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Changes in Chemical Constituents and
Kidney-Yang Tonifying of Traditional Herbs
After Processing: A Brief Review
Minh-Nhut Truong
1
, Hong-Hieu Nguyen Thi
1
, Hoang-Huy Tran
1
and Lan-Phuong Le Thi
1
Abstract
Background: Kidney-Yang deficiency is one of the common medical syndromes in traditional medicine, characterized by symp-
toms such as weakness, coldness in the lower back and knees, cold, fatigue, etc. In clinical practice, Yang tonifying medicines are
often used to treat patients with Kidney-Yang deficiency. Moreover, the medicinal processing method according to the principles
of traditional medicine can enhance the effects on the Kidney of these herbs. This brief overview aims to gather and assess the
post-processing modifications to the chemical composition and the kidney-Yang tonifying effects of specific traditional herbal
remedies. Methodology: Firstly, all kidney-Yang tonifying herbs were collected. Next, the selection was made based on the herbs
with processing procedures specified in Circular 30/2017/TT-BYT issued by the Vietnamese Ministry of Health. All studies on the
chemical composition and/or effects of processed drugs were searched in the PubMed and Google Scholar databases using the
search formula: processed +scientific name of herbal medicine. Finally, among the studies on the changes in effects after processing,
only studies on the tonifying Yang effect were included in this review. Results: The kidney Yang-nourishing effects of the five tra-
ditional herbal medicines prescribed in Circular 30/2017/TT-BYT by the Ministry of Health of Vietnam (Radix Morindae officinalis,
Cortex Eucommiae, Herba Cistanches, Semen Cuscutae, and Radix Dipsaci) have been demonstrated through several studies and
summarized. From the PubMed and Google Scholar databases, 25 studies were collected for the review. Additionally, the changes in
composition and content of certain active compounds in these herbal medicines have also been searched and
reported. Conclusion: This report provides a brief overview of the differences between chemical constituents and kidney-Yang
tonifying of some traditional herbs after processing to partially contribute scientific evidence for standardizing the preparation pro-
cesses and serve as an important reference for clinical practitioners of traditional medicine.
Keywords
kidney-Yang tonifying, traditional herbs, processing, chemical constituents, Yang tonifying herbs
Received: December 1st, 2023; Accepted: April 11th, 2024.
Introduction
The disease is a process that disrupts the balance between
various factors in the body and is used to explain the causes
of many pathological conditions in modern medicine, such as
gastric ulcers (imbalance between protective and ulcer-causing
factors), Parkinson’s disease (imbalance between acetylcholine
and dopamine levels in the brain), and more. Similarly, many
traditional medical syndromes are believed to be a result of
imbalances within the body, particularly imbalances between
Yin and Yang. According to the Eight Principles (eight diagnos-
tic principles of traditional medicine), Yin and Yang represent
the overall manifestation of the syndrome and are the first
factors considered in the diagnostic process.
1
In addition to Yin and Yang, the “Full-Empty”Pattern
is one of the four principles in the Eight Principles. It
encompasses the clinical manifestations of overall weakness
and depletion of the body’s vital energy (Qi). Within the cate-
gory of empty patterns, kidney-Yang deficiency is one of the
syndromes related to the Kidney organ, characterized by symp-
toms such as weakness, coldness in the lower back and knees,
feeling cold, fatigue, cold urine, frequent urination, nocturia,
edema in the ankles, loose stools, infertility in women,
1
Faculty of Traditional Medicine, University of Medicine and Pharmacy, Ho Chi
Minh City, Viet Nam
Corresponding Author:
Lan-Phuong Le Thi, Faculty of Traditional Medicine, University of Medicine
and Pharmacy, Ho Chi Minh City, Viet Nam.
Email: ltlphuong@ump.edu.vn
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(https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further per mission
provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
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impotence and decreased libido in men, premature ejaculation,
low sperm count, pale and wet tongue, and weak pulse. There
are several factors that can contribute to the development of
kidney-Yang deficiency, such as chronic internal injuries (due
to spleen-Yang deficiency or kidney-Yin deficiency), excessive
sexual activity, overexertion, irregular diet, etc.
1
In the clinical
treatment of kidney-Yang deficiency, traditional Vietnamese
medicine utilizes a group of Yang tonifying herbs in various
herbal formulas. Some valuable herbs used include Ba kích
(Morinda officinalis), Nhu
c thung dung (Cistanche deserticola), Tho
ty tử(Cuscuta chinensis), and so on.
The medicinal processing method is a unique technique in tra-
ditional medicine, both in general Eastern medicine and specifically
in Vietnamese medicine. The medicinal processing method is
based on theories (Yin and Yang, Five Elements, and Meridians)
and folk experiences that enhance the therapeutic effects or
create new therapeutic effects of medicines on the target organs.
Additionally, some other purposes of processing medicinal materi-
als may involve reducing or eliminating the adverse effects of
drugs, thus avoiding discomfort for the patients.
2
The processing procedures of traditional herbal medicines
have been standardized and published by the Vietnamese
Ministry of Health in Circular 30/2017/TT-BYT in 2017.
Out of the 103 traditional herbal medicines listed in this docu-
ment, five kidney-Yang tonifying herbs are processed using
various procedures (as presented in Table 1).
