key: cord-333119-vu4qbcy1 authors: Zhang, Xiao-rui; Li, Ting-na; Ren, Yuan-yuan; Zeng, Yi-jia; Lv, Hong-yang; Wang, Jin; Huang, Qin-wan title: The Important Role of Volatile Components From a Traditional Chinese Medicine Dayuan-Yin Against the COVID-19 Pandemic date: 2020-09-25 journal: Front Pharmacol DOI: 10.3389/fphar.2020.583651 sha: doc_id: 333119 cord_uid: vu4qbcy1 Aromatic Chinese herbs have been used to prevent plagues since ancient times. Traditional Chinese medicine has unique advantages in the prevention and treatment of epidemic diseases. According to the traditional Chinese medicine treatment plan in the National COVID-19 Diagnosis and Treatment Plan (Trial Seventh Edition) of the National Health Commission, Chinese patent medicines or prescriptions rich in aromatic Chinese herbs are selected for prevention and treatment during the period of medical observation, clinical treatment, and recovery of confirmed COVID-19 patients. Some local health committees or traditional Chinese medicine administrations recommend a variety of other ways of using traditional aromatic Chinese herbs to prevent and cure COVID-19. These involve external fumigation, use of moxibustion, and wearing of sachet. The efficacy of aromatic Chinese herbs plays a decisive role in the prevention and treatment of COVID-19. The unique properties, chemical composition, and mechanism of action of aromatic Chinese herbs are worthy of extensive and in-depth experimental and clinical research. The findings are expected to provide a reference for follow-up treatment of novel coronavirus and the development of corresponding drugs. In 2003, Dayuan-Yin produced excellent results in the treatment of the SARS virus. Individually, 112 confirmed cases were administered this drug between January and April 2003, and more than 93.7% of the patients showed noticeable mitigation of the symptoms, as well as recovery. Dayuan-Yin also was selected as one of the nationally recommended prescriptions for the COVID-19. Based on the national recommendation of Dayuan-Yin prescription, this review discusses the role of volatile components in the prevention and treatment of COVID-19, and speculates the possible mechanism of action, so as to provide a basis for the prevention and treatment of COVID-19. Most of the volatile components of Dayuan-Yin have been elucidated, and their structures are well established (Table 1) . However, there are no data on volatile components extracted from Areca catechu L. Based on clinical evidence of therapeutic results with Dayuan-Yin, we summarized its potential bioactive volatile components in the treatment of COVID-19. The biological benefits of Dayuan-Yin seem to involve anti-inflammatory, antiviral, antibacterial, and immunomodulatory effects ( Table 2) . In autopsy studies and animal models, COVID-19 manifests mainly as acute viral pneumonia leading to respiratory failure (Chan et al., 2020; Yao et al., 2020) . Antiviral drugs have been used to treat common cold, fever and influenza viruses by destroying the viral surface structure and inhibiting its entry (Hsieh et al., 2012) , suggesting that antiviral drugs can be used for COVID-19. Unfortunately, no specific antiviral treatment has been recommended for COVID-19 treatment because of insufficient evidence from randomized trials (Hung et al., 2020) . It has been shown that many re-purposed drugs have effects against close relatives of SARS-COV-2, such as bcoronavirus, in vitro. Furthermore, lopinavir and many interferons, especially interferon beta, have moderate effects against SARS-COV in vitro and can be used in combination with ribavirin (Chen et al., 2004; Chan et al., 2013) . Administration of antiviral drugs soon after symptoms appear reduces the release of virus in respiratory secretions of patients with COVID-19, thereby decreasing their infectivity to others. Targeted preventive treatment for contacts reduces their risk of infection (Welliver et al., 2001; Oriol and Bonaventura, 2020) . Patchouli oil is extracted from Pogostemon cablin (Blanco) Benth. Some studies in vitro have shown that patchouli oil exerted anti-viral effects against Coxsackie virus (IC 50 = 0.081 mg/ ml, TI 1.25), adenovirus(IC 50 = 0.084 mg/ml, TI 1.20), influenza A virus (IC 50 = 0.088 mg/ml, TI 1.15), and respiratory syncytial virus (IC 50 = 0.092 mg/ml, TI 1.10) (Wei et al., 2012) . Evaluation of the antiviral properties of six chemical compositions of Atractylodes lancea (Thunb.) D DPPH.C. revealed that atractylodin produced the most significant effect at doses of 10-40 mg/kg for five days, and attenuated IAV−induced pulmonary injury via regulation of the TLR7 signaling pathway (Cheng et al., 2016) . Moreover, 1,8-cineole, the major constituent of the essential oil of Lanxangia tsao-ko (Crevost & Lemarie) M.F.Newman & Skornick., is commonly