Trying to Explain the Theoretical Basis of Traditional Chinese Medicine “Huashi Baidu Fang” in the Treatment of Coronavirus Disease 2019 with Western Medical Theory: A Review

Purpose: This work is aimed to explain the theoretical basis of “Huashi Baidu Fang” in the treatment of coronavirus disease 2019 (COVID-19) with western medical theory. Methods: We analyze the “Diagnosis and Treatment Protocol for COVID-19 (Version 1 to Version 7)” made by China, “Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected—Interim guidance” made by World Health Organization (WHO), “Therapeutic Guidelines: Respiratory (Version 5)”, “Therapeutic Guidelines: Gastrointestinal (Version 5)” and “Therapeutic Guidelines: Antibiotic (Version 15)” published by Australia, and the origin of classical prescription of “Huashi Baidu Fang”: “Shanghanlun (Treatise on Febrile Diseas-es)”, “Jinkui Yaolue (Synopsis of Golden Chamber)” and “Wenyi Lun (The Epidemic Febrile Disease)”. We search the dictionary of traditional Chinese medicine (Version II) manually. And we search literatures from 2001 to 2020 on Wiley online library. We conduct a comparative study among the symptoms of TCM formulations in “Huashi Baidu Fang”, the pathogenesis and clinical manifestation of COVID-19 and COPD with acute gastrointestinal inflammation. And we carry out pharmacological inquiry of “Huashi Baidu Fang”. Results: The clinical manifestations of respiratory symptoms and gastrointestinal tract of syndrome of lung obstruction due to epidemic toxin and acute exacerbation of COPD are almost the same; The formulations used in “Huashi Baidu Fang” are consistent with the pharmacological activity of the drug recommended in the Therapeutic Guidelines. Conclusion: “Huashi Baidu Fang” may play a positive role in COVID-19.


Introduction
Since COVID-19 has a breakout in Wuhan, China, in December 2019, more than 9 million people have been diagnosed with COVID-19 globally and more than 400,000 have died. The epidemic of COVID-19 has seriously affected the political, economic and social operation of different countries around the world, seriously affected people's work, life and study, and more seriously affected people's life, health and safety.
We take "Huashi Baidu Fang" as a research subject to study the origin of clas-

Methods
The retrieval results are summarized and recorded. And a comparative study is conducted on the pathogenesis, clinical manifestations, symptomatic diagnosis, therapeutic methods and pharmacology of TCM and western medicine.

The Contrast among TCM Formula Symptoms of "Huashi Baidu Fang", Acute Exacerbation of COPD and the Pathogenesis and Clinical Manifestation of COVID-19
"Huashi Baidu Fang" is a TCM prescription for syndrome of lung obstruction due to epidemic toxin. The clinical manifestation of syndrome of lung obstruc-

Comparison of TCM Formula Symptoms of "Huashi Baidu
Fang" and Therapeutic Methods of Acute Exacerbation of COPD with Acute Gastrointestinal Inflammation 3.2.1. Comparison of TCM Formula Symptoms of "Huashi Baidu Fang" and Diagnosis and Therapeutic Methods of Acute Exacerbation of COPD Acute exacerbation of COPD in Therapeutic Guidelines are treated by inhaling bronchodilators to relieve symptoms, long-acting bronchodilators reduce acute exacerbations, using systemic glucocorticoids to shorten hospital stays, promote recovery of lung function to baseline, and control symptoms well, using antibiotics to treat secondary infections. If the patient has hypoxemia, oxygen therapy to bring the blood oxygen saturation to 88% -93%, and mechanical ventilation is used if the patients are with type II respiratory failure and acidosis.
TCM formula symptoms of "Huashi Baidu Fang": Zhang Zhongjing discussed exogenous typhoid fever in "Shanghan Lun (Treatise on Febrile Diseases)": symptoms include headache, stiff neck, fear of cold, fever or no fever, and asthma after sweating, using Mahuang Xingren Gancao Shigao Decoction to treat these symptoms. In "Jinkui Yaolue (Synopsis of Golden Chamber)", Zhang Zhongjing argued that if the disease progresses to pulmonary inflammation and secondary D. D. Song, H. L. Chen

Etiology
In "Wenyi Lun (The Epidemic Febrile Disease)", Wu Youxing discussed that the disease has been infected with pestilential qi, which has mouth and nose transmission and contact transmission, whether old, young, strong or weak, will be

The Pharmacology Basis of TCM Formula in "Huashi Baidu
Fang" (Table 3(a) and Table 3
3) Gan Cao (Radix Glycyrrhizae) The main pharmacological action is adrenocortical hormone like action, fighting ventricular arrhythmia and reduce of ventricular fibrillation action [5]. It has analgesic, antipyretic and sedative effects on the central nervous system. It also has anti-peptic ulcer, anti-intestinal spasm, expectorant and antitussive effect. Glycyrrhizin enhances the non-specific immune function, has the synergistic effect with the glucocorticoid, and has the effect of liver protection and detoxification [5]. Besides, it has antiviral activity and anti-methicillin-resistant staphylococcus aureus activity [6].

