Table 2.

The regulatory effects of Chinese herbal formula on signal pathways related to POI

Recipe	Compositions	Classification	Efficacies	Pathways	Targets	Experimental model	Roles
Yulinzhu [6]	Radix Angelicae Sinensis, Radix Rehmanniae Praeparata, Semen Cuscutae, ginseng, branched Atractylodes macrocephala, Poria, Radix Paeoniae Alba, Cortex Eucommiae, Zanthoxylum piperitum. Rhizoma Ligustici, Radix Glycyrrhizae	Tonic prescriptions	Warming the kidneys and strengthening the spleen to produce essence	PI3K/Akt/mTOR signaling pathways	TSC1↓, TSC2↓, Rheb↑, P-s6k1↑, P-4e-bp1	SPF BALB/c female mice with normal motility cycles at 6 to 8 weeks of age.	It can inhibit microenvironmental oxidative stress.
Jiajian Guishen pill [8]	Semen Cuscutae, semen spleen, Radix Rehmanniae, Radix Rehmanniae, Radix Angelicae Sinensis, Radix Paeoniae Alba, Salviae miltiorrhiza	Tonic prescriptions	Tonifying the kidney, strengthening the spleen, tonifying the liver, and invigorating the blood	PI3K/Akt/mTOR signaling pathway	PI3K↑, Akt↑, mTOR mRNA↑	SPF ICR female mice.	Improve ovarian reserve function and increase the number of follicles.
Xianzi Yizhen capsule [9]	Radix Rehmanniae Praeparata, Radix et Rhizoma Polygonati, Radix et Rhizoma Drynariae, Radix et Rhizoma Continuum, Semen Cuscutae, semen spleen	Tonic prescriptions	Tonifying the kidney and filling the essence	PI3K/Akt/mTOR signaling pathways	Ki67↑, Akt↑, PI3K↑	SPF female C57BL/6J type mice.	Increase the content of primordial follicles, secondary follicles and sinus follicles, and decrease the content of atretic follicles.
Guiluo's Anzang decoction [12]	Radix Rehmanniae Praeparata, Fructus Fritillariae, Semen Cuscutae, Radix et Rhizoma Polygoni, Paeoniae Alba	Tonic prescriptions	Nourishing Yin, tonifying the kidneys, calming the mind, and relieving irritability	Bax/CytC/Caspase-3 signaling pathways	Bcl-2↑, Bax↓	SPF healthy female SD rats	Reduce granulocyte apoptosis and increase granulocyte secretion.
Kuntai capsule [14, 38, 39, 46, 47, 57]	Radix Rehmanniae Praeparata, Rhizoma Polygonati, Radix Paeoniae Alba, Radix Scutellariae Praeparata, Radix Aconiti, Poria	Tonic prescriptions	Nourishing Yin, clearing heat, calming the mind, and relieving irritability	Bax/CytC/Caspase-3 signaling pathways, p-38/Fas/FasL signaling pathways, TGF-β/Smads signaling pathways, NF-kB signaling pathways	Bcl-2↑, Bcl-xl↑, Bax↓, Bad↓, Fas mRNA↑, FasL mRNA↓, GDF-9↑, EGR-1↑, Smad7↓, VEGF↑, bFGF↑	SPF healthy female SD rats	Maintain the balance between pro-apoptotic and anti-apoptotic proteins and improve ovarian reserve function; improve ovarian blood supply, promote follicle development, reduce follicular atresia and increase the number of mature follicles present in rats.
Yangyin Shugan granule [15]	Radix Bupleurum, Radix Paeoniae Alba, etc.	Mediative formulas	Nourishing Yin and soothing the liver	Bax/CytC/Caspase-3 signaling pathways	Bcl-2↑, Bax↓, Caspase-3↓, FOXO3a↓	SPF healthy female SD rats	It can inhibit apoptosis.
Zuogui pill [17, 18, 21, 41, 48, 64]	Radix Rehmanniae Praeparata, Rhizoma Dioscoreae, Fructus Lycii, Cornu Cervi Pantotrichum, Radix Achyranthes Bidentatae, Semen Cuscutae, antler gum, turtle board gum	Tonic prescriptions	Nourishing Yin, tonifying the kidney, and nourishing the blood	Bax/CytC/Caspase-3 signaling pathways, FOXO3, SCF, TGF-β/Smads signaling pathways	Bcl-2 mRNA↑, Bax↓, FOXO3a↓, CTX↑, Cx43 mRNA↑, Smad2↑, GDF-9↑	Human ovarian granulosa cells; SPF 8-week-old BALB/c female mice	It can inhibit chemotherapy-induced granulosa cell apoptosis and protect ovarian function; improve suture junctions; promote recruitment of initiating follicles, promote follicular development, inhibit follicular atresia, and regulate ovarian function.
Erxian decoction [20, 52]	Herba dipteris, Epimedium herba, Phellodendron phellodendron, Euphorbia officinalis, Angelica, Anemone anemone	Tonic prescriptions	Warming kidney Yang, tonifying kidney essence, and dipping kidney fire	FOXO3 transcription factor -P27/Bim	FOXO3↓, P27KiPi↓, Bim↓	Clean-grade SD healthy female rats	Promote granulosa cell proliferation and inhibit granulosa cell regulation; promote the secretion of vascular growth factor associated with premature ovarian failure in rats, and enhance ovarian reserve function.
