Developments in the study of Chinese herbal medicine's assessment index and action mechanism for diabetes mellitus

In traditional Chinese medicine(TCM),based on various pathogenic symptoms and the‘golden chamber’medical text,Huangdi Neijing,diabetes mellitus falls under the category‘collateral disease’.TCM,with its wealth of experience,has been treating diabetes for over two millennia.Different antidiabetic Chinese herbal medicines re-duce blood sugar,with their effective ingredients exerting unique advantages.As well as a glucose lowering effect,TCM also regulates bodily functions to prevent diabetes associated complications,with reduced side effects compared to western synthetic drugs.Chinese herbal medicine is usually composed of polysaccharides,saponins,al-kaloids,flavonoids,and terpenoids.These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion,enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals.These actions regulate glycolipid metabolism in the body,eventually achiev-ing the goal of normalizing blood glucose.Using different animal models,a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer.Nonetheless,there is a dearth of scientific data about the pharmacology,dose-effect relationship,and structure-activity relationship of TCM and its constituents.Further research into the efficacy,toxicity and mode of action of TCM,using different metabolic and molecular markers,is key to developing novel TCM antidiabetic formulations.

Design,preparation,application of advanced array structured materials and their action mechanism analyses for high performance lithium-sulfur batteries

Lithium-sulfur battery(LSB)has brought much attention and concern because of high theoretical specific capacity and energy density as one of main competitors for next-generation energy storage systems.The widely commercial application and development of LSB is mainly hindered by serious“shuttle effect”of lithium polysulfides(Li PSs),slow reaction kinetics,notorious lithium dendrites,etc.In various structures of LSB materials,array structured materials,possessing the composition of ordered micro units with the same or similar characteristics of each unit,present excellent application potential for various secondary cells due to some merits such as immobilization of active substances,high specific surface area,appropriate pore sizes,easy modification of functional material surface,accommodated huge volume change,enough facilitated transportation for electrons/lithium ions,and special functional groups strongly adsorbing Li PSs.Thus many novel array structured materials are applied to battery for tackling thorny problems mentioned above.In this review,recent progresses and developments on array structured materials applied in LSBs including preparation ways,collaborative structural designs based on array structures,and action mechanism analyses in improving electrochemical performance and safety are summarized.Meanwhile,we also have detailed discussion for array structured materials in LSBs and constructed the structure-function relationships between array structured materials and battery performances.Lastly,some directions and prospects about preparation ways,functional modifications,and practical applications of array structured materials in LSBs are generalized.We hope the review can attract more researchers'attention and bring more studying on array structured materials for other secondary batteries including LSB.

Study on the Mechanism of Action of Glyasperin A in the Treatment of Atherosclerosis Based on Network Pharmacology and Molecular Docking

[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.

Adjustment mechanism of blasting dynamic-static action in the water decoupling charge

Water decoupling charge blasting excels in rock breaking,relying on its uniform pressure transmission and low energy dissipation.The water decoupling coefficients can adjust the contributions of the stress wave and quasi-static pressure.However,the quantitative relationship between the two contributions is unclear,and it is difficult to provide reasonable theoretical support for the design of water decoupling blasting.In this study,a theoretical model of blasting fracturing partitioning is established.The mechanical mechanism and determination method of the optimal decoupling coefficient are obtained.The reliability is verified through model experiments and a field test.The results show that with the increasing of decoupling coefficient,the rock breaking ability of blasting dynamic action decreases,while quasi-static action increases and then decreases.The ability of quasi-static action to wedge into cracks changes due to the spatial adjustment of the blast hole and crushed zone.The quasi-static action plays a leading role in the fracturing range,determining an optimal decoupling coefficient.The optimal water decoupling coefficient is not a fixed value,which can be obtained by the proposed theoretical model.Compared with the theoretical results,the maximum error in the model experiment results is 8.03%,and the error in the field test result is 3.04%.

