Chinese Medicine, 2011, 2, 84-92
doi:10.4236/cm.2011.23015 Published Online September 2011 (http://www.SciRP.org/journal/cm)
Alternative Medicine and Molecular Mechanisms in
Chronic Degenerative Diseases
Alma Lorena López Velazquez1, María de la Luz Miranda Beltrán2, Arturo Panduro3,
Luis Huacuja Ruiz1
1Chronic Degenerative Disease Institute, Centro Universitario de Ciencias de la Salud (CUCS),
University of Guadalajara, Guadalajara, México
2Biomedical Applications Laboratory, Centro Universitario de los Lagos (CU-Lagos),
University of Guadalajara, Lagos de Moreno, México
3Molecular Biology in Medicine Laboratory, Fray Antonio Alcalde Hospital, Guadalajara, México
Received April 4, 2011; revised April 18, 2011; accepted April 28, 2011
Abstract
Knowledge of healing plants worldwide properties it has-been extensively studied by their biological activi-
ties. The increasing number of plant users for healthcare originated the Research Center in Complementary
Alternative Medicine, National Institute of Health (NIH) whose primary function is to be alert with a strictly
scientific sense about de use of plants as main source of Complementary Alternative Medicine. It is currently
about the synergy known that Is achieved on the hepatoprotective, antioxidant and hypoglycaemic activities
with mixtures formed by selected plants and combined. These plants are characterized by their content of
hidroxyphenolic compounds as cynarin, rosmarinic acid, flavonoids silybin and among others. Actually this
kind of herbal preparations are investigated in patients with cirrhosis, type II diabetes mellitus, breast cancer
and arthritis diseases. Patients with Chronic Degenerative Diseases are in state of stress and Its metabolism
produces free radicals such as superoxide ºO2, hydroxyl ºOH and peroxynitrite highly reactive with unsatu-
rated fatty acids of cell membranes producing lipid peroxidation. The main product of this process is the
peroxyl, that when it’s reduced forms hydroxiperoxyle its decomposition forms MDA and 4-hidroxialquenal.
These substances bind to R-SH2 of the aminoacids of the proteins and to the thymine of DNA, altering their
biological function. Before the treatments with selected and micropulverized plants to patients, it is neces-
sary and required in animal models demonstrate that plants do not produce toxic effects. Using mixtures of
plants micropulverized is good choice because these microparticles behave as micro-releasing their con-
stituents with increased activity and bioavailability to target cells so it will be possible to achieve greater
power to control their activity and perhaps cure the disease, and provide patients an effective herbal medicine
safe, free of toxic effects and low cost.
Keywords: Alternative Medicine, Mixture of Plants, Stress, Lipoperoxidatio
1. Introduction
Since ancient times man has learned to live with envi-
ronmenta l plant and s uddenl y he reali zed that some pl ants
had medicinal properties, but some could intoxicate him
until provoke the death. He learned to classify and dis-
tinguish it of which were harmful and those were medi-
cated, thus becoming th e pr imitive h erbalist o r chief ph y-
sician, if, that herbal medicine is as old as the m an [1-3]. It
is concluded that knowledge about the use of medicinal
plants since ancient times, have been transmitted from
generation to generation, giving rise to the Traditional
Medicine, which has evolved to Herbal Medicine and
Scientific Medicine. The first relates to semi-purified
herbal products consist of two, three or more compounds
whose effects are investigated experimentally and its
therapeutic efficacy is proven in clinical studies by me-
dical practice and are employed in the field of scientific
medicine is used as an active substance or drug [4-7].
Phytotherapy is the treatment of plants and vegetable
substances, and also designating the treatments with the
preparations of herbal remedies containing refined vege-

A. L. L. VELAZQUEZ ET AL.85
table ingredients, extracts of plants or parts of them. It has
been demonstrated that in general the biological activity
of plants is greater when using mi xed [6,8-11], in t his way
they, achieve a positive synergy with the advantage of
minimizing any risk of toxicity [6,8] This synergistic
effect is even greater when the plants a re selected for their
biological activity and physico-chemical properties sim-
ilar.
