TCM Pharmacology of Influenza by M.M. Van Benschoten, OMD

TCM Pharmacology of Influenza by M.M. Van Benschoten, OMD

Influenza is a seasonal viral disease that causes illness, hospitalizations, and deaths. From 1977 to 2006 annual flu related deaths in the U.S. varied from 3,000 to 49,000 persons. Death rates from H3N2 viruses are double compared to H3 and type B viruses. Up to 8.5% of pneumonia related and 2.1% of cardiorespiratory deaths are due to influenza. The incubation period for influenza viruses lasts from 1 to 4 days with transmission through direct droplet spread or hand contact.

There are 12 different options for influenza vaccines, including trivalent, quadrivalent, injectable, and nasal mist. Flu vaccine is recommended for all persons over six months of age. Contraindications include egg allergy and previous adverse reactions to flu vaccines. Epidemics of influenza that occur every 3-5 years may infect up to 10% of the population. Vaccine effectiveness may vary from 15-70% in a given year due to constant mutation of the virus that generates antigenic drift.
Specific herbal medicines can assist in improving immune responses to vaccines.

Asparagus (tian men dong), astragalus (huang qi), epimedium (yin yang huo), ganoderma (ling zhi), ginseng (ren shen), isatis root (ban lan gen), and polygala (yuan zhi) increase vaccine titers, IgA antibody production, NK cell activation, and phagocytosis. Adding yin tonics ligustrum (nu zhen zi) and lycium fruit can improve resistance against effects of seasonal air travel and respiratory illness.

Symptoms of influenza closely resemble syndromes of cold damage from the Shang Han Lun. Chai Hu Gui Zi Tang has pharmacological actions that address the root and branch of acute viral infection, alleviating fever, pain, and cough. Influenza complicated by secondary bacterial infections responds best to formulas derived from Wen Bing Lun warm illness patterns that include clear heat toxin herbs with antibacterial effects, such as Yin Qiao San combined with Lung wind heat phlegm expelling formulas such as Qing Fei Tang or Zhi Sou Tang. Modifying classical by considering antimicrobial and immune regulatory effects of additions such as houttuynia (yu xing cao) or ganoderma (ling zhi) produces superior clinical responses.

Patients with preexisting asthma or cardiovascular disease may have exacerbations of their condition during an episode of influenza. Bronchodilating, antiarrhythmic, and cardioprotective herbs with antiviral and antibacterial effects should be included in these cases. Frequency of dose should be every two hours for the first 24 to 48 hours until significant improvement and reduction of symptoms are achieved, followed by four times daily after meals and at bedtime. As the antimicrobial effects of herbal medicines are 100 fold weaker than pharmaceutical antibiotics, a course of treatment must be at least 30 to 90 days. Formula ingredients should be changed every four to six weeks to avoid resistance and address new symptoms.

Analgesic/Antiinfluenza/Antipyretic - bupleurum (chai hu), cinnamon twig (gui zhi), licorice (gan cao), moutan (mu dan pi), perilla leaf (zi su ye), polygonum cuspidatum (hu zhang)

Antihistamine/Antiinfluenza - camellia (lu cha), moutan (mu dan pi), perilla leaf (zi su ye), prunella (xia gu cao)

Antiinfluenza/Antistreptococcus/Antitussive - bupleurum (chai hu), houttuynia (yu xing cao), licorice (gan cao), polygonum cuspidatum (hu zhang)

Antiinfluenza/Antimycoplasma - houttuynia (yu xing cao), isatis root (ban lan gen), phellodendron (huang bai)

Antiinfluenza/Bronchodilator - houttuynia (yu xing cao), perilla leaf (zi su ye), pyrossia (shi wei), schizandra (wu wei zi)

Antiinfluenza/Antistreptococcus - andrographis (chuan xin lian), chrysanthemum indicum (ye ju hua), coptis (huang lian), elsholtzia (xiang ru), forsythia (lian qiao), isatis root (ban lan gen), lonicera (jin yin hua), mahonia (gong lao ye), moutan (mu dan pi), paeony red (chi shao), peucedanum (qian hu), phellodendron (huang bai), prunella (xia gu cao), scute (huang qin), terminalia (he zi)

Improving immune responses to influenza requires upregulation of interferon and natural killer cell functions. In some cases, viral infections cause low white blood cell and/or platelet counts, which must be addressed by modifications that enhance bone marrow function.

