Potential Preventive and Therapeutic Effects of Traditional Chinese Medicine Compound Prescription and Traditional Chinese Medicine Products on COVID-19

Wen ZHONG, Haisheng ZENG, Xiumei MA, Jiangcun WEI, Dongmei HUANG, Chengtong LIU, Mengxia YANG

1. Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China; 2. Guangxi International Zhuang Medicine Hospital, Nanning 530201, China

Abstract This paper mainly analyzes the traditional Chinese medicine compound prescription and traditional Chinese medicine products with remarkable epidemic prevention effect since the outbreak of COVID-19, and discusses their potential prevention and treatment effects, so as to provide a basis for the further development and application of traditional Chinese medicine compound prescription and traditional Chinese medicine products against COVID-19.

Key words Traditional Chinese medicine compound prescription, COVID-19, Prevention and treatment, Anti-virus

1 Introduction

At the beginning of 2020, COVID-19 spread rapidly all over the world, and broke out in the United States, South Korea and other countries in the world. COVID-19 has the characteristics of rapid spread, general susceptibility and strong infectivity, so the situation of prevention and control is very grim. At present, there is no specific drug for COVID-19, and the diagnosis and treatment of COVID-19 in China is still being optimized and improved, and it mainly focuses on symptomatic support treatment. Therapeutic drugs are selected mainly based on inhibiting viral nucleic acid replication, blocking virus invasion and spread and viral protein synthesis, combined treatment and regulating immunity of the body and other aspects[1]. Among them, the inhibitor of virus replication may be an effective drug for the treatment of COVID-19 patients, while traditional Chinese medicine has accumulated rich experience in long-term epidemic prevention practice, with broad-spectrum immunity and universality, and plays an important antiviral role in many plague and epidemic outbreaks. This paper mainly analyzes the traditional Chinese medicine compound prescription and traditional Chinese medicine products with remarkable epidemic prevention effect since the outbreak of COVID-19, such as Qingfei Paidu decoction, Shufeng Jiedu capsule (granule), Lianhua Qingwen capsule (granule), and discusses their potential prevention and treatment effect, so as to provide a basis for the further development and application of traditional Chinese medicine compound prescription and traditional Chinese medicine products against COVID-19.

2 Understanding of COVID-19

COVID-19 falls within the category of "epidemic disease" in traditional Chinese medicine. Fundamentally, it is caused by the evil of "epidemic", which is the "epidemic due to noxious dampness". Traditional Chinese medicine[2]believes that the pathogenesis of COVID-19 originates from the cold and dampness of the south at the end of winter, which closes the lungs and suppresses yang and causes the disease. The toxin enters through the qi channel, the lung qi is repressed, the toxin accumulates in the chest and diaphragm, and spleen deficiency produces phlegm. Therefore, fever occurs in patients at the initial stage, mostly cough and gasp and asthma or accompanied by dry pharynx and tongue and other symptoms. In discussing the etiology and pathogenesis of COVID-19, Zhou Yongxue[3]believes that dampness and heat are trapped in the lungs, and the disease is mostly located in the lung and muscle surface. The lung qi is injured by poisonous pathogens, causing respiratory tract congestion, lung qi obstruction, cough, choking and rough breath, so there are symptoms including cough, sore throat and so on. Some researchers[4-5]believe that the lung is the location of the lesion of COVID-19, and it shows a long incubation period, fatigue, tiredness, accompanied by digestive system symptoms, and the tongue coating is often greasy, which accords with the characteristics of "dampness" in traditional Chinese medicine. It can be summarized as dampness, deficiency, poison and blood stasis. The treatment of the disease is to remove pathogens. COVID-19 patients fall ill due to epidemic, coupled with heat, dryness, cold, dampness, blood stasis and other evils. After infringing upon the human body, it will permeate the exterior and interior. If it is not treated in time, it can cause extensive damage to multiple viscera. Jia Zhenhua[6]thinks that the lesion of COVID-19 is mainly caused by toxic heat, and the blood injury occurs in the collateral channels, showing the signs of blood stasis and blocking collaterals, which indicates that the blood is in a state of hypercoagulability and hyperfibrinolysis.

3 Traditional Chinese medicine compound prescription for prevention and treatment of COVID-19

Traditional Chinese medicine compound prescription has complex active components and multiple pharmacological targets, which jointly play a role in resisting COVID-19. The following is an analysis of traditional Chinese medicine compounds such as Qingfei Paidu decoction, Shufeng Jiedu capsule (granule) and Lianhua Qingwen capsule (granule), which have remarkable epidemic prevention effect.