3
This brief review aims to gather and assess the post-
processing modifications to the chemical composition and the
kidney-Yang tonifying effects of specific traditional herbal rem-
edies. This intends to be a valuable resource for clinical practi-
tioners of traditional medicine and provide scientific evidence
for standardizing the preparation procedures.
Processing Procedures and Changes of Five
Kidney-Yang Tonifying Herbs
Our review strategy is as follows: firstly, all kidney-Yang tonify-
ing herbs categorized according to “The Foundations of
Chinese Medicine: A comprehensive text, 3rd edition”were col-
lected. Next, the selection was made based on the herbs with
processing procedures specified in Circular 30/2017/
TT-BYT issued by the Vietnamese Ministry of Health. All
studies on the chemical composition and/or effects of pro-
cessed drugs were searched in the PubMed and Google
Scholar databases up to November 1, 2023, using the search
formula: processed +scientific name of herbal medicine.
Finally, among the studies on the changes in effects after pro-
cessing, only studies on the Tonifying Yang effect were included
in this review.
Five traditional herbs met the aforementioned selection cri-
teria. From the PubMed and Google Scholar databases, 25
studies were collected for the review.
Radix Morindae officinalis—Vietnamese Name:
Ba Kích
Processing
White Wine-Processed. A medicinal alcohol solution containing
30% to 40% alcohol (ratio 15% to herb ingredient, v/w) is
mixed with Radix Morindae officinalis. The mixture is incu-
bated for about 1 to 2 hours until the alcohol is fully absorbed
and roasted with low heat until dry.
3
Salt-Processed. A 5% saline solution (NaCl) (ratio 15% to herb
ingredient, v/w) is mixed with Radix Morindae officinalis.
The mixture is incubated for about 2 to 4 hours for being
fully absorbed and roasted with low heat until dry.
3
Licorice Decoction-Processed. Licorice (ratio 15% to herb ingredi-
ent, w/w) is decocted by boiling three times with water (at a
3-fold amount compared to the Licorice root) for 30 minutes
each time and concentrating through evaporation to a specific
volume (at a 15% ratio to the herbal material, v/w). The decoc-
tion is then mixed with Radix Morindae officinalis and the
mixture is incubated for about 6 hours for being fully absorbed
before being roasted with low heat until dry.
3
Changes in Chemical Constituents
The phytochemical compounds of Radix Morindae officinalis
have been extensively studied and reported to predominantly
Table 1. List of Processed Kidney-Yang Tonifying Herbs from Vietnamese Ministry of Health.
3
No. Name of ingredients Plant name Crude drug Part used Processing method
1 Ba kích Morinda officinalis How. Radix Morindae officinalis Root White wine-processed
Salt-processed
Licorice decoction-processed
2Đo
tro
ng Eucommia ulmoides Oliv. Cortex Eucommiae Stem bark White wine-processed
Salt-processed
Charcoal-processed
3 Nhu
c thung dung Cistanche deserticola Y.C.Ma Herba Cistanches Stem White wine-processed
4Tho
ty tửCuscuta chinensis Lam. Semen Cuscutae Seed Salt-processed
5Tu
cđoa
nDipsacus asperoides C.Y.Cheng, et
T.M.Ai./Dipsacus japonicus Miq.
Radix Dipsaci Root White wine-processed
Salt-processed
2Natural Product Communications
belong to various groups of compounds, including iridoid gly-
cosides, anthraquinones, polysaccharides, organic acids, volatile
oils, and more.
4
Among the mentioned compound groups, the iridoid glyco-
side group exhibits many characteristic biological effects for
Radix Morindae officinalis herbal medicine. One specific
iridoid glycoside component in Radix Morindae officinalis
was monotropein, which was determined to decrease in concen-
tration by more than 30% after salt processing.
5
A total of 55 chemical compounds between raw Radix
Morindae officinalis and salt-processed Radix Morindae offi-
cinalis were found to undergo changes in their levels after
analysis using ultra-performance liquid chromatography
quadrupole time-of-flight mass spectrometry (UPLC-Q-
TOF/MS) technique. Among these compounds, 29 belonged
to the fructo-oligosaccharide group (including GF2 and GF21),
1,3-dihydroxy-2-methylanthraquinone-3-O-β-D-fructofuranose-
(l→2)-β-D-fructofuranoside, monotropein, and deacetylasperulo-
sidic acid. These compounds were found to have higher levels
in raw Radix Morindae officinalis compared to salt-processed
Radix Morindae officinalis. On the other hand, 26 compounds,
including difructose anhydrides, iridoid glycoside derivatives,
and sucrose, were found to have higher levels in salt processing
herb.
6
The content of polysaccharide compounds such as oligosac-
charides GF7 (Fructo-oligosaccharide DP8) and GF8
(fructo-oligosaccharide DP9) decreased, while GF1 (sucrose)
and GF2 (1-ketose) in Radix Morindae officinalis increased
after processing (with salt and licorice decoction). Specifically,
salt-processed Radix Morindae officinalis had a higher total oli-
gosaccharide content compared to licorice decoction-
processing one.
7
Changes in Kidney-Yang Tonifying Activities
The pharmacological effects of Radix Morindae officinalis have
been extensively studied and have been reported to have
notable activities such as antioxidant, analgesic (pain-relieving),
anti-inflammatory, anti-osteoporosis (bone-strengthening),
and anxiolytic (reducing anxiety and depression) effects.
