Dr. J.E. Williams on Viral Immunity has recommended is his book,

http://www.amazon.com/exec/obidos/tg/detail/-/1571742654/102-9836365-4168917?v=glance

the use of formulas that
contain gentiana such as Longdan Xiegan Tang, for herpes.

Perl von Molson

http://www.itmonline.org/arts/chinchiu.htm
CHIN-CHIU and GENTIANA

Herbs for Deficiency and Excess Liver/Gallbladder Fire

by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional
Medicine, Portland, Oregon

Chin-chiu (qinjiao; root of Gentiana macrophylla; see Figure 1) is
frequently recommended for treating deficiency heat syndromes
involving liver/gallbladder fire. Deficiency heat refers to a heat
syndrome that arises because of deficiency in the cooling,
moisturizing yin essences or where this deficiency is caused by a
prolonged disease of hot nature that damages the yin essences.
Usually, these patients are in a weakened condition and also suffer
from some degree of qi deficiency. Liver/gallbladder fire represents
one major subset of fire syndromes, where these organs (as
functionally defined by the traditional Chinese system) participate
directly in the pathology. It is said that the liver has a natural
tendency to become overheated, so this is an organ that is easily
stirred to generate fire when a pathogen reaches the central viscera.
Chin-chiu is included in prescriptions that contain mild-natured heat
clearing herbs that will be tolerated by the weakened patient; these
herbs are usually accompanied by tonics, especially those that nourish
yin and blood.

Chin-chiu is categorized in the Materia Medica with the herbs that
expel wind-dampness, which are the ones primarily used in treatment of
rheumatism: this is just one of the applications of chin-chiu. The
liver is said to nourish the tendons and ligaments; chin-chiu is
particularly used in cases where these connective tissues become
hypercontracted due to insufficient nourishment (e.g., deficiency of
liver yin), yielding spasms that run from the joints to the muscles.
It is claimed that, unlike most other herbs used for wind-damp
syndromes, which typically have a drying nature, this one does not
damage the yin (1).

Chin-chiu is as often indicated for "bone fever." This strange term
refers to syndromes with fever and sweating in which the person feels
as if there is steam coming from the bones, heating up the skin. The
Advanced Textbook on Traditional Chinese Medicine and Pharmacology (2)
states: "As deficiency of yin gives rise to internal heat which steams
inside, a burning sensation in the chest, palms, and soles appears; if
the fire goes upward, malar flush occurs."

In the past, the most common disease calling for chin-chiu was
probably tuberculosis. This disease, in the absence of effective early
treatment, is consumptive in nature. The person becomes very
deficient, experiences night sweats, intermittent fevers, and
weakness. In modern times, where antibiotics often control the
feverish and consumptive diseases, chin-chiu is being used for
non-fever diseases, particularly autoimmune disorders, such as lupus.
The autoimmune diseases that affect the connective tissues (of which
lupus is a prime example) count as deficiency heat syndromes during
their active, inflammatory stage.

Gentiana (longdan or longdancao; root of Gentiana scabra; see Figure
2) is a related herb that is stronger in its heat clearing actions and
classified with the herbs for clearing heat and drying dampness.
Gentiana is often used in the treatment of excess-type liver syndrome,
with fire flaring upward to cause red face, red eyes, headache, and
hypertensive symptoms (including tinnitus that sounds like rushing
waves). Gentiana is especially used when damp-heat congests the liver
and gallbladder. This can cause swelling and pain in the region of the
liver accompanied by jaundice (i.e., hepatitis) or the heat and
dampness may flow downward to cause swellings and sores in the lower
body (such as modern use in treating genital herpes). As stated in the
Advanced Textbook:

The liver meridian curves around the external genitalia. The damp-heat
goes downward along the meridian to permeate the scrotum, thus causing
eczema with unbearable itching. Steaming of the testes stagnates the
circulation of qi and blood and, therefore, manifests itself as
swelling and burning pain of the testes. If the vagina is steamed by
damp-heat, yellow and foul leukorrhea and pruritis vulvae appear.

Like chin-chiu, gentiana is included in some formulas for treating
rheumatism; like gentiana, chin-chiu is used in some formulas for
treating hepatitis. Gentiana is selected for the cases of excess and
chin-chiu for the cases of deficiency heat. Both chin-chiu and
gentiana were described in the Shennong Bencao Jing (3):

Chin-chiu is bitter and balanced. It mainly treats cold and heat, evil
qi, and cold-damp-wind impediment with pain in the limb joints. It
precipitates water and disinhibits urination.