Antiinfluenza/Interferon inducer - coptis (huang lian), ganoderma (ling zhi), licorice (gan cao), lonicera (jin yin hua), schizandra (wu wei zi)

Antiinfluenza/Leukocyte count increase - ganoderma (ling zhi), polygonum cuspidatum (hu zhang), pyrrosia (shi wei), schizandra (wu wei zi)

Antiinfluenza/NK Cell activating - bupleurum (chai hu), ganoderma (ling zhi), licorice (gan cao), scute (huang qin)

Leukocyte count increase/Platelet elevating - angelica sinensis (dang gui), ciboteum (gou ji), cistanche (rou cong rong), cornus (shan zhu yu), longan (long yan rou), notoginseng (san qi), rehmannia raw (sheng di huang)

NK cell activating/Platelet elevating - cordyceps (dong chong xia cao), jujube (da zao)

Cardiac complications of influenza are common, and patients with preexisting coronary artery disease or arrhythmias are especially at risk. Sheng Mai San modified by replacing ginseng with crataegus may be combined with antiinfluenza herbs to address reduced cardiac output and cough due to respiratory infection especially after jet fuel exposure due to air travel.

Antiarrhythmic/Antiinfluenza - bupleurum (chia hu), cinnamon twig (gui zhi), coptis (huang lian), eleutherococcus (ci wu jia), licorice (gan cao), paeony red (chi shao)

Antiinfluenza/Cardioprotective - gambir (gou teng), hibiscus (fu rong), peucedanum (qian hu), rhodiola (hong jing tian), schizandra (wu wei zi), terminalia (he zi)

Antiinfluenza/Coronary vasodilator - coptis (huang lian), ganoderma (ling zhi), polygonum cuspidatum (hu zhang)

Post influenza fatigue can occur due to residual viral and bacterial infection, antimitochondrial immune responses, or reactivation of herpes viruses, including CMV, EBV, and HHV6. Antiviral herbs with protective effects on mitochondrial function can assist in the restoration of normal energy and activity levels. Antibiotic resistance can be due to biofilm formation in which colonies of bacteria communicate in a process known as quorum sensing and synthesize extracellular polymers that protect the bacteria from destruction.

Antiinfluenza/Mitochondrial protection - belamcanda (she gan), hibiscus (fu rong), prunella (xia gu cao), rhodiola (hong jing tian), schizandra (wu wei zi), scute (huang qin)

Antiherpesvirus/Antiinfluenza - belamcanda (she gan), ganoderma (ling zhi), houttuynia (yu xing cao), lonicera (jin yin hua), paeony red (chi shao), polygonum cuspidatum (hu zhang), prunella (xia gu cao), pyrossia (shi wei), sargassum (hai zao), terminalia (he zi)

Antibiofilm/Antiinfluenza - camellia (lu cha), forsythia (lian qiao), gardenia (shan zhi zi), mume (wu mei), polygonum cuspidatum (hu zhang), scute (huang qin)

When immunizations fail to provide complete protection from influenza, and antibiotic therapy results in partial resolution of symptoms, Chinese herbal medicines can assist recovery and clearance of pathogenic factors. Classical formulas from the Shang Han Lun, Wen Bing Lun, and modern sources modified with additions based on specific pharmacological actions and immune regulation results in optimum clinical responses.

Case Study

Ms. A is twenty three year old female with a two month history of ear and sinus infection treated with Amoxicillin for ten days. Shortness of breath and GI distress prompted a return to Urgent Care where antihistamine, steroids, and Keflex were prescribed. Lab work was negative for mononucleosis with a low platelet count, chest Xray indicated viral pneumonia. Increased shortness of breath after returning to work for one week resulted in a repeat chest Xray and CT scan of spleen, both negative, so she was referred to a hematologist for further investigation of low platelets. A repeat lab test one week later indicated platelets increasing from 95,000 to 120,000. She continues to have fatigue, shortness of breath, sinus, ear, and chest pain.

