Review
Copyright ©The Author(s) 2024.
World J Diabetes. Jun 15, 2024; 15(6): 1122-1141
Published online Jun 15, 2024. doi: 10.4239/wjd.v15.i6.1122
Table 1 Various medicinal plants with vasorelaxant activities and beneficial effects on diabetes
PlantVasorelaxation
Diabetes
1Ref.
Component/extract
Part
Effect
Component/extract
Part
Effect
Securigera securidaca L.Hydroalcoholic extractSeedEndothelium-dependent vasorelaxation in hyper-cholesterolemic ratsHydroalcoholic extractSeedAnti-diabetic[61,62]
Parkia biglobosaAqueous extractSeedSmooth muscle vasorelaxation via endothelium due to PGsHydromethanolic extractStem barkAnti-diabetic[63,64]
Orthosiphon stamineusEupatorin-Endothelium-intact aortic ring vasorelaxation on contraction by KCl and endothelium-denuded aortic ring vasorelaxation on contraction by PEWater extract, methanolic extractAerial partsAnti-diabetic[65,66]
Rosa damascena Mill.2-phenyl ethyl alcoholSpent flowerVasorelaxation on rat aorta and mesenteric artery without vascular endothelium effectMethanolic extractFlowerα-glucosidase inhibitor[67,68]
Eruca sativa Mill.Crude extract, fractions-Endothelium-dependent vasorelaxation on aortic rings of normotensive rats and endothelium-independent vasorelaxation on aortic rings of hypertensive ratsHexane fraction and its fatty acid-rich fractionLeafAnti-diabetic[69,70]
Echinodorus grandiflorusEthanolic extract and its butanol fractionLeafVasorelaxation on resistance vessels by releasing PGI2 and NO through B2-bradykininergic and endothelial M3- muscarinic receptors and then activating K+ channels in vascular smooth muscleEthanolic extractLeafAntiglycation[52,71]
Gynura procumbensAqueous extract, methanolic extractLeafVasorelaxation by activating muscarinic M3 receptors in the existence of endothelium and vasorelaxation on rat thoracic aorta through cholinergic pathwayLeaf extractLeafAnti-diabetic[52,72]
Garcinia cowaLeaf extractLeafVasorelaxation by activating KATP and generating prostanoids and NOCompounds 4 and 8Leafα-glucosidase inhibitor[73,74]
Bauhinia forficata LinkEthyl-acetate plus butanol fraction, kaempferitrin, kaempferolLeafVasorelaxation on the thoracic aorta of hypertensive and normotensive ratsMethanolic extractLeaf, stemHypoglycemic[39,75]
Nelumbo nuciferaExtracts of sporniodermSporniodermEndothelium-dependent vasorelaxation by activating PI3K-eNOS-sGC pathwaySeed extractSeedHypoglycemic[76,77]
Cimicifuga racemosaBlack cohosh extractVasorelaxation by way of endothelium-dependent and -independent mechanisms on pre-contracted rat thoracic aortic rings by NEExtract Ze 450Decreasing plasma glucose in ob/ob mice with diabetes[78,79]
Crocus sativus L.CrocetinEndothelium-dependent vasorelaxation through endothelial NOCrocinsStigmaDecreasing levels of glucose and increasing expression of insulin in zebrafish embryo[80,81]
Morus albaRoot bark extractRoot barkEndothelium-dependent vasorelaxation partially via NO-cGMP pathway containing TEA sensitive K+ channels activationKuwanon H, morin, morusin, oxyresveratrol, kuwanon GRoot barkα-glucosidase inhibitor[46,82]
Erigeron breviscapus Hand Mazz.ScutellarinEndothelium-independent vasorelaxation on thoracic artery rings by blocking the influx of extracellular Ca2+ as independent from VDCCsScutellarinInduces autophagy signal pathway by upregulating autophagy-related factors and blocks apoptotic signal pathway by downregulating apoptosis-related factors, and consequently relief of type 2 DC[83,84]
