key: cord-0952537-41pr3dwa authors: Zhang, Dan; Zhang, Bing; Lv, Jin-Tao; Sa, Ri-Na; Zhang, Xiao-Meng; Lin, Zhi-Jian title: The clinical benefits of Chinese patent medicines against COVID-19 based on current evidence date: 2020-05-05 journal: Pharmacol Res DOI: 10.1016/j.phrs.2020.104882 sha: 30927bae22efe9770880518c8e680103fa3b0b40 doc_id: 952537 cord_uid: 41pr3dwa Abstract The outbreak of emerging infectious pneumonia caused by 2019 Novel Coronavirus (2019-nCoV) has posed an enormous threat to public health, and traditional Chinese medicine (TCM) have made vast contribution to the prevention, treatment and rehabilitation of coronavirus disease 19 (COVID-19) among Chinese population. As an indispensable part of TCM, Chinese patent medicines (CPMs) are highly valued and critically acclaimed in their campaign to contain and tackle the epidemic, they can achieve considerable effects for both suspected cases under medical observation period, and confirmed individuals with serious underlying diseases or critical conditions. Given this, based on the Guideline on Diagnosis and Treatment of Coronavirus Disease 2019 in China, the present review summarized the basic information, clinical evidence and published literatures of recommended CPMs against COVID-19. The details were thoroughly introduced involving compositions, therapeutic effects, clinical indications, medication history of CPMs and the profiles of corresponding research. With regard to infected patients with different stages and syndrome, the preferable potentials and therapeutic mechanism of CPMs were addressed through the comprehensive collection of relevant literatures and on-going clinical trials. This study could provide an insight into clinical application and underlying mechanism of recommended CPMs against COVID-19, with the aim to share the Chinese experience in clinical practice and facilitate scientific development of TCM, especially CPMs in the fierce battle of COVID-19. In the theory of traditional Chinese medicine (TCM), 2019-nCoV infected pneumonia was deemed to the category of "Pestilence", and the characteristics of its pathogenesis was "dampness, toxin, stasis and closure" [19] [20] . Over the past few months, TCM exhibited remarkable benefits against COVID-19 in China, and it was convinced that TCM achieved satisfactory therapeutic superiority for patients infected by 2019-nCoV with regard to preventive treatment of diseases, comprehensive therapies and rehabilitation by the accumulation of clinical experience and scientific evidence [21] [22] . As recommended in the Guideline on Diagnosis and Treatment of Coronavirus Disease 2019 (Revised 7th version) which was officially released by National Health Commission of the People's Republic of China, TCM could exert favorable effects for patients with different syndromes and distinct stages of COVID-19, contributing to infections in the periods of both medical observation and clinical treatment [23] . Recently, the latest official data showed that 91.5% of confirmed subjects with COVID-19 (74,187 cases) received TCM in China, and increasing results of clinical observation indicated that the total effective rate of TCM reached more than 90% [24] . These promising advantages were associated with its unique therapeutic principles including syndrome differentiation and treatment, boosting the individual's endogenous healing ability, balancing Yin and Yang, various therapies and personalized treatment in first-line clinic [25] [26] . With the development of technology in TCM domain, Chinese herbal products were transformed into varied dosage forms, Chinese patent medicines (CPMs) were consumer-near and popular "folk medicine" that contributed to widely application in clinical practice among Chinese citizens [27] [28] . Compared to herbal decoction, CPMs had the advantages of stable quality, curative efficacy, considerable safety, rapid absorption, high bioavailability, convenience of taking, carrying and storing [29] [30] . Similarly, as an indispensable part of TCM, CPMs were substantial utilized in combination with western medicine for the management of COVID-19, and proposed as adjunctive and therapeutic options to fight the public health emergency of 2019-nCoV by national and provincial guidelines in China [31] [32] [33] . Given the paucity of published English research concerning CPMs against COVID-19 currently, the present review performed a descriptive analysis of recommended CPMs from both clinical trials and published literatures, based on the following aspects: information retrieved from their instructions (compositions, therapeutic effects, and clinical indications), medical evidence, pharmacodynamic mechanism, dominant components, applicable