Phytotherapeutics in Treating Diabetes

13CHAPTER

Phytotherapeutics in Treating Diabetes

C. Vennos, H. Schwabl, C. Bommeli

PADMA AG, Schwerzenbach, Switzerland

1. INTRODUCTION

As the diabetes epidemic is growing worldwide, remedies for treating diabetes are
becoming more important than ever (Zimmet et al., 2001). Although increased blood
glucose is the defining parameter of the disease, glycemic control is only one aspect of
integrated diabetes management, which includes preventive measures that target the
many pathogenic factors leading to diabetes as well as prevention and treatment of the se-
quelae of diabetes, as shown in Figure 13.1 (Vennos and Uehlinger, 2010). Diabetes-
associated diseases are gaining more importance as the spectrum of drugs to control blood
glucose is continuously growing and the life expectancy of diabetic patients is increasing.
In addition, because of the chronic nature of the disease, an integrative therapeutic
approach and long-term treatment are necessary. Therefore special importance lies not
only in the effectiveness but also in the safety and tolerability of the medicines used.

Phytotherapeutic drugs are complex mixtures of many chemical constituents in
relatively low doses. Monosubstances isolated from plant material are not considered
as phytotherapeutics and are not included in this evaluation, because they do not show
the characteristics of whole plant preparations. In herbal preparations, the different kinds
of constituents act synergistically on different pathogenic mechanisms in a multitarget
mode of action. This quality is utilized in a special category of phytotherapeutics, where
different herbal drugs are assembled in multicompound formulas. These can be seen as
new, man-made plants tailored to specific disease states or to the constitution and con-
dition of individual patients. Such complex phytotherapeutics are used in many Asian
medicine systems such as Japanese Kampo Medicine, Chinese Medicine, Tibetan Med-
icine, or the Indian system of Ayurveda, each featuring an extensive materia medica.

Because of the synergistic, antagonistic, and additive interactions between their
chemical ingredients, phytotherapeutics mostly exhibit a favorable safety profile. Thus,
together with their multitarget approach, they offer valuable options in complex diseases
with a multifaceted etiology such as diabetes and diabetic complications. Here we give an
overview of phytotherapeutics whose application in integrative diabetes management is
supported by the scientific literature from Medline-based literature searches and Swiss
scientific libraries. For some examples, the possible modes of action of phytotherapeutic
drugs in different diabetic disease stages are discussed.

Bioactive Food as Dietary Interventions for Diabetes # 2013 Elsevier Inc. 139
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140 C. Vennos et al.

Phytotherapeutics Phytotherapeutics Phytotherapeutics
in prevention and treatment
in prediabetes with blood glucose of diabetes-accociated diseases

and prevetion lowering effects

Susceptibility to
infections

Risk factors: Neutrophil Predisposition to:
Lifestyle factors function parodontitis, de-
pression, dementia,
(obesity, unsatura- Protein Alzheimer’s disease
ted fats, oxidative glycation,
stress, inflamma- Hyperglycemia
tory chronic states) AGEs
Chronic Blood vessel damage
age, genetic low-level Directly and via (atherosclerosis, endothelial
predisposition, inflammation protein- and
lipid oxidation dysfunction)
gender Oxidative
stress

Disturbed blood Hypertension
circulation

Factors and mechanisms Nerve damage Diabetic foot PAOD, CHD,
that can be influenced syndrome ischemic infarction
by phytotherapeutics
Paresthesia, pain Diabetic retinopathy,
nephropathy

Figure 13.1 Pathogenic mechanisms in the development of diabetes and diabetes-associated diseases, in which oxidative stress and chronic
low-level inflammation play a pivotal role. Broad arrows indicate fields that can be targeted by phytotherapeutics. AGEs, advanced glycation end
products; PAOD, peripheral arterial occlusive disease; CHD, coronary heart disease). Adapted from Vennos, C., Uehlinger, S., 2010. Das Potenzial von
Padma 28 bei Folgeerkrankungen des Diabetes mellitus [The potential of Padma 28 in diabetes mellitus associated diseases]. Schweizerische Zeitschrift
für Ganzheitsmedizin 22, 344–348.

Phytotherapeutics in Treating Diabetes 141

2. PHYTOTHERAPEUTICS IN PREDIABETES

Prediabetes is mostly defined by laboratory parameters such as impaired glucose tolerance
or increased fasting glucose levels that are not high enough to be classified as diabetes
mellitus. The main treatment goal in prediabetic patients is the same as in high-risk
patients, namely the reduction of risk factors and prevention of overt diabetes.

