molecules

Review
The Traditional Medicine and Modern Medicine from
Natural Products
Haidan Yuan 1,2 , Qianqian Ma 1 , Li Ye 1 and Guangchun Piao 1,2, *
1 College of Pharmacy, Yanbian University, Yanji 133002, China; [email protected] (H.Y.);
[email protected] (Q.M.); [email protected] (L.Y.)
2 Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules,
Ministry of Education, Yanbian University, Yanji 133002, China
* Correspondence: [email protected]; Tel.: +86-433-243-6008

Academic Editor: Derek J. McPhee

Received: 19 March 2016; Accepted: 25 April 2016; Published: 29 April 2016

Abstract: Natural products and traditional medicines are of great importance. Such forms of medicine
as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have
been practiced in some areas of the world and have blossomed into orderly-regulated systems of
medicine. This study aims to review the literature on the relationship among natural products,
traditional medicines, and modern medicine, and to explore the possible concepts and methodologies
from natural products and traditional medicines to further develop drug discovery. The unique
characteristics of theory, application, current role or status, and modern research of eight kinds
of traditional medicine systems are summarized in this study. Although only a tiny fraction of
the existing plant species have been scientifically researched for bioactivities since 1805, when the
first pharmacologically-active compound morphine was isolated from opium, natural products
and traditional medicines have already made fruitful contributions for modern medicine. When
used to develop new drugs, natural products and traditional medicines have their incomparable
advantages, such as abundant clinical experiences, and their unique diversity of chemical structures
and biological activities.

Keywords: natural products; traditional medicines; drug discovery; traditional uses; chemodiversity

1. Introduction
Since prehistoric times, humans have used natural products, such as plants, animals,
microorganisms, and marine organisms, in medicines to alleviate and treat diseases. According to
fossil records, the human use of plants as medicines may be traced back at least 60,000 years [1,2]. The
use of natural products as medicines must, of course, have presented a tremendous challenge to early
humans. It is highly probable that when seeking food, early humans often consumed poisonous plants,
which led to vomiting, diarrhea, coma, or other toxic reactionsperhaps even death. However, in this
way, early humans were able to develop knowledge about edible materials and natural medicines [3].
Subsequently, humans invented fire, learned how to make alcohol, developed religions, and made
technological breakthroughs, and they learned how to develop new drugs.
Traditional medicines (TMs) make use of natural products and are of great importance. Such
forms of medicine as traditional Chinese medicine (TCM), Ayurveda, Kampo, traditional Korean
medicine (TKM), and Unani employ natural products and have been practiced all over the world for
hundreds or even thousands of years, and they have blossomed into orderly-regulated systems of
medicine. In their various forms, they may have certain defects, but they are still a valuable repository
of human knowledge [2,4].

Molecules 2016, 21, 559; doi:10.3390/molecules21050559 www.mdpi.com/journal/molecules

Molecules 2016, 21, 559 2 of 18

In the case of China, Western medicine was introduced in the sixteenth century, but it did not
undergo any development until the nineteenth century. Before that, TCM was the dominant form of
medical care in the country [5]. Now TCM still plays an important role in China, and it is constantly
being developed. TCM is based on 5000 years of medical practice and experience, and is rich in data
from clinical experiments which guarantee its effectiveness and efficacy. It has developed techniques
with respect to such areas as correct dosage, methods of preparing and processing materials, and the
appropriate time to collect the various medicinal parts of plants. It is notable that there is increasing
convergence between TCM and modern medicine. With the development of modern technology, it
has become possible to determine the pharmacology and mechanisms of action of many Chinese
herbs, and TCM has become comprehensible in terms of modern medicine [69]. With advances in the
theoretical background, therapeutic principles, associated technologies, and understanding of the life
sciences, a clearer understanding of the active compounds of TCM has become possible [5].
At the beginning of the nineteenth century, the era of modern drugs began. In 1805, the
first pharmacologically-active compound morphine was isolated by a young German pharmacist,
Friedrich Sertrner, from the opium plant [10,11]. Subsequently, countless active compounds have
been separated from natural products. Among them, some follow their traditional uses and the
others do not. Later, the development of synthetic techniques led to a significant reduction in the
importance of natural products, and there were concerns that the use of some natural products for
medicinal purposes might be completely banned. However, natural products are important for the
development of new drugs, and these products have been in constant use. Some type of medicines,
such as anticancer, antihypertensive, and antimigraine medication, have benefited greatly from natural
products [10,12].
The development of new drugs relying purely on modern technology appears to be reaching
something of a limit. In developing new drugs, the pharmaceutical industry has tended to adopt
high-throughput synthesis and combinatorial chemistry-based drug development since the 1980s;
however, the considerable efforts made in this direction have not resulted in the expected drug
productivity. Some large pharmaceutical companies are facing great challenges to develop new
products. Over the past dozen years, increasing attention has accordingly been paid to natural
products in the search for novel drugs in combination with new technology, such as high-throughput
selection [13,14].
Natural products, which have evolved over millions of years, have a unique chemical diversity,
which results in diversity in their biological activities and drug-like properties. Those products have
become one of the most important resources for developing new lead compounds and scaffolds.
Natural products will undergo continual use toward meeting the urgent need to develop effective
drugs, and they will play a leading role in the discovery of drugs for treating human diseases, especially
critical diseases [15].

2. Natural Products
Natural products have a wide range of diversity of multi-dimensional chemical structures; in the
meantime, the utility of natural products as biological function modifiers has also won considerable
attention. Subsequently, they have been successfully employed in the discovery of new drugs and have
exerted a far-reaching impact on chemicobiology [1618]. From the past century, the high structural
diversity of natural products have been realized from the perspective of physical chemistry. Their
efficacy is related to the complexity of their well-organized three-dimensional chemical and steric
properties, which offer many advantages in terms of efficiency and selectivity of molecular targets.
As a successful example of drug development from natural products, artemisinin and its analogs are
presently in wide use for the anti-malaria treatment. This shows how research using natural products
has made a significant contribution in drug development [19,20].
Among anticancer drugs approved in the time frame of about 19402002, approximately 54% were
derived natural products or drugs inspired from knowledge related to such. For instance, the Vinca
Molecules 2016, 21, 559 3 of 18

alkaloids from Catharanthus roseus, and the terpene paclitaxel from Taxus baccata, are among successful
anticancer drugs originally derived from plants [12,21]. During the period between 1981 and 2002, the
application of natural products in the development of new drugsespecially in the search for novel
chemical structuresshowed conspicuous success. In that 22-year time frame, drugs derived from
natural products have been significant. That is especially true in the case of antihypertensives, where
about 64% of newly-synthesized drugs have their origins in natural product structures [12].
Considering their incomparable chemical diversity and novel mechanisms of action, natural
products have continued to play a pivotal role in many drug development and research programs.
With time, those natural products have undergone interesting and meaningful developments in their
ability to interact with numerous, varied biological targets, and some have become the most important
drugs in health care system [14,22,23]. For example, plants, microorganisms, and animals manufacture
small molecules, which have played a major role in drug discovery. Among 69 small-molecule new
drugs approved from 2005 to 2007 worldwide, 13 were natural products or originated from natural
products, which underlines the importance of such products in drug research and development [12,13].
Over the past 50 years, there has been a great diversity of new drugs developed using
high-throughput screening methods and combinatorial chemistry; however, natural products and
their derived compounds have continued to be highly-important components in pharmacopoeias.
Of the reckoned 250,000500,000 existing plant species, only a tiny proportion has been scientifically
researched for bioactivities [13]. Therefore, there is great potential for future discoveries from plants
and other natural products which, thus, offer huge potential in deriving useful information about
novel chemical structures and their new types of action related to new drug development.

