Antiosteoporosis Effect and Possible Mechanisms of the Ingredients of Fructus Psoraleae in Animal Models of Osteoporosis: A Preclinical Systematic Review and Meta-Analysis

Table 2

Characteristics of the included studies.

Study (year)	Species (sex, , age)	Weight	Model (method)	Anesthetic	Experimental group	Control group	Outcome index	Intergroup differences
Chai et al. (2018) [21]	Female SD rats (20/20, 6 months old)	NG	By intramuscular injection of DXM (2.5 mg/kg, biw) for 12 weeks	Chloral hydrate	By oral gavage of ISO (25 mg/kg/d, qd) after modeling lasted 12 weeks	By oral gavage of isometric NS after modeling lasted 12 weeks	(1) BMD (F-BMD; L-BMD; P-BMD; total-BMD); (2) Tb.N, BV/TV; (3) Serum ALP, TRACP, Ca, P; (4) PPAR-γ, Axin2, β-catenin protein expression	(1); (2); (3); (4)
van Luijk et al. (2013) [22]	Female SD rats (9/9, 7 weeks old)	180-220 g	By oral gavage of tretinoin (70 mg/kg/d, qd) for 2 weeks	NG	By oral gavage of ISO (100 mg/kg/d, qd) after modeling and lasted 12 weeks	By oral gavage of isometric NS after modeling and lasted 12 weeks	(1) BMD (F-BMD; L-BMD); (2) Serum Ca; (3) Serum P; (4) OCN; (5) Runx2, MMP 13 mRNA, and protein expression	(1); (2); (3); (4); (5)
Moher et al. (2009) [23]	Female SD rats (10/10, NG)	200-280 g	Bilateral oophorectomy was performed on rats	Chloral hydrate	By oral gavage of PSO (88 mg/kg/d, qd) after modeling and lasted 12 weeks	By oral gavage of isometric NS after modeling and lasted 12 weeks	(1) BMD (F-BMD; L-BMD); (2) Serum Ca, PINP, OCN; (3) Serum BMP2, VEGF; (4) PI3K, AKT, mTOR mRNA, and protein expression	(1); (2); (3); (4)
Macleod et al. (2004) [24]	Female and male Wistar rats (12/12, NG)	160-200 g	By intramuscular injection of DXM (2.5 mg/kg, biw) for 12 weeks	NG	By oral gavage of PSO (126 mg/kg/d, qd) after modeling and lasted 9 weeks	By oral gavage of isometric NS after modeling and lasted 9 weeks	(1) BMD (F-BMD); (2) Elasticity modulus, maximum load, yield load; (3) Content of bone mineral salt; (4) RANKL, OPG protein expression	(1); (2); (3); (4)
Guyatt et al. (2011) [25]	Female SD rats (10/10, 3 months old)	NG	Bilateral oophorectomy was performed on rats	NG	By oral gavage of PSO (1.26 g/kg/d, qd) after modeling and lasted 12 weeks	By oral gavage of isometric NS after modeling and lasted 12 weeks	(1) BMD (F-BMD); (2) BV/TV, Tb.Th, Tb.N, Tb.Sp; (3) Elasticity modulus, maximum load; (4) Serum PINP, CTX, ALP; (5) Serum AST, ALT; (6) Runx2, OPG, RANKL, collagen-I protein expression	(1); (2); (3); (4); (5); (6)
Balshem et al. (2011) [26]	Female SD rats (20/20, 8 months old)	200-220 g	By oral gavage of prednisone (0.005 mg/kg/d, qd) for 14 weeks	Chloral hydrate	By oral gavage of ISO (25 mg/kg/d, qd) after modeling and lasted 14 weeks	By oral gavage of isometric NS after modeling and lasted 14 weeks	(1) BMD (F-BMD; L-BMD; P-BMD; total-BMD); (2) Serum BAP, OCN, OPG, RANKL, TRACP5b; (3) CAT, SOD, MDA; (4) Elasticity modulus, bending energy, maximum load, stiffness coefficient; (5) FoxO3a, Axin2, β-catenin protein expression	(1); (2); (3); (4); (5)
Wang et al. (2021) [27]	Female ICR mice (12/11, 6 weeks old)	20-22 g	Bilateral oophorectomy was performed on rats	Chloral hydrate	By oral gavage of bakuchiol (20 mg/kg/d, qd) after modeling and lasted 8 weeks	By oral gavage of isometric NS after modeling and lasted 8 weeks	(1) BV/TV, Tb.Th; (2) Tb.N, Tb.Sp, DA; (3) Maximum load; (4) Serum OCN; (5) Serum ALP, TRACP	(1); (2); (3); (4); (5)
Heinrich et al. (2020) [14]	Female and male Wistar rats (12/12, NG)	190-210 g	By oral gavage of tretinoin (70 mg/kg/d, qd) for 2 weeks	Pentobarbital sodium	By oral gavage of PSO (0.9 g/kg/d, qd) after modeling and lasted 8 weeks	By oral gavage of isometric NS after modeling and lasted 8 weeks	(1) Of BV, Conn.D; (2) Tb.N, Tb.Sp; (3) Tb.Th; (4) Serum ACP; (5) Serum ALP, ALP/ACP	(1); (2); (3); (4); (5)
Shang et al. (2021) [28]	Female SD rats (10/10, 3 months old)	210-230 g	Bilateral oophorectomy was performed on rats	Chloral hydrate	By oral gavage of ISO (25 mg/kg/d, qd) after modeling and lasted 12 weeks	By oral gavage of isometric NS after modeling and lasted 12 weeks	(1) BMD (F-BMD; L-BMD; total-BMD); (2) Elasticity modulus, bending energy, maximum load; (3) Serum OCN, TRACP 5b; (4) OPG, RANKL protein expression	(1); (2); (3); (4)
Chen and Tang (2021) [29]	Male C57BL/6 mice (10/10, 9 weeks old)		Bilateral oophorectomy was performed on rats	NG	By oral gavage of PSO (20 mg/kg/d, qd) after modeling and lasted 6 weeks	By oral gavage of isometric NS after modeling and lasted 6 weeks	(1) Serum ALP, CTX; (2) Elasticity modulus, maximum load	(1); (2)
Zhou et al. (2020) [30]	Male C57BL/6 mice (6/6, NG)	NG	Bilateral oophorectomy was performed on rats	NG	By oral gavage of ISO (20 mg/kg/d, qd) after modeling and lasted 8 weeks	By oral gavage of isometric NS after modeling and lasted 8 weeks	(1) BV/TV, Tb.Th, Tb.N, Tb.Sp; (2) Runx2, PPAR-γ protein expression	(1); (2)
Liu et al. (2020) [31]	Female SD rats (12/12, 4 months old)		Bilateral oophorectomy was performed on rats	Pentobarbital sodium	By oral gavage of PSO (1 g/kg/d, qd) after modeling and lasted 12 weeks	By oral gavage of isometric NS after modeling and lasted 12 weeks	(1) BMD (F-BMD; L-BMD); (2) BV/TV, Tb.Th, Tb.N, Tb.Sp; (3) Elasticity modulus, maximum load; (4) Serum ALP, IL-1, IL-6	(1); (2); (3); (4)
Wang et al. (2019) [32]	Female SD rats (18/17, 3 months old)		Bilateral oophorectomy was performed on rats	Pentobarbital sodium	By oral gavage of bavachin (50 mg/kg/d, qd) after modeling and lasted 12 weeks	By oral gavage of isometric NS after modeling and lasted 12 weeks	(1) BMD (F-BMD); (2) Urinary Ca; (3) GABA, GABABRI	(1); (2); (3)
Zhang et al. (2019) [33]	Female SD rats (12/12, 4 months old)	230 g	Bilateral oophorectomy was performed on rats	Pentobarbital sodium	By oral gavage of psoralidin (16 mg/kg/d, qd) after modeling and lasted 13 weeks	By oral gavage of isometric vegetable oil after modeling and lasted 13 weeks	(1) BMD (F-BMD; L-BMD); (2) Serum estradiol, calcitonin; (3) Elasticity modulus	(1); (2); (3)
Liu et al. (2017) [34]	Female Wistar rats (8/7, 4 months old)		Bilateral oophorectomy was performed on rats	Ketamine	By oral gavage of PSO (60 mg/kg/d, qd) after modeling and lasted 12 weeks	By oral gavage of isometric NS after modeling and lasted 12 weeks	(1) BMD (F-BMD); (2) Serum estradiol; (3) Serum OCN, 1,25-dihydroxyvitamin D3, TNF-α	(1); (2); (3)
Huang and Zhou (2017) [35]	Female SD rats (10/10, 5 weeks old)	NG	Bilateral oophorectomy was performed on rats	NG	By subcutaneous injection of bakuchiol (30 mg/kg/d, qd) after modeling and lasted 6 weeks	By oral subcutaneous injection of isometric NS after modeling and lasted 6 weeks	(1) BMD (F-BMD); (2) Serum ALP, P, Ca, estradiol	(1); (2)