patients, clinical cautions and so on. As regarding to some types of CPMs without accessible published evidence for treating 2019-nCoV, we introduced the relevant results of infectious or health-threatening diseases. The aim of present review was to provide the scientific basis and share clinical experiences for promising choices of CPMs against COVID-19. J o u r n a l P r e -p r o o f First, the comprehensive retrieval of electronic databases in both Chinese and English (the China National Knowledge Infrastructure Database, WangFang Database, Sinomed Database, PubMed and Embase) was performed for collecting the published research from inception to Apr 10, 2020. On the one hand, the following terms of COVID-19 were adopted: "COVID-19 [Supplementary Concept]," "2019 novel coronavirus", "COVID19", "SARS-CoV-2", "2019-nCoV", "coronavirus disease 2019", "coronavirus disease-19". On the other hand, the searching terms of CPMs mainly included their Mandarin Chinese and trade name. The results of literature search were displayed in Figure 1A , a total of 28 citations were yielded initially for eight CPMs. Only one eligible study was in English, focused on the anti-viral and anti-inflammatory activities of Lianhuaqingwen Capsule for treating COVID-19, which published by the team of distinguished Academician Nanshan Zhong. In addition, the on-going clinical trials concerning on CPMs anagist COVID-19 were supplemented to identify the potential evidence by utilizing the platform of Chinese Clinical Trial Figure 1B ). According to aforementioned guidelines of COVID-2019 in China, totally 14 types of CPMs were officially issued to prevent and treatment COVID-19, 57.14% (8 types) of them were Chinese herbal injection, and others were oral dosage forms of TCM. As illustrated in Figure 2 Figure 3 . Further, the details involving compositions, therapeutic effects, clinical indications for recommended CPMs were summarized in Table 1 , to provide the relative references for clinician J o u r n a l P r e -p r o o f and specialists to control the spread of this fatal disease. Based on the findings of related review, the CPMs including Huoxiang Zhengqi Capsule, Jinhua Qinggan Granules, Lianhua Qingwen Capsule, Shufeng Jiedu Capsule could be presumably as preventive measure for the patients in the medical observation period [34] . It was noteworthy that early treatment was essential for suspected or mild cases, accumulated evidence of bioinformatics, pharmacodynamics and clinical findings suggested that these multiple component Chinese herbal products also exerted effects on immune regulation, symptom improvement, anti-inflammation and so on during the treatment of COVID-19. The results of previously pharmacological research indicated that Huoxiang Zhengqi Capsule or other dosage forms could improve gastrointestinal dysfunction, modulate immune responses, and anti-inflammation [35] . With regard to the national and provincial guidelines against COVID-19 in China, Huoxiang Zhengqi Capsule was recommended for patients with fatigue and gastrointestinal discomfort [36] . Through the techniques of network pharmacology and molecular docking, Huoxiang Zhengqi Oral Liquid could regulate multiple signaling pathways involving Hepatitis B, small cell lung cancer, non-small cell lung cancer and inhibit the replication of 2019-nCoV to exhibit the preventive or therapeutic effects on COVID-19, and its active compounds had definite affinity with angiotensin converting enzyme II (ACE2) and 3-chymotrypsin-like protease (3CLpro) [37] [38] . Compared with other recommended CPMs, Jinhua Qinggan Granules posed the shorter period of medication history, nevertheless, it was proved that the application of Jinhua Qinggan Granules could significantly alleviate clinical symptoms such as fever, cough, fatigue, expectoration, and relieve psychological anxiety of mild cases suffered from COVID-19 [39] . The results of systems biology and bioinformatics revealed that the mechanism of Jinhua Qinggan granules in the treatment of COVID-19 involving multiple targets, namely MAPK1, CASP3, TP53, ALB, TNF, IL6, and multiple pathways, which might be related to antiviral, immune regulation, inflammation inhibition and apoptosis regulation via PI3K-Akt, HIF-1, TNF, MAPK, NF-κB pathways, and dominant principles including kaempferol, baicalein and oroxylin A could take participate in multiple signal pathways (such as PTGS2, HSP90AB1, PTGS2, BCL2 and CASP3) by binding with ACE2 [40] [41] [42] . Relieving typical symptoms and representative complications, diminishing inflammation and infection, the Chinese herbal products of Lianhua Qingwen Capsule was recognized as an excellent antidote in this anti-epidemic by adequate clinical and fundamental