An Appraisal of Pharmacological actions of Morus indica: The Indian mulberry with a detailed investigation on its Anti-diabetic potential

 

Ms. Flowerlet Mathew¹*, Ms. Bimi Varghese², Mr. Dhanish Joseph³, Dr. Manju Maria Mathews⁴, Ms. Betsy Sunny⁵, Ms. Junia George⁶

^1,3Assistant Professor, Department of Pharmaceutics, Nirmala College of Pharmacy, Kerala.

⁴Associate Professor, Department of Pharmaceutics, Nirmala College of Pharmacy, Kerala.

^{2, 5, 6}Department of Pharmaceutics, Nirmala College of Pharmacy, Muvattupuzha P.O, Kerala.

 

ABSTRACT:

Herbal plants do have a unique place in the traditional or Ayurvedic system of medicines from ancient times onwards. The wider acceptance of herbal medicines is due to the low cost, fewer side effects, availability, and their superiority over allopathic medicines in terms of safety and efficacy. Morus indica is such a herbal plant which is being used in various ailments because of its wider spectrum of pharmacological actions. It grows as an ornamental plant in gardens of Kerala. It is commonly known as Indian mulberry. Besides its application in sericulture, it possesses various pharmacological actions such as Hypoglycemic, Hypolipidemic, Antiphlogistic, Diuretic, Expectorant, Hypotensive etc. Moreover, the plant also has many traditional uses. In addition to that, the leaves of Indian mulberry are reported with significant anti-diabetic activity. But it doesn’t have any known anti-diabetic marketed products yet. The meticulous use of this plant can be a boon to diabetic patients in the future in all aspects.

 

 

 

INTRODUCTION:

Diabetes mellitus is a cluster of metabolic disorders characterized by the disturbances in carbohydrate, protein, and lipid metabolism and is followed by microvascular and macrovascular complications. The worldwide prevalence of diabetes mellitus is increasing nowadays. This disease is a huge burden to the society regarding the quality of life, cost of treatment, emotional and social well-being, and loss in productivity of patients. In the present scenario, the treatment strategy includes oral hypoglycaemic agents plus insulin and lifestyle modifications. The expensive pharmacological interventions and their associated adverse effects urge a great demand for herbal remedies which are considered to be safe, less toxic than synthetic agents. Morus indica is one such herbal medicinal plant which can be a boon to diabetic patients in the future.

 

It is a perennial woody plant belongs to family Moraceae. Moraceae possesses about 10-16 species of genus Morus that are found in subtropical, warm and temperate regions of Asia, Africa, and North America. Most of them have strong environmental adaptability and have major contributions to sericulture industry because of the high yield and nutritional quality of mulberry leaf which is good for silkworm Bombyx mori L. The higher moisture content, total sugar, soluble carbohydrate and less mineral of mulberry leaves promotes the growth and development of silkworm by favoring the ingestion, digestion, and assimilation of nutrients. Indian mulberry is a very good source of ascorbic acid of which over 90% is present in a reduced form. Besides ascorbic acid, it also contains carotene, vitamin b1, folic acid, isoquercetin, quercetin, tannins, flavonoids, and saponins etc. Considering all the facts above and by combining traditional knowledge with modern science and technology, developing a herbal medicine for diabetes with superior efficacy and safety will set a milestone in the treatment strategy of diabetes mellitus. Therefore the aim of this work is to evaluate the anti-diabetic potential and the other pharmacological activities of Morus indica by a scrutinized review of various literature.^1-5

 

METHODOLOGY:

The main sources of various research and review articles are from Google scholar, pub med, scincedirect, researchgate etc. Research articles having both in-vitro and in-vivo studies have been chosen for the work.

 

Table No: 1 Common Names⁶:

Languages	Names
English	Indian mulberry
Hindi	Karun, shehtut, shiah-tut, sia tut, sia-tut, shetut, sia, siahtut, tut, tutri
Malayalam	Brahmanyam, cherukamuka, tankanakam, tulam, yusham
Tamil	Kamalapputtiri, kambali, kambali chedi, tippilinaval, avantinavval, catini, cuccikanavvalmaram, kambalikkondan
Telugu	Putika, kambali, kambali-buchi-chettu, kambali-chettu, kambalibuchi
Kannada	Brahmadaaru, brahmadaru, hile, hippalinerale, kambli hannu, korigida
Sanskrit	Shalmali, tuda, brahmacari, brahmadaru, brahmakashtha, brahmakastakam, brahmaneshta, brahmanya.

