2.1. Herbal drugs
Herbal medicine is extremely popular since ancient times in Ayurveda, Siddha, Chinese, and Unani systems of medicine [3, 33]. Many plants and/or their extracts have been used to prevent hair loss and treat alopecia. These plants and their properties are summarized in Table 2.
|Botanical name||Family||Possible mechanisms of action|
|Thuja orientalis||Cupressaceae||Inhibition of 5α-reductase enzyme|
|Citrullus colocynthis||Cucurbitaceae||Antiandrogenic effect|
|Rosmarinus officinalis||Lamiaceae||Increasing the circulation of the scalp|
|Camellia sinensis||Theaceae||Inhibition of 5α-reductase enzyme|
|Asiasari radix||Aristolochiaceae||Inducing early telogen-to-anagen conversion|
|Polygonum multiflorum||Polygonaceae||Proliferation of dermal papilla cells, expression of FGF-7, up-regulating Shh and β-catenin expression|
|Allium tuberosum Rottler ex Spreng||Liliaceae||Stimulating expression of IGF-1|
|Cucurbita pepo||Cucurbitaceae||Inhibition of 5α-reductase enzyme|
|Serenoa repens||Arecaceae||Inhibition of 5α-reductase enzyme, decreasing DHT uptake by hair follicle, decreasing the binding of DHT to androgenetic receptors|
|Panax ginseng C.A. Meyer||Araliaceae||Expression of VEGF, antiapoptotic activity|
|Eclipta alba||Asteraceae||Anagen phase induction, reducing level of TGF-β1|
|Avicennia marina||Acanthaceae||Inhibition of 5α-reductase enzyme|
|Phyllanthus niruri||Euphorbiaceae||Inhibition of 5α-reductase enzyme|
|Oryza sativa||Inhibition of 5α-reductase enzyme|
|Sophora flavescens Aiton||Leguminosae||Inhibition of 5α-reductase enzyme, vasodilator and antiandrogen effects|
|Chrysanthemum zawadskii var. latilobum||Asteraceae||Anti-inflammatory effect|
|Scutellaria baicalensis||Lamiaceae||Inhibiting nuclear translocation of the androgen receptor, enhance proliferation of human dermal papilla cells|
|Cuscuta reflexa Roxb||Convulvulaceae||Inhibition of 5α-reductase enzyme|
|Pueraria thomsonii||Leguminosae||Inhibition of 5α-reductase enzyme|
|Curcuma aeruginosa||Zingiberaceae||Inhibition of 5α-reductase enzyme|
|Hura crepitans||Euphorbiaceae||Inhibition the neurotrophin (NT)-4 activation|
|Tobacco leaves||Solanaceae||Inhibition of 5α-reductase enzyme|
|Tectona grandis Linn||Verbinaceae||Unknown|
|Boehmeria nipononivea||Urticaceae||Inhibition of 5α-reductase enzyme|
Some plants used for hair loss and their properties.
2.1.1. Thuja orientalis
Thuja orientalis (T. orientalis, family Cupressaceae), also known as T. occidentalisin Eastern or Arbor vitae or white cedar, is a plant that is widely distributed in East Asia [34, 35]. In addition to grown as an ornamental tree in Europe, it has been used to treat various diseases concerning respiratory system, skin disorders, and urinary system. Nowadays, it is often used in homeopathy and evidence-based phytotherapy . It has also been traditionally used to promote hair growth in the oriental medicine. Although T. orientalishas a strong 5α-reductase inhibitor effect, the exact mechanism of hair-promoting effect of T. orientalisis still unknown. In the literature, there are few studies investigating the association between T. orientalisand hair growth. In animal studies, it was demonstrated that topically application of T. orientalisextract induced an earlier anagen phase and prolonged the mature anagen phase. In immunohistochemistry analysis, it was also shown that the expression levels of β-catenin and sonic hedgehog (Shh) were upregulated in T. orientalisextract-treated group at 14 days, compared to those in the control or 1% minoxidil-treated group. In mice treated with T. orientalis, authors observed an increase in both the number and size of hair follicles [34, 36]. Even, cubosomal suspension of T. orientalisextract was found to be more effective due to increased skin penetration of the T. orientalis.
