Review of Chinese Herbal Medicines 1(1) 2009
This the first issue of a new journal aimed at communicating the quality research
which is taking place in China to a wider English reading audience. It begins with an
preface to the journal and its goals in the form of a letter from the editor Xiao PeiGen. It then presents three review papers, four research papers, a short
communication and an introduction to the institutes who sponsor the journal.
The stated aims of the journal are admirable and if effective will be of huge benefit
to us all (assuming we can still prescribe herbs in April 2011!). There are huge
amounts of research taking place in China and if these can be accessible to the
English reading scientific and biomedical contingent then perhaps more respect for
the profession of TCM herbalist will be engendered. What this journal does show is
the quality investigation and rigorous science being adhered to. Sadly the short
communication has a more familiar style “we did this study and got great results,
but we aren’t really sharing any of the details of how we got there” that we often
see. To be fair, some of the issues of communication are partially due to the
language barrier. This is gradually being broken down as China opens up to the
western world permitting its citizens exposure to English, and the western speaking
world into China to learn mandarin.
The journal aims to cover the broad scope of issues relating to Chinese herbal
medicine including source materials both crude and processed, research into
phytochemistry, bioassay, pharmacology, toxicology, pharmokinetics, formulation
and clinical use.
The first review is of the “Challenges in research and development of
traditional Chinese medicines” written by both the editor and three colleagues
from the two sponsoring organisations. The review begins by discussing the history
of books of Chinese herbal medicines from the Shennong Bencao in 2BC to the
Pharmacopeia of the Peoples Republic of China (PPRC) the first of which was written
in 1953 and the most recent in 2005. To date 7295 plant species with therapeutic
value have been identified, 500 of which are commonly used.
The challenges for Chinese herbal medicines which are discussed in the paper include
the need for cultivation of what are primarily still wild collected herbs necessitated
due to habitat destruction and pollution through deforestation, urbanisation and
industrialisation. Management of access to wild grown herbs to ensure sustainability
is necessary. Gene banks are being created of wild grown herbs to maintain
authenticity in the face of cultivation; currently 500 Chinese herbal medicines have
been preserved. At present 100 species of plant are being cultivated.
There is also work in place to acclimatise the herbal products which are not local
grown but are imported to meet the high demand for local use such as American
ginseng.
With the increasing agricultural production of Chinese herbal medicines the Good
Agricultural Practices (GAP) passed by the Chinese State Drug Administration in
2002 aims to ensure continued quality and sustainability. Despite non local collection
of plants it is vital to retain the local people’s knowledge of when to collect and how
to prepare the herbs or treatments will fail. In addition to GAP there is the
implementation of standards for Good Manufacturing Practice, Good Supply Practice,
Good Laboratory Practise and Good Clinical Practices. These came into being as part
of The National Programme for Modernization of Traditional Chinese Medicines
(2002-2010)
There is an extensive discussion on safety, toxicity and pharmacovigilence. At
present just 49 of the 534 Chinese herbal medicines in the PPRC have high toxicity.
Just 6061 cases of adverse effects have been recorded from 1915 to 1994. A grading
system has been put in place from Grade 1, food herbs to Grade 5 known toxic. In
this paper details of adverse effects and toxic herbs are discussed at length.
There is also a large section about the pharmacologically active compounds present
in Chinese herbal medicines of which 600 have been isolated, 100 subject to careful
investigation and 60 of which have been developed into new pharmaceutical drugs.
Several of these are explored in greater detail looking at their chemical structure and
therapeutic properties. There are significant challenges in finding and isolating a new
compound, in showing its safety, understanding its pharmokinetics and then proving
its worth to an international community.
This is both a broad and in depth look at the history and current challenges facing
Chinese herbal medicines. It is I feel slightly sad that much of the enthusiasm for
research is along the lines of developing new drugs rather than leaving the
compounds nestled in the balance of the plant of origin and focussing on the efficacy
of medicines as they have been used for so many years. The reductionist approach is
incredibly useful in communicating to the scientific community that there is
something in it, but this reduction is in contrast to the ethos of TCM.