Vernonia amygdalinaEthanolic extractLeafVasorelaxation by upregulating NO/cGMP and PGI2 signalization pathways and modulating muscarinic and β2-adrenergic receptor levels, and Ca2+/K+ channelsLeaf extractsLeafα-amylase inhibitor[54,85]
Glycyrrhiza uralensis50% ethanolic extractVasorelaxation in endothelium-intact aortic rings pre-contracted with PE and KClGlycyrrhiza flavonoidsRootα-glucosidase inhibitor[86,87]
Salvia miltiorrhizaS. miltiorrhiza extractVasorelaxation of renal, mesenteric, and femoral arteries at low extract concentration and vasorelaxation of coronary arteries at all extract concentrations testedS. miltiorrhiza extractRootHypoglycemic[88,89]
Sophora alopecuroidesOxysophoridineVasorelaxation on thoracic aorta rings by being related to KATP and KV channelsAloperineAerial partsHypoglycemic[90,91]
Coriandrum sativumCoriander crude extractVasorelaxation on contracted rabbit aorta with PE and K+ (80 mM)Aqueous extractLeaf, stemα-glucosidase inhibitor[53,92]
Ligusticum chuanxiong Hort.Ethanolic extractRhizomeInduction of eNOS-derived NO productionEthanolic extractRhizomeAmelioration of diabetic nephropathy[58,93]
Sorbus commixta Hedl.Methanolic extractCortexVasorelaxation on vascular smooth muscle through NO-cGMP pathwayLupenone, lupeolStem barkPTP1B inhibitor[94,95]
Aronia melanocarpaConjugated cyanidins, chlorogenic acidsJuiceInducing endothelial NO production in a coronary artery by getting eNOS phosphorylation due to redox-sensitive activation of the Src/PI3-kinase/Akt pathwayJuiceHypoglycemic[96,97]
Annona squamosaEsquamosanLeafEndothelium-independent vasorelaxation on isolated rat aorta via prevention of intracellular Ca2+ increasing by blocking VDCCs and intracellular storage channels in VSMCsHexane extractHypoglycemic[98,99]
Artemisia herba albaAqueous extractVasorelaxation through endothelial NO productionAqueous extractLeaf or barkLowering blood glucose levels[100,101]
Ajuga iva (L.) Schreber (Labiatae)Aqueous extractIn vitro, NO-mediated and NO-independent vasorelaxation; ex vivo, endothelium-independent vasorelaxationLyophilized aqueous extractWhole plantHypoglycemic[102,103]
Mansoa hirsuta D.C.Ethanolic extractLeafEndothelium-dependent vasorelaxationFractionα-amylase inhibitor[104,105]
Mentha longifoliaN-butanol fractionAerial partsEndothelium-independent relaxation owing to increase of cAMP and cGMP levels by blocking diverse PDEsAnti-diabetic[40,106]
Euphorbia humifusa Willd.Total flavonoids of E. humifusaVasorelaxation on rat thoracic aorta with endothelium-dependent NO-cGMP signaling by inducing PI3K/Akt-and Ca2+-eNOS-NO signaling pathway; relaxation of VSMCs by stimulating NO-sGC-cGMP-protein kinase G signaling via L-type Ca2+ channel activity inhibitionVitexin and astragalinWhole plantAnti-diabetic[42,107]
Sophora flavescensEthanolic extractRootRelaxation of vascular smooth muscle via the endothelium-dependent NO-sGC-cGMP signaling pathwayFour minor flavonoids (1-4)Rootα-glucosidase inhibitor[108,109]
Kaempferia parvifloraEthanolic extractRhizomeVasorelaxation in a dose-dependent manner on aortic rings pre-contracted with PEAnti-diabetic[19,110]
Angelica decursiva70% ethanolic extractRootEndothelium-independent vasorelaxation via KATP channels as well as blocking of Ca2+ influx through VDCCs and ROCCsCoumarins 1-6α-glucosidase inhibitor, PTP1B inhibitor[111,112]
Hintonia latifloraH. latiflora extract, neoflavonoid coutareageninBarkVasorelaxation on aortic rings pre-contracted with NEH. latiflora extract, neoflavonoid coutareageninBarkDiminishing blood glucose[113,114]