applied for treating inflammatory diseases of the respiratory tract caused by viruses since it potentiates the antiviral effect of IRF3, in addition to its inhibitory effect on proinflammatory NF-kB signaling (Müller et al., 2016) . The levels of proinflammatory factors i.e. IL-2, IL-7, IL-10, GCSF, IP10, MCP1, mip1a, and TNF -a in the plasma of critically-ill patients were higher than those in plasma of patients who were not in intensive care, suggesting that "cytokine storm" is closely related to the severity of COVID-19 . Cytokine storm is a very prominent pathophysiological feature of COVID-19 infection (Lin et al., 2020) . Extensive endothelial barrier disruption and uncontrolled cytokine storm promote uncontrolled inflammatory response which is the basis of the core mechanism underlying acute respiratory distress syndrome (ARDS) (Huang et al., 2017) , although this phenotype varies among individuals. Experimental models of acute lung injury (ALI) and human genome-wide association studies of ARDS indicate that cytokine storm plays an essential role in the pathophysiology of ARDS ( Biondi et al., 1986; Huang et al., 2017) . Moreover, the most common and severe complication of COVID-19 is ARDS (Huang et al., 2017) . Therefore, an understanding of the cytokine storm that aggravates ARDS in COVID-19 may lead to early and effective intervention in critically-ill COVID-19 patients. It seems necessary to directly inhibit inflammatory response in the lungs because cytokine storm can be alleviated with inflammatory therapy (Cao P. et al., 2020) . Previous studies have shown the benefits of antiinflammatory drugs in lung disease: they slow down impairment of lung function, reverse the inflammatory parameters nearly back to normal values, and improve patients' survival (Konstan et al., 2011; Lubamba et al., 2011) . Ibuprofen, a popular antiinflammatory drug, is recommended for airway inflammation in cystic fibrotic lung disease (Flume et al., 2007) . Studies have shown Pogostemon cablin (Blanco) Benth. volatile oils Patchoulene: cyclin E↓, cyclin B↓, CDK1↓; the subsequent S-phase arrest, IFN-gamma↓, IL-10↓ Pogostemon cablin (Blanco) Benth. volatile oils: TNF-a↓, IL-6↓, IL-10↑, NP-SH↑ (Chen et al., 2015) Patchoulene: regulates on the balance between Nrf2 and NF-kB p65 signaling pathways (Yang et al., 2018) Patchoulene: vitro neutrophil fMLP chemotaxis↓, phagocytic activity↑; ear edema↑, myeloperoxidase (MPO) activity↑ that long-term prediagnostic use of nonaspirin NSAIDs (e.g., ibuprofen) is associated with a significant reduction in lung cancer survival (Brasky et al., 2012) . In addition, barictinib, fedratinib, and ruxolitinib are active and selective JAK inhibitors which have been approved for rheumatoid arthritis and myelofibrosis. All three drugs are effective anti-inflammatory agents, and as JAK-STAT signaling inhibitors, they may be effective against the consequences of elevated levels of cytokines (including interferon-g) usually observed in patients with COVID-19 (Stebbing et al., 2020) . The UK is currently conducting a randomized evaluation of COVID-19 treatment (recovery) trial, based on the announcement on June 16, 2020, that dexamethasone had been shown to significantly improve the prognosis of COVID-19 patients receiving respiratory support (Recovery, Randomised Evaluation of COVid-19 therapy trial, 2020). Dexamethasone is a glucocorticoid which can be used as a synthetic form of the natural hormone cortisol (Cain and Cidlowski, 2017) . It has the same anti-inflammatory effect as cortisol. It inhibits the release of inflammatory chemokines by immune cells, thereby improving the prognosis of patients by reducing the severity of ARDS (Lester et al., 2020) . In European patients, low-dose dexamethasone reduces mortality by 33% in critically patients requiring invasive ventilation (Lim et al., 2020) . However, the implementation of appropriate dexamethasone use in low-and-middle-income countries has been a challenge. For example, corticosteroids may cause sepsis in some prevalent parasitic infections in Africa (Nutman, 2020) . Therefore, the use of dexamethasone in African patients who have not been b-eudesmol has two-way regulation of gastrointestinal motility, which may be anticholinergic or directly acting on gastrointestinal smooth muscle. (Wang et al., 2002) Hinesol: H + , K + -ATPase activity↓ (Kanako et al., 2000 (Guo et al., 2005) Falcarindiol inhibited DC maturation by blocking the canonical pathway of nuclear factor-kappaB and phosphorylated p38. (Mitsui et al., 2010) Falcarindiol inhibit Pseudomonas aeruginosa by repressing virulencerelated genes, including the T3SS; quorum sensing synthase genes lasIR and rhlIR; lasB; motility-related genes fliC and fliG; and phenazine synthesis genes phzA1 and phzA2. diagnosed with COVID-19 may lead to unexpected