3. Traditional Medicines
TM is the oldest form of health care in the world and is used in the prevention, and treatment
of physical and mental illnesses. Different societies historically developed various useful healing
methods to combat a variety of health- and life-threatening diseases. TM is also variously known as
complementary and alternative, or ethnic medicine, and it still plays a key role in many countries
today [24,25].
The medicaments used in TM are mostly derived from natural products. In TM, clinical trials
have been conducted since ancient times. In the case of TCM, considerable experience and advances
have been accumulated and developed over the past thousands of years with respect to methods of
preparation, selection of herbs, identification of medicinal materials, and the best time for obtaining
various different plants. Appropriate processing and dose regulation are urgently needed in TCM to
improve drug efficacy and reduce drug toxicity. Considerable amounts of data have been acquired
through clinical experiments, and in this way TM has assisted in the development of modern drugs.
Through its use of natural products, TM offers merits over other forms of medicine in such areas as
the following: discovery of lead compounds and drug candidates; examining drug-like activity; and
exploring physicochemical, biochemical, pharmacokinetic, and toxicological characteristics. If any
form of TM is applied successfully, it may surprisingly assist in the development of new drugs, thereby
resulting in many benefits, such as significant cost reductions.
TCM is now an inseparable part of the Chinese public health system. In recent years, TCM
has gradually gained considerable approval as a complementary or alternative medicine in Western
countries. Chinese herbal medicine, which is the most important component of TCM, is currently
used in the health care of an estimated 1.5 billion people worldwide [26,27]. It should be noted that
in TCM, several herbs and ingredients are combined according to strict rules to form prescriptions,
which are referred to as formulas (fang ji in Chinese). Commonly, a classic formula is composed of four
elementsthe monarch, minister, assistant, and servantaccording to their different roles in
the formula, each of which consists of one to several drugs. Ideally, these drugs constitute an organic
group to produce the desired therapeutic effect and reduce adverse reactions [28].
Molecules 2016, 21, 559 4 of 18

Kampo is the TM of Japan. Between the fifth and sixth centuries, TCM was introduced to Japan
from China; since then, TCM has been significantly altered and adapted by Japanese practitioners
to meet their particular circumstances and gradually evolved into Kampo [29]. A recent study has
found that some physicians in Japan use Kampo medicines in their daily practicesometimes as the
preferred medication [2931]. Together with radiotherapy or chemotherapy, some Japanese physicians
frequently utilize Kampo medicines in treating cancer patients. This indicates how modern Western
medicine can be well integrated with TM [30,32]. As the use of Kampo continues to rise in conjunction
with Western medicine, there is growing realization of the urgent need to study the interactions
between these two types of medicines [28].
Unani is an ancient Greek holistic medical system with a history that can be traced back 2500
years [33]. Since the mid-1970s, when the WHO began to place a greater focus on TM, Unani has
attracted considerable attention all over the world, especially in India, where it has been integrated
into the national health care system [34].
It was reckoned by WHO that a large quantity of people in the world still depend on TMs for
health care [35]. The current status of TM differs in different countries. In 2012, the total value of the
TCM industry was equivalent to around one-third of the total for Chinas pharmaceutical industry [36].
It has been determined that 80% of the population in Africa makes use of TMeither alone or in
conjunction with conventional medicine [37]. By contrast, traditional Aboriginal medicine in Australia
is in danger of vanishing owing to the prevalence of conventional medicine [38]. In the case of Israel
with its ethnic diversity, modern medicine is prevailing, and TM is declining [39]. Many practitioners
of Western medical science think such TM systems as being short of reliability; however, they are
adopted by the majority of people in the world [35]. It is possible to produce remarkable synergy and
yield great benefits in developing reformed medicines and new drugs by connecting powerful modern
scientific techniques and methods with the reasonable ethnobotanical and ethnomedical experiences
of TM. Characteristics of several TM systems are summarized in Table 1.

4. Drugs Developed from Traditional Medicines that Follow the Traditional Uses
TM is too valuable to be ignored in the research and development of modern drugs. Though it
has an enigmatic character, there are also wide contexts for its use in terms of non-Western medical
technology or activities. In TM, a single herb or formula may contain many phytochemical constituents,
such as alkaloids, terpenoids, flavonoids, etc. Generally speaking, these chemicals function alone or in
conjunction with one another to produce the desired pharmacological effect [35]. It is notable that a lot
of plant-originated drugs in clinical medicine today were derived from TM [21]. In addition, it has
been demonstrated that the many valuable drugs derived from plants were discovered through their
application in TM [2].
Almost 20 years ago, a thorough investigation of the pharmacopoeias of developed and
developing nations and the associated world scientific literature was conducted as part of the WHOs
TM Program. The aim of that study was to determine whether TM really had inspired modern drug
discoveries and whether there was any correlation between the current use of various compounds and
their application in TM. The study focused on various compounds used in drugs derived from plants
in different countries, and it established that TM had indeed played a significant role in developing
effective new drugs. That study focused on 122 compounds, 80% of which were found to be related to
pharmaceutical effects in folk medicine, and it was determined that these compounds originated from
94 plant species [2].
Molecules 2016, 21, 559 5 of 18

Table 1. Characteristics of several important traditional medicine systems.

Name Origin and Developing Nation Characteristics of Theory or Application Current Role or Status Modern Research

Both TCM and conventional

medicine exist at every
TCM is based on Yinyang and gradation of the health-care The pharmacology of TCM
Wuxing concepts. system, and both are covered has made great advancements.
A TCM formula includes a group of under public and In recent decades, many TCM
various drugs that function together private insurance. active compounds and
Traditional Chinese medicine China congenially to achieve a There is a TCM division in compound-based therapeutics
(TCM) [26,28,4043] Thousands of years ago. synergistic effect. most ordinary hospitals and have been discovered.
A classic formula is composed of four TCM services are supplied for Great efforts have been made
elements: monarch, minister, assistant, both inpatients to reveal the underlying
and servant according to their roles in and outpatients. molecular mechanisms
the formula. TCM is attracting increasing of TCM.
attention, interest, and
acceptance around the world.

Ayurveda uses natural elements to

eradicate the main cause of the disease
by reinstating balance. More than 400,000 Ayurveda
Pharmacologically-active
India The Ayurvedic philosophy is to live a practitioners are registered.
compounds of Ayurvedic
Ayurveda can be dated back healthy life to avoid the appearance of The Indian government has an
Ayurveda [35,44] medicine and their
to the pre-Vedic epochs imbalance and unnecessary pain. official body to ensure
effectiveness in treatment has
(4000 BC1500 BC) In many Ayurvedic treatments, Ayurvedas educational
been increasingly recognized.
multiple herbs are united in a special efforts, quality, and practice.
quotient to create an ideal therapeutic
effect and lessen the toxicity.

It treats a persons body, mind, and

soul as a whole. Unani is accepted by India as
Unani looks upon the human body as meeting the health-care needs
India a single unit, which consists of four of people and has gained
Unani medicine derived from basic elements which have four formal status. Many bioactive ingredients
Greco-Arabic medicine dating disparate temperaments respectively. Unani has been acknowledged have been separated from
Unani medicine [33,34,45,46] back 2500 years and A persons temperament reflects their by the WHO as an alternative mangrove plants which are
developed during the physical characteristics and health-care system. used in Unani medicine.
Arab civilization. natural disposition. Unani is one of the most
Disproportion in temperament makes important traditional
the human body susceptible to medicine systems.
many illnesses.
Molecules 2016, 21, 559 6 of 18

Table 1. Cont.

