The potential mechanism of Isodon suzhouensis against COVID-19 via EGFR/TLR4 pathways

Corona Virus Disease 2019(COVID-19)has brought the new challenges to scientific research.Isodon suzhouensis has good anti-inflammatory and antioxidant stress effects,which is considered as a potential treatment for COVID-19.The possibility for the treatment of COVID-19 with I.suzhouensis and its potential mechanism of action were explored by employing molecular docking and network pharmacology.Network pharmacology and molecular docking were used to screen drug targets,and lipopolysaccharide(LPS)induced RAW264.7 and NR8383 cells inflammation model was used for experimental verification.Collectively a total of 209 possible linkages against 18 chemical components from I.suzhouensis and 1194 COVID-19 related targets were selected.Among these,164 common targets were obtained from the intersection of I.suzhouensis and COVID-19.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enriched 582 function targets and 87 target proteins pathways,respectively.The results from molecular docking studies revealed that rutin,vitexin,isoquercitrin and quercetin had significant binding ability with 3 chymotrypsin like protease(3CLpro)and angiotensin converting enzyme 2(ACE2).In vitro studies showed that I.suzhouensis extract(ISE)may inhibit the activation of PI3K/Akt pathway and the expression level of downstream proinflammatory factors by inhibiting the activation of epidermal growth factor receptor(EGFR)in RAW264.7 cells induced by LPS.In addition,ISE was able to inhibit the activation of TLR4/NF-κB signaling pathway in NR8383 cells exposed to LPS.Overall,the network pharmacology and in vitro studies conclude that active components from I.suzhouensis have strong therapeutic potential against COVID-19 through multi-target,multi-pathway dimensions and can be a promising candidate against COVID-19.

Study on the Action Mechanism of Isodon suzhouensis Stems in the Treatment of Prostate Cancer Based on UPLC-Q-TOF-MS/MS Combined with Network Pharmacology and Molecular Docking

[Objectives]This study was conducted to explore the action mechanism of chemical components from stems of Isodon suzhouensis on prostate cancer based on UPLC-Q-TOF-MS/MS technique,network pharmacology,and molecular docking validation.[Methods]UPLC-Q-TOF-MS/MS was applied to search active components in stems of I.suzhouensis,and SwissTargetPrediction and PharmaMapper databases were used to predict their potential targets.The GeneCards database was adopted to screen the targets of prostate cancer,and the targets of the active components and the targets of prostate cancer were intersected to obtain common targets.A protein-protein interaction network was constructed,and also,an"active component-target-disease-pathway"network was constructed using Metascape for gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Moreover,AutoDock was adopted to perform molecular docking verification on key active components and core targets.[Results]Sixty three active components were screened from stems of I.suzhouensis,and they had 233 common targets with prostate cancer,mainly involving biological processes such as protein phosphorylation,response to hormones,active regulation of cell movement,cell response to lipids,and response to oxidative stress,as well as pathways in cancer,prostate cancer,micro ribonucleic acids in cancer,p53 signaling pathway,NF-κB signaling pathway and other signaling pathways,exerting anti-tumor effects.Molecular docking showed that the top 5 key active components had good binding ability with the top 5 core targets.[Conclusions]Active components from stems of I.suzhouensis can exert therapeutic effects on prostate cancer through multiple targets and pathways.

Two New ent-Kauranoids from Isodon tenuifolia

Two new ent-kauranoids, tenuifolin A (3beta,6alpha, 15beta-trihydroxy-1alpha, 7beta-diacetoxy-11beta, 16beta-epoxy-ent-kaurane) (1) and tenuifolin B (1alpha,6alpha, 11beta-trihydroxy-3beta,7beta-diacetoxy-ent-kaur-16-en-15-one) (2), together with four known compounds were isolated from the aerial parts of Isodon tenuifolia (W. W. Smith) Kudo collected from Zhongdian County, Yunnan Province, China. Their structures were determined by the spectral methods (including 2D NMR techniques).

A New Lignan from Isodon lophanthoides var. gerardianus (Labiatae)

A new lignan, together with a known one, was isolated from Isodon lophanthoides var. gerardianus [Bentham] H. Hara. The structure of the new lignan was elucidated as 1_acetoxyl_2e_piperonyl_6e_[6_methoxyl_piperonyl]_3,7_dioxabicyclo_[3,3,0]_octane mainly by 1D and 2D NMR techniques.

ent-Kaurene Diterpenoids from Isodon adenanthus

Three new ent-kaurene diterpenoids, adenanthins N, 0 and P (1-3), and four known diterpenoids, leucophyllin E (4), glabcensin C (5), adenanthin A (6), leucophyllin B (7), together with a highly unsaturated fatty acid, 9,16-dioxo-10,1 2,14-octadeca-trienoic acid (8), were isolated from Isodon adenanthus (Diels) Kudo. The structure of compound 4 was revised accordingly. Compound I showed significant cytotoxic activity against K562 cells with IC50 = 0.45 mug/mL.

Two new ent-kaurane diterpenoids from Isodon excisoides

Two new ent-kaurane diterpenoids taihangexcisoidesin A and B （1 and 2）, were isolated from the EtOAc extract of the leaves of lsodon excisoides. Their structures were determined on the basis of spectroscopic methods.