Kaempferia galanga L.Ethyl-p-methoxycinnamateRhizomeEndothelium-independent but K+ channel-dependent vasorelaxationNovel K. galanga rhizome essential oil rich in ethyl p-methoxy cinnamateRhizomeAnti-diabetic[115,116]
Prunus mume Sieb. et Zucc.70% ethanolic extractBarkEndothelium-dependent vasorelaxation on isolated rat aortic rings through NO/sGC/cGMP and PGI2 pathway; vasorelaxation partially via KCa, KATP, KV, and Kir channels70% ethanolic extractLeafAnti-diabetic[116,117]
Bacopa monnieriSaponins (bacoside A and bacopaside I), flavonoids (luteolin and apigenin)Endothelium-intact vasorelaxation and endothelium-denuded vasorelaxationBacosineAntihyperglycemic[118,119]
Haloxylon scopariumAqueous extractVasorelaxation via Ca2+ channels blockadeDecoctate, methanolic extract, macerated methanol, ethyl; acetate extractAerial partA-glucosidase inhibitor, a-amylase inhibitor, ß-asides inhibitor[56,120]
Swietenia macrophylla King50% ethanolic extractSeedInhibiting IP3R, blocking VOCC and activating K+ channels; vasorelaxation via β2-adrenergic pathway and NO/sGC/cGMP signaling pathwaysLimonoidsFruitAnti-diabetic[48,121]
Eucalyptus globulusAqueous extractLeafDose-dependent vasorelaxation on aortic rings by inducing NO productionAmelioration of hyperglycemia[122,123]
Plumeria rubraAqueous-methanolic extractLeafConcentration-dependent vasorelaxation on PE-induced spastic contractions and K+ (80 mM)-induced spastic contractionsCompounds 1-4, 7, 8, and 16Flowerα-glucosidase inhibitor, PTP1B inhibitor[41,124]
Prunus persicaP. persica extractBranchEndothelium-dependent vasorelaxation via NO-sGC-cGMP, vascular PGI2, and muscarinic receptor transduction pathways; vasorelaxation partially through KATP, BKCa, and KV channelsAnti-diabetic[19,125]
Prunus yedoensis Matsum.Methanolic extractBarkVasorelaxation due to activation of NO production through L-Arg and NO-cGMP pathways; vasorelaxation through blockade of extracellular Ca2+ channelsP. yedoensis extractLeafAntihyperglycemic[126,127]
Xanthoceras sorbifolia BungeEthanolic extractLeafVasorelaxation on vascular smooth muscle through Akt- and SOCE-eNOS-sGC pathwaysWoodα-glucosidase inhibitor[128,129]
Passiflora edulisHydroethanolic extractFruit peelVasorelaxation on mesenteric artery rings via activation of K+ channelsAqueous extractFruit peelAnti-diabetic[129,130]
Apium graveolens L.Seed extractSeedVasorelaxation through inhibition of ROCCs and VDCCs, the release of EDHF, and activation of Kv channelsLeaf extractLeafReducing pre-prandial blood glucose levels and post-prandial blood glucose levels in pre-diabetic elderly patients[60,131]
Phyllanthus niruri L.Methyl brevifolincarboxylateLeafInhibition of NE-induced vasoconstriction via ROCCs partially mediated by (Ca2+)i decreaseAqueous extract, ethanolic extractAerial partα-glucosidase inhibitor[132,133]
Marrubium vulgareCrude extractsAerial partInhibiting KCl-induced contraction on the rat aortaAqueous extractAnti-diabetic[134,135]
Psoralea corylifolia L.P. corylifolia extract, bakuchiol, isobavachalcone, isopsoralen, psoralenSeedEndothelium-dependent vasorelaxation through NO-cGMP pathway; attenuating PE-induced vasoconstriction by inhibiting TRPC3 channels in a dose-dependent mannerCompounds 1, 2, 3, 6, 8SeedDGAT1 inhibitor, α-glucosidase inhibitor[57,136]
Ginkgo bilobaTerpenoids (bilobalide, ginkgolides A, B, and C) and flavonoids (quercetin and rutin)Concentration-dependent vasorelaxationG. biloba extractAntihyperglycemic[137,138]
