Keywords: Adulterant, adulteration, St. John's wort, Hypericum perforatum, Hypericum barbatum,
Hypericum hirsutum, Hypericum montanum, Hypericum patulum,
Hypericum tetrapterum, food dyes, E123 Amaranth, E133 Brilliant
Blue, E110 Sunset Yellow, E102 Tartrazine)
Goal:
The goal of this bulletin is to provide timely information and/or updates on
issues of adulteration of St. John's wort (Hypericum
perforatum, Hypericaceae) to the international herbal industry and extended
natural products community in general. It is intended to complement the
previously published works with information on St. John's wort (SJW)
adulteration, e.g., the American Herbal
Pharmacopoeia (AHP) SJW monograph,1 by presenting new data on
the occurrence of adulteration, the market situation, and consequences for the
consumer and the industry.
1 General Information
1.1 Common name: St. John's wort
1.2 Other common names:
English: Common St. John's wort, perforate St.
John's wort, goatweed, Klamath weed, racecourse weed, tipton weed2-4
Chinese: Guan ye lian qiao (贯叶连翘),3-5 qian
ceng lou (千層樓)
2
Dutch: Sint-janskruid2,3
French: Millepertuis,
herbe à mille trous;
millepertuis perforé, herbe de la Saint Jean, toutsaine2,3
German: Johanniskraut, Johannisblut,
Herrgottsblut, Tüpfelhartheu, Tüpfel-Johanniskraut2,3
Italian: Iperico, erba di San Giovanni, iperico
perforato, perforata, pilatro2,3
Portuguese:
Hipericão, milfurada3
Russian: Zveroboj
obyknovenny,4 zwieroboij2,3
Spanish: Corazoncillo,
hierba de San Juan, hipericón2,3
South African:
Johanneskruid3,4
Swedish: Äkta johannesört,4
Johannesört3
1.3 Accepted Latin binomial:
Hypericum perforatum L.6,7
1.4 Synonym: H. vulgare Lam.3
1.5 Botanical family: Hypericaceae
1.6 Botanical
taxonomy: The genus Hypericum
consists of over 490 species, which are subdivided into 36 sections. SJW is a
member of the section Hypericum, which also includes the closely related
species H. attenuatum, H. elegans, H. maculatum, H. scouleri,
H. tetrapterum, and H. undulatum, among others.8-10
SJW shares many morphological features in common with H. attenuatum and H.
maculatum in particular and it is thought that SJW arose from a hybrid
cross between these two species. Identification is complicated by the fact that
H. perforatum forms hybrid
back-crosses with these species (see Robson9 for a key to identify
SJW hybrids). Natural populations of SJW are composed mostly of tetraploids but
diploids, hexaploids and polyploids also occur. Based on morphological features
and geographical ranges, Robson described four intergrading subspecies of SJW,
subsp. perforatum, subsp. chinense, subsp. songaricum, and subsp. veronense.9,10
1.7
Distribution range: SJW
is broadly distributed throughout the temperate regions of the world. Its
natural range includes all of Europe (except the extreme north), northwest
Africa, Canary Islands, Madeira, Azores, Turkey, Cyprus, the Levant (eastern
Mediterranean countries) and western Saudi Arabia to northwest India (Uttar
Pradesh), Transcaucasia, Turkmenistan to Altai, the Angara-Sayan region and northwestern
Mongolia. In China, H. perforatum
subsp. songaricum is limited to northwestern
Xinjiang near the border with Kazakhstan and H. perforatum subsp. chinense
is distributed throughout much of the country, from eastern Qinghai and Gansu,
east to Hebei, south to Jiangxi and west to Yunnan.8-10
SJW has been introduced into many other parts of the world; it is a
naturalized weed in Canada, United States, Mexico, Cuba, Haiti, Brazil,
Uruguay, Argentina, Chile, Sudan, South Africa, Réunion, Australia, New
Zealand, and Japan.
