REVIEW ON NARINGIN: METHOD OF ISOLATION, ANALYTICAL DEVELOPMENT, AND ITS RECENT PHARMACOLOGICAL ACTIVITIES

REVIEW ON NARINGIN: METHOD OF ISOLATION, ANALYTICAL DEVELOPMENT, AND ITS RECENT PHARMACOLOGICAL ACTIVITIES

B. Sudarshana, T. Nilotpal, S. Bhupendra and J. Honey *

Department of Pharmaceutical Analysis, Himalayan Pharmacy Institute, Majhitar, Sikkim, India.

ABSTRACT: Naringin is a flavonoid isolated from different citrus fruits like Grapefruit, Orange, Pomelo, Lemon, etc, which are commonly called local fruit. Naringin is found in the white spongy portion of citrus peel. Its content varies from 0.65 mg/gm in the mandarin peel to 14.40mg/gm in the grapefruit peel. Naringin is metabolized to the flavanone naringenin by the enzyme Naringinase present in the liver. It can be analyzed by using various analytical techniques such as HPLC, TLC, UV, HPTLC, mass spectroscopy, Liquid chromatography, chiral chromatography and LC/Mass spectroscopy. Naringin can act as an antioxidant and scavenge free radicals. Naringin mainly focuses on in-vitro and in-vivo animal studies showing its beneficial effects on cardioprotective, antioxidant, anti-inflammatory, antimicrobial, hypolipemiant, neurological, thermogenic, pulmonary disorders and antidiabetic. Naringin is also treated as a most promising treatment strategy against Covid-19 due to its antiviral and anti-inflammatory effects. Recently, Naringin has proven its activity in various molecular docking studies. Naringin keeps the body healthy against various illnesses and major lifestyle disorders.

Keywords: Naringin, Flavonoid, Citrus fruit, Free radical, spectroscopy

INTRODUCTION: Nowadays, scientists are more interested in naturally occurring drugs. Naturally obtained drugs are rich in their secondary metabolites, becoming popular in treating different diseases, and have also proven success stories among patients. Also, herbs are economical, easily available, reduce adverse drug reactions, and reduce rehospitalization. These insights made herbs proven to be possible as a promising agent for future perspective. Numerous studies have been included in the pharmaceutical sciences, such as anti-diabetic, hepatoprotective, free radical scavenging activity, and anti-hyperlipidemic ^{1, 2, 3}. Citrus fruits are a good source of flavonoids.

Naringin (NAR) is a common flavonoid in citrus fruits like Grapefruit, Orange, Pomelo, Lemon, etc. All these fruits are easily available in India, called local fruit or seasonal fruit. The proportion of Naringin is found in each citrus depends on the variety of fruit, state of ripening, and the climatic conditions it has been exposed to. Citrus fruits are a good source of antioxidants, especially flavonoids, which are mainly two types; flavanone glycoside and polymethoxylated glycoside ^4-6.

It contains a mainly bitter principle isolated in 1866 by De Vry in Java from grapefruit blossoms. It exerts various pharmacological effects such as antioxidant, blood lipid-lowering, anticarcinogenic activity & anti-diabetic activity. It also inhibits the selected cytochrome P450 enzymes, including CYP3A4 & CYP1A2, which may result in several drug interactions in-vitro. In human Naringin is metabolised to the flavanone Naringenin. Naringin is also a most promising treatment strategy against Covid-19 due to its antiviral and anti-inflammatory effects. It is proven that the consumption of either grapefruit, orange, or Naringin itself keeps the body healthy and active against various illnesses. It is highly active against various major lifestyle disorders and even as an antineoplastic agent ⁷. The class of flavanones is specific to citrus products (fruit, juice). They largely contribute to the total daily flavonoid intake range is 150-600 mg/day. Among flavanones found in Citrus co-products, Naringin has interesting biologic activities like antioxidant and antimutagenic activities. Naringin can reduce the level of cholesterol in the plasma, reduce the risk of atherosclerosis, protect the level of vitamin E in the plasma, enhance flavors for sweets, drinks and bakery products and stabilize oils. Naringin is found in the white spongy portion of citrus peel. Its content varies from 0.65mg/gm in the mandarin peel to 14.40mg/gm in grapefruit peel ^{8, 9}. Citrus is the most important cultivated fruit in the world with reported production of about 89 million tons in 2014(USDA, 2014). Estimated 26% of Citrus fruits are industrially processed into juice. The amount of industrial Citrus coproducts is estimated at 15 ×10⁶ tons and it consists essentially of seeds, peels, and pulp residue. Indeed, Citrus co-products are rich in bioactive molecules (pigments, fibers, essential oils, flavonoids) which can constitute a high added value for industrialists ^{10, 11}.

Metabolism of Naringin in the Body: In humans, Naringinase is available in the liver, and it rapidly metabolizes naringin into Naringenin. It occurred in two steps- first, Naringin is hydrolyzed by the α-L-rhamnosidase activity of naringinase to rhamnose and prunin. The prunin formed is then hydrolyzed by the β-d-glucosidase activity of Naringinase into Naringenin and glucose. Naringinase is an enzyme that has a wide occurrence in nature; in plants, yeasts, and fungi. It is commercially attractive due to its bitterness removal properties ^4-7.

FIG. 1: METABOLISM OF NARINGIN IN THE BODY

Chemistry of Naringin: Flavonoids are composed of two aromatic rings linked to three carbon atoms forming an oxygenated heterocycle. Flavonoids are a widely distributed group of polyphenolic compounds characterized by a common benzo-pyrone structure. Over 4,000 different flavonoids have been described and categorized into flavonols, flavones, flavanones, isoflavones, catechins and anthocyanidins.

