Table 3.
In vitro and in vivo studies of herbal formula decoctions (n=10).
| Interventions | Components | Target cells or animal models | Herbal extraction | Route of administration | Dosage | Results | Author (year) |
|---|---|---|---|---|---|---|---|
| Bushen Tongmai Recipe | Astragalus membranaceus Bge, Radix Polygoni Multiflori, Herba Cistanches, Radix Salviae Miltiorrhizae, Radix Notoginseng, Radix Puerariae, Herba Epimedii, Rhizoma Chuanxiong, and Radix Rehmanniae | <in vivo>(6)
Female SD rats (aged 22 days) |
not reported | Gastric perfusion | 1.5 ml For 14 days |
1) Morphology: stratum granulosum of ovarian follicles ↑ 2) FBG (-), serum fasting insulin ↓, insulin sensitive index ↑ 3) mRNA expressions of PKBα in the hepatic, adipose, and skeletal muscle tissues ↑, protein expressions of PKBα in the hepatic and adipose tissues ↑, protein expressions of PKBα in thecal and granulosa cells of antral follicles ↑ |
Li et al. (2010) |
| Changbudodam-Tang & Yongdamsagan-Tang |
Rhizoma atractylodis, Rhizoma cyperi, Fructus ponciri, Pericarpium citri nobilis, Poria, Arisaematis Rhizoma, Radix glycyrrhizae, Massa Medicata Fermentata, and Zingiberis Rhizoma & Radix gentianae, Bupleuri Radix, Alimatis Rhizoma, Lignum akebiae, Plantaginis Semen, Hoelen, Rehmanniae Radix, Angelicae Gigantis Radix, Gardeniae Fructus, Scutellariae Radix, and Radix glycyrrhizae |
<in vivo>(3)
Virgin adult cycling SD rats (190–210 g) |
Solvent: 1,000 ml of boiling distilled water Time: 43 h |
Oral (zonde needle) | 50 mg/kg/2d for Changbudodam-Tang, & 40 mg/kg/2d for Yongdamsagan-Tang For 60 days |
1) Morphology: numbers of corpora lutea and corpora albicantia ↑, number of cystic follicles ↓, number of growing secondary follicle ↑ 2) Expression of NGF in ovaries ↓, expression of NGF in pituitary and hippocampus (-) 3) Ovarian weight ↑, body weight (-) |
Lee et al. (2003) |
| CHM1 & CHM2 |
Radix Astragali, Radix Rehmanniae Preparata, Cuscuta chinensis Lam, Fructus Ligustri Lucidi, Fructus Psoraleae, Radix Salviae Miltiorrhizae, Rubus idaeus Linn & Cuscuta chinensis Lam, Fructus Ligustri Lucidi, Rubus idaeus Linn |
<in vivo>(2)
Neonatal female SD rats (aged 9 days) |
Solvent: boiling water Time: twice for 60 min |
Oral | 0.54(CHM1), 0.24(CHM2) g/kg/d For 12 weeks |
1) Recovery of estrous cycle 2) LH/FSH ↓, free androgen index ↓, androstenedione ↓ 3) mRNA expression of PPARG1 in ovaries ↑, mRNA expression of HDAC3 in ovaries ↓ |
Gu et al. (2015) |
| GZYKF | Semen Cuscutae, Rhizoma Atractylodis Macrocephalae, Angelica sinensis, Adenophora tetraphylla, Plantago asiatica, Rubia cordifolia, and Luffa cylindrica | <in vitro> Granulosa cells from female SD rats (aged 23–25 days, 60 ± 10 g) |
Solvent: water Time: room temperature for 1 h and 100˚C for 1 h |
– | 13% rat serum containing GZYKF (administration of 5, 10, 20 g/kg/d for 4 days in low, medium, high-dose rat groups) For 72 h |
1) mRNA expression of Beclin-1 ↓ 2) mRNA expression of LC3 ↓ (only from high-dose group) 3) protein expression of Beclin-1 ↓ 4) Protein expression of LC3 (-) 5) mRNA expression of tumor suppressor p53 ↓, mRNA expression of sestrin2 ↓(only from low and medium-dose groups) 6) mRNA expressions of TSC1, TSC2 and mTOR (-) 7) mRNA expression of AMPK ↑(only from high-dose group) 8) Protein expressions of mTOR, p-mTOR, tumor suppressor p53, AMPKα and sestrin ↑ |