Characteristics of Theory or
Name Origin and Developing Nation Current Role or Status Modern Research
Application

Kampo was developed over the

Kampo formulas are
past 1400 years and has been
produced by certificated drug
organically unified with
firms under strict quality
Japanese original therapies.
management standards.
Kampo treats every human
Both the government and
being as a complete and
drug firms are deeply
Japan self-controlled whole in which Kampo is incorporated into the
involved in surveillance of all
Kampo was introduced from body and mind health-care system in Japan.
Kampo (traditional processes to ensure the quality
China via the Korean impact mutually. All citizens can use of Kampo
Japanese medicine) [30,47] and safety of
peninsula in the 5th or Diseases are thought to originate herbal formulas approved by
Kampo formulas.
6th century. from the disorders of psyche the government.
There has also been a focus on
and soma and herbals are
examining the efficacy of
trusted to affect the soul and the
Kampo formulas and
body equally.
exploring related mechanisms.
Kampo therapy places emphasis
Kampo is regarded as
on the sufferer as a whole
very safe.
instead of on the illness.

SCM classifies persons into four

Although the conventional The Lee Jema project to supply
Sasang types: Tae-Yang,
health-care organization is quite scientific proof of SCM began
So-Yang, Tae-Eum, and So-Eum
good in Korea, 86% of people in 2006 and is supported by
according to his/her
Traditional Korean SCM is a division of Korean still employ SCM. the Korean government.
inborn features.
medicine (TKM), Sasang traditional medicine. Traditional medicine doctors can It has gained many significant
SCM is holistic.
constitutional medicine It was first introduced in the supply Korean SCM both in achievements involving
SCM is theoretically similar to
(SCM) [42,4850] mid-19th century. private and public hospitals. constitution-diagnostic means,
personalized medicine.
Both national medical insurance constitution-specific disease
SCM supplies individualized vulnerabilities, and
and private insurance cover
and constitution-specific genetic research.
Korean SCM services.
treatments for various problems.

Currently, there is only one

national folk organization
in operation.
Indigenous peoples of Australia During 20102011, 32.1% of the
believe that health problems chief, indigenous health-care
Traditional Aboriginal Australia have three types of causes: organizations in Australia
medicine [38,50] natural bodily causes, harmful provided some kind of
spirits, or witchcraft. traditional medicine services.
Because of colonization,
traditional Aboriginal medicine
is in danger of becoming extinct.
Molecules 2016, 21, 559 7 of 18

Table 1. Cont.

Characteristics of Theory or
Name Origin and Developing Nation Current Role or Status Modern Research
Application

Eighty percent of African

Traditional medicine doctors
people use traditional
treat patients holistically.
medicine either by itself or
They generally seek to
with conventional medicine.
recombine the mental and social Research on Hydnora africana,
Up to 80% of Ghanaians and
equipoise of sufferers according which is used as
Ethiopians depend on
Traditional medicine in to social relationships and rules. ethnomedicine in Africa, has
Africa traditional medicine for their
Africa [25,37,38,51] The accessibility of traditional demonstrated the antioxidant
main health-care demands.
medicine is one of the most and antibacterial activities of
Ghanas traditional medical natural products.
important reasons for its
system has been integrated
popularity across Africa.
into the national health-care
Traditional medicine exemplifies
system and, therefore, it is
respect for the cultural heritage.
comparatively well organized.

Due to the special geographical

Herbal therapy is a formal and
environment of Russia, Russian
independent department of
herbal therapy has collected and Soviet/Russian researchers
medicine in Russia; thus,
adopted traditional medicine have focused mainly on the
herbal medicinal products are
methods that were introduced development of adaptogens
Russia regarded as official remedies.
Russian herbal medicine [52] from Europe and Asia. derived from plants.
10th century A recent survey shows that
The Russian Federation follows The collection of plants with
14% of the Russian people
the State Pharmacopoeia of the expectorant effects shows
frequently use herbal
USSR; 32 of 83 individual plant huge potential.
remedies and 44% use
monographs are found only in
them occasionally.
this Pharmacopoeia.
Molecules 2016, 21, 559 8 of 18

The acceptability, convenience, and accessibility of TMs have been, and will be, helpful for new
drug research [13]. As noted above, artemisinin and other antimalarial drugs are examples of modern
drugs based on TMs. Early in Chinas Jin Dynasty, Doctor Hong Ge (AD 284384) recorded the efficacy
and related details of Artemisia annua L. in treating malaria in his book Zhou Hou Bei Ji Fang. That is
the earliest record anywhere of treating malaria with Artemisia annua L., and it shows that Chinese
physicians 1700 years ago had reached a sophisticated level of medical treatment [53,54].
Artemisinin is known as qinghaosu in Chinese, and its study has made significant progress,
including the synthesis of new artemisinin analogs and derivatives, and research efforts into the
biological activities and related mechanisms. As a result, artemisinin, as well as its effective derivatives,
are extensively applied throughout the world as new-type anti-malarial drugs [55].
The discovery of artemisinin can be traced back to the 1960s, when tropical malaria was a serious
problem during the Vietnam War. North Vietnam requested China to help tackle the malaria problem.
The Chinese government approved a project for malaria control and drug research in 1967. The research
group made its investigations and carried out a large-scale search of the literature on the subject. As
part of the phytochemical and pharmacological research effort, a lot of Chinese herbal medicines
were screened and investigated with respect to their toxicity or efficacy. Eventually artemisinin was
derived from Artemisia annua L. in 1972 [53,55,56]. Artemisinin is quite different from previously-used
antimalarial drugs, such as chloroquine, in that it has a novel structure, with a sesquiterpene
lactone bearing a peroxy group, and it does not contain nitrogen heterocycles. Compared with
previous antimalarial drugs, artemisinin has the merit of high efficiency, quick effect, and low toxicity.
Artemisinin is effective in treating various forms of malaria, such as falciparum and cerebral malaria,
which are resistant to chloroquine, and its mechanism of action is different from traditional antimalarial
drugs. The discovery of artemisinin was a great success for TCM at a special period in Chinas history,
and it was achieved through a well-organized team of hundreds of researchers [56]. Since that
breakthrough, scientists have conducted comprehensive research in such areas as pharmaceutical
chemistry, organic synthetic chemistry, and chemical biology. Through etherification and esterification,
they have produced a series of well-known new drugs, such as artemether and artesunate. Those
drugs have improved efficacy and solubility, which are of benefit for patients receiving oral or
intravenous administration and have overcome the high parasite recrudescence rate and low solubility
of artemisinin [5557]. Most importantly, one of these scientists, Youyou Tu, was just awarded the 2015
Nobel Medicine Prize for her significant devotion in discovering artemisinin.
The discovery of artemisinin illustrates how TCM constitutes a great store of knowledge about
natural products, such as Chinese herbs, and holds much future promise. The discovery of successful
new drugs can proceed by profiting from this knowledge [56]. Some drugs or compounds isolated
from Chinese herbal medicines which follow the ethnomedical uses are summarized in Table 2.
 Molecules2016,
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Molecules 2016, 21, 559 88 of 16
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Molecules 2016, 21, 559 21, 559 8 of 16 9 of 18
Table2.2.Some
Table Somedrugs
drugsororcompounds
compoundsisolated
isolatedfrom
fromChinese
Chineseherbal
herbalmedicines
medicineswhich
whichfollow
followthe
thetraditional
traditionaluses.
uses.
Table 2. Some drugs or compounds isolated from Chinese herbal medicines which follow the traditional uses.
Table 2. Some drugs or compounds isolated from Chinese herbal medicines which follow the traditional
2.orSome drugs or compounds isolated from Chinese herbal medicines which followAncient Ancient
Ancient Chinese
uses.
Chinese LiteratureRecording
Literature Recording
Drugsor
Table
Drugs
the Chinese
traditional Literature
uses. Recording
PlantOrigin
Plant Origin Drugs or Chemical Structures
Chemical Structures
Structures Effects
Effects oror Indications
or Indications
Indications Chinese Herbal
Chinese Chinese Medicines
Herbal Medicines
Medicines with
with Same
Same
Plant Origin Compounds
Compounds Chemical Effects Chinese
Ancient Herbal Literature with Same
Recording
Compounds
Drugs or Effects
Effects and the
and the
the Published
Published Time
Time
Plant Plant
OriginOrigin Drugs or Compounds Chemical
Chemical Structures
Structures Effects orIndications
Effects or Indications Effects
Ancient
Chinese and
Chinese
Herbal Published
Literature
Medicines Time
Recording
with SameChinese Herbal
Compounds Medicines with Same Effects and the Published Time
H
H Effects and the Published Time
H
H
O
O
ZhouHou
HouBei BeiJiJiFang
Fang
O
O H
Zhou
O H
Artemisiaannua
annuaL.L.[53,55]
[53,55] Artemisinin Anti-malarial Zhou Hou Bei Ji Fang
H
H
O
Artemisia Artemisinin Anti-malarial
OO
Artemisia annua L. [53,55] Artemisinin O O
O
O Anti-malarial (Jin
ZhouDanasty,
Hou
(Jin Danasty,
Danasty, AD
Bei
AD Ji 266420)
Fang
266420)
Artemisia annuaannua
Artemisia L. [53,55]
L. [53,55] Artemisinin
Artemisinin O
O Anti-malarial
Anti-malarial (Jin
Zhou Hou Bei JiAD
Fang266420)
(Jin Danasty, AD 266420)
O
O (Jin Danasty, AD 266420)
O
O
O
O