Prescription 1
Aster (zi wan), ganoderma (ling zhi), licorice (gan cao), and phellodendron (huang bai) have antiinfluenza and antitussive effects. Agrimonia (xian he cao), cistanche (rou cong rong), sophora flower (huai hua), rehmannia raw (sheng di huang), ligustrum (nu zhen zi) increase platelet counts and promote phagocytosis. Lycium fruit (gou ji zi), scrophularia (yuan shen), and perilla leaf (zi su ye) increase cytotoxic T cells and boost interferon production.

Verbena (ma bian cao), lippia (ya she huang), and typha (pu huang) are added to the above formula ten days later to address increased sinus and ear pain and to reinforce the platelet count.

One week later migrating chest pain and increased fatigue indicate the viral and bacterial infection has mutated and become resistant to the previous formula. The prescription is changed to address inflammation of the pleura and to restore mitochondrial function.

Prescription 2
Gardenia (shan zhi zi), paeony red (chi shao), arctium (niu bang zi), eupatorium chinensis (liu yue xue) are antiinfluenza and treat pleurisy. Belamcanda (she gan) and lonicera (jin yin hua) are antiinfluenza, antistreptococcus, and address sore throat and ear pain. Schizandra (wu wei zi) and rhodiola (hong jing tian) protect mitochondrial function, reduce fatigue, and increase NK cell and interferon production.

The Shang Han Lun recommends Zhi Shi Zhi Zi Tang, Citrus and Gardenia formula for post illness relapses. Here the formula is modified by removing Zhi Shi, substituting antiinfluenza species from Yin Qiao San that clear heat toxins with additional tonics to support Zheng qi.

After prescription 2, chest pain are reduced and breathing is easier. Persistent pain in posterior ribs and left shoulder is accompanied by continued fatigue. Retention of phlegm in the channels and collaterals causing qi and blood deficiency requires continued administration of antiinfluenza herbs with antiinflammatory and cardiotonic effects.

Prescription 3
Polygonatum root (huang jing) and scute (huang qin) are antiinfluenza, increase T cells, and inhibit COX 2 to alleviate inflammation. Acanthopanax senticosus (ci wu jia) has antiinfluenza and cardiotonic effects. Cnidium (chuan xiong), poria (fu ling), and gynostemma (jiao gu lan) are cardiotonic and improve coronary arterial circulation to address fatigue.

This case study reflects the contemporary clinical realities of TCM practice. Patients begin treatment after extensive biomedical and pharmaceutical interventions with retention of multidrug resistant pathogens. Combining classical formulations with pharmacological insights can help to restore health after seasonal influenza and secondary bacterial infections.

references
http://www.cdc.gov/flu/weekly/ [1]
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6207a1.htm?s_cid=rr6207a1_w#Tab1 [2]
http://en.wikipedia.org/wiki/Biofilm [3]

Effectiveness of an adjuvanted monovalent vaccine against the 2009 pandemic strain of influenza A(H1N1)v, in Stockholm County, Sweden. Clin Infect Dis. 2011 May;52(10):1203-11. doi: 10.1093/cid/cir182. Ortqvist A, Berggren I, Insulander M, de Jong B, Svenungsson B. Department of Communicable Diseases Control and Prevention, Stockholm County, Sweden. ake.ortqvist@sll.se [4]

Influenza vaccination and risk of hospitalization among adults with laboratory confirmed influenza illness. Vaccine. 2013 Nov 26. pii: S0264-410X(13)01594-6. doi: 10.1016/j.vaccine.2013.11.060. [Epub ahead of print] McLean HQ, Meece JK, Belongia EA. Marshfield Clinic Research Foundation, Marshfield, WI, USA. Electronic address: mclean.huong@mcrf.mfldclin.edu [5].