Liver-Assist, Antiviral Research Review

Several years ago I began to research a Chinese herbal formula that I had been using successfully to lower elevated liver enzymes for my hepatitis patients. I was curious to find out if there were any studies backing up my experiences and good results. It was late at night and I was typing in the Chinese names of the formula only to find that the results coming back from cyberspace were slim pickings indeed! I then tried the English names of the formula, only to find slim pickings again. On a whim, I then tried using the Japanese names; this time, to my astonishment, I found more than 120 papers and human studies originating mainly out of research done in Japan.

Over ninety percent of chronic hepatitis sufferers in Japan, some 1.5 million people, are taking a safe, natural medicine recommended by conventional physicians and proven effective in hundreds of papers and studies. To my knowledge, the community of Traditional Chinese Medical practitioners in the West knew nothing of this amazing research. Here was the treasure chest of information I had been hoping to find. After spending weeks reading the research, I found the results astonishing. Most interesting to me were two double-blind, five-year studies and one seven-year study. It appeared that herbal protection truly was available to prevent the progression of hepatitis into cirrhosis and cirrhosis into liver cancer. One study showed the herbal treatment was 50% more effective than the conventional control treatment. That we in the West knew nothing about it -- that this herbal protection was available and not being used to prevent suffering and progression of chronic hepatitis -- was both disappointing and shocking. This was my motivation to try to get this information in the hands of as many practitioners and patients as possible. I wrote an article that was published in several magazines, journals and physician’s newsletters.



Hepatoprotective, antiproliferative and immunostimulant

However, this formula and article were only the first step. Since that time, I have researched and worked with hundreds of hepatitis sufferers and have developed a larger, more comprehensive and detailed protocol of how to work with the different stages of hepatitis. Unfortunately, herbal medicine is still relatively unknown and under-utilized in America. This can create a barrier against its use and recommendation by the conventional medical services. The formulation comprised of seven Chinese herbs will be studied by Memorial Sloan-Kettering Cancer Center entitled "Sho-Saiko-To after Ablation for Non-Resectable Hepatocellular Carcinoma: A Phase II Trial with Historical Control." Hepatocellular carcinoma
(HCC) has a poor prognosis, especially when surgical resection is contraindicated. Previous Japanese research (on Sho-saiko-to has demonstrated its hepatoprotective, antiproliferative and immunostimulant effects in vitro. Moreover, in a randomized trial, cirrhotic patients receiving sho-saiko-to had a lower incidence of developing HCC and greater survival compared to placebo. There is sufficient clinical pharmacokinetic and laboratory data on Shosaiko- to, especially with respect to dosage, to warrant a Phase II trial. Sho-saikoto^s in-vitro, in-vivo and clinical activity seems to be primarily to inhibit tumor proliferation rather than to kill tumor cells. The patients, approximately 80 in number, will be treated over a two-year period, and then their progress followed for another year. This herbal medicine has massive clinical usage, with I.5 million hepatitis patients in Japan protecting themselves with the sho-saiko-to formula.


This herbal formula, studied by scientists in modern Japan, is from Ancient China. The formula name in english is “Minor Bupleurum,” first reported in the Shan Han Lun, “Discussion of Cold Induced Disorders,” written between 300 B.C. and 300 A.D. In China, one southern province of Guangdong is known to have one of the highest rates of hepatitis B infection in the world. Blood samples taken from patients during hospital visits indicate 10 million people, or 75% of the population of this Province, have Hepatitis B, according to figures collected by Luo Huiming of the Guangdong Disease Control and Prevention Center. Luo also said, in an interview posted on, that “earlier surveys have shown that two-thirds of China^s 1.26 billion people are infected with hepatitis”. If this is true, there is a staggering possibility that 420 million people have the virus in China. This compares with one in 20 Americans. China has the largest hepatitis epidemic in the world. Because of tradition, as well as cost concerns, China relies heavily on herbal medicine to treat this epidemic. Herbal medicine plays a significant role in the Chinese healthcare system; the experience gathered there about formulas and individual herbs is invaluable to the rest of the world. I have relied heavily on this research during the development of my herbal strategies and formulas for hepatitis.

