TRADITIONAL CHINESE HERBAL REMEDIES
As evidenced by a February 18th tweet from China Xinhua News, healthcare practitioners across China are relying on centuries-old remedies to treat the novel coronavirus. In the absence of targeted drugs and vaccines, with continual updates to the national diagnosis and treatment program for novel coronavirus, the role of traditional Chinese medicine (TCM) is on the rise. More COVID-19 patients are being treated with Chinese medicine or integrated Western-Chinese medicine, and the role of TCM herbal prescription formulas is expanding. What formulas are they using? What do the properties of these herbs tell us about TCM approaches to the virus?

USE OF CHINESE HERBS TO TREAT THE CORONAVIRUS
With an array of treatment methods and a wealth of experience in its arsenal, Chinese medicine has been used to fight plagues and epidemics for thousands of years. The focus of TCM is not just the virus itself but also symptoms and changes to the body caused by the invasion of the virus. Treatment starts with the patient as a whole, to identify patterns and then dispel sickness and support health.

HERBAL FORMULA USAGE RATES 80% TO 95%
Reports from throughout China indicate TCM formula usage rates of 80% to 95% in confirmed cases of novel coronavirus. One specialist described isolation wards containing a mix of mild, typical, and severe cases of novel coronavirus. Typical cases are characterized as imaging findings in the lungs but the absence of disease progression to respiratory failure. In hospitals, traditional Chinese medicine plays a significant role in regulating diarrhea, constipation, and other gastrointestinal symptoms; in addition, intervention with Chinese medicine may stop the condition from progressing to the severe and critical stages.

WHAT FORMULAS ARE BEING USED? WHAT FORMULAS HAVE BEEN VALIDATED?
清肺排毒汤
The National Health Commission and the State Administration of Traditional Chinese Medicine recommend Qingfei Paidu decoction (清肺排毒汤); clinical observation and data analysis have been performed on the therapeutic efficacy of this classical TCM formula. One formula for Qingfei Paidu decoction appearing on multiple sites, including Baidu, listed 21 ingredients. The top ingredients in terms of quantity are calcium sulfate, Radix bupleuri (common name bupleurum, effective in the treatment of alternating chills and fever; may induce headache or nausea), Poria cocos (efficacy in draining dampness and transforming phlegm; concurrent administration of diuretics contraindicated), Radix dioscoreae (Chinese yam, known to tonify qi and yin of the lungs, spleen, and stomach; may have hypoglycemic effects, use with caution in comorbid hepatobiliary disease).

肺炎一号
Pneumonia Formula No. 1 (肺炎一号), developed by the Chinese Medicine Department at Guangzhou Eighth People's Hospital, and its variations Pneumonia Formula No. 2, Pneumonia Formula No. 3, Pneumonia Formula No. 4, and Pneumonia Formula No. 5 are also in use. Formula No. 1 has achieved favorable clinical results in Guangzhou. Formula No. 1 includes two herbs that clear heat and relieve toxicity, Flos lonicerae (honeysuckle flower) and Fructus forsythiae (forsythia fruit), along with 16 other ingredients.

VARIATIONS
In Chinese medicine, the treatment regimen adopted varies by person. If a patient is in poor physical condition, dispelling disease is not enough, treatment must focus on supporting health. For example, in those with poor appetite it is necessary to focus on spleen health; in patients with damp-heavy qi and thick tongue coating it is necessary to improve the flow of urine. Ear needling (acupuncture) may be used to treat the patient’s psychological state and resolve issues of insomnia, in order to restore the patient’s biological clock.

Just as treatment varies by individual patient, the virus varies by region. This too is a factor in treatment selection. It would not be appropriate to select one uniform formula for the entire nation.

NOT ADVOCATED FOR THE HEALTHY
NOT ADVOCATED FOR THE PREVENTION OF CORONAVIRUS
According to the head of a university of traditional Chinese medicine, the entire populace does not need to take this medicine. Healthy people need to improve resistance in order to avoid getting sick. High-risk populations, including healthcare providers, may take herbal remedies as appropriate.

Practitioners emphasized that these are treatment prescriptions and are not recommended as preventive prescriptions. The general public should not self-administer these prescriptions.
 

ASTRAGALUS
Originating in northeastern China, central Mongolia, and Manchuria, the root of the herbaceous perennial Astragalus membranaceus or 黃芪 (huangqi) is a staple of traditional Chinese medicine. Mild in strength, with a sweet and slightly warm nature and an affinity for the spleen and lungs, astragalus is used as a general tonic to improve endurance, immune resistance, and energy, and to promote blood flow to the surface. ​Astragalus is useful for viral infections and increases the action of interferon alpha-1. It tonifies the spleen, the qi, and the blood. It is indicated for energy deficiency, fatigue, prolapse of rectum, womb, or other organs, profuse sweating due to external “empty” ailments, stubborn abscesses, facial swelling, and diabetes. ​

The use of astragalus root as a general tonic dates to the 28th century BCE and the mythical Chinese ruler Shennong, the legendary author of the first materia medica. Astragalus root has a long, cylindrical taproot, which is internally yellowish in color, but rootlets should be absent. The constituents of astragalus root include triterpenoid saponins, astragalosides I-VIII, astramembranins I and II, isoglavones including formononetin and kumatakenin, and polysaccharides known as astrogaloglucans. There is anecdotal but little clinical evidence that astragalus alone or in combination aids in the treatment of the common cold or impaired immunity. Clinical studies supported by data from over 1000 patients in China confirm the use of astragalus as an immunostimulant for use in colds and upper respiratory infections. It is also used prophylactically. In general, astragalus is well tolerated but should probably be avoided in autoimmune diseases. 

