Antidiabetic Effect of Gymnema montanum/Momordica charantia/Moringa oleifera: History
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Gymnema montanum (G. montanum, GM) is a plant belonging to Apocynaceae family, an endemic, woody climbing shrub found mainly in Africa and India. Momordica charantia (M. charantia, MC), a plant belonging to the Cucurbitaceae family, is commonly known as a bitter gourd, balsam pear, bitter melon, or Karela and could be found in India, Japan, Singapore, Vietnam, Cuba, Ghana, Haiti, the Middle East, Central and South America and many other regions. Moringa oleifera (M. oleifera, MO) Lam is a plant that belongs to the Moringaceae family and naturally occurs widely in many tropical and subtropical areas.

In vitro and animal model studies are of great interest for selecting new phytochemicals, including polyphenols with antioxidative properties, as candidates for antidiabetic drugs.

This review provides evidence from a critical literature data analysis on the effects of plant extract supplementation in diabetes mellitus management. Authors considered and meta-analyzed the efficacy of oral supplementation of plant extracts in animal model studies and examined physiological and oxidative stress parameters.

The extracts of Gymnema montanum, Momordica charantia and Moringa oleifera represent a promising and attractive source of phytochemicals with proven antidiabetic and antioxidant activity in rat models of diabetes. They increase pancreatic insulin and insulin sensitivity in peripheral tissues, reduce insulin resistance and hepatic gluconeogenesis, and have a modulatory effect on glycolysis, gluconeogenesis and antihyperlipidemic properties. All three extracts reduced oxidative stress and revealed antiperoxidative features to protect β-cells against ROS.

They are, therefore, good candidates for the management and treatment of diabetes in mammals, especially humans. Moreover, all three plants have been widely used in traditional medicine.

  • Gymnema montanum
  • Momordica charantia
  • Moringa oleifera
  • Antidiabetic Effect

1. Introduction

According to the WHO, diabetes mellitus (DM) is one of the most widespread chronic diseases, and the number of cases is rising rapidly. The number of affected patients in 2014 reached 422 million, an almost two-fold increase compared to 1980 [1]. Current estimations predict that diabetic patients will reach 578 million by 2030 and 700 million by 2045 [2].
Oxidative stress (OS) is one of the leading causes of the development of diabetes and its complications [3]. Although organisms have an integrated antioxidant defense system to block the negative impact of reactive oxygen species (ROS), diabetes can cause this system to fail. Hence, supplementation with exogenous plant-derived antioxidants might possess capacities to avert oxidative stress-induced diseases.
Recently, there have been numerous studies in which plant extracts were used to treat various diseases with traditional medicines [4]. It is estimated that nearly a quarter of all modern medicines are derived from natural products [5]. Among the renowned antioxidant properties of several plants––including green tea, cinnamon, curcumin, grape seeds, and many berries––several new species used in traditional medicine have been documented. In vitro and animal model studies reflect an interest in selecting new phytochemical resources that possess antioxidative properties as candidates for drugs in antidiabetic approaches.

2. Gymnema montanum Effect on Diabetes

Gymnema montanum (G. montanum, GM) is an endemic, woody climbing shrub found mainly in Africa and India. Leaves of GM have medical applications, and they have a long history of use in India’s Ayurvedic medicine as an antidiabetic drug, diuretic, and digestive stimulant [7].
Currently, extracts from Gymnema leaves have found application in metabolic syndrome, weight loss, and cough.
It is postulated that phytochemicals present in GM extract, particularly gallic acid, resveratrol and quercetin, possess the antioxidative, antidiabetic and antihyperlipidemic properties [22] that play a pivotal role in lowering blood glucose in diabetic patients and in improving the action of insulin.