In many of these
countries, the proliferation of SJW has led to its classification as noxious
weed that is subject to concerted efforts to eradicate it.4,9-11
1.8 Plant part, form, and production method: The dried flowering aerial parts, collected
just before or during flowering, consisting of stem, leaves, buds, flowers, and
fruit (capsules) are sold cut, powdered, and as aqueous infusions, oil
infusions, and aqueous-alcohol extracts. Types of extracts include tinctures (1:5),
fluid extracts (1:1), and powdered extracts. The extracts are often
standardized to contain 0.3% hypericin or 2-5% hyperforin as markers for
consistency.1
1.9
General use(s): As an herbal medicine, SJW is predominantly used for the treatment of mild-to-moderate
depression. Other uses include anxiety, restlessness, insomnia, neuralgia,
pain, and inflammation. As a dietary supplement, SJW is typically represented
as “supporting emotional well-being” or other similar structure and function
claims. Oil preparations are used internally to treat inflammatory
gastrointestinal conditions, and topically to treat bites, bruises, burns,
hemorrhoids, lacerations, muscle pain, sunburn, urticaria, and wounds.1,12
2 Market
2.1
Importance in the trade:
From 2012 to 2015, retail sales of SJW dietary supplements in the Natural
channel in the United States (US) remained relatively constant with only a
slight decline/increase each year. Similar trends can be observed for sales in
the Mainstream Multi-Outlet channel where sales and rankings from 2013 to 2015
have been quite consistent. The 2012 sales data, which are significantly higher
in this channel, include numbers from Walmart, club, and dollar stores. Data
from these retailers were no longer available in the following years.
Table
1. SJW Dietary Supplement Sales in the US from 2012-2015
Channel
|
2012
|
2013
|
2014
|
2015
|
|
Rank
|
Sales
[US$]
|
Rank
|
Sales
[US$]
|
Rank
|
Sales
[US$]
|
Rank
|
Sales
[US$]
|
Naturala
|
32
|
2,310,361
|
34
|
2,265,796
|
36
|
2,289,098
|
35
|
2,461,235
|
Mainstream Multi-Outletb,c
|
19
|
12,149,908
|
29
|
5,774,343
|
34
|
5,577,820
|
35
|
6,046,190
|
aAccording
to SPINS (SPINS does not track sales from Whole Foods Market.)
b According
to SPINS/IRI (The Mainstream Multi-Outlet channel was formerly known as the
Food, Drug, and Mass Market channel [FDM], exclusive of possible sales at
Walmart, a major retailer in the US and beyond.)
c Data
for 2012 are according to Symphony/IRI and include Walmart, club stores (Sam’s,
Costco), military and dollar stores.
Sources: T. Smith (American
Botanical Council) e-mail to S. Gafner, September 2, 2015 and September 3, 2015.
K. Kawa (SPINS) e-mail to S. Gafner, July 11, 2016.
In addition to the dietary supplement
industry, SJW is used as an ingredient in the distillation of vodka, herbal
tea, and as a source of red, yellow, purple and orange dyes.3
2.2 Market dynamics: For the dietary supplement market in
the United States, SJW was a
relatively obscure plant used in traditional medicine until the late 1990s when
it skyrocketed in popularity following major media coverage of European clinical
research documenting its safety and efficacy for the treatment of mild-to-moderate
depression. In 1998, SJW was the second best-selling botanical dietary
supplement in the US mainstream market.13 The soaring demand quickly
out-paced the supply from wildcrafters in Europe and the United States, driving
up the wholesale price and motivating manufacturers to secure new sources of
supply. This global shortage in supply led to the appearance of commercial SJW products from Asia and in some cases, of unknown
origin containing other species of Hypericum
with differing chemical compositions and no proof of efficacy.14,15 "Given
the variation of the constituents, it was suggested that the drugs could not be
considered as pharmaceutically and therapeutically equivalent" to the SJW
extracts with clinically documented efficacy.15
The first reports of interactions
between SJW and several classes of prescription drugs were published in 1999
and were rapidly followed by others in the years 2000-2003. These articles
received considerable negative publicity and sales began to falter. In the
