Table 5.

In vivo studies on Wistar rats.

Classification	Compound/Extract	Source	Experimental Model	Dose; Duration	Efficacy	Mechanism	Reference
Flavone	Baiclin	Scutellaria baicalensis	1) NCI–H295R 2)Wistar rats	1) 0.1, 1, 12.5, 25, 50, 100, 200 mmol/L; 24, 48, 72 h 2)20 mg/kg/day; 4 weeks	Improvement of hyperandrogenism in PCOS	↓HSD3B2, GATA1	[48]
Alkaloid	Berberine	Coptis sp. and Berberis sp	Wistar rats	100, 200 mg/kg/day;	Improvement of ovulation and endometrial receptivity in PCOS	↑Cyp19a1 ↓ $\alpha \mathrm{\nu }\beta$ 3, LPAR3	[49]
Tannin	Hydrolyzable tannin		Wistar rats	1.5, 2%/kg/body weight; 42 days	Improvement of PCOS	↑IgM	[50]
Isoflavone	Nanocurcumin	Curcuma longa	Wistar rats	100, 200 mg/kg; 15 days	Reduction of PCOS risk	↑miR-223-3p, GSH, CAT, β-cell ↓LC3II, p62, IL-6, NF-κB	[51]
Flavonol	Quercetin	Plants polyphenolic flavonoid	Wistar rats	100 mg/kg BW/day; 15 days	Alleviation of polycystic ovary	↑SOD, CAT, GST, ATPase, Ca2+ ATPase, H+ ATPase, Bcl2, E-Cadherin ↓MDA, VEGF, TNF-$\alpha$, mRNA AR gene, Bax	[52]
Terpene	Thymoquinone	Nigella sativa L.	Wister rats	0.75 mg/100 mL olive oil/rat, or 15 mg/kg body weight; 16 h, 40 h	Improvement of PCOS	↑Cyp19a1, Sqstm1, P62/SQSTM1 ↓AR, Beclin1, Atg5, Map-LC3- I, Map-LC3- II, P65	[53]
Vitamin	Vitamin C	Tropical fruits	Wistar rats	150 mg/kg BW/day; 15 days	Protection against polycystic ovary	↑CAT, ATPase enzymes activity, Bcl-2, E-cadherin ↓MDA, TNF-$\alpha$, VEGF, AR, Bax	[54]
Plant	Bee pollen	Anthophila	Wistar rats	50,100,200 mg/kg/day; 21 days	Therapeutic effect on PCOS	↑Bax, Caspase-3, Sirt-1 ↓Bcl-2	[55]
Plant	Caesalpenia bonducella ethanol extract	Guilandina bonduc	Wistar rats	200, 400 mg/kg; 28 days	Improvement of PCOS	↑SOD CAT, GST, ↓GPx, GR	[56]
Plant	Chamomile	Matricaria chamomilla L.	Wistar rats	75 mg/kg/day; 30 days	Improvement of PCOS	↑GPx, CAT ↓caspase-3, MDA,	[57]
Plant	Fennel seed extract	Foeniculum vulgare	Wistar rats	150 mg/kg/day; 15 days	Regulation of the hormonal and biochemical changes of PCOS	↑FSH, HDL ↓Insulin, LH, FBS, testosterone, total triglycerides, total cholesterol	[58]
Plant	F. religiosa 10 % fresh leaf extract	Ficus religiosa	Wistar rats	1.0 mL/kg/day; 30 days (oral, spray)	Alleviation of PCOS	↑GSH, GPx, SOD, CAT, Cyp19a1, PPAR-$\gamma$ ↓3 $\beta$-HSD, 17 $\beta$-HSD, HmG-CoA reductase, TC	[59]
Plant	F. religiosa aqueous dry leaf extract	Ficus religiosa	Wistar rats	100, 300 mg/kg/day; 30 days	Alleviation of PCOS	↑GSH, GPx, SOD, CAT, Cyp19a1, PPAR-$\gamma$ ↓3 $\beta$-HSD, 17 $\beta$-HSD, HmG-CoA reductase	[59]
Plant	Ginger extract	Zingiber officinale Roscoe	Wistar rats	175,350 mg/kg/day; 88 days	Improvement of PCOS	↑LH, estrogen; ↓progesterone, FSH	[60]
Plant	Gymnema sylvestre ethanol extract	Gymnema sylvestre	Wistar rats	100 mg/kg/day; 28 days	Inhibition in insulin resistance and androgen production	↑Luteinizing hormone, testosterone, estrogen; ↓follicle-stimulating hormone, progesterone	[61]
Plant	Hedge woundwort	Stachys sylvatica L.	Wistar rats	100, 250, 500 mg/kg; 10 days	Improved obesity. Reduced cystic follicles.	Improvement of folliculogenesis and regulation of gonadotropins synthesis	[62]
Plant	Majoram extract	Origanum majorana	Wistar rats	20 mg/kg/day; 24 days	Beneficial ameliorative effects against PCOS	↑SOD, GPx ↓IL-6	[63]
Plant	Pergularia daemia ethanol extract	Pergularia daemia	Wistar rats	300 mg/kg/day; 28 days	Improvement of ovulation and menstrual irregularity	↓follicle-stimulating hormone, progesterone	[61]
Plant	Chitosan-engaged tripolyphosphate ions and concurrent loading of the biomolecules of the ethanolic extract of fennel seed	Foeniculum vulgare	Wistar rats	50 mg/kg/day; 15 days	Regulation of the hormonal and biochemical changes of PCOS	↑FSH, HDL ↓Insulin, LH, FBS,	[58]
Decoction	Combination of Gymnema sylvestre, Pergularia daemia ethanol extract	Gymnema sylvestre, Pergularia daemia	Wistar rats	400 mg/kg/day; 28 days	Synergistic effects against PCOS	↑Luteinizing hormone, testosterone, estrogen	[61]
Plant	Actaea racemosa and Vitamin C	Cimicifuga racemosa	Wistar rats	AR extract 7.14 mg/kg, vitamin C 500 mg/kg; 28days	Alleviation of PCOS without hepatic adverse effect	↑GSH, Ki-67, Cyp19a1 ↓MDA	[64]
Decoction	Chia seed, Walnut	Salvia hispenica, Prunus dulcis	Wister rats	40 g, 40 g, 20 g & 20 g/day; 15 days	Regulation of the hormone level	↓body and ovarian weights	[65]
Decoction	Fennel essential oil, flaxseed oil	Foeniculum vulgare, Linum usitatissimum	Wistar rats	(1)100 mg/kg (2) 429 mg/kg (3) combination 100 mg/kg & 429 mg/kg; 50 days	Improvement of the follicle conditions of PCOS	↓cystic follicles	[66]
Decoction	Hochu-ekki-to		Wistar rats	500 mg/kg/day; 7 days	Improvement of ovarian reproductive and immune functions.	↑ER-$\alpha$, ER-$\beta$, IL-2, IL-4, IFN-$\gamma$, ↓AR, NGFR, GR, MAP2K-2, Hsp 90	[67]
Decoction	Kañcanāra Guggulu	Bauhinia variegate L., Terminalia chebula Retz., Terminalia bellerica, Emblica officinalis, Zingiber officinale, Pipernigrum, Piper longum Linn., Crataeva nurvala, Elettaria cardamomum, Cinnamomum zeylanicum, Commiphora mukul	Wistar rats	100 mg/kg/day; 28 days	Regularization of the estrous cycle	↓body weight, lipid profile, Blood glucose	[68]
Decoction	Niśāmalakī	Curcuma longa, Emblica officinalis	Wistar rats	0.9 g/kg/day; 28 days	Correction of changes induced by PCOS	↓body weight, lipid profile, Blood glucose	[68]
Decoction	Sahoyao-gancao decoction	Radix Paeoniae Alba., Glycyrrhizae uralensis	rats	12.5, 25,50 g/kg; 14 days	Treatment of PCOS	↑IκB. ↓TNF-α, IL-1β, IL-6, and IL-18, P– NF-κB, p- NF-κB p65	[69]
Decoction	Unkeito	Paeonia lactiflora, Cinnamomum cassia	rats		Improvement of the follicle conditions of PCOS	↑gonadotropins	[70]