3. Momordica charantia Effect on Diabetes

Momordica charantia (M. charantia, MC), a plant belonging to the Cucurbitaceae family, is commonly known as a bitter gourd, balsam pear, bitter melon, or Karela. All plant parts have a bitter taste, including the fruit. India, Japan, Singapore, Vietnam, Amazon, East Africa, Brazil, Malaya, China, Thailand, Colombia, Cuba, Ghana, Haiti, India, Mexico, New Zealand, Nicaragua, Panama, the Middle East, Central and South America are the regions where MC is cultivated. At maturation, the fruit of M. charantia can be used as a dietary food, and because of its multiple beneficial activities, has also been used as a herbal medicine [23].
In ancient history, the seed and fruit were used as medication for diabetes. The other fractions of M. charantia––roots, leaves and even vines––have been used in folk medicine to treat other diseases like diarrhea, toothache and furuncle. Therefore, this plant is the subject of many ongoing studies investigating its potential in preventing and treatingseveral diseases. Each year, more and more papers reveal the plausible effects of supplementation with M. charantia, thereby strongly indicating that this plant possesses various pharmacological functions: antidiabetic, anthelmintic, abortifacient, antimalarial, antimutagenic, antilipolytic, antifertility, hepatoprotective, anti-inflammatory, contraceptive and laxative, anti-ulcerogenic, antioxidative and immune-modulatory [24].
A more comprehensive application of M. charantia in multiple areas of medicine is still restricted due to adverse effects observed in many studies. Some of these are hypoglycemic coma in children, and toxicity or even death in laboratory animals [23].
Based on the abovementioned activities of particular chemical components of M. charantia extract and broad literature data, it can be reasserted that, in correlation with its composition, the MC extracts possess the following general activities: antidiabetic, antioxidant, antiviral, antimicrobial, anthelmintic, abortifacient, antimalarial, antimutagenic, antilipolytic, antifertility, hepatoprotective, anti-inflammatory, antitumor, hypolipidemic, immunomodulatory, and wound healing.

4. Moringa oleifera Effects on Diabetes

Moringa oleifera (M. oleifera, MO) Lam is a plant that belongs to the Moringaceae family and naturally occurs widely in many tropical and subtropical areas [38,39]. This plant originates from the western and sub-Himalayan tracts, India, Pakistan, Asia Minor, Africa and Arabia [40,41]. It is well-known as the “drumstick tree” or “the horseradish tree” based on the taste of ground root preparations and the ben oil tree from seed-derived oils [41]. Diverse parts of M. oleifera (leaves, fruits, flowers, and roots) are commonly used as food, nutraceuticals, traditional medicine, water sanitization, and biofuel production due to their rich source of many vital nutrients bioactive compounds [42].
Mounting evidence reports that M. oleifera parts, especially the leaves, have nutritional properties or can be used in diet supplementation [43]. Using M. oleifera extract in food products has improved overall nutritional quality, sensory properties and shelf life. The use of leaves, seed and flower powder is well known in various food applications, such as in fortifying amala (stiff dough), ogi (maize gruel), bread, biscuits, yoghurt, cheese, and soups [42].
Moringa in non-traditional medicine is known for treating many diseases, including diabetes, cancer, cardiovascular, neurological, gastroenterological, and inflammatory disorders. Moringa oleifera leaves are the most commonly used part of this plant and contain beta-carotene, vitamins B, C, E, minerals, polyphenols [44,45,46], oxidase, catalase, alkaloids, glucosinolates, isothiocyanates, tannins, and saponins [38,47]. In Moringa seeds, niazimicin and niazirin and a rhamnosyl benzyl carbamate, rhamnosyl benzyl isothiocyanate, and various derivatives of β-sitosterol were identified. This plant’s stems, roots, and other morphological parts are not well researched, unlike the leaves and seeds; therefore, the data on the composition is relatively limited [47].
Based on the available literature, about 20 pharmacological properties can be attributed to this plant [53]. It is evident that various Moringa extracts can have hypoglycemic effects in different in vitro and in vivo models [48,54,55]. 

5. Meta-analysis

The following analysis was aimed to systematically evaluate the literature and indicate potent plant candidates for a restricted meta-analysis. Authors applied Cochrane guidelines to investigate the efficacy of oral supplementation of subjected plant origin extracts in diabetes mellitus management in animal model studies.

The initial literature search revealed about 300 original papers indicating three potent plant extracts for further analysis, of which only 23 articles were finally included in the restricted meta-analysis, revealing the experimentally confirmed in vivo and in vitro antidiabetic properties of Gymnema montanum (9 articles),
Momordica charantia (7 articles) and Moringa oleifera (7 articles).

