Effects and Mechanisms of Five Psoralea Prenylflavonoids on Aging-Related Diseases

Table 2

Experimental summary of five psoralea prenylflavonoids improving aging-related diseases.

Classification	Model	Stimulation	Active ingredient	Dosage	Pharmacological effect	Reference number
Cardiovascular function regulation	Male SD rat aortic rings and HEK293 cells	Exposure to 60 μmol/L KCl followed by two exposures to 1 μmol/L phenylephrine to precontract rings	Isobavachalcone	50 μmol/L for aortic rings and 150 μmol/L for hTRPC3 test	(i) Caused the relaxation of precontracted aortic rings in the presence of endothelium; (ii) Isobavachalcone-induced vasodilation was blocked by NOS inhibitor L-NAME and SGC blocker ODQ; (iii) Inhibited hTRPC3 currents ()	[51]
	Platelets from fresh rabbit blood	Induction with collagen (col), arachidonic acid (AA), or platelet-activating-factor (PAF)	Isobavachalcone; Neobavaisoflavone	2, 5 or 80 nmol/L	(i) Concentration-dependent inhibition of platelet aggregation; (ii) IC50 for isobavachalcone: (col), (AA), and (PAF); IC50 for neobavaisoflavone: (col), (AA), and (PAF)	[52]
	Rat liver microsome; And HepG2 cells	Non	Bavachin; Isobavachalcone	3.0, 9.3, 30, and 8, 93.0, 300 μmol/L	(i) Inhibits ACAT activity; (ii) IC50 values were 86.0 μmol/L (bavachin) and 48.0 μmol/L (isobavachalcone) in the ACAT assay system; (iii) Isobavachalcone inhibited cholesteryl ester formation in a dose-dependent fashion with an IC50 value of 100.2 μmol/L in HepG2 cells	[7]
	HUVEC	Induction of senescent cells by hydrogen peroxide	Bavachalcone	2.5, 5, 10, 20 μmol/L	(i) Inhibited acidic beta-galactosidase activity; (ii) Induced RORα1 expression in RORα reporter luciferase activity, mRNA, and protein levels in a dose-dependent manner and enhanced the circadian amplitude of Bmal1 mRNA expression after serum shock; (iii) Suppressed senescence in human endothelial cells and mRNA expression of p16 (ink4a) (a marker of replicative senescence) and IL-1α (a proinflammatory cytokine of the senescence-associated secretory phenotype)	[57]
	HUVEC	Induction of senescent cells by hydrogen peroxide	Bavachalcone	1, 2, 5 μmol/L	(i) Inhibited acidic beta-galactosidase activity; (ii) Promoter and increased MnSOD mRNA and protein expressions; (iii) Suppressed the mitochondrial superoxide production in endothelial cells; (iv) Stimulated liver kinase B1 and AMPKα phosphorylation; (v) AMPK knockdown by shRNA-AMPK reversed the effects of bavachalcone on MnSOD	[58]
	(1) HUVECs; (2) EA.hy926 cells; (3) Rat bone marrow mesenchymal cells; (4) Male Wistar rat	Rat ischemic hindlimb model	Bavachalcone	1, 2, 5 μmol/L for cell culture and 3 mg/kg daily intragastric administration for in vivo experiments	(i) Low-dose bavachalcone administered orally for 14 days stimulated the recovery of ischemic hindlimb blood flow in rat hindlimb ischemia models; (ii) Increased circulating EPCs and promoted capillary angiogenesis; (iii) Bavachalcone treatment of rat bone marrow cells for 24 h initiated the AMP-activated protein kinase activity; (iv) Enhanced the activity of RORα1 and EPO luciferase reporter gene; (v) Bavachalcone treatment elevated EPO mRNA and protein expression in vitro and in vivo and the circulating EPO levels in rats; (vi) Bavachalcone induced differentiation of bone marrow cells into endothelial progenitor cells; (vii) Increased number of EPCs and the level of EPO in the circulation in rats	[59]
Diabetes and obese intervention	Mouse 3T3-L1 pre-adipocytes	Media containing MDI (1 μg/mL isobutyl-methylxanthine, 1 μM dexamethasone, and 1 μg/mL insulin)	Bavachin	2 μmol/L	(i) Increased the expression and secretion of adiponectin; (ii) Enhanced glucose uptake via GLUT4 translocation	[45]