 

Ecology:

Mulberry is extensively cultivated as its leaves are food for silkworms. It is doubtfully distinguished from Morus alba because both species have the same habit. The leaves are usually smaller having long points, a deeply cut edge with small differences in the flowers. It is used primarily as a leafy shrub at high altitudes.⁷

 

Uses:

Food - fruit, fodder - leaves, as an ornamental shrub, for shade, soil conservation, live fence, and windbreak.⁷

Description:

Usually a well-branched shrub or small tree, having2-3 m height. Barks are rough grey-brown in nature. Leaves are ovate, tip long and thin, edge widely and unevenly toothed, rough above, about 5-12 cm long. Male and female flowers are separate and fruits are dark red, small and, cylindrical. And is propagated by cuttings.⁷

 

Composition:

Proximate composition of leaves is ash (11.0%), moisture (78.5%), carbohydrate (18.3%), lipid (4.0%), crude fiber (8.8%) and protein (24.8%). It also contains Iron, Calcium, Phosphorus, Copper, Manganese, Zinc, Sodium, Potassium, Magnesium and chromium. ^{3, 5}

 

LITERATURE REVIEW:

Mulberry is known for its potential in the sericulture industry. Besides that it possesses various pharmacological actions like; Hypoglycemic, Hypolipidemic, Hepatoprotective, Antimicrobial, Antioxidant, Anti-inflammatory activity etc.

 

Anti-diabetic potential of Morus indica:

Morus indica possesses pronounced anti-diabetic potential. Various parts of mulberry have been reported with various activities. And leaves of mulberry majorly contribute to its anti-diabetic potential. In alcoholic extract form and also as dry powder, Morus indica produced significant activity. Maximum percentage reduction of blood glucose level reported is 72% in combination with Asystasia gangetica. Along with a reduction of blood glucose level, it also reduces the diabetic associated complications like reduction in total cholesterol, LDL, oxidative stress and increase in HDL, total protein level etc.

 

 

Table No: 2 Summary of in-vivo anti-diabetic studies of Morus indica

Plant part/ Standard drug used	Extraction method	Animal/ Induction	Dose	% Reduction in glucose	Reference
leaf	ethanol extract	alloxan induced (150 mg/kg b.wt.) male Wistar  rats of body weight 180–200 g	400 mg/kg, per os	62.11%	R Pradeep Kumar et al., 20108
			Asystasia gangetica leaf (100 mg/kg, per os) + Morus indica (400 mg/kg, per os)	72.40%
			DC	222.3±18.44
Glibenclamide			500 µg/kg, per os	58.36%
leaf	powder	STZ induced (55mg/kg b.wt.)  male albino Wistar rats (150-200g)	500mg/kg	69.06%	D. Vishalakshi Devi et al., 20149
			DC	481 ± 25.11
insulin			5 units/kg/b.wt.	79%
Glibenclamide			400mg/kg body weight	74.42%
leaf	powder	STZ induced (55 mg/kg b.wt.) male albino Wistar  rats (150-200g)	500mg/ kg	38%	Asna urooj et al., 200810
			DC	459±63.7

STZ – streptozotocin                                                                                 DC- diabetic control

 

Hypolipidemic:

Hypoglycemic and Hypolipidemic effect of Morus Indica and Asystasia gangetica was investigated in alloxan-induced diabetic male Wistar rats of body wt. 180–200 g. Diabetes was induced by alloxan (150mg/kg i.p) into rats. Ethanolic extract of leaves of Morus Indica (400mg/kg, p.o.) and Asystasia gangetica (100mg/kg, p.o.) was administered to alloxan induced diabetic rats. Glibenclamide (500µg/kg, p.o.) was used as a reference standard. Blood glucose, serum triglycerides, total cholesterol, HDL, LDL, and total proteins were estimated by using standard kits. Administration of ethanolic extract of leaves of Morus Indica and Asystasia gangetica decreased the significant increase in the level of biochemical parameters in all groups.⁸

 

Antimicrobial:

The antimicrobial study of leaves of Morus indica from both methanolic and ethanolic extracts was evaluated against the growth of bacterial strains such as Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and fungal strain such as Aspergillus and Penicillium species. The Ethanolic extract of Morus indica (mulberry) was most potent against Staphylococcus aureus with the largest diameter of inhibition zone i.e. 15 mm whereas, methanolic extract reported with the smallest zone of inhibition i.e. 12 mm. Both ethanolic and methanolic extracts did not show any resistance against   E.coli.  The methanolic and ethanolic extract of mulberry and both the antibiotics (Penicillin and Streptomycin) does not show any zone of inhibition against the pathogen Escherichia coli and Pseudomonas aeruginosa.¹¹