consequences (Brotherton et al., 2020) . During the treatment of COVID-19, Dayuan-Yin also reduces the severity of ARDS by inhibiting the release of inflammatory chemokines from immune cells. As a classic prescription in ancient China, Dayuan-Yin can play a safe and effective role in the treatment of respiratory infections in a more adverse environment. Thus, it can avoid such problems in a large extent. Anti-inflammatory property is widespread in various sources of volatile components. Several data have found that 1,8-cineole significantly improved lung function and health conditions, and reduced dyspnea in patients with asthma, acute bronchus, and chronic obstructive pulmonary disease (COPD). Moreover, it significantly reduced the frequency of cough in patients with acute bronchitis, and alleviated frequent exacerbations in patients with COPD and frequent exacerbations, notably (Worth et al., 2009; Worth and Dethlefsen, 2012; Fischer and Dethlefsen, 2013; Vogelmeier et al., 2018) . In a mouse model of LPS-induced acute pulmonary inflammation, 1,8-cineole upregulated IL-10 in lung tissues, and decreased the expressions of TNF-a, IL-1b, NF-kB's subunit p65 and TLR4 (Zhao et al., 2014) . Moreover, 1,8-cineole was shown to inhibit LTB4 and PGE2 (pathways of AA-metabolism in human blood monocytes) in bronchial asthma in vitro (Juergens et al., 1998b) . In addition, 1,8-cineole decreased levels of TNFa, IL-1b, leukotriene B4, and thromboxane B2 in human blood monocytes in vitro (Juergens et al., 1998a) . Pogostone, a bioactive component extracted from Pogostemon cablin (Blanco) Benth., reduced the total population of T cells under ConA stimulation by blocking T cell proliferation via downregulation of cyclin E, cyclin B, and CDK1. Subsequent S-phase arrest inhibited the production of IFN-gamma and IL-10 . Simultaneously, pogostone pretreatment mitigated ethanolinduced gastric ulcer in rats by downregulation of IL-6 and TNFalpha, and upregulation of IL-10 and non-protein-sulfhydryl (NP-SH) groups in the gastric mucosa (Chen et al., 2015) . In lung disease, pogostone exerted potent protective effects against lipopolysaccharide-induced acute lung injury in mice by decreasing TNF-a-induced cell injury in A549 cells through modulation of the balance between Nrf2 and NF-kB-p65 signaling pathways (Yang et al., 2018) . Pogostone significantly inhibited the protein and mRNA expressions of proinflammatory mediators such as TNF-a, IL-6, IL-1b, NO, and PGE2. Pogostone also significantly reduced LPS-induced mortality in mice, suppressed the production of proinflammatory mediators in serum. And it attenuated liver and lung injury via downregulation of the mRNA expressions of inflammatory mediators in multiple organs due to inhibition of activation of NF-kB and phosphorylation of p38 MAPK (Li et al., 2014) . Pre-treatment with pogostone markedly mitigated LPS-induced acute lung injury in mice, improved survival, attenuated histological alterations in the lungs, reduced MPO and MDA levels, decreased the wet/dry weight ratio of lungs, and down-regulated proinflammatory mediators, such as TNF-a, IL-1 beta and IL-6. Furthermore, pretreatment with pogostone enhanced the Nrf2dependent genes NQO-1, GCLC, and HO-1, but suppressed the NF-kappa B regulated genes TNF-alpha, IL-1 beta, and IL-6. The mechanism involved in the protective effect of pogostone was correlated with its regulation of the balance between Keap1-Nrf2 and NF-kappa B signaling pathways . Moreover, volatile oils from Pogostemon cablin contain a bioactive component named b-patchoulene which has been shown to significantly decrease mortality and lung wet/dry weight ratio of mice, and mitigate pathological changes in lungs, when compared to model group. It suppressed LPS-induced activation of NF-kappa B, and markedly upregulated Nrf2 and miR-146a (Chen et al., 2017) . Oxidative stress and inflammation form a positive feedback cycle (Mittal et al., 2014) . In lung disease, excessive inflammation and oxidative stress lead to adverse outcomes. For instance, patients with COPD are usually affected by other diseases (Rabe and Watz, 2017) . Several mechanisms in lung inflammation and oxidative stress destroy DNA and lead to an imbalance between tissue repair and cell proliferation, which seems to promote the link between COPD and lung cancer (Wilson et al., 2008; Houghton, 2013; Durham and Adcock, 2015) . Under normal conditions, the production and elimination of ROS maintain a crucial balance between oxidation and antioxidation (Cao et al., 2019) . In such a balance, the signal pathways are regulated, and cell proliferation can be guaranteed. When inflammatory factors destroy this balance, oxidative stress enhances the maturation of proinflammatory factors, leading to oxidative damage to cells and multisystem diseases (Sies, 2015; Kruk et