O
O
O
O
Corydalisyanhusuo
yanhusuo LeiGong
GongPao
PaoZhi
ZhiLun
Lun
O
Corydalis
Corydalis yanhusuo
O Lei
Lei Gong Pao Zhi Lun
Corydalis yanhusuo Tetrahydropalmatine Analgesic Lei Gong Pao Zhi Lun
O
O
Tetrahydropalmatine
Tetrahydropalmatine Analgesic
Analgesic
W.T.Wang
Corydalis
W.T.Wang
W.T.Wang [58,59]
yanhusuo
[58,59]
[58,59] Tetrahydropalmatine
Tetrahydropalmatine
O
Analgesic
Analgesic (Nanchao
(Nanchao
(Nanchao Song
Lei Gong Song
Song Dynasty,
Dynasty,
Song Dynasty,
Pao Zhi Dynasty, AD
Lun AD
AD 420479)
420479)
AD 420479)
(Nanchao 420479)
Song Dynasty, AD 420479)
W.T.Wang [58,59] (Nanchao
O
O
W.T.Wang [58,59] O

O
O
O
O
Ligusticum chuanxiong Mmyocardial ischemia- Shen Nong Ben Cao Jing
Tetramethyl-pyrazine N
Ligusticum
Ligusticum chuanxiong
Hort.chuanxiong
[60] N
N Mmyocardial ischemia-
reperfusionischemia-
Mmyocardial injury ShenNong
(Donghan
Shen Nong BenCao
Dynasty,
Ben CaoJing
AD Jing
25220)
Ligusticum chuanxiong Tetramethyl-pyrazine Mmyocardial ischemia- Shen Nong Ben Cao Jing
N
Ligusticum chuanxiong Tetramethyl-pyrazine Mmyocardial ischemia-reperfusion
Hort.Hort.
Hort. [60][60]
[60] Tetramethyl-pyrazine
Tetramethyl-pyrazine reperfusion
reperfusion injury
injury (Donghan
Shen Nong BenDynasty, AD 25220)
Cao Jing (Donghan
(Donghan Dynasty,
Dynasty, ADAD 25220)
25220)Dynasty, AD 25220)
Hort. [60] N
N
N
N
reperfusion
injury injury (Donghan

Paeonia lactiflora Pall. Shen Nong Ben Cao Jing

Paeoniflorin O
O Analgesic
[61,62] HO
HO
OH
OH
O
O (Donghan Dynasty, AD 25220)
HO OH
Paeonia lactiflora Pall. ShenNong
NongBen
BenCaoCaoJing
Jing
HO OH H O
PaeoniaPaeonia
lactiflora Pall. Shen
O
Paeonia lactiflora Pall. Paeoniflorin Analgesic Shen
Nong Nong Ben Cao Jing Dynasty, AD 25220)
H O
lactiflora Pall. HH O
[61,62] Paeoniflorin
Paeoniflorin
Paeoniflorin HO
HO O
O
H
H
Analgesic
Analgesic
Analgesic
Analgesic (Donghan
Shen BenDynasty,
Cao Jing AD 25220)
(Donghan
[61,62]
[61,62][61,62] HO
HO O
O H
H
OH (Donghan Dynasty,
(Donghan Dynasty, ADAD 25220)
25220)
OH
OH
O OH OH
O
O OH
OH
O OH O O
O
O O
O
O O
H
Epimedium brevicornum H
H
H Shen Nong Ben Cao Jing
Icariin Osteoporosis
Maxim. [63,64] (Donghan Dynasty, AD 25220)
O
OH O
O
Epimedium brevicornum Shen Nong Ben Cao Jing
OH O

Epimedium brevicornum Shen Nong Ben Cao Jing Dynasty, AD 25220)

OH
OH
Epimedium brevicornum
Epimedium brevicornum Icariin Osteoporosis Shen Shen
Nong Nong Ben Cao Jing
HO O O

Icariin
Icariin Osteoporosis
Osteoporosis Ben Cao Jing (Donghan
HO O O
Maxim. [63,64] Icariin Osteoporosis (Donghan Dynasty,AD
AD25220)
25220)
HO
HO O
O O
O O
Maxim. [63,64]
Maxim. [63,64]
[63,64] (Donghan Dynasty,
Dynasty,
OH
Maxim. (Donghan AD 25220)
O OH
O O
O OH
O OH
HO O O
HO O O
HO
HO O
O
OH O OH
HO OH O HO OH
Pueraria lobata HO
HO
HO
OH
OH O
O HO
HO
OH
OH Shen Nong Ben Cao Jing
Puerarin HO
Diabetes
(Willd.) Ohwi [65] (Donghan Dynasty, AD 25220)
 Molecules 2016, 21, 559 10 of 18

Table 2. Cont.
Molecules 2016,
Molecules 21, 559
2016, 21, 559 9 of
of 16
16
Molecules
Molecules 2016, 21,21,
2016, 559559 99 of
Ancient Chinese Literature Recording 9Chinese
of 16 Herbal
16
Plant Origin Drugs or Compounds Chemical Structures Effects or Indications
Medicines with Same Effects and the Published Time
OH
OH OH
OH
OH
OH OH
OH

