Wuzi Yanzong prescription (五子衍宗丸) from Traditional Chinese Medicine for male infertility: a narrative review

doi:10.19852/j.cnki.jtcm.20221214.001

Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (2): 416-428.DOI: 10.19852/j.cnki.jtcm.20221214.001

Wuzi Yanzong prescription (五子衍宗丸) from Traditional Chinese Medicine for male infertility: a narrative review

CHEN Zhimin¹, AO Mingyue¹, LIAO Yujiao¹, YU Lingying¹, YANG Zhuo², HU Lin¹, LI Wenbing³, HU Changjiang¹(), GAO Yongxiang¹()

1 Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2 Department of Pharmacy, Chengdu Women’s & Children’s Central Hospital, Chengdu 610074, China
3 Institute of Qinghai-tibetan Plateau, Southwest Minzu University, Chengdu 610041, China

Received:2021-11-19 Accepted:2022-03-17 Online:2023-04-15 Published:2023-03-14
Contact: Prof. HU Changjiang, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. 654460129@qq.com;Prof. GAO Yongxiang, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.drgaoyx@cdutcm.edu.cn. Telephone: +86-15528352916
Supported by:
National Natural Science Foundation of China: Study on the Mechanism of “Stir-frying with Salt-water Into the Kidney, Kidney Governing Reproduction” Based on Composition of Wuzi Yanzong Wan Before and After Salted(81773899);Fellowship of China Postdoctoral Science Foundation: Study on the Material Basis and Mechanism of Huangsi Yujin Vinegar for “Soothing the Liver and Relieving Pain”(2020M673567XB);Key R & D projects of Science & Technology Department of Sichuan Province: National Intangible Cultural Heritage-Protection, Inheritance and Development of Sichuan Traditional Chinese Medicine Processing Skills(2020YFS0359);Xinglin Scholar Research Premotion Project of Chengdu University of TCM: Research on the Scientific Connotation of Wuzi Yanzong Pill Processing Efficiency Enhancement Based on “Composition Target Path”(BSH2019026);Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China: Study on the Scientific Connotation of Wuzi Yanzong Pill Processing(2020BSH012)

Abstract

Abstract:

Wuzi Yanzong prescription (WYP), as a classical prescription for male infertility with kidney essence deficiency, is composed of Gouqizi (Fructus Lycii), Tusizi (Semen Cuscutae), Wuweizi (Fructus Schisandrae Chinensis), Fupenzi (Fructus Rubi Chingii) and Cheqianzi (Semen Plantaginis). It has been used for hundreds of years in the treatment of male infertility, known as “the first prescription of ancient and modern seeds”, with convincing clinical evidence. At present, more than 100 chemical compounds have been isolated from WYP, including polysaccharide, fatty acids, flavonoids, phenylpropanoids, organic acids, alkaloids, terpenoids, etc. Pharmacological and clinical studies show that WYP has an obvious effect on reproductive system diseases, especially male infertility, which has a very wide application prospect. It also has effects on the nervous system, inhibiting liver injury, lowering blood sugar and blood lipid, anti-aging, improving immunity, resisting hypoxia and fatigue effects. This study reviewed the chemical constituents, quality control, pharmacology, and clinical application of WYP. There is no doubt about the clinical value of WYP, but its quality control system is not perfect, pharmacological mechanism is not fully explained, and clinical applications need to be reevaluated. Therefore, the follow-up researches should proceed from the theory of Traditional Chinese Medicine (TCM) and clinical applications, further explain the theoretical connotation, reveal the mechanism of action, and provide the basis for the secondary development of classic famous prescriptions. In addition, WYP is mostly used in combination with western medicines besides being used alone. Whether it can improve the efficacy and reduce side effects will also be a meaningful research direction in the future.