 

Antioxidant effect:

Antioxidant effect has been investigated using a combination of herbal drugs, that is, ethanolic extracts of leaves of Asystasia gangetica and Morus indica against alloxan-induced diabetic male Wistar rats having body weight 180–200 g and also assessed for the effect of selected plant extracts for their effect on Superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and Lipid peroxidation (LPO) in the homogenates of the pancreas. Standard drug was Glibenclamide (500µg/kg, per os). The levels of the protective antioxidant enzymes like SOD, CAT, and GSH were increased significantly along with a decrease in the LPO levels.¹²

 

Anti-inflammatory effect:

Anti-inflammatory and antipyretic activities of Morus indica (methanolic root extract) have been done on male albino rats weighing120-160g. The extract was found to exert an inhibitory effect on carrageenin (10mg/ml) induced or other mediator induced-edema and the extract will also inhibit protein exudation and leukocyte migration in inflammatory conditions and granuloma formation. The extract was effective in experimentally induced arthritic conditions and it reduced the body temperature in pyretic rats.¹³

 

Amelioration of Oxidative Stress:

Amelioration of oxidative stress have been investigated on  mulberry (Morus indica) leaves in streptozotocin (STZ)-diabetic rats, as the leaves of mulberry (Morus indica/) of Moraceae, are reported to be rich in a number of bioactive principles such as antioxidant vitamins, flavonoids, and moracins that have substantial effect on oxidative stress in diabetes. For the study, normal Wistar albino rats and Streptozotocin-induced diabetic rats were treated with dried mulberry leaf powder at 25% in the diet for a period of 8 weeks. The assessment of the antioxidant effect of the mulberry leaves was based on hepatic lipid peroxidation. The activity of hepatic antioxidant enzymes and serum antioxidant vitamins then compared with untreated normal and diabetic rats. The mulberry leaves could counter the increased oxidative stress, increased the activity of catalase (CAT) in hepatic tissue, decreased the levels of serum ascorbic acid (vitamin C) and tocopherol (vitamin E) in diabetic rats and, increased the activities of hepatic antioxidant enzymes such as glucose-6-phosphate dehydrogenase (G6PDH), glutathione peroxidase (GPx), glutathinoneS-tranferase (GST) and superoxide dismutase (SOD) by 34%, 61%, 19%, and 53% respectively in mulberry leaves-treated diabetic rats when compared with diabetic control rats.¹⁴

 

α- amylase inhibitory effect:

The α-amylase inhibitory effect has been investigated on Morus indica (Mulberry) and Costus speciosus (Insulin plant) in an in vitro system. Methods used were Glucose adsorption, diffusion and starch hydrolysis of Mulberry leaf powder (MLP) and Insulin plant powder (IPP) that simulates gastrointestinal conditions and then compared with commercial dietary fiber sources such as wheat bran (WB), acarbose (ACB) and guar gum (GG) at three different levels (2, 4, and 6%). The a-amylase inhibitory effect was 51% for Morus indica. The effect of samples on glucose diffusion was studied in a system comprising of starch-a-amylase sample. The glucose diffusion rate was significantly low in the system for Morus indica (6%) comparing to the positive control and to commercial sources of fiber (Acarbose and Guar gum).¹⁵

 

Hepatoprotective effect:

Hepatoprotective effect of Morus indica have been studied using Morus indica aqueous (MAq) and dechlorophyllised (MDc) extracts against the carbon tetrachloride (CCl induced hepatotoxicity in rats which then compared with standard drug Liv52. The experimental group rats were pretreated with MAq, MDc, and Liv52 for 7days. Healthy control and positive control group animals were fed with Olive oil and after 7days two doses of CCl was given at 12 and 36 hrs intervals to all the animal groups. The activity of hepatic enzymes such as AST, ALT, and ALP was less in Liv52 and Morus treated groups. Pre-treatment with Liv52 and Morus extracts significantly reduced the ALP, AST and ALT activities compared to CCl. The activity of hepatic enzymes was higher than the control in all the groups, however, the Liv52 and other Morus treated MAq and MDc were less than CCl. The MAq showed better activity than MDc. The total cholesterol and triglyceride levels in Morus treated groups were significantly (p ≤ 0.05) lower than Liv52, CCl, and healthy control groups. Also, pretreatment with Morus extracts restored the hepatic architecture near to the standard drug treatment which is shown in histopathological sections of the liver.¹⁶

 

RESULT AND DISCUSSION:

Based on the above results, a graph can be plotted by taking doses of plant parts in the form of extract or dry powder on X-axis and their corresponding % blood glucose reduction on Y-axis.