Mainstream Multi-Outlet channel, SJW fell to fifth place in 2001 and sales
continued to drop dramatically in 2002 (-40%), placing SJW in seventh place.16,17
Over the following decade, US sales of SJW continued to decline, albeit more
gradually (see Table 1 for 2012-2015 sales data). While it is tempting to blame
the decrease in US sales of SJW on the safety concerns raised by herb-drug
interaction studies and case reports, and questions raised about the touted anti-depressant
benefits after a highly publicized large NIH-funded clinical trial had a
negative outcome in people with major depression,18 the glut of
adulterated products with dubious therapeutic benefits which appear to have
become more available in the market also may have contributed to the deterioration
in SJW popularity in the US market.*
2.3 Supply sources: The supply of SJW for the European herbal
medicine market was traditionally obtained from wildcrafters in Eastern
European countries.12,19,20 Some of the global supply still comes
from these sources; according to the International Trade Centre (ITC) Market
Insider (2015), European manufacturers obtain most of their raw material from
producers and suppliers in Albania, Austria, Bosnia and Herzegovina, Bulgaria,
Croatia, Germany, Hungary, Italy, Kosovo, Poland, Romania, Serbia, and
Macedonia.21
In North America, SJW was traditionally
harvested from naturalized plants in the Pacific Northwest and eastern states.1
In 2015, most of the North American supply of commercial SJW extracts was
obtained from China (R. Das [BI Nutraceuticals] e-mail communication, September
15, 2016).
3 Adulteration
3.1 Known
adulterants: Other Hypericum species that have been
identified as historical SJW adulterants include H. barbatum, H. hirsutum, H. maculatum, H. montanum, H. tetrapterum,22
H. patulum,23 and
H. crux-andreae (syn. Ascyrum crux-andreae, Ascyrum stans).24
Also the following admixture of dyes have
been reported as co-occurring SJW adulterants: E123 Amaranth (FD&C Red #2), E133 Brilliant Blue (FD&C
Blue #1), E110 Sunset Yellow (FD&C Yellow #6), and E102 Tartrazine (FD&C
Yellow #5).25
3.2 Sources of information confirming adulteration: Historically, scientific reports of
SJW adulteration in the United States may be traced back to 1876.24 Although
there are no published systematic reviews on adulteration of SJW, there are
numerous reports of adulteration in the literature based on morphological,
chemical, and genetic evidence.
3.2.1 Morphological and chemical evidence: In the book Teedrogen, Wichtl (1984) stated that SJW is frequently adulterated
with the Hypericum species H. barbatum, H. maculatum, and H. montanum
which co-occur within the range of SJW.26 Berghöfer and Hölzl (1986)
also reported that SJW is frequently adulterated with other species of Hypericum, which occur within the European
range of SJW, and added the species H.
hirsutum and H. tetrapterum to
this list.22 They also remarked that SJW often interbreeds with the species
H. maculatum and H. tetrapterum to form hybrids with
intermediate features that are more challenging to classify taxonomically. Mitra
and Kannan (2007) briefly mention that, in India, where the availability of SJW
is limited, the Indo-Nepal species H.
patulum is sold as H. perforatum.23
In 1998, Kurth and Spreeman observed that the boom in the US market and
subsequent shortage of high quality material corresponded with the appearance of "more and
more" poor quality products with chemical profiles that differed
significantly from those of the clinically proven European SJW extracts.14
They describe a proliferation of commercial extracts from the "Far
East" (Asia) and "Chinese herb" with relatively high levels of
quercetin (degradation product), significantly lower levels of other flavonoids,
especially rutin, isoquercitrin, and biapigenin, and an inverse ratio of
pseudohypericin to hypericin (nearly 1:1 or 1:3) compared to the 1.5:1 or 2:1
ratio characteristically seen in European SJW extracts. The authors attributed
these findings to the use of other Hypericum species and they point out that
spectrophotometric methods for characterizing SJW can be manipulated by adding
colorants. The botanical identity of the adulterant Hypericum species was not
reported.