INGREDIENTS
​
Root herbs astragalus, ginseng, eleuthero
Six cups low-salt soup broth
2 tablespoons olive oil
2 cloves garlic
​4 carrots
1 onion
1-2 pounds chicken (optional - for added immunity)
2 cups of chopped greens (spinach, chard, kale)
4 sprigs of parsley
2-3 sprigs of sage
6 slices of ginger root
 
Step 1: Soak root herbs in large pot with soup broth while preparing Steps 2 and 3. 
Step 2: Mince garlic, chop carrots and onion. Sauté  in olive oil over low heat until onions are translucent.
Step 3: Add chicken to above and brown on both sides.
Step 4: Add sautéed carrots, onions, and garlic, as well as chopped greens, sprigs of parsley and sage, slices of ginger, and chicken to soup broth.
Step 5: Simmer soup 3-4 hours, then remove root herbs, ginger slices, and sprigs of parsley and sage. 
Step 6: Season to taste with salt and pepper or soy sauce/hot oil/sesame oil. 

Active ingredients in herbs from traditional Chinese medicine have shown promising efficacy in rehabilitating and protecting the liver after injury from excess acetaminophen. 

Drug-induced liver injury
A significant number of cases of acute liver failure are caused by acetaminophen, also known as paracetamol. Acetaminophen is not toxic to the liver, but its reactive metabolite may cause liver injury. Excess quantities of acetaminophen can deplete the glutathione needed to convert the toxic metabolite NAPQI into a nontoxic metabolic product. Toxins generated during metabolization, mitochondrial dysfunction, inflammatory response, oxidative stress, the release of damage-associated molecular patterns (DAMPs), autophagy, endoplasmic reticulum stress, and microcirculatory dysfunction are among the mechanisms of injury.
 
Limits of pharmacologic drugs 
The chief pharmacologic agent used for the clinical treatment of acetaminophen-induced liver injury is N-acetylcysteine (NAC), but NAC has limited treatment results and its administration is time-sensitive. For optimal results, NAC is administered approximately one hour after oral acetaminophen.
 
Protective effects of traditional Chinese medicine
A number of active ingredients discovered in Chinese herbs suppress liver toxicity. These compounds vary in how they benefit liver injury: they may alleviate liver disease, mitigate damage to liver tissue, reduce the degree of liver injury, and prevent or ameliorate side effects by suppressing the pathways and mechanisms of liver injury. These active ingredients are fast acting, with notable efficacy and few toxic side effects, and include polyphenol compounds, flavonoid compounds, saponins, organic acids, terpenoid compounds, phenylpropanoids, polysaccharides, and alkaloids. 

Polyphenol compounds
Polyphenol compounds are widely present in traditional Chinese herbal remedies. Polyphenols  can affect the production of biomarkers associated with oxidative stress, a major cause of hepatotoxicity induced by acetaminophen overdose. In the research of Hasanein (2017), rosmarinic acid (found in basil, rosemary, and lemon balm) produced remarkable hepatoprotective effects by inhibiting CYP2E1 activity in the liver and lipid peroxidation.
 
Flavonoid compounds 
The protective effects of flavonoid compounds include the effects of ginseng anthocyanins on acetaminophen-induced hepatotoxicity (Qi 2017) and hyperoside which can hinder the formation of toxic intermediates and boost acetaminophen detoxification in the liver (Xie 2016). Fu (2018)  discovered that α-mangostin notably suppressed acetaminophen-induced oxidative stress; α-mangostin, a xanthone derivative found in the pericarp of mangosteen fruit, also reduced  inflammatory response through the anti-inflammatory mechanism mediated by the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Lu (2018) demonstrated that licochalcone A isolated from the root of Glycyrrhiza glabra had a protective effect on acetaminophen-induced liver injury through the Nrf2-mediated oxidative stress defense mechanism.
 
Saponins
Xu (2017) discovered that the antioxidant, anti-apoptotic, and anti-inflammatory actions of saponins (ginsenosides) had a protective effect on acetaminophen-induced liver injury in mice. Hu (2017) found that ginsenoside Rk1 pretreatment of acetaminophen-induced liver injury in mice significantly lowered levels of the lipid peroxidation product MDA. By increasing Bcl-2 and reducing Bax protein expression, ginsenoside Rk1 impeded activation of the apoptosis pathway. In Ning (2018), ginsenoside Rg1 prevented acetaminophen-induced liver injury through in vivo and in vitro activation of the Nrf2 signaling pathway. Leng (2018) proved that Platycodon grandiflorum saponins had pronounced protective effects on acetaminophen-induced liver injury through the NF-κB and AMPK/PI3K/Akt signaling pathways.

