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Table 3 Pharmacological effects of monomers derived from natural medicines for PAH

From: Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension

Natural medicines Efficacy Cell lines/animals Dose/concentration Mechanisms of action Refs
Ligustrazine Regulating calcium homeostasis SD rats 100 mg/kg (p.o.) HIF-1α↓, basal [Ca2+]i↓, SOCE↓, TRPC1↓, TRPC6↓ [75]
Regulating vasomotor factors PAH patient 120 mg/day (i.v.) ET-1↓, NO↑ [76]
Tetrandrine Inhibiting oxidative stress SD rats 50 mg/kg (i.p.) iNOS↓, PKG-1↑, SOD↑, MDA↓ [77, 78]
Breviscapine Regulating vasomotor factors PAH patient 50 mg/day (i.v.) ET-1↓, NO↑ [79]
Puerarin Inhibiting PASMC proliferation SD rats 80 mg/kg (p.o.) LC3B-II↓, BECN-1↓, ATG5↓, SQSTM1↑ [80]
Inhibiting oxidative stress HPAECs 30 µmol/L BMPR2/Smad↑, PPARγ/PI3K/Akt↑ [81]
Genistein Inhibiting oxidative stress PASMCs 50 µmol/L ROS↓, SOD↑, H2O2 [82]
Baicalein Inhibiting inflammatory response SD rats 100 mg/kg (p.o.) TNF-α↓, IL-1β↓, IL-6↓ [83]
Inhibiting inflammatory response Wistar rats 100 mg/kg (p.o.) NF-κB p65↓, BMPR2↑, BMP-4↑, BMP-9↑, Smad1/5/8↑ [84]
Quercetin Inhibiting PASMC proliferation PASMCs 60 µmol/L MMP2↓, MMP9↓, Bax/Bcl-2↑; Cyclin B1↓ [85]
Isoquercitrin Inhibiting PASMC proliferation PASMCs 30 µmol/L PCNA↓, α-SMA↓, Cyclin D1↓, CDK4↓, p-PDGF-Rβ↓ [86]
Dihydromyricetin Inhibiting PASMC migration PASMCs 100 mg/kg MMP9↓, p-STAT3↓ [87]
Danshensu Inhibiting PASMC proliferation PASMCs 30 µg/mL Regulating TGF-β-smad3 pathway [88]
Salvianolic acid A Improving pulmonary vascular remodelling SD rats 3 mg/kg (p.o.) AST↓, ALT↓, NT-proBNP↓, RVSP↓, ET-1↓, BMPR2↑, Smad1/5↑ [89]
STS Inhibiting PASMC proliferation PASMCs 10 ng/mL mTOR↓, eIF2α↓, c-myc↓ [90]
Activating BMPR2 signalling pathway SD rats 30 mg/kg (i.p.) BMPR2↑, CAV1↑, p-smad1/5/8↑ [91]
Resveratrol Inhibiting inflammatory response SD rats 40 mg/kg (p.o.) TNF-α↓, IL-1β↓, IL-6↓ [92]
Dihydroartemisinin Inhibiting HPAEC proliferation HPAECs 60 µmol/L ROS↓, NO↑, SOD↑ [93]
Triptolide Inhibiting MMP pathways SD rats 0.25 mg/kg (i.p.) MMP2↓, MMP9↓ [94]
Inhibiting PASMC proliferation SD rats 0.25 mg/kg (i.p.) PCNA↓, caspase-3↑ [95]
Paclitaxel Inhibiting autophagy SD rats 5 mg/kg (i.v.) p-FoxO1↓, RVSP↓, LC3A↓, LC3B↓ [96]
Glycyrrhizin Inhibiting inflammatory response SD rats 50 mg/kg (i.p.) HMGB1↓, survival rate↑, ET-1↓ [98]
Thymoquinone Inhibiting pulmonary arterial remodelling SD rats 16 mg/kg (p.o.) PCNA↓, α-SMA↓, MMP2↓, Bax/Bcl-2↑, cleaved caspase-3↑ [99]
Hydroxysafflor yellow A Inhibiting PASMC proliferation Wistar rats 10 mg/kg (i.p.) RVHI↓, PCNA↓ [101]
Salidroside Promoting apoptosis BALB/C mice 32 mg/kg (p.o.) Bax/Bcl-2↑, caspase 9↑, cleaved caspase-3↑, A2aR↑ [102]
Inhibiting PASMC proliferation PASMCs 500 µmol/L AMPKα1↑, P53↑, P27↓, P21↓, PCNA↓, caspase-3↑ [103]
Polydatin Inhibiting PASMC proliferation PASMCs 100 ng/mL PCNA↓, α-SMA↓ [104]
Icariin Regulating vasomotor factors SD rats 40 mg/kg (p.o.) NO↑, eNOS↑, cGMP↑, PDE5↓ [105]
Arctigenin Inhibiting inflammatory response SD rats 50 mg/kg (i.p.) NLRP3↓, IL-1β↓ [106]
Praeruptorin A Inhibiting PASMC proliferation PASMCs 20 µmol/L Basal Ca2+↓, SOCE↓ [108]
Astragalus polysaccharides Inhibiting inflammatory response SD rats 200 mg/kg eNOS↑, NO↑, TNF-α↓, IL-1β↓, IL-6↓ [109]