2.1.2. Citrullus colocynthis
Citrullus colocynthis (C. colocynthis)Shrad (family Cucurbitaceae), known as Indrayan, is one of the numerous herbal drugs recommended by the traditional system of medicine for hair growth promotion in India [38, 39]. It contains β-sitosterol, campesterol, stigmasterol, α-spinasterol, and cucurbitacin glycosides. It has several pharmacological effects such as immunostimulating, antiandrogenic, antibacterial, and hypoglycaemic in addition to hair-promoting effect . There are few animal studies evaluating hair growth-promoting activities of the C. colocynthis. Roy et al. reported that topical application of C. colocynthisplant, especially petroleum ether extracts, had an astonishing effect on hair growth initiation time, complete hair growth, and the length of hair follicle in albino rats. In qualitative studies, hair growth was initiated in the denuded area on the 4th day and 5th day with 5 and 2% ointment of petroleum ether extract of C. colocynthis, respectively. But, hair growth initiation was noted on the 6th day and the second week in minoxidil-treated standard group and in control group, respectively. Complete hair growth was recorded on the 16th, 18th, 19th, and 24th days in the 5% petroleum ether extract group, 2% petroleum ether extract group, minoxidil group, and control group, respectively. In quantitative studies, at 30 days after treatments with extracts of C. colocynthis, anagenic population were recorded as 67 and 47% in the minoxidil group and control group, whereas it was noted as 75 and 72% in the 5 and 2% petroleum ether extract groups, respectively. In both 2 and 5% petroleum ether extract groups, approximately 50% of hair population had length of 0.5 mm and above at 30 days after treatment . In another study, Dhanotia et al. evaluated the hair growth-promoting activities of the petroleum ether extract from the fruit of C. colocynthison albino mice using a testosterone-induced alopecia model. As a result of both qualitative and quantitative studies on hair growth, they suggested to present the inhibition of androgenic activity and altered anagen/telogen ratio and follicular density . Polyherbal formulation including C. colocynthiswas also shown to present hair growth-promoting activity on rats. Hair growth initiation time was markedly reduced to one-third on treatment with the prepared formulation compared to control group. The time required for complete hair growth was also reduced by 32%. Quantitative analysis of hair growth cycle after treatment with formulations and 2% minoxidil solution (positive control group) exhibited greater number of hair follicles in anagenic phase compared with control .
2.1.3. Rosmarinus officinalis
Rosmarinus officinalis (R. officinalis), commonly known as Rosemary, is a plant that belongs to family Lamiaceaeand naturally grows in all Mediterranean countries [41, 42]. It has antiandrogenic effect and hair growth-promoting activity apart from antioxidative, anti-inflammatory, antibacterial, and antitumor effects . In CAM, R. officinalisis often used in aromatherapy to treat anxiety-related conditions and increase alertness, although it has occasionally been used to stimulate hair growth . The exact mechanism of hair growth is still unclear, but it is believed to act by increasing the circulation of the scalp. Murata et al. showed that topical administration of R. officinalisextracts solution (2 mg/day/mouse) improved hair regrowth in the testosterone-treated C57BL/6NCrSIc mice. They also showed significant promotion of hair growth after 16 days of topical administration. Among the some constituents of R. officinalis[i.e., rosmarinic acid, ursolic acid, 12-methoxycarnosic acid (12-MCA)], it was demonstrated that inhibitory activity of 12-MCA on 5α-reductase was higher than rosmarinic acid and ursalic acid (82.4, 14.2, and 2.5% inhibition at 200 μg/ml, respectively) .
2.1.4. Green tea
Green tea (Camellia sinensis, family Theaceae) is a well-known plant since ancient times, especially in China. It has been regarded to possess numerous pharmacological effects such as antimetastatic, anticancer, hepatoprotective, antidiabetic, antiobesity, anti-atherosclerotic, antibacterial, antiviral, anti-inflammatory, and antioxidant effects. It has been preferred in various dermatological diseases due to its mentioned beneficial effects worldwide. Human papilloma virus (HPV)-induced cervical cancer, genital warts, acne, rosacea, wound healing, atopic dermatitis, and keloids are diseases that green tea is commonly used. Apart from these diseases, it can be used to prevent or treat AGA by selectively inhibiting 5α-reductase activity. Catechins, a group of very active flavonoids, are a major component of green tea representing 60–80% of all polyphenols [44, 45]. There are four major catechins in green tea: epigallocatechin-3-gallate (ECGC), epigallocatechin (EGC), epicatechin gallate, and epicatechin [46, 47]. ECGC is the most highly bioactive catechin among these constituents . In a study, EGCG was found to cause significant human hair follicle elongation ex vivo. Indeed, it was also shown proliferative and antiapoptotic effects of ECGC on dermal papilla cells through the upregulations of phosphorylated Erkand Aktand by an increase in the ratio of Bcl-2/Bax ratio . Esfandiari et al. also reported that 33% of the mice that received 50% fraction of polyphenol extract from dehydrated green tea in their drinking water had significant hair regrowth within a period of 6 months compared with control group received regular drinking water .