3
According to traditional medicine, Radix Morindae officinalis
is considered a Yang tonifying herb with a pungent and sweet
taste, and warm nature, and it is associated with the Kidney
meridian. In clinical practice, Radix Morindae officinalis is
used for its functions of tonifying the kidney Yang, strengthen-
ing the tendons and bones, tonifying the Spleen and Stomach,
benefiting essence, and more. It is commonly used to treat con-
ditions such as kidney-Yang deficiency, spermatorrhea, impo-
tence, knee weakness, and joint pain.
8
Salt-processed Radix Morindae officinalis has been found to
have better effects than licorice decoction-processing and raw
ones in improving parameters such as body weight, testicular
coefficient (the ratio of testicular weight to body weight), epidid-
ymal coefficient (the ratio of epididymal weight to body weight),
serum testosterone, serum cortisol, and serum creatinine in
adenine-induced kidney-Yang deficiency mice.
9
Moreover, the
energy exchange capacity in methimazole-induced kidney-
Yang deficiency rats significantly increased when using salt-
processed Radix Morindae officinalis compared to the group
using the raw herb.
10
Cortex Eucommiae—Vietnamese Name:
ĐoTro
ng
Processing
Salt-Processed. A saline solution (NaCl) (ratio 17% to herb ingre-
dient, v/w, prepared by dissolving 0.03 g of salt in 170 mL of
distilled water) is mixed with Cortex Eucommiae. The
mixture is incubated for about 1 hour for being fully absorbed
and roasted with medium heat until the threads break.
3
White Wine-Processed. A medicinal alcohol solution (ratio 20% to
herb ingredient, v/w) is mixed with Cortex Eucommiae. The
mixture is incubated for about 1 hour for being fully absorbed
and roasted with medium heat until the threads break.
3
Charcoal-Processed. Cortex Eucommiae is roasted with a strong
heat, stirring continuously until white smoke appears and all
the threads break. A small amount of distilled water is
sprayed and the material is roasted with a small heat for
about 2 to 3 minutes before removing and cooling.
3
Changes in Chemical Constituents
More than 200 phytochemical compounds have been extracted,
isolated, and successfully identified in Cortex Eucommiae,
belonging to various groups such as lignans, iridoids, flavo-
noids, phenolic acids, sterols, fatty acids, volatile oils, and
more. Among these, lignans are a group of compounds that
exhibit numerous valuable biological effects of Cortex
Eucommiae.
11
The number of compounds as well as the content of pinor-
esinol diglucoside in salt processing Cortex Eucommiae was
lower compared to raw herbal medicine when analyzed by high-
performance liquid chromatography (HPLC). The evaluated
chemical compounds included pinoresinol diglucoside,
genipin, geniposide, geniposidic acid, caffeic acid, chlorogenic
acid, and quercetin, which showed a dramatical decrease in
content after processing (salt processing and charcoal process-
ing), as demonstrated in Table 2.
12
The charcoal-frying process of Cortex Eucommiae was
proven to degrade several chemical compounds, such as geni-
posidic acid, chlorogenic acid, genipin, licoagrosid F, and syrin-
garesinol di-O-β-D-glucopyranoside. The compounds wogonin
and oroxylin A were completely degraded after charcoal
frying, while three other compounds, geniposide,
pinoresinol-di-O-β-D-glucopyranoside, and baicalein, had an
increase after the processing. On the other hand, the salt-
processed process increased the extractability of chlorogenic
Truong et al. 3
acid in Cortex Eucommiae without statistically degrading other
compounds.
13
Changes in Kidney-Yang Tonifying Activities
Studies on the pharmacological effects of Cortex Eucommiae
have provided scientific evidence of its medicinal effects,
including blood pressure-lowering, blood sugar-lowering, anti-
bacterial, anti-inflammatory, immune-modulating, anti-tumor,
antioxidant, and anti-osteoporosis effects.
11
According to tradi-
tional medicine, Cortex Eucommiae is described as having a
sweet and spicy taste, and warm properties, and acts to the
Kidney and Liver organs. It is believed to tonify the Kidney,
strengthen the tendons and bones, support pregnancy, and reg-
ulate blood pressure. Moreover, Cortex Eucommiae is used
clinically to treat conditions such as liver–kidney deficiency,
lower back pain, knee weakness, joint pain, spermatorrhea,
impotence, and more.
8
Raw Cortex Eucommiae was proven to have a regulatory
effect on the secretion of corticosterone in the adrenal cortex
and tri-iodothyronine, and tetra-iodothyronine in the hypothal-
amus–pituitary–thyroid axis in kidney-Yang deficiency mice.
On the other hand, salt-processed herbal medicine showed
improvements in these parameters in the treating group.
14
Herba Cistanches—Vietnamese Name: Nhu c
Thung Dung
Processing
An alcohol solution (ratio 30% to herb ingredient, v/w) is
mixed with Herba Cistanches. The mixture is steamed for
about 24 to 48 hours until black or golden brown in color.
3
Changes in Chemical Constituents
Chemical composition analysis papers of Herba Cistanches
have demonstrated the presence of over 100 compounds.
Common groups of compounds found in Herba Cistanches
include essential oils, iridoids, lignans, alditols, polysaccharides,
phenylethanoid glycosides, and more.