O
O O
PuerariaPueraria
Pueraria lobata lobata
lobata
O OH
OH OH Shen Nong
Shen Nong Ben
Ben Cao
Cao Jing
Jing
Pueraria
Pueraria lobata
lobata Puerarin
Puerarin
OH
Diabetes
Diabetes Shen
Shen Nong
Nong Ben
Ben Cao
Cao Jing
Jing
(Willd.) Ohwi [65] Puerarin
Puerarin Diabetes
Diabetes (Donghan Dynasty, AD 25220) Dynasty, AD 25220)
HO O
(Willd.) (Willd.)
Ohwi [65]Ohwi Puerarin HO HO O Diabetes Shen Nong
(Donghan Ben Cao
Dynasty,Jing
AD (Donghan
25220)
(Willd.)
(Willd.) Ohwi
Ohwi [65]
[65] (Donghan
(Donghan Dynasty,
Dynasty, ADAD 25220)
25220)
HO O O
[65]

O
O O
O OH
OH OH
OH

OH
OH OH
OH
O
O O
O
OH
OH OH
OH
OH
OH OH
OH
Salvia miltiorrhiza
Salvia miltiorrhiza HO O OH O
OH
OH OH Cardiovascular and
Cardiovascular and Shen Nong
Shen Nong Ben
Ben Cao
Cao Jing
Jing
Salvia
Salvia miltiorrhiza
miltiorrhiza
Salvia miltiorrhiza Salvianolic
Salvianolic acid
acid B
B
HO HO
HO O O
O OH OH
OH O
O O
O
OH
Cardiovascular
Cardiovascular
Cardiovascular and
and
and cerebrovascular Shen
Shen Nong
Nong Ben
Ben Cao
Cao Jing
Jing
Bunge [66,67]
Bunge [66,67] Salvianolic
Salvianolic
Salvianolic acid
acid
acid BB
B O O
O
cerebrovascular
cerebrovascular diseases
diseases (Donghan
Shen Nong Dynasty,
(Donghan AD(Donghan
Ben Cao Jing
Dynasty, AD 25220) Dynasty, AD 25220)
25220)
Bunge
Bunge [66,67]
[66,67]
Bunge [66,67]
O O
O
O O
O cerebrovascular
cerebrovascular
diseases diseases
diseases (Donghan
(Donghan Dynasty,
Dynasty, ADAD 25220)
25220)
O O
O O O
O OH
OH OH
OH

HO
HO HO
HO OH
OH OH
OH

N
N N
N
Uncaria rhynchophylla
rhynchophylla Ming YiYi Bie
Bie Lu
Lu
O
Uncaria Uncaria O
Ming
Uncaria
Uncaria rhynchophylla
rhynchophylla Ming
Ming Yi
BieBie
LuLuLiang Dynasty, AD 502557)
Yi(Nanchao
O O
Rhynchophy-lline
Rhynchophy-lline Antihypertensive
Antihypertensive
(Miq.) Jacks.
Jacks. [68]
[68]
rhynchophylla Rhynchophy-lline
Rhynchophy-lline
Rhynchophy-lline Antihypertensive
Antihypertensive
Antihypertensive (Nanchao Liang
Ming Yi Bie Dynasty,
Lu AD 502557)
502557)
H
(Miq.) (Nanchao Liang Dynasty, AD
H
(Miq.)
(Miq.) Jacks.
Jacks. [68] [68]
[68] (Nanchao
(Nanchao Liang
Liang Dynasty,
Dynasty, ADAD 502557)
502557)
N O H H
N
H O
(Miq.) Jacks. N
H
H
N
H
O O
O O
O O
O O O O

H
H H
H O O
Saussurea lappa lappa Anti-gastric ulcer,
ulcer, Shen Nong
Nong Ben
Ben Cao
Cao Jing
Jing
O O O O
Saussurea O O
Saussurea
Saussurea
Saussurea lappa
lappaC.B.
lappa Costunolide Anti-gastric
Anti-gastric
Anti-gastric ulcer,
ulcer, Shen
Shen
Shen Nong
Nong Ben
Ben Cao
Cao Jing Dynasty, AD 25220)
Jing
(Decne.) C.B.
(Decne.)
Clarke [69] Costunolide
Costunolide
Costunolide
Costunolide Anti-gastric ulcer, antispasmodic
antispasmodic
Shen Nong
(Donghan
Ben Cao
Dynasty,
Jing
AD
(Donghan
25220)
(Decne.)
(Decne.) C.B.
(Decne.)
C.B. Clarke
C.B. Clarke
Clarke
Clarke [69]
[69]
[69]
[69] H
antispasmodic
antispasmodic
antispasmodic (Donghan
(Donghan
(Donghan Dynasty,
Dynasty,
Dynasty, AD
ADAD25220)
25220)
25220)
H H
H

HO
HO HO
HO

Gastrodia dlata Bl.

HO
HO HO Shen Nong
Shen Nong Ben
Ben Cao
Cao Jing
Jing
Gastrodia dlata
Gastrodia dlata Bl.
Bl. [70,71]
[70,71] Gastrodin
Gastrodin
Gastrodin
HO O
O O
OH
OH OH Anti-convulsion,
Anti-convulsion, analgesic
Anti-convulsion, analgesic
analgesic Shen Shen
Shen
Nong Nong
Nong
Ben Ben
Ben
Cao Cao
Cao
Jing Jing Dynasty, AD 25220)
Jing
(Donghan
Gastrodia
Gastrodia dlata
dlata Bl. [70,71]
Bl.[70,71]
[70,71] Gastrodin
Gastrodin Anti-convulsion,
Anti-convulsion, analgesic
analgesic (Donghan Dynasty, AD 25220)
O OH

HO O (Donghan
(Donghan
(Donghan Dynasty,
Dynasty,
Dynasty, AD
ADAD25220)
25220)
25220)
HO HO
HO O O
O
OH
OH OH
OH
Molecules 2016, 21, 559 11 of 18

