. 2020 Aug 12;11:1192. doi: 10.3389/fphar.2020.01192

Table 2.

In vitro and in vivo studies of individual herbal extracts (n=11).

Interventions	Target cells or animal models	Herbal extraction	Route of administration	Dosage	Results	Author (year)
Aloe vera gel	<in vivo>⁽⁴⁾ Adult virgin female Charles Foster rats (aged 3–4 months, 200–225 g)	not reported	Oral	1 ml (10 mg)/d For 30 days	1) Ovarian weight (-) 2) 3β HSD activity ↓, 17β HSD activity (-) 3) Improved OGTT profile 4) Body weight ↓ 5) Plasma levels of TC ↓, TG ↓, HDL-C ↑, and LDL-C ↓ 6) Liver cholesterol ↓ 7) Activity of HMG-CoA reductase ↓ 8) Activity of LCAT (-)	Desai et al. (2012)
Aloe vera gel	<in vivo>⁽⁴⁾ [1] Adult virgin Charles Foster female rats (200–225 g) <in vitro> [2] Ovarian protein (30–35 g)	not reported	Oral	[1] 1 ml (10 mg)/d For 45 days [2] 1 mg For 1 h	[1] 1) Body weight ↓, ovarian weight ↓ 2) Recovery of estrous cycle 3) Improved OGTT profile 4) Histology: ovary atretic cysts ↓, normalization of follicular growth 5) Activities of ovarian 3β HSD and 17β HSD ↓ 6) Serum glutamate pyruvate (-), transaminase (-), creatinine (-) [2] 1) Activities of ovarian 3β HSD and 17β HSD ↓	Maharjan et al. (2010)
Atractylodes macrocephala koidz	<in vivo>⁽²⁾ [1] Female SD rats <in vitro> [2] Human ovarian granulosa-like KGN cells	Solvent: ethanol (70%) Time: three times for 0.5 h	Oral	[1] 0.1, 0.3, 0.9 g/kg/d For 8 weeks [2] 50, 200, 800 μg/mL For 24 h	[1] 1) Recovery of estrous cycle 2) Body weight ↓(only 0.3, 0.9 g/kg/d), ovarian weight ↓(only 0.9 g/kg/d), uterus weight (-) 3) T ↓, SHBG (-), free androgen index ↓, androstenedione ↓, LH ↓(only 0.3, 0.9 g/kg/d), FSH ↑, LH/FSH ↓, AMH ↓ 4) mRNA expression of FSHR in ovaries ↓, mRNA expression of AQP-9 in ovaries ↑ 5) Protein expression of FSHR in ovaries ↓, protein expression of AQP-9 in ovaries ↑ 6) ALT (-), AST (-), GGT (-) [2] 1) Protein expression of FSHR ↓, protein expression of AQP-9 ↑	Zhou et al. (2016)
Chamomile	<in vivo>⁽³⁾ Virgin adult cycling Wistar rats (aged 8 weeks, 200–220 g)	Solvent: ethanol (70%)	Intraperitoneally	25, 50, 75 mg/kg/d For 10 days	1) Morphology: cysts in ovarian tissue ↓(only 50 mg/kg/d), number of dominant follicles ↑(only 50 mg/kg/d), better endometrial tissue arrangements (only 50 mg/kg/d) 2) Serum levels of E2, LH, and FSH ↓	Zangeneh et al. (2010)
Cocus nucifera flower	<in vivo>⁽⁴⁾ Wistar female rats (100–150 g)	Solvent: aqueous alchhol (75%) Time: 12 h	Oral	100, 200 mg/kg/d For 4 weeks	1) Recovery of estrous cycle 2) Blood sugar level ↓ 3) TC ↓, VLDL-C ↓, HDL-C ↑, TG ↓ 4) Uterus weight ↑, ovary weight ↓ 5) Histophthology: number and diameter of cysts ↓, normal developing primary follicles ↑(only 200 mg/kg/d)	Soumya et al. (2014)
Flaxseed	<in vivo>⁽³⁾ Adult female SD rats (200 ± 20 g)	Solvent: ethanol (70%)	Gavage	200 mg/kg/d For 30 days	1) P ↑, T ↓, E2 (-), dehydroepiandrosterone (-) 2) Histomorphometric study: number of preantral follicles, antral follicles and corpora lutea ↑, number of cystic follicles and diameter of antral follicles ↓, number of primary follicle (-), thickness of granulosa layer ↑, thickness of theca layer and tunica albuginea ↓	Jelodar et al. (2018)
Foeniculum vulgare seeds	<in vivo>⁽³⁾ Adult female Wistar rats (200 ± 20 g)	Solvent: 400 ml of distilled water Time: 24 h	Gavage	100, 150 mg/kg/d For 4 weeks	1) Serum creatinine (-), serum urea ↓(only 150 mg/kg/d) 2) Histopathology: normal glomerulus, normal basement membrane, and capillaries; Bowman’s space (urinary space) and acute tubular necrosis were improved towards normal	Sadrefozalayi and Farokhi (2014)
Ginger	<in vivo>⁽³⁾ Neonatal female SD rats (aged 7–8 weeks, 170–200 g)	Solvent: ethanol (70%) Time: 48 h	Oral	4, 350 mg/kg/d For 88 weeks	1) LH ↓, FSH ↑, E ↓, P ↑	Atashpour et al. (2017)
Korean red ginseng	<in vivo>⁽³⁾ SD female rats (190–210 g)	not reported	Oral	200 mg/kg/d For 60 days	1) Histology: numbers of corpora lutea and corpora albicantia ↑, number of cystic follicles ↓ 2) mRNA expression of NGF in ovaries ↓, protein expression of NGF in ovaries ↓	Jung et al. (2011)
Korean red ginseng	<in vivo>⁽³⁾ SD female rats (190-210 g)	not reported	Oral	200 mg/kg/d For 60 days	1) Histology: numbers of corpora lutea and corpora albicantia ↑, number of cystic follicles ↓ 2) mRNA expression of NGF in ovaries ↓, protein expression of NGF in ovaries ↓	Pak et al. (2009)
Labisia pumila var. alata	<in vivo>⁽⁵⁾ Wistar female rats (aged 21 days)	Solvent: hot distilled water (80˚C) Time: 3 h	Oral	50 mg/kg/d For 4–5 weeks	1) Body weight (-), body composition (-) 2) Uterine weight ↑, weights of the inguinal, parametrial, retroperitoneal and mesenteric adipose tissue depots (-), weights of different hind limb muscles and the liver (-) 3) Size of adipocytes in mesenteric adipose tissue (-) 4) Glucose infusion rate ↑, plasma glucose (-) 5) TC ↓, TG ↓, HDL-C (-), LDL-C (-), resistin ↑, adiponectin (-), leptin (-) 6) mRNA expression of leptin in mesenteric adipose tissue ↓, mRNA expressions of resistin and adiponectin in mesenteric adipose tissue (-)	Mannerås et al. (2010)