research [34, 43] . According to preliminary clinical evidence of retrospective, multicenter study and cases reports, for general type patients and suspected cases with COVID-19, the scheme of Lianhua Qingwen Capsule combined Among them, only Xiyanping Injection was applied for treating severe patients, whereas others were also recognized as the complementary choices for critical cases with COVID-19. Compared with oral administration of TCM, the Chinese herbal injections possessed the benefits of rapid onset, high bioavailability, and content accuracy [57], therefore, they were more suitable for the severe or critical patients with COVID-19. Some scholars concluded that Xiyanping Injection was reputed as effective alternative to antibiotics in clinical practice [58] . Modern pharmacological studies showed that its active ingredient, sulfonated andrographolide had notable effects of antipyretic, anti-inflammation to treat various infectious diseases [59] . In addition, prevenient Chinese research pointed out its clinical J o u r n a l P r e -p r o o f advantages that were related to improve respiratory symptoms, inhibit concurrent bacterial infection, and regulate immune function, superior clinical safety, especially certain hepatoprotective effects, suggesting it might have potentials to relieve some drug-induced liver injury during the treatment of COVID-19 for serious cases [60] . Remarkably, it was reported that andrographolide sulfonate could ameliorate sepsis in mice through suppressing MAPK, STAT3 and NF-κB pathways, these pathways also played the important role in pulmonary diseases [61] [62] [63] . The prescription of Xuebijing Injection originated from therapeutic principles of TCM, that was proposed by famous integrative medicine emergency experts, Professor Jin-Da Wang, it was approved as second grade national new medicine for treating sepsis in China over 15 years [64] [65] . In this clinical fight against COVID-19, considerable effects of Xuebijing injection had been displayed by retrospective study and relevant review, the results revealed that Xuebijing injection could promote the absorption of lung infection, and improve clinical efficacy and negative rate of nucleic acid [66] [67] . Besides, some research demonstrated its characteristics of multi-target and multi-pathway in treating COVID-19 based on the approaches of network pharmacology and molecular docking. Among a series of involved signaling pathways, such as HIF-1 and PI3K-Akt were represented pathways against COVID-19 in terms of lung inflammation, virus infection and lung injury. Besides, core targets including TNF, MAPK1, JUN, IL6, STAT3, EGFR, etc. were closely correlation with the inhibition of cytokine storm in severe cases, and fatal risk of cytokine storms in the immune system of serious patients might result in organ failure and even death [68] [69] [70] . Reduning Injection was widely utilized to treat upper respiratory tract infection with multiple functions such as clearing heat, dispelling wind, and detoxification, and previous pharmacological research proposed that it could ameliorate paraquat-induced acute lung injury involved in regulating AMPK/MAPK/NF-κB signaling pathways [71] . In this regard to treating COVID-19, Reduning injection might be related to anti-inflammatory, immunoregulation of active compounds through multi-target and multi-pathway. On the one hand, the critical targets were namely PTGS2, PTSG1, CCL2, RELA, NOS2, HMOX1, CASP3, IL6 and MAPK1, some of them belonged to chemokines, which posed the immune activation profiles of 2019-nCoV. On the other hand, KEGG pathway enrichment analysis revealed 45 related pathways, mainly IL-17, C-type lectin receptor, HIF-1 and NF-κB signaling pathways [72] [73] . A large number of clinical data had accumulated to confirm superior efficacy of Tanreqing Injection in the treatment of acute bronchitis disease, tuberculosis and so on [74] [75] . In particular, the severe patients with COVID-19 suffered similar clinical manifestations of its dominant diseases. Meanwhile, the underlying mechanism and binding activity of Tanreqing Injection were elucidated, the results in molecular level showed that it might be potential as antiviral agent due to critical Interesting, the core targets involved IL6, IL1B, MAPK1, IL10, IL4, CXCL8, IP10, etc. [76] . This finding was consistent with former clinical report regarding severe patients with higher level of IL2, IL7, IL10, GSCF, IP10 in the plasma [77] . The commercialized injectable product of Xingnaojing Injection was extracted and refined scientifically from classic Chinese emergency prescription "Angong Niuhuang Pill", it had the functions of clearing heat and detoxication, cooling blood and