Effects of Puerarin on Bone Density in Rats and Mice: A Meta-analysis

doi:10.12300/j.issn.1674-5817.2023.127

Abstract

Abstract:

Objective To evaluate the effects of puerarin on bone density in rats and mice through a meta-analysis. Methods The databases, including CNKI, SinoMed, Wanfang data, VIP, PubMed, EMBase, Web of Science, the Cochrane Library, and Scopus from their inception to November 6, 2023, were searched for literature on the effects of puerarin treatment on bone density in rats and mice. Inclusion criteria for the literature were randomized controlled trials with a placebo or blank control group; the subject animals were rats or mice; the intervention was puerarin; and the results included bone density measurements. Exclusion criteria included combination therapy with puerarin; lack of original research data; unpublished studies; and using mandible as the measurement site for bone density. Risks of bias were assessed using SYRCLE's RoB tool. Data analysis was conducted with Stata 16.0 and Rev Man 5.3 software. Results After applying the inclusion and exclusion criteria, a total of 429 records were identified and 42 articles covering 41 studies were ultimately included. 925 animals were involved and the data analysis results indicated that puerarin improved bone density in rats and mice compared to the control group: femur [37 studies, n=824, standardized mean difference （SMD)=2.12, 95% confidence interval (CI)=1.69-2.54, P < 0.000 1], lumbar spine (13 studies, n=271, SMD=2.25, 95% CI=1.49-3.01, P < 0.000 1), tibia (4 studies, n=95, SMD=0.94, 95% CI=0.05-1.83, P=0.04), and the whole body (4 studies, n=94, SMD=1.89, 95% CI=0.50-3.29, P=0.008), with all inter-group differences in bone density being statistically significant. Conclusion Puerarin can improve bone density in rats and mice. This study provides a valuable reference for clinical studies on the prevention and treatment of osteoporosis with puerarin.

Key words: Puerarin, Bone density, Meta-analysis, Rats, Mice

CLC Number:

Q95-22

Jinhua HU,Jingjie HAN,Min JIN,et al. Effects of Puerarin on Bone Density in Rats and Mice: A Meta-analysis[J]. Laboratory Animal and Comparative Medicine, 2024, 44(2): 149-161. DOI: 10.12300/j.issn.1674-5817.2023.127.