Currently the use of Traditional Medicine has diver-
sified extensively in the biological activity possessed by
plants as antiviral [12-15], antimicrobial [16,17], immu-
nological [18], anticarcinogenic [19,20], contraceptive
[5,21] and liver disease [22-24], gastrointestinal [25], ar-
thritis [26] and antidiabetic [6,27-29] among others. In the
use of Alternative Medicine it is n otable that it increases
with development, income and younger patients [30,31].
Ernst and col carried out a bibliographic review of treat-
ments used by cancer pat ients in 2 6 stages in 13 countries.
The authors report certain variation in the use of Alterna-
tive Medicine is between 14.2% to 64% [31] Figure 1. In
Latin America, the countries that stand ou t as Alternative
Medicine users are Brazil, Argentina, and Mexico as re-
vealed by their scientific communications [4] Figure 2.
Due to the increase in users of plan ts for treating their
illnesses by decree in 1999 the Institute of Comple-
mentary Alternative Medicine (CAM) at the National
Figure 1. Frequency of patients with cancer patients of MAC users. This figure shows significant variation in the use of MAC
by patients with breast cancer, although in the United States showed the lowest percentage of these users, is the country with
the greatest number of research projects at different institutes, research centers and universities.
0
500
1000
1500
2000
2500
3000
3500
4000
Brazil
 Mexico 
A
rgentina ChileVenezuela Colombia PeruCuba Uruguay 
Count ries
Numberofpapers
Figure 2. Scientific production plants in selected Latin American countries in the 1984-2004 periods. This figure shows
countries with the high scientific production is Brazil and then Mexico and Argentina, the rest of the countries with a
difference in their scientific production plants significantly lower.

A. L. L. VELAZQUEZ ET AL. 86
Institute of Health (NIH) [19] was established in response
to high demand information on CAM became the Na-
tional Center for Complementary Alternative Medicine
(NCCAM) whose primary function is to support research
with plants in a rigorous scientific context and provide
authoritative information to researchers and the general
public. Thus, the real benefits of herbal products are
categorized in a higher level of scientific corroboration
and validation applied to a wide variety of therapeutic
possibilities as in patients suffering from chronic degen-
erative diseases, fibrosis/cirrhosis, arthritis, cancer and
diabetes mellitus type 2, among others, cases in which
conventional medicine has reached its limit [32].
It is important to note that the empirical use of herbal
preparations involves risk, impro per use can pose a public
health problem, and the greatest danger is when the plants
are use used indiscriminately. In this sense, many people
wrongly believe that plants are safe and secure employ-
ments are to be of natural origin. There are often in hos-
pitals with poisoning attributed to misuse of the plants,
mainly due to the self limitation, lack of plant species used
or the dose abuse it is necessary that herbal therapies are
prescribed by professionals in the knowledge of plant use
and monitor the effectiveness and safety of treatments.
Today herbs are the main source of Complementary
Alternative Medicine (CAM), medical groups such theo-
ries, attitudes and treatment practices used to counteract
the side effects of conventional medicine [33-35]. The
patients using t his type of m edicine are c onvinced that t he
treatments are natural, safe and effective, stimulating the
immune system, are cheaper, and better control their
disease.
The processes of scientific research of plants requires a
comprehensive knowledge of them and their chem ical and
physicochemical characteristics and involved in mole-
cular mechanisms of its activity and then apply metho-
dological and novel therapeutic strategies in order to
verify the effectiveness and safety the healing properties
of plants. It is important to stress that various molecular
mechanisms in the biological activity of several plants
have been pu bl ished with much intere st in t he co ntrol a n d
development of chronic degenerative diseases such as
DM2, fibrosis/cirrhosis, cancer, arthritis and obesity [7].
