SHUANGHUANGLIAN:
Potent Anti-Infection Combination of Lonicera, Forsythia, and Scute
Shuanghuanglian (SHL for short) is a modern formula that was devised in the 1960s to treat a variety of infections. It is comprised of the alcohol-water extracts of three herbs: lonicera (shuanghua, often called jinyinhua), scute (huangqin), and forsythia (lianqiao). The joining of forsythia and lonicera in a formulation represents a long tradition of Chinese herb prescribing for treatment of infections. The addition of scute in this small formula represents one of the newer developments of Chinese medicine, especially based on research involving its main active constituent, the flavonoid baicalin (see Appendix). Typically, in the ancient style formulas, lonicera and forsythia would be combined with various wind dispelling, surface relieving herbs, as is done in the well-known Yin Qiao San; in this case, they are combined with the heat clearing herb scute.
One of the early preparations of the SHL was a tablet made of equal proportions of the extracts of each herb. This was used to treat leptospirosis, a disorder caused by a spirochete bacteria, related to the organism that causes Lyme disease. Leptospirosis causes initial symptoms of fever and chills, headache, and muscle ache (especially in the shoulders); these are consistent with "flu-like" symptoms described for the onset of many acute infections. In a 1971 report, the formula was described as being made in 500 mg tablets derived from 3.7 grams of the crude herbs, and being administered in doses of 10-15 tablets (thus, equivalent to the extract of 37-55 grams of herbs) every 6 hours (1), a very high dosage.
SHL was then developed in an injection form, and adopted to treatment of respiratory tract infections. In a pharmacology study, it was confirmed that the injection could inhibit the effects of respiratory syncytial virus (2). This virus is one cause of the common cold, and it is a frequent cause of serious lung infections that affect children. The use of the injection form of SHL for treating infectious diseases of many types became a common practice in China. It appears to be a safe treatment, though there have been rare reports of allergic reaction to it, similar in frequency and severity to those observed in injection forms of several other herbs. One hospital reported using the injection for over 2,000 cases of viral and bacterial infections during a four-year period, out of which two cases of anaphylactic response arose, one in a patient with bronchitis and another with encephalitis (3); both developed pruritis minutes after the intravenous injection (and recovered with palliative treatment). The intraprostatic injection has been used clinically in treatment of chronic prostatitis, with results somewhat better than those attained using the antibiotic Cyprofloxacin; of 30 patients receiving SHL, one developed a skin rash, and there were four instances of temporary hematuria during treatment (4).
Shuanghuanglian is currently a proprietary product of the Harbin Pharmaceutical Group, which produces a powder for making the injection form, an oral liquid, and an aerosol. Studies were conducted in Harbin to determine the best extraction procedures. The active components that could serve as quality markers were identified: baicalin in scute, chlorogenic acid in lonicera, and phillyrin in forsythia (see Figure 1). At the First Affiliated Hospital of Harbin Medical University a common spectrophotometry method was shown to be an easy and effective way to monitor the ingredients in the injections (5). Additional research at the same hospital showed that baicalin would be extracted rapidly and completely in an 85% alcohol solution (6).
To evaluate the best delivery method for the herbs, SHL was administered to more than 200 patients with acute respiratory disease at the same hospital. Syncytial virus accounted for nearly two-thirds of the cases and adenovirus was the likely cause in nearly one-third of cases. A treatment course of 7 days was used, and patients were divided into three groups: one using the aerosol (which was the newer preparation being evaluated), another using the injection, and the third using the oral liquid. Significant improvement, such as reduction of fever, was noted in three days for many patients. All three methods of administration were apparently effective (7). At the Second Affiliated Hospital of Xi'an Medical University, SHL injection was applied to treating restricted ventilation (atelectasis, inability to expand the lungs fully) due to pulmonary tuberculosis; it was reported that the herb formula performed as well as a modern medical therapy based on multiple antibiotics (8) and that it could treat post-chemotherapy pneumonia in lung cancer patients as a result of its ability to normalize leukocyte counts (9). Clinical and laboratory studies in Harbin showed that SHL could promote natural killer cell activity and production of interferon, displaying broad antibacterial and antiviral actions (10). A follow-up laboratory study in Denmark showed that SHL could inhibit Pseudomonas infections by boosting immune attack against these organisms that are of particular concern for patients with cystic fibrosis (11).