Bushen Jianpi decoction [29, 30]	Polygonatum officinale, Radix et Rhizoma Polygonatum, Radix et Rhizoma Polygonatum, Fructus Lycii, Atractylodes Macrocephala, Poria	Tonic prescriptions	Tonifying the kidneys and strengthening the spleen	ER/c-myc/TERT signaling pathways	c-Myc↑, TERT↑	B6AF1 female mice	It can promote the proliferation and development of ovarian granulosa cells and the maturation of oocytes.
Bushen Tiaochong decoction [33, 42, 55]	Cuscuta seed, Euphorbia officinalis, Ripe Rehmannia, Cistanche, yellow essence, amethyst, Schisandra fruit, Angelica, Ligusticum wallichii, etc	Tonic prescriptions	Tonifying the kidneys and regulating the flushing process	P53, SCF, NF-kB signaling pathways	P53↓, GnRHR↑, Cx-37↑, SCF↓, VEGF↑, bFGF↑, TNF-α↓, IFN-γ↓	Clean-grade female SD rats	Prolong the time of apoptosis, reduce the occurrence of follicular atresia, improve the reserve capacity of ovarian receptors and thus coordinate ovarian function; promote the growth and development of early follicles, improve the function of ovarian tissue gap junctions and thus repair ovarian function damage in rats.
Bushen Huoxue decoction [36, 50]	Herba epimedium, Semen Cuscutae, Fructus Lycii, Fructus Lycii, Fructus Morindae, mulberry, raspberry, yam, Radix Codonopsis, Radix Astragali, Radix Paeoniae Alba, Fructus Ulmoides, bark, Salviae Miltiorrhiza, Radix Angelicae Sinensis, Radix Angelicae Sinensis	Tonic prescriptions	Tonifying the kidney and invigorating the blood	Ki67/ERK	p-ERK1/2↑, ERK1/2↑	Mouse intrasinus follicular granulosa cells	It can improve follicular development and increase the proliferation of follicular granulosa cells and granulosa cells of the oocyte complex in mice with reduced ovarian reserve function at an advanced age.
Gui Zhi Fu Ling capsule [40]	Cassia twig, Poria cocos, peony bark, peony root, peach kernel	Blood-regulating formula	Promoting blood circulation, removing blood stasis, and eliminating symptoms	p-38/Fas/FasL	Fas/FasL↓	SPF female Wistar rats	Reduce ovarian apoptosis.
Kun Bao pill [43]	Chasteberry, raspberry, Cuscuta, etc.	Tonic prescriptions	Nourishing the liver and kidneys, calming and tranquilizing the mind, nourishing the blood, and opening the meridians	SCF, TGF-β	CTGF↓, TGF-β1↓, SCF↓	SPF healthy female SD rats	Reduce ovarian fibrosis.
Siwu mixture [45]	Radix Rehmanniae Praeparata, Radix Angelicae Sinensis, Radix Paeoniae Alba, Ligustici wallichii	Tonic prescriptions	Nourishing Yin and replenishing blood	TGF-β/Smads signaling pathways	Smad2/3↑, Cyp19a1↑	Healthy female SD rats	It can promote follicular growth and development and slow down follicular atresia.
Yiqi Yangrong Fujing formula [54]	Astragalus, Bacopa monnieri, Dendrobium Ferrugineum, Rhizoma Polygonatum	Tonic prescriptions	Benefiting Qi, warming Yang, nourishing Yin, and restoring essence	NF-kB signaling pathways	IL-2↑, TNF-α↑	Healthy female C57BL/6 mice	Inhibit the apoptosis of ovarian granulosa cells, restore ovarian function, and enhance ovarian reserve capacity.
Bushen Culuan formula [61]	Radix chasteberry, Semen Cuscutae, Fructus Lycii, Radix et Rhizoma mulberry, Radix et Rhizoma Sequoiae, Radix Angelicae Sinensis, Radix Paeoniae Alba, Radix Zelenium	Tonic prescriptions	Tonifies the kidneys and enhances the essence	Bax/CytC/Caspase-3 signaling pathways, Keap1/Nrf2/ARE signaling pathways	Akt↓, mTOR mRNA↓, PI3K mRNA↓, Bcl-2↑, Keap1↓, Bach1↓	SPF 8-week-old female BALB/c mice	Reverse excessive apoptosis of granulosa cells, reduce follicular atresia, reduce excessive activation of primordial follicles, and protect ovarian reserve; reduce ovarian oxidative damage.
Yiguan Jian decoction [62]	Raw Rehmanniae, Radix Aristophanae, Angelica, Wolfberry, chinaberry	Tonic prescriptions	Nourishing Yin and softening the liver	Keap1/Nrf2/ARE signaling pathways	T-SOD↑, CAT↑, MDA↓, Caspase-3↓	SPF healthy female SD rats	Protect normal ovarian cells.