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Rosemary (Rosmarinus officinalis L.): extraction techniques, analytical methods and health-promoting biological effects

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Abstract

Rosemary (Rosmarinus officinalis L.) of the Lamiaceae family represents an evergreen medicinal plant with various health-promoting pharmacological effects. This paper provides a complete overview of diverse biological activities of rosemary extracts, essential oils as well as their numerous bioactive compounds, ranging from antioxidative, anti-inflammatory, and antimicrobial over cognitive enhancing to their anticarcinogenic effects. In addition, state of the art extraction, distillation, fractionation, and characterization techniques for obtaining high-quality rosemary extracts and essential oils as well as methods for determining their antioxidative, antimicrobial, anti-inflammatory, and anticarcinogenic potentials are also presented. Finally, new ideas for future computational studies on chemical reactivities and binding affinities of health-promoting rosemary compounds together with suggestions for their improved bioavailability through diverse encapsulation techniques are introduced.

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Code availability

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Abbreviations

ABTS:

2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)

ACC:

Acetyl-CoA carboxylase

ACR:

Acrylamide

AD:

Alzheimer’s disease

AIA:

Adjutant-induced arthritis

Akt:

Protein kinase B

ALP:

Alkaline phosphatase

ALT:

Alanine transaminase

AM:

Alveolar macrophage

AMPK:

AMP-activated protein kinase

AAPH:

2,2′- Azo-bis(2-amidinopropane) dihydrochloride

AST:

Aspartate transaminase

Bad:

Bcl-2 associated agonist of cell death

Bax:

Bcl-2 associated x protein

Bcl-2:

B-cell lymphoma 2

Bcl-x:

B-cell lymphoma x

BHA:

Butylated hydroxyanisole

BHT:

Butylated hydroxytoluene

BID:

BH3 interacting domain death agonist

BOLD:

The Barcode of Life Data System

CAT:

Catalase

CCl4:

Carbon tetrachloride

CHOP:

C/EBP homologous protein

cIAP-1:

Cellular inhibitor of apoptosis protein 1

CNS:

Central nervous system

COL1A1/2:

Type I collagen alpha 1 and 2

COX-2:

Cyclooxygenase-2

CRP:

C-reactive protein

DAD:

UV-diode array detector

DBMA:

7, 12-Dimethylbenzanthracene

DMH:

1,2-Dimethylhydrazine

DNCB:

2,4-Dinitrochlorobenzene

DPPH:

2,2-Diphenyl-1-picrylhydrazil

DPP-IV:

Dipeptidyl peptidase-IV

DR5:

Death receptor 5

EC50 :

Efficient concentration

EFSA:

European Food Safety Authority

EMA:

European Medicinal Agency

eNOS:

Endothelial nitric oxide synthase

EO:

Essential oils

ERK1/2:

Extracellular signal-regulated kinases 1 and 2

ERK:

Extracellular signal-regulated kinases

ESI:

Electrospray ionization

EU:

European Union

FADD:

Fas-associated via death domain

Fas:

Fas cell surface death receptor

FasL:

Fas ligand

FID:

Flame ionization detector

G6Pase:

Glucose-6-phosphatase

GABAA :

γ-Aminobutyric acid

GC:

Gas chromatography

GIO:

Glucocorticoid-induced osteoporosis

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Reduced glutathione

GSK-3β:

Glycogen synthase kinase 3β

GSSG:

Oxidized glutathione

HD:

Hydrodistillation

HIF-α:

Hypoxia-inducible factor 1-alpha

HIV-1:

Human immunodeficiency virus type 1

HO-1:

Heme oxygenase-1

HPLC:

High-performance liquid chromatography

HRMS:

High-resolution mass spectroscopy

HSA:

Human serum albumin

HS-SPME:

Headspace solid-phase microextraction

IAP:

Inhibitor of apoptosis

IC50 :

Inhibitory concentration

IEC6:

Small intestine epithelial cells

IFN-γ:

Interferon-gamma

IgE:

Immunoglobulin E

IKK:

IκB kinase

IL-6:

Interleukin 6

iNOS:

Inducible nitric oxide synthase

iPSC:

Induced pluripotent stem cells

JAK:

Janus kinase

JNK:

CJun N-terminal kinase

LC:

Liquid chromatography

LDLR:

Low-density lipoprotein receptor

L-NAME:

Nω-Nitro-L-arginine methyl ester hydrochloride

LP:

Lipid peroxidation

LPS:

Lipopolysaccharide

Lrp-5:

Lipoprotein-receptor-related protein 5

Lrrk2:

Leucine-rich repeat kinase 2

LTQ:

Linear Trap Quadrupole

MAE:

Microwave-assisted extraction

MAHD:

Microwave-assisted hydrodistillation

MAPK:

Mitogen-activated protein kinases

MBC:

Minimum bactericidal concentration

Mcl-1:

Myeloid leukemia cell differentiation protein

MDA:

Malondialdehyde

MD:

Molecular dynamics

MHDG:

Microwave hydro diffusion and gravity

MIC:

Minimum inhibitory concentration

MKP-1:

MAP kinase phosphatase 1

MMP-9:

Matrix metalloproteinase 9

MRSA:

Methicillin-resistant Staphylococcus aureus

MS:

Mass spectrometry

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

MW:

Molecular weight

NADH:

Nicotinamide adenine dinucleotide

NADPH:

Nicotinamide adenine dinucleotide phosphate

NDEA:

N-nitrosodiethylamine

NF-κB:

Nuclear factor-kappa B

NLRP3:

Nicotine-induced NLR family pyrin domain containing 3

NMDA:

N-methyl-D-aspartic acid

NO:

Nitric oxide

Nrf2:

Nuclear factor erythroid-2 related factor-2

OPCML:

Opioid binding protein/cell adhesion molecule

OVA:

Ovalbumin

PARP:

Poly(ADP-ribose) polymerase

PDA:

Photodiode array detector

PDE4:

CAMP-phosphodiesterase 4

PDIA3:

Protein disulfide-isomerase A3

PD:

Parkinson’s disease

PEGylated:

Polyethylene glycol

PGC-1α:

γ Coactivator 1-α

PHWE:

Pressurized hot water extraction

PI3K:

Phosphatidylinositol 3-kinase

P-IκB:

Phospho-inhibitory subunit of NF-κB

PLE:

Pressurized liquid extraction

PP2A:

Phosphatase 2A

PPAR:

Peroxisome proliferator-activated receptor

Q-TOF:

Quadrupole-time of flight

RORγ:

RAR-related orphan receptor gamma

ROS:

Reactive oxygen species

SAR:

Structure-activity relationship

SD:

Steam distillation

SFE:

Supercritical-fluid extraction

SFME:

Solvent-free microwave distillation extraction

sICAM-1:

Soluble intercellular adhesion molecule 1

SIRT1:

Sirtuin 1

SNpc:

Substantia nigra pars compacta

SOD:

Superoxide dismutase

Sp1:

Specificity protein 1

STAT3:

Signal transducer and activator of transcription 3

STZ:

Streptozotocin

SWE:

Superheated or subcritical water extraction

TCTP:

Translationally controlled tumor protein

Th2:

T helper cell type 2

TNF-α:

Tumor necrosis factor-alpha

TPA:

12-O-tetradecanoyl-phorbol-13-acetate

TRPV1:

Transient receptor potential cation channel subfamily V member 1

UAE:

Ultrasound-assisted extraction

UHPLC:

Ultra-high performance liquid chromatography

VCAM-1:

Vascular cell adhesion molecule

WHO:

World Health Organization

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Acknowledgments

We are grateful to Vesna Mlinarič Lešnik for the rosemary plant photograph presented in Fig. 1.

Funding

Financial support through the Slovenian Research Agency project grants J1-6736, P2-0046, and L7-8269 as well as through the Slovenian Ministry of Education, Science and Sports program grants C3330-19–952021, F4F, and AB FREE is gratefully acknowledged.

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  1. Samo Lešnik and Veronika Furlan have contributed equally to this work.

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  1. Laboratory of Physical Chemistry and Chemical Thermodynamics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova 17, 2000, Maribor, Slovenia

    Samo Lešnik, Veronika Furlan & Urban Bren

  2. Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Glagoljaška 8, 6000, Koper, Slovenia

    Urban Bren

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Lešnik, S., Furlan, V. & Bren, U. Rosemary (Rosmarinus officinalis L.): extraction techniques, analytical methods and health-promoting biological effects. Phytochem Rev 20, 1273–1328 (2021). https://doi.org/10.1007/s11101-021-09745-5

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