activating blood circulation, inducing resuscitation and widely used in the treatment of intracerebral haemorrhage, cerebral ischemia, and nervous system disorders in China [78] [79] [80] . In view of critical cases with COVID-19 might suffer from consciousness disturbance, Xingnaojing Injection had major biological effects to relax the cerebral vascular and protect the mature neuron, in vivo and in vitro research, it was confirmed that the mechanism of cerebrovascular protection might be relevant to the activation of PI3K/Akt/eNOS signaling pathways and the suppression of NLRP3 inflammasomes [81] [82] . In aforementioned guidelines, five CPMs were recommended as adjuvant rescue just for critical infections with COVID-19, namely Suhexiang Pill, Angong Niuhuang Pill, Shenfu Injection, Shengmai Injection, Shenmai Injection. Currently, there were paucity of accessibly published evidence concerning on these CPMs and 2019-nCoV simultaneously, it was urgent and essential that subsequently clinical trials or pharmacological research to provide sufficient references for clinical recommendation. Herein, we brief summarized the findings in the field of infectious or health-threatening diseases to supplement the correlative knowledge. Although both of them were famous Chinese emergency prescription and contained same resuscitation-inducing aromatic herbs as Bingpian (Borneolum Syntheticum), Suhexiang Pill and Angong Niuhuang Pill were used for patients with opposite syndromes. The former was adopted to seizures, infantile convulsions and stroke with cold syndromes [83] , therefore, Suhexiang Pill might achieve therapeutic effectiveness for COVID-19 cases with critical conditions such as delirium, phlegm syncope, central nervous depression, and coma or worsen. Its neuroprotective, anticonvulsant and antioxidative effects had been proven by fundamental research both in vitro and in vivo, suggesting its pharmacological mechanism involved the suppression of JNK hyperactivation and apoptosis, inhibition of EGFR/ERK pathways and glial cell proliferation, decreasing ROS formation and restoring mitochondrial function [84] [85] [86] [87] . As a recipe of "Liangkai Sanbao" in TCM theory, the latter was recognized to treat heat diseases only, including acute ischemic stroke, viral encephalitis, acute hemorrhagic stroke, and trauma brain injury, Angong J o u r n a l P r e -p r o o f Niuhuang Pill could play desirable role for treating critical infections with 2019-nCoV in attenuating the negative symptoms including hyperthermia, stupor, coma, etc. [88] . Meanwhile, based on the research was conducted on a high-fat and vitamin D3-induced rodent model of atherosclerosis, the results presented that Angong Niuhuang Pill had antiplatelet aggregation, lipid regulatory, antioxidant, anti-inflammatory and anti-apoptotic properties contributing to robust antatherosclerosis and cardio-protective effects [89] , which might be beneficial for critical cases with cardiovascular and cerebrovascular diseases. The mechanisms of Angong Niuhuang Pill exhibited the neuroprotection was related to depressed Bax/Bcl-2 ratio and caspase-3 level, resulting the inhibition of apoptotic cell [90] . Injection had similar therapeutic effects of tonifying Qi and preventing exhaustion, they could be adjuvant rescue and alternative treatment of COVID-19 patients with septic shock, viral myocarditis, and cardiogenic shock in clinical practice [91] [92] [93] . For example, in rabbits with LPS-induced septic shock, Shenfu injection could increase mean arterial pressure, decrease the serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and glutamate transaminase (ALT) levels, improve the tissue morphology of heart, liver and kidney, and increase the contents of ATP and taurine in the heart tissue during septic shock [94] . Besides, previous studies demonstrated that Shenfu Injection, Shengmai Injection and Shenmai Injection were associated with protective effects on lung ischemia-reperfusion injury, reducing chemotherapy-induced adverse effects, and promoting cellular immunity and cognitive dysfunction and so on, presumably, these clinical functions might improve symptoms of critical patients with COVID-19 in terms of lung inflammation, virus infection, drug-induced disease lung injury [95] [96] [97] [98] . Since the globally health-care-associated outbreaks of 2019-nCoV, in China, the implementing "attach equal importance to TCM and Western medicine" policy in clinical practice exerted essential effects for treating COVID-19 [99] [100] . Based on unique guiding principles of syndrome differentiation and treatment in TCM, its clinical superiority had considerable recognition and public acclaim in the furious battle for 2019-nCoV, the