This natural medical and herbal approach is still unknown in the West to the millions suffering viral hepatitis in the United States. Studies have shown that the chief herbal formula used to treat hepatitis in China and Japan, sho-saiko-to, or Minor Bupleurum, strengthens the immune system, reduces viral loads, and can stop the progression of chronic viral hepatitis into serious liver damage, cirrhosis and even liver cancer. I hope you will suspend any bias you may have and read through the information contained in this article with an open mind. Then decide if you can use this herbal protection in your Veterinary practice.


According to the Hepatitis Foundation International, the Hepatitis B and C viruses have infected 520 million people globally, 6 million in the U.S. alone, and most do not know they are infected. Hepatitis is not a single disease but is actually a term meaning "inflammation of the liver." This disease has been plaguing human beings for millions or years. There are reports describing hepatitis in the literature of traditional Chinese medicine going back thousands of years. Hippocrates noted occurrences of jaundice epidemics around battlefields with the concentrated populations of soldiers
and their attending unhygienic conditions. During the American Civil War, at least
70,000 soldiers fell ill with infectious hepatitis. Today science has identified an entire alphabet soup" of hepatitis viruses: Hepatitis A, B, C, D, E, F and G.

Other viruses, (such as Cytomegalovirus and Epstein Barr) can cause hepatitis and can also activate sleeping hepatitis viruses lying dormant in liver cells. Hepatitis can also be chemically induced.

Hepatitis A (HAV), once known as infectious hepatitis, is short-term and selflimiting. HAV is the least dangerous of the hepatitis viruses, with an incubation period of 2 to 6 weeks. HAV is spread by direct contact from an infected person or through fecal infected food or water. It can be stopped with injections of gamma globulin.

Hepatitis B (HBV) is more serious and, like HCV, is known as the "silent killer." It was clinically distinguished from (HAV) in the 1930^s, and has an incubation period of 6 weeks to 6 months. Fortunately there is a vaccination for HBV. Classified as a venereal disease, it can be passed by seminal fluid, vaginal secretions, contaminated blood, and blood products or via tiny cuts and abrasions, using an infected needle or even toothbrush, body piercing, dental work or childbirth. Before routine testing of the U.S. blood supply in the 1990^s, HBV infected and killed thousands of people. It is 100 times more infectious than HIV, and every year 5,000 Americans die from cirrhosis and 1,000 from liver cancer caused by HBV. Some Symptoms of HVB according to CDC:
· eyes or skin may turn yellow
· may lose their appetite
· may have nausea. vomiting, fever, stomach or joint pain
· may feel extremely tired and not be able to work for weeks or months

Hepatitis C (HCV) is transmitted through tainted blood, sharing of needles, personal care items or transplant of infected tissue. It is not easily spread through sex. It is responsible for up to 4 million infections nationwide with 30,000 new cases and 8,000 to 10,000 deaths reported each year. HCV infection is expected to triple in the next 10 to 20 years. It is estimated that 75% to 85% of those infected will be infected for life, and 70% may develop chronic liver disease. According to the Center for Disease Control, 15% will go on to develop cirrhosis (a scarring of the liver), and 20% to 30% of those will develop liver cancer. Of every 100 persons infected with HCV about:  75 to 85 persons may develop long-term infection (if 100%=80 average then 70 persons may develop chronic liver disease (if 100% =80, then of those
infected 87.5% go on to chronic liver disease) 15 persons may over a period of 20 to 30 years develop cirrhosis ( If 100% 15
Less than 3% of persons may die from the consequences of long term
infection (liver cancer or cirrhosis) over 20-30 years

HCV is called the hidden epidemic because it can go undetected for many years. When symptoms do appear, often the damage is already done. It could cost up to $26 billion nationwide and is the leading cause of liver transplants. The mortality rate is rapidly rising because many people were originally infected ten, twenty or even thirty years ago, mainly through transfusions before blood supply screening started in 1992. Early detection is very important. Although 15% are able to successfully fight off the virus, about 85% of those infected with HCV go on to develop liver disease.