Rubus chingiiEthanolic extractDried fruitVasorelaxation via Ca2+-eNOS-NO signaling in endothelial cells and later NO-sGC-cGMP-KV channel signaling in VSMCsUrsane-type triterpenesFruitPTP1B inhibitor[55,139]
Bidens pilosaNeutral extractLeafVasorelaxation and behaving as a Ca2+ antagonistB. pilosa formulationAnti-diabetic[140,141]
Allium sativumL-arginine in aged garlic extractEndothelium-dependent vasorelaxation on the aorta by inducing NO formationSilver nanoparticles BulbAnti-diabetic[142,143]
Petroselinum crispumAqueous extractAerial partVasorelaxation via VOCCs and ROCCs P. crispum extractLeafDecreasing blood glucose[144,145]
Curcuma longaCurcubisabolanin ARhizomePartially endothelium-dependent vasorelaxation by regulating NO production in vascular endothelial cells via the PI3K/Akt/eNOS signaling pathwayEnhancing postprandial serum insulin levels with ingestion of 6 g of C. longa[146,147]
Allium cepaA. cepa peel hydroalcoholic extractPeelDecreasing aortic contractions probably through depression of Ca2+ influx from extracellular to intracellular, without including endothelium, NO, cGMP, and PGsDiminishing blood glucose[148,149]
Alpinia zerumbetEssential oilLeafVasorelaxation by inhibiting both Ca2+ influx and Ca2+ release from intracellular storage; vasorelaxant effect via NOS/sGC pathwayLabdadieneRhizomeAntiglycation[43,150]
Paeonia suffruticosa Andr.1,2,3,4,6-penta-O-galloyl-beta-d-glucoseRoot cortexConcentration-dependent vasorelaxation on rat aorta pre-contracted with PEExtract of moutan cortexRootImproving inflammation in AGEs-induced mesangial cell dysfunction and high-glucose-fat diet and STZ-induced DN rats[151,152]
Nigella sativaSeed extractSeedEndothelium-independent vasorelaxation on contraction stimulated by PE and KCl via inhibition of extracellular Ca2+ influx, KATP channels, and IP3-mediated receptorsCrude aqueous extractSeedIn vitro, suppressing electrogenic intestinal absorption of glucose directly; in vivo, ameliorating both body weight and glucose tolerance after chronic oral administration in rats[153,154]
Myrciaria cauliflora BergHydroalcoholic extractFruit peelEndothelium-dependent vasorelaxation via NO/sGC/cGMP pathwayM. cauliflora extractLyophilized fruitHypoglycemic[155,156]
Morus bombycis Koidzumi100% ethanolic extractRoot barkVasorelaxation on isolated rat aortic preparations2,5-dihydroxy-4,3-di(beta-D-glucopyranosyloxy)-trans-stilbeneRootHypoglycemic[157,158]
Humulus lupulus L.Aqueous hop extractVasorelaxation through NOS activation, COX products, and Ca2+ pathways in both male and female ratsXanthohumolα-glucosidase inhibitor[159]
Sesamum indicum L.Petroleum ether soluble fraction of root extractRootEndothelium-dependent vasorelaxationDecreasing fasting blood sugar[160,161]
Hibiscus sabdariffaHibiscus acidVasorelaxation by depression of intracellular Ca2+ influx through VDCCsEthyl acetate extract, ethanolic extract, aqueous extractFlowerAnti-diabetic[162,163]
Jasminum sambacHydroalcoholic leaf extractLeafVasorelaxation completely on endothelium-intact rabbit aorta contracted with PE; vasorelaxation partially on endothelium-intact rabbit aorta contracted with NEPolyphenol extractLeafPreventing and having a therapeutic effect on DC[59,164]
Hancornia speciosa GomesEthanolic extractLeafNO- and endothelium-dependent vasorelaxation on rat aortic preparations through PI3K activationAqueous extractLatexHypoglycemic[165,166]
Pseuderanthemum
palatiferum