Organic acids 
In Heidari (2016), taurine effectively relieved acetaminophen-induced liver injury and its complications in mice. Jiang (2017) established that, by reducing thiobarbituric acid reactive substances (TBARS) which form as a byproduct of lipid peroxidation and reducing iNOS, COX-2, TNF-2, IL-12, and IL-6, the acids from Potentilla chinensis inhibited inflammation and oxidative stress to alleviate acetaminophen-induced liver injury. Cha (2018) discovered that p-coumaric acid (an abundant isomer of hydroxycinnamic acid widely found in fruits and vegetables) suppressed acetaminophen-induced hepatocyte apoptosis by modulating the MAPK signaling axis in a reactive oxygen species (ROS)-dependent manner and by alleviating response and inflammation from ROS-mediated DNA damage . 

Terpenoid compounds  
In Uchida (2017), compounds in the essential oil of Cymbopogon citratus (lemongrass) hindered neutrophil migration and antioxidant activity in mice with acetaminophen-induced liver injury, thus relieving hepatotoxicity. The research of Zhang (2017) proved that by inhibiting the TNF-α-mediated JNK signaling pathway and the phosphorylation ERK and P38 pathways, pretreatment with astaxanthin (natural sources include shrimp, algae, yeast, and salmon) reduced hepatocellular necrosis, blocked the formation of ROS, prevented oxidative stress, and diminished cellular apoptosis, protecting the liver and alleviating drug-induced liver injury. In Yoshioka  (2017), kamebakaurin (isolated from Rabdosia excisa) improved hepatotoxicity from acetaminophen overdose by inhibiting lipid peroxidation and inflammatory response in mice. 

Phenylpropanoids 
Fructus schisandrae (schisandra fruit) is widely used for liver protection in traditional Chinese medicine and the research of Jiang (2015) proved that lignan components in Fructus schisandrae ameliorated acetaminophen-induced liver injury by inhibiting acetaminophen's CYP-mediated biologic and metabolic pathways. Furthermore, in Jiang (2016) schisandrin B increased liver detoxification and antioxidation by activating the Nrf2/ARE pathway and regulating the Nrf2 target gene, reflecting its hepatoprotective effects. Yan (2018) demonstrated that, by activating sustained autophagy, glycycoumarin relieved acetaminophen-induced oxidative stress and thus prevented liver injury. 

Polysaccharides 
Lin (2018) found that polysaccharides of Dendrobium officinale played a hepatoprotective role by lowering oxidative stress and activating the Nrf2-Keap1 signaling pathway. And in Zhao (2018) the anti-inflammatory effects of polysaccharides of Coreopsis tinctoria regulated the expression of apoptosis-related proteins such as Bax and Bcl-2 to prevent acetaminophen-induced hepatotoxicity. Wu (2018) proved that polysaccharides of Poria cocos played a protective role against acetaminophen-induced liver injury in mice and their molecular mechanism was associated with suppression of the hepatocellular inflammatory response and apoptosis. 

Alkaloids
Li (2014) discovered hepatoprotective effects of berberine on liver fibrosis via activation of AMP-activated protein kinase; and Zhao (2018) found that berberine had pronounced prophylactic effects on acetaminophen-induced hepatotoxicity by inhibiting oxidative stress, hepatocellular necrosis, and inflammatory response. In Park (2016), the alkaloids of Aconitum carmichaelii  protected the organism against acetaminophen-induced injury by suppressing mitochondrial dysfunction and defending liver cells, although the herb is toxic when taken in excess. In 2018, a trial by Bian confirmed that ligustrazine (an alkaloid isolated from Ligusticum wallichii) improved acetaminophen-induced liver injury in mice by regulating the NF-κF and MAPK signal transduction pathways. 

Other compounds  
In Wangkheirakpam (2018), Auricularia delicata demonstrated antimicrobial, antioxidant, and protective effects on acetaminophen-induced liver injury in rats. In Guo (2018), Rhizoma pinelliae  extract regulated bile acid transporter protein in mice with acetaminophen-induced liver injury. By activating Nrf2 and inhibiting NF-κB signal transduction, Garcinia cambogia extract played a protective role in acetaminophen-induced liver injury in mice (Ibrahim 2018). The antioxidant, anti-inflammatory, and anti-apoptotic actions of tannic acid demonstrated significant hepatoprotective effects on acetaminophen-induced hepatotoxicity in the work of Zhang (2017).  

Acetaminophen is a leading cause of drug-induced liver injury and recent research findings indicate that the use of active ingredients from traditional Chinese medicinal herbs might ameliorate such injury. Research on mechanisms of liver injury and the means by which such compounds protect against and alleviate injury holds promise for future antidotes to drug-induced liver injury.