Because plants are the main source of alternative medi-
cine as they are learning mechanisms of its activity, it is
very clear trend of acceptance in universities, hospitals
and medical centers of the Mexican Institute Social Se-
curity (IMSS). In the first International Congress of In-
tegrative Medicine held in Guadalajara in December 2004
officially announced the acceptance of traditional medi-
cine in universities and health cen ters to he lp preven t and
even cure with allopathic treatments.
It is shown that the greatest future of Complementary
Alternative Medicine is the use of plants combined to
form mixt ures [6,11,18,36], of course, to try t o understand
the mecha nism of act i on i s re qui re d t o know the chemical
composition and structure of its constituents [11]. It has
been described that a different mix of plants and shown to
be more effective than single or composite plant just to
produce the desired effect, these preparations are com-
monly used in health care as has been demonstrated by
clinical treatments [8,9,36]. Their constituents are acting
more integrated not only into a specific organ as does an
active ingredient or drug but also do so in receptor cells of
other tissues involved in disease.
In another context, we investigated different drug elu-
ting systems such as microspheres [37] polymeric mi-
celles [38,39] or nanotubes that release anticancer drugs
to tumors in different parts of the body [40,41]. In this
sense, the strategy of using mixtures of plants micropul-
verized is good choice because these microparticles be-
have as micro-releasing their constituents with greater
bioavailability to target cells. This assertion is based on
the benefits achieved with the treatments of different
mixtures of plants [6,9,11,18,36,42] and to synergize the
effect does not pr oduce to xic e ffects or at lea st reduced to
a minimum. We have shown that such preparations mi-
cropulverized selected plants to a pa rticle size of 20 t o 200
microns combined in appropriate proportions to form
mixtures; these preparations do not produce toxic effects
during or at the end of treatment in anim al models induced
T2DM. In chronically infertile patients has been achieved
100% restore the quality of se men with the possibility of
inducing spontaneous pregnancies what we have ac hieved
with 2 of 8 cases.
Before treatments to patients with multifactorial dis-
eases it is necessary to demonstrate through pharmaco-
logical studies in animal models for mixtures of selected
plants micropulverized not produce evidence of any signs
of toxicity in subchronic 30-day treatment and thus is
relevant propose that these preparations are feasible and
effective for the control of various diseases.
Using mixtures of plants mi cropulverized is good choice
because these microparticles behave as micro-releasing
their constituents with increased activity and bioavailability
to target cells so it will be possible to achieve greater power
to control their activity and perhaps cure the disease, and
provide patients an effective herbal medicine safe, free of
toxic effects and low cost.
It is necessary that medical professionals learn more
about current therapies of Alternative Med icine Comple-
mentary and very respectfully ask their patients whether
or not users of some form of Alternative Medicine and
thus able to advise their patients on the use of this plants.
There is no doubt that plants are an extraordinary remedy
of nature because they have a veritable arsenal of poten-

A. L. L. VELAZQUEZ ET AL.87
tially useful biomolecules to develop new effective and
safe phytotherapeutic strategies with the possibility of
increasing the effectiveness of conventional medicine
treatments for chronic diseases mainly degenerative dis-
eases such as fibrosis/cirrhosis, type 2 diabetes, arthritis
and breast cancer.
2. Molecular Mechanisms of Medicine in
Multifactorial Diseases
First, the processes of scientific research on medicinal
plants requires a comprehe nsi ve knowledg e of them , their
chemical and physicochemical characteristics and their
association with the molecular mechanisms of its activity
and then develops and implement innovative methodo-
logical strategies in order to try to know molecular level
the healing properties of plants described by the Com-
plementary Alternative Medicine. By this approach, there
have been reported various mechanisms of activity of
many plants with great impact on prevention, develop-
ment and eve n cur e ch ronic de gene rative dise ases. Peopl e
with any of these diseases, accelerate the excessive pro-
duction of free rad icals and induce non-enzymatic glyca-
tion of proteins and peroxidation of polyunsaturated fatty
acids in the cell membrane, these processes are involved
in the development of DM2 [43] and other diseases such
as cirrhosis [22,33]. The close relationship between lipid
peroxidation and nonenzymatic glycosylation of proteins
suggests that the antidiab etic activity of p lants is due to a
synergistic effect of antioxidant and antiglycaemic ac-
tivities as has been recently confirmed by the plant extract
rich in saponins very active in inactivation (53.85% to
91.15%) of free radicals [43,44].