Xing et al. (2017) |
| HemoHIM | Angelica Radix, Cnidii Rhizoma, and Paeonia Radix | <in vivo>(3)
SD female rats (210–230 g) |
Solvent: boiling water Time: 4 h |
[1] Oral [2] Intraperitoneally |
[1] 100 mg/kg/d For 35 days [2] 50 mg/kg/2d For 35 days |
1) Body weight (-), ovary weight ↑(only oral 100 mg/kg/d) 2) Morphology: number and size of corpora lutea ↑, cystically dilated atretic follicles ↑ 3) Level of NGF protein in ovaries ↓ |
Kim et al. (2009)
Pak et al. (2009) |
| Heqi san | Curculigo orchioides Gaertn., Schisandra chinensis (Turcz.) Baill., Cynanchum otophyllum 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., and Epimedium davidii Franch. | <in vivo>(1)
Female SD rats (aged 3 months, 300 ± 20 g) |
Solvent: ddH2O Time: twice for 1.5 h |
Oral cannula | 8.1 g/kg/d For 30 days |
1) LH ↓, T ↓, E2 (-) 2) Insulin resistance ↓ 3) Histology: ovarian volume ↓, organ coefficient ↑, cystic dilatation in the ovarian follicles ↓, the oocytes in the follicles ↑, the number of granule cell layers ↑ 4) mRNA expressions of GLUT4 and PTEN in ovaries ↑ 5) Protein expressions of IRS-1 and PTEN in ovaries ↓ 6) Protein expressions of GLUT4 and p-IRS-1 in ovaries (-) 7) Expression of rno-miR-144-3p in ovaries ↓ 8) Expressions of rno-miR-30c-2-3p, rno-miR-486, and rno-miR-3586-3p in ovaries ↓ 10) Expression of rno-miR-146b-5p in ovaries ↑ |
Zhao et al. (2017) |
| IMOD | Rosa canina, Urtica dioica, and Tanacetum vulgare | <in vivo>(4)
Adult female albino Wistar rats (200 ± 10 g) |
Solvent: ethanol (96%) Time: 30 days |
Intraperitoneally | 30 mg/kg/d For 21 days |
1) Body weight ↓, ovarian weight ↓ 2) Recovery of estrous cycle 3) Histomorphology: total populations of ovarian atretic and cystic follicles ↓, number of corpora lutea ↑ 4) Serum levels of lipid peroxidation, peroxynitrite, TNF-α, and T ↓; serum levels of SOD, catalase, GPx, P, and E2 ↑ 5) Ovarian levels of lipid peroxidation, peroxynitrite, PGE ↓; ovarian levels of SOD, catalase, and GPx ↑ |
Rezvanfar et al. (2012) |
| Kyung-Ok-Ko | Rehmannia glutinosa Liboschitz var. purpurae Makino (Scrophulariaceae), Lycium chinense Miller (Solanaceae), Aquillaria agallocha Roxburgh (Thymelaeaceae), Poria cocos Wolf (Polyporaceae), Panax ginseng C.A. Meyer (Araliaceae), and honey | <in vivo>(1)
Female SD rats (aged 23 days) |
Solvent: hot water (80˚C) Time: 72 h |
Oral | 0.5, 1.0, 2.0 g/kg/d For 40 days |
1) Body weight ↓ 2) Ovary weight ↓(only 2.0 g/kg/d) 3) Number of follicular cysts ↓(only 2.0 g/kg/d), size of follicular cysts ↓(only 2.0 g/kg/d) 4) Insulin (-), insulin resistance (-) 5) E2 ↓(only 2.0 g/kg/d), P (-) 6) Recovery of estrous cycle (only 2.0 g/kg/d) 7) CD8 (+) in lymph node ↓(only 2.0 g/kg/d), CD4 (+) in lymph node (-) 8) CD8 (+) in ovary ↓(only 2.0 g/kg/d) 9) mRNA expressions of CD11b and CD3 in ovaries ↓(only 2.0 g/kg/d), Iba-1 immunoreactivity ↓(only 2.0 g/kg/d) 10) mRNA expressions of IL-1β, IL-6, TNF-α, IL-8, MCP-1, and iNOS in the ovaries ↓(only 2.0 g/kg/d) 11) mRNA expressions of EGF and TGF-β in the ovaries ↑(only 2.0 g/kg/d) |
Jang et al. (2014) |
| Rehmannia glutinosa, Liboschitz var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey | <in vivo>(1)
Female SD rats (aged 23 days) |
not reported | Oral | 2.0 g/kg/d For 20 days |