The second review is titled “Safety issues of Chinese medicine: A review of
intoxication cases in Hong Kong”. Hong Kong is the largest trading partner with
mainland China and Chinese herbal medicine has been used by 60% of the
population with its practitioners providing 20% of overall healthcare. Adverse
reaction are looked at in four categories that of predictable toxicity, pharmacological
interaction and overdose; idiosyncratic reactions; adverse effects due to long term
therapy and delayed effects such as carcinogenecityy and teratogenecity. There are
a number of known toxic herbs discussed such as aconite and aristalochia.
The paper goes through a range of these toxic herbs explaining their toxic effects,
mechanisms of action and exploring some case studies. Adulteration of herbal
formulae with prescription only medicines can cause problems. So too can herb
interactions with western drugs and the administration of certain herbal products can
cause complications during surgery. Authentication and quality control can be used
to tackle some of these problems for example verifying the aconite root has been
appropriately treated and that species substitution does not occur. Improvements in
analytical methods for detection and quantification of toxic substances is of great
importance in diagnosis and prognosis.
The conclusion includes that there is a misconception that herbal products are
natural therefore safe. Intoxication cases are rare but they need to be identified and
investigated and suggests a Chinese herbal drug control agency should be set up to
manage this process. Adequate training needs to be provided for practitioners,
dispensers and patients to ensure the safety and therapeutic potency of Chinese
herbal medicine in Hong Kong.
This is a clearly written and focussed look at a very important topic. Recognising that
these issues do from time to time occur and that through education and quality
control they can be avoided and through thorough investigation and understanding
cases which do slip through the net can be managed and a favourable prognosis
achieved.
The final of the three reviews is a “Highlight of publications on Chinese
Traditional and Herbal drugs in 2008”. This papers reviews a journal in Chinese
language founded in 1970. The journal covers four main areas. The first is chemistry
and new compounds, a leading area in the modernisation of Chinese herbal
medicine. There were 132 papers published, 120 on botanical materials of which 30
are popular herbal medicines. It covers analytical and quality control, primarily HPLC
fingerprints for identification. There is work on pharmaceutics using identification,
isolation and stabilization of identified compounds. The last area of focus is that
pharmacology and safety where currently much work is focussed on safety of aconite
and pharmacology of the antitumor activity of ginseng saponins.
Four research papers were presented. These are all well written papers presenting
thorough and reproducible methodologies. The justification and application of the
knowledge was less consistently explained.
The first paper “Oligomeric procyanidins induce generation of reactive oxygen
species and collapse of mitochondrial membrane potential in glioblastoma
cell lines” explores the mechanism by which procyanidins are able to destroy glial
cell brain tumours. It is justified in that these types of cancer cells are extremely
drug resistant leading to poor patient survival. Procyanidinds are found frequently in
food, grapes being particularly rich, the majority of the substance being found in the
grape seeds. The study used cell cultures both human and rat in order to test the
mechanisms by which the procyanidins were able to destroy the cancer cells. Their
results are stated in the title of the paper; reactive oxygen species levels increased
and the membrane potentials of the mitochondria were reduced.
The second paper “Studies in absorption and transport of limoninoids from
Fructus Evodiae in Caco-2 cell monolayer” again uses a cell culture, this time to
analyse how isolated compounds from the herb are absorbed and how they move
across cell membranes. This aims to examine the bioavailability of the active
compounds in this herb. The absorpation and transport mechanisms of three
limonoids are examined using cell cultures. There is no clear justification as to why
liminoids are examined in preference to other identified compounds of the herb
which are stated to be indole, quinoline, alkaloids and essential oil. The herb is used
for gastrointestinal disorders, headache, abdominal pain, dysentery and post partum
haemorrhage but it is not clear if the limonoids are indicated in these particular
therapeutic actions. Of the three compounds tested it is suggested that limonin and
evodol are well absorbed compounds and the third, shihulimonin may well be
involved in the transport mechanism.
