Anti–Diabetic Activity of Murraya koenigii – A Comprehensive Review

Diabetes mellitus, one of the noncommunicable illnesses, is a severe problem worldwide as one of the leading causes of death. Because existing synthetic medications have various drawbacks, researchers are still looking for better anti-hyperglycemic treatments. Plants have been used in ancient medicine for thousands of years. India is the biggest producer of medicinal plants and is aptly regarded as the "World's Botanical Garden." Murraya koenigii Linn, also known as Meethi neem, is a Rutaceae plant. Curry trees are unique to India and likely found almost everywhere else on the subcontinent, except in the Himalayan highlands. For centuries, curry leaves were used as an antiemetic, diarrhea remedy, febrifuge, and blood purifier. Curry leaves are useful as an antioxidant, anti-diabetic, antibacterial, antihypertensive, cytotoxic, and in treating bronchial respiratory problems. Traditionally, the leaves were utilized as a spice in curries as well as other dishes. It includes coumarins and derivatives, alkaloids, flavonoids, phenolic compounds, and essential oil. Numerous studies have found that these phytochemicals have a significant effect on type 2 diabetes. This review focuses on this plant's anti-diabetic action and concludes that it has the potential to be evaluated as a candidate for developing a new diabetes mellitus medication. Review Article Rekha et al.; JPRI, 33(58B): 462-470, 2021; Article no.JPRI.78628 463


INTRODUCTION
Diabetes mellitus, among the most frequent endocrine and metabolic illnesses, has caused enormous morbidity and death as a result of microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (heart attack, stroke, and peripheral vascular disease) effects. In human bodies, anti-oxidative processes, both enzymatic and non-enzymatic, contribute to the reduction of reactive oxygen species, which are linked to a number of degenerative disorders, including diabetes [1]. The sickness is spreading swiftly over the world and is impacting people in every country. Diabetes patients have elevated blood glucose levels due to insulin insufficiency [2]. Type 2 diabetes, also called the non diabetic Mellitus, has to be the most common type of diabetes, accounting for 90 percent to 95 percent of instances in which the body fails to make sufficient insulin or use it properly [3]. According to the World Health Organization, the diabetes population will reach 300 million or more by [4]. Insulin and various oral anti-diabetic medications, including sulfonylureas, biguanides, and glinides, are currently available for diabetes treatment. Many of them have a variety of significant side effects; as a result, one of the most critical areas of research is the search for more effective and safer hypoglycemic agents [5].

COST OF DIABETES
Numerous research on the cost of sickness have been conducted as a result of the economic burden of diabetes mellitus. Diabetes costs may be divided into three categories: direct costs, indirect costs, and intangible costs [6,7]. Both direct health care expenditures (diagnostic, treatment, care, and preventive) and direct nonhealth care costs are included in direct costs (transport, housekeeping, social service and legal cost). With complications, the total direct cost is ₹ 28,888/per year [8]. Absenteeism, lost output, and incapacity are all examples of indirect costs. With complexity, the total indirect cost is 1746/-per annum. [9]. Finally, intangible costs include costs associated with social isolation and dependency, low socioeconomic status, mental health and behavioural disorders, and a reduction in quality of life. [10].

PLANT AS ALTERNATIVE SOURCE
The hypoglycemic impact of various plants used as anti-diabetic agents has been established, and the mechanisms underlying this effect are being researched. This article discusses natural compounds with anti-diabetic characteristics that operate as insulin-mimetic or secretagogues. Traditional remedies derived from commonly available medicinal plants hold considerable promise for developing new anti-diabetic medications [11].
Certain medicinal herbs have recently been described to be effective in the treatment of diabetes throughout the world, and they have been used empirically in anti-diabetic and antihyperlipidemic drugs.
Plants' antihyperglycemic action is mainly related to their capacity to restore pancreatic tissue function by increasing insulin secretion, inhibiting glucose absorption in the intestine, or facilitating metabolites in insulin-dependent activities. Even though literature lists over 400 plant species with hypoglycemic action, hunting for new antidiabetic medications from natural plants remains appealing since they contain chemicals that have alternative and harmless effects on diabetes mellitus.
Curry leaves are Murraya koenigii (M. koenigii) (L) Spreng of the Rutaceae family. M. koenigii is found all across the world's tropical and subtropical regions. [13]. Only two Murraya species, M. koenigii and M. paniculate are found in India, out of 14 worldwide. M. koenigii is more important because of the wide range of traditional therapeutic characteristics it possesses. This plant has been utilized in various ways for millennia and is known as "krishnanimba" in Indian Ayurvedic medicine [14]. M. koenigii's leaves, roots, bark, and fruit have been demonstrated to support a range of biological activities. Even after drying, aromatic bioactive components in M. koenigii leaves retain their flavor and other properties [15]. The leaves of M. koenigii have a slightly bitter taste, a pungent odor, and are somewhat acidic. They are used as antihelminthics, analgesics, digestives, and appetizers in Indian cuisine [16]. Piles, inflammation, itching, fresh cuts, diarrhea, bruising, and edema are treated using M.
Koenig's green leaves. To some extent, the roots are purgative. They are stimulating and are used to treat aches and pains in the body. The bark can be used to treat snakebites [17]. The essential oil obtained from M. koenigii leaves has been proven in animal models to have antioxidative and hepatoprotective properties [18] antibacterial, antifungal, anti-inflammatory, and nephroprotective effects [19]. Several chemical elements of distinct carbazole alkaloids and other significant metabolites, such as terpenoids, flavonoids, phenolics, carbohydrates, carotenoids, vitamins, and nicotinic acid, have been attributed to the therapeutic qualities of M. koenigii from various regions of the plant.
M. koenigii has received increased interest in traditional medicines and home cures in recent years. On the other hand, few research have been undertaken to assess M. koenigii's pharmacological and therapeutic usefulness in improving health and healing sickness [20]. This review aims to present previous and existing major studies on M. koenigii activity in diabetics.