Gentiana is bitter and astringent. It mainly treats cold and heat in
the bones, fright epilepsy, and evil qi. It mends expiry and damage,
settles the five viscera, and kills gu toxins.

These descriptions are somewhat similar, with chin-chiu specified for
treating dampness and getting rid of excess water, and gentiana
specified for agitation and fright, and for getting rid of gu toxins,
a group of pathogens that appears to correspond mainly to parasites.
The calming effect of gentiana is related to its ability to purge
excess liver fire that binds up the flow of qi. As stated in the
Advanced Textbook: "Once the function of the liver in promoting the
free flow of qi is impeded, irritability and easy anger may result.
Disturbance of the mind by fire-heat produces insomnia and
dream-disturbed sleep."

In the revision of the Materia Medica by Tao Hongjing (ca. 500 A.D.),
gentiana was categorized with the "upper class" herbs and said to be
of benefit for health and longevity with prolonged use. Today, the
situation is different: caution is expressed over this very bitter
herb, for fear that it will damage the spleen/stomach system and cause
diarrhea if the dosage is too high or if it is taken for too long. By
contrast, chin-chiu was categorized by Tao with the "middle class" of
herbs, indicating that it would be useful in treating diseases, but
not of value for prolonged administration to attain long life. This is
consistent with the modern understanding of the herb, though it is
believed that chin-chiu, unlike gentiana, can be administered over a
prolonged period, as may be necessary to treat chronic diseases, such
as rheumatoid arthritis.

Chin-chiu is named for its original main growing location, Jinzhong
(Chin-chung in Wade-Giles transliteration), in Shanxi Province (4).
The root is in the form of a mass of small intertwined rootlets: the
character for jiao, or chiu in Wade-Giles transliteration, is derived
from the character jiu, for the number 9 also meaning many, with a
"grass radical" above, indicating that it makes reference to a plant
name. Gentiana is named for its extreme bitter taste: longdan means
dragon's bile (cao means weed). In the Chinese pharmacies, chin-chiu
is provided in thin slices from the main part of the root (see Figure
3); the numerous entangled root ends are more easily seen in
longdancao, which is kept whole (see Figure 4).

USE IN TRADITIONAL FORMULAS
Gentiana is an ingredient in several traditional formulas, but most
references to use of this herb are associated with the well-known
Longdan Xiegan Tang, commonly called Gentiana Combination (longdan =
gentiana; xiegan = cleanse the liver, referring to clearing liver
fire; tang = decoction). This extremely bitter formula has become
widely used as a pill as well as the decoction. In virtually all
clinical reference books, this formula is mentioned among the first
possibilities for treating any syndrome of liver fire or
liver/gallbladder damp-heat with an excess type condition. The
prescription for the decoction is (5):

Gentiana 6 g
Scute 9 g
Gardenia 9 g
Alisma 12 g
Akebia 9 g
Plantago seed 9 g
Tang-kuei 3 g
Rehmannia, raw 9 g
Bupleurum 6 g
Licorice 6 g

This formula purges fire from both the liver and gallbladder and
clears damp-heat accumulating in the lower warmer. It was first
recorded in the Yifang Jijie (Analytic Collection of Medicinal
Formulas; 1682) by Wang Ang, and, with its adoption as a standard
reference formula during the 20th century, it displaced most other
formulations from prior centuries that included gentiana. According to
Qin Bowei, one of the leading physicians involved in the development
of modern TCM: "In general, when there are symptoms of liver fire,
Gentiana Combination with modifications can be relied upon (6)."

The only other formulas frequently referenced in modern Chinese
literature with this herb are Danggui Longhui Wan (Tang-kuei,
Gentiana, and Aloe Pill), a formula attributed to Zhu Danxi in the
book Danxi Xinfa (ca. 1340), and Xieqing Wan (Drain the Green Pill,
referring to clearing heat from the wood element), a pediatric formula
by Qian Yi, the author of Rehmannia Six Formula (ca. 1100). Danxi's
formula includes the strong laxatives aloe and rhubarb, and the rare
musk gland, making it impractical for modern uses. It was prescribed
for excessive fire of the liver and gallbladder leading to more severe
symptoms than those for which Gentiana Combination might be given, and
for cases accompanied by abdominal fullness, constipation, and scanty
urine. It is possible that Longdan Xiegan Tang was designed as a
replacement for this older formula, as they both contain gentiana,
gardenia, scute, and tang-kuei. Yi's pediatric formula also included
gentiana, gardenia, and tang-kuei. It was indicated for infantile
convulsions, irritability, and insomnia accompanied by constipation
(treated by rhubarb).

