Effects of Withania somnifera on Reproductive System: A Systematic Review of the Available Evidence

Table 2

Characteristics and results of animal studies investigating effects of Withaniasomnifera on reproductive system.

Number	Author/year	Plant extract	Participant	Intervention protocol	Duration; of studies	Results	Place
(1)	AL-Qarawi et al., 2000 [27]	Lyophilized aqueous extract	Immature female Wistar rats (); 6 groups: 17-day-old rats; G1 (10), G2 (10), control (),; 25-day-old rats G1 (), G2 (), control (); G1 = C. coccineumG2 = W. somnifera	47 mg/100 g body; weight/stomach tube	6 days	In 25-day-old rats; ↑ FSH levels (), ↑ ovarian weight and deep folliculogenesis and proliferation of granulosa (); In 17-day-old animals; ↑ body weight () no significant changes in the ovarian weight and folliculogenesis and FSH and LH	Kingdom of Saudi Arabia
(2)	Mali et al., 2008 [28]	50% ethanolic extract; of fruits	Fertility proven, adult healthy male albino rats	50 mg/kg/PO/day	60 days	↓ sperm motility, ↓ density of testicular and cauda; epididymal sperms, ↓ weight of testes and seminal vesicle, ↓ ascorbic acid, ↓ sialic acid, ↓ cholesterol, ↓ protein, ↓ fructose, ↓ acid phosphatases, degenerative changes in the seminiferous tubules and germinal epithelium, ↓ spermatogenic elements, in treated rats	India
(3)	Belal et al., 2012 [29]	Root power	Adult male albino rats (); alloxan induced diabetes; 4 groups: control (), nondiabetic WS-treated (), diabetic rats (), diabetic group treated with WS ()	Mixed with basal diet at ratio of 6.25%/po	4 weeks	No significant alteration estrogen and cholesterol in treated with WS both diabetic and nondiabetic rats compared to controls groups (), progesterone in both diabetic and nondiabetic treated with WS (), T (), LH () in nondiabetic treated with WS groups compared to the control group, ↓ TG in diabetic treated with WS compared to diabetic rats (), ↓ FSH in WS-treated groups (), not considered hypoglycemic effect	Egypt
(4)	Ilayperuma et al., 2002 [30]	Methanolic extract of roots	Proven fertility, adult male Wistar rats (); 4 groups: control 1, control 2 () and WS 1, WS 2 ()	3000 mg/kg/PO/day	7 days	Considerable weakness in libido, sexual performance, sexual vigour, and penile erectile dysfunction, no marked change in SGOT, SGPT, urea nitrogen, pH of the seminal vesicular fluid, wet weight of the organs and no deaths in treated period	Sri Lanka
(5)	Abdel-Magied et al., 2001 [31]	Lyophilized aqueous extracts of leaves	Immature male Wistar rats (); 3 groups: control (), C. coccineum (), WS ()	47 mg/100 g body weight/d/stomach tube	6 days	↑ LH, FSH, T, ↑ testicular weight, ↑ STD, ↑ number of seminiferous tubular; cell layers (CL) and diameters, ↑ spermatogenesis in treated groups compared to control group	Saudi Arabia
(6)	Dhas et al., 2015 [32]	Ethanolic; extracts	Female and male fish (Etroplussuratensis); 4 groups: control and WS with different ratio + M. pruriens + Moringa oleifera	120-200-300 mg/kg WS; thrice in a day	ND	↑ Gonadosomatic Index (GSI), ↑ fecundity, ↑ striping response, ↑ percentage of fertilization, ↑ percentage of hatching, percentage of deformed, ↑ formed larvae, ↑ volume of milt, ↑ number of sperm cell, ↑ percentage of sperm motility, ↑ sperm survival time, ↑ percentage of active sperm after treatment diets especially the EXD3 contain 300 mg/kg ()	India
(7)	Shaikh et al., 2015 [33]	Glycowithanolides extract of fresh leaves	Adult Swiss albino male mice (); 4 groups: D-galactose treated (), control (), protective (), curative ()	20 mg/kg/injected subcutaneously	20 days	↑ epididymal sperm count (), ↑ weight of testes and epididymis and body () and returned to normal histology of testes in protective and curative group compared to D-galactose treated group and no significant increase in weight of testes, epididymis and seminal vesicle in the curative compared to protective group	India
(8)	Kumar et al., 2015 [15]	Ethanolic root extract	Males Charles Foster rats (); arsenic induced testicular toxicity; 3 groups: control (), arsenic and WS-treated ()	100 mg/Kg/PO/day	30 days	↑ sperm count, ↑sperm motility, ↑ T, LH, LPO (), normalization the spermatogenetic stages, after treatment compared to before treatment	India
(9)	Walvekar et al., 2013 [34]	Glycowithanolides extract of fresh leaves	Adult Swiss albino male mice (); 4 groups: D-galactose (), control (), protective (),; curative ()	20 mg/kg injected subcutaneously	20 days	total and mitochondrial LPO, fluorescence product in testes, epididymis and seminal vesicle in protective and curative groups () compared to D-galactose	India