al., 2019) . Antioxidant drugs have been used in lung diseases. For example, antioxidants have been recommended for reduction of mortality or prevention of organ damage in animal models of acute lung injury induced by lipophilic acids (Hsu et al., 2006; Zhu et al., 2020) . Vitamin C has also been shown to reduce the incidence of pneumonia in several controlled trials for human subjects (Hemila, 2017) . The essential oil of Magnolia officinalis Rehder & E.H. Wilson exerts antioxidant effect by scavenging 1,1-diphenyl-2picrylhydrazyl (DPPH) radical and superoxide anion radical. The essential oil contains b-eucalyptol with a hydroxyl group which can provide hydrogen atom for scavenging DPPH radical. Moreover, with increase in volatile oil concentration, the antioxidant capacity gradually increased (Guo, 2012) . The essential oil from Atractylodes lancea (Thunb.) DC. showed a strong antioxidant effect in vitro and indicated by DPPH-radical scavenging property, with an IC 50 of 288.7 mg/ml. Moreover, it inhibited lipid peroxidation, and affected total antioxidant capacity (T-AOC) in the serum and organ tissues of mice . In short-term cigarette smoke (CS)induced acute lung inflammation, 1,8-cineole decreased oxidative stress involving reactive oxygen species, by increasing superoxide dismutase and catalase, while reducing levels of malondialdehyde, inflammation, and the NF-kappa B p65 subunit (Kennedy-Feitosa et al., 2016) . The major components of Pogostemon cablin (Blanco) Benth. are carvacrol (47.5%) and p-cymene (15.2%). It completely inhibits the growth of E. coli at a level of 0.05% (Lin et al., 2016) . The essential oil of Atractylodes lancea (Thunb.) DC. exhibited antibacterial effects against Gram-positive and Gram-negative bacteria due to the cell membrane . In chronic Zhang et al. Dayuan-Yin Against the COVID-19 Pandemic Frontiers in Pharmacology | www.frontiersin.org September 2020 | Volume 11 | Article 583651 rhinosinusitis, 1,8-cineole suppressed the growth of S. aureus, Escherichia coli, Moraxella catarrhalis due to downregulation of significant and critical players in biofilm generation (Agra, Sara, and s B ) (Schürmann et al., 2019) . On the other hand, the major constituent of the essential oil of Atractylodes lancea (Thunb.) DC. is b-eudesmol. In terms of intestinal flora, b-eudesmol has two-way regulation for gastrointestinal motility: anticholinergic pathway and direct effect on gastrointestinal smooth muscle. Antibacterial effect is an essential pharmacological property of volatile compounds (Houdkova et al., 2017; Riad et al., 2020) . Secondary bacterial co-infection is common in patients with COVID-19 infection, and it leads to adverse prognosis (Macintyre et al., 2018) . At present, many antibiotics have been used in the treatment of COVID-19. For example, Shufeng Jiedu Capsule (SFJD) prevents acute upper respiratory tract infection and positively affects fever, cough, and headache. Studies have shown that SFJD significantly reduced the levels of serum PGE2, IL-1 b, and TNF-a in rats with acute pharyngitis (Qian, 2019) . Being a popular antiviral and antibacterial drug, SFJD is one of the drugs for COVID-19 treatment in China (Pan X. et al., 2020) . In addition, Shuanghuanglian (SHL) is a popular anti-bacterial drug. It has various pharmacological potential such as antibacterial, antiviral, and immune-enhancing properties which can be exploited in the treatment of acute upper respiratory tract infection (Zhang et al., 2013) . Preliminary studies in vitro showed that SHL oral liquid inhibited SARS-COV-2. Indeed, SHL has been used to carry out clinical research on COVID-19 in Shanghai Public Health Clinical Center and Tongji Hospital Affiliated to Huazhong University of Science and Technology (Pan X. et al., 2020) . The antibacterial effects of volatile components of Dayuan-Yin are not limited to upper respiratory tract infections: these volatile components also regulate intestinal flora, treat gastric ulcers, and improve gastrointestinal symptoms. Human gut microbes are the "second genome" of the human body (Backhed et al., 2005; Gill et al., 2006; Cani and Delzenne, 2007) . The composition of intestinal flora is closely related to human health status, and it plays an essential role in maintaining physiological balance (Schuijt et al., 2016) . It has been confirmed that intestinal flora reduces ventilatorassociated pneumonia and enteritis by enhancing the function of primary alveolar macrophages (Bradley et al., 2019) . Patients with COVID-19 showed intestinal microbial malnutrition and decreased microbial flora levels of some probiotics such as Lactobacillus and Bifidobacterium. The latest version of novel coronavirus pneumonia diagnosis and treatment plan released by the People's Republic of China National Health Council suggests that intestinal