Plants selected for their hepatoprotective and anti-
oxidant activities are characterized by their conten t of hi-
droxiphenolic compounds as flavonoids, carnosol [45],
cinarina, boldin [46], rosmarinic acid [22] baicalin and
baicalein [18], and brevifolina [14] compounds highly
active against free radicals protecting the cell membrane
lipoperoxidation. Figure 3. These plants have anticirrho-
tic and antioxidant activity [8,22,23], stimulate the im-
mune system [18] and against hepatitis B virus [13,14]. It
was concluded a study in Wistar rats with liver damage
with carbon tetrachloride and treated with the mixture of 7
plants which showed no changes in the cytoarchitecture of
the liver parenchyma or biochemical parameters indica-
tive of metabolism such as transaminase, cholesterol,
triglycerides, lipoproteins, bilirubin, protein and albu min.
These effects produced by mixtures of plants pr o bably do
in part by the reaction of the hydroxyl group of the aro-
matic ring of the constituents of plants against free radi-
cals and preventing lipid peroxidation possibly by in-
hibiting the activation of stellate cells to cause fibrosis/
cirrhosis.
In the case of DM2, we know that the development of
this disease is associa ted with multiple int eracting genetic,
environmental and cultural. DM2 patients are under
chronic stress very aggressive chemistry that leads to
Figure 3. Hepatoprotective and antioxidant molecules from plants.

A. L. L. VELAZQUEZ ET AL. 88
diabetes to an inability to metabolize glucose (hypergly-
cemic) and increased lipolysis, which develop a patient
glucolipointoxicación insulin resistance (Figure 4). Given
this loss of metabolic homeostasis of lipids and carbohy-
drates, synthet ic drugs have been used wit h hypoglycemic
activity but most adverse effects [33-35]. Given these
complications has been investigated in experimental
animals and humans many plants with hypoglycaemic
effect [6,28,47] and has proposed that the hypoglycemic
effect of plants occurs through three mechanisms: first,
increased insulin secretion, second, increased glucose
uptake by muscle and adipose tissue an d third, inhibition
of glucose absorption from the intestine [7].
The natural juice of Opuntia ficus indica lyophilized
showed potent antioxidant, protects chondrocytes from
damage from free radicals produced more potent than
hyaluronic acid also has antioxidant effects. It is sug-
gested that the increased activity of Opuntia is due to
polysaccharides that are more resistant to depolymeriza-
tion [26]. It is proposed that the greatest future of the
MAC is the use of plants combined to form mixtures, of
course, to try to understand its mechanism of action is
required know the chemical composition and structure of
its constituents [14,36] have described different mixtures
of plants and shown to be more effective than a single
compound to produce the desired effect, these prepara-
tions are commonly used common in the healthcare and
clinical treatments [8,36]. High correlation was found
between the content of compounds such as chlorogenic
acid and hidroxifenólicos cinarina with the decrease of
transaminases, malondialdehyde and increased flow bile
in rats poisoned with carbon tetrachloride [24].