Key words: quality control, pharmacology, clinical applications, chemical constituents, Wuzi Yanzong prescription, review

CHEN Zhimin, AO Mingyue, LIAO Yujiao, YU Lingying, YANG Zhuo, HU Lin, LI Wenbing, HU Changjiang, GAO Yongxiang. Wuzi Yanzong prescription (五子衍宗丸) from Traditional Chinese Medicine for male infertility: a narrative review[J]. Journal of Traditional Chinese Medicine, 2023, 43(2): 416-428.

Figures/Tables 7

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Dosage form	Control ingredients and medicinal materials	Developing solvent	Reference
Wuzi Yanzong Wan	Scopoletin	Petroleum ether (30-60)-ethyl formate-formic acid (20:20:0.1)	Chinese Pharmacopoeia (2020)
	Wuweizi (Fructus Schisandrae Chinensis), Schisandrin	Methylbenzene-ethyl acetate (6:4)
	Gouqizi (Fructus Lycii)	Ethyl acetate-trichloromethane-formic acid (3:2:1)	Xin Yao Zhuan Zheng Biao Zhun
	Tusizi (Semen Cuscutae)	Petroleum ether (30-60)-butyl acetate-butanone-methyl alcohol-water (15:25:3:7:1)
	Schisandrin A	Methylbenzene-ethyl acetate (9:1)
	Gallic acid	Methylbenzene-ethyl acetate-formic acid (6:3:1)
Wuzi Yanzong Pian	Tusizi (Semen Cuscutae)	Methylbenzene-ethyl acetate-formic acid (5:5:3)	Chinese Pharmacopoeia (2020)
	Scopoletin	Petroleum ether (30-60)-ethyl formate-formic acid (20:20:0.1)
	Wuweizi (Fructus Schisandrae Chinensis), Gomisin A	Methylbenzene-ethyl acetate (6:4)
Wuzi Yanzong Ruanjiaonang	Gouqizi (Fructus Lycii)	Petroleum ether (60-90)-ethyl acetate-formic acid (13:5:1)	Xin Yao Zhuan Zheng Biao Zhun
	Tusizi (Semen Cuscutae)	Methylbenzene-ethyl acetate-formic acid (5:5:3)
	Schisandrin A, Schisandrin	Petroleum ether (30-60)-ethyl acetate-formic acid (15:5:1)	Xin Yao Zhuan Zheng Biao Zhun
	Gouqizi (Fructus Lycii)	Acetate-trichloromethane-formic acid (2:3:0.1)
	Quercetin	Acetate-trichloromethane-formic acid (26:13:5)
Wuzi Yanzong Jiaonang	Gouqizi (Fructus Lycii)	Trichloromethane-ethyl acetate-benzene-formic acid (5:6:3:1)	Xin Yao Zhuan Zheng Biao Zhun
	Wuweizi (Fructus Schisandrae Chinensis)	Petroleum ethe (30-60)-ethyl acetate-formic acid (15:5:1)
Wuzi Yanzong Koufuye	Gouqizi (Fructus Lycii)	Trichloromethane-ethyl acetate-benzene-formic acid (5:6:3:1)	Zhong Yao Cheng Fang Zhi Ji