Meier (2003) noted "Recently, deviations [from the characteristic
high-performance liquid chromatography (HPLC) fingerprint of SJW] have been
increasingly observed: in the dried herb H. perforatum of Oriental origin,
especially China, with a botanically definitive identity, rutin is missing.27
Rutin has been included in the European monograph (Ph Eur) because in a whole
series of possible adulterations (other Hypericum species) this rutin is
missing." Kabelitz (2005) also remarked on the shortage of SJW following
the market boom and that "very soon considerable variability of
characteristic markers was apparent in the drugs offered for sale."15
He presented thin layer chromatography (TLC) data showing that rutin was
lacking in samples of H. elegans, H. indorum, H. maculatum, and H. montanum.
However, his chromatograms showed that in samples of "Chinese SJW," rutin
was present, and hypericin and/or pseudohypericin were missing.
A chromatographic and spectroscopic study by Huck-Pezzei et al. found
that commercial SJW extracts of "Chinese provenance" could be
distinguished from products of European origin using TLC, HPLC, and attenuated
total reflection mid-range infrared (ATR-MIR) and near infrared spectroscopy
(NIR) but not Fourier-transformed infrared (FTIR).28 TLC
chromatograms developed using the European Pharmacopoeia 8.0 (Ph Eur 8.0) method showed that the Chinese samples had an additional orange
fluorescent band below hypericin that was not present in the European samples.29
The European material contained the characteristic 1.5-2:1 ratio of
pseudohypericin to hypericin, while the Chinese samples exhibited the inverse
(1:2 pseudohypericin:hypericin); therefore, this ratio can be used as an
indication for the presence of an alternative species instead of H. perforatum.
The Chinese samples also contained relatively high amounts of quercetin and low
amounts of flavonol glycosides; in many cases, rutin and hyperforins could not be
detected by HPLC-UV. The authors concluded that the Chinese samples did not contain
SJW but rather another Hypericum species. They identified the adulterant species
as H. hirsutum based on the presence of the compounds kushenols G and H.
The
analysis of 37 commercial SJW products using high performance thin-layer
chromatography (HPTLC) with the conditions specified in the Ph Eur 8.0,29
United States Pharmacopeia 37 (USP
37),30 and USP 3831 identified 14 suspect samples.25
Eight samples (three commercial dry extracts and five capsules labeled to
contain SJW extract) produced a green color when solubilized in methanol (in
contrast to the expected red-brown color). Using the conditions specified in USP
38, the corresponding HPTLC chromatograms exhibited four atypical features
compared to authenticated reference samples. These findings suggested the
presence of other Hypericum species and/or
the presence of polar compounds not present in authentic SJW samples. A reverse-phase
(RP)-HPTLC method was developed to separate and identify the polar additives
found at the application position with the USP 38 method. These substances were
subsequently determined to be the dyes Amaranth, Brilliant Blue FCF, Sunset Yellow FCF, and Tartrazine. The dyes were present at concentrations
ranging from 0.51% and 1.33% among samples from different suppliers, and concentrations
also varied among batches from the same source. Overall, the pattern that
emerged was a formula of very little tartrazine, roughly equal amounts of
amaranth and brilliant blue, and a large quantity of sunset yellow. The authors
note that the flavonoid patterns exhibited in these chromatograms were similar
to those of the Chinese material described above by Huck-Pezzei et al.28
Of
the same 37 samples, another six samples (two containing raw herb of Chinese
origin, one finished product, and three dry extracts) produced the same atypical
chromatograms as the samples adulterated with dyes. However, when these six
samples were analyzed using the RP-HPTLC method, no dyes were detected. Microscopic