Figures/Tables 8

References 60

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51	王振昊, 林涨源. 葛根素联合锌治疗去势大鼠骨质疏松症的实验研究[J]. 中华全科医学, 2019, 17(9):1450-1453. DOI: 10.16766/j.cnki.issn.1674-4152.000967 .
	WANG Z H, LIN Z Y. Experimental study on treatment of osteoporosis with puerarin and zinc in ovariectomized rats[J]. Chin J Gen Pract, 2019, 17(9):1450-1453. DOI: 10.16766/j.cnki.issn.1674-4152.000967 .
52	杨占华, 郝连升, 张建新. 葛根素对骨质疏松大鼠氧化应激反应、骨代谢和骨密度的影响[J]. 中国骨质疏松杂志, 2021, 27(3):413-417. DOI: 10.3969/j.issn.1006-7108.2021.03.020 .
	YANG Z H, HAO L S, ZHANG J X. Effects of puerarin on oxidative stress response, bone metabolism, and bone mineral density in osteoporotic rats[J]. Chin J Osteoporos, 2021, 27(3):413-417. DOI: 10.3969/j.issn.1006-7108.2021.03.020 .
53	YANG Y R, CHEN D Y, LI Y L, et al. Effect of Puerarin on Osteogenic Differentiation in vitro and on New Bone Formation in vivo [J]. Drug Des Devel Ther, 2022, 16:2885-2900. DOI: 10.2147/DDDT.S379794 .
54	周昊楠, 陈远明. 葛根素防治绝经后骨质疏松症的研究进展[J]. 广西医学, 2019, 41(7):878-883. DOI: 10.11675/j.issn.0253-4304.2019.07.20 .
	ZHOU H N, CHEN Y M. Research progress of puerarin in prevention and treatment of postmenopausal osteoporosis[J]. Guangxi Med J, 2019, 41(7):878-883. DOI: 10.11675/j.issn.0253-4304.2019.07.20 .
55	LV H H, CHE T J, TANG X L, et al. Puerarin enhances proliferation and osteoblastic differentiation of human bone marrow stromal cells via a nitric oxide/cyclic guanosine monophosphate signaling pathway[J]. Mol Med Rep, 2015, 12(2):2283-2290. DOI: 10.3892/mmr.2015.3647 .
56	WANG Y, WANG W L, XIE W L, et al. Puerarin stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and PI3K/Akt activation[J]. Phytomedicine, 2013, 20(10):787-796. DOI: 10.1016/j.phymed.2013.03.005 .
57	ZHANG Y, YAN M, YU Q F, et al. Puerarin prevents LPS-induced osteoclast formation and bone loss via inhibition of Akt activation[J]. Biol Pharm Bull, 2016, 39(12):2028-2035. DOI: 10.1248/bpb.b16-00522 .
58	罗琳. 葛根素联合阿仑膦酸钠治疗绝经后骨质疏松症的效果观察[J]. 中国骨质疏松杂志, 2018, 24(7):930-933, 943. DOI: 10.3969/j.issn.1006-7108.2018.07.019 .
	LUO L. Observation on the effect of puerarin combined with alendronate in the treatment of postmenopausal osteoporosis[J]. Chin J Osteoporos, 2018, 24(7):930-933, 943. DOI: 10.3969/j.issn.1006-7108.2018.07.019 .
59	彭诗洁. 葛根素配合阿仑膦酸钠治疗绝经后骨质疏松症的效果观察[J]. 西南国防医药, 2019, 29(5):543-546. DOI: 10.3969/j.issn.1004-0188.2019.05.010 .
	PENG S J. Observation on the effect of Puerarin combined with alendronate sodium in the treatment of post-menopausal osteoporosis[J]. Med J Natl Defending Forces Southwest China, 2019, 29(5):543-546. DOI: 10.3969/j.issn.1004-0188.2019.05.010 .
60	申彦菊, 沈亚非. 葛根素联合阿仑膦酸钠对绝经后骨质疏松症患者骨密度的影响[J]. 北方药学, 2019, 16(7):93-94. DOI: 10.3969/j.issn.1672-8351.2019.07.065 .
	SHEN Y J, SHEN Y F. Effect of puerarin combined with alendronate on bone mineral density in postmenopausal osteoporosis patients[J]. J N Pharm, 2019, 16(7):93-94. DOI: 10.3969/j.issn.1672-8351.2019.07.065 .