Chin-chiu is included in several traditional prescriptions for
treating fever and inflammation in persons with deficiency syndrome.
For this purpose, it is usually combined with ching-hao (qinghao;
Artemisia annua) to help purge heat from the gallbladder. Ching-hao
not only clears heat, it also has a fragrant quality associated with
regulating the flow of qi in the liver and gallbladder. From the
perspective of Chinese medical theory, the heat syndrome that is
treated by these herbs is one in which deficiency comes first: this
deficiency is understood to give rise to the fire (because the yin
essence doesn't control it). From the Western viewpoint, the diseases
being treated by these herbs can cause one to become quite weak.

A good example of the formulas with chin-chiu and ching-hao is, Qinggu
San (qing = to cleanse; specifically, to cleanse heat; gu = bone; san
= powder; hence, the powder to clear heat from the bone). The
prescription is:

Stellaria 5 g
Picrorrhiza 3 g
Chin-chiu 3 g
Turtle shell 3 g
Lycium bark 3 g
Ching-hao 3 g
Anemarrhena 3 g
Licorice 2 g

The herbs stellaria, picrorrhiza, lycium bark, and anemarrhena are
used in the treatment of deficiency heat syndromes. Turtle shell helps
treat the deficiency by nourishing yin and blood; it also lowers fire
and prevents bleeding due to heat agitating the blood. The most severe
form of disorder treated by this formula is described as a "steaming
sensation in the bone." The deficiency syndrome is marked by a thin
pulse, and a dry reddish tongue, fatigue, and ease of sweating.

Other formulas that are of similar nature are Qinjiao Fulei Tang
(Decoction with Chin-chiu to Support the Lungs), Qinjiao Biejia San
(Powder of Chin-chiu and Turtle Shell), and Huangqi Beijie San (Powder
of Astragalus and Turtle Shell). These formulas all include chin-chiu,
lycium bark, and turtle shell to clear heat and alleviate the
"bone-steaming fever." Qinjiao Biejia San also includes ching-hao.
These formulas were originally designed to treat tuberculosis and
similar disease patterns; they were adopted into Kampo (Japanese
herbal medicine) and are still mentioned in modern Chinese herb texts
(7, 8).

The best-known arthritis formula with chin-chiu is Duhuo Jisheng Tang
(Tu-huo and Loranthus Combination); the herb is also a key ingredient
in Da Qinjiao Tang (Major Chin-chiu Combination), used for apoplexy
and paralysis. These two are similar formulations with a large number
of ingredients, many of them tonics, in which chin-chiu plays a modest
role: it is the ingredient in largest amount in Da Qinjiao Tang,
making up 15% of the formula; it contributes to 7.5% of Duhuo Jisheng
Tang. Although arthritis and apoplexy are very different disorders, in
the Chinese medical view, both are engendered by wind that penetrates
the vessels that are not full of qi and blood; these formulas are both
indicated for patients who have a deficiency syndrome.

MODERN EVALUATIONS
The botanical origin of chin-chiu is mainly Gentiana macrophylla, but
other sources include G. tibetica, G. straminea, G. crassicaulis, and
G. dahurica. Gentiana (longdancao) is mainly derived from G. scabra,
but is also obtained from G. triflora and G. regescens. The roots are
the part used for both herb materials, and they are collected in the
spring and fall seasons (9, 10).

The dominant active components in the Gentiana genus, including both
chin-chiu and gentiana, are the secoiridoid glycosides, mainly
gentiopicroside (see Figure 5), with lesser amounts of sweroside and
swertiamarin (named for another genus of the Gentianacea, Swertia,
where they were first found). The secoiridoids and iridoids of similar
structure form the largest class of naturally-occurring monoterpenes.
They are well represented not only in this genus, but throughout the
Gentianaceae Family, and are responsible for their bitter taste (11).
Formerly, it was reported that chin-chiu contained alkaloids, but it
was later found that these compounds (e.g., gentianine) were artifacts
generated during extraction and isolation of the compounds when
ammonia was introduced and served as a nitrogen source (10). There are
no significant amounts of alkaloids in the herbs.

Recent analysis (12) of an extract of the roots of Gentiana
macrophylla revealed two novel and six known secoiridoids, along with
kurarinone and kushenol (flavonoids also found in sophora root,
kushen) and isovitexin (a flavonoid, named for its occurrence in
vitex). Other components were the oily materials beta-sitosterol,
stigmasterol, daucosterol, and beta-sitosterol-3-O-gentiobioside
(these are all sterols, fatty components with anti-inflammatory
activity found in numerous plants) and oleanolic acid (a basic
triterpene).

