. For pharyngitis in influenza, seeds mixed with clove and a pinch of common salt and then chewed b. For common cold, a tablespoonful of T. ammi seeds crushed and tied in a cloth as a bundle, which is then inhaled by the patient	85
Gegen Qinlian decoction		a. A classical traditional Chinese medicine (TCM) formula, which consists of Radix puerariae (Gegen), Radix scutellariae (Huangqin), Rhizoma coptidis (Huanglian), and Radix glycyrrhizae (Gancao) b. Activated a balanced inflammatory response in the host to limit immune pathological injury and improve clinical and survival outcomes and can have protective systematic effect on influenza virus infection	86,87
Ge Gen decoction		Famous TCM, which is also common in Japan and Korea. The prescription consists of Pueraria lobata, Ephedra sinica, Cinnamomum cassia, Glycyrrhiza uralensis, Paeonia lactiflora, Zingiber officinale, and Ziziphus jujuba. It is mainly used to treat common cold. It has also anti-influenza A virus (anti-IAV) activity and can modulate the immune system to relieve lung inflammation	88
IMOD and Arbidol combination		a. IMOD (immunomodulator drug) is formulated from extracts of Tanacetum vulgare, Urtica dioica, and Rosa canina. b. Arbidol is a synthetic, broad-spectrum antiviral agent with immunomodulating effects c. Their combination can increase their immunomodulatory effects as a novel medicine to prevent and cure all types of influenza and flu	89
Jinchai		TCM consists of Jinyinhua (Flos lonicerae), Chaihu (Radix bupleuri), Huangqin (Radix astragali), and Dangshen (Radix codonopsis). As the most important component in the capsule, Lonicera japonica contains chlorogenic acid, isochlorogenic acid, and hyperin, and plays an implicit role as an anti-influenza antiviral agent	90,91
Rorrico		Extract prepared with a TCM prescription comprising 21 Chinese medicines formulated for treating influenza, including human H1N1 swine flu	92
Yi-Zhi-Hao pellet (CYZH)		Famous formula from TCM, which exhibits a broad-spectrum anti-influenza activity and inhibits the expression of viral RNA and proteins in vitro	93,94
Xin-Jia-Xiang-Ru-Yin		A Chinese herbal compound prescription that has been used to treat summer influenza	95

Table 2

Traditional Chinese Medicine Treatments for Different COVID-19 cases. ⁹⁶

Clinical feature	Recommended Chinese patent medicine	Ingredients
Suspected COVID-19 case
Muscle fatigue accompanied by gastrointestinal discomfort	Huoxiang Zhengqi capsules	Pogostemonis Herba, Glycyrrhizae Radix et Rhizoma, Praeparata cum Melle, Atractylodis Macrocephalae Rhizoma, Pinelliae Rhizoma, Citri Reticulatae Pericarpium, Magnoliae Officinalis Cortex, Platycodonis Radix, Perillae Folium, Arecae Pericarpium, Poria, Angelicae Dahuricae Radix, Zingiberis Rhizoma Recens, and Jujubae Fructus
Muscle fatigue accompanied by fever	Jinhua Qinggan granules	Lonicerae Japonicae Flos, Gypsum Fibrosum, Ephedrae Herba Praeparata cum Melle, Armeniacae Semen Amarum, Scutellariae Radix, Forsythiae Fructus, Fritillariae Thunbergii Bulbus, Anemarrhenae Rhizoma, Arctii Fructus, Artemisiae Annuae Herba, Menthae Haplocalycis Herba, and Glycyrrhizae Radix et Rhizoma
	Lianhua Qingwen capsules	Forsythiae Fructus, Lonicerae Japonicae Flos, Ephedrae Herba Praeparata cum Melle, Armeniacae Semen Amarum, Gypsum Fibrosum, Isatidis Radix, Dryopteridis Crassirhizomatis Rhizoma, Houttuyniae Herba, Pogostemonis Herba, Rhei Radix et Rhizoma, Rhodiolae Crenulatae Radix et Rhizoma, Menthae Haplocalycis Herba, and Glycyrrhizae Radix et Rhizoma
	Shufeng Jiedu capsules	Polygoni Cuspidati Rhizoma et Radix, Forsythiae Fructus, Isatidis Radix, Bupleuri Radix, Patriniae Herba, Verbenae Herba, Phragmitis Rhizoma, and Glycyrrhizae Radix et Rhizoma
	Confirmed COVID-19 case
Qingfei Paidu decoction	Application: based on the clinical observations made by clinicians across different regions. This is a basic Chinese herbal medicine formula applied to mild, moderate, and severe cases. It may also apply to critical cases, depending on the condition of individual patients. Where appropriate, medical professionals may choose to prescribe other formulae introduced in the subsequent sections of this article, based on the TCM diagnosis of patients	Basic formula: Ephedrae Herba 9  g, Glycyrrhizae Radix et Rhizoma Praeparata cum Melle 6  g, Armeniacae Semen Amarum 9  g, Gypsum Fibrosum 15-30  g (decoct first), Cinnamomi Ramulus 9  g, Alismatis Rhizoma 9  g, Polyporus 9  g, Atractylodis Macrocephalae Rhizoma 9  g, Poria 15  g, Bupleuri Radix 16 g, Scutellariae Radix 6  g, Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine 9  g, Zingiberis Rhizoma Recens 9 g, Asteris Radix et Rhizoma 9 g, Farfarae Flos 9  g, Belamcandae Rhizoma 9  g, Asari Radix et Rhizoma 6  g, Dioscoreae Rhizoma 12  g, Aurantii Fructus Immaturus 6  g, Citri Reticulatae Pericarpium 6  g, and Pogostemonis Herba 9  g