纳入研究 Included studies	动物 Animal	动物数量/只 Animal quantity n	周期/周 Period/week	动物模型 Animal model	葛根素剂量/ (mg·kg^-1) Puerarin dosage	检测部位 Detection site
Li B (2020)^[12]	SD大鼠，雌	30	14	去卵巢骨质疏松模型	50～100 (ig qd)	股骨
Li B (2022)^[13]	SD大鼠，雌	20	14	去卵巢骨质疏松模型	100 (ig qd)	股骨
Li BB (2014)^[14]	SD大鼠，雌	6	12	去卵巢骨质疏松模型	50 (ip qod)	胫骨
Guo CJ (2019)^[9]	SD大鼠，雌	12	14	链脲佐菌素诱导糖尿病模型	50 (ig qd)	股骨
QIN CY (2023)^[15]	SD大鼠，雌	6	12	去卵巢骨质疏松模型	8 (ip qd)	股骨/腰椎
Yang D (2023)^[16]	SD大鼠，雌	29	6	去卵巢骨质疏松模型	15～30 (ip qd)	股骨/腰椎
Wang GB (2020)^[17]	SD大鼠，雌	40	6	去卵巢大鼠骨折模型	35 (ih qd)	股骨
Li H (2012)^[18]	SD大鼠，雌	48	4～20	去卵巢骨质疏松模型	50 (ih qd)	股骨
Liang H (2012)^[19]	SD大鼠，雌	18	12	去卵巢骨质疏松模型	20 (ig qd)	股骨/腰椎
Liu H (2012)^[20]	SD大鼠，雌	20	12	去卵巢骨质疏松模型	5 (ip qd)	股骨
Huang HL (2011)^[21]	SD大鼠，雌	20	10～20	去卵巢骨质疏松模型	50 (ih qd)	股骨
Xi HR(1) (2018)^[22]	Wistar大鼠，雌	24	8	/	15.4 (ig qd)	股骨/椎骨/全身
Xi HR(2) (2018)^[23]	Wistar大鼠，雌	20	12	/	15.4 (ig qd)	股骨/椎骨/全身
Yue HZ (2021)^[24]	SD大鼠，雌	24	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎
Li K (2019)^[25-26]	Wistar大鼠，雌	20	4	废用性骨质疏松模型	15.4 (ig qd)	胫骨/腰椎
Xiao L (2009)^[27]	大鼠，雌	24	12	去卵巢骨质疏松模型	50 (ih qd)	股骨/胫骨/腰椎
Xiao L (2020)^[28]	C57BL/6J小鼠，雌	10	6	去卵巢骨质疏松模型	100 (ip qod)	股骨
Lyu LT (2022)^[29]	KKAY45+C57BL/6J15小鼠	30	8	链脲佐菌素诱导糖尿病模型	1.3 (ig qd)	全身
Lyu LT (2023)^[30]	Wistar大鼠，雌	30	4	去卵巢骨质疏松模型	80 (ih qd)	股骨
Wang PP (2012)^[31]	SD大鼠，雌	8	12	去卵巢骨质疏松模型	20 (ig qd)	股骨
Tian Q (2006)^[32]	SD大鼠，雌	26	7	去卵巢骨质疏松模型	20～100 (ih qd)	股骨/腰椎
Zhou Q (2006)^[33]	SD大鼠，雌	40	8	去卵巢大鼠闭合性骨折模型	5～20 (ig qd)	股骨
Yu S (2019)^[34]	SD大鼠，雌	16	8～16	去卵巢骨质疏松模型	40 (ih qd)	股骨
Zhou SH (2010)^[35]	SD大鼠，雌	20	12	去卵巢骨质疏松模型	500 (ig qd)	腰椎
Zeng SL (2018)^[36]	SD大鼠，雌	30	12	去卵巢骨质疏松模型	50～100 (ig qd)	股骨
Zeng SL (2019)^[37]	SD大鼠	20	8	激素性股骨头坏死模型	200 (ip qd)	股骨
Yuan SY (2016)^[38]	昆明小鼠，雌	32	4	去卵巢骨质疏松模型	2～8 (qd)	股骨
Niu SZ (2019)^[39]	SD大鼠，雌	28	8	去卵巢骨质疏松模型	50 (ih qd)	股骨
Huang T (2010)^[40]	SD大鼠，雌	40	12	去卵巢骨质疏松模型	5～20 (ig qd)	股骨
Tang WK (2020)^[41]	SD大鼠，雄	15	4	股骨溶解模型	15.4～30. 8 (ip qd)	股骨
Chen WM (2021)^[42]	Wistar大鼠，雌	18	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎
Yang X (2017)^[43]	SD大鼠，雌	12	12	去卵巢骨质疏松模型	4 (ig qd)	股骨
Li XJ (2009)^[44]	Wistar大鼠，雌	15	12	去卵巢骨质疏松模型	20 (ig qd)	股骨
Xu XS (2021)^[45]	C57BL/6小鼠，雌	20	8	去卵巢骨质疏松模型	100 (ig qd)	股骨
Fang XY (2021)^[46]	大鼠，雌	16	4～12	去卵巢骨质疏松模型	50 (ig qd)	股骨
Huang YL (2004)^[47]	SD大鼠，雌	16	10	去卵巢骨质疏松模型	50 (ih qd)	股骨
Gao YM (2019)^[48]	SD大鼠，雌	20	8	/	30.82 (ig qd)	股骨/全身
Qiu ZC (2022)^[49]	SD大鼠，雌	45	5～12	去卵巢骨质疏松模型	50～150 (ig qd)	胫骨
Fang ZH (2020)^[50]	SD大鼠，雌	15	3	去卵巢骨质疏松模型	50～75 (ih qd)	股骨
Wang ZH (2019)^[51]	SD大鼠，雌	20	10	去卵巢骨质疏松模型	50 (ig qd)	股骨/腰椎
Yang ZH (2021)^[52]	SD大鼠，雌	22	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎

纳入研究 Included studies	动物 Animal	动物数量/只 Animal quantity n	周期/周 Period/week	动物模型 Animal model	葛根素剂量/ (mg·kg^-1) Puerarin dosage	检测部位 Detection site
Li B (2020)^[12]	SD大鼠，雌	30	14	去卵巢骨质疏松模型	50～100 (ig qd)	股骨
Li B (2022)^[13]	SD大鼠，雌	20	14	去卵巢骨质疏松模型	100 (ig qd)	股骨
Li BB (2014)^[14]	SD大鼠，雌	6	12	去卵巢骨质疏松模型	50 (ip qod)	胫骨
Guo CJ (2019)^[9]	SD大鼠，雌	12	14	链脲佐菌素诱导糖尿病模型	50 (ig qd)	股骨
QIN CY (2023)^[15]	SD大鼠，雌	6	12	去卵巢骨质疏松模型	8 (ip qd)	股骨/腰椎
Yang D (2023)^[16]	SD大鼠，雌	29	6	去卵巢骨质疏松模型	15～30 (ip qd)	股骨/腰椎
Wang GB (2020)^[17]	SD大鼠，雌	40	6	去卵巢大鼠骨折模型	35 (ih qd)	股骨
Li H (2012)^[18]	SD大鼠，雌	48	4～20	去卵巢骨质疏松模型	50 (ih qd)	股骨
Liang H (2012)^[19]	SD大鼠，雌	18	12	去卵巢骨质疏松模型	20 (ig qd)	股骨/腰椎
Liu H (2012)^[20]	SD大鼠，雌	20	12	去卵巢骨质疏松模型	5 (ip qd)	股骨
Huang HL (2011)^[21]	SD大鼠，雌	20	10～20	去卵巢骨质疏松模型	50 (ih qd)	股骨
Xi HR(1) (2018)^[22]	Wistar大鼠，雌	24	8	/	15.4 (ig qd)	股骨/椎骨/全身
Xi HR(2) (2018)^[23]	Wistar大鼠，雌	20	12	/	15.4 (ig qd)	股骨/椎骨/全身
Yue HZ (2021)^[24]	SD大鼠，雌	24	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎
Li K (2019)^[25-26]	Wistar大鼠，雌	20	4	废用性骨质疏松模型	15.4 (ig qd)	胫骨/腰椎
Xiao L (2009)^[27]	大鼠，雌	24	12	去卵巢骨质疏松模型	50 (ih qd)	股骨/胫骨/腰椎
Xiao L (2020)^[28]	C57BL/6J小鼠，雌	10	6	去卵巢骨质疏松模型	100 (ip qod)	股骨
Lyu LT (2022)^[29]	KKAY45+C57BL/6J15小鼠	30	8	链脲佐菌素诱导糖尿病模型	1.3 (ig qd)	全身
Lyu LT (2023)^[30]	Wistar大鼠，雌	30	4	去卵巢骨质疏松模型	80 (ih qd)	股骨
Wang PP (2012)^[31]	SD大鼠，雌	8	12	去卵巢骨质疏松模型	20 (ig qd)	股骨
Tian Q (2006)^[32]	SD大鼠，雌	26	7	去卵巢骨质疏松模型	20～100 (ih qd)	股骨/腰椎
Zhou Q (2006)^[33]	SD大鼠，雌	40	8	去卵巢大鼠闭合性骨折模型	5～20 (ig qd)	股骨
Yu S (2019)^[34]	SD大鼠，雌	16	8～16	去卵巢骨质疏松模型	40 (ih qd)	股骨
Zhou SH (2010)^[35]	SD大鼠，雌	20	12	去卵巢骨质疏松模型	500 (ig qd)	腰椎
Zeng SL (2018)^[36]	SD大鼠，雌	30	12	去卵巢骨质疏松模型	50～100 (ig qd)	股骨
Zeng SL (2019)^[37]	SD大鼠	20	8	激素性股骨头坏死模型	200 (ip qd)	股骨
Yuan SY (2016)^[38]	昆明小鼠，雌	32	4	去卵巢骨质疏松模型	2～8 (qd)	股骨
Niu SZ (2019)^[39]	SD大鼠，雌	28	8	去卵巢骨质疏松模型	50 (ih qd)	股骨
Huang T (2010)^[40]	SD大鼠，雌	40	12	去卵巢骨质疏松模型	5～20 (ig qd)	股骨
Tang WK (2020)^[41]	SD大鼠，雄	15	4	股骨溶解模型	15.4～30. 8 (ip qd)	股骨
Chen WM (2021)^[42]	Wistar大鼠，雌	18	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎
Yang X (2017)^[43]	SD大鼠，雌	12	12	去卵巢骨质疏松模型	4 (ig qd)	股骨
Li XJ (2009)^[44]	Wistar大鼠，雌	15	12	去卵巢骨质疏松模型	20 (ig qd)	股骨
Xu XS (2021)^[45]	C57BL/6小鼠，雌	20	8	去卵巢骨质疏松模型	100 (ig qd)	股骨
Fang XY (2021)^[46]	大鼠，雌	16	4～12	去卵巢骨质疏松模型	50 (ig qd)	股骨
Huang YL (2004)^[47]	SD大鼠，雌	16	10	去卵巢骨质疏松模型	50 (ih qd)	股骨
Gao YM (2019)^[48]	SD大鼠，雌	20	8	/	30.82 (ig qd)	股骨/全身
Qiu ZC (2022)^[49]	SD大鼠，雌	45	5～12	去卵巢骨质疏松模型	50～150 (ig qd)	胫骨
Fang ZH (2020)^[50]	SD大鼠，雌	15	3	去卵巢骨质疏松模型	50～75 (ih qd)	股骨
Wang ZH (2019)^[51]	SD大鼠，雌	20	10	去卵巢骨质疏松模型	50 (ig qd)	股骨/腰椎
Yang ZH (2021)^[52]	SD大鼠，雌	22	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎

纳入研究 Included studies	评估内容 Evaluation contents										评分 Score
纳入研究 Included studies	1	2	3	4	5	6	7	8	9	10	评分 Score
Li B (2020)^[12]				√		√		√	√	√	5
Li B (2022)^[13]				√		√		√	√	√	5
Li BB (2014)^[14]				√		√			√	√	4
Guo CJ (2019)^[9]				√		√			√	√	4
QIN CY (2023)^[15]						√		√	√	√	4
Yang D (2023)^[16]						√		√	√	√	4
Wang GB (2020)^[17]						√		√	√	√	4
Li H (2012)^[18]				√		√		√	√	√	5
Liang H (2012)^[19]						√		√	√	√	4
Liu H (2012)^[20]						√		√	√	√	4
Huang HL (2011)^[21]				√		√		√	√	√	5
Xi HR(1) (2018)^[22]	√			√		√		√	√	√	6
Xi HR(2) (2018)^[23]	√					√		√	√	√	5
Yue HZ (2021)^[24]	√					√		√	√	√	5
Li K (2019)^[25-26]	√					√		√	√	√	5
Xiao L (2009)^[27]				√		√		√	√	√	5
Xiao L (2020)^[28]						√			√	√	3
Lyu LT (2022)^[29]				√		√		√	√	√	5
Lyu LT (2023)^[30]	√					√		√	√	√	5
Wang PP (2012)^[31]						√		√	√	√	4
Tian Q (2006)^[32]						√		√	√	√	4
Zhou Q (2006)^[33]	√					√		√	√	√	5
Yu S (2019)^[34]						√		√	√	√	4
Zhou SH (2010)^[35]						√		√	√	√	4
Zeng SL (2018)^[36]						√		√	√	√	4
Zeng SL (2019)^[37]						√		√	√	√	4
Yuan SY (2016)^[38]				√		√		√	√	√	5
Niu SZ (2019)^[39]						√		√	√	√	4
Huang T (2010)^[40]						√		√	√	√	4
Tang WK (2020)^[41]						√		√	√	√	4
Chen WM (2021)^[42]				√		√		√	√	√	5
Yang X (2017)^[43]				√		√		√	√	√	5
Li XJ (2009)^[44]						√		√	√	√	4
Xu XS (2021)^[45]	√					√		√	√	√	5
Fang XY (2021)^[46]				√		√		√	√	√	5
Huang YL (2004)^[47]						√		√	√	√	4
Gao YM (2019)^[48]						√		√	√	√	4
Qiu ZC (2022)^[49]	√			√		√		√	√	√	6
Fang ZH (2020)^[50]				√		√		√	√	√	5
Wang ZH (2019)^[51]						√		√	√	√	4
Yang ZH (2021)^[52]	√					√		√	√	√	5