Recently, Shuanghuanglian has been applied successfully to treatment of Coxsackie B3, which is the virus responsible for causing most cases of viral myocarditis. Pharmacology studies showed that SHL plus interferon could strongly inhibit the virus (12). SHL has been used as an adjunct to conventional therapy for treating Coxsackie myocarditis in children (13), with the claim that the addition of the herbs could markedly improve the effect of treatment particularly in respect to relieving symptoms and signs of the disease and improving immune functions. The formula was among those recommended by an expert panel in China for treatment of SARS, the pneumonia-like viral infection (14).
The general indications for SHL, according to the Harbin factory, are "relieving the exterior syndrome, clearing away heat and toxic material," and its indications are "treatment of fever, cough, and sore throat that arise from wind-heat syndrome." It is said to have "a good action in treating upper respiratory tract infection, tonsillitis, laryngopharyngitis, pneumonia, acute enteritis, viral dysentery, etc., when caused by virus or bacterial infection."
An American patent for a version of Shuanghuanglian was submitted in 2002 by a group in Shanghai (15). The formula is designed with lonicera, forsythia, and scute in a ratio of 2:1:1, with each herb extracted individually, using a process that preserves the essential oils, such as pinene and linalool. The inventors claim, based on pharmacology studies and clinical use in China, that this formulation "possesses antiviral effects, namely, inhibition of influenza virus, parainfluenza virus, herpes I virus and herpes II virus."
   Figure 1. Baicalin (top), chlorogenic acid (middle), and phillyrin (bottom), marker compounds from scute, lonicera, and forsythia, respectively. Baicalin is known to be the main active component of scute with antiviral activity; chlorogenic acid and phillyrin are active components-but may not be the key elements-in lonicera and forsythia, respectively. |  Figure 2. Portion of box of Shuanghuanglian Oral Liquid in glass vials. |
September 2003
The active constituents of scute have been identified as a group of similar flavonoids, dominated by baicalin, which makes up 12-17% of the root. A typical hot water extraction of scute yields about 26% baicalin, 10% wogonin glucuronide, 2% baicalein, and 0.2% wogonin. Commercial extracts, which usually involve alcohol-water extraction media, are still dominated by baicalin, but have a relatively higher yield of the alcohol-soluble aglycones (molecules without attached glucose) baicalein and wogonin. It is likely that baicalin is metabolized in the body to baicalein either by the effects of intestinal bacteria or during passage through the liver.
Baicalin is being investigated for numerous potential therapeutic applications based on: inhibition of cancer cell proliferation; protecting bone marrow and promoting hemopoiesis during cancer therapies and protecting the intestines from adverse chemotherapy effects; and inhibition of infections (especially respiratory tract viral infections). The following are also pharmacological properties of baicalin: anti-inflammatory (e.g., for asthma or atopic dermatitis), blood pressure lowering, sedative, bile-secreting, and both neuroprotective and hepatoprotective effect. With regard to the latter, both scute and isolated baicalin are widely used in China for treatment of viral hepatitis and are believed to have potent protective action against liver fibrosis caused by viral activity.
In China, baicalin is prepared in injection form for rapid action. The dosage is 60-120 mg of baicalin intramuscularly, 1-2 times per day; or a daily IV drip containing 500-1200 mg may be utilized for more severe diseases. Orally, scute is given in decoction, with dosages of about 6-12 grams per day, yielding baicalin in amounts of 1-2 grams. Baicalin tablets, and highly purified baicalin extracts in powder form (with 95% flavonoid content) are used at doses of 1-2 grams per day. These treatments are usually for acute syndromes; lower doses of baicalin in complex formulas would be utilized for prolonged therapy.
ITM has introduced two formulations based on baicalin in the White Tiger series. One is Baicalcumin, which provides 500 mg of the 95% baicalin extract in four tablets (recommended dosing: up to 8 tablets for short term therapy) and the other is Myrolea-B, which is a derivative of Shuanghuanglian; it provides 800 mg of the same baicalin extract in four tablets (recommended dosing: up to 6 tablets for short term therapy). Both formulations may be used as part of the treatment for viral infections and/or inflammatory disorders.