2.1.5. Asiasari radix
Asiasari radix (A. radix, family Aristolochiaceae)or the radix of Asiasarum heterotropoides var. mandshuricumF. Maekawa usually grows in Korea, Japan, and China. A. radixis also called as ‘seshin’in Korea, as ‘saishin’in Japan, or Chinese wild ginger in English [50, 51]. It is used to treat various oral mucosal diseases such as aphthous stomatitis, gingivitis, local pain, and toothache apart from hair loss. A study from Korea showed its potent hair growth effect in mice. Though A. radixhad not inhibitory effect on 5α-reductase enzyme, authors suggested that the extract of the plants induced early telogen-to-anagen conversion. They also demonstrated expression of vascular endothelial growth factor (VEGF) in human dermal papilla cells cultured in vitro .
2.1.6. Allium cepa L
Onion juice (Allium cepaL., family Liliaceae)may be used in patients with AA because of garlic-like activity. Both herbal medicines have similar chemical constituents, especially Allicin. The exact mechanism of onion juice in the treatment of AA is still unknown [53, 54]. In the study by Sharquie and Al-Obaidi, at 4 and 6 weeks after topical application of onion juice twice a day, hair regrowth was observed as 73.9 and 86.9% of patients with AA, respectively. Patients should be informed about skin irritation on the skin surface in contact with the onion juice .
2.1.7. Polygonum multiflorum
Polygonum multiflorum(P. multiflorum, family Polygonaceae) is a very popular plant that has been widely used to treat various diseases in traditional Chinese medicine due to its different pharmacological effects such as antiaging, immunomodulating, antihyperlipidemia, hepatoprotective, anticancer, and anti-inflammatory. Besides these pharmacological effects, some studies have been reported related to hair growth promotion activity and hair-blacking effect [55, 56]. An active component of P. multiflorum, known as 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (THSG), has melanogenesis-stimulating effect in melanocytes . A new compound isolated from P. multiflorum, known as torachrysone-8-O-β-d-glucoside, induces a strong increase in the proliferation of dermal papilla cells and significantly increases the hair-fiber length of rat vibrissa follicles . Li et al. investigated hair growth promotion activities and their possible mechanism of P. multiflorumRadix (PMR) and P. multiflorumRadix Preparata (PMRP), both of them originated from P. multiflorum, in C57BL/6J mice. While hair covered skin ratio was higher in oral PMR groups than in PMRP groups, hair covered skin ratio was lower in topical PMR groups compared with topical PMRP groups. It was also demonstrated that the most possible cytokines regarding hair growth-promoting activity were fibroblast growth factor-7 (FGF-7) and Shh . Another animal study suggested that anagen phase was induced in resting hair follicles through upregulating Shh and β-catenin expression after topical application of P. multiflorum.
2.1.8. Allium tuberosum Rottler ex Spreng
Allium tuberosum Rottler ex Spreng(ATRES, family Liliaceae) is one of the Allium species like Allium tuberosumand Allium cepaL. It is widely distributed in East Asia and has been used for treating abdominal pain, diarrhea, hematemesis, and asthma in traditional medicine. Choline acetyltransferase activity of ATRESwas also reported [54, 59]. In the first study, evaluating the hair growth-promoting activity and its mechanism of action, ATREShas strong hair-promoting activity through stimulating expression of insulin-like growth factor-1 (IGF-1). Especially, the n-butanol extract of ATRESwas found to have most hair growth-promoting activity among the other compared groups including minoxidil, ethanol, n-hexane, distilled water groups on telogenic C57BL6/N mice .