Hepatitis D (HDV) only thrives in the presence of HBV, worsening its symptoms. It survives and thrives off
the HBV virus coating material.

Hepatitis E (HEV) is rare in the United States, confined to tropical areas after flooding, producing a similar
symptom pattern as HAV.

Hepatitis F (HFV) is very rare. HFV is passed from primates to humans.

Hepatitis G (HGV) is mild and does not commonly cause serious liver damage, yet it accounts for 9% of all hepatitis infections. HGV has been recently identified as a group of three virus sub-types of HCV. HBV and HCV are the most serious of the whole "alphabet soup" of hepatitis viruses and according to some sources, 10% of HBV and 85% of HCV can develop into chronic forms.34 Symptoms range from asymptomatic, to mild flu-like symptoms, dark urine, light stools, jaundice, chronic fatigue, serious liver damage and even death. HCV has the ability to escape detection by our immune system and thus leads to the high chronic infection rate. Experts agree that sub-type HCV:1b leads to the most aggressive disease and is the least responsive to Interferon treatment.


HIV and HVC Infection.
About one quarter of HIV-infected persons in the United States are also infected with hepatitis C virus
(HCV). HCV is one of the most important causes of chronic liver disease in the United States and HCV
infection progresses more rapidly to liver damage in HIV-infected persons. Chronic HCV infection
develops in 75%-85% of infected persons and leads to chronic liver disease in 70% of these chronically
infected persons. HIV-HCV coinfection has been associated with higher titers of HCV, more rapid
progression to HCV-related liver disease, and an increased risk for HCV-related cirrhosis (scarring) of the

Herbal Treatment of Hepatitis
There is a large body of evidence building over the last 20 years, primarily by Japanese researchers, for
the use of the specific traditional Chinese herbal formula Minor Bupleurum, or SST (sho-saiko-to), for the
protection of the liver. There are currently 171 papers and studies listed in a conventional medical
database under the Japanese name, Sho Saiko To (SST,) outlining its use for treatment of hepatitis in
China and Japan. Robert Rister states in his book, Japanese Herbal Medicine, "Usefulness [of SST] in
hepatitis treatment has been confirmed by dozens of studies in Japan, over 90% of chronic hepatitis
patients [in Japan] take this formula." In another study it was estimated that 1.5 million people in Japan
suffering from hepatitis were taking this formula. Studies show the effectiveness of this formula at nearly
every stage of infection for hindering and even stopping the progression of the hepatitis viruses.

What does the herbal formula SST (sho-saiko-to) do?
SST increases the immune system components that both keep the virus from forming proteins and
attacks the virus directly. SST has also been shown to boost the immune system through its effects on
macrophage functions. "These results suggest that SST enhances the immune response through at
least two different routes, that is, through eliminating the inhibition of lymphocyte functions by
prostaglandin E2 and through presenting antigen more efficiently." 22

SST has demonstrated that it can treat viral hepatitis. In a clinical trial the efficacy of SST on 222
patients with chronic active hepatitis was studied in a double-blind, multi-center clinical study. One
hundred and sixteen patients received SST in a daily oral dose of 5.4 gm for twelve weeks, followed by the
same dose for a further twelve weeks. One hundred and six patients received a placebo containing 0.5 g
of SST for twelve weeks, followed by a crossover to SST for a further twelve weeks. Among the liver tests,
serum AST and ALT values decreased significantly with the administration of SST. The difference of the
mean value between the SST group and the placebo group was significant after twelve weeks.18

The anti-tumor activity of this formula is well documented, especially for liver cancer, but also lung
cancer and renal cell carcinomas. 2,3,4,21 One study was performed to evaluate the preventative effect of
SST on liver cancer development in chronic viral hepatitis, because of the anti-tumor effects documented
in experimental animals.2,3,4 It studied 260 patients with cirrhosis over five years in control groups to
determine liver cancer protection. The patients in the trial group were given SST at a daily oral dose of 7.5
gm per day in addition to the conventional drugs given to the control groups. The patients were monitored
for sixty months and the cumulative incidence of liver cancer and the survival rate in the two groups were
calculated. The conclusion was that SST helped to prevent the development of liver cancer in patients
with viral hepatitis.5 (Currently being studied by Memorial Sloan-Kettering Cancer Center (
to determine its effect against liver cancer. This study is entitled "Sho-Saiko-To after Ablation for Non-
Resectable Hepatocellular Carcinoma: A Phase II Trial with Historical Control.)