Network Pharmacological Analysis of Action Mechanism of Mongolian Medicine Rhododendron micranthum Turcz. in Treating Lung Cancer

[Objectives]To explore the action mechanism of Mongolian medicine Rhododendron micranthum Turcz.on lung cancer by network pharmacology.[Methods]Based on the high-throughput experiment and reference database(HERB)of traditional Chinese medicine,component target database(Swiss ADME),small molecule drug target prediction online platform(SWISS Target Prediction),human gene business card database(GENECARD),the database of genes and mutation sites related to human diseases(DISGENET)and other databases,the target genes of drugs and diseases were screened out.Venny software was used for obtaining the target intersection of active components of the Mongolian medicine R.micranthum Turcz.and the lung cancer,a CytoNCA plug-in in cytoscape 3.10.0 software was used for screening candidate core target genes,and related effective components were obtained in a reverse direction.A drug-active ingredient-gene-disease regulation network was established,a protein-protein interaction(PPI)network was established by means of the STRING database to screen core genes,and common targets were screened by the David database.Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for enrichment analysis.[Results]There were 13 effective components of Mongolian medicine R.micranthum Turcz.for treating lung cancer and 115 drug disease intersection target genes.Core genes affecting the disease included SRC,HSP90AB1,EGFR,AKT1,and ERBB2.GO functional enrichment analysis involved 462 items of biological processes,64 items of cellular components and 126 items of molecular functions.Enrichment analysis of KEGG signaling pathways screened out cancer pathways,endocrine resistance,PI3K-Akt signaling pathways,proteoglycans in cancer and other signaling pathways.[Conclusions]Mongolian medicine R.micranthum Turcz.can inhibit the proliferation of lung cancer cells from multiple targets and pathways,and the results of network pharmaceutical analysis provide a theoretical basis for further experimental research.

Naturally derived anti-hepatitis B virus agents and their mechanism of action

Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved therapeutic drugs(including interferonalpha and nucleoside analogues)have their limitations.No drugs or therapeutic methods can cure hepatitis B so far.Therefore,it is urgently needed to discover and develop new anti-HBV drugs,especially nonnucleoside agents.Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms.In this review,the natural products against HBV are discussed according to their chemical classes such as terpenes,lignans,phenolic acids,polyphenols,lactones,alkaloids and flavonoids.Furthermore,novel mode of action or new targets of some representative anti-HBV natural products are also discussed.The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20years,especially novel skeletons and mode of action.Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date,scarcely any of them are found in the list of conventional anti-HBV drugs worldwide.Additionly,in anti-HBV mechanism of action,only a few references reported new targets or novel mode of action of antiHBV natural products.

Recent progress in preventive effect of collagen peptides on photoaging skin and action mechanism

Ultraviolet(UV)-induced photoaging skin has become an urgent issue.The functional foods and cosmetics aiming to improve skin photoaging are developing rapidly,and the demand is gradually increasing year by year.Collagen peptides have been proven to display diverse physiological activities,such as excellent moisture retention activity,hygroscopicity,tyrosinase inhibitory activity and antioxidant activity,which indicates that they have great potential in amelioration of UV-induced photoaging.The main objective of this article is to recap the main mechanisms to improve photoaging skin by collagen peptides and their physiological activities in photo-protection.Furthermore,the extraction and structural characteristics of collagen peptides are overviewed.More importantly,some clinical trials on the beneficial effect on skin of collagen peptides are also discussed.In addition,prospects and challenges of collagen peptides are emphatically elucidated in this review.This article implies that collagen peptides have great potential as an effective ingredient in food and cosmetics industry with a wide application prospect.

Effects of diphosphonic acid on ilmenorutile collecting property and research of action mechanism

The effects of several collectors and their dosage on pure ilmenorutile atdifferent pH values were studied and the collecting strength of several representative collectorswas investigated. The experimental results indicate that diphosphonic acid is a good collector forilmenorutile and the recovery of ilmenorutile ranges from 90.87 percent to 91.70 percent when thepulp pH value is 2.0-4.0 and the dosage is 75 mg/L. The sequence of collecting ability for severalcollectors is as follows: diphosphonic acid> TF279 > cyclic allryl hydroximic acid > benzyl arsenicacid> salicylic hydroximic acid> alkyl hydroximic acid. Meanwhile, IAS (infrared absorptionspectrum) and XPS (X-ray photoelectron spectroscopy) were used to detect and analyze the actionmechanism of diphosphonic acid on ilmenorutile. IAS results showed that the characteristicabsorption peak relating to P=O as well as P-O vibration occurred between wave numeber 1140 and 1032cm^(-1), and diphosphonic acid had adsorbed on the surface of ilmenorutile. XPS results indicatedthat the binding energy of P2P peak of ilmenorutile had changed 0.45 eV after treated bydiphosphonic acid. This proves that the adsorption is mainly chemical adsorption.