2.1.9. Pumpkin seed oil
Pumpkin seed oil (PSO, family Cucurbitaceae) has been used for treating symptomatic benign prostatic hyperplasia through its inhibitory effect on 5α-reductase and antiandrogenic effect [60, 61]. In a randomized, double-blind, placebo-controlled study, self-rated improvement score, and self-rated satisfaction scores in the PSO-treated group were higher compared with the placebo group after oral administration of PSO at dosage of 400 mg/day for 24 weeks. At 24 weeks, mean hair count was recorded as increase of 40 and 10% in the PSO-treated group and placebo group, respectively. But, there was no significant difference in hair thickness between groups .
2.1.10. Serenoa repens
Serenoa repens(S. repens, family Arecaceae) is a native plant in West India and is grown in large quantities on the Atlantic southeast coast of North America. Saw palmetto is extracted from the berries of this plant. It is one of the herbal medicines that have inhibitory effect on both types 1 and 2 of 5α-reductase enzyme. In addition to inhibitory effect on 5α-reductase, S. repensmay also decrease DHT uptake by hair follicle and decrease the binding of DHT to androgenetic receptors [62, 63]. Anti-inflammatory effect has been demonstrated with a composition containing saw palmetto, carnitine, and thioctic acid in hair follicle keratinocytes . Both oral and topical use of S. repenscould be effective for treating androgen-induced alopecia in both sexes . In an open label study, 50 male patients with mild to moderate AGA were treated with S. repens320 mg/day for 24 months. After this period, only 38% of patients had an increase in hair growth. But, this improvement was lower than the group treated with finasteride (68% of patients) . Satisfactory results were also observed after application of topical products containing S. repensextract for 24 weeks in male patients with AGA . Recommended dose is 320 mg/day orally . Side effects of S. repensare minimal. The most known side effects are related to gastric symptoms, although contact dermatitis, feeling of coldness, mild burning sensation, undesirable smell, itching, and acne are the reported adverse events after topical application [63, 65, 66].
Ginseng (family Araliaceae) is traditionally used as an important herbal medicine in East Asian countries such as China, Korea, and Japan. It is divided into three categories: fresh ginseng, red ginseng, and white ginseng [67, 68]. Red ginseng is extracted from the steamed root of Panax ginseng C.A. Meyer, or known as Korean ginseng, and has various effects such as antiaging, antidiabetic, immunoregulatory, anticancer, neuroregulation, lipid-regulating and antithrombotic activities, and wound- and ulcer-healing activity [68, 69]. In addition to these properties, it has also been used for treating numerous hair diseases such as AGA and AA due to its promoting hair growth activity [70, 71]. There are very important chemical constitutes such as polysaccharides, ginsenosides (or known as saphonins), alkaloids, glucosides, and phenolic acid in ginseng . Ginsenosides are the major pharmacologically active ingredients of ginseng. To date, approximately 70 ginsenosides have been isolated from ginseng. In a study, it has been demonstrated that ginsenoside Rg3 had upregulated the expression of VEGF in human dermal papilla cells and mouse hair follicles . Antiapoptotic activity of fructus panax ginsengwas also shown in human dermal papilla cells .
2.1.12. Eclipta alba (L.) Hassk
Eclipta alba(L.) Hassk. (E. alba, family Asteraceae) is a medicinal plant commonly used for treating gastrointestinal disorders, respiratory tract disorders, fever, liver disorders, skin disorders, spleen enlargement, and cuts and wounds as well as hair loss and graying of hair. Numerous pharmacological activities including hepatoprotective, hair growth-promoting activity, antidiabetic, analgesic, anti-inflammatory, neuropharmacological activities, antioxidant, antimicrobial, antimalarial, cardiovascular effects, immunomodulatory, antiepilepsy, anticancer, antiulcer, and antihelmintic activities have been demonstrated. E. albaphytoconstituents including wedelolactone, eclalbasaponins, α-amyrin, oleanolic acid, ursolic acid, luteolin, and apigenin are responsible from main medicinal effects . Hair growth-promoting activity has been investigated on animals. The methanol extract of E. albahas been tested for its efficacy for hair growth in pigmented C57/BL6 mice. While the transition of telogen phase to anagen phase of hair growth was observed in approximately 87.5% animals treated with 3.2 mg/15 cm2 of methanol extract of E. alba, 50% of the animals treated with 1.6 mg/15 cm2 of methanol extract of E. albawas observed transition from telogen phase to anagen phase of hair growth. The rate of anagen induction was dependent on concentration of methanol extract of E. alba. The petroleum ether extract of E. albawas also investigated for its hair growth stimulatory effects in nude mice. This fraction of E. albasignificantly reduced the levels of transforming growth factor-β1 (TGF-β1) expression during early anagen and anagen-catagen transition, so that authors suggested that the duration of terminal differentiation was extended . Roy et al. also reported that the petroleum ether and ethanol extracts of E. alba(incorporated into ointment base in concentration of 2 and 5%, respectively) significantly reduced the time taken for hair growth initiation and completion in albino rats treated with the extracts .