Although the pathogenic mechanisms of insulin resistance are not yet fully under-
stood, oxidative stress seems to play a pivotal role in the development of diabetes as well
as its complications (Maritim et al., 2003). Obesity has been identified as a main risk factor
for developing type 2 diabetes (T2D) as well as metabolic syndrome. In its endocrine
function, adipose tissue induces an inflammatory status, which may play a pathogenic role
in the development and progression of the disease (Shoelson et al., 2006). To achieve
weight loss and thus reduce the main risk factors, changes in diet and lifestyle including
reduced calorie intake and physical training remain the only measures with proven effects
of significant magnitude. Some herbal substances have shown weight loss effects in
scientific studies (Hasani-Ranjbar et al., 2009) and may enhance the effect of lifestyle
changes. With the use of most of these medicinal herbs, a change in lipid metabolism
was also found, which could constitute the mechanism of action or be an additional
effect.

Besides a dysregulation of the lipid metabolism, risk factors that are known to enhance
obesity are insufficient physical exercise, disturbed sleep or lack of sleep, or proinflam-
matory processes. These can also be targeted by phytotherapeutics to reduce the risk of
diabetes. Herbal medicines can, for example, support physical activity as so-called adap-
togens or as enhancers of blood circulation (Feldhaus, 2010), reduce sleep disorders
(Head and Kelly, 2009), or reduce inflammatory mediators such as inflammatory cyto-
kines (Spelman et al., 2006). Examples of herbal substances that can be used in prediabetes
and diabetes risk management are shown in Table 13.1.

3. PHYTOTHERAPEUTICS FOR GLYCEMIC CONTROL

Blood glucose homeostasis is achieved by diverse biochemical mechanisms. Medicines
for glycemic control may therefore target one or more of these mechanisms, for example,
by reducing glucose absorption from the small intestines, increasing or regenerating pan-
creatic beta cells, suppressing hepatic gluconeogenesis, increasing insulin sensitivity in
tissues, or by enhancing peripheral glucose uptake (Yeh et al., 2003).

Examples of herbal substances and complex phytotherapeutics from traditional med-
icine systems with scientific evidence of their glucose-lowering effects are listed in
Table 13.2.

In a whole system approach, the effects of different polyherbal formulations from
Tibetan medicine on blood glucose levels were analyzed. Two hundred newly diagnosed

142 C. Vennos et al.

Table 13.1 Phytotherapeutics in the prevention and treatment of high-risk patients and prediabetics:

examples of herbal drugs, for which a benefit could be shown in factors of diabetes pathogenesis, such

as supporting lifestyle changes or reducing risk factors

Herbal drug Effects, mechanisms

Zingiber officinale Roscoe Weight loss
Cissus quadrangularis L. Weight loss
Momordica charantia L. Weight loss
Valeriana officinalis L. Sleep disorders
Humulus lupulus L. Sleep disorders
Melissa officinalis L. Sleep disorders
Srog ’zin 10 (Tibetan Medicine System: 10 herbal ingredients) Sleep disorders, stress resistance
Panax ginseng C.A. Mey. Enhances physical activity
Padma 28 (Tibetan Medicine System: 21 herbal ingredients Enhances physical activity
and calcium sulfate)
Allium sativum L. Enhances physical activity
Rhodiola rosea L. Enhances physical activity, stress
resistance

Table 13.2 Phytotherapeutics in glycemic control: examples of herbal drugs, for which an effect in

glycemic control could be shown in scientific studies

Herbal drug Effects, mechanisms

Panax quinquefolium L. Antihyperglycemic
Gymnema sylvestre (Retz.) R.Br. ex Schult. Antihyperglycemic, different
pathways
Cinnamomum aromaticum Nees Antihyperglycemic
Momordica charantia L. Hypoglycemic
Trigonella foenum-graecum L. Blood glucose lowering
Glucolevel (Greek–Arab medicine system: 4 plants) Blood glucose lowering
Individualized combinations of Tibetan formulations Improved glycemic control
Kyura-6, Aru-18, Yungwa-4, Sugmel-19
Huang-Lian-Jie-Du-Tang/Oren-gedoku-to (Chinese/ Increased insulin secretion,
Japanese Medicine system: 4 plants) Improved glucose tolerance

diabetes patients were treated with individualized combinations of at least two of four
herbal formulations (Kyura-6, Aru-18, Yungwa-4, and Sugmel-19; Namdul et al., 2001).