4) Huoxiang (Herba Pogostemonis) The main ingredient is pogostemon al-
cohol, which can promote the secretion of gastric juice, enhance the digestive power, and have the effect of relieving the spasm in stomach and intestine [7]. It has antifungal and antibacterial activities, anti-atherosclerosis effect, expansion of microvessels and slight sweating effect [8].

5) Houpo (Cortex Magnoliae Officinalis) Magnolol shows significant liver
protection and tumor inhibition [9]. Honokiol has a strong inhibition of a va-  [10]. It has strong anti-hepatitis C virus activity at non-toxic concentration [11], and has protective effect on the intestinal injury induced by oxaliplatin in mice [12]. Magnolol and Honokiol has antibacterial activities against vancomycin-resistant and methicillin-resistant Staphylococcus aureus at the lowest concentration, anti-biofilm and bactericidal effects [13], significant central inhibitory effect, significant inhibition of platelet aggregation and ATP release and neuroprotective effect [14]. Magnolol also has anti-depressants, anti-anxiety and sleep aids effects [15]. 6) Cangzhu (Rhizoma Atractylodis) The volatile oil of Cangzhu (Rhizoma Atractylodis) has the function of anti-intestinal spasm, relaxation of enteric muscle, promoting gastrointestinal movement, and weak contraction of gastric smooth muscle [16]. It has sedative effects on the central nervous system at low dose and inhibitory effect on the central nervous system at high dose [17]. 7) Caoguo (Fructus Tsaoko) The α-pinene β-pinene of Caoguo (Fructus Tsaoko) has antitussive and expectorant effects. 1, 8-Eucalyptus has analgesic, antipyretic and antiasthmatic effects. β-pinene has strong anti-inflammatory and antifungal effects, small amount of oral has a mild diuretic effect [18] [19].

8) Banxia (Rhizoma Pinelliae preparatum) It can restrain vomiting center
and stop vomiting, and has obvious effect of relieving cough [20]. It also has a wide range of anti-tumor and anti-inflammatory effects [21]. Besides, it can inhibit the secretion of gastric juice and resist gastric ulcer [21]. 9) Fuling (Poria cocos) The content of β-pachyman accounted for 93% of the dry weight. It can promote cellular immunity and humoral immunity [22], protect liver injury, and has obvious diuretic effect. In addition, it can inhibit gastric ulcer, and reduce gastric secretion and free acid content [23].

10) Dahuang (Radix et Rhizoma Rhei) Rhubarb anthraquinone and aloe
emodin have synergistic effect in large intestine propulsion and water secretion, which can significantly stimulate large intestine propulsion and synergistic diarrhea [24]. Emodin inhibits systemic inflammatory response [25], and has anti-acute necrotizing pancreatitis and anti-colitis effects [26]. Apart from that emoidin can inhibit the 3a ion channel of SARS-COV and HCOV-0C43 and the virus release of HCOV-0C43 [27]. Chrysophanol can inhibit the formation of biofilm and has antibacterial effect [28].

11) Huangqi (Radix Astragali) Radix Astragalus, its polysaccharide and
other components can significantly improve the non-specific immune function, have the promotion or enhancement effect on humoral immunity and cellular immunity. It has an obvious stimulation effect on interferon system, has its own induced and active volatilization effect [29]. Radix Astragalus polysaccharides can prevent bleomycin-induced pulmonary fibrosis [30]. Astragaloside IV has the function of bone marrow hematopoietic, cerebral ischemia and heart protection, preventing the apoptosis of cultured rat myocardial cells induced by daunoruthromycin [31]. It also has bidirectional regulation of blood sugar, anti-fatigue, anti-hypoxia and so on [32].

Correspondence between Signs, Symptoms and Vital Organs of COVID-19 and Pharmacological Action of TCM Decoction Pieces of "Huashi Baidu Fang"
Pharmacology studies according to literature retrieval showed that the TCM decoction pieces in "Huashi Baidu Fang" have anti-asthmatic activity in respiratory system, antitussive pharmacological activity and expectorant effect. In digestive tract system, they have antiemetic effects, have the function of repairing gastric injury, promoting gastrointestinal functional movement. In addition, they also have liver protective activity, kidney protective effect, cardioprotective effect (Table 4).