5. Drugs Developed from Natural Products

In clinical practice in China in the 1960s, it was found that Schisandra chinensis (Turcz.) Baill.a
traditional Chinese herbhad obvious enzyme-reducing and hepatoprotective effects. Chinese
scientists then began isolating the chemical constituents of S. chinensis. In the subsequent total chemical
synthesis and pharmacodynamic study of schisandrin C (which is one of the compounds of S. chinensis),
researchers found that the intermediate compound bifendate had a stronger pharmacological activity
and that the cost of preparation was low. They discovered that it may be used to lower the enzyme
content in the treatment of hepatitis B virus [57].
Since the end of the 1980s, chemists and pharmacologists at the Chinese Academy of Medical
Sciences have been closely cooperating in studying the structure and activity relationships of
bifendate and its analogs. As part of their research, a series of novel derivatives were synthesized.
After screening using a number of chemical and pharmaceutical liver injury models, it was found
that the hepatoprotective activities of the derivatives were closely related to the locations of
dimethylenedioxy in two benzene rings, the length of the side-chain carboxylic acid, and the
heterocycle between the two benzene rings. Finally, a new compound, bicyclolformulated as
4,4-dimethoxy-5,6,51 ,61 -bis(methylene-dioxy)-2-hydroxy-methyl-21 -methoxycarbonyl biphenylwas
designed and synthesized. Bicyclol had greater in vivo absorption, and better bioavailability and
biological activity, than bifendate owing to the introduction of the 6-hydroxymethyl group and
61 -carbomethoxy in the side chain [72]. Pharmacological results of bicyclol showed antifibrotic and
hepatoprotective effects against liver injury and liver fibrosis induced by CCl4 or other hepatotoxins in
mice and rats; it also exhibited the antihepatitis virus effect in the 2.2.15 cell line and duck model with
viral hepatitis [73,74].
In clinical trials, it was found that the increased levels of serum alanine aminotransferase and
aspartate aminotransferase were dramatically decreased by bicyclol. It was also found that bicyclol
prohibited hepatitis B virus replication in chronic hepatitis B patients [75]. Compared with previous
anti-hepatitis drugs, bicyclol exhibited a more consolidated effect after the drug was discontinued;
the rebound rate was low, with fewer adverse reactions and higher oral bioavailability [76]. Based on
previous studies in such areas as synthesis, pharmacology, toxicology, pharmacokinetics, preparation,
and quality control, researchers determined that the new antihepatitis drug bicyclol offered significant
hepatoprotective effects, antihepatitis virus activity, and fewer adverse reactions [57]. Bicyclol has been
approved for the treatment of chronic viral hepatitis in China since 2004 [73]. Bicyclol has independent
intellectual property rights and belongs to Class 1 of Chinas New Chemical Drug. The drug is one of
the anti-inflammatory and hepatoprotective drugs recommended by the Guidelines on Liver Disease
Clinical Diagnosis and Treatment in China, and it has been exported to many countries [57,76].
In the same decade in which Chinese scientists found that S. chinensis (Turcz.) Baill. had obvious
enzyme-reducing and hepatoprotective effects, a program screening for cancer drugs from plants
began in 1960 at the National Cancer Institute in the United States. Neither China nor the United States
knew what the other was doing in this area. In that US project, 650 plant samples were gathered in
three states. After the initial cytotoxicity tests were carried out using crude extracts, Taxus brevifolia
was chosen for further research.
Taxol was isolated as a new compound from T. Brevifolia. Taxol has an unusual chemical structure
and radically distinctive mechanism of action and was developed as a novel anticancer drug in
subsequent decades. Nevertheless, the drug attracted little attention during the early stage of its
development because of its poor solubility in water, low yield from natural products, and other
disadvantages, particularly by the medical society. The story of Taxol involved many events that
nearly resulted in discontinuation of the research. Fortunately, it underwent extraction, isolation, and
structural determination; its activity against solid tumors and its mechanism of action were established,
and it became developed for clinical practice. Finally, Taxol was approved by the US Food and
Drug Administration for treating ovarian cancer in 199221 years after the initial breakthrough paper
recording its isolation and structural identification. Taxol has remained a basic drug for treating various
Molecules 2016, 21, 559 12 of 18

forms of cancer, and is still being used to develop new synergistic groups of anticancer drugs [7779].
Molecules
Molecules2016,
Molecules2016,21, 559
21,21,
2016, 559559 11
11of
11of16
1616
of
Some drugs
Molecules or21,
compounds
2016, 21,
Molecules 2016, 559
559
isolated or developed from natural products are summarized in Table11 3.of
11 of 16
16
Molecules
Molecules 2016, 2016, 21, 559
21, 559 11 of 16
11 of 16
Table
Table
Table3.3.Some
Some
3. Somedrugs
drugs or
drugs compounds
oror
compounds
compounds isolated
isolated or
isolated developed
oror
developed
developedfrom
from natural
fromnaturalproducts.
products.
natural products.
Table
Table 3.
Table 3.
3. Some
SomeSome drugs
drugs or
drugs or
or compounds
compounds
compounds isolated
isolated or
isolated or developed
developed
or developed from
from natural
natural
from products.
products.
natural products.
Origin (Plant, etc.)Table 3. Some
Drugs or drugs or compounds isolated or developed from
Table 3. Some drugs or compounds isolated or developed from natural products.natural products.
Origin (Plant,
Origin etc.)
(Plant, etc.) Drugs
DrugsorCompounds
Compounds
or Compounds Chemical
ChemicalStructures
ChemicalStructures
Structures Effects
Effectsor
orIndication
Effects Indication
or Indication
Origin
Origin (Plant,
(Plant, etc.)
etc.) Drugs
Drugs or
or Compounds
Compounds Chemical
Chemical Structures
Structures Effects
Effects or
or Indication
Indication
Origin
Origin
Origin (Plant,
(Plant,
(Plant, etc.)etc.) Drugs
etc.) Drugs ororCompounds
Compounds
or Compounds
Drugs Chemical
Chemical
Chemical Structures
Structures
Structures
O
O
Effects
Effects
Effects or Indication
or Indication
or Indication
O
O
O
O O O
O O
O OH
O OH OH
O OO OO
OH
Schisandra
Schisandra chinensis
Schisandrachinensis
chinensis Schisandrin
Schisandrin C,
SchisandrinC,bicyclol,
bicyclol,
C, bicyclol,
O
O
OO O
O
OH
OH OH Hepatoprotective,
Hepatoprotective,
Hepatoprotective,
Schisandra chinensis Schisandrin C, bicyclol, Hepatoprotective,
O
(Turcz.) Baill. [55,7276] bifendate anti-hepatitis BBvirus
O
Schisandra chinensis Schisandrin C, bicyclol, Hepatoprotective,
O
(Turcz.) Baill. [55,7276] bifendate anti-hepatitis virus
O O
(Turcz.) Baill. [55,7276] bifendate anti-hepatitis B virus
O
Schisandra
Schisandra
Schisandra chinensis Schisandrin
chinensis
chinensis Schisandrin
Schisandrin C,bicyclol,
C, bicyclol,
C, bicyclol,
O O
O O O
Hepatoprotective,
Hepatoprotective,
Hepatoprotective,
(Turcz.) Baill.
Baill. [55,7276] bifendate anti-hepatitis B virus
O
(Turcz.) [55,7276] bifendate anti-hepatitis B virus
O O
(Turcz.)
Baill.Baill. [55,7276] bifendate anti-hepatitis B virus
O O
(Turcz.) Baill. [55,7276] bifendate anti-hepatitis B virus
O O O O
(Turcz.) [55,7276] bifendate O O
O
anti-hepatitis B virus
O O
O O O O

O
O
bicyclol
bicyclol
O
bicyclol
O

bicyclol
bicyclol
bicyclol
bicyclol
bicyclolO
O O
OO
O OO O O OO OH
OOH
OH
OH OO O
O
H
OH OH
O O OH
O OH O
OH
NH H OH O OH
H
N N OH O
OH O H H
Taxus brevifolia [7780] Taxol, docetaxel Antitumor
HH OH
Taxus brevifolia
Taxus [7780]
brevifolia [7780] Taxol, docetaxel
Taxol, docetaxel O N
NN
H H
N O O
OO
O H O
HH
H
Antitumor
Antitumor
Taxus brevifolia [7780] Taxol, docetaxel Antitumor
O O O O H OH O
Taxus brevifolia [7780] Taxol, docetaxel Antitumor
O H
TaxusTaxus brevifolia [7780] Taxol, docetaxel Antitumor
O O
Taxus brevifolia
brevifolia [7780]
[7780] Taxol, docetaxel Antitumor
OH
Taxol, docetaxel O
O
O
O
O
O
OH OH H
O
O OH O
O
O
O
Antitumor
O O OH H O O HO
OH O O OO
OH O OH
O O O
O O OOO
O O
O
taxol
taxol
taxol O
O
O

taxol
taxol
taxol
O taxol
taxol
O O
OH
OH OH
O
O OH
OH
O
O OO O OH OH

O
O
Aspergillus
Aspergillusterreus
terreus
Aspergillus [81]
[81]
terreus [81] Lovastatin
Lovastatin
Lovastatin O
O HO
O O
Hyperlipoidemia
Hyperlipoidemia
Hyperlipoidemia
Aspergillus
Aspergillus
Aspergillus terreus
terreus
terreus[81]
[81]
[81] Lovastatin
Lovastatin
Lovastatin H H Hyperlipoidemia
Hyperlipoidemia
Hyperlipoidemia
Aspergillus terreus
Aspergillus terreus [81] [81] Lovastatin
Lovastatin
O
O
O HH O
Hyperlipoidemia
Hyperlipoidemia
H H