15
The total content of phenylethanoid glycosides, polysaccha-
rides, isoacteoside, and osmanthuside B in wine-processed
Herba Cistanches was significantly higher compared to raw
herbal medicine. Additionally, the content of phenylethanoid
glycosides with a 6′-O-caffeoyl group attached to the
8-O-β-D-glucopyranosyl moiety, such as isoacteoside, isocista-
noside C, isocampneoside I, and isomartynoside, was
also numerous higher in the processed one. However, the
content of 2′-acetylacteoside, acteoside, and phenylethanoid
glycosides with a 4′-O-caffeoyl group attached to the
8-O-β-D-glucopyranosyl moiety (acteoside, cistanoside C, camp-
neoside II, osmanthuside) decreased substantially after process-
ing with wine.
16,17
The results of the ultra-performance liquid chromatography–
tandem mass spectrometry (UPLC–MS/MS) analysis combined
with proposed molecular networking data identified 34 chemical
compounds that can be used to differentiate raw and wine-
processed Herba Cistanches (marker compounds). Among these
compounds, 6 belong to the iridoid group (kankanoside B, mus-
saenosid acid, 8-epiloganic acid, adoxosidic acid, kankanoside A,
and kankanoside N), 20 belong to the phenylethanoid glycoside
group (kankanoside F, decaffeoylacteoside, cistantubuloside
C1/2, cistanoside H, campneoside II, decaffeoylacteoside, acteo-
side, crenatoside, isocampneoside I, brandioside, isosyringalid A
3′-α-L-rhamnopyranoside, kankanoside J1, pheliposide, kankano-
side G, isocistanoside C, osmanthuside B, cistubuloside B, and
tubuloside E), and 12 are other compounds (kankanose, cistanoside
F, (2E,6Z)-8-β-D-glucopyranosyloxy-2,6-dimethyl-2,6-octadienoic
acid, kankanoside O, (+)-pinoresinol-O-β-D-glucopyranoside,
(+)-syringaresinol-O-β-D-glucopyranoside, salsaside B, and
dibutyl sebacate).
18
In 2023, Hou et al conducted a study on the changes in poly-
saccharide composition among different forms of Herba
Cistanches, including raw samples, enzymatic hydrolysis, hot
air drying, wine processing, and high-pressure steaming. The
results revealed that the polysaccharide component of the wine-
processing Herba Cistanches exhibited compact structures and
had the largest molecular chain compared to the polysaccharide
components in the other forms of herbal medicine.
19
Changes in Kidney-Yang Tonifying Activities
Research on the biological activities of Herba Cistanches has
been conducted and reported with pharmacological effects
such as improving brain function, enhancing libido, and boost-
ing the immune system.
15
According to traditional medicine,
Herba Cistanches is believed to have functions in tonifying
the Kidney, strengthening Yang, and promoting bowel move-
ments, and is used in treating syndromes related to kidney-
Yang deficiency or constipation.
8
Kidney-Yang deficiency male mice treated with raw Herba
Cistanches showed restoration of the levels of sex hormones
(testosterone and estradiol), improvement in antioxidant
effects, and increased kidney, seminal vesicle, epididymis, and
testicular weights. Specifically, the group of mice treated with
Table 2. The Changes in the Content of Several Compounds in Salt
Processing and Charcoal Processing Cortex Eucommiae.
12
Chemical compound
Decrease in content (compared to raw
form)
Salt-processed Charcoal-processed
Pinoresinol diglucoside 30% 85%
Genipin 25% 98%
Geniposide 40% 70%
Geniposidic acid 40% 70%
Caffeic acid 75% 75%
Chlorogenic acid 40% 75%
Quercetin 60% 50%
4Natural Product Communications
wine-processed Herba Cistanches exhibited typically better
increases in kidney and seminal vesicle weights compared to
unprocessed ones.
19
In 2020, Liu et al conducted a study comparing the
immune-endocrine function of different forms of Herba
Cistanche in kidney-Yang deficiency rats induced by glucocorti-
coids. The results showed that the groups of rats treated with
both raw and processed Herba Cistanche exhibited increased
weights of the adrenal glands and spleen. They also showed dra-
matic changes in the levels of serum hormones such as testos-
terone, CRH, ACTH, CORT, and cortisol. The immune factors
IL-4 and IL-8, the CD4+/CD8+ratio, and the expression of
Bcl-2, caspase-3, Fas, FasL, and CaM in the pseudo-synovial
tissue were also significantly different compared to the
control group. Additionally, the concentrations of IL-6,
TNF-α, IFN-γ, and the expression of CaM mRNA in the hypo-
thalamic–pituitary region decreased in the experimental
groups.
20
Semen Cuscutae—Vietnamese Name: Tho
ty tử
Processing
A saline solution (ratio 15% to herb ingredient, v/w, pre-
pared by dissolving 20 g of salt in 150 mL of distilled
water) is mixed with Semen Cuscutae. The mixture is incu-
bated for about 30 minutes for being fully absorbed and
roasted with low heat until the particles start to expand,
and the mixture turns a golden brown color with a mild
and pleasant aroma.
3
Changes in Chemical Constituents
The reports on the phytochemical composition of Semen
Cuscutae indicate the presence of various chemical compounds
belonging to different groups such as flavonoids, polysaccha-
rides, alkaloids, steroids, volatile oils, lignans, and more. These
compounds are believed to contribute to the therapeutic
effects of the herbal medicine.
21
Figure 1 illustrates the chemical
structures of some compounds in Semen Cuscutae that were
affected by the processing procedures.
