Phytochemicals: Alternative for Infertility Treatment and Associated Conditions

Table 1

Medicinal plants used for the treatment of infertility and associated conditions.

Sl. no.	Plant	Common/traditional names	Extract/phytoconstituents	Part used	Mode of administration	Dose	Duration	Mechanism of action	References
1	Cinnamomum zeylanicum (Lauraceae)	Dalchini	Cinnamon oil (cinnamaldehyde)	Bark	Gavage	100 mg/kg	10 weeks	Increases sperm quality and improves sperm motility, helpful in asthenozoospermic conditions	[14, 19]
2	Punica granatum (Lythraceae)	Anaras pomegranate	Pomegranate extract		Gavage	100 mg/kg, 200 mg/kg, 400 mg/kg	8 weeks	Reduces estrogen, andrestandion, and free testosterone hormones in polycystic ovary syndrome (PCOS)	[14, 20–22]
			Pomegranate juice	Fruit	Oral	2 L/week		Increases fertility in male and increases live births
			Pomegranate juice	Fruit	Oral	50 mg/kg		Reduces testosterone level in polycystic ovary syndrome (PCOS)
			Methanol extract of pomegranate pericarp (PME)	Peel	Oral	100 mg/kg		Inhibits proliferation of cervical, endometrial, and ovarian carcinoma cell lines
3	Withania somnifera (L.) Dunal (Solanaceae)	Ashwagandha, Indian ginseng	Hydroalcoholic extract (combination of Withania somnifera and Tribulus terrestris)	Root (WS), fruit (TT)	Oral	100 mg/kg (WS), 98 mg/kg (TT)	28 days	Increases follicle-stimulating hormone (FSH) level	[14, 23, 24]
								Decreases luteinizing hormone (LH) and testosterone levels
								Prevents ovarian dysfunction
			Methanolic extract	Roots		400 ng/μL		Reduces preantral and antral follicles and corpus luteum
								Increases gonadotropin hormone secretion and thus improves the process of oogenesis via GABA- (gamma-aminobutyric acid-) mimetic properties
4	Matricaria chamomilla (chicory)	Chamomile	Hydroalcoholic extract	Whole plant	Oral	25 mg/L, 50 mg/L	12 days	Increases progesterone, dehydroepiandrosterone, and 17β-estradiol levels	[14, 25, 26]
								Decreases ROS (reactive oxygen species), antrum formation, and follicular diameter
								Prolongs oocyte survival
			Aqueous extract	Flower	Oral	5 mL, twice daily	4 weeks	Decreases serum prolactin levels in idiopathic hyperprolactinemia
5	Camellia sinensis (Theaceae)	Chinese tea	Black tea extract	Leaves	Oral	1 mL/100 g body weight daily	28 days	Increases serum estradiol	[14, 27–29]
								Decreases estrogen-dependent menopausal symptoms
			Crude phenolic extract	Leaves	Oral	100, 200, and 400 mg/kg body weight	15 days	Increases serum prolactin level
			Green tea extract	Leaves		50, 100, and 200 mg/kg body weight	29 days	Restores concentration and secretion of FSH (follicle-stimulating hormone), LH (luteinizing hormone), estradiol, and testosterone in letrozole-induced PCOS (polycystic ovary syndrome)
6	Phoenix Dactylifera (Arecaceae)	Date palm	Ethanol extract		Gavage	25, 50, 100, 150, 200, and 250 mg/kg/day	8 weeks	Decreases levels of testosterone and estradiol	[14, 30]
7	Foeniculum vulgare (Umbelliferae)	Fennel	Acetone extract	Fruit	Oral	5-10 g	15 days (male)	Decreases total protein concentration in the vas deferens and testes but increases in the prostate gland and seminal vesicles	[14, 31, 32]
			Fennel oil				10 days (female)	Leads to vaginal cornification and oestrus cycle
								Increases the growth of mammary glands and induces prolactin secretion for the presence of dianethole and photoanethole