纳入研究 Included studies	评估内容 Evaluation contents										评分 Score
纳入研究 Included studies	1	2	3	4	5	6	7	8	9	10	评分 Score
Li B (2020)^[12]				√		√		√	√	√	5
Li B (2022)^[13]				√		√		√	√	√	5
Li BB (2014)^[14]				√		√			√	√	4
Guo CJ (2019)^[9]				√		√			√	√	4
QIN CY (2023)^[15]						√		√	√	√	4
Yang D (2023)^[16]						√		√	√	√	4
Wang GB (2020)^[17]						√		√	√	√	4
Li H (2012)^[18]				√		√		√	√	√	5
Liang H (2012)^[19]						√		√	√	√	4
Liu H (2012)^[20]						√		√	√	√	4
Huang HL (2011)^[21]				√		√		√	√	√	5
Xi HR(1) (2018)^[22]	√			√		√		√	√	√	6
Xi HR(2) (2018)^[23]	√					√		√	√	√	5
Yue HZ (2021)^[24]	√					√		√	√	√	5
Li K (2019)^[25-26]	√					√		√	√	√	5
Xiao L (2009)^[27]				√		√		√	√	√	5
Xiao L (2020)^[28]						√			√	√	3
Lyu LT (2022)^[29]				√		√		√	√	√	5
Lyu LT (2023)^[30]	√					√		√	√	√	5
Wang PP (2012)^[31]						√		√	√	√	4
Tian Q (2006)^[32]						√		√	√	√	4
Zhou Q (2006)^[33]	√					√		√	√	√	5
Yu S (2019)^[34]						√		√	√	√	4
Zhou SH (2010)^[35]						√		√	√	√	4
Zeng SL (2018)^[36]						√		√	√	√	4
Zeng SL (2019)^[37]						√		√	√	√	4
Yuan SY (2016)^[38]				√		√		√	√	√	5
Niu SZ (2019)^[39]						√		√	√	√	4
Huang T (2010)^[40]						√		√	√	√	4
Tang WK (2020)^[41]						√		√	√	√	4
Chen WM (2021)^[42]				√		√		√	√	√	5
Yang X (2017)^[43]				√		√		√	√	√	5
Li XJ (2009)^[44]						√		√	√	√	4
Xu XS (2021)^[45]	√					√		√	√	√	5
Fang XY (2021)^[46]				√		√		√	√	√	5
Huang YL (2004)^[47]						√		√	√	√	4
Gao YM (2019)^[48]						√		√	√	√	4
Qiu ZC (2022)^[49]	√			√		√		√	√	√	6
Fang ZH (2020)^[50]				√		√		√	√	√	5
Wang ZH (2019)^[51]						√		√	√	√	4
Yang ZH (2021)^[52]	√					√		√	√	√	5

分组 Group	纳入研究/篇 Included studies/piece	动物数量/只 Animal quantity （n）	I²值 I square	效应模型 Effect model	效应量 Effect size	效应量（95%CI） Effect size (95% confidence interval)	P值 P value
给药方式Tyeps of administration
口服Oral	18	397	75	随机效应	SMD	2.30 (1.73, 2.88)	<0.001
皮下注射Hypodermic injection	13	327	86	随机效应	SMD	1.68 (0.90, 2,45)	<0.001
腹腔注射Intraperitoneal injection	6	100	71	随机效应	SMD	2.57 (1.43, 3.70)	0.004
给药剂量Dosage
≤20 mg/kg	15	296	75	随机效应	SMD	2.00 (1.35, 2.64)	<0.001
20～50 mg/kg	23	476	80	随机效应	SMD	2.23 (1.65, 2.80)	<0.001
＞50 mg/kg	6	104	89	随机效应	SMD	2.29 (0.29, 4.28)	0.020
治疗周期Therapy period
≤8 weeks	22	487	83	随机效应	SMD	2.11 (1.50, 2.72)	<0.001
＞8 weeks	18	353	70	随机效应	SMD	2.06 (1.53, 2.58)	<0.001
动物模型Animal model
未造模Blank model	3	64	88	随机效应	SMD	3.21 (0.93, 5.49)	0.006
去卵巢Ovariectomized	30	693	79	随机效应	SMD	1.90 (1.45, 2.35)	<0.001
其他模型Other models	4	67	69	随机效应	SMD	3.28 (1.79, 4.77)	<0.001
葛根素来源Source of puerarin
单体成分Monomer component	18	396	77	随机效应	SMD	2.36 (1.76, 2.96)	<0.001
药品注射剂Drug injection	15	344	85	随机效应	SMD	1.86 (1.11, 2.61)	<0.001
其他Others	4	84	64	随机效应	SMD	1.93 (0.87, 2.99)	<0.001