microbiota should be used in severe and critical cases to maintain intestinal micro ecological balance (General Office of the National., Health Commission of the people's Republic of China. et al., 2020) . Apart from the biological effects of the volatile components mentioned above, other non-volatile components of Dayuan-Yin also have abundant pharmacological properties. (Zhang T. T. et al., 2014) (Mitsui et al., 2010) . Falcarindiol inhibited the growth of Pseudomonas aeruginosa by repressing virulencerelated genes, including the T3SS; quorum sensing synthase genes lasIR and rhlIR; lasB; motility-related genes fliC and fliG; and phenazine synthesis genes phzA1 and phzA2 . It is obvious that Dayuan-Yin exerts extensive biological properties such as antiviral, anti-inflammatory, antioxidative, and antibacterial effects. It can be inferred that Dayuan-Yin may play an essential role in preventing COVID-19 pandemic. At present, there are no conventional drugs that can cure COVID-19 (Cao B. et al., 2020) . However, according to data collected by the National Health Commission of the people's Republic of China, clinical practice in Chinese hospitals have reported that traditional Chinese medicine has a definite therapeutic effect in the early stages of COVID-19 infection . As a significant part of medical practice, Chinese medicine has been used to treat human diseases for more than 5,000 years (Li and Kan, 2017) . In recent decades, volatile compounds extracted from medicinal plants have attracted more and more attention due to their important biological effects such as antiviral, anti-inflammatory, and antibacterial properties. Besides, they are non-toxic and have few side effects, making them suitable for use as drugs. This review discussed the potential role of traditional Chinese medicine in terms of volatile components. The antiinflammatory, antiviral, antibacterial and immunomodulatory effects of these volatiles seem to play the most critical roles in treating patients infected with COVID-19. However, there are still lack of clinical trials on Dayuan-Yin. These need to be done in future. In China, the situation of COVID-19 pandemic prevention and control has improved. The national pandemic situation has been controlled. However, with the resumption of factory work, re-opening of shopping malls, and resumption of transportation, the cross-flow of personnel has increased significantly, and the probability of close contact between people has increased tremendously too. In particular, with likelihood of increase in imported cases from abroad, the epidemic prevention and control should not be relaxed. It is essential to improve the ability of the human body to withstand infection. In addition to frequent washing of hands, wearing masks, social distancing and other measures, the "Chinese medicine sachet" can be used as an essential means of prevention. This stems from a very important theory of traditional Chinese medicine, namely "treating predisease". This idea in traditional Chinese medicine originated in the Yin and Shang Dynasties, took shape in Zhouyi, and formed in Huangdi Neijing . Chinese doctors in the past dynasties attached great importance to the prevention and treatment of diseases. They emphasized the prevention of diseases first, especially infectious diseases (Lian et al., 2020) . Wearing Chinese medicine sachet is another special treatment of "treating pre-disease" . Chinese medicine sachet has been used to prevent disease since ancient times. In this method, aromatic Chinese medicine is put into a unique bag and worn on the chest to prevent respiratory diseases. This is known as "Xiangpei therapy" (Zhang Q. et al., 2014) . From the perspective of modern medicine, the medicinal fragrance (i.e., volatile oil components) of Chinese medicine sachet stimulates the nasal mucosa, promotes the secretion of immunoglobulins, and kills all kinds of viruses at the same time, thereby playing multiple roles in regulating immune function, and exerting antibacterial and anti-viral effects (Lvy and Bai, 2017) . Interestingly, early intervention with aromatic Chinese medicine blocks the course of diseases and relieves symptoms in clinical practice through oral administration, external fumigation, and moxibustion (Lun and Chen, 1987; Chen et al., 2013) . Aromatic Chinese medicine dispels exterior pathogenic factors, regulates qi, activates blood circulation, breaks blood stasis, and disperses nodules. The application of aromatic Chinese medicine embodies the theory of "internal disease and external treatment" of traditional Chinese medicine (Hu et al., 2010) . Since the outbreak of COVID-19, fumigation has been used for air disinfection to prevent the spread of the virus. In the clinical treatment period, the application of moxibustion plays the role of anti-inflammatory