8	Nigella sativa (Ranunculaceae)	Black cumin	Hydroalcoholic extract	Seed	Oral	50, 100, and 200 mg/kg	30 days	Increases LH (luteinizing hormone) and testosterone and estrogen levels and decreases progesterone and antioxidant enzymes in PCOS (polycystic ovary syndrome)	[14, 33, 34]
			Ethanol extract	Seed	Parenteral	50 μg/mL	20 days	Increases rate of maturation, fertilization, and blastocyst formation
								Increases ovulation in PCOS (polycystic ovary syndrome) by reducing LH (luteinizing hormone) dominance over FSH (follicle-stimulating hormone)
9	Glycyrrhiza glabra (Fabaceae)	Licorice—liquorice	Ethanol extract	Plant	Gavage	100-150 mg/kg/day	3 weeks/21 days	Decreases ovarian cyst in PCOS (polycystic ovary syndrome)	[14, 35, 36]
								Improves oocyte fertilization rate and embryonic development in PCOS (polycystic ovary syndrome)
			Ethanol extract	Root	Oral	3000 mg/kg/day	6 weeks	Reduces endometrial implants in endometriosis by inhibiting COX-2 (cyclooxygenase-2) and IL-6 (interleukin-6) and decreasing expression of VEGF (vascular endothelial growth factor)
10	Crataegus monogyna (Rosaceae)	Hawthorn	Aqueous extract	Fruit	Gavage	20 mg/kg/day BW	28 days	Increases semen quality and decreases DOX (doxorubicin) toxic effects	[37, 38]
								Increases testosterone, LH (luteinizing hormone), and FSH (follicle-stimulating hormone) levels
11	Crocus sativus L. (Iridaceae)	Saffron	Saffron aqueous extract (crocin and safranal)	Stigma	Oral	200 mg, every morning	10 days	Increases erectile function in erectile dysfunction condition and increases sexual desires and intercourse satisfaction	[39–41]
			Hydroalcoholic extract		Parenteral	1, 2, and 4 dg/kg	10 days	Increases the concentration of LH (luteinizing hormone), FSH (follicle-stimulating hormone), and estradiol levels, produces significant effect on ovarian weight, and enhances folliculogenesis, thereby increasing secondary follicles in the ovary
12	Nigella sativa L. (Ranunculaceae)	Black cumin	Nigella sativa oil	Seed	Oral	2.5 mL, twice a day	2 months	Improves sperm count, pH, and motility	[39, 42–44]
								Also improves semen quality and volume
			Hydroalcoholic N. sativa seed extract	Seed				Increases corpus luteum and folliculogenesis
			N. sativa capsule		Oral	2 g, per day	3 months	Increases levels of serum LH (luteinizing hormone), FSH (follicle-stimulating hormone), and testosterone, increases semen volume and quality, and also increases sperm count and motility
13	Sesamum indicum L. (Pedaliaceae)	Sesame	Ethanol extract		Oral	100 mg/mL, 300 mg/mL	15 days	Increases FSH (follicle-stimulating hormone)	[39, 45]
								Decreases the total cholesterol levels which are increased in PCOS (polycystic ovary syndrome)
14	Trigonella foenum-graecum L. (Leguminosae)	Fenugreek	Seed extract (Furocyst)	Seed	Oral	500 mg, twice daily	3 months or 90 days	Increases levels of FSH (follicle-stimulating hormone) and LH (luteinizing hormone)	[46, 47]
								Decreases ovarian cysts and ovarian volume in PCOS (polycystic ovary syndrome)
								Causes regularity in menstruation
15	Lavandula angustifolia (Lamiaceae)	Lavender	Lavandula essential oil	Aerial parts	Parenteral	5 mg/kg, 10 mg/kg, and 20 mg/kg	14 days	Improves serum FSH (follicle-stimulating hormone) levels	[48, 49]
								Improves sperm viability and motility
16	Petroselinum sativum Hoffm. (Apiaceae)	Parsley	Hydroethanolic extract	Aerial parts	Oral	500 and 1000 mg/kg	28 days	Increases uterine protein levels and serum estradiol	[48, 50]