(10)	Kumar et al., 2015 [35]	Alcoholic root extract (5)%	Female Swiss albino mice; chlorpyrifos induced toxicity ovaries; 4 groups: control, chlorpyrifos, WS, curcuma	50 mg/kg/day	8 weeks	↓ estrogen, ↓ cholesterol and restoration in germinal epithelium, graafian follicles and corpus luteum of ovary in WS-treated group compared to chlorpyrifos group	India
(11)	Patil et al., 2012 [36]	Ethanolic extract of fresh leaves	Healthy male albino mice (); D-galactose induced stress; 3 groups: D-galactose (), control (), WS + D-galactose ()	2% extract	15 days	↓ total and mitochondrial LPO, sperm count, recovery of degenerative changes in histological structure both testis and epididymis after the treatment WS compared with D-galactose group	India
(12)	Rajashree et al., 2011 [37]	Alcoholic root extract	Male albino rats (); streptozotocin-induced diabetic; 4 groups: STZ (), normal; Control (), WS + STZ (), STZ + insulin ()	500 mg/kg/PO/day	30 days	weight of testes, caudal sperm count, weight of cauda epididymis in WS-treated diabetics compared to insulin treated groups	India
(13)	Kiasalari et al. 2009 [38]	Root; powder	Wistar male rats (): ZTZ induced diabetic; 4 groups: ZTZ (), control (), WS + STZ (), sham ()	Plant-mixed pelleted food at ratio of 6.25%/po/day	4 weeks	↓ FSH (), LH (), progesterone (), T (), nonsignificant changes on estrogen in somnifera-treated diabetic, nondiabetic group compared to nontreated diabetic and nondiabetic, ns difference glucose, cholesterol after WS treatment, ↓ TG in somnifera-treated diabetic group	Iran
(14)	Rahmati et al., 2016 [39]	Root powder	Male rats (); 4 groups: morphine induced addiction: addicted (),; control (),; WS-treated control (),; WS-treated addicted ()	Plant-mixed pelleted food at ratio of 6.25%; ( g/kg/day)	21 days	estrogen in WS-treated control groups () compared to control group, no marked effect in addict group, T, LH in WS-treated addicted group () compared to control and addicted groups, FSH in WS-treated control group compared to control group ()	Iran
(15)	Prabu et al., 2014 [40]	Hydroalcoholic root extract	Male Wistar rats (); 2 groups: control () and WS ()	1000 mg/kg/PO (gavage)	70 days	↓ WBC, ↓ LYM values (), insignificant neutrophil, RDW, ↓ monocyte, ↓ eosinophil, ↓ RBC counts, ↓ PCT values, no significant difference in body weight, testes and seminal vesicles weight, sperm count, morphology and biochemical parameters between treated group and control group (). No side effects in during treatment	India
(16)	Bhargavan et al., 2015 [41]	Ethanolic root extract	Healthy adult male Wistar rats (); 4 groups: ethanol induced oxidative damage in the testes (), control (),; WS + alcohol (), WS ()	200 mg/PO/day	28 days	testicular weight, body weight and recovered histopathological changes in the seminiferous tubules, sperm count, motility, ↓ sperm abnormality, ↓ MDA (), GSH (), CAT (), T in alcohol + WS cotreatment group compared with alcohol group	India
(17)	Nirupama and Yajurvedi, 2015 [42]	Chloroform and ethanolic extracts of roots	Adult male rats (); 6 groups: chronic stress exposed on testis (), control (), positive control (), stress + ethanolic WS (), stress + mifepristone (), stress + chloroform extract of WS ()	10 mg/kg/day/orally (intubation)	1 month	testicular 3β HSDH activity, ↓ adrenal 3β HSDH activity (), ↓ abnormal sperm count (), ↓ MDA, T (), total epididymal sperm count (), spermatogenesis, (SOD, CAT, GPx, GST, GR), ascorbic acid, tocopherol in WS-treated group compared to stressed rats	India
(18)	Kumar et al., 2013 [43]	Alcoholic extract of root	Female Swiss albino mice (); chlorpyrifos induced toxicity of ovary; WS + chlorpyrifos (); control ()	50 mg/kg/day	8 weeks	↓ estrogen and cholesterol (), recovery of ova, granulosa cells, germinal epithelium, mature graafian follicle, mitochondrial cristae of ovary and chromatin material after WS administration compared to before treatment	India
(19)	Kumar et al., 2012 [44]	Aqueous extract of roots	Male mice (); endosulfan exposed spermatozoa; 2 groups: control () and endosulfan + WS ()	1000 mg/kg/day	8 weeks	↓ MDA, T, ↓ calcium, restoration of spermatozoa structure such as normal plasma and nuclear membrane, Golgi complex, chromatin material and mitochondrial cristae after WS treatment compared to before treatment	India
