Table 4.

In vivo studies in Sprague Dawley rats.

Classification	Compound/Extract	Source	Dose; Duration	Efficacy	Mechanism	Reference
Alkaloid	Berberine	Coptis chinensis Franch, Phellodendron chinensis var. glabriusculum.	95, 190 mg/kg/day; 4 weeks	Attenuation of PCOS	PI3K/AKT pathway	[34]
Stilbene	Resveratrol	Berberis integerrima	20 mg/kg/day; 42 days	Treatment of PCOS	↑SOD, TAC ↓MDA, TNF-$\alpha$	[35]
Plant	Allium fistulosum root extract	Allium fistulosum	500 mg/kg/body weight; 2 weeks	Improvement of ovarian function progression	↑Kitl, Bmp, Pgr, ESR1, Cyp19a1	[36]
Plant	Berberis integerrima hydroalcoholic extract	Berberis integerrima	3 gr/kg/day; 42 days	Treatment of PCOS	↑SOD, TAC ↓MDA, TNF-$\alpha$	[35]
Plant	Flaxseed hydroalcoholic extract	Linum usitatissimum	200 mg/kg; 30 days	Amelioration of PCOS sign	↑Progesterone, preantral follicles, antral follicles, and corpus luteum, the thickness of the granulosa layer; ↓testosterone, the thickness of the theca layer, and tunica albuginea	[37]
Decoction	Combination of Berberis integerrima hydroalcoholic extract and Resveratrol	Berberis integerrima, Resveratrol	20 mg/kg+3 gr/kg/day; 42 days	Treatment of PCOS	↑SOD, TAC ↓MDA, TNF-$\alpha$	[35]
Decoction	Bao Gui capsule	Herba Epimedium, Rhizome polygonati, Fructus Psoraleae, Carapex et Plastrum Testudinis, Radix Rehmanniae, Rhizoma Anemarrhenae, Radix Angelicae Sinensis, Semen Persicae, Rhizoma Acori Tatarinowii, Radix Polygoni Cuspidati, Herba Verbenaeofficinalis, Radix Ophiopogonis	0.28,0.57 g/kg/day; 21 days	Treatment of PCOS	↑P450arom, GLUT4 ↓P450c17 $\alpha$, IL-6, TNF-$\alpha \text{,}$ NF-$\kappa B$, IKK $\beta$, SOCS3	[38]
Decoction	Cangfu Daotan Decoction	Atractylodis Rhizoma, Cyperi Rhizoma, Fructu Ponciri, Fabanxia, Pericarpium Citri Nobilis, Poria, Arisaematis Rhizoma, Glycyrrhizae Radix, Zingiberis Rhizoma.	1.42,5.68 g/kg/day; 14 days	Treatment of PCOS	↑OATP2B1, OATP3A1 ↓IL-1 $\beta$, IL-6, TNF-$\alpha$	[39]
Decoction	Cangfu Daotan Decoction	Atractylodis Rhizoma, Cyperi Rhizoma, Pinellia ternata, Pericarpium Citri Reticulatae, Poria Cocos, Arisaematis Rhizoma, Astragalus membranaceus, Aurantii Fructus, Codonopsis Radix, Epimrdii Herba, Crataegus pinnatifida Bge, Radix Salviae, licorice, white mustard, Endothelium Corneum Gigeriae Galli, Gleditsiae Spina	15, 30 g/kg/day; 4 weeks	Regulation of PCOS	↑bcl-2, p-Akt/Akt, p-PI3K/PI3K ↓TNF-α, IL-1β, IL-6, Bax, Bad, IGF-1	[40]
Decoction	Guizhi fuling wan	Cinnamomum cassia J. Presl, Poria cocos Wolf, Paeonia veitchii Lynch, Prunus persica Batsch, Paeonia suffruticosa Andr.	0.31, 0.62, 1.24 g/kg/day; 30 days	Attenuation of ovulation disorder	↑P62, p-P13K, p-AKT, p-mTOR ↓LC3-II, Beclin1, Atg5, c-PARP, c-caspase-3, c-caspase-9	[41]
Decoction	Heqi san	Curculigo orchioides Gaertn, Schisandra chinensis Baill, Cynanchum podophyllum C. K. Schneid, Citrus medica L. var. sarcodactylis Swingle, Crataegus pinnatifida Bunge, Rhus chinensis Mill, Clinopodium megalanthum (Diels) C. Y. Wu & Hsuan ex H. W. Li, Cuscuta chinensis Lam, Poncirus trifoliata (L.) Raf, Hordeum vulgare L, Polygala tenuifolia Willd, Epimedium davidii Franch	8.1 g/kg/day; 30 days	Improvement of PCOS	↑GLUT4, PTEN, p-ERK, p-AKT, p-GSK3β, IRS-1	[42]
Decoction	Liuwei Dihuang pills	Rehmanniaglutinosa DC. rhizome, Cornus officinalis Siebold & Zucc. fructus, Dioscorea opposita Thunb. Rhizome, Alisma plantagoaquatica Subsp. orientale Juz. tuber, Paeonia suffruticosa Andr. root bark, Poria cocos Wolf. sclerotium	1.2, 3.6 g/kg/day; 21 days	Amelioration of PCOS	↑P-IRS-1, FSHR, Cyp19a1 ↓P-PI3Kp85α, P-Akt, P-FoxO1a	[43]
Decoction	Mahuang tang	Ephedra Herba, Cinnamomi Ranulus, Glycyrrhizae Radix et Hizoama, Armeniacae Semen, Allii Radix, Zingiberis Rhizoma Crudus,	500 mg/kg/day; 2 weeks	Protection of PCOS	↑Cyp19a1, Hsd17b1 ↓Cyp11a1	[44]
Decoction	Spearmint and flaxseed extract		40 mg/kg spearmint + 200 mg/kg flaxseed extract; 30 days	Treatment of PCOS		[45]
Decoction	Xiao-Yao-san	Radix bupleuri, Angelica gigas Nakai., Radix paeoniae Alba., Atractylodes macrocephala Koids., Poria cocos Wolf, Zingiber officinale Roscoe., Mentha haplocalyx Briq., Glycyrrhizae glabra L.	0.505, 1.01 g/kg/day; 4 weeks	Amelioration of PCOS	↑AKT and S6K1 ↓DbH, c-fos, b2R	[46]
Decoction	Yingyanghuo, Xianmao	Epimedium brevicornum Maxim., Curculiginis Rhizoma	7.5 g/kg; 7 days	Alleviation of PCOS	↑AKT1	[47]