			Polyphenolic extract			200 mg/kg	28 days	Produces protective effects on fallopian tubes as inflammation or infection may cause infertility in females
17	Fumaria parviflora Lam. (Fumariaceae)	Indian fumitory	Ethanolic extract	Leaves	Gavage, once daily	100, 200, and 400 mg/kg body weight	70 days	Increases sperm count, serum testosterone level, sperm density, number of Leydig cells, spermatocytes, spermatozoids, spermatogonium, and weight of the testis and epididymis	[51]
18	Allium sativum (Amaryllidaceae)	Garlic	Aqueous garlic extract		Gavage(gastro-oral), once daily	60 or 120 mg/kg	28 days	Decreases the semen MDA (malondialdehyde) activity, weakens the chromic chloride effects on semen TAS (total antioxidant status), and enhances male fertility due to its antioxidant properties. These mechanisms suggest the protection of semen oxidation, a major cause of male infertility.	[51–53]
19	Origanum vulgare (Lamiaceae)	Oregano	Essential oil obtained by hydrodistillation	Leaves	Incubation	1.5 μL	5-10 minutes	Improves the parameters of mobility of sperms such as VCL (curvilinear velocity), VAP (average path velocity), ALH (amplitude of lateral head displacement), and VSL (linear velocity)	[53–55]
			Ethanol extract	Leaves	Intraperitoneal	100-400 mg/kg	28 days	Increases LH (luteinizing hormone) and testosterone levels eventually increasing sperm density
20	Panax ginseng Meyer (Araliaceae)	Ginseng	Aqueous extract		Oral	200 mg/kg	6 months	Improves germ cell counts, Sertoli cells, sperm number, and Sertoli cell index in aged males	[37, 56]
								Improves spermatogenesis by increasing testicular antioxidant concentration (ascorbic acid, glutathione, and α-tocopherol) and upregulated expressions of fatty acid-binding protein 9, triosephosphate isomerase 1 protein, and phosphatidylinositol transfer protein
21	Tribulus terrestris L. (Zygophyllaceae)	Puncture vein	Dried extract (androsten capsule)		Oral	250 mg (contains 37.5 mg protodioscin), every 8 hours	3 months	Increases serum DTH (dihydrotestosterone) concentration and improves sperm count and motility	[57, 58]
22	Chlorophytum borivilianum (Liliaceae)	Safed musli	Aqueous extract	Root	Oral by gavage, once daily	125 mg/kg/day and 250 mg/kg/day	28 days	Increases sperm count and enhances sexual arousal and libido	[57, 59, 60]
			Water soluble extract	Root tubers	Oral	500 mg, in two divided doses	12 weeks	Improves the quantity and quality of sperm and serum testosterone level
23	Mucuna pruriens (Fabaceae)	Kapikacchu	Seed powder	Seed	Oral	5 g/day	90 days	Increases concentration of sperm in oligozoospermic males and also increases sperm motility in asthenozoospermic condition	[57, 61]
								Improves semen quality
24	Cynomorium coccineum L. & Cynomorium songaricum Rupr. (Cynomoriaceae)	Desert thumb	Water extract (Cynomorium coccineum)		Oral	47 mg/100 kg BW	6 days	Increases ovarian weight and folliculogenesis and elicits changes in gonadotrophin levels	[57, 62]
		Suo Yang (Chinese)	Cynomorium songaricum		Oral	1 g/kg/day	56 days	Increases epididymal sperm count and testis weight, increases GDNF (glial cell-derived neurotrophic factor) expression, and enhances spermatogenesis
25	Butea superba (Leguminosae)	Red Kwao Krua	Ethanolic extract	Tuberous root	Oral	0.01, 0.1, or 1.0 mg/kg BW, daily	6 months	Increases sperm count and enhances sperm motility	[57, 63, 64]
			Powdered crude	Tuber root	Enteral (gastric tube)	2, 25, 250, and 1250 mg/kg/day	8 weeks	Increases sperm count and weight of the testis