SST also proves effective in preventing or stopping the progression into liver cancer for patients with
cirrhosis. One double-blind study of 260 HBV patients with cirrhosis of the liver were paired together
matched for age, sex, and HBV antigens. The trial group was given 7.5 gm of SST daily; the control group
was given conventional medical treatment. After 34 months, SST outperformed the conventional
treatment and the authors of the study concluded, "SST may prevent or delay the emergence of latent
Hepatocellular cancer, in patients with cirrhosis."29
Analysis of this formula is very interesting; it shows the effectiveness is derived from complex molecules
found in the whole herbs themselves and not in the simple chemical extracts taken from the herbs.26
The treatment of children with SST has shown to be especially effective in a number of studies.13,17,26
One clinical trial concluded, "SST seemed to promote clearance of HBeAg in children with chronic HBV
infection and with sustained liver disease. SST may be a very useful drug for such patients."17
Another clinical trail concluded the same and identified the mechanism "by the production of gamma
interferon which interferes with the virus^s ability to reproduce. Not only able to promote clearance of
HbeAg, this formula can prevent the progression of HCV."26

SST has been shown to increase the effects of prednisolone.14,15 It showed the mild anti-inflammatory
action and significantly increased the anti-inflammatory effect of prednisolone (pediaped, prelone).
Bupleurum, the main ingredient of SST, has saikosides that along with other chemicals, stimulate the
pituitary gland into directing the adrenal glands to produce glucocorticoids, which reduce
inflammation.32,33 Bupleurum also increases the effectiveness of glucocorticoid drugs such as
prednisone. This has matched my own anecdotal experience in practice; always use SST to help
minimize the side-effects and withdrawal symptoms from prednisone.
Contraindications. The use of SST has been shown to be contraindicated with Interferon treatment as it
increases the side effects of the drug. SST has been demonstrated to increase the production of the
body^s own natural interferon, (which explains why, it increases the side-effects of the synthetic drug


SST is an interferon inducer. There are some cases where HBV and HCV patients have
developed pneumonitis or pneumonia using SST in conjunction with Interferon drug therapy.1 Supervision
by an M.D. is absolutely essential under these conditions. Also some contraindications have been
reported for patients with liver cancer and cirrhosis.

A major anti-viral agent, SST has been shown to be useful against other viruses. In HIV studies it was
shown to produce a 50% reduction in the ability of HIV to replicate itself and jumps to 80% for leukemia

SST has also been used traditionally against the influenza virus when used at a certain stage of
influenza viral attack, when, according to Traditional Chinese Medicine (TCM), the pathogen is stuck in a
superficial "lesser yang" level of disease stalemate. Chronic hepatitis can also be classified by TCM and
Japanese Herbal Medicine, Kampo, (on a deeper level) as a disease of the lesser yang level. In this
scenario, the body^s defenses and the invader have reached a stalemate that can last for many years. The
influenza virus has proven vulnerable to SST in this lesser yang stage, where the forces of the pathogen
and those of the body are equally matched.

Bupleurum is one of the main ingredients of SST and recent studies indicate that the particular species
used in the SST formula makes a significant difference on the therapeutic impact of the formula. A simple
and quick quantitative analysis of saikosaponins a, c and d, the major bioactive principles contained in
Bupleurum species, by TLC scanner described the following results: with Bupleurum kaoi, the species
native to Taiwan, showed that the roots, rhizomes and aerial parts (leaves and stem) have greater
quantities of saikosaponins than cultivated B. falcatum var. komarowi and B. chinense used in many
commercially available formulas. The liver protective effects of the three different Bupleurum species
were evaluated using CCl4-induced toxicity in rats. The acute increase of serum transaminase (SGOT
and SGPT) levels caused by CCl4 administration (3.0 ml/kg, s.c.) was dramatically reduced when treated
with SST prepared with the roots of B. kaoi.19 It may have been this particular species had encountered
some history fighting bacteria or viruses that has left this species with compounds supportive for the liver
and hepatitis.