cumulative number of research revealed that its curative advantages involved in whole treatment process, namely prevent disease progression, alleviate clinical symptoms, improve the hospital stay and negative results of nucleic acid detection, and promote the physical recovery [21] [22] 101] . [104] [105] . Moreover, our study highlighted that its clinical beneficial effects in severe cases was closely associated with the inhibition of cytokine storm, improve virus infection and lung injury, superior binding activities with 3CLpro and ACE2. In addition, three types of recommended herbal injectable dosage forms contained Hongshen (Ginseng Radix Et Rhizoma Rubra), ginseng was generally known for its tonic properties, and previous findings also suggested it might be a promising supplemental remedy against infectious diseases, this administration of ginseng could fast and accurate adjust excess or deficiency between Yin or Yang and restore their balance among critical patients [106] [107] [108] . When great attention was paid to the application of TCM in real-world, there were growing concerns related to the potential toxicity or inevitable ADRs of herbal medicines. The results of pharmacovigilance pointed out the risk factors of ADRs triggered by TCM including responsible Chinese materia medica, susceptible patients and clinical administration [109] . In this regard, our research should emphasize the following aspects, including poisonous composition, the safety status of Chinese herbal injection, special population, and irrational drug use. First, Angong Niuhuang Pill contained cinnabar (HgS) and realgar (As 2 S 2 ) which were correlated to hepatorenal toxicity [110] . Fuzi (Aconiti Lateralis Radix Praeparaia) in Shenfu Injection was associated with narrow therapeutic window, its cardiac ADRs has been frequently observed that mainly manifested as palpitations, hypotension, arrhythmia, ventricular fibrillation, and even shock [111] [112] . Second, compared with other dosage forms of TCM medications, Chinese herbal injections were associated J o u r n a l P r e -p r o o f with the higher risk of ADRs, especially serious side effects [113] [114] . Therefore, during the treatment of COVID-19, corresponding measures including drug safety monitoring and risk management for CPMs should be strengthened to achieve optimal benefits and minimal hazards. Third, the available evidence highlighted that special population including children, gravida and elderly people were particularly vulnerable to unfavorable drug responses, because their pharmacokinetic and pharmacodynamic profiles differed from the general population [115] . Indeed, clinical medication was complicated, the irrational uses reflected in misuse or abuse application of in the treatment of COVID-19 was more effective than patients receiving western medicine alone, which can significantly shorten the hospitalization, improve clinical symptom and imaging results [117] . In conclusion, the present study was devoted to summarize the comprehensive information and The authors of the manuscript that titled "The clinical benefits of Chinese patent medicines against COVID-19 based on current evidence" declared that there are no conflicts of no financial/personal interest. Emerging understandings of 2019-nCoV COVID-19: what is next for public health? National Health Commission of the People's Republic of China. The guideline on diagnosis and treatment of coronavirus disease 2019 (Revised 6th version) Clinical course and mortality risk of severe COVID-19 Clinical characteristics of coronavirus disease 2019 in China Thinking globally, acting locally -The U.S. response to Covid-19 Global outbreak of 2019-nCoV, a new challenge? statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-theoutbreak-of-novel-coronavirus-(2019-ncov) Governmental public health powers during the COVID-19 pandemic: stay-at-home orders, business closures, and travel restrictions First case of 2019 novel coronavirus in the United States Transmission of 2019-nCoV infection from an asymptomatic contact in Germany World Health Organization. Coronavirus disease (COVID-19) Situation dashboard World Health Organization. Coronavirus disease (COVID-19) Pandemic National Health Commission of the People's Republic of China. The epidemic situation coronavirus disease (COVID-19) up to 4 Misguided drug advice for COVID-19 COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment or prevention of corona virus infection? Aging Chloroquine and hydroxychloroquine to treat COVID-19: between hope and caution Thoughts on prevention and treatment of coronavirus disease 2019(COVID-19) by traditional Chinese medicine Therapeutic strategy of traditional Chinese medicine for 2019 