	9-week-old female db/db mice	High-fat diet	Bavachinin	50 and 100 mg/kg/day	(i) Bavachinin dose-dependently induced the transcriptional activities of the mouse ligand-binding domain of PPARγ and PPARα; (ii) Ameliorates diabetes and hyperlipidaemia in db/db and in diet-induced obese mice; (iii) Decreased lipid accumulation in liver in db/db and in diet-induced obese mice; (iv) Regulates PPAR gene expression in vitro and in vivo; (v) Occupies a novel alternative binding site in addition to the canonical site of synthetic agonists of PPARγ	[80]
	3T3-L1 preadipocytes and Zebrafish	Media containing MDI (1 μg/mL isobutyl-methylxanthine, 1 μM dexamethasone, and 1 μg/mL insulin)	Isobavachalcone	2, 10, 40 μmol/L	(i) Decreased protein levels of PPARγ and C/EBPα; (ii) Gene expression levels of SREBP1c, adiponectin, ACC1, and FAS; (iii) Inhibited adipogenesis and prevents lipid accumulation in high cholesterol-diet Zebrafish larvae	[81]
Neuroprotection	BV-2 microglia	LPS; 450 μmol/L of H2O2 solution	Bavachin; Bavachinin; Bavachalcone; Isobavachalcone	1, 10, 100 μmol/L	(i) Inhibited neuroinflammation, oxidative damage, and key AD-related protein targets in BV-2 microglia; (ii) Inhibited β-secretase (BACE-1), glycogen synthase kinase 3β (GSK-3β), and acetylcholinesterase (AChE) expression; (iii) Bavachalcone and isobavachalcone exhibited strong inhibitory activities on Aβ42 aggregation	[82]
	SH-SY5Y cell; Yeast two hybrid	Aβ42	Isobavachalcone (IBC); Bavachinin (BCN)	3 μmol/L (IBC) and 30 μmol/L (BCN)	(i) Inhibited Aβ42 aggregation; (ii) Attenuated Aβ42-induced cell toxicity	[83]
	Mouse BV-2 cells; Neuro-2a cells; Male C57BL/6 mice	LPS; Preadministration of MPTP (20 mg/kg)	Isobavachalcone	0.1, 1, 5, 10, 20 μmol/L; 50 mg/kg	(i) Improved the motor, balance, and coordination abilities of PD mouse; (ii) Inhibited the activation of microglia and astrocytes and the necrosis of neurons injured by MPTP; (iii) Decreased the levels of IL-6 and IL-1β in PD mouse and of TNF-α, IL-6, IL-1β, and IL-10 in BV-2 cells stimulated by LPS; (iv) Inhibited the activation of p65 subunit in brain tissues the expression of p65 in BV-2 cells; (v) Inhibited the levels of NO and the expression of iNOS in LPS-treated BV-2 cells	[84]
	BV-2 cells; HT22 hippocampal cells	LPS (1 μg/mL); 250 μmol/L of H2O2	Isobavachalcone; Neobavaisoflavone	5, 10, 20 μmol/L	(i) Protective effects against H2O2-induced neuronal cell damage in HT22 hippocampal cells; (i) Isobavachalcone had the most significant inhibitory effect on the LPS-induced NO production in dose-dependent manners in BV-2 cells	[85]
	Human hMAO-A and hMAO-B	Non	Bavachinin	10, 20, and 40 μmol/L or 18.75, 75, and 300 μmol/L	(i) Selectively inhibited MAO-A and MAO-B activity; (ii) With IC50 of 8.82 μmol/L (hMAO-B) and 189.28 μmol/L (hMAO-A); (iii) Bavachinin C7-methoxy group had higher affinity for hMAO-B using molecular docking examination	[86]
Regulation of bone formation and absorption	HeLa cells	Non	Bavachin; Isobavachalcone; Neobavaisoflavone	10^-9, 10^-8, 10^-7, 10^-6 mol/L	(i) Activated transcription of ERα or ERβ in HeLa cells	[126]
	Female SD rats; Human osteoblasts	Ovariectomy	Bavachin	8 mg/kg/day; 0.5, 5, 50 μmol/L	(i) Increased the thickness and integrality of femur cortical bone; (ii) Increased the mRNA level of OPG in the OVX femur; (iii) Promoted the proliferation of human osteoblasts; (iv) Induced primary human osteoblast differentiation by upregulated the Wnt3a/β-catenin signaling pathway; (v) Increased ALP, Runx2, OCN, Col-I, and LRP5 expression	[127]
	MC3T3-E1cells	Non	Neobavaisoflavone	1, 5, 10, 15, 20 μmol/L	(i) Induced mineralization in MC3 T3-E1 cells; (ii) Upregulated the expression of Runx2 and Osx; (i) Induced activation of ALP, the expression of Col-I, OCN, and BSP	[130]
	Bone marrow-derived macrophages	RANKL; Vitamin D3 (10^-6 mol/L) and PGE2 (10^-8 2mol/L).	Bavachalcone	0.5, 1, 2, 5 μmol/L	(i) Inhibited osteoclastogenesis in coculture of whole bone marrow cells and calvarial osteoblasts and inhibited bone resorption; (ii) With the IC50 of approximately 1.5 μmol/L; (iii) Suppressed the expression of c-Fos and NFATc1 by RANKL; (iv) Reduced activation of MEK, ERK, and Akt by RANKL	[135]