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An update on the bioactivities and health benefits of two plant-derived lignans, phyllanthin and hypophyllanthin

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Abstract

Polyphenols are notable phytochemicals mostly found in plant-based foods, with many reported health benefits. Only limited information is available in the literature on polyphenolic lignans; hence, this review highlights the findings from an extensive open-ended search performed on many databases and search engines, using the keywords “phyllanthin” and “hypophyllanthin” inserted separately and jointly into these databases. Up to 2700 distinct articles were generated, most of which were related to plants of the Phyllanthus species. Plant extract-based articles were excluded. 468 original articles and bibliographic reviews that met the inclusion criteria were selected. Our search showed that both lignans were mostly isolated from plant sources, and some of their biological and pharmacological activities have been previously studied in in silico, in vitro and in vivo experimental models. Only a few human studies were reported, mainly in ex-vivo studies with blood samples and parasites. The antioxidant, anti-inflammatory and immunomodulatory, cardiovascular and cardioprotective, antimicrobial, antiviral, antiparasitic, neuroprotective and neuroactive, anti-diabetic, reno-protective and uricosuric, hepatoprotective, metabolic as well as anticancer effects are well-documented and described in the different sections of this review, as summarized in Table 1. No direct toxicity and side effects were reported. The health benefits identified in the reviewed articles potentially provide some rationale for further scientific research on these lignans’ toxicology, safety profiles, pharmacokinetics, and pharmacodynamics, with a view to progressing through the clinical trial phases of the drug discovery and development process.

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Abbreviations

ACE:

Angiotensin-converting enzyme

ADH:

Alcohol dehydrogenase

AGEs:

Advanced glycation end products

AHR:

Airway hyperresponsiveness

Alb:

Albumin

ALK5:

Activin receptor-like kinase 5

ALT:

Alanine transaminase

Ang:

Angiotensin

AP2:

Adipocyte lipid-binding protein

AR:

Aldose reductase

AST:

Aspartate aminotransferase

BCSCs:

Breast cancer stem cells

BNP:

Brain natriuretic peptide

CAM:

Complementary and alternative medicine

CCl4:

Carbon tetrachloride

CAT:

Catalase

CK-M:

Creatine kinase muscle-type

CPP:

Cell-penetrating peptide

DEN:

Diethylnitrosamine

DM:

Diabetes mellitus

DPPH:

2,2-Diphenyl-1-picryl-hydrazyl-hydrate

EAC:

Ehrlich Ascites Carcinoma

ER:

Endoplasmic reticulum

ET-1:

Endothelin-1

GABA:

Gamma-aminobutyric acid

GPx:

Glutathione peroxidase

GSH:

Glutathione

GSSG:

Oxidized glutathione

H1R:

Histamine 1 receptor

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HDAC1:

Histone deacetylase 1

HDL:

High-density lipoprotein

HFD:

High-fat diet

HKLs:

Head kidney leukocytes

HRAR:

Human recombinant aldose reductase

IFN-γ:

Interferon-γ

IgE:

Immunoglobulin E

IL-6:

Interleukin-6

iNOS:

Inducible NOS

LDH:

Lactate dehydrogenase enzyme

LPO:

Lipid peroxidation

MAPKs:

Mitogen-activated protein kinases

MDA:

Malondialdehyde

MDR:

Multi-drug resistance

MetS:

Metabolic syndrome

MMLF:

Mixed micellar lipid formulation

MMP9:

Matrix metallopeptidase 9

MRP2:

Multidrug resistance protein 2

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NSAID:

Non-steroidal anti-inflammatory drug

OVA:

Ovalbumin

PEG:

Polyethylene glycol

P-gp:

P-glycoprotein

PKC-α:

Protein kinase C alpha

PMNs:

Polymorphonuclear leukocytes

PTP1B:

Protein tyrosine phosphatase 1B

RKAR:

Rat kidney aldose reductase

RLAR:

Rat lens aldose reductase

ROC:

Receptor-operated Ca2+ channels

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

T1D:

Type 1 diabetes

T2D:

Type 2 diabetes

T-AOC:

Total antioxidant capacity

TEA:

Tetraethylammonium

TH:

Thyroid hormone

TNF-α:

Tumour necrosis factor-alpha

TP:

Total protein

TSH:

Thyroid-stimulating hormone

UHPLC-MS/MS:

Ultra-high-pressure liquid chromatography-tandem mass spectrometry

VOC:

Voltage-operated Ca2+ channels

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SIO, JD, TSK and ZR: wrote the first draft of the manuscript; SIO: Conceptualization, methodology, writing-original draft, writing-review and editing. AAH, DEL, and OEE: writing-review and editing.

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Sylvester I. Omoruyi has no conflict of interest. Joshua Delport has no conflict of interest. Tusekile S. Kangwa has no conflict of interest. Ziyaad Rahman has no conflict of interest. Ahmed A. Hussein has no conflict of interest. Dietrich E. Lorke has no conflict of interest. Okobi E. Ekpo has no conflict of interest.

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Omoruyi, S.I., Delport, J., Kangwa, T.S. et al. An update on the bioactivities and health benefits of two plant-derived lignans, phyllanthin and hypophyllanthin. ADV TRADIT MED (ADTM) (2024). https://doi.org/10.1007/s13596-023-00738-7

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