4. PHYTOTHERAPEUTICS IN DIABETES-ASSOCIATED DISEASES

As indicated in Figure 13.1, secondary diabetic complications such as atherosclerosis,
diabetic retinopathy, or the diabetic foot syndrome have a shared multifactorial etiology.
Systemic glucose activates neutrophil function and, via nonenzymatic protein glycation,

Phytotherapeutics in Treating Diabetes 143

leads to advanced glycation end products (AGEs), to increased oxidative stress, and, grad-
ually, to a proinflammatory environment (Figure 13.1). This is a normal development with
increasing age and contributes to the state of inflammaging, a so-called silent inflammation,
which plays a pivotal role in the development of many diseases of old age (Yan et al., 2003).

In diabetic patients, even if the blood glucose/HbA1c levels are well controlled and lie
within the target range, glucose levels and, thus, oxidative stress and proinflammatory processes
are increased compared to nondiabetics. These accelerate inflammaging and are the main
factors leading to damage of blood vessels and nerves, finally resulting in diabetes-associated
conditions such as atherosclerosis, paresthesias, diabetic foot syndrome, or retinopathy.

Phytotherapeutics, which usually contain antioxidative secondary plant substances,
offer valuable options in the prevention and treatment of secondary diabetic diseases.
With their multitarget effects, herbal multicompound medicines also act via other mech-
anisms. Among these are the inhibition of AGE generation (e.g., Vitis vinifera, Ginkgo
biloba, Allium sativum) and antiatherogenic effects (e.g., Panax ginseng, the Tibetan herbal
formula Padma 28, Chinese/Japanese medicine Huang-Lian-Jie-Du-Tang/Oren-
gedoku-to). Furthermore, some herbal preparations have antibacterial properties relevant
to the susceptibility to infections often observed in diabetes patients (e.g., Cinnamomum
aromaticum, the Tibetan herbal formula Padma 28) and lead to improvement in blood
circulation (e.g., the Tibetan herbal formula Padma 28, G. biloba; Table 13.3).

5. SUMMARY: PHYTOTHERAPEUTICS IN INTEGRATIVE DIABETES
MANAGEMENT

From the point of view of integrative medicine, diabetes management goes far beyond
glycemic control. It encompasses preventive strategies, lowering of hyperglycemia, and
prevention and treatment of diabetes-associated diseases.

Table 13.3 Phytotherapeutics in diabetes-associated diseases: Examples of herbal drugs with effects

in the prevention and treatment of diabetes-associated diseases with, for example, antioxidative, anti-

inflammatory, AGE-formation inhibiting, cell and tissue protecting activities, or circulation enhancing

properties

Herbal drug Effects, mechanisms

Panax ginseng C.A. Mey. Anti-inflammatory
Padma 28 (Tibetan Medicine System: 21 herbal Inhibits atherosclerosis,
ingredients and calcium sulfate) antiinflammatory
Allium sativum L. Inhibits AGE formation
Vitis vinifera L. Inhibits AGE formation, improves
macrovascular parameters
Ginkgo biloba L. Inhibits atherosclerosis
Huang-Lian-Jie-Du-Tang/Oren-gedoku-to (Chinese/ Inhibits atherosclerosis
Japanese Medicine system: 4 plants)

144 C. Vennos et al.

Phytotherapeutics can be applied in all stages of diabetes as indicated by the arrows in
Figure 13.1.

Because of their multitarget mode of action, herbal medicines can act on different
pathogenic mechanisms at the same time. While in prediabetes, they may support lifestyle
changes and weight loss, some herbal preparations have scientifically been shown to
reduce blood glucose.

The multitarget approach is especially promising in the diabetes-associated diseases,
the pathogenesis of which includes oxidative stress, the formation of AGE, and low-level
inflammation.

The prevalence of T2D mellitus and therewith also of diabetes-associated diseases is
growing globally. Diagnosis and therapy of hyperglycemia are improving, and the num-
ber of patients with secondary diabetic complications will show an epidemical increase in
the future.

Because of their differentiated multitarget mode of action, their effectiveness, and
their generally high safety and tolerability, phytotherapeutics offer valuable preventive
and therapeutic options in holistic diabetes management.

REFERENCES

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