analysis of the raw material samples of Chinese origin revealed the presence of
an unknown plant. In a comparative analysis of H. hirsutum, H. montanum,
H. perforatum, H. tetrapterum, and H.
undulatum HPTLC chromatograms, the botanical adulterant present in the 14
suspect samples most closely resembled but was not identical to that of H. undulatum. It is noted that while the
adulterant Hypericum species was
detected in both raw material and finished product samples, the adulterating
suite of dyes were found only in SJW extracts.25
Another
2016 study, which evaluated 48 commercial SJW products, also detected dyes in
nine of the samples (A. Booker email communication to S. Gafner, August 10,
2016.). Seven of the nine products were from the United States, while the other
two were sold in the United Kingdom. Adulteration of botanical dietary
supplements with dyes has previously been reported with bilberry (Vaccinium
myrtillus, Ericaceae) fruit32 and
goldenseal (Hydrastis canadensis, Ranunculaceae)
root and rhizome.33
3.2.2 DNA-based
evidence: Howard et al. analyzed three commercial SJW products containing
dried ground plant material using the polymerase chain reaction (PCR) method
and primers to amplify the nuclear ribosomal internal spacer (ITS) sequences.34,35
DNA from nine of the 490 Hypericum
species was analyzed and, from these data, the following primers (markers) were
selected: a ~750 base pair (bp) "generic" ITS sequence, a 160 bp "genus
specific" sequence common to all nine species, and a 80 bp "species-specific"
sequence unique to H. perforatum. For
two of the products, the 160 bp Hypericum
genus-specific, and 80 bp H. perforatum
species-specific sequences were obtained, indicating that the products
contained SJW. For the third product (an herbal combination containing material
from several plant species), the generic ITS region was amplified but was of
smaller size compared to SJW and none of the two shorter Hypericum specific sequences were amplified, suggesting that
amplifiable DNA was present in the sample; however, it was not from H. perforatum.
Kazi et al. analyzed 13 commercial
SJW products (6 capsules, 5 tablets, and two tinctures) using the same primers
as Howard et al.36 The 80 bp H.
perforatum species-specific primer was amplified in each of the products,
indicating the presence of SJW material. However, only four products (all
capsules) yielded amplicons of the longer, generic ITS region, indicating that
the DNA in the other nine products was degraded or fragmented.
The botanical identity of the
contents of 44 North American single-ingredient commercial herbal products (N =
30 species) was assessed using DNA universal barcoding of the rbcl and ITS2 regions.37
Of the three products labeled as “St.
John’s wort” that were analyzed, one was found to contain barcodes of a
Fabaceae species, possibly senna (Senna
alexandrina, Fabaceae) only and no SJW barcodes. Barcodes for rice
(Oryza sativa, Poaceae) only were obtained
from the second SJW product; the authors suggest that this was possibly due to
the use of rice flour as an excipient. SJW
barcodes were amplified from the samples of the third SJW product. However, failure
to obtain SJW barcodes from two of the SJW products does not necessarily mean
the products did not contain SJW;
it demonstrates only that SJW DNA was not detected. It should be noted that the
veracity and reliability of these findings have been challenged.38
Using
real-time PCR assays and high resolution melting (HRM) analysis, Costa et al. assessed
DNA mini-barcodes for the ITS1 and maturase
kinase (matK) regions of 13
commercial herbal infusions labeled as containing either H. perforatum or H.
androsaemum. Detectable PCR products were 85 bp or 116 bp for ITS1, and 92
bp for matK.39 One product
labeled as containing only H. androsaemum
also tested positive for H. perforatum
DNA and another product labeled as containing H. perforatum tested positive for H. androsaemum DNA. The other 11 products tested positive only for
the DNA of the Hypericum species
indicated on the product label. The confidence level for species identification
using HRM was 98.5-99.9%.
3.3 Accidental or intentional adulteration: The botanical identification of SJW
is complicated by the significant natural variation observed throughout its
range (in both morphological features and chemical profiles), the many features
SJW shares in common with the other species in the section Hypericum, and the
propensity of SJW to interbreed with these closely-related species to produce
intermediate hybrids.8-10 Given these facts, the reports of frequent
adulteration with other Hypericum
species that are similar in appearance and co-occur within the range of SJW (i.e.,
H. barbatum, H. hirsutum, H. maculatum, H. montanum, and H. tetrapterum) are understandable and may be attributed to misidentification
or irresponsible wildcrafting.
It
seems less likely that adulteration with H.
patulum or H. undulatum may be accidental,
because these two species are noticeably different in appearance from SJW and they
do not grow in the same native habitats as SJW. Certainly, the adulteration of
SJW with other Hypericum species and
the suite of dyes described by Frommenwiler et al. constitute intentional
adulteration.25
3.4
Frequency of occurrence:
There are no published studies on the frequency of SJW adulteration. The reports
by Wichtl26 and Berghöfer and Hölzl22 that SJW is
frequently adulterated with other Hypericum
species have been cited by numerous other authors25,40 and is
reiterated on some manufacturer websites.41 Although corroborating
reports are lacking, given the challenges discussed in section 3.3 above,
adulteration with other Hypericum species
can be expected.