ALT, Alanine aminotransferase; AMH, Anti-Müllerian hormone; AQP, Aquaporin; AST, Aspartate aminotransferase; E, Estrogen; FSH, Follicle-stimulating hormone; FSHR, Follicle-stimulating hormone receptor; GGT, Gamma glutamyltransferase; HDL-C, High density lipoprotein cholesterol; HMG-CoA, β-Hydroxy β-methylglutaryl-CoA; HSD, Hydroxysteroid dehydrogenase; LCAT, Lecithin–cholesterol acyltransferase; LDL-C, Low density lipoprotein cholesterol; LH, Luteinising hormone; NGF, Nerve growth factor; OGTT, Oral glucose tolerance test; P, Progesterone; SD, Sprague-Dawley; SHBG, Sex hormone-binding globulin; T, Testosterone; TC, Total cholesterol; TG, Triglyceride; VLDL-C, Very low density cholesterol.

In vivo polycystic ovary model by using ⁽¹⁾ dehydroepiandrosterone; ⁽²⁾ testosterone propionate; ⁽³⁾ estradiol valerate; ⁽⁴⁾ letrozole; ⁽⁵⁾ dihydrotestosterone; ⁽⁶⁾ sodium prasterone sulfate; and ⁽⁷⁾ chronic unpredictable mild stress.