agent, regulates immune function, and prevents deterioration of the patients (Zhang, 2012; Liu K. et al., 2020) . Some local health committees or Chinese medicine administration bureaus are actively involved in promoting aromatic traditional Chinese medicine as an anti-epidemic, as well as the use of fumigation or Chinese medicine sachet to prevent and control COVID-19 . There is no doubt that the pharmacological effects of volatile components of traditional Chinese medicine are beneficial in the global fight against COVID-19. However, each TCM prescription has multiple goals and links in the treatment of diseases, making it difficult to clearly and thoroughly explain its mechanism in a short period. More research should be carried out on volatile components of traditional Chinese medicine to elucidate the associated regulatory mechanism, evaluate possible side effects, and conduct standard clinical trials. The insights provided in this review may help ease the COVID-19 pandemic worldwide. Q-wH and JW are the corresponding authors on the study. X-rZ and T-nL are first authors and responsible for collecting materials and writing the paper. Y-yR, Y-jZ, and H-yL helped in organizing the information and edited the article pictures. All authors contributed to the article and approved the submitted version. This work is financially supported by the Xinglin Scholar Talent Promotion Plan of Chengdu University of Traditional Chinese Medicine (QNXZ2018023, XSGG2019008). We are indebted to our alma mater, Chengdu University of Traditional Chinese Medicine for provided convenience in the collection of documents. Thanks for all the help from everyone in our lab. Research progress on the clinical effects of Chinese herbal sachets in preventing colds Hypolipidemic and antioxidant activities of thymoquinone and limonene in atherogenic suspension fed rats Host-bacterial mutualism in the human intestine The inflammation: lipoprotein cycle Anti-rheumatoid arthritic effect of volatile components in notopterygium incisum in rats via antiinflammatory and anti-angiogenic activities The acute respiratory distress syndrome Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection Pressssdiagnostic nonsteroidal anti-inflammatory drug use and lung cancer survival in the VITAL study Dexamethasone for COVID-19: data needed from randomised clinical Dayuan-Yin Against the COVID-19 Pandemic Frontiers in Pharmacology | www Immune regulation by glucocorticoids Gut microflora as a target for energy and metabolic homeostasis Chemical Composition and Antiinflammatory Effects of Essential Oil from Houpo (Magnolia Officinalis Bark) The Preventative Effects of Procyanidin on Binge Ethanol-Induced Lipid Accumulation and ROS Overproduction via the Promotion of Hepatic Autophagy A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19 The important role of polysaccharides from a traditional Chinese medicine-Lung Cleansing and Detoxifying Decoction against the COVID-19 pandemic Citrus reticulata peel oil inhibits non-small cell lung cancer cell proliferation in culture and implanted in nude mice Citrus reticulata peel oil as an antiatherogenic agent: Hypolipogenic effect in hepatic cells, lipid storage decrease in foam cells, and prevention of LDL oxidation Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility The quality of Chinese medicine and its rational application In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds Protective effects of pogostone from Pogostemonis Herba against ethanol-induced gastric ulcer in rats b-Patchoulene from patchouli oil protects against LPS-induced acute lung injury via suppressing NF-kB and activating Nrf2 pathways Discussion on role of aromatic Chinese herbs in prevention and treatment of COVID-19 based on theory of traditional Chinese medicine Antiviral activities of atractylon from Atractylodis Rhizoma Insecticidal compounds from the essential oil of Chinese medicinal herb Atractylodes chinensis Anti-infectious efficacy of essential oil from Caoguo (Fructus Tsaoko) Anti-Inflammatory Effects of Essential Oils of Amomum aromaticum Fruits in Lipopolysaccharide-Stimulated RAW264.7 Cells Chemical composition and in vitro inhibitory effects of essential oils from fruit peel of three Citrus species and limonene on mycelial growth of Sclerotinia sclerotiorum The relationship between COPD and lung cancer A comparative study on chemical composition and antioxidant activity of ginger (Zingiber officinale) and cumin (Cuminum cyminum) Efficacy of cineole in patients suffering from acute bronchitis: a placebo-controlled double-blind trial Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health Metagenomic analysis of the human distal gut microbiome Impact of air pollution on the burden of chronic respiratory diseases in China: time for urgent action The Anti-viral