2.1.13. Zizyphus jujuba
The plant, Zizyphus jujuba(Z. jujuba, family Rhamnaceae), is a widely distributed both in the Mediterranean regions and in the tropical and subtropical region of Asia and America. It can be used for several diseases such as diabetes, diarrhea, skin infections, liver complaints, urinary disorders, obesity, fever, pharyngitis, bronchitis, anemia, insomnia, and cancer . There is no sufficient data related to its hair growth-promoting effect. In a study by Yoon et al., a greater effect on length of hair was reported in mice treated with 1 and 10% of Z. jujubaessential oil after 21 days of treatment as compared to control group. Although the length of hair was measured as 9.96 mm with 1% of oil and 10.02 mm with 10% of oil, respectively, the length of hair was measured as 8.94 mm in the control group .
2.1.14. Allium sativum
Allium sativum(family Liliaceae), known as garlic, is one of the most popular herbal medicine and can be used in the treatment of various dermatologic conditions such as psoriasis, AA, keloid scar, wound healing, cutaneous corn, viral and fungal infection, leishmaniasis, and skin-aging and rejuvenation. Constituents of garlic include enzymes (e.g., alliinase), sulfur-containing compounds (e.g., alliin), compounds produced enzymatically from alliin (e.g., allicin), arginine, oligosaccharides, flavanoids, and selenium . In a double-blind randomized-controlled study, Hajheydari et al. reported that combination of topical garlic gel and betamethasone valerate cream was more effective than betamethasone valerate cream alone in patients with localized AA at the 3rd month. The number of total and terminal hairs in the group treated with garlic gel was significantly higher than those of the control group at the third months .
2.1.15. Avicennia marina
Avicennia marina(A. marina), also known as grey or white mangrove, is a traditional herbal plant belonging to family of Acanthaceae. However, it is traditionally used to treat various skin diseases in Egypt, antiandrogenic activity of A. marinaand a compound, avicequinone C, isolated from the hearthwood of A. marinawas firstly reported by Jain et al. . The results revealed that A. marinawas a potent 5α-reductase type 1 inhibitor, reducing the 5α-DHT production by 52% at the final concentration of 10 μg/mL . Moreover, among the thirty different extracts, the highest inhibitory activity was observed from the crude extract of A. marinaat a final concentration of 10 g/ml through the reduction in 5α-DHT formation by more than 50% .
2.1.16. Phyllanthus niruri
Phyllanthus ninuri(P. niruri, family Euphorbiaceae) is a widely used plant of genus Phyllanthusin traditional medicine. It is also known as ‘chanka piedra,’ ‘bhuiamlki,’ ‘zhuzicao,’ ‘dukung anak,’ ‘quebra-pedra,’and ‘chanca piedra.’ P. niruriusually grows in tropical and subtropical regions in Central and South American countries, India and East Asia and has several biologic activities such as antidiabetic, analgesic, wound healing, and immunomodulatory effects. It is traditionally used to cure of jaundice, fever, malaria, stomachache, urolithiasis, vaginal candidiasis, varicella, and tuberculosis by people living in these countries [84, 85]. Newly, inhibitory activity of petroleum ether extract of P. nirurion 5α-reductase type 2 enzyme was shown, and it has been suggested to be useful in the treatment testosterone-induced alopecia .
