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Chinese Herbal Therapy Efficacious Against Influenza

Amesh A. Adalja, MD, FACP, August 19, 2011

Traditional Chinese medicines, many of which have not been tested in rigorous clinical trials, are used for a variety of ailments, including infectious diseases. Although some of these substances do not pass muster when studied appropriately, some do, including the first line anti-malarial, artemesinin (qinghaosu). Another traditional Chinese medication, maxingshigan-yinqiaosan (MY), was used during the 2009 H1N1 influenza pandemic in rural areas where drugs like oseltamivir were scarce. Wang and colleagues have now published the results of their prospective, non-blinded, randomized controlled trial comparing oseltamivir with MY for treatment of H1N1 influenza.1

MY’s mechanism of action is its ability to regulate T-cell populations and direct viral inhibitory effects, which include interfering with adsorption, inhibiting proliferation, and protecting cells from infection. In contrast, neuraminidase inhibitors inhibit the viral neuraminidase enzyme preventing separation from a host cell, while adamantanes block the action of the viral M2 protein, preventing viral uncoating.

MY Compared with Oseltamivir

The study included 410 subjects aged 15 or above who presented within 72 hours of onset of flu-like symptoms and had PCR confirmation of H1N1 influenza A infection. Those who were immunosuppressed, pregnant, or had taken medicinal herbs or antivirals were excluded, as were those with radiographic evidence of pneumonia.

The formulation of MY used in the study was composed of 12 herbs, detailed in Table 1. All of the herbs were obtained from a single supplier and were tested for heavy metals, microbial contamination, and pesticides. MY was administered as a 200 mL liquid 4x daily for 5 days. Oseltamivir was administered  at a dose of 75 mg 2x daily for 5 days.

Table I: Composition of maxingshigan-yinqiaoson

Zhimahuang  (honey-fried Herba Ephedrae)
Chaoxingren (stir-baked Semen Armeniacae Amarum)
Zhimu (Rhizomua Anemarrhenae)
Lianqiao (Fructus Forsythiae)
Qinghao (Herba Aremisiae Annuae)
Bohe (Fructus Forsythiae)
Shigao (Gypsum Fibrosum)
Zhebeimu (Bulbus Fritillariae Thunbergii)
Yinhua (Flos Lonicerae Japonicae)
Niubangzi (Fructus Arctii Tosum)
Huangqin (Radix Scutellariae)
Gancao (Radix Et Rhizoma Glycyrrhizae)

The primary end point was time to fever resolution. Secondary outcomes were the proportion of patients who became afebrile, improvement in symptom scores, side effects, and incidence of influenza complications. PCR quantification of oropharyngeal viral titers was performed daily on 148 participants.

The study subjects were divided into 4 groups: placebo, oseltamivir, MY, and oseltamivir + MY.  Antibacterial therapy was more commonly used in the control arm while acetaminophen use was similar across the 4 groups.

Herbal Formulation Effective at Ameliorating Fever

Several important clinical findings were revealed upon analysis of results:

  • Time to fever resolution was reduced in all 3 treatment arms (20 hours in the oseltamivir group; 16 hours in the MY group; 15 hours in the combination group) as compared with the placebo group (26 hours). The differences among the treatment groups were not statistically significant, though all were statistically significant when compared with placebo.
  • Symptoms scores were not different across the study groups.
  • Of those with viral load measurements, all groups, including the control, showed significant viral load decreases over the 5 days of the study. There was not a statistically significant difference among the groups.
  • No significant side effects were reported, and no differences in complications were observed.

Clinical Implications for U.S. Clinicians

While the study results are fascinating and encouraging, this study had its limitations, and more trials  are needed to fully understand  the benefits of MY. Because MY is a combination of 12 different herbs, the component parts have to be studied separately in order to isolate the most essential components. This is especially important because MY contains ephedra compounds, and their use is controversial. Also to be determined is whether MY contains anti-pyretic compounds, which may explain its effect. The study’s other limitations are that it was not blinded, pharmocodynamic/pharmacokinetic data were not acquired, patients with pneumonia were excluded, and only a subgroup of study participants had PCR viral load measurements.  A larger more robust study would address those concerns. Moreover, studies powered to address the rate of influenza complications (death, hospitalization, pneumonia, etc.) are needed. Nevertheless, with mounting concern for potential widespread resistance to influenza antivirals, a substance with an alternate mechanism of action would be a welcome addition to the influenza armamentarium.

Reference

Wang C, Cao B, Liu Q, et al. Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza. Ann Intern Med 2011; 155:217-225.