A new ent-kaurane diterpenoid from Isodon japonica

One new ent-kaurane diterpenoid,named maoyecrystal L was isolated from the EtOAc extract of the dried leaves of lsodon japonica.Its structure was established by various spectroscopic means and confirmed by X-ray crystallographic analysis.

Two new diterpenoids from Isodon serra

From the aerial part of Isodon serra, two new ent-6,7-seco-kaurane-type diterpenoids, 15α,20β-dihydroxy-6β- methoxy-6,7- seco-6,20-epoxy-1,7-olide-ent-kaur-16-ene （1） and 6α,15α-dihydroxy-20-aldehyde-6,7-seco-6,11α-epoxy-1,7-olide-ent-kaur-16- ene （2） were isolated. Their structures were elucidated by spectroscopic means.

New diterpenoids from Isodon excisoides

Two new ent-kaurane diterpenoids,taihangexcisoidesin C(1) and its acetonide,taihangexcisoidesin D(2) were isolated from the leaves of Isodon excisoides.Their structures were determined by 1D and 2D spectroscopic analysis.

New ent-kaurane-type diterpenoids from Isodon nervosus

Two new ent-kaurane-type diterpenoids,6β,7β,13α-trihydroxy-1α-acetoxy-7α,20-epoxy-ent-kaur-16-en-15-one（1）and 15β- hydroxy-6,7-seco-6,11β：6,20-diepoxy-1α,7-olide-ent-kaur-16-ene（2）were isolated from the Isodon nervosus,and the structures were elucidated by spectroscopic analysis.

Two New ent-Kaurane Diterpenoids from Isodon japonica

Two new ent-kauranoids, named maoyecrystals A (1) and B (2), were isolated from the EtOAc extract of the dried leaves of Isodon japonica (Burman f.) Hara collected in Tongbai mountains, Henan Province. Their structures were determined on the basis of spectral data, especially by 2D NMR.

A new ent-abietane diterpenoid from Isodon macrophyllus

A new ent-abietane diterpenoid, named dayecrystal C, was isolated from the EtOAc extract of the dried leaves of Isodon macrophyllus. Its structure was determined on the basis of spectroscopic methods.

Two new diterpenoids from Isodon eriocalyx

Two new diterpenoids, maoecrystal U and epi-maoecrystal P were isolated from the leaves of Isodon eriocalyx. Their structures were determined as 6 beta-acetoxy-15 beta-hydroxy-3 alpha, 20epoxy-ent-kaur-16-ene-1,7-dione 1 and 16 (s)-methoxymethyl-6 beta,7 beta-dihydroxy-7 alpha,20-epoxy-ent-kaur-2,3-ethenylene-1, 15-dione 2 respectively, by spectroscopic methods.

Two New Diterpenoids from Isodon rubescens

Two new diterpenoids taibairubescensin A (1) and B (2) have been isolated from Isodon rubescens. The structures of compound 1 and 2 were elucidated as 2 beta,3 beta-diacetoxy-11 beta,13 alpha-dihydroxy-ent-kaur- 16-en-15-one (1) and 3 beta,11 beta-diacetoxy-2 beta,6 alpha-dihydroxy-ent-kaur-16-en-15-one (2) on the basis of spectroscopic analysis.

Two New ent-Kauranoids from Isodon sculponeata

Two new ent-kaurane diterpenoids, sculponeatins L (1) and M (2), were isolated from the EtOAc extract of Isodon sculponeata. Their structures were elucidated by spectroscopic evidences. The cytotoxicities of 1 and 2 against human tumor cells K562 and T24 were tested.

A New 1β-hydroxy-ent-kaurenoid From Isodon Enanderianus

A new 1β-hydroxy-ent-kauren diterpenoid, enanderianin C1, has been isolated from the leaves of Isodon enanderianus, and its structure has been elucidated by spectroscopic evidences.

Two new 19-oxygenated ent-kaurane diterpenoids from Isodon pharicus

Two new 19-oxygenated ent-kaurane diterpenoids,pharicinins D and E(1 and 2),together with an artifact,pharicinin D acetal (3) were isolated from the leaves of Isodon pharicus.Their structures were determined by 1D and 2D NMR spectroscopic analysis. All of them were evaluated for their cytotoxicity.

Four new diterpenoids from Isodon eriocalyx var.laxiflora

Four new diterpenoids,laxiflorins S-V(1-4),bearing four different types,and one known compound,laxiflorin O(5),were isolated from Isodon eriocalyx var.laxiflora.Compound 1 was the first example of ent-kauranoids bearing a unique C_(24) carbon framework and compound 4 was the first example of 3,4-seco-ent-abietane diterpenoids from the Isodon genus.Their structures were determined by spectroscopic methods(UV,IR,MS,NMR).

DITERPENOID CONSTITUENTS OF ISODON PARVIFOLIA:STRUCTURE ELUCIDATION OF NEW DITERPENOID,PARVIFOLIN

On the basis of chemical and spectroscopic evidence,the structure of parvifolin was established as ent-7β,20-epoxy-kaurane-15-oxo-1α,6β,7β,11β,16α-pentaol.

世界香茶菜属(Isodon)植物地理分布及其药用前景展望

香茶菜属植物现有96种,基本属于东亚—非洲间断分布,中国横断山区是其现代分布中心和强烈的分化中心,也可能是其起源中心。该属植物有着丰富的药源植物,具有广阔的开发利用前景。