In the meta-analysis protocol, data on physiological and oxidative stress parameters extracted from the original papers were examined and statistically analyzed.  The categories of the analyzed parameters and observed tendencies of changes are presented in Table 2 [1].

Table 2. Distribution and changes of analyzed parameters in meta-analysis.

Plant

Physiological Efficacy Parameters

Oxidative Stress Parameters

Momordica

charantia

vs control

no data analyzed Ø

Glycemia

Insulinemia↑

body weight ↔
glucose uptake by diaphragm↑

Gymnema

montanum

vs control

vs drug

vs control

vs drug

Glycemia↓

Insulinemia↑

body weight ↑

food intake↓

Glycemia↓

Insulinemia↓

body weight ↔

food intake ↓

TBARS ↓

Hydroperoxides↓

TBARS ↓

Hydroperoxides↓

Moringa

oleifera

vs control

vs control

Glycemia↓

Insulinemia↔
body weight ↑

SOD↓

CAT↑

Changes of parameters in experimental group: —decrease, ↑—increase, ↔—unchanged, Ø—not analyzed.

 

6. Results and Conclusions

Finally, 23 articles were included in the meta-analysis, revealing three plants with experimentally confirmed in vivo and in vitro antidiabetic properties: Gymnema montanum, Momordica charantia and Moringa oleifera.

The following parameter changes resulted from an investigation of the supplementation: reduced oxidative stress, decreased insulin resistance, increased insulin release, reduced adiposity, and a modulatory effect on glycolysis and gluconeogenesis, as well as attenuation of diabetes-associated weight loss, reduced fasting blood glucose and lowered oxidative status.

A comparison of Gymnema montanum versus Glybenclamide revealed the superiority of extracts over drug administration in some aspects.

The presented meta-analysis confirmed that extracts of Gymnema montanum, Momordica charantia and Moringa oleifera represent a promising and attractive source of phytochemicals with proven antidiabetic and antioxidant activity in rat models of diabetes. They increase pancreatic insulin and insulin sensitivity in peripheral tissues, reduce insulin resistance and hepatic gluconeogenesis, and have a modulatory effect on glycolysis, gluconeogenesis and antihyperlipidemic properties. All three extracts reduced oxidative stress and revealed antiperoxidative features to protect β-cells against ROS.

They are, therefore, good candidates for the management and treatment of diabetes in mammals, especially humans. Moreover, all three plants have been widely used in traditional medicine.

Despite the limitations, the results of this meta-analysis strongly encourage further studies to evaluate the impact of plant-derived extracts on diabetic patients’ physiological and oxidative status parameters. Further study to investigate the activity of these analyzed extracts in humans is strongly recommended since there is no direct way to extrapolate results obtained from animals to humans due to their complexity. There is always a risk of severe adverse events and toxicity from such supplementation in humans. It is crucial to indicate the differences between the animal model of diabetes and the physiology of human patients with this disease, and this constitutes a critical limitation at the entry point of study design and on further data analysis. The abovementioned results are promising and may trigger the further development of experimental and clinical approaches to investigate the application of these plant extracts in more advanced and detailed studies. Considering all the strengths and limitations, this meta-analysis is a reliable source of data and might constitute an inducement for further physiological and mechanistic studies.

This review would shed light on how plant-based drugs could potentially be a beneficial agents in treating of aging, oxidative stress and hyperglycemia-associated abnormalities.

This entry is adapted from the peer-reviewed paper 10.3390/cimb44020049

References

  1. Michal Krawczyk; Izabela Burzynska-Pedziwiatr; Lucyna Alicja Wozniak; Malgorzata Bukowiecka-Matusiak; Evidence from a Systematic Review and Meta-Analysis Pointing to the Antidiabetic Effect of Polyphenol-Rich Plant Extracts from Gymnema montanum, Momordica charantia and Moringa oleifera. Current Issues in Molecular Biology 2022, 44, 699-717, 10.3390/cimb44020049.
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