Gentiana scabra, the main source of longdancao, has the highest
gentopicroside concentration in the fall during the third year of
growth, reaching 7.8% in the roots (only about 1% in the above-ground
portions). Other species collected for this herb have lower amounts,
ranging from 1.8% to 6.7%. Gentiana macrophylla and Gentiana dahurica,
two major sources of chin-chiu, have only 0.2-1.4% gentopicroside
(10). These differences in content explain why gentiana is considered
a much stronger herb than chin-chiu and why Gentiana scabra is the
desired source for gentiana.

The biological and pharmacological effects of the secoiridoids include
stomachic, choleretic (promotes bile flow), and antihepatotoxic
activities (11). These functions explain the traditional use of the
herbs in treating hepatitis. Secoiridoids are found also in cornus
(shanzhuyu), swertia (zhangyacai), patrinia (baijiangcao), and
lonicera (jinyinhua), which are also included in treatments for
hepatitis. In addition, these constituents have anti-inflammatory,
antifungal, and antihistamine activities (9, 10, 12, 13).

Pharmacology studies of gentiopicroside include recent tests for
therapeutic effects on two hepatic injury models, chemical and
immunological (14). An increase in serum level of hepatic enzymes
induced by oral treatment of carbon tetrachloride was suppressed by
pretreatment with gentiopicroside at 30-60 mg/kg/day for 5 consecutive
days. An increase of these enzymes triggered by an intravenous
infusion of lipopolysaccharide (in mice primed with bacteria to yield
an autoimmune hepatitis) was also inhibited by gentiopicroside
pretreatment at the same dose. In the latter case, tumor necrosis
factor (TNF), a major inflammatory mediator, was increased in serum of
control animals with a peak at 90-120 minutes following
administration, then followed by an increase of the serum liver enzyme
levels. Gentiopicroside significantly suppressed the increase of TNF
in serum at the therapeutic doses, suggesting it protected against
hepatitic inflammation by inhibiting the production of TNF. It is
known that TNF-alpha-and possibly other related cytokines-are involved
in the perpetuation of the inflammatory cascades in autoimmune
diseases. Blockade of TNF-alpha leads to rapid improvement of
rheumatoid arthritis disease activity and can prevent tissue
destruction. TNF-alpha appears to also be involved in the inflammatory
stage of lupus.

In the treatment of viral hepatitis (mainly hepatitis A and B), a
formula known as Ku Jiao Tang (Sophora and Chin-chiu Decoction) was
administered in 86 patients (15). The formula was comprised of
chin-chiu, sophora, salvia, and serissa (liuyuexue). According to the
clinical report, administration of the decoction twice per day
normalized liver enzymes in 11-36 days of treatment.

In the treatment of systemic lupus erythematosus (SLE), 81 patients
were treated with either Compound Qinjiao Tablet, prednisone, or the
combination of the two (16). The tablet is comprised of chin-chiu,
zaocys, astragalus, scrophularia, rehmannia, salvia, hoelen, alisma,
and phellodendron. When given alone (54 patients), it was administered
at 5 tablets, three times per day; in combined therapy (8 patients),
it was administered at 10 tablets, twice per day with prednisone at
10-30 mg per day. As controls (19 patients), prednisone was given
without the herbs. Treatment time averaged 9.3 months for the herb
groups and 7.3 months for the control group. Among the 54 cases
treated by herbs alone, it was reported that all but 12 cases improved
and in the combined therapy group all cases improved; in the control
group, all but one case had improved. However, in the herb groups,
there were a higher proportion of cases going into complete remission.
Further, the herb treatment was reported to be more effective for the
improvement of nephropathy, arthralgia, and erythema, and for
restoring normal erythrocyte sedimentation rate and complement (C3)
levels than prednisone alone. No apparent side effects of the herb
treatment were found in this observation.

In another trial for treatment of lupus (17), patients received
combination treatment with prednisone and Lingdan Pian, which was
composed of chin-chiu, ching-hao, moutan, turtle shell, buffalo horn,
rehmannia, licorice, scrophularia, and other herbs. Each tablet
contained 0.5 g crude herbs, given at 5 tablets a time, 3 times per
day. As in the above trial, the use of the herb with prednisone was
reported to produce better results, and fewer side effects, than
prednisone alone. Rehmannia and scrophularia contain iridoid
glycosides, which have similar pharmacological action as the
secoiridoids. In a screening of 29 Chinese medicinal materials for
immunomodulatory action, 14 showed significant effects, including
chin-chiu, cornus, hoelen, and turtle shell (18), which may help
explain the apparently favorable action of these formulas in treating
lupus.