3.1QingfeiPaidudecoctionQingfei Paidu decoction (hereinafter referred to as QDPD) is an optimized combination of the classic prescriptions in theTreatiseonFebrileandMiscellaneousDiseaseswritten by Zhang Zhongjing in the Han Dynasty. Its nature is mild, including Maxing Shigan decoction, Shegan Mahuang decoction, Xiao Chaihu decoction, Wuling powder, Juzhijiang decoction. Mahuang decoction and Wuling powder in the prescription can dispel cold and dampness, Xiao Chaihu decoction can treat exogenous heat pathogen, andA.rugosusis fragrant and can remove dampness. QDPD has many clinical effects, such as anti-inflammation, anti-virus, strengthening immunity, inhibiting the development of pulmonary fibrosis, protecting heart and lung, treating asthma, and regulating gastrointestinal tract.

QDPD is a multi-component prescription of traditional Chinese medicine, which is widely used in the treatment of COVID-19 in China. Studies have revealed that QDPD has a safe and effective protective effect on COVID-19 by regulating a complex molecular network, and some of the mechanisms are related to the regulation of anti-viral, anti-inflammatory activity and metabolism[7]. Zhou Mengqietal.[8]explored the possible mechanism of QDPD in the treatment of COVID-19 from the perspective of cytokine storm (TNF, NOD-like receptor, toll-like receptor and other pathways), suggesting that QDPD inhibited cytokine storm through multiple components. QDPD[9]may play a therapeutic role in treating pneumonia, fever and cough by regulating interleukin (IL) signal pathway and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) inflammatory signaling pathway. QDPD plays an overall regulatory role through the lung and spleen, and regulates a number of proteins co-expressed with ACE2 and a series of signal pathways closely related to the occurrence and development of the disease, and targets viral replication of essential ribosomal proteins to inhibit viral mRNA translation, inhibit proteins interacting with viral proteins, and play an anti-COVID-19 role[10]. As a general prescription for the treatment of COVID-19, QDPD has great clinical value, and its diagnosis and treatment plan is included in the first choice in the clinical treatment of traditional Chinese medicine. It can provide inspiration for the effective components that can resist COVID-19 and its mechanism of action, and it is expected to provide evidence and new insights for the further study of QDPD in the treatment of COVID-19.

3.2ShufengJieducapsule(granule) Shufeng Jiedu capsule (granule) (hereinafter referred to as SFJD) is mainly used in patients with acute upper respiratory tract infection falling within wind-heat syndrome.

The main drugs areP.cuspidatum,R.Isatidis,F.suspensa,R.Bupleuri,H.Patriniaeand so on.P.cuspidatuminduces diaphoresis to dispel wind;F.suspensaandR.Isatidisdispels wind and heat from the body;R.Bupleurican relieve exterior syndrome and promote sweating;H.Patriniaecan remove carbuncle and swelling; verbena can clear heat and relieve internal heat or fever;R.phragmitisclears the lung and stomach, with the functions of clearing heat and inducing sweat, anti-inflammation and other functions, and it has definite curative effect on respiratory diseases including viral pneumonia, cough and sore throat, and has potential antiviral effect.

SFJD is an effective prescription for the treatment of COVID-19 selected by first-line clinicians. Liu Jingetal.[11]found that SFJD had a significant antipyretic effect by reducing the levels of inflammatory factor PGE2 and cytokines, reducing heat-inducing medium and increasing the amount of AVP, suggesting that it played an antipyretic effect on fever and other symptoms of COVID-19 by using the model of yeast-induced fever in rats. Qu Xiangkunetal.[12]found that the use of SFJD combined with Western medicine in the treatment of COVID-19 could significantly shorten the improvement time of clinical symptoms such as respiratory distress syndrome and the time of SARS-CoV-2 turning negative. Shen Fuetal.[13]suggested that luteolin and quercetin in SFJD might play an important role in inhibiting SARS-CoV virus replication. The chemical components of SFJD are involved in a variety of biological processes and pathways to treat COVID-19 by combining with key target proteins such as IL-6, ALB, and MAPK3. Studies have shown that SFJD can reduce the lung injury induced byP.aeruginosa(PAK) in KM mice, improve the upper respiratory tract infection induced by PAK, and has a good therapeutic effect on lung injury[14]. It provides a reference for COVID-19 patients to improve the degree of lung injury and delay the pathological changes of lung caused by COVID-19.