 

a – Leaf ethanolic extract (400 mg/kg, per os). b - Leaf ethanolic extract {Asystasia gangetica leaf (100 mg/kg, per os) + Morus indica (400 mg/kg, per os)}. c, d – Leaf powder (500mg/kg). e – Glibenclamide (500 µg/kg, per os). f – Glibenclamide (400mg/kg body weight). g –Insulin (5 units/kg/b.wt)

Figure no: 1 – percentage glucose reduction of Morus indica

 

Though the plant possesses significant anti-diabetic activity, few in-vivo studies have been only conducted. Dry powder form has a prominent effect than the extract. Mostly streptozotocin is used to induce diabetics in animals at a dose of 55mg/kg body weight. And most used animals in in-vivo studies are male albino Wistar rats. From the studies it evident that synergistic effect with other plants has more effect when it is given alone in any form, which is comparable to that of standard drugs. Most commonly used standard drug is Glibenclamide. And the lowest dose of Glibenclamide has more anti-diabetic activity. But insulin has the most anti-diabetic potential than the corresponding plant and the oral hypoglycemic agent.

Medicinal plant or herbal medicine is a major component of traditional medicine. Traditional medicine is a set of empirical practices embedded in the knowledge of a social group often transmitted orally from generation to generation with the intent to solve health problems. It is an alternative to Western medicine and is strongly linked to religious beliefs and practices of indigenous cultures. Herbal medicines are being used by nearly about 80% of the world population, primarily in developing countries for primary health care. Herbs are still an important part of traditional healing systems. Herbal preparations are natural, intrinsically harmless and produce desired pharmacological effects. The unprecedented global upsurge of interest in herbal medicine is perhaps a measure of a more realistic perception of the limitations of orthodox medicines in terms of cost, accessibility, effectiveness, and safety.  Unfortunately, there is a lack of common standards and understanding and appropriate methods for evaluation of traditional medicine to ensure the safety, efficacy and quality control of traditional/herbal medicine. Also, improvement in science and technology and the problem of mass-producing herbal medicine were among the issues that promoted the growth of synthetic medicines. Though herbal remedies are not better than conventional drugs, still many patients prefer ‘natural’ treatments. A perhaps more convincing reason is that its adverse effects profile is preferable. It is observed that herbal medicines are being used by around 80% of the present day global population as a supplement to conventional medicine. The use of herbal medicines is a popular healthcare approach in the US, UK, and EU countries, and there are signs that marketing of such products is continuing to increase and may reach three trillion markets in 2050. Investigation on new oral hypoglycemic compounds from medicinal plants will set a milestone for the development of pharmaceutical entities or as a dietary adjunct to existing therapies in the future like mulberry, insulin plant, jamun etc. Herbal approaches can be a new advancement in the field of Parkinson’s disease management, hepatoprotective action, and wound healing. But when it comes to the effectiveness of medicines and traditional medicines, often over time, the response to Parkinson's symptoms will stop responding. Wound healing is a complex and dynamic process of replacing devitalized and missing cellular structures and tissue layers. Medicinal plants have been shown to possess wound healing activity in animal studies. To recover from wound healing within the shortest time period with minimal pain, discomfort and scarring to the patient it is important to explore nutritional and herbal influences on wound outcome, have recently been granted a generally recognized as safe status by the World Health Organization and incorporated in several pharmaceutical products and formulations. Coming to the hepatoprotective effect, nearly 150 phytoconstituents from 101 plants have been claimed to possess liver protecting activity. In India, more than 87 medicinal plants are used in different combinations and in most of these studies, marginal or moderate levels of hepatoprotective activities were observed.^17-27

 

CONCLUSION:

Since the usage, dependence and side effects of synthetic drugs are increasing nowadays, the importance and marketing demands of herbal drugs are at its peak. Because of their availability, reliability, fewer side effects and cost effects, and cost-effectiveness. Morus indica or Indian mulberry is one such a herbal plant which is using traditionally for several ailments and is commonly available in India. It is also seen as an ornamental plant in south Indian gardens, also has much importance in sericulture industry. Leaf of Morus indica has excellent anti-diabetic potential which is comparable to that of commonly available synthetic medicines. For the welfare of mankind, further researches on this plant about its anti-diabetic activity are needed to decrease the demand for synthetic medicines and to make the treatment more reliable and safe.

 

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Accepted on 14.05.2019           © RJPT All right reserved

Research J. Pharm. and Tech 2019; 12(8):3654-3658.