26	Anthocleista vogelii Planch (Loganiaceae)	Cabbage tree	Ethanolic extract	Leaves	Oral	100 and 200 mg/kg BW	14 days	Increases estradiol level and induces production of estrogen	[65]
								Decreases CD4+ (cluster of differentiation 4) and CD8+ (cluster of differentiation 8) cytokine production
								Increases the activation of monocytes and granulocytes
27	Moringa oleifera (Moringaceae)	Drumstick tree	Ethanolic extract	Leaves		20, 50, and 100 μg/mL	28-29 hours	Improves the rate of oocyte maturation	[66–68]
			Hexane extract	Leaves	Gavage	0.5, 5, and 50 mg/30 g BW daily	21 days	Increases epididymal maturity thus enhancing spermatogenesis
								Increases the testis, seminal vesicles, and epididymis weights
								Increases thickness of the epididymal wall and seminiferous tubule diameter
28	Prunus persica (Rosaceae) Peach gum polysaccharides	Peach	Hydroalcoholic extract (ethanol)	Trunk	Gavage, twice daily	100 mg/kg	21 days	Increases sperm motility, sperm density, and normal sperm morphology rate	[69]
29	Arctium lappa L. (Compositae)	Burdock	Ethanolic extract	Root	Oral	200 or 300 mg/kg	1 month	Increases serum levels of LH (luteinizing hormone), FSH (follicle-stimulating hormone), and testosterone in nondiabetic condition	[70]
								Also increases sperm count and sperm viability in nondiabetic condition
30	Lycium barbarum (Solanaceae)	Wolfberry	Ethanolic extract	Fruit	Intragastric	20% for 0.2 g/kg, 40% for 0.4 g/kg, and 60% for 0.6 g/kg (once per day)	5 days	Increases sperm motility, density, and rate of normal sperm morphology rate	[69]
								Provides protective effect on male spermatogenesis, induced by cyclophosphamide
31	Globularia alypum L. (Globulariaceae)	Turbith	Aqueous extract	Leaves	Oesophagus cannula	300 mg/kg/day and 600 mg/kg/day	30 days	Activates spermatogenesis in males	[71, 72]
						100 mg/kg/day	15 days
32	Zingiber officinale (Zingiberaceae)	Ginger	Methanolic extract	Root	Oral	50, 100, and 150 mg/kg BW	48 days	Increases sperm count and sperm motility and increases seminiferous testicular volume	[71, 73]
								Increases testosterone level as well
								Decreases testicular damage, induced by busulfan
33	Glycyrrhiza uralensis Fisch (Leguminosae)	Licorice	Licorice extract	Rhizome		0.2, 2, and 20 μmol/L	72 hours	Increases spermatogonia proliferation and spermatocyte differentiation	[46, 74]
34	Morinda officinalis (Rubiaceae)	Indian mulberry	Morindae radix aqueous extract	Root	Incubation	10, 50, 100, and 250 mg/mL	24 hours	Increases levels of testosterone in H2O2- (hydrogen peroxide-) induced oxidative stress conditions	[46, 75]
35	Taraxacum officinale (Asteraceae)	Dandelion	Aqueous extract			1, 10, 25, and 50 mg/mL	12 and 48 hours	Increases testosterone levels in Leydig cells of males	[46, 76]
								Increases the protein and mRNA (messenger ribonucleic acid) levels of steroidogenic enzymes
36	Typha capensis (Rohrb.) N.E.Br. (Typhaceae)	Bulrush	Aqueous extract	Rhizomes	Incubation	10 and 100 μg/mL	24 and 96 hours	Increases testosterone levels	[46, 77]
			F1 fraction
37	Ferula hermonis Boiss (Apiaceae)	Lebanese viagra	Methanolic extract	Root	Oral	6 mg/kg	4 days	Improves LH (luteinizing hormone), FSH (follicle-stimulating hormone), estrogen, and progesterone levels thus helping in the maturation and growth of immature oocytes	[78]
								It also helps in uterine and endometrial development.