novel coronavirus pneumonia Traditional Chinese medicine for COVID-19 treatment Can Chinese medicine be used for prevention of corona virus disease 2019 (COVID-19)? A review of historical classics, research evidence and current prevention programs National Health Commission of the People's Republic of China. The guideline on diagnosis and treatment of coronavirus disease Press conference of the important role and effective drugs of traditional Chinese medicine in the prevention and treatment of COVID-19 on Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective Traditional Chinese Medicine: an effective treatment for 2019 novel coronavirus pneumonia (NCP) Traditional Chinese herbal injection: Current status and future perspectives Analysis on dosage form theory and current application situation of traditional Chinese medicine pill Chinese propriety medicines: an "alternative modernity?" The case of the anti-malarial substance artemisinin in East Africa Establishment of a quality marker (Q-marker) system for Chinese herbal medicines using burdock as an example COVID-19: An update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative Chinese-Western medicine for the management of 2019 novel coronavirus disease Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19 in Wuhan Expert consensus on prescription comment of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2) Effects of huoxiangzhengqi liquid on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea Research progress on potential application of Huoxiang Zhengqi in prevention and treatment of coronavirus disease 2019 Study on active compounds from Huoxiang Zhengqi Oral Liquid for prevention of coronavirus disease 2019(COVID-19) based on network pharmacology and molecular docking Preliminary study on the effective components and mechanism of Huoxiang Zhengqi Decoction in inhibiting the replication of novel coronavirus Clinical observation of novel coronavirus infected pneumonia treated by Jinhua Qinggan Granule Exploring active compounds of Jinhua Qinggan Granules for prevention of novel coronavirus pneumonia (COVID-19) based on network pharmacology and molecular docking Study on the active components in the adjuvant treatment of novel coronavirus pneumonia (COVID-19) with Jinhua Qinggan Granules based on network pharmacology and molecular docking Discussion on the mechanism of Jinhua Qinggan Granule in the treatment of novel coronavirus pneumonia The efficacy of Lianhua Qingwen combined with western medicine scheme on COVID-19 general type patients Crystal structure and anti-inflammatory and anaphylactic effects of andrographlide sulphonate E in Xiyanping, a traditional Chinese medicine injection Theoretical basis and effect characteristics of andrographolide against COVID-19 Water-soluble andrographolide sulfonate exerts anti-sepsis action in mice through down-regulating p38 MAPK, STAT3 and NF-κB pathways Beneficial effects of naringenin in liver diseases: Molecular mechanisms NF-κB and STAT3 -key players in liver inflammation and cancer Xuebijing injection alleviates Pam3CSK4-induced inflammatory response and protects mice from sepsis caused by methicillin-resistant staphylococcus aureus Therapeutic effect of Xuebijing, a traditional Chinese medicine injection, on rheumatoid arthritis. Evid Based Complement Alternat Med Clinical observation of Xuebijing in the treatment of COVID-19 Current evidence and research prospects of Xuebijing Injection in treating novel coronavirus-infected pneumonia (COVID-19). Modernization of Study on the overall regulation of Xuebijing injection in treating corona virus disease 2019 Potential mechanism of Xuebijing Injection in treatment of coronavirus pneumonia based on network pharmacology and molecular docking COVID-19: consider cytokine storm syndromes and immunosuppression Reduning injection ameliorates paraquat-induced acute lung injury by regulating AMPK/MAPK/NF-κB signaling Study on mechanism of Reduning Injection in treating novel coronavirus pneumonia based on network pharmacology Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19 Tanreqing injection for acute bronchitis disease: A systematic review and meta-analysis of randomized controlled trials Clinical efficacy and safety of Tanreqing Injection for pulmonary infection in patients with tuberculosis: a meta-qnalysis Mechanism of Tanreqing Injection on treatment of coronavirus disease 2019 based on network pharmacology and molecular docking Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet Role of Xingnaojing combined with naloxone in treating intracerebral haemorrhage: A systematic review and meta-analysis of randomized controlled trials Meta-analysis of the effects of Xingnaojing Injection on consciousness