Sales of Sho Saiko To in Japan in 1999 were 111 million dollars.


Footnotes for the Hepo-Protect Formula including Andrographis
1. Ishizaki T., Sasaki F., Ameshima S., Shiozaki K., Takahashi H., Abe Y., Ito S., Kuriyama M., Nakai T.,
Kitagawa M. Pneumonitis during interferon and/or herbal drug therapy in patients with chronic active
hepatitis. Eur Respir J. 1996 Dec 9 (12): 2691-6.
2. Further characterization of the Sho-saiko-to-mediated anti-tumor effect on melanoma developed in
RET-transgenic mice. J. Invest Dermatol. Mar 2000 114 (3): 599-601.
3. Sho-saiko-to: Japanese herbal medicine for protection against hepatic fibrosis and carcinoma. J.
Gastroenterol Hepatol. Mar 2000 15 Suppl: D84-90.
4. Huang Y., Marumo K., Murai M. Anti-tumor effects and pharmacological interaction of xiao-chai-hu-tang
(sho-saiko-to) and interleukin 2 in murine renal cell carcinoma. Keio J. Med Sep 1997 46(3): 132-7.
5. Oka H., Yamamoto S., Kuroki T., Harihara S., Marumo T., Kim S.R., Monna T., Kobayashi K., Tango T.
Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer 1995
Sep 1 76(5): 743.
6. Effects of TJ-9 Sho-saiko-to (kampo medicine) on interferon gamma and antibody production specific
for hepatitis B virus antigen in patients with type B chronic hepatitis. Int J Immunopharmacol. 1991 13(2-
3): 141-6.
7. Yamashiki M., Nishimura A., Suzuki H., Sakaguchi S., Kosaka Y. Department of Laboratory Medicine,
Mie University School of Medicine Tsu, Japan. Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-
9) on in vitro interleukin-10 production by peripheral blood mononuclear cells of patients with chronic
hepatitis. Ihon Kyobu Shikkan Gakkai Zasshi. Dec 1995 33(12): 1361-1366.
8. Yamashiki M., Nishimura A., Huang X.X., Nobori T., Sakaguchi S., Suzuki H. Effects of the Japanese
herbal medicine "Sho-saiko-to" (TJ-9) on interleukin-12 production in patients with HCV-positive liver
cirrhosis. Dev Immuno. 1999 7(1): 17-22.
9. Chen, Y.Y., Yang, Y.Q. Studies on the SGPT-lowering active component of the fruits of Schizandra
rebriflora Rhed et Wils. Yao Hsueh Hsueh Pao-Acta Pharmaceutica Sinica. April 1982 17 (4), 312-313.
10. Ko, K.M., Ip S.P., Poon, M.K., Wu, S.S., Che, C. T., Ng, K.H., Kong, Y.C. Effect of a lignan-enriched
Fructus Schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride
toxicity, Planta Medica. April 1995 61(2), 134-137.
11. (TJN-101), a lignan compound isolated from shisandra fruits, on liver function in rats, Nippon
Yakurigaku Zasshi -Folia Pharmacologica Japonica. April 1988 91(4), 237-244.
12. Ohkura, Y., Mizoguchi, Y., Sakagami, Y., Kobayashi, K., Yamamoto, S., Morisawa, S., Takeda, S.,
Aburada, M. Inhibitory effect of TJN-101 ((+)-(6S, 7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy-6,7-
dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]-cyclooctenol) on immunologically induced liver injuries,
Japanese Journal of Pharmacology. June 1987 44(2), 179-185.
13. Tajiri H., Kozaiwa K., Ozaki Y., Miki K., Shimuzu K., Okada S. Effect of sho-saiko-to(xiao-chai-hu-tang)
on HBeAg clearance in children with chronic hepatitis B virus infection and with sustained liver disease.
Department of Pediatrics, Osaka University Hospital, Japan.
