Advances in plant-based inhibitors of P-glycoprotein

Yu, Jun; Zhou, Peng; James, Alexandra; Yang, Xiaodan; Wang, Chun; Wei, Wei

doi:10.3109/14756366.2016.1149476

Cited by 55 publications

(27 citation statements)

References 127 publications

(161 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, wogonin has the ability to suppress the P-glycoprotein, which is an ATP-binding cassette export protein with the function of transporting the drugs back into the blood. Nevertheless, the ability of this compound to penetrate the BBB is not confirmed by any direct evidence [205]. Interestingly, hesperetin and its glycoside hesperidin are other flavonoid compounds that can provide protection, through downregulation of the Aβ-activated autophagy, to neuronal cells against Aβ-stimulated impairment of glucose transport and glucose uptake [206].…”

Section: Role Of Flavonoids In Autophagymentioning

confidence: 99%

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

et al. 2020

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is one of the utmost chronic neurodegenerative disorders, which is characterized from a neuropathological point of view by the aggregates of amyloid beta (Aβ) peptides that are deposited as senile plaques and tau proteins which form neurofibrillary tangles (NFTs). Even though advancement has been observed in order to understand AD pathogenesis, currently available therapeutic methods can only deliver modest symptomatic relief. Interestingly, naturally occurring dietary flavonoids have gained substantial attention due to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties as alternative candidates for AD therapy. Experimental proof provides support to the idea that some flavonoids might protect AD by interfering with the production and aggregation of Aβ peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aβ peptides and inhibit tau phosphorylation by the mTOR/autophagy signaling pathway. Moreover, due to their cholinesterase inhibitory potential, flavonoids can represent promising symptomatic anti-Alzheimer agents. Several processes have been suggested for the aptitude of flavonoids to slow down the advancement or to avert the onset of Alzheimer’s pathogenesis. To enhance cognitive performance and to prevent the onset and progress of AD, the interaction of flavonoids with various signaling pathways is proposed to exert their therapeutic potential. Therefore, this review elaborates on the probable therapeutic approaches of flavonoids aimed at averting or slowing the progression of the AD pathogenesis.

show abstract

Section: Role Of Flavonoids In Autophagymentioning

confidence: 99%

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Therefore, due to their low toxicity level research on natural P-gp inhibitors is presently gaining interest. Challenges of using natural molecules in place of conventional synthetic molecules are stated as structural diversity, non-specific binding with the targets, unwanted pharmacokinetic changes may take place and extensive research is needed to establish the drug-like charecteristics of these molecules [ 259 ], but there are ceratain good aspects in using natural products like their variety of structures, less toxicity and the natural products would be helpful in designing and synthesizing new molecules with more selectivity towards P-gp transporters. Conventional P-gp inhibitors have some limitations and always produce toxic effects towards normal cells.…”

Section: P-glycoprotein Inhibitionmentioning

confidence: 99%

Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition

et al. 2017

View full text Add to dashboard Cite

Multidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to P-glycoprotein (P-gp) and its down-regulation by natural bioactive molecules. P-gp, a unique ATP-dependent membrane transport protein, is one of those key regulators which are present in the lining of the colon, endothelial cells of the blood brain barrier (BBB), bile duct, adrenal gland, kidney tubules, small intestine, pancreatic ducts and in many other tissues like heart, lungs, spleen, skeletal muscles, etc. Due to its diverse tissue distribution, P-gp is a novel protective barrier to stop the intake of xenobiotics into the human body. Over-expression of P-gp leads to decreased intracellular accretion of many chemotherapeutic agents thus assisting in the development of MDR. Eventually, the effectiveness of these drugs is decreased. P-gp inhibitors act by altering intracellular ATP levels which are the source of energy and/or by affecting membrane contours to increase permeability. However, the use of synthetic inhibitors is known to cause serious toxicities. For this reason, the search for more potent and less toxic P-gp inhibitors of natural origin is underway. The present review aims to recapitulate the research findings on bioactive constituents of natural origin with P-gp inhibition characteristics. Natural bioactive constituents with P-gp modulating effects offer great potential for semi-synthetic modification to produce new scaffolds which could serve as valuable investigative tools to recognize the function of complex ABC transporters apart from evading the systemic toxicities shown by synthetic counterparts. Despite the many published scientific findings encompassing P-gp inhibitors, however, this article stand alones because it provides a vivid picture to the readers pertaining to Pgp inhibitors obtained from natural sources coupled with their mode of action and structures. It provides first-hand information to the scientists working in the field of drug discovery to further synthesise and discover new P-gp inhibitors with less toxicity and more efficacies.