3.3LianhuaQingwencapsule(granule) Lianhua Qingwen capsule (granule) (hereinafter referred to as LHQW) consists of Zhi Ma Huang, gypsum, fried bitter almonds and licorice to form Ma Xing Shigan decoction, which can relieve the exterior syndrome with drugs pungent in flavor and cool in property, clear the lungs and relieve asthma and remove wind pathogen. Honeysuckle,R.Isatidis,F.suspensa, peppermint,D.crassirhizomaandH.cordatacan dispel wind and heat from the body, clear away heat and toxic material, and reduce swelling and sore. Patchouli can resolve dampness and induce sweat, andR.roseaL. can replenish qi and relieve blood stasis, which is suitable for the clinical symptoms such as fever, cold, muscle soreness, cough and headache, nasal obstruction and runny nose caused by heat toxin attacking lung.

LHQW has positive curative effect and remarkable epidemic prevention effect, so it is recommended as the first choice by diagnosis and treatment plan. The results showed that LHQW could inhibit the activity of novel coronavirus in vitro and significantly improve the fever, cough, fatigue and other symptoms of COVID-19 patients[15]. Xia Jingwen[16]found that LHQW might regulate host immune regulation, inhibit the release of inflammatory factors and down-regulate the level of inflammatory factors by inhibiting NF-κB pathway, so as to reduce inflammation caused by infection and protect lipopolysaccharide-induced acute lung injury. LHQW[17]may exert its anti-COVID-19 effect by inhibiting the phosphorylation of p65 induced by A/PR/8/34 virus, inhibiting the activation of NF-KB, and reducing the expression of IL-6, IL-8, TNF-α and other genes induced by COVID-19 virus. Studies[18]have shown that LHQW can inhibit the aggregation of neutrophils in respiratory tract and lung tissue, reduce the expression of inflammatory factors such as IL-6, IL-1β and mRNA in lung tissue of mice, reduce capillary permeability, and improve the pathological injury of lung tissue, indicating that it can improve the lung tissue injury induced by COVID-19. Most of the patients with COVID-19 have severe pulmonary fibrosis. LHQW plays an active role in anti-COVID-19 by inhibiting pulmonary fibrosis to improve the degree of lung injury in patients with COVID-19, relieving lung heat, and clearing away communicable diseases and toxins. Rational use of this prescription and speeding up the development of related preparations may be the direction to defeat COVID-19.

3.4OthercompoundprescriptionsoftraditionalChinesemedicineIn addition, Liu Zhonghuaetal.[19]found that Huoxiang Zhengqi capsule could enhance the antiviral ability of mice infected with avian influenza virus. Jinhua Qinggan granule[20-21]contains core components such as formononetin, dehydrated icariin, stigmasterol and β-sitosterol, or exert anti-COVID-19 effect through PI3K-Akt, HIF-1, TNF, MAPK and other signal pathways. Huoxiang Zhengqi capsule and Jinhua Qinggan granule can clear heat and toxins, clear heat from throat, also playing a positive role in preventing COVID-19.

4 Prevention and treatment of COVID-19 with traditional Chinese medicine products

4.1TraditionalChinesemedicinesachetThe traditional Chinese medicine sachet uses aromatic drugs to play the roles of eliminating dampness, clearing away heat and toxic materials, eliminating filth and warding off pathogenic factors through the absorption in human mouth, nose, skin pores and meridians and acupoints, thus achieving the role of "preventive treatment of diseases" in traditional Chinese medicine. This therapy comes from "Yiguan therapy"[22]. The study[23]shows that the aromatic smell of Chinese herbal medicine in the sachet forms a high concentration of aromatic microenvironment around the human body to sterilize and inhibit bacteria. Traditional Chinese medicine with strong volatile effect is often used in sachet, which can increase the content of secretory immunoglobulin A (sIgA) antibody on nasal mucosa, act on systemic lymph nodes and inflammatory sites, prevent virus adhesion, proliferation and spread on nasal mucosa, dilate nasal mucosal blood vessels and enhance nasal mucosal defense function, so as to reduce the chance of human infection. Studies[24]have shown that sachet can increase the number of peripheral blood lymphocyte subsets CD3+ and CD4+ cells, the CD4+/CD8+ ratio and serum INF-γ, thus enhancing the immune function of respiratory tract. The analysis of Luo Jingetal.[25]suggests that HIF-1 signal pathway may be one of the main pathways involved in aromatic traditional Chinese medicine interfering with COVID-19. Traditional Chinese medicine sachet often contains patchouli,Atractylodesand other medicinal materials. Among them, patchouli volatile oil can inhibit the expression of tumor necrosis factor-α in serum, reduce the damage of lipid peroxidation, enhance the ability of antioxidation, and increase the expression of interleukin-10 and interferon-γ.Atractylodesvolatile oil inhibits ribonucleoprotein anaplastic lymphoma kinase signal pathway and mitogen activated protein kinase phosphorylation. This shows that traditional Chinese medicine sachet plays a role in the prevention and treatment of COVID-19 by regulating the inflammatory mediators[26-27]. At present, some teachers and students in some colleges and universities in Guangxi wear traditional Chinese medicine sachet or hang it in houses, so it can be seen that traditional Chinese medicine sachet plays a positive role in the epidemic situation of COVID-19.