disturbance Meta-analysis for clinical evaluation of Xingnaojing Injection for the treatment of cerebral infarction Xingnaojing Injection protects against cerebral ischemia reperfusion injury via PI3K/Akt-mediated eNOS phosphorylation XingNaoJing injections protect against cerebral ischemia/reperfusion injury and alleviate blood-brain barrier disruption in rats, through an underlying mechanism of NLRP3 inflammasomes suppression SuHeXiang Wan essential oil alleviates amyloid beta induced memory impairment through inhibition of tau protein phosphorylation in mice Neuroprotective effect of SuHeXiang Wan in Drosophila models of Alzheimer's disease Neuroprotective effects of Suhexiang Wan on the in vitro and in vivo models of Parkinson's disease Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer's disease Inhibitory effects of the essential oil from SuHeXiang Wan on the central nervous system after inhalation Use of angong niuhuang in treating central nervous system diseases and related research. Evid Based Complement Alternat Med Anti-atherosclerosis and cardio-protective effects of the Angong Niuhuang Pill on a high fat and vitamin D3 induced rodent model of atherosclerosis An-Gong-Niu-Huang Wan protects against cerebral ischemia induced apoptosis in rats: up-regulation of Bcl-2 and down-regulation of Bax and caspase-3 Shenfu Injection attenuates rat myocardial hypertrophy by up-regulating miR-19a-3p expression An overview of systematic reviews of shenmai injection for healthcare. Evid Based Complement Alternat Med Herbal medicines for viral myocarditis Effect of Shenfu injection on lipopolysaccharide (LPS)-induced septic shock in rabbits Protective effect of Shenfu injection preconditioning on lung ischemia-reperfusion injury Effects of Shenfu injection on chemotherapy-induced adverse effects and quality of life in patients with advanced nonsmall cell lung cancer: A systematic review and meta-analysis Comments on Shenfu injection for improving cellular immunity and clinical outcome in patients with sepsis or septic shock Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution Administrations of preoperative Shenmai injection and postoperative Shenfu Injection, two ginseng containing TCM formulas, improve cognitive dysfunction in aged rats Effects of Shengmai injection add-on therapy to chemotherapy in patients with non-small cell lung cancer: a meta-analysis Interpretation of the Expert guidance on a comprehensive intervention program of Traditional Chinese Medicine for the recovery of Novel Coronavirus Pneumonia(Draft) In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus Clinical features and treatment of COVID-19 patients in northeast Chongqing Protective effect of phillyrin on lethal LPS-induced neutrophil inflammation in zebrafish Phillyrin is an effective inhibitor of quorum sensing with potential as an anti-Pseudomonas aeruginosa infection therapy Protective effects of phillyrin against influenza A virus in vivo Efficacy of Xuebijing injection for sepsis (EXIT-SEP): protocol for a randomised controlled trial Microcirculatory disorders and protective role of Xuebijing in severe heat stroke Effects of radix ginseng on microbial infections: a narrative review Protective roles of ginseng against bacterial infection The characteristics and regularities of cardiac adverse drug reactions induced by Chinese materia medica: A bibliometric research and association rules analysis A review of cinnabar (HgS) and/or realgar (As4S4)-containing traditional medicines Study on cardiotoxicity and mechanism of "Fuzi" extracts based on metabonomics A review of traditional and current methods used to potentially reduce toxicity of Aconitum roots in Traditional Chinese Medicine Safety profile of traditional Chinese herbal injection: An analysis of a spontaneous reporting system in China Safety concerns of traditional Chinese medicine injections used in Chinese children Respiratory syncytial virus prophylaxis and the "special population Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Observation on clinical effect of modified Qingfeipaidu decoction in treatment of COVID-19 This work is supported by the Programs Foundation for Leading Talents in State Administration of Traditional Chinese Medicine of China-"Qihuang scholars" Project (10400633210004), the National Natural Science Foundation of China (Grant No. 81874349), and National special support plan for high-level talents (Plan of ten thousand people)-Famous Teacher Program to Professor Bing Zhang. Heat diseases including invasion of pericardium by evil, febrile convulsion, coma and delirium. Apoplectic coma, encephalitis, cephalomeningitis, toxic encephalopathy, hematencephalon, septicemia belongs to the above syndromes.