Existing form and action mechanism of minor scandium and zirconium in Al-Cu-Mg alloy

In order to investigate the existing form and action mechanism of minor scandium （Sc） and zirconium （Zr） in AI-Cu-Mg alloy, microstructures of Al-4Cu-1Mg-Sc-Zr alloy under different conditions, including states of as-cast, homogenized, hot-rolled, as-solution and natural aged, were observed by scanning electron microscopy （SEM）, X-ray diffractometry （XRD） and transmission electron microscopy （TEM）. It is revealed that Sc and Zr are completely dissolved into the supersaturated solid solution in as-cast ingot, but grain refinement is not observed. Coffee-bean-like AI3（Sc, Zr） particles deposit during homogenization of ingot induce an increase in hardness. Al3（Sc, Zr） particles are slightly coarsened in as-solution samples, but they still maintain coherent to matrix, which indicates a high thermal stability of these particles. Good coherency ofAl3（Sc, Zr） particles makes some benefits for inhibiting recrystallization and reserving work-hardening.

Antimicrobial peptides: mechanism of action, activity and clinical potential

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

Comparison of Hypolipidemic Effect of Refined Konjac Meal With Several Common Dietary Fibers and Their Mechanisms of Action

The effects of RKM in comparison with pectin, algin and agar on lipid levels in serum and liver and on liver histopathology in rats were studied. In addition, the effects of all the tested materials on the composition and output of fecal bile acid were observed. All four kinds of dietary fiber were given at a level of 5% of diet to young male rats of Wistar strain fed on a lipid-rich diet contalning 5 % lard, 1% cholesteral and 0. 25 % cholate. All the dietary fibers tested have similar effects on serum lipid composition. In all groups, these substances prevent ed increases in total cholesterol in fasting serum, but the level of triglyceride was tmchangd.The concentrations of totaI cholesterol and triglyceride in the liver were lower in the RKM group than in the control group and the other three groups. Hepatic histopathological exami nation also showed the most significant lipotropic effect in the RKM group. The daily output of fecal bile acids (CDCA+GDCA) was significantly increased in the four experimental groups than in the normal group and the control group. The increase of CDCA was more significant than GDCA, suggesting that the increase of fecal bile acids, especially CDCA, may be one of the mechanisms by which RKM and the other three dietary fibers exerts a hypocholesterolemic effect

Preparation and Action Mechanism of Inclusion Complex of β-cyclodextrin and Sulfurized Isobutylene as Additives in Solution of Polyethylene Glycol-600

The inclusion complex of β-cyclodextrin (β-CD) and sulfurized isobutylene (T321) was prepared with a co-precipitation method. The tribological properties of the complex with different concentrations were investigated by a four-ball tester in the solution of polyethylene glycol-600 (PEG-600). The experimental results suggest that the complex exhibits better anti-friction and anti-wear properties than β-CD under different load conditions. The tribo-system shows the least friction coefficient when the concentration of the complex is 0.8%. During the friction process, the complex was decomposed into various molecular fragments and the T321 molecules were released onto the friction interface to provide effective lubrication. The XPS analytical results on the worn surfaces reveal that sulfide film formed by the released T321 plays a major role, and the iron alkoxide and carbon deposition films formed by the β-CD fragments have better anti-friction effect on the sulfide film surface. The interactions of different films result in the formation of a mixed boundary lubrication film.

