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Pharmacological properties of mangiferin: bioavailability, mechanisms of action and clinical perspectives

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Abstract

This review aims to provide an in-depth analysis of the pharmacological properties of mangiferin, focusing primarily on its bioavailability and mechanisms of action, and its potential therapeutic applications, especially in the context of chronic diseases. We conducted a comprehensive examination of in vitro and in vivo studies, as well as clinical trials involving mangiferin or plant extracts containing mangiferin. The primary source of mangiferin is Mangifera indica, but it’s also found in other plant species from the families Anacardiaceae, Gentianaceae, and Iridaceae. Mangiferin has exhibited a myriad of therapeutic properties, presenting itself as a promising candidate for treating various chronic conditions including neurodegenerative disorders, cardiovascular diseases, renal and pulmonary diseases, diabetes, and obesity. Despite the promising results showcased in many in vitro studies and certain animal studies, the application of mangiferin has been limited due to its poor solubility, absorption, and overall bioavailability. Mangiferin offers significant therapeutic potential in treating a spectrum of chronic diseases, as evidenced by both in vitro and clinical trials. However, the challenges concerning its bioavailability necessitate further research, particularly in optimizing its delivery and absorption, to harness its full medicinal potential. This review serves as a comprehensive update on the health-promoting and therapeutic activities of mangiferin.

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Abbreviations

α-SMA:

alpha smooth muscle actin

A1/G1 (ABCA1/G1):

ATP binding cassette

AChE:

acetylcholinesterase

Ab1-40:

amyloid beta peptide 1–40

Ab1-42:

amyloid beta peptide 1–42

ABCG2:

ATP-binding cassette superfamily G member 2

ADPS:

average daily pain diary score

AKT:

protein kinase B

AMPK:

AMP-activated protein kinase

APAF-1:

apoptosis protease-activating factor-1

APP:

amyloid precursor protein

APP/PS1:

mouse model of Alzheimer’s disease

AQP-2:

aquaporin-2

AR-29:

Anoxybacillus sp. AR-29 strain

ASC:

artificial cerebrospinal fluid

ASK1:

apoptosis signal-regulating kinase 1

ATP:

adenosine triphosphate

β-LG:

β-LACTOGLOBULIN

Bcl-2:

B-cell lymphoma 2

BCS:

biopharmaceutics Classification System

BDNF:

brain-derived neurotrophic factor

BV-2:

immortalized murine microglial cell line

CAT:

catalase

CLP:

cecal ligation and puncture

Col I:

collagen type I alpha 1

COMT:

catechol-O-methyltransferase

COX-2:

cyclooxygenase

DCM:

diabetic cardiomyopathy

DSS:

dextran sulphate sodium

E2(PGE2):

prostaglandin E2

EEG:

electroencephalogram

EPM:

elevated plus maze

ESI-MSn:

electrospray ionization mass spectroscopy

F2a(8–150-PGF2a):

8–150-prostaglandin F2α

Fas:

apoptosis antigen 1

FFA:

free fatty acids

FN:

formononetin

FST:

forced swimming test

GIT:

gastrointestinal regulation

GLUT4:

glucose transporter 4

GLUT9:

glucose transporter 9

GPX:

glutathione peroxidase

GRAS:

generally recognized as safe

GSH:

hippocampal glutathione

HDL:

high-density lipoprotein cholesterol

HO-1:

hemeoxygenase-1

HPLC:

high-performance liquid chromatography

HSV-1:

herpes simplex virus

IBs:

inflammatory bowel syndrome

IC50:

inhibitory concentration

ICAM-1:

intercellular adhesion molecule 1

IκBα:

nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

IL-1b:

interleukin 1b

IL-6:

interleukin 6

IL-18:

interleukin 18

iNOS:

inducible nitric oxide synthase

IUPAC:

International Union of Pure and Applied Chemistry

KATP-channels:

ATP-sensitive potassium channel

KOS:

herpes simplex virus type 1 (HSV-1) strain KOS

LD50:

lethal dose

LDL:

low-density lipoprotein cholesterol

LPS:

lipopolysaccharide

LXRα:

liver X receptor-α

MANG:

bacteroides

MAOA:

monoamine oxidase A

MAOB:

monoamine oxidase B

MAP:

mitogen-activated protein

MCP-1:

monocyte chemoattractant protein 1

MeSH:

medical subject headings

MGF:

mangiferin

MMP-2:

matrix metallopeptidase 2

MMP-9:

matrix metallopeptidase 9

mRNA:

messenger ribonucleic acid

MWM:

Morris water maze

NF-kB:

nuclear factor kappa-light-chain-enhancer of activated B cells

NGF:

nerve growth factor

NLRP3:

NLR family pyrin domain containing 3

NO:

nitric oxide

NOR:

novel object recognition

NOS-II:

nitric oxide synthase II

Nrf-2:

nuclear factor erythroid 2-related factor 2

OAT1:

organic anion transporter 1

OVA:

ovalbumin

p38 MAPK:

p38 mitogen-activated protein kinases

PGE2:

prostaglandin E2

PAT:

passive avoidance test

PI3K:

phosphoinositide 3-kinase

PPAR-γ:

peroxisome proliferator-activated receptor gamma

PTEN:

fosfatidilinositol-3,4,5-trisfosfato 3-fosfatasa

ROS:

reactive oxygen species

rRNA:

ribosomal ribonucleic acid

SAMP 8 :

senescence-accelerated mouse

SCA-2:

spinocerebellar ataxia type 2

SD:

sleep deprivation

SKIP:

sphingosine kinase interacting protein

Smad2/3:

mothers against decapentaplegic homolog 3

SOD:

superoxide dismutase

STAT:

signal transducer and the activator of transcription

STZ:

streptozotocin

TAU:

tubulin-associated unit

tBHP:

t-butyl hydroperoxide

tBid:

truncated bid protein

TCM:

traditional Chinese medicine

TG:

serum thyroglobulin

TGF-β:

transforming growth factor beta

TGF-β1:

transforming growth factor beta 1

Th9:

T helper type 9 cells

Th17 :

T helper type 17 cells

TLR4:

toll-like receptor 4

TNF-a:

tumor necrosis factor α

TRIP :

turning research into practice

TXNIP:

thioredoxin-interacting protein

U138-MG:

glioblastoma cells

URAT1:

solute carrier family 22 (organic anion/cation transporter), member 12S

WOMAC:

Western Ontario and Mc Master Universities

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Authors and Affiliations

  1. Institute for Medicinal Plants Research “Dr. Josif Pančić”, Tadeuša Košćuška 1, Belgrade, Serbia

    Jelena Zivković

  2. Department of Obstetrics and Gynecology, Division of Basic Sciences and Translational Medicine, University of Texas Medical Branch, Galveston, TX, 77555, USA

    Kammala Ananth Kumar

  3. Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology (SRMIST), Kattankulatur, 603203, Tamil Nadu, India

    Rapuru Rushendran

  4. School of Pharmacy, Hindustan Institute Technology and Science, Padur, Chennai, 603 103, India

    Kaliappan Ilango

  5. Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt

    Nouran M. Fahmy, Heba A. S. El-Nashar & Mohamed El-Shazly

  6. Center of Drug Discovery Research and Development, Ain Shams University, Cairo, Egypt

    Nouran M. Fahmy & Heba A. S. El-Nashar

  7. Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt

    Mohamed El-Shazly

  8. Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt

    Shahira M. Ezzat

  9. Pharmacognosy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, 12451, Egypt

    Shahira M. Ezzat

  10. Instituto de Ciencias Básicas, Universidad Veracruzana, Avda. Castelazo Ayala S/N, 91190, Xalapa, Veracruz, Mexico

    Guiomar Melgar-Lalanne

  11. Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, 04510, Ciudad de México, Mexico

    Alejandra Romero-Montero, Sheila I. Peña-Corona & Gerardo Leyva-Gomez

  12. Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador

    Javad Sharifi-Rad

  13. Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania

    Daniela Calina

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  1. Jelena Zivković
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  14. Daniela Calina
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All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas that is, revising or critically reviewing the article, giving final approval of the version to be published; agreeing on the journal to which the article has been submitted; and confirming to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Jelena Zivković, Javad Sharifi-Rad or Daniela Calina.

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Zivković, J., Kumar, K.A., Rushendran, R. et al. Pharmacological properties of mangiferin: bioavailability, mechanisms of action and clinical perspectives. Naunyn-Schmiedeberg's Arch Pharmacol 397, 763–781 (2024). https://doi.org/10.1007/s00210-023-02682-4

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