Third paper is concerned with tea polyphenols, in particular green tea. These antioxidants are epigallocatechin-3-gallate (EGCG), epicatechin- 3-gallate (ECG),
epigallocatechin (EGC), and epicatechin (EC). Tea has long been considered to have
benefits to health including cancer prevention, lowering of blood lipids and glucose
levels and reducing obesity. This study “Excretion of Four Catechins in Tea
Polyphenols in Rats” looks at how these compounds are excreted in rats whether it
be through the bile, urine or faeces. Of the four compounds tested EGCG and EC
were excreted predominantly in the urine, ECG via the bile and EGC in the faeces.
There was not a great deal of explanation certainly for a relatively lay reader as to
the importance of this in terms of its therapeutic use and although tea could be
considered a medicinal food is not obviously helpful in raising the profile of Chinese
herbal medicines or the wider understanding of why the herbs are important or
valuable.
The final research paper is concerned with the identification of the compounds within
Gymnocladus chinensis and its title is “Chemical Constituents from Fruits of
Gymnocladus chinensis”. This plant is a tree widely distributed in South China and
used as a herb, pinyin Feizaojia, which is used for its diuretic and expectorant
properties. On close examination using chromatography ten distinct compounds were
isolated one of which was completely novel and 6 of which had not been isolated
from this herb before. There was no further information as yet about what
therapeutic uses this compound might have.
The journal ends with a communication about the fact the evidence based medicine
in the study of Chinese herbal medicine is essential. We need to have clinical trials to
show efficacy. This is what I was hoping to see in the body of the journal, although
interesting in their own right the research papers presented were on tea and
polyphenols which are considered generally to be more of a food than a herbal
medicine, about the transport mechanisms of one isolated compound from a Chinese
herb and about the discovery of a novel compound amongst 9 known compounds
extracted from a herbal medicine. The isolation of compounds is without a doubt one
important aspect of understating the mechanisms by which Chinese herbal medicines
are effective, clinical trials to show this are also of great import. I concur with the
short communication and am surprised by the lack of evidence presented. Frustrated
that the short communication discusses trials in which clinical efficacy is stated but
without the full methodology to be proven to stand up as rigorous science.
The two trials discussed focus on treating heart disease, rationalised as important
due to the poor outcome for western drugs in treating anti-arrhythmia and the
associated side effects. One of these studies looked at the use of Shensong Yangxin
capsule in the treatment of non organic premature ventricular contractions in 32
hospitals and 1437 patients. The capsule was said to be significantly more effective
than placebo and better than mexiletin. No details of the how the study was
conducted was presented nor any ethical information. Placebo to people with a heart
condition sounds risky to me. No information is presented as to how significant the
results were.
The second of the discussed papers is concerned with the use of another capsule,
this time Tong Xin Luo capsule. The details of this one were more difficult to decipher
with some confusing language, essentially I believe it was saying that this capsule
was effective in preventing and controlling the need for intervention for patients
suffering acute myocardial infarction with no reflow. The communication states that
international standards were adhered to and there was close monitoring of the nine
hospitals involved but again no details nor even a link to the original research.
Without a doubt the aims of the journal are admirable and both editorial staff and
contributors are educated people with some fascinating research to reveal. I look
forward to future issues where full papers are published detailing the trials showing
clinical efficacy of Chinese herbal medicines. It will be interesting to follow the
progress made on increasing quality control and safety issues as these are concerns
which have much tarnished the reputation of the profession, especially with the
latest case making big waves in the UK. We can only hope that a safety scare, my
deepest sympathies to the lady who is now on dialysis for life and fighting bladder
cancer, will spur the government into completing on their promises of statutory
regulation. Whilst the scientists unpick the details of the compounds within a herbs
and create new drugs let us hope that there is sufficient support for those scientists
interested in investigating the much more complex multi compound interactions that
take place within individual herbs and within those long trusted formulae from the
classics.