2.1.17. Rice bran
It has been believed that rice bran extract, which is produced by milled rice (Oryza sativa), has antioxidant, anticancer, and antihyperlipidemic effects as well as 5α-reductase inhibitory activity . The compounds having antioxidant activity are phenolic acids, flavonoids, anthocyanins, proanthocyanidins, tocopherols, tocotrienols, γ-oryzanol, and phytic acid . Very few studies exist to support the claims of the efficacy of rice bran. The hair growth-promoting activity of rice bran supercritical CO2 extract (RB-SCE) and its two components (linoleic acid and γ-oryzanol) were shown using real-time reverse transcriptase-polymerase chain reaction in C57BL/6 mice by Choi et al. . In a double-blinded randomized-controlled study, dermal application of 0.5% of RB-SCE (8 ml/day) to the head skin significantly increased hair density and hair diameter in male patients with alopecia for 16 weeks .
2.1.18. Sophora flavescens Aiton
Sophora flavescens Aiton(S. flavescens, family Leguminosae) is one of the important plants used in traditional Chinese medicine [89, 90]. It has been used for treating viral hepatitis, cancer, viral myocarditis, heat dysentery, hemafecia, jaundice, anuresis, leucorrhoea with reddish discharge, vulval swelling, pruritus vulvae, eczema, and trichomonas vaginalis [90, 91]. It is a strong inhibitor of 5α-reductase enzyme in addition to its vasodilatory and antiandrogen effects. Despite lack of proper clinical trials to support its efficacy for hair loss, the mechanism of affect on hair loss treatment is thought to be through these activities. It was demonstrated that the isolated two pterocarpans, L-maackiain and medicarpin, promoted the proliferation of human hair keratinocytes .
2.1.19. Laminaria japonica
Laminaria japonica(L. japonica) is a kind of brown algae and called as ‘kombu’in Japanese, ‘dashima’in Korean, and ‘haidai’in Chinese. The most consumed countries of L. japonicaare Far Eastern countries such as Korea, Japan, and China. L. japonicais believed to have beneficial effects for health; however, the mechanism of beneficial effects is not fully understood [92, 93]. The combination of L. japonicaextract and Cistanche tubulusaextract has the potential to promote hair growth. Oral administration of both L. japonicaextract at dosage of 54 mg/kg and Cistanche tubulusaextract at dosage of 162 mg/kg exhibited an excellent hair regrowth activity on mice. It has been thought that anti-inflammatory activities of the both plant extracts could play an important role to prevent hair loss and improve alopecia .
2.1.20. Chrysanthemum zawadskii var. latilobum
Chrysanthemum zawadskii var. latilobum(C. zawadskii, family Asteraceae) has been used for the treatment of pneumonia, bronchitis, cough, common cold, pharyngitis, bladder-related disorders, gastrointestinal disorders, and hypertension in traditional medicine for ages. Essential oil of the plant contains 27 hydrocarbons, 12 alcohols, 7 ketones, 4 esters, 1 aldehyde, 1 amine, and 3 miscellaneous components [95, 96]. Although recent studies have expressed anti-inflammatory effect and protective effects from liver damage of C. zawadskii, there is little experimental evidence suggesting that the extract stimulates hair growth in humans and animals. In mice study, topical methanol extract of C. zawadskiiwas more effective compared to minoxidil-treated group. In the C. zawadskii-treated and minoxidil-treated groups, while the maximum hair scores in the first hair-growth generation were recorded as 2.5 ± 0.29 and 2.5 ± 0.28, hair coverage scores in the second hair-growth generation were noted as 2 ± 0.41 and 1.5 ± 0.29, respectively. Rapid hair loss seen in minoxidil-treated mice was not observed in C. zawadskii-treated group after the first hair growth generation .
2.1.21. Scutellaria baicalensis
Scutellaria baicalensis(S. baicalensis, family Lamiaceae), also known as Huang Qin, mostly grows in China, Japan, Korea, Mongolia, and Russia [97, 98]. S. baicalensisis likely to have hair growth-promoting effect by means of its active substances. It has been reported that the compound possessing this activity is an active flavonoid isolated from S. baicalensisnamed ‘Baicalin’. In recent years, it has also suggested that both the extract of S. baicalensisand baicalin inhibit nuclear translocation of the androgen receptor stimulated by DHT in human dermal papilla cells and enhance proliferation of human dermal papilla cells in vitro .