NG: not given; SD: Sprague-Dawley; DXM: dexamethasone; ISO: isopsoralen; PSO: psoralen; NS: normal saline; BMD: bone mineral density; F-BMD: femoral bone mineral density; L-BMD: lumbar bone mineral density; P-BMD: pelvis bone mineral density: BV/TV: bone volume over total volume; Tb.N: trabecular linear density; Tb.Th: trabecular thickness; Tb.Sp: trabecular separation; ALP: alkaline phosphatase; ACP: acid phosphatase; AST: aspartate aminotransferase; ALT: alanine aminotransferase; TRACP: tartrate-resistant acid phosphatase; Ca: calcium; P: phosphorus; PPAR-γ: peroxisome proliferator activated receptor γ; OCN: osteocalcin; Runx2: runt-related transcription factor 2; MMP 13: matrix metalloproteinase 13; PINP: N-terminal propeptide of type 1 procollagen; BMP2: bone morphogenetic protein 2; VEGF: vascular endothelial growth factor; PI3K: phosphatidylinositol 3-kinase; AKT: protein kinase B; mTOR: mammalian target of rapamycin; RANKL: receptor activator of nuclear factor-κB ligand; OPG: osteoprotegerin; CTX: C-terminal cross-linked telopeptide of type I collagen; CAT: catalase; SOD: superoxide dismutase; MDA: malondialdehyde; FoxO3a: forkhead box O3a; Conn.D: connectivity density; IL-1: interleukin-1; IL-6: interleukin-6; GABA: gamma-aminobutyric acid; GABA_BRI: gamma-aminobutyric acid receptor; qd: once a day; biw: twice a week.