Water extractLeafVasorelaxation via partially vascular endothelium not with NO production and muscarinic receptor activation80% ethanolic leaf extractLeafHypoglycemic[167,168]
Terminalia superbaMethylene chloride extract, methylene chloride-methanol extractStem barkVasorelaxation partially via depression of extracellular Ca2+ influx and/or suppression of intracellular Ca2+ releasing in VSMCs; vasorelaxation via endothelial NOMethylene chloride-methanol extractLeafAnti-diabetic[49,169]
Guazuma ulmifoliaProcyanidin fractionBarkVasorelaxation through endothelium-related factors, including NOAqueous extractAnti-diabetic[170,171]
Persea americana Mill.Aqueous leaf extractLeafVasorelaxation through endothelial NO production and releasingHydroalcoholic extractLeafAnti-diabetic[172,173]
Capparis aphyllaCrude extractAerial partEndothelium-dependent vasorelaxation partially via atropine-sensitive NO pathway; endothelium-independent vasorelaxation partially via the Ca2+ channel blocking activityMethanolic extract, active fractionStemDecreasing blood glucose levels[174,175]
Rheum undulatumPiceatannol in rhizome extractRhizomeVasorelaxation through endothelium-dependent NO signaling pathwayE-viniferin, piceatannol, and δ-viniferin in methanolic extractRhizomePTP1B inhibitor[176,177]
Globularia alypumG. alypum extractVasorelaxation due to EDHF via endothelial muscarinic receptor activationMethanolic extract, water extractLeafReducing fasting blood glucose[178,179]
Gmelina arboreaHexane extractLeafConcentration-dependent vasorelaxation on isolated rat aortaAqueous extractBarkAntihyperglycemic[50,180]
Coscinium fenestratumC. fenestratum extractEndothelium-dependent and -independent vasorelaxation on isolated aortic rings precontracted with PE and KClAlcoholic stem extractStemAnti-diabetic[181,182]
Myrtus communis L.Crude methanolic extractAerial partVasorelaxation on isolated rabbit aorta preparations contracted with PE and K+Volatile oilHypoglycaemic[183,184]
Thymus linearis Benth.N-butanolic fractionAerial partEndothelium-independent vasorelaxation due to increase in cAMP and cGMP via inhibition of several PDEsEthyl acetate extract, combined extractAerial partΑ-amylase inhibitor[185,186]
Vitex agnus-castusV. agnus-castus extractFruitEndothelium-dependent vasorelaxation via NO/cGMP and PGs production in the aortaHydroalcoholic extractDesiccated fruitHypoglycemic[51,187]
Anogeissus leiocarpusAqueous extractTrunk barkEndothelium-dependent NO-mediated vasorelaxation on porcine coronary arteries via redox-sensitive Src/PI3-kinase/Akt pathway-dependent activation of eNOSSupernatant fraction, total extractRootAnti-diabetic[188,189]
Zanthoxylum armatum DCTambulin in methanolic extractFruitInfluencing directly vascular smooth muscle through cAMP and/or cGMP-related relaxing pathwaysFruit, bark, and leaf extractsFruit, bark, and leafAnti-diabetic[190,191]
Cymbopogon martiniiCrude methanolic extractLeafPartial vasorelaxation on isolated rabbit aortic preparations contracted with PE and K+Α-glucosidase inhibitor[192,193]
Moringa oleiferaM. oleifera leaf extractLeafEndothelium-dependent vasorelaxation through EDHF-mediated hyperpolarization; endothelium-independent vasorelaxation due to inhibition of extracellular Ca2+ influx through VOCCs and ROCCs and suppression of sarcolemmal Ca2+ releasing through IP3R Ca2+ channelsMethanolic extractPodsAnti-diabetic[194,195]