SUMMARY
Chin-chiu and gentiana are related herbs from the same genus
(Gentiana) that have similar chemical constituents and overlapping
actions and uses. Chin-chiu is traditionally administered for cases of
yin deficiency heat and rheumatism, while gentiana is traditionally
used for cases of liver fire and liver/gallbladder damp-heat. Gentiana
Combination has become the standard formula referenced for liver fire
syndromes of the excess type; there are a number of formulas with
chin-chiu mentioned in the literature, but the ones with ching-hao and
turtle shell are most often mentioned for treatment of deficiency heat
syndromes.

One of the significant differences between these herbs, from the
modern viewpoint, is the amount of the main bitter principals, the
secoiridoids, which are far higher in gentiana than in chin-chiu. With
the lower amount of secoiridoids in chin-chiu, the effects of other
components, such as flavonoids, may be more notable. The active
constituents, including iridoids, flavonoids, and oily compounds, have
anti-inflammatory properties. Chin-chiu, in particular, has gained
increasing use in treatment of autoimmune disorders: in addition to
the long-standing tradition of treating rheumatoid arthritis, it is
now often administered for lupus.

REFERENCES
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Belgium.
State Administration of Traditional Chinese Medicine, Advanced
Textbook on Traditional Chinese Medicine and Pharmacology, (vol. 1)
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Yang Shouzhong (translator), The Divine Farmer's Materia Medica, 1998
Blue Poppy Press, Boulder, CO.
Hsu HY, et al., Oriental Materia Medica: A Concise Guide, 1986
Oriental Healing Arts Institute, Long Beach, CA.
Huang Bingshan and Wang Yuxia, Thousand Formulas and Thousand Herbs of
Traditional Chinese Medicine, vol. 1, 1993 Heilongjiang Education
Press, Harbin.
Chace C and Zhang Ting Liang, A Qin Bowei Anthology, 1997 Paradigm
Publications, Brookline, MA.
Hsu HY and Hsu CS, Commonly Used Chinese Herb Formulas with
Illustrations, 1980 revised edition, Oriental Healing Arts Institute,
Long Beach, CA.
Bensky D and Barolet R, Chinese Herbal Medicine: Formulas and
Strategies, 1990 rev. ed., Eastland Press, Seattle, WA.
Zhu Youping, Chinese Materia Medica: Chemistry, Pharmacology, and
Applications, 1998 Harwood Academic Publishers, Amsterdam.
Tang W and Eisenbrand G, Chinese Drugs of Plant Origin, 1992
Springer-Verlag, Berlin.
Wang Ying and Lou Zhicen, A review on the studies of the Chinese herb
qinjiao, Chinese Pharmaceutical Bulletin 1987; 22(3): 153-159.
Rodriguez S, et al., Iridoids and Secoiridoids in the Gentianaceae,
Organic Chemistry, 1998; 2 (6): 627-648.
Tan RX, et al., Acyl secoiridoids and antifungal constituents from
Gentiana macrophylla, Phytochemistry 1996;42(5):1305-1313.
Kondo Y, Takano F, and Hojo H, Suppression of chemically and
immunologically induced hepatic injuries by gentiopicroside in mice,
Planta Medica 1994; 60(5): 414-416.
Li Botang, Treatment of 86 cases of viral hepatitis with Kujiao Tang,
Zhejiang Journal of Traditional Chinese Medicine 1989; 24(9): 391.
Yuang Zhaozhuang and Feng Jingchun, Treatment of systemic lupus
erythematosus with compound qinjiao tablet and minimum dose of
prednisone, Chinese Journal of Integrated Traditional and Western
Medicine, 1989; 9(3): 156-157.
Zhong Jiaxi, et al., 25 cases of systemic lupus erythematosus treated
by integrated traditional Chinese medicine and Western medicine,
Chinese Journal of Integrated Traditional Chinese Medicine and Western
Medicine 1999; 19(1): 47-48.
Tan Yunyu, et al., Screening 29 species of medicinal materials for
immunomodulation activity, Journal of Beijing University of
Traditional Chinese Medicine 1994; 17(2): 28-30.
March 2002

Figure 1: Gentiana macrophylla.

Figure 2: Gentiana scabra.

Figure 3: Chin-chiu.

Figure 4: Gentiana.

Figure 5: Active components of Gentiana.