3. Oxidative Stress
It is well known that patients suffering from a chronic
degenerative disease such as T2DM, fibrosis/cirrhosis,
cancer or obesity are in a state of very aggressive per-
oxidative stress caused by multiple stressors such as in-
fection by viruses or bacteria, compounds toxins, poor
diet including psychosocial factors of modern life as it is
becoming increasingly difficult to obtain enough satis-
factions for a quality life which causes distress, frustration,
resentment and consequently a state of stress. In these
stressful conditions produced substances nitrogen and
oxygen called free radicals and superoxide anions ºO2,
Figure 4. Pathophysiology of Diabetes Mellitus 2. This figure shows the interaction of key actors in the development of DM2,
liver, pancreas, adipose tissue and muscle. It is very obvious that the balance between hydr olysis and synthesis of glycogen is
altered. Hydrolysis of glycogen in the liver beyond normal so this organ blood exported to high glucose concentrations, an
exaggerated adipocyte lipolysis exports high concentrations of free fatty acids, this glucolipointoxicacion makes insulin
resistant muscle. In this process a very important part of the insulin receptor in muscle and liver receptors alpha and beta
adrenergic and glucagon that facilitate the entry of calcium and cyclic AMP are necessary to preserve the hydrolysis and
synthesis of glycogen.

A. L. L. VELAZQUEZ ET AL. 89
hydroxyl ºOH, NO peroxynitrite ºONO2, nitroxyl RNOº,
phenoxyl, alcohoxile RCO, peroxyl RCOOº the among
other highly reactive polyunsaturated fatty acids in the
membranes of cel ls producing the per oxyl radical pri mary
product of l ipid per oxidation in the pre sence of a red ucing
agent as hydroperoxide [48] whose decomposition gives
rise to mal ondialdehyde and 4 hy droxy alquenal, Fi gure 5,
that bind to RSH2 of the amino acids in prote ins and D NA
thymine which metal ions (trace elements) can lead to
mutations [49].
When agents are an intense impact stressors and
chronic natural antioxidant defenses of our body such as
glutathione, vitamin E and superoxide dismutase are not
able to neutralize excess free radicals as cell membranes
are damaged severely. Oxidative stress can be measured
by enzyme superoxide dismutase (SOD), lipoperoxidase
(LP), uric acid and malondialdehyde (MDA) the major
molecular markers of oxidative stress [50]. The antioxi-
dant propert i es o f u ri c aci d have been st udi ed recentl y , it s
plasma concentration is 10 times greater than vitamins E
and C [51], its soluble form in plasma urate, captures the
radical superoxide (ºO2), hydroxyl radical (H Oº), inhibits
Figure 5. Lipoperoxidation of polyunsaturated fatty acids.
The lipid peroxidation process involving free radicals super-
oxide (2) and hydroxyl (OHº) this by reacting with the
poly-insaturated fatty acid, lose a hydrogen atom in the
presence of •OH radical produce a water and lipid radical.
The main product of these process is the peroxyl that when
its reduced forms hydroperoxyle, its decomposition forms
malondial- dehyde and 4 hydroxialquenal. These substances
are very reactives with R-SH2 of proteins and with DNA
thymine.
o
O
the reaction of nitric oxide (NO) with O2 and prevents the
formation of highly toxic peroxynitrite causes cell dam-
age by nitration tyrosine residues of proteins. Uric acid,
helps maintain normal levels of NO and endothelial
function t o pre vent de gradat i on of t he enzy m e sup er oxi de
dismutase extracellular enzyme that is essential in main-
taining vascular en dothelial function.
Oxidative stress induces excessive entry of free fatty
acids to the liver where it is stored as triglycerides. This
accumulation of lipids in the liver, the mitochondria con-
tribute to losing the ability to oxidize fatty acids by β
oxidation and transported to the cytoplasm. In these cir-
cumstances the liver key organ in maintaining homeosta-
sis, has transformed liver fat and there is a pathophysio-
logical state known as steatohepatitis that develops fi-
brosis/cirrhosis and consequently the altered metabolism
in peripheral organs: muscle, brain, heart, kidney and
pancreas.