Dosage form	Control ingredients and medicinal materials	Developing solvent	Reference
Wuzi Yanzong Wan	Scopoletin	Petroleum ether (30-60)-ethyl formate-formic acid (20:20:0.1)	Chinese Pharmacopoeia (2020)
	Wuweizi (Fructus Schisandrae Chinensis), Schisandrin	Methylbenzene-ethyl acetate (6:4)
	Gouqizi (Fructus Lycii)	Ethyl acetate-trichloromethane-formic acid (3:2:1)	Xin Yao Zhuan Zheng Biao Zhun
	Tusizi (Semen Cuscutae)	Petroleum ether (30-60)-butyl acetate-butanone-methyl alcohol-water (15:25:3:7:1)
	Schisandrin A	Methylbenzene-ethyl acetate (9:1)
	Gallic acid	Methylbenzene-ethyl acetate-formic acid (6:3:1)
Wuzi Yanzong Pian	Tusizi (Semen Cuscutae)	Methylbenzene-ethyl acetate-formic acid (5:5:3)	Chinese Pharmacopoeia (2020)
	Scopoletin	Petroleum ether (30-60)-ethyl formate-formic acid (20:20:0.1)
	Wuweizi (Fructus Schisandrae Chinensis), Gomisin A	Methylbenzene-ethyl acetate (6:4)
Wuzi Yanzong Ruanjiaonang	Gouqizi (Fructus Lycii)	Petroleum ether (60-90)-ethyl acetate-formic acid (13:5:1)	Xin Yao Zhuan Zheng Biao Zhun
	Tusizi (Semen Cuscutae)	Methylbenzene-ethyl acetate-formic acid (5:5:3)
	Schisandrin A, Schisandrin	Petroleum ether (30-60)-ethyl acetate-formic acid (15:5:1)	Xin Yao Zhuan Zheng Biao Zhun
	Gouqizi (Fructus Lycii)	Acetate-trichloromethane-formic acid (2:3:0.1)
	Quercetin	Acetate-trichloromethane-formic acid (26:13:5)
Wuzi Yanzong Jiaonang	Gouqizi (Fructus Lycii)	Trichloromethane-ethyl acetate-benzene-formic acid (5:6:3:1)	Xin Yao Zhuan Zheng Biao Zhun
	Wuweizi (Fructus Schisandrae Chinensis)	Petroleum ethe (30-60)-ethyl acetate-formic acid (15:5:1)
Wuzi Yanzong Koufuye	Gouqizi (Fructus Lycii)	Trichloromethane-ethyl acetate-benzene-formic acid (5:6:3:1)	Zhong Yao Cheng Fang Zhi Ji

Dosage form	Determination of components	Detection method (wavelength)	Reference
Wuzi Yanzong Wan	Hyperoside, Gomisin A	HPLC (360, 250 nm)	Chinese Pharmacopoeia (2020)
	Hyperoside, Kaempferide, Schisandrin, Schisandrin A, Schisandrin B	HPLC/PDA (360, 250 nm)	23
	Hyperoside, Quercitrin, kaempferol-3-rutinoside, Schisandrin, Schisandrin A, Schisandrin B	HPLC/PDA (254 nm)	24
	Betaine	HPLC (192 nm)	25
	Scopoletin	HPLC-FLD (343 nm,458 nm)	26
Wuzi Yanzong Pian	Hyperoside, Gomisin A	HPLC (360，250 nm)	Chinese Pharmacopoeia (2020)
	Schisandrin A	HPLC (230 nm)	Xin Yao Zhuan Zheng Biao Zhun
Wuzi Yanzong Jiaonang	Schisandrin	HPLC (254 nm)	Xin Yao Zhuan Zheng Biao Zhun
Wuzi Yanzong Keli	Rutin	HPLC (254 nm)	Xin Yao Zhuan Zheng Biao Zhun

Dosage form	Determination of components	Detection method (wavelength)	Reference
Wuzi Yanzong Wan	Hyperoside, Gomisin A	HPLC (360, 250 nm)	Chinese Pharmacopoeia (2020)
	Hyperoside, Kaempferide, Schisandrin, Schisandrin A, Schisandrin B	HPLC/PDA (360, 250 nm)	23
	Hyperoside, Quercitrin, kaempferol-3-rutinoside, Schisandrin, Schisandrin A, Schisandrin B	HPLC/PDA (254 nm)	24
	Betaine	HPLC (192 nm)	25
	Scopoletin	HPLC-FLD (343 nm,458 nm)	26
Wuzi Yanzong Pian	Hyperoside, Gomisin A	HPLC (360，250 nm)	Chinese Pharmacopoeia (2020)
	Schisandrin A	HPLC (230 nm)	Xin Yao Zhuan Zheng Biao Zhun
Wuzi Yanzong Jiaonang	Schisandrin	HPLC (254 nm)	Xin Yao Zhuan Zheng Biao Zhun
Wuzi Yanzong Keli	Rutin	HPLC (254 nm)	Xin Yao Zhuan Zheng Biao Zhun