The
report of frequent substitution of SJW with H.
patulum by Mitra and Kannan23 has been repeated (verbatim) by
several other authors;42-44 however, the actual rate of occurrence
remains unknown.
Frommenwiler
et al. reported that almost 40% of the 37 commercial samples analyzed presented
atypical fingerprints indicative of adulteration with other Hypericum species and an additional 21%
were also adulterated with a suite of synthetic dyes.25 Booker et
al. found 19% of the 48 commercial products tested were adulterated with dyes.
3.5 Possible safety/therapeutic issues: The possible safety issues arising from the
substitution of SJW with other Hypericum species have not been evaluated
and few of these species have a history of traditional use as medicines. The
potential impact on therapeutic efficacy remains unknown. While several authors
have postulated that other Hypericum species with chemical profiles
similar to SJW may have therapeutic potential, supporting clinical evidence is
lacking and it is equally possible that such substitutions may significantly reduce
efficacy.45-47
Adulteration with dyes poses both
safety and legal issues. Amaranth E is banned in the United States due to
the potential toxicity of this dye.48 Although brilliant blue E133, sunset
yellow E110, and tartrazine E102 are approved colorants in the United States,
they are subject to batch certification by the FDA to ensure they meet the requirements for composition and
purity stated in the regulation. "Using uncertified versions of color
additives that are subject to FDA certification is illegal in foods, drugs,
cosmetics, and medical devices, and will adulterate these products."49
Although batch-certified brilliant blue, sunset yellow, and tartrazine
are approved colorants in the United States, they have been banned in a number
of countries due to safety concerns including behavioral problems in children, carcinogenicity,
and exacerbation of asthma and allergies.50,51 In the European Union, foods
containing sunset yellow and tartrazine must carry the additional labeling
"may have an adverse effect on activity and attention in children."52
The addition of these illegal dyes signals a deliberate effort to mask
the substitution of SJW with other Hypericum species that do not have a
history of safe use and may have decreased or no therapeutic benefits.
3.6 Pharmacopeial standards: The AHP monograph defines SJW as the
whole, fresh, or dried plant or its components, containing not less than 0.04%
naphthodianthrones of the hypericin group calculated as hypericin.1 The
USP requires not less than 0.04%
of hypericin and pseudohypericin combined and not less than 0.6% of hyperforin.31
The Ph Eur29 and WHO2 monographs specify a content of not
less than 0.08% total hypericins expressed as hypericin.
Frommenwiler
et al. observed that the 14 suspect samples they identified would fail the Ph Eur
identity test but would theoretically pass the USP identity test even though an
additional zone was present on the latter chromatograms.25 They
propose the addition of the following check to the USP 38 method: in cases
where an additional blue zone is observed at the application position, the
RP-HPTLC method to detect adulterant dyes should be conducted.
3.7 Analytical methods to detect adulteration: For whole and cut material,
botanical identity may be confirmed by a qualified analyst based on
organoleptic and macroanatomical characteristics. The identity of powdered
material may be determined using a combination of organoleptic, microscopic,
and chemical techniques such as TLC or HPTLC. According to Meier, the flavonoid
pattern in SJW is quite consistent, making chemical fingerprinting methods a
valuable approach to determine identity.27 There are numerous
chemical techniques that may be used to authenticate SJW extracts, including
TLC,22 HPTLC,25 HPLC-ultraviolet spectroscopy (HPLC-UV),
HPLC-mass spectroscopy (HPLC-MS), MIR and NIR spectroscopy,28
nuclear magnetic resonance (NMR), and various combinations of these methods. The
USP and Ph Eur provide official HPTLC and HPLC methods for identification. DNA barcoding
techniques may also be used to determine the botanical identity of raw
materials; however, the DNA in some extracts and finished products may be too
degraded for reliable identification,53,54 and additional techniques
must be used to confirm that the sample is composed of the correct plant parts.