Studies of Notopterygium incisum Headspace Solid-Phase Microextraction-Gas Chromatography-Mass Spectrometry for the Analysis of Volatile Compounds from A.lancea Research about Effective Ingredients of Magnolia Officinalis Based on Their Antioxidant Activity Inhibitory effects of atractylone on mast cell-mediated allergic reactions Antioxidant and antibacterial activities of essential oil from Atractylodes lancea rhizomes Vitamin C and Infections Evaluation of antibacterial potential and toxicity of plant volatile compounds using new broth microdilution volatilization method and modified MTT assay Mechanistic links between COPD and lung cancer Mechanism by which ma-xing-shi-gan-tang inhibits the entry of influenza virus Attenuation of endotoxin-induced oxidative stress and multiple organ injury by 3,4-Methylenedioxyphenol in rats Application of aromatic herb in external therapy Experimental Lung Injury Reduces Krüppel-like Factor 2 to Increase Endothelial Permeability via Regulation of RAPGEF3-Rac1 Signaling Clinical features of patients infected with 2019 novel coronavirus in Wuhan Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial Dayuan-Yin Against the COVID-19 Pandemic Frontiers in Pharmacology | www Metabolite profiles of essential oils in citrus peels and their taxonomic implications COVID-19 Dashboard by the Inhibition of cytokine production and arachidonic acid metabolism by eucalyptol (1.8-cineole) in human blood monocytes in vitro Antiinflammatory effects of euclyptol (1.8-cineole) in bronchial asthma: inhibition of arachidonic acid metabolism in human blood monocytes ex vivo Inhibition of H+,K+-ATPase by hinesol, a major component of So-jutsu, by interaction with enzyme in the E1 state Eucalyptol attenuates cigarette smoke-induced acute lung inflammation and oxidative stress in the mouse Exhibits Anti-Inflammatory Activity Through the Suppression of MAPKs and the NF-kB Pathway in Mouse Peritoneal Macrophages Atractylone, an active constituent of KMP6, attenuates allergic inflammation on allergic rhinitis in vitro and in vivo models Clinical use of dornase alpha is associated with a slower rate of FEV1 decline in cystic fibrosis Oxidative stress in biological systems and its relation with pathophysiological functions: the effect of physical activity on cellular redox homeostasis Analysis of tetramethylpyrazine in Ephedrae herba by gas chromatography-mass spectrometry and highperformance liquid chromatography The use of dexamethasone in the treatment of COVID-19 Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects Pogostone suppresses proinflammatory mediator production and protects against endotoxic shock in mice 1, 8-Cineol Protect Against Influenza-Virus-Induced Pneumonia in Mice Two Cases of COVID-19 Treated Effectively with Modified Da Yuan Drinking Review of Classical Famous Prescription "Dayuanyin" Used for the Treatment of COVID-19 and Analysis of Pulmonary Classical Famous Prescriptions Discussion on TCM Theories of "Qingwen Pihui San" to Prevent New Coronavirus Pneumonia Effect of Dexamethasone in Hospitalized Patients with COVID-19 -Preliminary Report Essential oils from Taiwan: Chemical composition and antibacterial activity against Escherichia coli Cytokine Storms, Hyper-Inflammatory Phenotypes, and Acute Respiratory Distress Syndrome. Genes Dis Attach importance to research and development of Chinese materia medica based on prevention and control needs of SARS-CoV-2 infection Feasibility Analysis of Moxibustion Whole Process Intervention in the Prevention and Treatment of COVID-19 70 Vardenafil as anti-inflammatory drug in the treatment of cystic fibrosis lung disease Prevention and treatment of aromatic Chinese medicine Study on the Mechanism of Aromatic Traditional Chinese Medicine Compound on Prevention and Treatment of New Coronavirus Pneumonia Discussion on the effect of air disinfection for aromatic smell of traditional Chinese medicine Sachet The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09 Retinal findings in patients with COVID-19 Supercritical CO2 extracts and essential oil of ginger (Zingiber officinale R.): Chemical composition and antibacterial activity The herbal medicine compound falcarindiol from Notopterygii Rhizoma suppresses dendritic cell maturation Reactive oxygen species in inflammation and tissue injury 1,8-Cineole potentiates IRF3-mediated antiviral response in human stem cells and in an ex vivo model of rhinosinusitis Effect of some volatile oils on the affinity of intact and oxidized lowdensity lipoproteins for adrenal cell surface receptors General Office of China., Health Commission of the People's Republic Of and Medicine Human infection with Strongyloides stercoralis and other related Strongyloides species Use of antiviral drugs to reduce COVID-19 transmission Qualitative Study on Volatile Components