The HPLC analysis results showed that Semen Cuscutae can
be differentiated between the raw form and the salt processing
form based on five compounds: hyperoside, astragalin, kaemp-
ferol, isorhamnetin, and quercetin. The content of hyperoside
was found to decrease in the salt-processed Semen Cuscutae,
while the other four compounds (astragalin, kaempferol, iso-
rhamnetin, and quercetin) were found to have higher levels in
the processed form compared to the raw one. Furthermore,
the total flavonoid content in the salt-roasted Semen Cuscutae
extract showed a statistically significant increase compared to
the raw herb.
22
Another published study reported a statistically significant
increase in the content of certain chemical compounds
(3-caffeoylquinic acid, 4-caffeoylquinic acid, 3,4-dicaffeoylquinic
acid, 3,5-dicaffeoylquinic acid, caffeic acid, 5-O-feruloylquinic
Figure 1. The chemical formulas of the five compounds in Semen Cuscutae influenced by the processing method.
Truong et al. 5
acid, p-hydroxycinnamic acid, astragalin, kaempferol, isorhamne-
tin, isoquercitrin, and luteolin-7-O-glucoside) in Semen Cuscutae
after salt and wine processing. The analysis results revealed that
two compounds, hyperoside, and 3-caffeoylquinic acid, had high
levels in the processed Semen Cuscutae samples.
23
In addition, Changli et al demonstrated that the processing
temperature was a factor that led to changes in the content of
six phytochemical compounds (neoclorogenic acid, cryptophyl-
logenic acid, caffeic acid, quercetin, isorhamnetin, and kaemp-
ferol) between raw and processed Semen Cuscutae.
24
Changes in Kidney-Yang Tonifying Activities
Semen Cuscutae has been extensively studied and shown to
possess numerous pharmacological effects such as skin protec-
tion, liver protection, anti-osteoporosis properties, immune-
modulating effects, antioxidant activity, anti-aging effects,
effects on the reproductive system, and kidney protection.
21
In traditional medicine, Semen Cuscutae is used for its tonifying
and strengthening properties on the kidney Yang, brightening
eyes, and benefiting urinary function. It is commonly utilized
in the treatment of diseases related to kidney-Yang deficiency,
liver–kidney weakness, frequent urination, and blood in the
urine.
8
Hydrocortisone sodium succinate-induced kidney-Yang
deficiency rats treated with raw Semen Cuscutae increased in
the weight of the kidney, testes, epididymis, and prostate. On
the other hand, treatment with salt-processed Semen
Cuscutae led to an increase in the weight of the kidney, testes,
epididymis, and seminal vesicles. Furthermore, both raw and
processed herbal medicine treatments showed positive signs
in immune function, including the regulation of T-cell sub-
groups and a decrease in the concentration of IgG and IgM
in the blood.
22
Radix Dipsaci—Vietnamese Name: Tu cĐoa
n
Processing
Salt-Processed. A saline solution (ratio 2% to herb ingredient,
v/w) is mixed with Radix Dipsaci. The mixture is incubated
for being fully absorbed and roasted with small heat until dry.
3
White Wine-Processed. A medicinal alcohol solution (ratio
15%-20% to herb ingredient, v/w) is mixed with Radix
Dipsaci. The mixture is incubated for being fully absorbed
and roasted with small heat until dry.
3
Changes in Chemical Constituents. The studies on the chemical
composition of Radix Dipsaci indicated that phytochemical
properties belonging to the group of oleanane-type triterpe-
noids are the main components responsible for its biological
effects. Additionally, various compounds from different
groups such as iridoids, phenolics, essential oils, alkaloids,
lignans, fatty acids, and others have been isolated and identified
through research. These findings highlight the diverse array of
chemical constituents present in Radix Dipsaci, which contrib-
ute to its therapeutic properties.
25
In 2014, Song et al conducted a study on the variation of
asperosaponin VI, a signature compound of Radix Dipsaci,
through alcohol frying using HPLC analysis. Three factors of
the processing procedure of Radix Dipsaci were investigated
using an orthogonal design at four levels: alcohol-to-herb
ratio (10, 15, 20, and 25%), frying time (6, 8, 10, and
12 minutes), and frying temperature (100, 130, 160, and 190 °
C). The results revealed that the frying temperature had a signif-
icant impact on the variation of asperosaponin VI content in
Radix Dipsaci, and an optimized processing procedure was pro-
posed, which included an alcohol-to-herb ratio of 15%, a frying
time of 6 minutes, and a frying temperature of 100 °C.
26
In 2015, Luo et al reported the differences in chemical com-
position between raw Radix Dipsaci and Radix Dipsaci pro-
cessed with alcohol using HPLC analysis. The results
indicated that the processing with alcohol increased the
content of asperosaponin VI in Radix Dipsaci and revealed
the appearance of two new peaks in the chromatographic fin-
gerprint region. This suggested that the processing method
with alcohol-induced changes in the chemical profile of Radix
Dipsaci led to the alteration and emergence of additional com-
pounds in its chromatographic pattern.
27
In 2016, using the advanced analytical technique
UPLC-Q-TOF/MS, Tao et al observed a greater variation in
the content of various plant phytochemicals in Radix Dipsaci
processed with alcohol. The analysis results revealed an increase
in the content of compounds such as asperosaponin VI, acety-
lated derivatives, and caffeic acid analogs in the alcohol-
processed Radix Dipsaci. However, the content of phenolic
compounds, such as dicaffeoylquinic acid, was lower in the
alcohol-processed herbal medicine.