3.8 Perspectives: Although SJW was been shown to be a
safe and effective treatment for mild to moderate depression,55,56
the market for this herb has been seriously undermined by negative publicity,
concerns about alleged and documented adverse herb-drug interactions, and the
sale of inferior products that do not have the same chemical profile/potency as
the SJW extracts demonstrated as efficacious in clinical trials. The onus (and
ability) to restore consumer confidence in the safety, efficacy, and high
quality of SJW products rests almost entirely on industry. An independent
assessment of the quality of SJW products currently on the market, specifically
focused on chemical profiles and phytoequivalency may significantly contribute
towards this objective.
It
may be questioned whether the reports of "Chinese SJW" with chemical
profiles inconsistent with that of "European SJW"14-15,25,27,28
are in fact cases of adulteration. Although all five articles imply that the
"Chinese SJW" samples contained H.
perforatum, Meier27 is the only researcher that explicitly
stated that the Chinese SJW material was authenticated as H. perforatum. Considering the distribution of SJW in China (see
section 1.7), the Meier samples most likely contained H. perforatum subsp. chinense.
The chemical profile of H. perforatum
subsp. chinense has not been
reported; however, it is possible that it may constitute a different chemotype
from that of the H. perforatum subspecies
which are distributed in Europe.
However,
this chemotype hypothesis does not explain the significant inconsistencies between
the chemical profiles ascribed to "Chinese SJW" by the different
research groups. Meier stated that rutin is missing in Chinese SJW27
and Huck-Pezzei et. al28 also did not detect rutin in Chinese SJW
samples. In contradiction, Kurth and Spreeman14 stated that Chinese
SJW herb and extract had low levels of flavonoids, especially rutin,
isoquercitrin, and biapigenin, and Frommenwiler et. al.25 and
Kabelitz15 demonstrated the presence of rutin in Chinese SJW samples.
Kabelitz also showed that pseudohypericin was absent in Chinese SJW. Although
pseudohypericin was present in the other Chinese SJW samples,14,25,27,28
Kurth and Spreeman14 and Huck-Pezzei et. al.28 reported
that Chinese SJW samples had an inverse ratio of pseudohypericin to hypericin (1:1
or 1:3) compared to "European SJW" which has ratios of 1.5:1 or 2:1.
This
variability in the chemical profile of "Chinese SJW" suggests that the
different "Chinese SJW" samples contained material from different
taxa; some "Chinese SJW" samples may contain H. perforatum subsp chinense,
or some may contain SJW hybrid(s) or other Hypericum
species, or some may contain a mixture of SJW and another Hypericum species as postulated by Frommenwiler et al.25
There are 64 Hypericum species (33
endemic) found in China, including the closely related species H. attenuatum and H. elegans, and the reported adulterants H. hirsutum and H. patulum.5
Clearly
further research is needed to determine the botanical identity or identities of
"Chinese SJW," as well as the chemical profile of H. perforatum subsp. chinense and its clinical efficacy. However,
the fact remains that these "Chinese SJW" samples do not present the
same chemical profile as the well-characterized SJW with demonstrated efficacy
and do not fulfill the Ph Eur 8.0 and USP 38 identity criteria for SJW.
4 Conclusions
The
occurrence of adulteration of SJW with other Hypericum species is an ongoing issue that must be addressed with appropriate
quality control protocols.
The
co-occurrence of adulteration with dyes and other Hypericum species raises safety and legal concerns. Industry
members are advised to have adequate assays to authenticate their SJW material,
and to add an appropriate analytical method to test for dyes to their quality
control protocol for SJW extracts.
Research
is needed to determine the botanical identity and clinical efficacy (i.e., the wound-healing
and antidepressant effects demonstrated with European supplies) of "Chinese SJW."
* A systematic review from 2016
including 35 randomized controlled clinical trials on a total of 6993 patients
concluded that SJW extracts were superior to placebo and similarly effective to
standard antidepressant drugs as a treatment for cases of mild and moderate depression.57
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