Dalbergia odorifera T. ChenButeinVasorelaxation on rat aorta; the novel cAMP-specific PDE inhibitor; vasorelaxant action related intact endotheliumCompounds in ethyl acetate soluble fractionHeartwoodα-glucosidase inhibitor[196,197]
Coptis chinensisBerberineDecreasing expression of miR-133a; enhancing BH4 levels and production of NOPolysaccharideAnti-diabetic[38,198]
Angelica keiskeiXanthoangelol, 4-hydroxyderricin, xanthoangelol E and F in EtOAc-soluble fraction, xanthoangelol B in EtOAc-soluble fractionRootBlocking PE-induced vasoconstriction through EDRF/NO synthesis and/or attenuation of PE-induced (Ca2+)i increase; blocking PE-induced vasoconstriction by reducing (Ca2+)i increase and directly inhibiting smooth muscle contractionFlavonoid-rich ethanolic extractLeafHypoglycemia[199,200]
Scutellaria baicalensis GeorgiBaicalinVasorelaxation on the mesenteric artery by stimulating BKCa channels and blocking VDCCs with endothelium-independent mechanisms, moreover by inducing cGMP/PKG and cAMP/PKA pathwaysRoot polysaccharideRootα-amylase inhibitor, α-glucosidase inhibitor[201,202]
Ocimum gratissimumEssential oilDose-dependent vasorelaxation on resistance blood vessels of rat mesenteric vascular beds completely via NO; dose-dependent vasorelaxation on rat aorta partially mediated by NOChicoric acid in leaf extractLeafHypoglycemic[203,204]
Table 2 Familial classification of various medicinal plants with vasorelaxant activities and beneficial effects on diabetes
Fabaceae
Lamiaceae
Rosaceae
Brassicaceae
Myrtaceae
Securigera securidaca L.; Parkia biglobosa; Bauhinia forficata Link; Dalbergia odorifera T. Chen; Glycyrrhiza uralensis; Sophora alopecuroides; Sophora flavescensi; Psoralea corylifolia L.Orthosiphon stamineus; Thymus linearis Benth; Gmelina arborea; Vitex agnus-castus; Ocimum gratissimum; Marrubium vulgare; Salvia miltiorrhiza; Mentha longifolia; Scutellaria baicalensis Georgi; Ajuga iva (L.) SchreberRosa damascena Mill.; Sorbus commixta Hedl.; Aronia melanocarpa; P. mume Sieb. et Zucc.; Prunus persica; P. yedoensis Matsum.; Rubus chingiiEruca sativa Mill.Eucalyptus globulus; Myrciaria cauliflora Berg; Myrtus communis L.
AlismataceaeAsteraceaeNelumbonaceaeClusiaceaeApocynaceae
Echinodorus grandiflorusGynura procumbens; E. breviscapus Hand Mazz.; Vernonia amygdalina; Artemisia herba alba; Bidens pilosaNelumbo nuciferaGarcinia cowaPlumeria rubra; Hancornia speciosa Gomes
IridaceaeMoraceaeApiaceaeAnnonaceaeSapindaceae
Crocus sativus L.Morus alba; Morus bombycis KoidzumiCoriandrum sativum; Angelica decursiva; Apium graveolens L.; Petroselinum crispum; L. chuanxiong Hort.; Angelica keiskeiAnnona squamosalXanthoceras sorbifolia Bunge
PoaceaeBignoniaceaeEuphorbiaceaeZingiberaceaePassifloraceae
Cymbopogon martiniiMansoa hirsuta D.C.E. humifusa Willd.Kaempferia parviflora; Kaempferia galanga L.; Curcuma longa; Alpinia zerumbetPassiflora edulis
RubiaceaePlantaginaceaeAmaranthaceaeMeliaceaePhyllanthaceae
Hintonia latifloraBacopa monnieri; Globularia alypumHaloxylon scopariumS. macrophylla KingPhyllanthus niruri L.
MoringaceaeGinkgoaceaeAmaryllidaceaePaeoniaceaeRanunculaceae
Moringa oleiferaGinkgo bilobaAllium sativum; Allium cepaP. suffruticosa Andr.Nigella sativa; Coptis chinensis; Cimicifuga racemosa
CannabaceaePedaliaceaeMalvaceaeOleaceaeAcanthaceae
Humulus lupulus L.Sesamum indicum L.Hibiscus sabdariffa; Guazuma ulmifoliaJasminum sambacP. palatiferum
CombretaceaeLauraceaeCapparaceaePolygonaceaeMenispermaceae
Terminalia superba; Anogeissus leiocarpusPersea americana Mill.Capparis aphyllaRheum undulatumCoscinium fenestratum
Rutaceae
Z. armatum DC