28
In 2018, Tao et al continued their research by developing a
simultaneous quantification method for eight chemical com-
pounds in Radix Dipsaci using UHPLC–MS/MS. They
applied this method to compare the chemical composition
between raw Radix Dipsaci and Radix Dipsaci processed with
alcohol. The quantification results showed that four out of
the eight chemical compounds increased in content after pro-
cessing, including loganic acid, chlorogenic acid, dipsacoside
B, and asperosaponin VI. On the other hand, the levels of
four compounds, namely 3,5-dicaffeoylquinic acid, 4-caffeoyl-
quinic acid, loganin, and sweroside, were lower in the alcohol-
processed Radix Dipsaci.
29
In 2019, Tao et al upgraded and improved the quantification
process of phytochemical compounds in Radix Dipsaci using
UPLC-Q-TOF/MS. The quantification method aimed to deter-
mine the levels of 10 compounds, including loganic acid,
loganin, 3,5-dicaffeoylquinic acid, 4-caffeoylquinic acid,
3,4-dicaffeoylquinic acid, sweroside, dipsacussaponin B, dipsa-
coside A, asperosaponin V, and asperosaponin VI, and
applied it to quantify these compounds in alcohol-processed
Radix Dipsaci. The results showed that five compounds,
6Natural Product Communications
Table 3. Summary of the Influence of Processing on Kidney-Yang Tonifying Herbal Medicines.
Name of herbal
medicine
The influence of processing
Chemical constituents Kidney-Yang tonifying effect
1 Ba kích (Radix
Morindae officinalis)
↓content: monotropein
5
, fructo-oligosaccharide DP8,
fructo-oligosaccharide DP9
6
↑content: sucrose, 1-ketose, difructose anhydride, and iridoid
glycoside derivatives
6,7
Improvement: body weight, testicular coefficient, epididymal coefficient, serum
testosterone, serum cortisol, serum creatinine, level of liver glycogen, muscule
glycogen, free fatty acid, lipoprotein lipase, liver lipase, Na
+
–K
+
-ATPase, Ca
2+
–Mg
2
+
-ATPase, SDH
9,10
Chemical compounds related to the Kidney-Yang tonifying effect: monotropein,
deacetyl asperulosidic acid, asperulosidic acid, and asperuloside
32
2Đo
tro
ng (Cortex
Eucommiae)
↓content: pinoresinol diglucoside, genipin, geniposide, geniposidic
acid, caffeic acid, chlorogenic acid, and quercetin
12
↑content: geniposide, pinoresinol-di-O-β-D-glucopyranoside, and
baicalein
13
Decomposition: wogonin and oroxylin A
13
Improvement: regulatory effect on the secretion of corticosterone in the adrenal cortex
and tri-iodothyronine, tetra-iodothyronine in the hypothalamus–pituitary–thyroid
axis
14
Chemical compounds related to the Kidney-Yang tonifying effect: geniposidic acid,
chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, and hyperoside
33
Kidney-Yang tonifying targeted proteins: AKT1 and PTGS2
14
3 Nhu
c thung dung
(Herba Cistanches)
↓content: 2′-acetylacteoside, acteoside, phenylethanoid glycosides
with a 4′-O-caffeoyl group attached to the 8-O-β-D-glucopyranosyl
moiety
16,17
↑content: phenylethanoid glycoside, polysaccharide, isoacteoside,
osmanthusid B, phenylethanoid glycosides with a 6′’-O-caffeoyl
group attached to the 8-O-β-D-glucopyranosyl moiety
16,17
↑:kidney, seminal vesicle, epididymis, testicular weights, adrenal glands, spleen,
testosterone, CRH, ACTH, CORT, and cortisol. The immune factors IL-4 and IL-8,
the CD4+/CD8+ratio, and the expression of Bcl-2, caspase-3, Fas, FasL, and CaM in
the pseudo-synovial tissue
19,20
↓:IL-6, TNF-α, IFN-γ, and the expression of CaM mRNA in the hypothalamic–pituitary
region
20
Kidney-Yang deficiency treatment mechanism: counteracting dysregulated
reproductive hormones and immune factors in mice subjected to excessive
glucocorticoid dosing; observing enhancing and restoring effects on the hypothalamic–
pituitary–adrenal axis and improving immune function
20
4Tho
ty tử(Semen
Cuscutae)
↓content: hyperoside
22
↑content: hyperin, quercetin, kaempferol, total flavonoid,
3-caffeoylquinic acid, 4-caffeoylquinic acid, 3,4-dicaffeoylquinic
acid, 3,5-dicaffeoylquinic acid, caffeic acid, 5-O-feruloylquinic acid,
p-hydroxycinnamic acid, astragalin, kaempferol, isorhamnetin,
isoquercitrin, and luteolin-7-O-glucoside
23
↑:weight of the kidney, testes, epididymis, and prostate (raw); weight of the kidney, testes,
epididymis, and seminal vesicles (processed)
22
Regulation of T-cell subgroups and a decrease in the concentration of IgG and IgM in the
blood
22
5Tu
cđoa
n (Radix
Dipsaci)
↓content: dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid,
4-caffeoylquinic acid, loganin, swerosid, and 3,4-dicaffeoylquinic
acid
27–30
↑content: asperosaponin VI, acetylated derivatives and caffeic acid,
loganic acid, chlorogenic acid, dipsacoside B, dipsacoside A, and
asperosaponin V
27–30
Optimized processing procedure: alcohol-to-herb ratio of 15%,
frying time of 6 minutes, and frying temperature of 100°C
26
↑:organ parameters, hormone levels, (ACTH, CORT, T4, TNF-α, testosterone, estradiol,
and GH), and activity of certain enzymes (cyclic adenosine monophosphate (cAMP),
cyclic guanosine monophosphate (cGMP), Na
+
–K
+
-ATPase); expression of proteins
Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 in kidney
31
Kidney-Yang deficiency treatment mechanism: intervention in the BMP-Smad
signaling pathway
31
Truong et al. 7
namely loganic acid, asperosaponin VI, dipsacus saponin B, dip-
sacoside A, and asperosaponin V, increased in content after pro-
cessing. Conversely, the remaining five chemical compounds
exhibited a decrease in content in the alcohol-processed
herbal medicine.