14. Homma M., Oka K., Ikeshima K., Takahashi N., Niitsuma T., Fukuda T., Itoh H. Different effects of
traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics.
Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
15. Shimizu K., Amagaya S., Ogihara Y. Combination effects of Shosaikoto (Chinese traditional
medicine) and prednisolone on the anti-inflammatory action. J Pharmacobiodyn. Dec 1984 7 (12): 891-9.
16. Liu G.T. Pharmacological actions and clinical use of fructus schisandrae. Chin Med J (Engl). Oct 1989
102 (10): 740-9.
17. Tajiri H., Kozaiwa K., Ozaki Y., Miki K., Shimuzu K., Okada S. Department of Pediatrics, Osaka
University Hospital, Japan. Effect of sho-saiko-to(xiao-chai HBeAg leads to enhancement of immune
23. Kapil A., Koul I.B., Banerjee S.K., Gupta B.D. Department of Pharmacology, Regional Research
Laboratory, Jammu, India. Anti-hepatotoxic effects of major diterpenoid constituents of Andrographis
paniculata. Biochem Pharmacol. July 1993 6; 46 (1):182-5.
24. Handa S.S., Sharma A. Hepatoprotective activity of andrographolide from Andrographis paniculata
against carbontetrachloride. Indian J Med Res. Aug 1990 92:276-83.
25. Ferenci P., Dragosics B., Dittrich H., Frank H., Benda L, Lochs H., Meryn S., Base W., Schneider B. 1st
Department of Gastroenterology and Hepatology, University of Vienna, Austria. Randomized controlled
trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. July 1989 9(1): 105-13.
26. Yamaoka, Y., Kawakita, T., Kaneko, M., Nomoto, K. A poly-saccharide fraction of shosaiko-to active in
augmentation of natural killer activity of oral administration. Biological & Pharmaceutical Bulletin. 1995 18
(6), 846-849.
27. Yamashiki, M., Nishimura, A., Suzuki, H., Sakaguchi, S., et al. Effects of the Japanese herbal medicine
^sho-saiko-to^ (TJ-9) on in vitro interleukein-10 production by peripheral blood mononuclear cells of
patients with chronic hepatitis C. Hepatology. June 1987 25 (6), 1390-1397.
28. Jean Barilla, M.S. Andrographis Paniculata, A Keats Good Health Guide.
29. Yamamoto, S., Oka, H., Kanno, T., Mizoguchi, Y., Kobayahi, K. Controlled prospective trial to evaluate
Syosakiko-to in preventing hepatocellular carcinoma in patients with cirrhosis of the liver. Gan to Kagaku
Ryoho - Japanese Journal of Cancer and Chemotherapy. April 1989 16 (4, Part 2-2), 1519-1524.
30. Ono, K., Nakane, H., Fukushima, M., Chermann, J.C., Barre-Sinoussi, F. Differential inhibition of the
activities of reverse transcriptase and various cellular DNA polymerases by a traditional Kampo drug, shosaiko-
to. Biomedicine and Pharmacotherapy. 1990 44 (1), 13-16.
31. Yamashiki, M., Kosaka, Y., Nishimura, A., Takase,
K., Ichida, F. Efficacy of an herbal medicine ^sho-saiko-to^ on the improvement of impaired cytokine
production or peripheral blood mononuclear cells in patients with chronic viral hepatitis. Journal of
Clinical and Laboratory Immunology. 1992 37 (3), 111-121.
32. Hiai, S., Yokoyama H., Nagasawa, T., Oura, H. Stimulation of the pituitary-adrenocortical axis by
saikosaponin of Bupleuri radix. Chemical Pharmaceutical Bulletin. 1981 29, 495-499.
33. Yamamoto, M., Kumagai, Y., Yokoyama Y. Structure and action of saikosaponins isolated from
Bupleurum falcatum L. Arzneimittel-Forschung. 1975 25, 1021-1040.