2.1.22. Cuscuta reflexa Roxb
Cuscuta reflexaRoxb. (C. reflexa, family Convulvulaceae) is a parasitic plant that is used as herbal medicine. It is also known as ‘Tukhm-e-Kasoos (dodder),’ ‘Aftimoon,’ or ‘Kasoos’ in Unani Tibbi, ‘Akashabela,’ or ‘Amarabela’ in Hindi, ‘Swarnalata’ in Bengali, and ‘Akakhilata’ in Assamese, in vernacular [99, 100]. It commonly grows on different host plants, mostly thorny herbs in all geographical regions of India [99, 101]. Many pharmacological activities such as relaxant and spasmolytic action, positive inotropic and cardiotonic activities, cholinergic action, anti-HIV, antioxidant, anti-steroidogenic, antibacterial, hepatoprotective, hypoglyceamic, diuretic, anticonvulsant, anti-inflammatory and anticancer activities as well as hair growth activity have been previously reported . A number of experimental observations have indicated that C. reflexahas hair growth-promoting and 5α-reductase inhibitory activities. Hair growth was shown after treatment of the petroleum ether extract solution (250 mg/kg, orally) of C. reflexaand the ethanolic extract solution (250 mg/kg, orally) of C. reflexain male albino rats with cyclophosphamide-induced alopecia at 19 days . In another animal study by Pandit et al. suggested that petroleum ether extract of C. reflexareversed androgen-induced alopecia by inhibiting conversion of testosterone to DHT . Polyherbal formulation including C. reflexawas also shown to present hair growth-promoting activity on rats. Hair growth initiation time was markedly reduced to one-third on treatment with the prepared formulation compared to control group. The time required for complete hair growth was also reduced by 32%. Quantitative analysis of hair growth cycle after treatment with formulations and 2% minoxidil solution (positive control group) exhibited greater number of hair follicles in anagenic phase compared with control .
2.1.23. Ishige sinicola
Ishige sinicola(I. sinicola) is a brown alga that has antibacterial and anti-inflammatory effects against acne. In 2013, a study firstly demonstrated that I. sinicolaextract and its component, octaphlorethol A, have the potential to promote hair growth via the proliferation of dermal papilla cells followed by the activation of β-catenin pathway, and the 5α-reductase inhibition .
2.1.24. Grateloupia elliptica
G. ellipticais the edible seaweed in some Asian countries. Although it is thought that potential anticancer activity, there is no enough evidence investigating the protective effect against hair loss and hair growth-stimulating effect of G. elliptica[103, 104]. Possible mechanisms including the proliferation of dermal papilla cells, inhibition of 5α-reductase enzyme, increase in prostaglandin E2 (PGE2) production, decrease in pro-inflammatory cytokine production, and inhibitory activity against Pityrosporum ovale(P. ovale) have been shown in the prevention of hair loss. A study showed that G. ellipticaextract promoted the proliferation of dermal papilla cells by 169.5% at the concentration of 100 μg/ml compared with the vehicle-treated control group. The study also indicated that G. ellipticaextract inhibited 5α-reductase enzyme and this activity increased with dosage .
2.1.25. Puerariae flos
Puerariae flos(the flowers of Pueraria thomsonii, family Leguminosae) extract (PF-ext) has inhibitory activity on testosterone 5α-reductase. The two major compounds, soyasaponin I and kaikasaponin III, are responsible for this inhibitory activity. In addition to inhibitory activity on testosterone 5α-reductase of both compounds, soyasaponin I possesses hepatoprotective, sialyltransferase inhibitory, and renin inhibitory activities, while kaikasaponin III possesses anti-hepatotoxic, hypoglycemic, hypolipidemic, and anti-herpes virus activities [105, 106]. Inhibitory activity of PF-ext on 5α-reductase is stronger than Puerariae Radixextract (PR-ext). In testosterone-sensitive male mice, hair regrowth was improved after the application of PF-ext solution in a dose-dependent manner via antiandrogenic activity. PF-ext can stimulate the induction of the hair cycle to anagen phase, but this mechanism has not been proven definitely .