PCOS, polycystic ovary syndrome; SOD, superoxide dismutase; TAC, total antioxidant capacity; MDA, malondialdehyde; TNF-α, Tumor necrosis factor-α; Kitl, KIT ligand; Bmp, bone morphogenetic protein; Pgr, progesterone receptor; ESR1, estrogen receptor 1; CYP19a1, cytochrome P450, family 19, subfamily a, polypeptide 1; P450arom, cytochrome P450 aromatase; GLUT4, glucose transporter 4; P450c17α, cytochrome P450c17α; IL-6, interleukin-6; NF-κB, nuclear factor- κB; IKKβ, nuclear factor- κB kinase subunit β; SOCS3, suppressor of cytokine signaling 3; OATP2B1, organic anion transporting polypeptides 2B1; OATP3A1, organic anion transporting polypeptides 3A1; IL-1 $\beta$, interleukin-1 $\beta$; IL-6, interleukin-6; Bcl-2, B-cell lymphoma 2; AKT, Protein kinase B; Bax, bcl-2-associated X protein; IGF-1, Insulin-like growth factor 1; p-P13K, phosphorylated-P13K; p-AKT, phosphorylated-AKT; p-mTOR, phosphorylated-mTOR; c-PARP, cleaved-PARP; c-caspase-3, cleaved-caspase-3; c-caspase-9, cleaved-caspase-9; GLUT4, Glucose transporter type 4; PTEN, Phosphatase and tensin homolog; IRS-1,Insulin receptor substrate 1; FSHR, Follicle Stimulating Hormone Receptor; FoxO1a, Forkhead box protein O1; Hsd17b1, Hydroxysteroid 17-Beta Dehydrogenase 1; Cyp11a1, Cytochrome P450 Family 11 Subfamily A Member 1; S6K1, Ribosomal protein S6 kinase beta-1; DbH, Dopamine beta-hydroxylase; b2R, Beta-2 adrenergic receptor; ↑, up-regulation; ↓, down-regulation.