Preparation and Action Mechanism of Inclusion Complex of/%cyelodextrin and Sulfurized Isobutylene as Additives in Solution of Polyethylene Glycol-600

The inclusion complex of fl-cyclodextrin （β-CD） and sulfurized isobutylene （T321） was prepared with a co-precipitation method. The tribological properties of the complex with different concentrations were investigated by a four-ball tester in the solution of polyethylene glycol-600 （PEG-600）. The experimental results suggest that the complex exhibits better anti-friction and anti-wear properties than fl-CD under different load conditions. The tribo-system shows the least friction coefficient when the concentration of the complex is 0.8%. During the friction process, the complex was decomposed into various molecular fragments and the T321 molecules were released onto the friction interface to provide effective lubrication. The XPS analytical results on the worn surfaces reveal that sulfide film formed by the released T321 plays a major role, and the iron alkoxide and carbon deposition films formed by the β-CD fragments have better anti-friction effect on the sulfide film surface. The interactions of different films result in the formation of a mixed boundary lubrication film.

Role and mechanism of action of leucine-rich repeat kinase 1 in bone

Leucine-rich repeat kinase 1 （LRRK1） plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrkl in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases. This review recent advances on the functions of the Lrrkl-related family members, Lrrkl deficiency-induced skeletal phenotypes, LRRK1 structure-function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.

The action mechanisms and structures designs of F-containing functional materials for high performance oxygen electrocatalysis

Non-renewable fossil fuels have led to serious problems such as global warming,environmental pollution,etc.Oxygen electrocatalysis including oxygen reduction reaction(ORR)and oxygen evolution reaction(OER)plays a central role in clean energy conversion,enabling a number of sustainable processes for future air battery technologies.Fluorine,as the most electronegative element(4.0)not only can induce more efficient regulation for the electronic structure,but also can bring more abundant defects and other novel effects in materials selection and preparation for favorable catalysis with respect to the other nonmetal elements.However,an individual and comprehensive overview of fluorine-containing functional materials for oxygen electrocatalysis field is still blank.Therefore,it is very meaningful to review the recent progresses of fluorine-containing oxygen electrocatalysts.In this review,we first systematically summarize the controllable preparation methods and their possible development directions based on fluorine-containing materials from four preparation methods.Due to the strong electron-withdrawing properties of fluorine,its control of the electronic structure can effectively enhance the oxygen electrocatalytic activity of the materials.In addition,the catalytic enhancement effect of fluorine on carbonbased materials also includes the prevent oxidation and the layer peeling,and realizes the precise atomic control.And the catalytic improvement mechanism of fluorine containing metal-based compounds also includes the hydration of metal site,the crystal transformation,and the oxygen vacancy induction.Then,based on their various dimensions(0D–3D),we also have summarized the advantages of different morphologies on oxygen electrocatalytic performances.Finally,the prospects and possible future researching direction of F-containing oxygen electrocatalysts are presented(e.g.,novel pathways,advanced methods for measurement and simulation,field assistance and multi-functions).The review is considered valuable and helpful in exploring the novel designs and mechanism analyses of advanced fluorine-containing electrocatalysts.

Pharmacological Studies of Meisoindigo: Absorption and Mechanism of Action

Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. Experiments have shown the improved absorption of meisoindigo, compared to indirubin to be one of the major reasons for the enhancement of antitumor activity. Studies on the mechanism of meisoindigo action indicate that it strongly inhibits DNA biosynthesis in tumor cells. Strong inhibition of the drug on assembly of microtubule protein was also obtained. By means of FCM technique the effects of meisoindigo on mouse leukemia L1210 cell cycle were examined. Experimental results showed that under the action of meisoindigo the S phase cells accumulated and the traverse of the cells in G2 + M phase to G1 phase may also be blocked to some extent.