O
O O
O
O
O
O O O NN N O

O
O NN
Camptotheca
Camptothecaacuminata
acuminata Camptothecin,
acuminata
Camptotheca Camptothecin,irinotecan
Camptothecin,irinotecan
irinotecan
O O
OHOO
O N N
HO HO Antitumor
Antitumor
Antitumor
Camptotheca
Decne.
Camptotheca
Camptotheca
Decne.acuminata
[1][1]acuminataCamptothecin,
[1]
acuminata
acuminata and
Camptothecin,
and irinotecan
Camptothecin,
topotecan irinotecan
irinotecan
topotecan
O
O
N
N N
Decne.
Camptotheca
Camptotheca acuminata and topotecan
Camptothecin,
Camptothecin, irinotecan
irinotecan HO O
O HO
Antitumor
Antitumor
Antitumor
Decne.
Decne. [1]
Decne. [1] [1] and topotecan
and topotecan
and topotecan
HO HO NN
Antitumor
Antitumor
Decne.
[1] [1] and topotecan
N
Decne. and topotecan
N

camptothecin
camptothecin
camptothecin
camptothecin
camptothecin
camptothecin
camptothecin
camptothecin
HH
HO H OH
HOH OHOH
HH HO H
OO OO HOH H HO OH
HO OH
OH OO
Gimkgo biloba L. [82]
Gimkgo biloba
Gimkgo L.
biloba [82] Ginkgolide
GinkgolideBB B O H
OHO O O OH OH O Cerebral
Cerebralinfarction
infarction
Gimkgo biloba L.L. [82]
[82] Ginkgolide
Ginkgolide B O O
H
H H O O Cerebral
Cerebral infarction
infarction
Gimkgo
Gimkgo biloba L.
L. [82]
bilobabiloba
[82]L. [82] Ginkgolide
Ginkgolide B
B
O O
OO O O O OOO O Cerebral
Cerebral infarction
infarction
Gimkgo
Gimkgo biloba L. [82] Ginkgolide
Ginkgolide B B O O OO O
OO
O Cerebral infarction
Cerebral infarction
OO O O
OH OH O
O O
OHOH O H H O O
O O
OH
OH O H
H
OH OH H H
OH
OH OH
HO
HO HO OH
OH
OH OH
HO
HO
HO HO
Polygonum multiflorum HO O OH
Polygonum multiflorum
O O
Polygonum multiflorum
HO HO OH OH
Polygonum multiflorum Stilbene glycoside Vascular dementia
Polygonum multiflorum
Thunb. [83] Stilbene glycoside
Stilbene
Stilbene glycoside
glycoside HO OH O OH Vascular
Vascular
Vascular dementia
dementiadementia
Polygonum multiflorum
OH OH O
Thunb. [83]
HO OH
Thunb.
Polygonum [83]
multiflorum Stilbene
O
Thunb.
Polygonum [83]
multiflorum Stilbene glycoside
glycoside
HO HO
HO
HO HO O OH OH
Vascular
Vascular dementia
dementia
Thunb. [83] Stilbene glycoside Vascular dementia
OH
Thunb. [83] [83]
Thunb. Stilbene glycoside HO
OH
OH Vascular dementia
Thunb. [83]
OH
HO
HO HO

OH
OH OH
OH
OH
OH
O OH
Ranunculus
Ranunculus
Ranunculusternatus
Ranunculus ternatus
ternatus
ternatus
O O O
Ternatolide Anti-tuberculosis
O O
Ternatolide
Ternatolide
Ternatolide
O Anti-tuberculosis
Anti-tuberculosis
Anti-tuberculosis
Ranunculus
hunb.
hunb.
hunb. ternatus
[84,85]
Ranunculus ternatus
[84,85]
[84,85]
O
O O
hunb. [84,85]
Ranunculus ternatus
Ranunculus ternatus Ternatolide
Ternatolide
O O
O O Anti-tuberculosis
Anti-tuberculosis
Ternatolide Anti-tuberculosis
O O O
hunb. [84,85]
hunb.hunb.
[84,85] Ternatolide Anti-tuberculosis
hunb. [84,85]
[84,85] O
O
O
O O O
O O O O
O
O OO
O OO O
Curcuma
Curcumalonga
CurcumalongaL.L.[86]
longa [86]
L. [86] Curcumin
Curcumin
Curcumin Hypolipidemic
Hypolipidemic
Hypolipidemic
Curcuma longa L.
L. [86] Curcumin Hypolipidemic
HO OH
Curcuma
Curcuma longa
Curcuma L. [86]L. [86]
longa longa
[86] Curcumin
Curcumin
Curcumin
HO HO
HO O O
OH OH
Hypolipidemic
Hypolipidemic
Hypolipidemic
HO O O O OH
OH
HO HO O OH OH
O
O O
O
O O O O
 OH

HO

Polygonum multiflorum HO O OH
Stilbene glycoside Vascular dementia
Thunb. [83]
OH
HO

Molecules 2016, 21, 559 13 of 18

OH

Table 3. Cont. O
Ranunculus ternatus O
Ternatolide Anti-tuberculosis
hunb. [84,85] O
Origin (Plant, etc.) Drugs or Compounds Chemical Structures Effects or Indication
O O

Curcuma
Curcuma longa
longa L. L. [86]
[86] Curcumin
Curcumin Hypolipidemic
Hypolipidemic
Molecules 2016,21,
Molecules2016, 21,559
559
HO OH 12
12ofof16
16
O O

HO
HO
O
HO O
O HOC
O C

CH2
HO OH CH2
HO OH
O
Ophiopogon
Ophiopogonjaponicus
Ophiopogon japonicus
japonicus
HO O
O HOC Anti-myocardial
Anti-myocardialcell
Anti-myocardial cell
Polysaccharide
PolysaccharideMDG-1
PolysaccharideMDG-1
MDG-1
O C
(L.f.)
(L.f.)Ker-Gawl.
(L.f.) Ker-Gawl.[87]
Ker-Gawl. [87]
[87] CH2 injury
injury
cell injury
OH CH2
OH O O O
O O HO O
O OH O OH O HO
O OH O OH O

OH CH2
OH OH OH OH CH2 n
OH OH OH n

O
O
O -
O i P-r r
iP
S
S
NH
H NH
H H
H
NH
Chromobacterium
Chromobacterium
Chromobacterium O
NH
Romidepsin
Romidepsin
Romidepsin
O
Antitumor
Antitumor
Antitumor
violaceum
violaceum[88]
violaceum [88]
[88] S S
O
O
S S
H -
H
NH i P-r r
NH i P
O
O
NH
NH
O
O