Dosage form	Detection Method (Wavelength)	Total chromatographic peak number	Chromatographic peak identification	Reference
Wuzi Yanzong Wan	HPLC (250 nm)	5	Hyperoside, Verbascoside, Kaempferide, Schisandrin	Chinese Pharmacopoeia (2020)
	HPLC (254 nm)	18	Hyperoside, Isoquercitrin, Kaempferol, Verbascoside, Astragalin, Gomisin A	27
	HPLC-DAD (254 nm)	24	Gallic acid, geniposidic acid, Chlorogenic acid, Hyperoside, Isoquercitrin, Verbascoside, Kaempferol-3-rutinoside, Isoverbascoside	28
	HPLC/PDA (360, 250 nm)	11	Chlorogenic acid, Hyperoside, Quercetin, Kaempferide,Verbascoside, Astragalin, Schisandrin, Gomisin A, Schisandrin A, Schisandrin B	23
	HPLC/PDA (254 nm)	10	Chlorogenic acid, Hyperoside, Verbascoside, Kaempferol, Schisandrin, Schisandrin A, Schisandrin B, Astragalin, Quercetin	29

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Wuzi Yanzong prescription (五子衍宗丸) from Traditional Chinese Medicine for male infertility: a narrative review

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References 90.

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Chemical component	Source	Type	Reference
Flavonoids	Tusizi (Semen Cuscutae)	41	6
	Gouqizi (Fructus Lycii)	-	7
	Wuweizi (Fructus Schisandrae Chinensis)	14	8
	Fupenzi (Fructus Rubi Chingii)	16	9
	Cheqianzi (Semen Plantaginis)	11, including flavonoids, flavonols and their glycosides	10-11
Polysaccharides	Tusizi (Semen Cuscutae)	Including neutral heteropolysaccharide, H3 acid polysaccharide	6
	Gouqizi (Fructus Lycii)	It's made up of six monosaccharides	12
	Wuweizi (Fructus Schisandrae Chinensis)	The polysaccharide content is 85.56%, which is composed of rhamnose, galactose, arabinose and glucose	13
	Cheqianzi (Semen Plantaginis)	It contains 10%-30% arabinose, xylose, mannose and galactose (5.6:9.4:1.3:1)	10-11
Phenylethanoid glycosides	Cheqianzi (Semen Plantaginis)	20，it is composed of caffeic acid, phenyl glycogen and glycogen	10-11
Iridoids	Cheqianzi (Semen Plantaginis)	22	10-11
Steroids	Tusizi (Semen Cuscutae)	6, β-sitosterol, carotenoside, 7-α-hydroxy sitosterol, rape oleosterol, stigmastol, △ 5-oatmasterol	6
	Fupenzi (Fructus Rubi Chingii)	6	9,14
	Cheqianzi (Semen Plantaginis)	-	10
Terpenoids	Tusizi (Semen Cuscutae)	9	6
	Wuweizi (Fructus Schisandrae Chinensis)	9	8
	Fupenzi (Fructus Rubi Chingii)	19	14
	Cheqianzi (Semen Plantaginis)	-	10
Alkaloids	Tusizi (Semen Cuscutae)	4	6
	Gouqizi (Fructus Lycii)	Betaine	15
	Fupenzi (Fructus Rubi Chingii)	7	14
	Cheqianzi (Semen Plantaginis)	-	10,12
Amino acid	Tusizi (Semen Cuscutae)	15	6
	Gouqizi (Fructus Lycii)	18	12
	Wuweizi (Fructus Schisandrae Chinensis)	16	16
	Cheqianzi (Semen Plantaginis)	-	11
Acids	Tusizi (Semen Cuscutae)	18	6
	Gouqizi (Fructus Lycii)	18%-22%	17
	Wuweizi (Fructus Schisandrae Chinensis)	14	8
	Fupenzi (Fructus Rubi Chingii)	8	14
	Cheqianzi (Semen Plantaginis)	5	18
Trace elements	Tusizi (Semen Cuscutae)	Ca, Mg, Fe, Mn, Zn, Pb, Sn, etc.	6
	Wuweizi (Fructus Schisandrae Chinensis)	K, Ca, Zn, Fe, etc.	8
	Cheqianzi (Semen Plantaginis)	Fe, Mg, Al, Zn, etc.	11
Lignans	Tusizi (Semen Cuscutae)	29	6
	Wuweizi (Fructus Schisandrae Chinensis)	31 (8%)	8
Volatile components	Cuscutae Semen	11	6
	Wuweizi (Fructus Schisandrae Chinensis)	5%-6%	16
Coumarins	Fupenzi (Fructus Rubi Chingii)	4, including esculetin, esculin, imperatorin, hexacosylp-coumarate	14
Others	Cuscutae Semen	Thymine, arbutin, etc.	19
	Gouqizi (Fructus Lycii)	Vitamins, 4-desmethylsterols, 4-methylsterols, 4'4-dimethylsterols, taurine, etc.	12
	Wuweizi (Fructus Schisandrae Chinensis)	neoisostegane, plaunol, gedunin, merulinic acid A, etc.	8
	Fupenzi (Fructus Rubi Chingii)	butyl dosocanoate, pentacosanol, liballino, 1H-2-indenone, etc.	9
	Cheqianzi (Semen Plantaginis)	Protein, Plantaginic Acid, Adenine, β-sitosterol, etc.	18