30
Changes in Kidney-Yang Tonifying Activities. Radix Dipsaci is a
medicinal herb that has been extensively studied in traditional
medicine for its various pharmacological effects. It has been
shown to have benefits such as anti-osteoporosis, bone fracture
healing, neuroprotective properties, uterine relaxation, anti-
aging effects, liver protection, anti-myocardial ischemia, anti-
inflammatory properties, and anti-rheumatic effects.
25
According to the theories of traditional medicine, Radix
Dipsaci is considered a Yang tonifying herb with actions that
tonify the Kidney, strengthen the tendons and bones, promote
Blood circulation, regulate the meridians, detoxify the body,
and treat acne.
8
Regarding the therapeutic effects on kidney-Yang deficiency,
rats treated with alcohol-processed Radix Dipsaci showed
improved organ parameters, hormone levels, and activity of
certain enzymes, which were statistically significant compared
to raw Radix Dipsaci.
31
Discussion
In the clinical practice of traditional medicine, tonic remedies
containing Yang tonifying herbs are commonly used to treat
kidney-Yang deficiency. Processing methods such as roasting
or salt-processed are employed to enhance the Yang nature
and reduce the Yin nature of the herbs.
1
Some herbs are pro-
cessed into charred form (Cortex Eucommiae) or salt-
processed form (Radix Morindae officinalis, Cortex
Eucommiae, Semen Cuscutae, and Radix Dipsaci) to direct
the herbs’effects toward the Kidney meridian, according to the
theories of Five Elements and Meridians. Additionally, three
herbs, namely Cortex Eucommiae, Herba Cistanches, and
Radix Dipsaci, can also be processed with white wine
(alcohol) to increase their warm and ascending properties,
thereby enhancing the Yang nature of the herbal medicine.
1
Currently, there have been numerous modern pharmacological
studies published to provide support for the theories of herbal
processing in traditional medicine, as presented in Table 3.
The correlation between the chemical components and the
Yang tonifying effects of salt-processed Radix Morindae offici-
nalis has been determined using modern analytical techniques
such as UPLC-DAD combined with multivariate statistical
analysis. Thirteen compounds that are correlated with the func-
tional properties of salt-processed Radix Morindae officinalis
according to traditional medicine have been identified, including
four compounds: monotropein, deacetyl asperulosidic acid,
asperulosidic acid, and asperuloside (as presented in Figure 2).
32
Monotropein, a major iridoid compound in Radix Morindae
officinalis, possessed various biological effects, with its most
prominent being its anti-osteoporotic activity.
34
According to
traditional medicine, the Kidney controls bones. When the
Kidney essence is abundant, the bone marrow is full, and the
limbs move gently, gracefully, and stand firmly.
1
Therefore,
the anti-osteoporotic effect of monotropein may be related to
its kidney-Yang tonifying properties in Radix Morindae offici-
nalis. Additionally, several other compounds in Radix
Morindae officinalis have been demonstrated to be associated
with kidney Yang-nourishing effects, including deacetyl asperu-
losidic acid, asperulosidic acid, and asperuloside (as presented
in Figure 2).
32
Although the processing of Radix Morindae
officinalis reduced the content of monotropein and deacetyl
asperulosidic acid, it increased the levels of two other iridoid
glycosides, asperulosidic acid, and asperuloside.
5,6
Additionally, the salt processing of Radix Morindae officinalis
has been demonstrated to enhance the absorption and bioavail-
ability of monotropein,
35
contributing to the increased
Yang-tonifying effects of the herbal medicine. However, the
mechanisms underlying the transformation of compounds in
Radix Morindae officinalis need to be further investigated.
Cortex Eucommiae is also a commonly used Yang-tonifying
herb in clinical practice. In addition to sensory characteristics
such as color and taste, the two forms of Cortex Eucommiae,
raw and salt-processed, can be differentiated through the anal-
ysis of 11 marker compounds. These compounds included gen-
iposidic acid, neochlorogenic acid, chlorogenic acid, caffeic acid,
geniposide, genipin, pinoresinol di-O-glucopyranoside, syringar-
esinol di-O-glucopyranoside, isochlorogenic acid A, pinoresinol
O-glucopyranoside, and isochlorogenic acid. Among these 11
marker compounds, six phytochemical compounds have been
demonstrated to be associated with the Yang tonifying effects
of Cortex Eucommiae, namely geniposidic acid, chlorogenic
acid, geniposide, genipin, pinoresinol diglucoside, and
Figure 2. Chemical formulas of the compounds with Yang tonifying
effects in Radix Morindae officinalis.