(20)	Kaspate et al., 2015 [45]	Hydroalcoholic extract of roots	Healthy female Wistar rats with tubal ligated (): 4 groups with various doses of WS	100, 200 and; 300 mg/kg/PO/day	21 days	sexual behavior, ↓ run time, proximity time, ↓ retreats (, ), serum estradiol with doses 200 and 300 mg/kg (, ), normalization in histology of genital organs like vagina, uterine horn and ovary in estrous female rats compared to estrous control female rats	India
(21)	De and Chakraborty, 2016 [46]	Root powder	Mixed-sex juveniles of Niletilapia (Oreochromisniloticus) (); 9 groups: control () and WS with various concentration ()	0.0, 2.0, 3.0, 3.5, 5.0, 6.5, 7.0, 8.0, 9.5 g/kg mixed food	30 days	Concentrations up to 7.0 g/kg have no side effect (), percentage of male and ↓ percentage of female with any concentration of WS (), high percentage of survival and male were at the concentration of 6.5 g/kg compared to control group	India
(22)	Jasuja et al., 2013 [47]	Methanolic extract of leaves and roots	Male albino rats (); 6 groups: control (), acephate for 15 days (), acephate for 30 days (), acephate for 15 days + WS for 15 days (), acephate + WS for 30 days (), acephate for 15 days and no treatment for next 15 days ()	100 mg/kg/PO/day	15–30 days	↓ testicular LPO, GSH, SOD, CAT, T, FSH, LH (, ), recovery of sperm count, motility, morphology, testis histology after WS treatment compared with acephate groups	India
(23)	Saritha et al., 2011 [48]	Leaf powder-mixed pelleted food	Female rats (); 5 groups: control (), 0.05% Pb + normal pellet diet (), 0.05% Pb + WS diet (), 0.15% Pb + normal pellet diet (), 0.15% Pb + WS diet ()	500 mg/kg/PO/day	45 days	↓ length of the diestrus phase (), the number of implantations (), the number of live foetuses (), ↓ pre- and postimplantation losses after treatment with WS compared with the rats exposed and no toxicity in all of animals during treatment	India
(24)	Garg and Parasar, 1965 [49]	Root power	Albino mice of either sex (); 2 groups: control () and WS group ()	25 mg/PO/day	10 days	↓ fertility rate by 25%, ↓ mating behavior, ↓ number of pups per litter from 5.25 to 3.0 in WS treatment group compared to control group	India
(25)	Sahin et al., 2016 [50]	Hydroalcoholic extract of roots	Male rats (); 5 groups: control (), sildenafil-treated (), Mucuna (), Tribulus (), WS ()	300 mg/kg/PO/day	8 weeks	No significant changes in body weight and reproductive organ weights, abnormal sperms, serum biochemical and hematology parameters (), ↓ mounting latency and intromission latency (), mounting frequency and intromission frequency values (), sperm counts, sperm motility, ↓ MDA, T () in WS groups compared to control group	Turkey
(26)	Shaikh et al., 2014 [51]	Glycowithanolides extract of fresh leaves	Adult Swiss albino male mice (); 4 groups: D-galactose treated (), control (), protective (),; curative ()	20 mg/kg/injected subcutaneously	20 days	SOD, GPx, CAT in testes and accessory reproductive organs () in protective and curative group compare to D-galactose group	India
(27)	Saiyed et al., 2016 [52]	Hydroalcoholic extract of roots	Female Wistar rats (); letrozole induced PCOS: 4 groups: negative control (), positive control (), WS and TT (), standard group with clomiphene citrate ()	198 mg/kg	28 days	number of days in estrus phase (), ↓ duration of diestrus phase in test group () returned to normalcy on FSH, ↓ LH, ↓ T, ↓ estradiol and recovery of ovary and uterine weight but no significant, ↓ cholesterol () compared to positive control group	India
(28)	Mali, 2013 [53]	Hydroalcoholic extract; of fruits	Healthy, male albino rats (); 2 groups: control () and WS ()	200 mg/kg/day/po	60 days	↓ primary and secondary spermatocytes, mature sperms, ↓ weight of testis and other accessory reproductive organs, abnormal seminiferous tubules, ↓ protein, ↓ sialic acid, ↓ fructose, ↓ ascorbic acid (, ) in WS groups compared to control group	India

ND, not determined; WS, Withania somnifera; FSH, follicular stimulating hormone; LH, luteinizing hormone; ALP, alkaline phosphatase; Cd, cadmium; GSH, glutathione peroxidase; SOD, superoxide dismutase; CAT, catalase; MDA, malondialdehyde; STD, seminiferous tubules diameter; T, testosterone; PRL, prolactin; LPO, lipid peroxidation; g, amino butyric acid; TG, triglyceride; EDSI, erectile dysfunction severity index; FSFI, female sexual function index; FSDS, female sexual distress scale; IMHQOL, Internet mental health quality of life scale; QEQ, quality of erection questionnaire; NZ, normozoospermic; OZ, oligozoospermic; AZ, asthenozoospermic; IDH, isocitrate dehydrogenase; LDH, lactate dehydrogenase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GPC, glycerophosphocholine; TT, Tribulus terrestris; WBC, white blood cell; LYM,lymphocytes.; , increase; ↓, decrease.