6. 6.6.Discussion
Discussion
Discussion

Human
Human
Human history
history
history isis also
is also thethe
also history
history
the history ofof medicines
of medicines medicines usedused to
to treat
used to treat
and and
and prevent
treatprevent various
prevent various
diseases.
various diseases.
To
diseases.
ToTocounter
counter counter the
the dangerthedanger fromfrom
danger serious
from serious illnesses
illnesses
serious andand
illnesses to
and to
toguarantee
guarantee
guarantee survival
survival
survival of
of theofthe species,
species,
the species, it isititis
isnecessary
necessary
necessary
toto to continually produce better drugs. With time, the use of these natural products as TMincreased.
continually
continually produce
produce better
better drugs.
drugs. With
With time,
time, the
the useuse of of these
these natural
natural products
products as asTM TM increased.
increased.
Modern
Modern
Modern medicine
medicine
medicine has has
has benefited
benefited
benefited considerably
considerably
considerably from
from fromTM TMTM ininintwo
two two areas:
areas:
areas: drugs
drugs
drugs with
with similar
similar
with similar effects
effects and
effects and
and
drugs
drugs withwith different
different effects
effects from from
those those
of of
TM. TM.
From From
the the
history history
drugs with different effects from those of TM. From the history of drug development, it is evident of drugof drug development,
development, it is it
evidentis evident
that
that
many many
thatdrugs
manyhavedrugs
drugs have
beenhave been
beenderived
derived derived
as a result as
asaaofresult
result ofofinspiration
inspiration inspiration
from TM. from
fromTM. TM.
TheThe
The application
application
application of,of,
of,
and and
and research
research
research into,
into,into, natural
natural
natural products
products
products arearefarfar
are far from
fromfrom satisfactory.
satisfactory.
satisfactory. AA Anumber
number
number ofof of
problems need to be addressed in the future. For example,
problems need to be addressed in the future. For example, synergistic effects may exist among the
problems need to be addressed in the future. For example, synergistic
synergistic effects
effects may may exist
exist among
among the the
compounds
compounds
compounds thatthat
that occur
occur
occur in in innatural
natural
natural products;
products;
products; however,
however,
however, thethe
the modes
modesmodes andand
and mechanisms
mechanisms
mechanisms of of
ofaction
action
action areare
are seldom
seldom
seldom
very
very clear. It is, therefore, necessary to make full use of such
very clear. It is, therefore, necessary to make full use of such synergetic effects toward improving
clear. It is, therefore, necessary to make full use of such synergetic
synergetic effects
effects toward
toward improving
improving thethe
the
effectiveness of drugs. However, it is also requisite that any
effectiveness of drugs. However, it is also requisite that any adverse effects of natural products
effectiveness of drugs. However, it is also requisite that any adverse
adverse effects
effects of of natural
natural products
products bebe be
properly
properly
properly reduced
reduced
reduced to totomeet
meet meet safety
safety
safety standards.
standards.
standards.
With
WithWith thethe
the riches
riches
riches of of of modern
modern
modern technology,
technology,
technology, suchsuch
such asas in in
as in synthesis,
synthesis,
synthesis, fermentation,
fermentation,
fermentation, pharmacology,
pharmacology,
pharmacology,
pharmacodynamicstogether with biological diversity,
pharmacodynamicstogether with biological diversity, chemodiversity, and great breakthroughs
pharmacodynamicstogether with biological diversity, chemodiversity,
chemodiversity, and
and great
great breakthroughs
breakthroughs inin in
evolutionary
evolutionary
evolutionary techniques
techniques
techniques oror orconceptscombined
conceptscombined
conceptscombined with
withwith aawealth
a wealthwealth ofofofknowledge
knowledge
knowledge about
about
about natural
natural
natural products,
products,
products,
ititwill
it will bebe
will be possible
possible
possible toto toestablish
establish
establish aalarge
a largelarge compound
compound
compound library
library
library forfor
for drug
drugdrug screening
screening
screening [89].
[89].
[89]. This
ThisThis
willwill
will enhance
enhance
enhance thethe
the
possibilities
possibilities for for individual
individual treatment
treatment and and prevention
prevention of of
possibilities for individual treatment and prevention of disease. Humankind needs to learn more
disease. disease.
HumankindHumankind needs needs
to learn to learn
more more
from
from
fromnatural
natural naturalproducts
products products and
and traditionalandtraditional
traditional
medicines. medicines.
medicines.
InIn order
order to to further
further promote
In order to further promote the development
promote the the development
development ofof ofmodern
modern
modern medical
medical
medical research
research
research ononon natural
natural
natural products,
products,
products,
humans
humans have
humans havehave to
to to face
face face up
up up to
to to various
various difficulties
various difficulties and
difficulties and and challenges.
challenges. Valuable
challenges. Valuable information
Valuable information on
information on on natural
natural
natural
products and TMs is mixed in a large number of documents,
products and TMs is mixed in a large number of documents, data, and useless rumors. Furthermore,
products and TMs is mixed in a large number of documents, data,
data, and and useless
useless rumors.
rumors. Furthermore,
Furthermore,
oneone
one plant
plant
plant orororformula
formula
formula ofof ofnatural
natural
natural products
products
products andand
andTMsTMs
TMs contains
contains
contains aalarge
a largelarge number
number
number ofofofchemical
chemical
chemical constituents,
constituents,
constituents,
including
including
including active,
active,
active, invalid,
invalid,
invalid, andand
and possible
possible
possible synergistic
synergistic
synergistic components.
components.
components. Therefore,
Therefore,
Therefore, great
great
great effort
effort
effort should
should
should bebe be
made
made at first to remove the dross and take the essenceprecious
made at first to remove the dross and take the essenceprecious experience of natural products and
at first to remove the dross and take the essenceprecious experience
experience of of natural
natural products
products andand
TMs.
TMs. TMs. Furthermore,
Furthermore,
Furthermore, ininin
manymany
many cases,
cases,
cases, the the
the
roleroleofof
role ofsingle
single
single compound
compound
compound from
fromfrom natural
natural
natural products
products
products and and
and TMs
TMs TMs is isis
paid
paid much
much attention
attention to. to. However,
However, as as aa matter
matter of of fact,
fact, oneone advantage
advantage of of TMs
TMs therapeutics
therapeutics isis the the
synergism; that is, often multiple components in TMs play
synergism; that is, often multiple components in TMs play a synergistic role which is greater than a synergistic role which is greater than
that
thatofofthe
theindividual
individualdrug. drug.In Inthe
themeantime,
meantime,the the1 1disease,
disease,11target,target,11drug
drugmode modecannotcannottreat treatsome
some
complex
complex diseases effectively, such as cardiovascular disease and diabetes. Thus, the treatmenthas
diseases effectively, such as cardiovascular disease and diabetes. Thus, the treatment has
seen
seenaashift
shiftto tothethemulti-drugs
multi-drugsand andmulti-targets
multi-targetsmode modefor forcombination
combinationtherapies.
therapies.Therefore,
Therefore,in inthethe
future, multidisciplinary collaborative research, closely cooperated with new ideas, such as network
Molecules 2016, 21, 559 14 of 18

paid much attention to. However, as a matter of fact, one advantage of TMs therapeutics is the
synergism; that is, often multiple components in TMs play a synergistic role which is greater than
that of the individual drug. In the meantime, the 1 disease, 1 target, 1 drug mode cannot treat
some complex diseases effectively, such as cardiovascular disease and diabetes. Thus, the treatment
has seen a shift to the multi-drugs and multi-targets mode for combination therapies. Therefore,
in the future, multidisciplinary collaborative research, closely cooperated with new ideas, such as
network pharmacology and big data, will be possible to explain the synergism and other mechanisms
of natural products and TMs from which more and better new drugs and treatment will be discovered
and inspired.

Acknowledgments: This review was supported in part by research grants (No. 81260669 and 81560698) from
National Natural Science Foundation of China, respectively.
Conflicts of Interest: The authors declare no conflict of interest.

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