Luo et al ⁹⁷ introduced Astragalus membranaceus, Glycyrrhizae uralensis, Saposhnikoviae divaricata, Rhizoma atractylodis macrocephalae, Lonicerae japonicae flos, Fructus forsythiae, Atractylodis rhizoma, Radix platycodonis, Agastacherugosa, and Cyrtomiumfortuna for prevention of COVID-19 infection, while Xu and Zhang ⁹⁸ recommended Astragalus membranaceus, Atractylodis rhizoma, Eupatorii herba, Agastache rugosa, Ophiopogon japonicas, Scrophularia ningpoensis, Rhizoma phragmitis, Adeinophora stricta, and Dendrobium nobile for the prevention of COVID-19 infection. Zhang et al ⁹⁹ reported a network pharmacology analysis predicting that the general in vivo roles of 25 herbal plants were related to regulating viral infection, immune inflammation reactions and hypoxia response. Some important chemical constituents of traditional herbs, which can be considered in the fight against COVID-10, are betulinic acid, coumaroyltyramine, cryptotanshinone, desmethoxyreserpine, dihomo-γ-linolenic acid, dihydrotanshinone I, kaempferol, lignan, moupinamide, N-cis-feruloyltyramine, quercetin, sugiol, and tanshinoneIIa. The 26 Chinese herbals screened and classic catalog are shown in Table 3.

Table 3

The 26 Chinese Herbals Screened and Classic Catalog. ⁹⁹

Herbal name (Latin)	Plant family	The number of antiviral natural compounds contained in the plant	Classic catalog (Latin/English)
Forsythiae fructus	Oleaceae	3	Antipyretic detoxifying
Glycyrrhiza glabra	Fabaceae	3	Qi-reinforcing
Mori cortex	Moraceae	3	Antitussive antiasthmatics
Chrysanthemi flos	Asteraceae	2	Pungent cool diaphoretics
Farfarae flos	Asteraceae	2	Antitussive antiasthmatics
Lonicerae japonicae flos	Caprifoliaceae	2	Antipyretic-detoxifying drugs
Morus alba L.	Moraceae	2	Pungent cool diaphoretics
Peucedani radix	Apiaceae	2	Phlegm-resolving medicine
Rhizoma fagopyricymosti		2	Antipyretic detoxifying
Tamaricis cacumen	Tamaricaceae	3	Pungent-warm exterior-releasing medicine
Erigeron breviscapus	Asteraceae	2	Pungent-warm exterior-releasing medicine
Radix bupleuri	Apiaceae	2	Pungent cool diaphoretics
Coptidis rhizome	Ranunculaceae	2	Heat-clearing and dampness-drying medicine
Houttuyniae herba	Saururaceae	2	Antipyretic-detoxifying
Hoveniaedulcis semen	Verbenaceae	2	Antipyretic-detoxifying
Inulaeflos	Asteraceae	2	Phlegm-resolving medicine
Eriobotryae folium	Rosaceae	3	Antitussive antiasthmatics
Hedysarum multijugum Maxim.	Fabaceae	3	Qi-reinforcing
Lepidii semen Descurainiae semen	Brassicaceae	3	Antitussive antiasthmatics
Ardisiae japonicae herba	Primulaceae	2	Antitussive antiasthmatics
Euphorbiae helioscopiae herba	Euphorbiaceae	2	Diuretic dampness-excreting
Ginkgo semen	Ginkgoaceae	2	Antitussive antiasthmatics
Anemarrhenae rhizome	Liliaceae	3	Fire-purging
Epimediiherba	Berbeidaceae	2	Yang-reinforcing
Fortunes bossfern rhizome	Polypodiaceae	2	Warming interior

Discussion and Conclusions

Asian herbal medicines, especially Chinese and Iranian, are commonly used for preventive and therapeutic purposes in Asia and beyond. There are 4 types of influenza viruses: types A, B, C, and D, of which A, B, and C infect humans. Type A viruses have caused pandemics, while influenza B causes seasonal epidemics, and influenza C causes mild human infection with little public health impact.The most important antiviral herbs for cold and flu are thyme leaf (Thymus vulgar), honeysuckle flowers (Lonicera japonica), andrographis (Andrographis paniculata), green chireta (Andrographis paniculata), peppermint leaf and oil (Menthapiperita), and Calendula (Calendula officinalis). The most important expectorant herbs for flu and cold are tulsi (Ocimum sanctum), snake root (Polygala senega), licorice root (Glycyrrhiza glabra), clove (Syzugium aromaticum), slippery elm and marshmallow osha root (Ligusticum porterii), and sage leaf (Salvia officinalis). Immunostimulant herbs for these 2 diseases are Echinacea root (Echinacea purpurea), eucalyptus (Eucalyptus globulus), garlic (Allium sativum), ginseng (Panaxquin quefolium), marshmallow (Althea officinalis), slippery elm (Ulmus fulva), Isatis root (Isatis tinctoria), Usnea lichen (Usnea barbata), myrrh resin (Commiphora myrrh), and ginger root (Zingiber officinale). The notable herbal prescriptions from East Asia, especially China, are Rorrico, Jinchai, Gegen Qinlian Decoction, Ge Gen Decoction, Yi-Zhi-Hao pellet, Xin-Jia-Xiang-Ru-Yin, IMOD, and Arbidol combination. Traditional herbal plants and prescriptions can be considered for treatment and prevention of cold and influenza in an organic life.