38	Justicia insularis T. Anders (Acanthaceae)		Aqueous extract	Leaves	Oral	50 mg/kg	20 days	Induces folliculogenesis and thus enhances corpus luteum number as well as implantation sites	[79]
39	Prunus mume (Rosaceae)	Chinese plum	Methanolic extract (3,4-dihydroxybenzaldehyde)	Fruit	Incubation		4 days	Increases estradiol secretion by granulosa cells via enhancing SF-1 (steroidogenic factor-1) gene expression and thus improves the quality of oocytes	[80]
40	Ginkgo biloba Linn. (Ginkgoaceae)	Maidenhair tree	Ginkgo biloba extract	Leaves	Gavage	50 mg/kg	One time	Increases testosterone and FSH (follicle-stimulating hormone) levels	[46, 81]
								Increases primary spermatocytes number, Leydig cells, round spermatids, and seminiferous tubule diameter
41	Eurycoma longifolia Jack (Simaroubacea)	Tongkat ali	Eurycoma longifolia extract		Oral	8 mg/kg BW	14 days	Increases sperm motility and sperm count, spermatogenesis, and testicular function	[46, 82]
								Decreases estrogen levels in males
42	Loranthus micranthus Linn. (Loranthaceae)		Aqueous methanolic extract	Leaves	Oral	100 and 200 mg/kg BW	14 days	Increases sperm viability and motility, Leydig cell count, testis weight, and diameter of seminiferous tubules	[46, 83]
								Decreases sperm abnormalities
43	Pedalium murex Linn. (Pedaliaceae)	Bada Gokhru	Methanol fruit fraction	Fruit	Oral	50 and 10 mg/kg BW	60 days	Increases fertility in males	[42, 84]
								Increases sperm motility and density, spermatogenesis, spermatocytes, spermatids, and interstitial and germinal cell count
								Increases LH (luteinizing hormone), FSH (follicle-stimulating hormone), and testosterone levels
44	Senecio biafrae (Oliv. & Hiern) J. Moore (Compositae)		Aqueous extract	Stems and leaves	Oral	8, 32, 64, and 128 mg/kg BW	20 days	Increases progesterone and estradiol levels and increases uterine weight	[85]
45	Milicia excelsa (Moraceae)	African teak	Aqueous extract	Root	Oral	14, 77, and 140 mg/kg/day BW	7 and 15 days	Increases LH (luteinizing hormone), FSH (follicle-stimulating hormone), estradiol, and progesterone levels	[46, 86]
								Decreases amenorrhea problems
46	Eucalyptus robusta Smith (Myrtaceae)	Safeda	Methanolic extract	Leaves	Oral gavage, once daily	25 mg/kg BW	9 days	Decreases endometritis in females by decreasing SAA (serum amyloid A), iNOS (inducible nitric oxide synthase), and NO (nitric oxide) and increasing COX-2 (cyclooxygenase-2)	[87]
47	Cyperus rotundus L. (Cyperaceae)	Nut grass	Water extract	Tubers	Oral	31.68 mg/kg/day	7 days	Increases LIF (leukemia inhibitory factor) and its binding to receptors in endometrium, thereby increasing integrins such as αVβ3 (alpha-v beta-3) and αVβ5 (alpha-v beta-5), resulting in increased trophoblastic cells adhesion and blastocyst implantation	[88]
48	Apium graveolens (Umbelliferae)	Celery	Aqueous extract	Leaves	Oral	100 and 200 mg/kg BW	1 month	Increases seminiferous tubule diameter	[33, 89]
								Increases spermatocytes number, spermatozoids, and spermatogonia
								Increases the number of spermatids with the intake of 200 mg/kg
								Increases the weights of the vas deferens, testes, and cauda epididymis
49	Phaleria macrocarpa (Thymelaeacea)	Mahkota dewa	Aqueous extract	Fruit	Oral	240 mg/kg	7 weeks	Increases sperm viability without any changes in sperm motility and morphology	[37, 90]
								Improves sperm quality
50	Anacyclus pyrethrum DC (Asteraceae)	Akarkara	Ethanolic extract	Root	Oral	50, 100, and 150 mg/kg	28 days	Increases sperm count, sperm viability, and sperm motility	[37, 91]
								Increases the testis weight, epididymis, seminal vesicles, and prostate
								Increases levels of LH (luteinizing hormone), FSH (follicle-stimulating hormone), and testosterone
								Enhances spermatogenesis