1) Body weight ↓ 2) Histomorphometric study: size and number of follicular cysts in the ovaries ↓, sizes of uteri ↓, outer diameters of uteri ↓, normalization of endometrium, myometrium, epimetrium, and cystic glands 3) Recovery of estrous cycle 4) Uterine weight ↓ 5) TUNEL positive cells ↓ 6) Iba-1+ macrophages ↓, CD4+ T cells ↓, CD8+ T cells ↓ 7) mRNA expressions of IL-1β, IL-6, IL-8, and MMP-3 in uteri ↓ 8) mRNA expressions of IGF-β, TGF-β, TGF-β1, and VEGF in uteri ↑ |
Lee et al. (2016) | |
| XYS | Radix Bupleuri, Angelica, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Ginger, Mint, and Glycyrrhizae | <in vivo>(7)
[1] Female SD rats (aged 8 weeks, 220 ± 20 g) <in vitro> [2] Granulosa cells from female SD rats (aged 21 days) |
not reported | Gavage | [1] 0.505, 1.01 g/kg/d For 4 weeks [2] 15% rat serum containing XYS (administration of 1.01 g/kg/d for 3 days in female SD rats) For 24 h |
[1] 1) Recovery of estrous cycle 2) Morphology: number of cystic follicles ↓, recovery of cystic follicles formation and follicle development abnormalities 3) Noradrenaline in serum ↓(only 0.505 g/kg), noradrenaline in ovary ↑, LH ↓(only 1.01 g/kg), E2 (-), P ↑(only 1.01 g/kg) 4) Expression of β2R in the primordial and primary follicles ↓ 5) TUNEL positive cells in the antral follicles ↓ 6) Bax/Bcl-2 (-), cleaved caspase-3/GAPDH ↓(only 1.01 g/kg) 7) Expression of LC3A in the granulosa cells of the antral and cystic follicles ↓ 8) Conversion of LC3A-I to LC3A-II ↓(only 1.01 g/kg), conversion of LC3BI to LC3B-II ↓ 9) Phosphorylation of S6K I and Akt in ovarian tissues ↑ 10) Expression of DβH and c-fos in locus coeruleus ↓(only 1.01 g/kg) [2] 1) Expression of β2R ↓ 2) Expression of LC3 ↓(only 1.01 g/kg) 3) Conversion of LC3A-I to LC3A-II ↓(only 1.01 g/kg), conversion of LC3BI to LC3B-II ↓(only 1.01 g/kg) 4) Phosphorylation of S6K I and Akt ↑(only 1.01 g/kg) |
Sun et al. (2017) |
Akt, protein kinase B; AMPK, Adenosine monophosphate-activated protein kinase; Bax, B-cell lymphoma-2 associated X protein; Bcl-2, B-cell lymphoma-2; CD, Cluster of differentiation; CHM, Chinese herbal medicine; Cleaved caspase-3, Cleaved cysteinly aspartate specific proteinase-3; DβH, Dopamine beta hydroxylase; EGF, Epidermal growth factor; FBG, Fasting blood glucose; FSH, Follicle-stimulating hormone; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; GPx, Glutathione peroxidase; GULT4, Glucose transporter type 4; GZYKF, Gui Zhu Yi Kun formula; HDAC, Histone deacetylase; Iba1, Ionized calcium-binding adapter molecule 1; IL, Interleukin; iNOS, Inducible nitric oxide synthase; IRS, Insulin receptor substrate; LC, Light chain; LH, Luteinising hormone; MCP-1, Monocyte chemoattractant protein-1; mTOR, Mammalian target of rapamycin; NGF, Nerve growth factor; PGE, Prostaglandin E; PKBα, Protein kinase Bα; PPARG, Peroxisome proliferator-activated receptor gamma; PTEN, Phosphatase and tensin homolog; S6K I, Ribosomal protein S6 kinase polypeptide I; SD, Sprague-Dawley; SOD, Superoxide dismutase; TNF, Tumor necrosis factor; TSC, Tuberous sclerosis protein; TUNEL, Terminal deoxynucleotidyl transferase dUTP nick end labeling; VEGF, Vascular endothelial growth factor; XYS, Xiao-Yao-San; β2R, Beta 2 adrenergic receptor.
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.