2.1.26. Curcuma aeruginosa
Curcuma aeruginosa(C. aeruginosa, family Zingiberaceae) is a native plant of India and Southeast Asia. The rootstock of C. aeruginosahas long been used in traditional medicine for various indications such as dysmenorrhea, exanthemas and fungal infections. The oils derived from this plant consist of 1,8-cineole, curserenone, furanogermenone, camphor, (Z)-3-hexenol, zedoarol, furanodienone, curcumenol, isocurcumenol, β-alemene, curzerene, and germacrone, among others. C. aeruginosahexane extract effects by inhibiting 5α-reductase activity, consecutively impairing the conversion of testosterone to DHT [107, 108]. Pumthong et al. investigated the effect of C. aeruginosahexane extract on male-pattern baldness with a randomized, double-blind, placebo-controlled study. The study has shown that 5% hexane extract of C. aeruginosaespecially combined with 5% minoxidil increased hair growth and decreased hair shedding .
2.1.27. Hura crepitans
Hura crepitans(H. crepitans, family Euphorbiaceae) has been used as a traditional medicine to treat some diseases such as Hansen’s disease and syphilis in the Amazon region. A compound in H. crepitans, daphne factor F3, can play an effective role the mechanism of the hair growth. But, interestingly, the amount of daphne factor F3 is very important for hair growth. While H. crepitansfrom Peru possesses hair regrowth activity, H. crepitansfrom Brazil is not affect hair growth. Because, the daphne factor F3 content of H. crepitansfrom Peru is about 30 times more than H. crepitansfrom Brazil [109, 110]. It has been suggested that H. crepitansinhibits the retardation of hair regrowth by DHT through inhibition the neurotrophin (NT)-4 activation induced by DHT .
2.1.28. Tobacco leaves
Tobacco leaves (family Solanaceae) are used in traditional medicine for promoting of hair growth. The leaves also used to treat bronchitis, asthma, skin diseases, headache, etc. Alkaloid nicotine is the main constituent of tobacco leaves. Alkaloids such as nicotine, nicotianin, nicotinine, nicoteine, and nicoteline, which are the constituent parts of tobacco leaves, selectively inhibit 5α-reductase activity. The microbial bio transformed extract of tobacco leaves in cow urine has been investigated to treat AGA, and it has been found that it promotes hair growth at concentration dependent manner. The study confirms that 30% concentrated lotion treatment is at par with 2% minoxidil treatment in potentiating hair growth promotion in male albino Wister rats [111, 112].
2.1.29. Tectona grandis Linn
Tectona grandis Linn. (T. grandis, family Verbinaceae) (teak tree) has been used to cure many diseases in traditional Indian medicine. T. grandisis called as ‘saka’ in Sanskrit, ‘sagun’in Hindi, ‘sagwan’in Marathi, and teak tree in English. It has also been used as a hypoglycaemic agent. According to the traditional Indian medicine, T. grandisroots are useful in anuria and urinary retention. The flowers have used to treat bronchitis, biliousness, and urinary discharge. The oil from the seeds is useful in scabies. The wood is used to relax and sedate the gravid uterus, heal headache and burning pains, cure liver problems, and even dysentery. T. grandishas been investigated in some studies for its anti-inflammatory and wound healing effects and is used as a topical treatment for burn wounds [113, 114]. Jaybhaye et al. investigated the effect of petroleum ether extract of T. grandis Linn. seeds on hair growth activity of albino mice. According to this study, topical application of the petroleum ether extract of T. grandisinduced hair growth initiation and was superior to standard therapy with minoxidil 2% solution. The combination of the petroleum ether extract (5%) with 2% minoxidil has the strongest effect on hair growth initiation .
2.1.30. Boehmeria nipononivea
Boehmeria nipononivea(B. nipononivea, family Urticaceae) is a Japanese plant and the use of acetone extract derived from this plant has been investigated for treatment of androgen-dependent alopecia. One study indicates that the acetone extract of B. nipononiveahas 5α-reductase inhibitory activity. The acetone extract derived from B. nipononiveawas investigated on mice for its hair growth effect, and it resulted with a significant hair regrowth starting on 15th day and continues until 22th day. The 5α-reductase inhibitory activity of the acetone extract of B. nipononiveais attributed to fatty acids contains such as α-linolenic acid, palmitic acid, oleic acid, elaidic acid, and stearic acid. The study reveals that both the acetone extract of B. nipononiveand three fatty acids (α-linolenic, elaidic, and stearic acids) have 5α-reductase activity and stimulates hair regrowth .