4. Discussion
To investigate the activity of a more comprehensive mix
seemingly more difficult than when investigating an ac-
tive substance or drug. However , this difficulty is partially
resolved by the engagement of researchers bound in their
respective areas of expertise assigned to different research
centers and institutes and thus to ensure the feasibility of
meeting the targets committed to projects resulting from
the research. This criterion is necessary and required to
perform more comprehensive investigation with the
mixture of plants through two stages of research: the first
basic research in animal models to demonstrate through
pharmacological studies of acute and chronic sub 30 days
that the mix of plants non-lethal effects or toxicity at the
therapeutic dose given to continue the second phase of
research in patients with clinical diagnosis of the disease.
In conducting research in this manner, it is possible to
scientifically validate the healing properties of plants of
Traditional Medicine are potentially useful for effective
and safe herbal therapies with significant impact on ap-
plied research. Of course, this implies strong support for
the institutions co ncerned to promote the develop ment of
substantive programs that allow plants to obtain optimum
crop quality in sufficient quantities and at appropriate
times. Also promote the linking programs with health
institutions to shape its application in clinical research
projects and marketing to reach prospective new phy-
tomedicines. Sinergistic effect is even greater when the
plants are selected for their biological activity and phy-
siochemical similar properties.
Since we now are getting to know the molecular me-
chanisms of activity of the plants investigated indi-
vidually or combined to form blends achieved a syner-

A. L. L. VELAZQUEZ ET AL. 90
gistic effect on the activity of plants without producing
toxic effects or at least reduce at minimum. The absence
of toxicity should be evaluated experimentally before
treatments in humans by identifying clinically relevant
biochemical parameters, transaminases, triglycerides, cho-
lesterol, glucose, bilirrubin, uric acid and total pro tein. In
Mexico it is very clear trend for the acceptance of me-
dicinal plants as the main resource of alternative medi-
cine in institutes, universities and the National Medical
Center, Mexican Institute of Social Security.
It is important to note that the empirical use of herbal
preparations involves risk, impro per use can pose a public
health problem, and the greatest danger is when the plants
are used indiscriminately. In this sense, many people
wrongly believe that plants are safe and secure employ-
ments are to be of natural origin. There are often in hos-
pitals with poisoning attributed to misuse of the plants,
mainly due to the self limitation, lack of plant species used
or the dose abuse it is necessary that herbal therapies are
prescribed by professionals in the knowledge of plant use
and monitor the effectiveness and safety of treatments.
There is growing interest in obtaining new plant pro-
ducts with quality and effective health care. To maximize
the potential of herbal medicine in diseases and achieve
better results when using phytomedicines, you should
meet the following recommendations. Know very well the
first plants to be used and preferably cut shortly before the
end of blooming with strict adherence to appropriate
procedures to obtain specimens in optimal conditions of
quality. Second, immediately disinfected with 1% bleach,
rinse with distilled water and transported carefu lly to the
laboratory, prepare specimens for identification by bo-
tanical experts, third dehydrate the plants at 50˚C, mi-
cro-pulverized and combine it res pect at the percentage at
the proportions appropriate to form a mixture; encapsulate
suitable quantities, stored in amber bottles and kept re-
frigerated sterile or room temperature if used in a recent.
5. Conclusions
Plants are an extraordinary remedy of nature by the wide
variety of molecular structures in their constitution that
can be used for different therapeutic proce dures in chronic
degenerative diseases such as type 2 Diabetes Mellitus
(DM2), cirrh osis, cancer and obesity which a re the greater
health impact.
Today herbal preparations are used to combine plants
in percentage proportions suitable for forming mixtures,
the use of mixtures has important advantages, is achieved
by a synergistic effect on the activity of interest also does
not prod uce toxic effects o r at least reduced t o a maximum
this is because the molecules are mixed, if not active in the
desired effect, antagonizing the activity of other mole-
cules that are also in the mix that might be causing to
produce toxicity.
The strategy of using mixtures of micropulverized
plants is a goo d choice becau se this micropa rticles beha ve
as microreleasing systems, their constituents with great
bioavailability to target cells without evidence of any
signs of toxicity in subchronic 30 day treatment and thus
is relevant propose that t hese preparations are feasible and
effective for the control of various diseases.
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