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Morinda Citrifolia) and Its Clinical Applications T Complementary Therapies in Medicine 47 (2019) 102206 Contents lists available at ScienceDirect Complementary Therapies in Medicine journal homepage: www.elsevier.com/locate/ctim Immunomodulatory actions of a Polynesian herb Noni (Morinda citrifolia) and its clinical applications T Madhukar Lohania, Mohammed Majrashib,e, Manoj Govindarajulub, Mansi Patelb, Sindhu Rameshb, Dwipayan Bhattacharyab, Sneha Joshib, Maali Fadanb, Rishi Nadarb, ⁎ Benjamin Darienc, Denzil V. Mauriced, Barbara Kemppainena, Muralikrishnan Dhanasekaranb, a Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn, AL 36830, USA b Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA c Department of Medical Sciences, College of Veterinary Medicine, University of Wisconsin-Madison, WI, 53706, USA d Animal and Veterinary Sciences, College of Agriculture, Clemson University, Clemson, 29634, USA e Department of Pharmacology, Faculty of Medicine, University of Jeddah, Jeddah, 23881, Saudi Arabia ABSTRACT Morinda citrifolia (Noni) is a popular traditional medicinal plant consumed in various forms in several countries around the world as a complementary and alternative treatment due to its established health benefits. Noni is rich in bioactive substances and has significantly exhibited pro-oxidant and immunomodulatory effects. In this review, we highlight the pharmacological basis related to the phytochemicals and polysaccharides present in Noni and its potential therapeutic effects. We screened electronic databases such as PubMed, Google Scholar, Scopus for scientific literature. Our results indicate that Noni is beneficial for various diseases with its crude extracts showing therapeutic benefit for a wide range of pathological diseases. We believe that further pharmacological and toxicological studies in addition to well-designed controlled clinical trials can validate Noni to be an effective and novel natural product for prophylactic and therapeutic use of several diseases. 1. Introduction natural product. Due to the exclusion of antibiotic prophylaxis in the animal food industry by several countries, and the possibility of a ban Noni; also known as Indian Mulberry, Hog apple, Canary wood Ba Ji subject in other countries, there is increasing demand for natural pro- Tian and Cheese Fruit, is a green shrub or small tree that grows in ducts with health benefits.10 Southeast Asia, USA (Hawaii) and Australia.1,2 Nearly all the parts The bioactive substances of the natural products can be generally obtained from Noni, including the roots, stem, bark, fruits and leaves classified into “phytochemicals and polysaccharides”. Phytochemicals have been useful as a curative or a preventive measure in managing are low molecular weight chemicals present in plants which are known various acute and chronic diseases in the Polynesian culture for the past to support human wellbeing and are mainly classified based on their 2000 years.3 Noni is considered as the original “canoe plant” brought chemical structures.11 The major chemical classes isolated from Noni by Polynesian colonists in their voyaging canoes to Hawaii. This herb are betalains, indoles, glucosinolates, organosulfides, sulfides, mono or has become a part of modern-day civilization and is one of the popular polyphenolic compounds, terpenes (isoprenoids, terpenoids) and or- dietary supplements in Asia, Europe, United States of America and ganic acids (Fig. 1). Phytochemicals exhibit their activities by rendering other Polynesian countries.4,5 Various preparations of Noni’s fruit and antioxidant action (scavenging free radicals), modulating endocrine leaves are available as capsule, tablet, liquid and powder formulations. functions (hormonal properties), regulating exocrine effects (potentiate Traditionally, Noni has been known to be used in the treatment of or inhibit enzyme activity or protein expression), inducing immune various diseases including: cancer, infections, cold, flu, diabetes mel- responses (immunomodulatory effects, anti-complementary), affecting litus, hypertension, arthritis, gastric ulcers, sprains, depression, senility, nucleic acid (prevent the replication of DNA & affect RNA), and ex- – muscle ache and pain.6 8 The anecdotal evidence indicates that Noni hibiting antibacterial functions (preventing the adhesion of pathogens prevents or treats various infections by stimulating the immune to mammalian cells, target the cell wall, affect the nutrients for the system.9 Considering the health benefits of Noni, the European Com- pathogen). Polysaccharides are polymeric carbohydrate structures of mission of Health and Consumer Protection accepted it as a novel simple sugars attached by glycosidic bonds and can be classified as ⁎ Corresponding