Diverse biochemical properties of flavonoids including naringin, hesperidin, diosmin, and rutin have provoked interest in biology and medicinal chemistry. Naringin is a flavanone-7-O-glycoside between the flavanone Naringenin and the Disaccharide neohesperidose. Naringin, the bitter principle of grapefruit (Citrus paradisi), is found in the fruit's juice, flower, and rind and constitutes up to 10% of the dry weight. Naringin and other Naringenin glycosides can be found in a variety of other sources. The flavonoid Naringin occurs naturally in citrus fruit, especially in grapefruit, where Naringin is responsible for the fruit's bitter taste. The chemical formula for Naringin is C₂₇H₃₂O₁₄ and its molecular weight is 580.4g/mol. The taste of NAR is bitter, and the color is beige. Its melting point ranges from 165⁰C to 170°C. Naringin is highly soluble in organic solvents; Ethanol, Methanol, and Dimethyl Sulfoxide and sparingly soluble in an aqueous buffer. It is stable for up to 2 years if stored at 20°C ⁴³.

FIG. 2: STRUCTURE OF NARINGIN

Isolation and Extraction of Naringin from Various sources: Isolation is a process by which we can obtain a purified compound, and an extraction process where moving one or more analytes from the sample to a physically separate location where further processing and analysis occurs. Mainly in extraction, it separates the compound from the mixture, and in the isolation process, purification of a compound occurs ⁹.

TABLE 1: NARINGIN EXTRACTION

FIG. 3: ISOLATION OF NARINGIN FROM DIFFERENT SOURCES

During the extraction analysis effect of the temperature, light, and oxygen shows that Naringin is a molecule that is very sensitive to its environment. Its degradation begins when temperatures are superior to 100°Cor in the presence of light. The antioxidant activity of the Naringin solutions varies during their degradation, so the biological activities of the Naringin can be modified during its extraction. In the extraction methods, there are different solvents used. The use of accelerators for solvent extraction is interesting because it makes the procedure less time-consuming. While Naringin, is a polar flavonoid because of that extraction temperature or pressure must be increased to obtain a high Naringin content. So, this temperature or pressure increase can cause Naringin superior to 100°C. During the Naringin extraction, two reactions occurparallelly with increasing extraction temperature or pressure. These two reactions are: (a) an increase of the Naringin released and (b) degradation of Naringin. The study of the effects is monitored; temperature, light and oxygen, showed that Naringin does not degrade with an oxygen content of 85% and for temperatures lower than 100°C. For the preservation of Naringin, direct light needs to avoid. If the extraction temperature is 80°C, it increases the Naringin content since naringin is not affected by temperatures under 100°C. When a temperature above 100°C is applied (microwave power of 400 W), then a decrease in the Naringin content is observed due to a degradation of the Naringin ¹³.

Analytical Methods for Naringin: Naringin is available as a powder and capsule. Analytical methods were developed for determining Naringin using RP-HPLC, Liquid Chromatography, Mass, HPTLC, LC-mass, and Spectrophotometry.

TABLE 2: REVIEW OF ANALYTICAL METHODS FOR THE ASSAY OF NARINGIN

TABLE 3: LIST OF ACTIVITIES REPORTED FOR PEEL OF NARINGIN OVER THE LAST 10 YEARS

TABLE 4: RECENT ACTIVITY OF NARINGIN

Future Prospective: In different studies, Naringin has been shown to reduce modern-daydiseases; diabetes, cancer, inflammation, etc. in various animal model systems. Its antioxidative property leads to the reduction in oxidative stress-mediated pathogenesis. However, in the context of the effect of Naringin on humans, no epidemiological study has been performed except for a linkage between citrus fruits and a lower rate in breast cancer patients. Naringin has been shown to reduce the development of diabetes and help prevent cancer in diabetic patients.

Based on the experienced gain from different studies, it could be safely concluded that Naringin may potentiate the outcome of radiotherapy by overcoming the radio-diminished immune response and giving a better clearance of tumor by activating the host cytotoxic immune response. Besides, Naringin may also reduce the damage to the normal cells during radiotherapy due to its differential effects on the normal and cancer cells.

CONCLUSION: Naringin is a citrus Flavonoid extracted from a grapefruit peel, Pomelo, Orange, Lemon, etc. It can be extracted from powder, not juice, due to higher flavonoid concentrations. As a common waste product, its usage for future work would likely be economical and reduce food waste.

For the analytical study, HPTLC, LC/MS, and HPLC methods were carried out, and have been found that the procedures are simple, rapid, accurate, reproducible, and applicable for the determination of naringin in grapefruit. From various pre-clinical reports, there is self-evident strength of Naringin in applications that deal with bone diseases or stem cells for osteogenic differentiation. Undeniably, Naringin can rectify various disorders and extend several pharmaceutical approaches.

ACKNOWLEDGMENT: We thank Director Dr. H.P. Chettri and Principal Dr. N. R. Bhuyan, Himalayan Pharmacy Institute, for their constant support and encouragement during the work.

CONFLICTS OF INTEREST: Nil

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    How to cite this article:

    Sudarshana B, Nilotpal T, Bhupendra S and Honey J: Review on naringin: method of isolation, analytical development, and its recent pharmacological activities. Int J Pharm Sci & Res 2023; 14(4): 1622-29. doi: 10.13040/IJPSR.0975-8232.14(4).1622-29.

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