show abstract

“…Among these, flavonoids (3,7-dihydroxyflavone; 2′,4′-dihydroxychalcone from Zuccagnia punctata , quercetin from Ginkgo biloba ; rutin from Ruta graveolens ; genistein from vegetables; kaempfero from Kaempferia galanga L. root; icaritin from Herba epimediu ; baicalein from the roots of Scutellaria ; biochanin A from the bark of Aesculus hippocastanum L., silymarin from the seeds of milk thistle, wogonin from the roots of Scutellaria baicalensi Georgi. ), alkaloids (glaucine from the stems of Corydalis yanhusuo , cepharanthine from the roots of Stephania cepharantha , pyrrolidine from Piper boehmeriifolium , tetrandrine and fangchinoline from the root of Stephania tetranda , indole-3-carbinol from Brassica, pervilleines B and C from Erythroxylum pervillei , stemocurtisine and oxystemokerrine from the roots of Stemona aphylla and Stemona burkillii ), coumarins (cnidiadin from Tordylium apulum , clausarin from Citrus sinensis , galbanic acid from the roots of Ferula szowitsiana , farnesiferol A from the roots of Ferula persica , GUT-70 from stem bark of Calophyllum brasiliense ), terpenoids ((R)-(+)-citronellal essential oil from Zanthoxyli fructus , abietic acid from pine and conifers, Glycyrrhetic acid from Glycyrrhizae radix , euphomelliferine and euphomelliferenes A from Euphorbia mellifera , Euphorbia factor L10 from Euphorbia lathyris , euphoportlandols A and B from Euphorbia portlandica ) and steroids (Paris saponin VII from Trillium tschonoskii , ginsenoside Rg 3 and protopanaxatriol ginsenosides from Panax ginseng , gracillin and polyphyllin D from Paris polyphylla ) were promising ( 31 ).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Herbal Bioenhancers in Veterinary Phytomedicine

2018

View full text Add to dashboard Cite

Herbal bioenhancers are active phytomolecules that increase the bioavailability, bioefficacy and biological activity of various drugs when coadministered at low concentrations. These valuable compounds reduce the dose, increase the treatment rate, decrease the treatment duration, drug resistance or related adverse reactions which have economical implications in livestock and pet medicine. Eventhough the concept of herbal bioenhancers are known for years through Ayurvedic medicine, the underlying mechanisms remains unclear. The main mechanisms involved are related to drug absorption (effect on solubility, drug efflux and transport proteins, increased permeability in gastrointestinal system) and drug metabolism (inhibition/induction of drug metabolysing enzymes, thermogenic effect). Due to species specific differences in these mechanisms, corresponding data on human and laboratory animal could not be attributed. As multidrug resistance is a major treat to both human and animal health, within “One Health” concept, efficient therapeutical strategies are encouraged by authorities, where focus on herbal supplements as a vast unexploited field remains to be researched within “Bioenhancement Concept.” This review brings insight to mechanims involved in bioenhancing effect, examples of herbal extracts and phytoactive compounds and their potential in the veterinary medicine including different classes of drugs such as antibiotics, anticancerous, antiviral, and antituberculosis.

show abstract

Advances in plant-based inhibitors of P-glycoprotein

Cited by 55 publications

References 127 publications

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition

Herbal Bioenhancers in Veterinary Phytomedicine

Contact Info

Product

Resources

About