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Regulatory mechanisms of Gentiopicroside on human diseases: a brief review

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Abstract

Gentiopicroside (GPS), a single compound isolated from Gentiana lutea L. and the crucial representative of secoiridoid constituent, has been permitted for centuries in traditional Chinese medicine. GPS and its metabolites have been increasingly used in the search for clinical management with therapeutic properties and fewer side effects. The objective of this review was to provide a comprehensive overview of the involvement of molecular pathways in the therapeutic effects of GPS on human diseases and chronic conditions. This study presents a meticulously conducted comprehensive search of the PubMed and Google Scholar databases (from 1983 to 2023), aimed at identifying articles relating to regulatory mechanisms of GPS on human diseases and the pharmacokinetics of GPS. The inclusion criteria were meticulously and precisely defined to encompass original research papers that explicitly focused on elucidating the regulatory mechanisms of GPS in various human diseases through in vitro and animal studies. Notably, these studies were mandated to integrate specific genetic markers or pathways as essential components of their research inquiries. The evaluated pharmacokinetic parameters included maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), area under the curve (AUC), clearance, and plasma half-life (t1/2). Subsequently, through a rigorous screening process of titles and abstracts, studies conducted in vitro or on animals, as well as those reporting pharmacokinetic data related to drugs other than GPS or language barriers, were systematically excluded. Drawing from the data and studies pertaining to this review, we conducted a thorough and informative analysis of the pharmacological characteristics and biological functions of GPS. These encompassed a wide range of effects, including hepatoprotective, anti-inflammatory, antifibrotic, antioxidant, analgesic, antitumor, and immunomodulatory properties. The analysis provided a comprehensive and insightful understanding of GPS’s pharmacological profile and its diverse activities. Enhancing theoretical and experimental methodologies could prove advantageous in expanding the clinical applications of GPS. This could involve optimizing the bioavailability and pharmacokinetics of GPS, uncovering additional biomarkers and potential biotransformation pathways, and investigating its combined effects with standard-of-care medications.

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This review is a concise presentation of a proposed hypothesis, and therefore, no scientific or experimental data was presented.

Abbreviations

AA:

Adjuvant-induced arthritis

ALD:

Alcoholic liver damage

ALDH1L1:

Aldehyde dehydrogenase family 1-member L1

ANCC:

Anterior cingulate cortex

ANIT:

Alpha-naphthylisothiocyanate

ARA:

Arachidonic acid

ASC:

Apoptosis-associated speck-like protein containing

AT1R:

Angiotensin II type 1 receptor

ATP:

Adenosine triphosphate

AUC:

Area under the curve

BALF:

Bronchoalveolar lavage fluid

Bas:

Bile acids

BDNF:

Brain-derived neurotrophic factor

BMSCs:

Bone mesenchymal stem cells

BUN:

Blood urea nitrogen

CAT:

Catalase

CC:

Cervical cancer

CF:

Cardiac fibrosis

CFs:

Cardiac fibroblasts

CIA:

Collagen-induced arthritis

CK2:

Creatine Kinase 2

CL:

Clearance

C max :

Maximum plasma concentration

CNS:

Central nervous system

CoA:

Coenzyme A

COX-2:

Cyclooxygenase-2

Cr:

Creatinine

CRP:

C-reactive protein

CTGF:

Connective tissue growth factor

Cyp7a1:

Cholesterol 7-alpha hydroxy-lase

DA:

Dopamine

DDB2:

DNA-binding protein 2

Dex:

Dexamethasone

DN:

Diabetic nephropathy

DPN:

Diabetic peripheral neuropathy

EF:

Ejection fraction

EMMPRIN:

MMP inducer

EMT:

Epithelial-mesenchymal transition

EPSCs:

Excitatory postsynaptic currents

ERK:

Extracellular signal-regulated kinase

FBG:

Fasting blood glucose

FFA:

Free fatty acid

FN:

Fibronectin

FS:

Fraction shortening

GCLM:

Glutamate-cysteine ligase regulatory subunit

GFP:

Green fluorescent protein

GPS:

Gentiopicroside

GSH:

Glutathione

GSH-Px:

Glutathione peroxidase

GSP:

Glycated serum protein

HbA1c:

Hemoglobin A1c

HFLS:

Human fibroblast-like synoviocytes

HG:

High glucose

HO-1:

Heme oxygenase-1

Hyp:

Hydroxyproline

IFN:

Interferon

IgE:

Immunoglobulin E

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

JNK:

Jun N-terminal kinase

LDL-C:

Low-density lipoprotein cholesterol

LEF:

Leflunomide

LVIDd:

Left ventricular diastolic dimension

LVIDs:

Left ventricular internal diameter systole

MAPK:

Mitogen-activated protein kinase

MAPKs:

Mitogen-activated protein kinases

MDA:

Malondialdehyde

MIC:

Minimum inhibitory concentration

MMP:

Matrix metallopeptidase

MPO:

Myeloperoxidase

Mrp4:

Multidrug resistance protein 4

MTX:

Methotrexate

NAFLD:

Nonalcoholic fatty liver disease

NCV:

Nerve conduction velocity

NE:

Norepinephrine

NF-κB:

Nuclear factor kappa B

NLRP3:

NOD-like receptor protein 3

NMDAR:

N-Methyl-Daspartate Receptors

NO:

Nitric oxide

NQO1:

NAD(P)H:quinone oxidoreductase 1

Nrf2:

Nuclear factor erythroid 2-related factor 2

OCN:

Osteocalcin

OPN:

Osteopontin

OSX:

Osterix

OVA:

Ovalbumin

OVX:

Ovariectomized

PA:

Palmitic acid

PAQR3:

AdipoQ receptor 3

PCA:

Principal component analysis

PCNA:

Proliferating cell nuclear antigen

PCO:

Protein carbonyl

PE:

Phenylephrine

PGE2:

Prostaglandin E2

PF:

Pulmonary fibrosis

PPARα:

Peroxisome proliferator-activated receptor α

RA:

Rheumatoid arthritis

RANKL:

Receptor activator of nuclear factor kappa B ligand

RAS:

Renin-angiotensin system

RASMCs:

Rat aortic smooth muscle cells

Runx2:

Runt-related transcription factor 2

SIRT1:

Silent information regulator 1

SNCV:

Sensory nerve conduction velocity

SOD:

Superoxide dismutase

SRB:

Sulpharhodamine B

Src:

Serum creatinine

SREBP-1c:

Sterol regulatory element-binding protein-1c

t1/2 :

Half-life

T-αMCA:

Tauro-α-mouse cholic acid

T-ωMCA:

Tauro-ω mouse cholic acid

TBA:

Total bile acids

TBIL:

Total bilirubin

TC:

Total cholesterol

TCA:

Taurocholic acid

TAG:

Triacylglycerol

Th2:

T helper type 2

TIF:

Tubulointerstitial fibrosis

TIMP-1:

Tissue inhibitor of metal protease1

T max :

Time to reach maximum plasma concentration

TNF:

Tumor necrosis factor

TUDCA:

Tauroursodeoxycholic acid

Ty:

Tyloxapol

UDCA:

Ursodeoxycholic acid

Up:

24-H urine protein

VEGF:

Vascular endothelial growth factor

VSM:

Vascular smooth muscle

5-HT:

5-Hydroxytryptamine

α-SMA:

α-Smooth muscle actin

β-MCA:

β-Mouse cholic acid

ω-MCA:

ω-Mouse cholic acid

ΔΨm:

Mitochondrial membrane potential

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Funding

This study was funded by National Natural Science Foundation of China (81873163) and the Key Project of Natural Science Foundation of Shandong Province (ZR2020KC024).

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Author notes

  1. Bin Liu and Feng Pang contributed equally to this work and should be regarded as co-first authors.

Authors and Affiliations

  1. Shandong University of Traditional Chinese Medicine, No. 4655#, Daxue Road, Jinan, 250355, China

    Bin Liu

  2. Department of Ophthalmology, Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital, No.4, Renmin Road, Qingdao, 266033, China

    Feng Pang

  3. Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao, 266033, China

    Feng Pang

  4. Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Shandong Academy of Eye Disease Prevention and Therapy, No. 48#, Yingxiongshan Road, Jinan, 250002, China

    Hongsheng Bi & Dadong Guo

  5. Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China

    Hongsheng Bi & Dadong Guo

Authors
  1. Bin Liu
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  2. Feng Pang
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  3. Hongsheng Bi
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  4. Dadong Guo
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Contributions

Bin Liu and Feng Pang: writing—original draft, visualization; Hongsheng Bi and Dadong Guo: conceptualization, resources, writing—review and editing, funding acquisition.

The authors confirm that no paper mill and artificial intelligence was used.

Corresponding author

Correspondence to Dadong Guo.

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The authors declare no competing interests.

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Highlights

1. GPS can treat arthralgia, stroke, hemiplegia, pains, jaundice, and infantile malnutrition.

2. GPS exhibits hepatoprotective, antifibrosis, antioxidant, and antitumor effects.

3. GPS can play a role in anti-inflammatory and immunomodulatory activities.

4. Regulatory mechanisms of GPS on multiple human diseases were illustrated.

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Liu, B., Pang, F., Bi, H. et al. Regulatory mechanisms of Gentiopicroside on human diseases: a brief review. Naunyn-Schmiedeberg's Arch Pharmacol 397, 725–750 (2024). https://doi.org/10.1007/s00210-023-02672-6

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  • DOI: https://doi.org/10.1007/s00210-023-02672-6

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