8Natural Product Communications
hyperoside (as presented in Figure 3).
33
The target proteins
involved in the Yang tonifying effects of these six chemical com-
pounds have been identified through molecular docking and
pharmacological network analysis as AKT1 and PTGS2.
14
Geniposide, found in Cortex Eucommiae, has been shown
to have various pharmacological effects such as inhibiting cog-
nitive decline (Alzheimer’s), reducing local ischemia, alleviating
depression, and modulating the immune system.
36
According to
traditional medicine theory, the Kidney is the “residence”of Will
power. When the Kidney is weakened, the willpower also
weakens, leading to weakness, lack of effort and initiative,
easily becoming disheartened, and being prone to giving up
on set goals. Lack of willpower and motivation are often key
factors in depression, and Kidney tonification generally yields
positive results. In elderly individuals, Kidney deficiency can
also manifest as decreased memory, and in more severe cases,
confusion.
1
Therefore, geniposide can be regarded as a
marker compound with Kidney-Tonifying effects in herbal
medicine. The process of charred Cortex Eucommiae is also
theoretically believed to enhance the effects of the herb on
the Kidney meridian according to traditional medicine. This
theory is supported by reports demonstrating an increase in
the levels of geniposide in charcoal-processed Cortex
Eucommiae.
13
However, there was conflicting data regarding
the content of geniposide in charcoal-processed Cortex
Eucommiae between the reports of Tao and Chai, and there
was no explanation regarding the mechanisms of compound
transformation. This difference may be influenced by process-
ing conditions such as processing temperature, processing time,
and frequency of material stirring. Furthermore, the content of
compounds in Charcoal-processed Cortex Eucommiae was
only determined in 1 or 2 batches of processed herbal materials,
which may not be representative of the overall processed Cortex
Eucommiae. Further research is needed to conduct compre-
hensive evaluations and provide more conclusive findings.
The processing of Herba Cistanches is believed to involve the
transformation of phenylethanoid glycosides through two reac-
tions: hydrolysis and esterification. In an ethanol environment,
the functional groups on phenylethanoid glycosides are replaced
by hydroxyl groups (-OH). Subsequently, the 4′-O-caffeoyl group
Figure 3. Chemical formulas of the compounds with Yang tonifying effects in Cortex eucommiae.
Truong et al. 9
was cleaved from the structure, forming caffeic acid, which reduced
the content of phenylethanoid glycosides with 4′-O-caffeoyl at the
8-O-β-D-glucopyranosyl position. The formed caffeic acid then par-
ticipatedinesterification reactions at the 6′-OH position, increasing
the content of phenylethanoid glycosides with 6′-O-caffeoyl at the
8-O-β-D-glucopyranosyl position. Additionally, Li et al suggested
the occurrence of a rearrangement reaction of the caffeoyl group
at the 4′-6′position of phenylethanoid glycosides during the pro-
cessing of Herba Cistanches. Figure 4 depicts the degradation
process of cistanoside C, a phenylethanoid glycoside compound,
during the processing of Herba Cistanches.
16,17
The Yang tonifying effects of raw/processed Herba
Cistanches have been demonstrated by Liu et al Based on
their research findings, the authors suggested that different
forms of Herba Cistanches were able to counteract dysregulated
reproductive hormones and immune factors in mice subjected
to excessive glucocorticoid dosing. They also observed enhanc-
ing and restoring effects on the hypothalamic–pituitary–adrenal
axis and improving immune function.
20
In addition to improving organ parameters, hormones, and
enzyme activities after treatment with different forms of Radix
Dipsaci, the expression of proteins Smad 1, Smad 4, Smad 5,
Smad 8, and BMP 7 in the kidneys of treated batches also
significantly increased. Specifically, signals observed in the
group treated with salt-processed Radix Dipsaci were more sig-
nificant compared to the raw form. Based on these findings, the
authors proposed that the mechanism of action for treating
kidney-Yang deficiency with salt-processed Radix Dipsaci
involved intervention in the BMP-Smad signaling pathway.
31
Conclusion
The kidney Yang-nourishing effects of the five traditional herbal
medicines prescribed in Circular 30/2017/TT-BYT by the
Ministry of Health of Vietnam (Radix Morindae officinalis,
Cortex Eucommiae, Herba Cistanches, Semen Cuscutae, and
Radix Dipsaci) have been demonstrated through several
studies and summarized in our review. Additionally, the
changes in composition and content of certain active com-
pounds in these herbal medicines have also been searched
and reported. However, the evidence regarding the mechanisms
of chemical compound transformation in these herbal medi-
cines, as well as the relationship between chemical composition
and kidney-Yang tonifying effects, is still limited. Therefore,
further research in this field is needed to gain a deeper
understanding.
Figure 4. The transformation process of active compounds in Herba Cistanches after processing (eg cistanoside C).
10 Natural Product Communications
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship,
and/or publication of this article.
ORCID iDs
Minh-Nhut Truong https://orcid.org/0009-0003-6483-4362
Lan-Phuong Le Thi https://orcid.org/0009-0008-3761-140X
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