4.2TraditionalChinesemedicinaldietUnder the guidance of the theory of traditional Chinese medicine, medicinal diet is a science which matches traditional Chinese medicine with some foods with medicinal value to achieve the purpose of disease prevention and treatment, rehabilitation and health care. Traditional Chinese medicine diet can be used as an effective measure for epidemic prevention to enhance physique and immunity. When influenza occurs frequently, you can prevent influenza by eating more porridge withE.scaberL. and lean meat. When respiratory susceptibility is strong, lily, Fritillaria and almond diet can strengthen defense and prevent respiratory diseases such as COVID-19. When you have a mild cold and cough, ginger and perilla porridge can significantly improve your physical symptoms. After a cold, you should have ginger porridge to help you sweat. Corn and rice porridge can treat palpitation, shortness of breath, fatigue, anorexia and so on[28]. Traditional Chinese medicinal diet in the four seasons can regulate the human body to prevent and resist respiratory virus, influenza virus, and to a certain extent, can play a role in the prevention of COVID-19. In addition, Jiang Nanetal.[29]believed that in the treatment of COVID-19, the spleen and stomach should be protected from beginning to end. According to the characteristics of COVID-19, the emphasis is on invigorating the spleen and removing dampness, and the diseases can be treated by tea, oral decoction and moxibustion.

5 Conclusion and prospect

According to traditional medicine, when the viscera function of the human body is normal, healthy qi is vigorous, qi and blood are filled smoothly, external pathogens are difficult to invade, and internal pathogens are difficult to produce, so diseases will not occur. Only when the healthy qi of the human body is relatively weak and the external defense is not solid, can the evil qi take advantage of the deficiency, resulting in pathological damage and disease. Under the guidance of the holistic concept of medicine, traditional medicine should carry out the policy of giving priority to prevention, prevent and control the epidemic situation, cure the disease, and prevent it before it happens. In recent years, the anti-COVID-19 mechanism of traditional Chinese medicine compound prescription such as Shufeng Jiedu capsule (granule), Qingfei Paidu decoction and Lianhua Qingwen granule has been revealed one after another. Many compound products of traditional Chinese medicine have also obtained the theoretical support of anti-COVID-19 prevention and treatment through modern pharmacological experimental research. Based on the law of anti-COVID-19 action in traditional Chinese medicine compound prescription and traditional Chinese medicine products, discovering the active components of anti-COVID-19 and elucidating their action mechanism are of great significance to exploring the new drugs that defeat COVID-19. However, the studies on the advantages of traditional Chinese medicine compound and traditional Chinese medicine products in anti-COVID-19 pathway and target, screening effective components and determining active components have not been fully carried out, and the specific mechanism of anti-COVID-19 has not been determined. Therefore, in the basic research of anti-COVID-19 traditional Chinese medicine, we should pay attention to the compatibility of many kinds of traditional Chinese medicine, fully respect the characteristics and mechanism of traditional Chinese medicine, and deeply explore its action mechanism and specific drug targets, so as to provide a solid theoretical basis for the development of safe and effective anti-COVID-19 traditional Chinese medicine compound prescription and traditional Chinese medicine related products. To sum up, compound drugs and traditional Chinese medicine products may continue to play a role in fighting the epidemic in the future, and we can continue to explore their therapeutic value in COVID-19 and provide a reasonable basis for the use of drugs in the fight against the epidemic.