PCOS, polycystic ovary syndrome; Bax, bcl-2-associated X protein; CYP19a1, cytochrome P450, family 19, subfamily a, polypeptide 1; LPAR3, lysophosphatidic acid receptor 3; GPx, glutathione peroxidase; CAT, catalase; MDA, malondialdehyde; miR, microRNAs; GSH, glutathione; LC3II, light chain 3 II; p62, Sequestosome 1; IL-6, interleukin 6; NF-κB, nuclear factor-kappa B; SOD, superoxide dismutase; GST, glutathione-S-transferase; MDA, malondialdehyde; VEGF, vascular endothelial growth factor; TNF-α, Tumor osis factor-α; mRNA AR gene, mRNA androgen receptor gene; Cyp19a1, Cytochrome P450 Family 19 Subfamily A Member 1; HSD3B2, Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- And Steroid Delta-Isomerase 2; GATA1, GATA Binding Protein 1; GSH, reduced glutathione; GPx, glutathione peroxidase; PPAR-$\gamma$, peroxisome proliferator-activated receptor-$\gamma$; 3 $\beta$-HSD, 3 $\beta$-Hydroxysteroid dehydrogenase; 17 $\beta$-HSD, 17 $\beta$- Hydroxysteroid dehydrogenase; GR, glucocorticoid receptor; Sqstm1, Sequestosome 1; AR, androgen receptor; Beclin1, Atg5, Autophagy Related 5; Map-LC3- I, Microtubule-associated proteins 1A/1B light chain 3B; ER-$\alpha$, estrogen receptor-$\alpha$; ER-$\beta$, estrogen receptor $-\beta$; IL-2, interleukin-2; IL-4, interleukin 4; IFN-$\gamma$, interferon-$\gamma$; NGFR, nerve growth factor receptor; MAP2K-2, mitogen-activated protein kinase kinase 2; Hsp 90, heat shock protein 90; IκB, IkappaB kinase; IL-1β, interleukin-1β; IL-18, Interleukin-18; ↑, up-regulation; ↓, down-regulation.