Important Laboratory Parameters of COVID-19 and Traditional Chinese Herbal Medicine Functional Groups with Clear Pharmacological Support
Analyzing literatures according to the pharmacological activity, we find that the  [25], and has anti-acute necrotizing pancreatitis, anti-colitis effect [26].
Honokiol has a strong inhibition of a variety of inflammatory responses [10].
And it is worth for further validation in COVID-19 (Table 5).

Discussion
Chinese medicine is based on thousands of years of history, and is an effective  For comparison purposes, the acute exacerbations of chronic obstructive pulmonary disease (COPD) as defined in the "Therapeutic Guidelines: Respiratory (Version 5)", by Australia, were used in this study. COPD caused by COVID-19 with acute gastrointestinal inflammation is a type of disease that develops into a severe form. The literature reports that respiratory symptoms occur in 68% -75.0% of all patients [36]. 3% -79% patients have gastrointestinal function affects [37], including anorexia, diarrhea, vomiting, nausea, etc. The proportion of gastrointestinal symptoms in severe patients was higher than that in non-severe patients [37], and pathology showed different degree of consolidation in lung and gastrointestinal tract [38]. Laboratory tests show the presence of a large number of inflammatory factors [39].
We should pay attention to the cytokine release syndrome (CRS) and inflammatory cytokine storm produced by increased inflammation of the gastrointestinal tract in patients with COVID-19 [39]. Increased inflammation can lead to secondary infections [40]. To treat viral gastrointestinal inflammation and respiratory inflammation, fluid rehydration and glucocorticoid include clear antivirals are used. However, the WHO document cautions against routine systemic use of glucocorticoids outside clinical trials for viral pneumonia or acute respiratory distress syndrome unless otherwise indicated. A systematic review of observational studies has shown that glucocorticoids do not improve and may harm survival in patients with acute respiratory distress syndrome. Use of glucocorticoids has both potential benefits (slightly reduced mortality) and potential negative effects (prolonged shedding of coronavirus in the respiratory tract).
Modern pharmacological experiments have shown that Houpo (Cortex Magnoliae Officinalis) and Dahuang (Radix et Rhizoma Rhei) have clear and powerful anti-inflammatory factors as well as significant antibacterial and antiviral effects. They can solve the contradiction between the use of glucocorticoid and antibacterial drugs, and reduce the aggravation of disease caused by inflammatory factor outbreak and secondary infection (3.6). In this sense, TCM has natural ad- In "Shanghan Lun (Treatise on Febrile Diseases)", Zhang Zhongjing said that between 196 and 206 A.D, more than two-thirds died of 200 people in his family, 70% of them died from typhoid fever. The epidemic, which was widespread, lasted for a long time and resulted in mass death, gave birth to Zhang Zhongjing's "Shanghan Lun (Treatise on Febrile Diseases)". There were four major epidemics between 200 and 219. In 217, a major epidemic occurred in northern China, causing sickness and death in every family [41]. "Jinkui Yaolue (Synopsis of Golden Chamber)" written by Zhang Zhongjing before 219 A.D, is a summary of zhang zhongjing's decades as a senior official and medical scientist in organizing epidemic prevention and actively treating patients. Zhang Zhongjing is a Chinese medical saint. In "Wenyi Lun (The Epidemic Febrile Disease)", Wu Youxing said that in 1641, the epidemic was prevalent in Shandong, Zhejiang, Beijing, Jiangsu and Anhui, and it was more serious in May and June, and some were infected in the whole family. In south of Baoding in Hebei, Dangshan in Anhui, Suqian in Jiangsu and North of Huaiyin (the ancient route of Yellow River in Ming Dynasty), from spring to summer, there was a pandemic of plague, which killed very many people. In 1628-1644 Ming Dynasty Chongzhen years, the epidemic almost every year [42], Wu Youxing wrote "Wenyi Lun (The Epidemic Febrile Disease)" in the accumulation of long-term medical knowledge and long-term medical practice, established a new set of theories and treatment system in line with the epidemic of temperature, and founded the Dayuan Yin [43]. Chinese medicine has also gained positive experience in treating infectious diseases [44].
Although TCM for COVID-19 itself we cannot sure is restrain or kill, but from the ease of the disease caused by COVID-19, from the evidence of phar-

Authors' Contribution
Dandan Song participated in the discussion of conception and framework, consulted the literatures and drafted the article. Hualiang Chen, has the same contribution, proposed the conception and framework of the paper, and reviewed the article.

Conflicts of Interest
There was no conflict of interest for each named author. The authors of this article have received no financial or material support from any corporation, foundation or individual.