of Different Reticulatae Pericarpium Products Based on GC-MS Potential drugs for the treatment of the novel coronavirus pneumonia (COVID-19) in China Antiinflammatory effects of ginger and some of its components in human bronchial epithelial (BEAS-2B) cells Dayuan-Yin Against the COVID-19 Pandemic Frontiers in Pharmacology | www Effect of Shufeng Jiedu Capsule on Serum PGE2, IL-1b and TNF-a in Rats with Acute Pharyngitis and Clinical Efficacy Observation Chronic obstructive pulmonary disease Traditional Chinese medicine for COVID-19 treatment Chemical screening and antibacterial activity of essential oil and volatile fraction of Dictyopteris polypodioides Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia The Therapeutic Effect of 1,8-Cineol on Pathogenic Bacteria Species Present in Chronic Rhinosinusitis Oxidative stress: a concept in redox biology and medicine Effect of patchouli (Pogostemon cablin) essential oil on in vitro and in vivo leukocytes behavior in acute inflammatory response COVID-19: combining antiviral and anti-inflammatory treatments Immunosuppressive activity of pogostone on T cells: Blocking proliferation via S phase arrest 1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late Rhinosinusitis Modern enlightenment on aromatic drugs in the prevention and treatment of epidemic diseases in Ming and Qing dynasties Protective effects of pogostone against LPS-induced acute lung injury in mice via regulation of Keap1-Nrf2/NF-kB signaling pathways Atractylodin attenuates lipopolysaccharide-induced acute lung injury by inhibiting NLRP3 inflammasome and TLR4 pathways Comparative Study on Chemical Composition and Antibacterial Activity of Essential Oils from Patchouli and Magnolia officinalis Alone and Combination Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19 Limonene: Aroma of innovation in health and disease Guideline for the Diagnosis and Treatment of COPD Patients -Issued by the German Respiratory Society and the German Atemwegsliga Experience in Treatment of COVID-19 by Elimination of Pathogens Through Purgation and Diuresis Effects of beudesmol, an active constituent from Rhizoma Atractylodis on small intestine movement in rats Study on the molecular mechanism of pogotone against Staphylococcus aureus A case of Dayuan Yin and LiuJunZi Decoction Treating with COVID-19 Study on the effect of anti-respiratory viruses of Patchouli Oil in vitro Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial The Pittsburgh Lung Screening Study (PLuSS): outcomes within 3 years of a first computed tomography scan Patients with asthma benefit from concomitant therapy with cineole: a placebo-controlled, double-blind trial Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: a placebo-controlled double-blind trial New guaiane sesquiterpenes and furanocoumarins from Notopterygium incisum A new coronavirus associated with human respiratory disease in China Orthogonal Array Design for the Optimization of Supercritical CO 2 Extraction of Volatile Oil from Amomum tsaoko Fruits Theoretical Origin and Practical Thinking of the Theory of Chinese Medicine Preventive Treatment of Disease Analysis of Volatile Components of Ephedra from Different Places Based on GC-MS Cytotoxic, apoptotic and antioxidant activity of the essential oil of Amomum tsao-ko Pogostone attenuates TNF-a-induced injury in A549 cells via inhibiting NF-kB and activating Nrf2 pathways GC-MS Analysis of Volatile Oil from Atractylodes chinensis A pathological report of three COVID-19 cases by minimal invasive autopsies. Zhonghua bing li xue za zhi = Chin Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in RAW 264.7 macrophages Chinese medicine injection shuanghuanglian for treatment of acute upper respiratory tract infection: a systematic review of randomized controlled trials Effect of Miao medicine Fanggan sachet on expression of NKp46 in peripheral blood of mice Bioactivity evaluation of ingredients identified from the fruits of Amomum tsaoko Crevost et Lemaire, a Chinese spice Dayuan-Yin Against the COVID-19 Pandemic Frontiers in Pharmacology | www Pseudomonas aeruginosaVirulence-Inhibiting Herbal Compound Falcarindiol Significantly Reduced Mortality in Mice Infected with The antibacterial effect of Cangzhu and its application in the disinfection of hospital environment 1,8-cineol attenuates LPS-induced acute pulmonary inflammation in mice Effect of alpha-pinene on nuclear translocation of NF-kappa B in THP-1 cells Effect of patchouli oil on acute bacterial upper respiratory infections model mice Alphalinolenic acid protects against lipopolysaccharide-induced acute lung injury through anti-inflammatory and anti-oxidative pathways The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Copyright © 2020 Zhang, Li, Ren, Zeng, Lv, Wang and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.