Pharmacological activity	Testing subject	Dosage	Effect	Reference
Effects on spermatogenesis	Oxidative damage of testis in mice	2, 4 g·kg^-1·d^-1，35 d	Significantly antagonize the testicular oxidative injury and spermatogenic cell apoptosis induced by cyclophosphamide	30
	Mice with oligospermia	1.56 g·kg^-1·d^-1, 14 d	Regulate the meiosis of spermatogenic cells, homologous recombination of testis, renin-angiotensin recombination of testis, renin-angiotensin system, cholesterol metabolism pathway and others,so as to repair the blocking of testicular spermatogenesis,by affecting the gene expression of testis tissue in mice with oligospermia	31
	AT1KO mouse	5.8 g/kg, 2 times a day	Has a positive regulatory effect on the sex hormone levels of male AT1+/- mice, increasing the levels of GnRH and FSH, and the degree of improvement is positively correlated with the intervention time, improving the reproductive function of male mice	32
	Testicular tissue of rats with kidney essence deficiency	0.01 mL/g, 30 d	Can reduce the apoptosis of spermatogenic cells in rat testis by inhibiting Bax and promoting the expression of Bcl-2 protein	33
Effects on sperm quality	Rat with oligospermia	1.96 g·kg^-1·d^-1, 60 d	Can correct HPG secretion disorder and improve sperm quality	34
Effects on Sertoli cells	Mouse Testis TM4 Sertoli Cells	12.0 g/kg, 2 times a day, 7 d	Serum can improve the secretory function of TM4 Sertoli cells by regulating the levels of ROS and autophagy	35
	Human testicular support cell line TM4 cells	0.2, 1.0, 5.0 mg/mL	Can improve oxidative stress injury of testicular support cells and inhibit cell apoptosis	36
	Heat stress model of rat Sertoli cells	20 g/L	Can reduce the generation of reactive oxygen species and the expression of heat shock protein 70 to protect heat stress	37
Effects on sperm mitochondria	Rats with Oligoasthenozoospermia	1, 2, 4 g·kg^-1·d^-1, 28 d	Can inhibit the opening of mitochondrial permeability transition pore (MPTP), improve the quality of spermatozoa, and reduce the apoptosis rate of spermatogenic cells (including spermatozoa)	38
	Rats with Oligoasthenozoospermia	4.0g·kg^-1·d^-1, 28 d	Can down-regulate the expression of Bax,VDAC1 and CypD proteins in rat testicular tissue, inhibit the over-opening of mPTP, and prevent the germ cell apoptosis caused by the activation of Caspase protein family	39

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