author. E-mail address: [email protected] (M. Dhanasekaran). https://doi.org/10.1016/j.ctim.2019.102206 Received 18 June 2019; Received in revised form 25 September 2019; Accepted 30 September 2019 Available online 03 October 2019 0965-2299/ © 2019 Published by Elsevier Ltd. M. Lohani, et al. Complementary Therapies in Medicine 47 (2019) 102206 Fig. 1. Major classes of phytochemicals present in Noni fruit. Table 1 Comparison between Polysaccharides and Phytochemicals. Bioactive Substances of Noni Polysaccharides Phytochemicals Molecular High Low weight Chemical classes Homopolysaccharides, Betalains, Indoles, Glucosinolates, Organosulfides, Sulfides, Mono or Heteropolysaccharides, Polyphenolic compounds Terpenes (Isoprenoids, Terpenoids) and Organic Complex heteropolysaccharides Acids, Iridoids, Flavonoids (Quercetin, kaempferol and catechin), Lignans Homogalacturonan, Rhamnogalacturonan, Arabinan, Type I (Matairesinol and Secoisolariciresinol, 3,3‘-Bisdemethylpinoresinol, arabinogalactan. Pectic polysaccharides (Arabinogalactan-protein Americanol A, Americanin A, Americanoic acid A, Morindolin and Xyloglucan, Heteroxylan and Heteromannan) Isoprincepin), Anthraquinones (Nordamnacanthal, Morindone, Rubiadin, and Rubiadin- 1-methyl ether, Anthraquinone glycoside) Functions Alters the mechanical properties, Reserves energy, Immunomodulation, Renders anti-oxidant action, Modulates endocrine and Modulates multiple regulatory processes of the cells, Enhances texture and Regulates exocrine effects, flavor of food products and beverages Induces immune responses, Affects nucleic acid, Exhibits antibacterial functions. homopolysaccharides (homoglycans-one sugar or one sugar derivative), 2. Phytochemicals in noni fruit exert immunomodulatory effects heteropolysaccharides (heteroglycans-two different units associated with proteins/glycoproteins and lipids) and complex hetero- Phytochemicals present in the Noni enhance the immune response polysaccharides (plant gums). The major functions of polysaccharides and suppress inflammation therefore, they can prevent a wide range of – are their ability to alter the mechanical properties (gelling and thick- disease states or symptoms.20 22 Noni has shown to reduce the in- ening), energy reservation, immunomodulation and modulation of the flammation and tissue damage in ulcerative colitis with minimal side multiple regulatory processes of the cells. Furthermore, homo- effects.1,22 Noni augmented the anti-inflammatory mediators and sig- polysaccharides are used to treat shock and are added in gels to en- nificantly suppressed the pro-inflammatory cytokines in mouse – hance the texture and flavor of food products and beverages (Table 1). models.23 25 Low molecular weight anti-inflammatory phytochemicals Nutrient composition and chemical analyses of Noni fruit suggest that of Noni could cross the blood brain barrier and prove effective against – its polysaccharides and phytochemicals have immunomodulatory ef- neurodegenerative diseases.26 28 Several in vitro and in vivo studies have – fects, as supported by in vitro and in vivo results.2,12 18 The traditional shown that Noni fruits have antioxidant, anti-inflammatory, anti-de- botanicals have been used for many generations and their consumption mentia, liver-protective, anticancer, analgesic, and immunomodulatory is conventional and generally recognized to be safe and effective.19 The effects6,29 (Table 1). current literature highlighted the following actions of Noni (Morinda ff fl citrifolia): Immunostimulatory e ects, antitumor, anti-in ammatory, 2.1. Mechanisms of immunomodulatory effects of Noni antidiabetic, anti-obesity, antibacterial / anti-septic, antifungal, anti- viral, antinociceptive / analgesic, antioxidant, neuroprotective, anti- Noni has shown to exert its immunomodulatory effect by influen- angiogenic, antiemetic and anti-nausea, anti-gastric ulcer / esophagitis, cing the various components of the immune system.30 Supplementation ff antimutagenic, antipsychotic, and anxiolytic e ects. Hence, in this of Noni in drinking water to broiler chickens significantly increased the fi scienti c review article, we focus on the immunomodulatory activities total antibody titers and reduced (75%) the mortality of broilers chal- of the bioactive substances (polysaccharides and phytochemicals) pre- lenged with the infectious bursal disease virus (IBDV).18 The feeding of sent in Noni. Noni to newborn calves enhanced the antibacterial properties against 2 M. Lohani, et al. Complementary Therapies in Medicine 47 (2019) 102206 Escherichia coli.31 Another study indicated a positive correlation be- 2.2.3. Lignans tween CD25+ expression and protection against infection by Noni.32 Lignans are an important class of phytoestrogens found in plants.
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