Exploring Action Mechanism of Sanzi Yangqin Decoction in Treating Bronchial Asthma Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the molecular mechanism of Sanzi Yangqin Decoction in the treatment of bronchial asthma based on network pharmacology and molecular docking.[Methods]The components of Fructus Perillae,Semen Raphani and Semen Sinapis three traditional Chinese medicine-related components and targets of Feiduqing Sanzi Yangqin Decoction were obtained using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the targets of bronchial asthma were obtained using Genecards and OMIM databases.Sanzi Yangqin Decoction"drug-active ingredient-target-disease"network was established with the aid of Cytoscape 3.7.2 software and network topology analysis was carried out.The gene ontology(GO)function enrichment analysis and the KEGG pathway enrichment analysis were performed by DAVID.The top 3 components and targets in the network topology analysis were respectively molecularly docked.[Results]Through network analysis,4 key active components were obtained,mainly luteolin,arachidonic acid,β-carotene,etc.;5 key targets,mainly NCOA2,PGR,PTGS2,etc.Through GO analysis,523 items(P<0.05)were obtained,including 396 items in biological process(BP),53 items in cell composition(CC),and 74 items in molecular function(MF).KEGG analysis generated 144 signal pathways(P<0.05),involving PI3K-Akt signal pathway,human cytomegalovirus infection,Kaposi's sarcoma-associated herpes virus infection,proteoglycans in cancer,prostate cancer,etc.The results of molecular docking showed that core active compounds such as luteolin andβ-carotene in Sanzi Yangqin Decoction had good affinity with NCOA2,PGR,PTGS2 and other target genes,which were similar to clinically recommended chemical drugs.[Conclusions]The active compounds luteolin and carotene in Sanzi Yangqin Decoction may mainly bind to targets such as NCOA2,PGR,PTGS2,and regulate multiple signaling pathways such as PI3K-Akt to play a role in treating bronchial asthma.It is intended to provide new ideas for the clinical application and research of Sanzi Yangqin Decoction.

Analysis on the medication rules and mechanisms of action of traditional Chinese medicine in treating cervical cancer

Objective: To summarize the rule of application of traditional Chinese medicine (TCM) in the prevention and treatment of cervical cancer, and to explore the molecular mechanism of the compatibility of core herbs. Methods: Collect relevant literatures on cervical cancer in Chinese National Knowledgey Ifrastructure (CNKI), use TCM inheritance platform system (TCMISSV2.5) for association rules and complex system entropy clustering analysis;use BATMAN-TCM online analysis tools to construct target-pathway-disease network to reveal the underlying mechanisms of action. Results: Among the 78 prescriptions selected, a total of 172 Chinese medicines were used, and the five most frequently used herbs were Huang-bo (Phellodendri Chinrnsis Cortex), Fu-ling (Poria Cocos), Huang-qi (Hedysarum Multijugum Maxim.), Bai-hua-she-she-cao (Hedyotis Diffusae Herba) and Gan-cao (Licorice). Bai-hua-she-she-cao (Hedyotis Diffusae Herba) and Huang-qi (Hedysarum Multijugum Maxim.), Bai-hua-she-she-cao (Hedyotis Diffusae Herba) and Fu-ling (Poria Cocos), Bai-zhu (Atractylodes Macrocephala Koidz.) and Fu-ling (Poria Cocos) are the three most commonly used medicine match. In addition, through cluster analysis, a total of 4 core herbs compatibility and 2 new prescriptions were excavated. Herbs in the new prescriptions which are used to clearing heat-toxin and removing dampness were most frequently used. Through the analysis of the signal pathway of high frequency Chinese medicines, we found that neuroactive ligand-receptor interaction pathway may play important roles. Conclusion: The core Chinese medicines for the prevention and treatment of cervical cancer are mainly clearing heat-toxin and removing dampness. The core Chinese medicines may play their anti-cervical cancer by interfering with the neuroactive ligand-receptor interaction signaling pathway.

Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species

Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed here.The most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune checkpoint.Different molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis.Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOK2 and JAK2,has been postulated with Nag-E.The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids.The mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.

Hinokiflavone and Related C-O-C-Type Biflavonoids as Anti-cancer Compounds:Properties and Mechanism of Action

Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apigenin units.This later sub-group of bisflavonyl ethers includes HNK,ochnaflavone,delicaflavone and a few other dimeric compounds,found in a variety of plants,notably Selaginella species.A comprehensive review of the anticancer properties and mechanism of action of HNK is provided,to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives,and HNK-containing plant extracts.The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9(with a potential direct binding to MMP-9).In addition,HNK was found to function as a potent modulator of pre-mRNA splicing,inhibit-ing the SUMO-specific protease SENP1.As such,HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds.Oral formulations of HNK have been elaborated to enhance its solubility,to facilitate the compound delivery and to enhance its anticancer efficacy.The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK.This compound deserves further attention as a regu-lator of pre-mRNA splicing,useful to treat cancers(in particular hepatocellular carcinoma)and other human pathologies.