TRADITIONAL AND MEDICINAL USES OF M. Koenigii
M. koenigii essential oils and fresh leaf powder can be used to season foods and make ready-toeat meals. The essential oil from leaf extracts can also be employed as a perfume, and taste agent in traditional practise due to its increased antibacterial activity [21]. Fresh curry leaves are cooked with coconut oil until they have been crushed to a black residue to make a great hair tonic for restoring normal hair tone and promoting hair development. Curry leaves have long been used as an antidiarrheal, antifungal, blood purifying, anti-inflammatory, and antidepressant medication, either whole or in little amounts. [22].
Different plant parts, like the leaves, roots, and bark, could be used as tonics to induce digestion and flatulence or as antiemetics [23]. The leaves turn unpleasant to the taste after infusion and are useful in lowering fever. The root's juice is used to treat kidney pain [24]. The leaves and roots can be used as an antihistamine, analgesic, piles treatment, body heat reducer, and thirst quencher, as well as to relieve inflammation and irritation. They're also suitable for treating leucoderma and blood problems. The green leaves can be consumed raw to treat diarrhea, and the paste made from boiling the leaves in milk can be used to treat toxic bites and eruptions.
[25].  [32]. Murrya koenigii is used to cure or prevent orofacial dyskinesia (OD), which is caused by neuroleptics [33]. The anti-Trichomonas gallinae action of carbazole alkaloids derived from Murrya koenigii extract and its derivatives [34]. Curry leaves and essential oil are used both orally and topically for healthy, long, strong, and glossy hair. A balanced diet with an equal percentage of vitamins, minerals, iron, and other nutrients is needed to keep hair healthy. [35]. Curry leaf oil aids in muscle and tissue contraction. Curry leaf extract aids in the reduction of white areas on the body and helps with pigmentation. Curry leaf fresh leaves, dried leaf powder, and essential oil are commonly used to flavour soups, curries, fish, meat, and egg meals, as well as classic curry powder mixes, seasoning, and ready-to-use other culinary preparations. Murraya koenigii essential oil is used in the soap and cosmetic sector for aromatherapy. Murraya koenigii is used to treat bruises, eruptions, and deadly animal attacks. [36].

PHYTOCHEMISTRY OF M. Koenigii
The

M. Koenigii
Because of their low cost, medicinal plants are particularly useful in managing diabetes mellitus in developing countries. Diabetes mellitus, a metabolic disorder, is rapidly being a major public health concern. In recent years, numerous phytochemicals with anti-diabetic properties have been found in plants. M. koenigii leaf alkaloids were examined and found to inhibit the aldose reductase enzyme, glucose consumption, and other enzyme systems, potentially extending anti-diabetic benefits [38]. The -glucosidase inhibitory property of M. koenigii was examined, and it was discovered to inhibit glycosidase. Patients with type 2 diabetes are commonly treated with alpha-glucosidase inhibitors [39]. According to one study, an ethanolic extract of M. koenigii reduced blood glucose levels significantly, and this action of M. koenigii reducing blood glucose is mediated by antioxidant properties and insulin-mimetic effects. M. koenigii also demonstrated a high antioxidant effect, lowering MDA levels, increasing GSH levels, and significantly lowering the homeostatic model assessment (HOMA)insulin resistance index. Overall, M. koenigii appears to have anti-diabetic and antioxidant properties in rats. [40].

HYPOGLYCEMIC ACTIVITY
Feeding the leaves to rats resulted in hypoglycemia because it enhanced hepatic glycogenesis, as evidenced by increased glycogen synthetase activity. The activity of glycogen phosphorylase and gluconeogenic enzymes reduced, indicating a reduction in glycogenolysis and gluconeogenesis. [41].
The hypoglycemic effect can be achieved by increasing insulin production from [beta]-cells of Langerhans islets in the pancreas or emancipating insulin from its bound state [42]. The antioxidant defence system of plasma and pancreas, as well as the probable protective impact of M. koenigii leaf extract against -cell damage, were examined in streptozotocininduced diabetic rats. It was determined that M. koenigii therapy protects against diabetes by lowering oxidative stress and pancreatic-cell damage.

ADVANTAGES OF M. Koenigii
The best health advantages of Curry Leaves are listed here:

DISADVANTAGES OF M. Koenigii
Although no harm has been recorded from curry leaves, it may be detrimental in some instances or at excessive quantities.
• Some individuals may experience allergic reactions. Its usage should be ceased in such a case. • Pregnant and breastfeeding women should see a doctor before using it, as some of its negative effects are common in this condition. • At the same time, in some situations, the use of its oil can weaken the hair roots and cause them to fall out.

CONCLUSION
The present review discusses M. koenigii's medicinal uses, phytochemical constituents, and pharmacological qualities, with a focus on its anti-diabetic properties. M. koenigii contains alkaloids, polyphenols, terpenoids, and flavonoids, among other bioactive substances. M. koenigii and its substances appear to have anticarcinogenic, proapoptotic, antiangiogenic, antimetastatic, immunomodulatory, and antioxidant properties. The broad activity of M. koenigii and its derivatives in cell signalling pathways at multiple levels in various illnesses illustrates the molecular processes behind these activities. M. koenigii and its derivatives reduce oxidative stress, neurotoxicity, neuroinflammation, neuronal loss, and cognitive dysfunctions. However, like other polyphenols, M. koenigii's actions are restricted to some extent by its bioavailability, and in such cases, increased efficiency should be pursued. As a result, future research should involve additional experimental studies on improving bioavailability and efficiency in clinical trials.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.