Antidiabetic Effect of Gymnema montanum/Momordica charantia/Moringa oleifera

Antidiabetic Effect of Gymnema montanum/Momordica charantia/Moringa oleifera: Comparison

Please note this is a comparison between Version 1 by Michał Szymon Krawczyk and Version 4 by Lindsay Dong.

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. 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.

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 ^[6][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 ^[7][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 ^[8][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 ^[9][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 ^[8][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 ^[10][11][38,39]. This plant originates from the western and sub-Himalayan tracts, India, Pakistan, Asia Minor, Africa and Arabia ^[12][13][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 ^[13][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 ^[14][42]. Mounting evidence reports that M. oleifera parts, especially the leaves, have nutritional properties or can be used in diet supplementation ^[10][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 ^[11][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 ^[12][13][14][44,45,46], oxidase, catalase, alkaloids, glucosinolates, isothiocyanates, tannins, and saponins ^[15][16][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 ^[16][47]. Based on the available literature, about 20 pharmacological properties can be attributed to this plant ^[17][53]. It is evident that various Moringa extracts can have hypoglycemic effects in different in vitro and in vivo models ^[18][19][20][48,54,55].

5. Conclusions

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 1Table 2 ^[1].

Table 12. Distribution and changes of analyzed parameters in meta-analysis.

Distribution and changes of analyzed parameters in meta-analysis.


SOD↓

CAT↑

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

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↑

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 ↑

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

6. Results and Conclusions

Gymnema montanumFinally, Momordica charantia23 articles were indcluded in Moringa oleiferathe metare-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 Gymnema montanummontanum versus Glybenclamide revealed the superiority of extracts over drug administration in some aspects.

EThe 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.

References

WHO Global Reports on Diabetes. 2016. Available online: https://www.who.int/diabetes/publications/grd-2016/en/ (accessed on 11 January 2022).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.
Saeedi, P.; Petersohn, I.; Salpea, P.; Malanda, B.; Karuranga, S.; Unwin, N.; Colagiuri, S.; Guariguata, L.; Motala, A.A.; Ogurtsova, K.; et al. Global and Regional Diabetes Prevalence Estimates for 2019 and Projections for 2030 and 2045: Results from The International Diabetes Federation Diabetes Atlas, 9th Edition. Diabetes Res. Clin. Pract. 2019, 157, 107843.
Bonnefont-Rousselot, D.; Bastard, J.P.; Jaudon, M.C.; Delattre, J. Consequences of The Diabetic Status on the Oxidant/Antioxidant Balance. Diabetes Metab. 2000, 26, 163–176.
Wojcik, M.; Krawczyk, M.; Wojcik, P.; Cypryk, K.; Wozniak, L.A. Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer. Oxidative Med. Cell. Longev. 2018, 2018, 9698258.
Yuan, H.; Ma, Q.; Ye, L.; Piao, G. The Traditional Medicine and Modern Medicine from Natural Products. Molecules 2016, 21, 559.
Vajravelu, E.B.P. Rare and Endemic Species Collected after Fifty Years or More from South India. In An Assessment of Threatened Plants of India. In Proceedings of The Seminar Onrare and Endemic Species Re-Collected after Fifty Years or More from Southindia; Jain, S.K., Raw, R.R., Eds.; Botanical Survey Of India: Howrah, India, 1983; Volume 14.
López-Vélez, M.; Martínez-Martínez, F.; Del Valle-Ribes, C. The Study of Phenolic Compounds as Natural Antioxidants in Wine. Crit. Rev. Food Sci. Nutr. 2003, 43, 233–244.
Grover, J.K.; Yadav, S.P. Pharmacological Actions and Potential Uses of Momordica Charantia: A Review. J. Ethnopharmacol. 2004, 93, 123–132.
Jia, S.; Shen, M.; Zhang, F.; Xie, J. Recent Advances in Momordica Charantia: Functional Components and Biological Activities. Int. J. Mol. Sci. 2017, 18, 2555.
Vargas-Sanchez, K.; Garay-Jaramillo, E.; Gonzalez-Reyes, R.E. Effects of Moringa oleiferaon Glycaemia and Insulin Levels: A Review of Animal and Human Studies. Nutrients 2019, 11, 2907.
Kou, X.; Li, B.; Olayanju, J.B.; Drake, J.M.; Chen, N. Nutraceutical or Pharmacological Potential of Moringa oleifera Lam. Nutrients 2018, 10, 343.
Stohs, S.J.; Hartman, M.J. Review of the Safety and Efficacy of Moringa oleifera. Phytother. Res. 2015, 29, 796–804.
Anwar, F.; Latif, S.; Ashraf, M.; Gilani, A.H. Moringa oleifera: A food plant with multiple medicinal uses. Phytother. Res. 2007, 21, 17–25.
Dhakad, A.K.; Ikram, M.; Sharma, S.; Khan, S.; Pandey, V.V.; Singh, A. Biological, the nutritional, and therapeutic significance of Moringa oleifera Lam. Phytother. Res. 2019, 33, 2870–2903.
Glover-Amengor, M.; Aryeetey, R.; Afari, E.; Nyarko, A. Micronutrient composition and acceptability of Moringa oleifera leaf-fortified dishes by children in Ada-East district, Ghana. Food Sci. Nutr. 2017, 5, 317–323.
Sreelatha, S.; Padma, P.R. Antioxidant activity and total phenolic content of Moringa oleifera leaves in two stages of maturity. Plant Foods Hum. Nutr. 2009, 64, 303–311.
Zhu, Y.; Yin, Q.; Yang, Y. Comprehensive Investigation of Moringa oleifera from Different Regions by Simultaneous Determination of 11 Polyphenols Using UPLC-ESI-MS/MS. Molecules 2020, 25, 676.
Manguro, L.O.; Lemmen, P. Phenolics of Moringa oleifera leaves. Nat. Prod. Res. 2007, 21, 56–68.
Falowo, A.B.; Mukumbo, F.E.; Idamokoro, E.M.; Lorenzo, J.M.; Afolayan, A.J.; Muchenje, V. Multi-functional application of Moringa oleifera Lam. in nutrition and animal food products: A review. Food Res. Int. 2018, 106, 317–334.
Saucedo-Pompa, S.; Torres-Castillo, J.A.; Castro-Lopez, C.; Rojas, R.; Sanchez-Alejo, E.J.; Ngangyo-Heya, M.; Martinez-Avila, G.C.G. Moringa plants: Bioactive compounds and promising applications in food products. Food Res. Int. 2018, 111, 438–450.
Lopez-Rodriguez, N.A.; Gaytán-Martínez, M.; de la Luz Reyes-Vega, M.; Loarca-Piña, G. Glucosinolates and Isothiocyanates from Moringa oleifera: Chemical and Biological Approaches. Plant Foods Hum. Nutr. 2020, 75, 447–457.
Forster, N.; Ulrichs, C.; Schreiner, M.; Arndt, N.; Schmidt, R.; Mewis, I. Ecotype variability in growth and secondary metabolite profile in Moringa oleifera: Impact of sulfur and water availability. J. Agric. Food Chem. 2015, 63, 2852–2861.
Borgonovo, G.; De Petrocellis, L.; Schiano Moriello, A.; Bertoli, S.; Leone, A.; Battezzati, A.; Mazzini, S.; Bassoli, A.; Moringin, A. Stable Isothiocyanate from Moringa oleifera, Activates the Somatosensory and Pain Receptor TRPA1 Channel In Vitro. Molecules 2020, 25, 976.