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Dietary isoflavone increases insulin-like growth factor-I production, thereby promoting hair growth in mice, Juan Zhao, J Nutr Biochem. 2011 Mar;22(3):227-33
Abstract
Sensory neurons release calcitonin gene-related peptide (CGRP) upon activation. We previously demonstrated that CGRP increases insulin-like growth
factor-I (IGF-I) production in various tissues of mice including the skin. We demonstrated that isoflavone increases the CGRP synthesis in the dorsal root ganglion (DRG) neurons in rats. Since IGF-I plays a critical role in hair growth, we hypothesized that isoflavones may promote hair growth by increasing the IGF-I production in hair follicles. We examined this hypothesis using wild-type
(WT) and CGRP-knockout (CGRP-/-) mice. Isoflavone significantly increased the CGRP mRNA levels in DRG neurons isolated from WT mice (Pb.01). Administration of isoflavone for 3 weeks increased the dermal levels of CGRP, IGF-I and
IGF-I mRNA in WT mice, but not in CGRP-/- mice. Isoflavone administration
increased the immunohistochemical expression of IGF-I in hair follicle dermal papilla cells in WT mice.
Significant enhancements of hair follicle morphogenesis, hair regrowth, and hair pigmentation were also observed in WT mice administered isoflavone. However,none of these effects in WT mice were observed in CGRP-/- mice. These observations strongly suggest that isoflavone might increase IGF-I production in the hair follicle dermal papilla cells in mice through increasing CGRP production in the sensory neurons, thereby promoting hair growth associated with melanogenesis in mice.
Introduction
The cyclical process of hair growth through three major stages (anagen, the growth phase; catagen, the involution phase; and telogen, the restingphase) is complex and regulated by several factors, including sensory neurons [1]. Sensory neurons contain neuropeptides such as calcitonine gene-related peptide (CGRP) and this CGRP is synthesized in the cell body and transported in vesicles to the peripheral nerve endings [2,3]. Previous reports have demonstrated that sensory neurons play important roles in the promotion of hair growth [4–6].
Insulin-like growth factor-I (IGF-I) is a basic peptide composed of 70 amino acids that is rather ubiquitously distributed in various organs and tissues, including the skin, and promotes growth, survival and differentiation of cells [7]. IGF-I is critically involved in promoting hair growth by regulating cellular proliferation and migration during the development of hair follicles [8,9]. IGF-I receptor null (Igf- 1r./.) mice exhibited hypotrophic skin with a reduced number and size of the hair
follicles [10]. Patients with Laron syndrome (primary IGF-I deficiency) show sparse hair growth and decreased epidermal thickness [11,12]. Also overexpression of IGF-I in proliferating and in differentiating keratinocytes resulted in hyperplasia and tumor formation [13,14]. These observations indicate that
IGF-I may be a critical component in the promotion of hair growth.
We previously demonstrated that stimulation of sensory neurons with capsaicin increased the IGF-I production by increasing CGRP release in mice [15]. Furthermore, we showed that administration of capsaicin increased the expression of IGF-I in the hair follicle dermal papilla cells, thereby promoting hair growth in mice [16]. Isoflavones have biological activities similar to those of estrogens in vitro and in vivo, and are thus referred as phytoestrogens [17–19]. Estradiol-17â has been shown to increase CGRP synthesis in the DRG neurons through NGF- mediated mechanisms [20]. In this context, we reported that isoflavones, as well as estrogen, increases the transcription of CGRP in the sensory neurons in rats [21]. Taken together, these observations strongly suggest that administration of isoflavones might increase the dermal levels of CGRP and IGF-I in mice, thereby promoting hair growth. In the present study, we examined this hypothesis using wild-type (WT) mice and CGRP-knockout (CGRP./.) mice.
Materials
Fujiflavone P40, contains 43.5% isoflavones which consist of 23.5% daidzin, 13.6% glycitin and 6.3% genistin
...
...
Discussion
In the present study, we demonstrated that while isoflavone increased CGRP production, it did not increase the release of CGRP, in DRG neurons isolated from WT mice. These observations are consistent with our previous report demonstrating that isoflavone increased CGRP production, but did not increase CGRP release, in DRG neurons isolated from rats [21].
We previously reported that capsaicin administration increased IGF-I production by increasing CGRP release in the skin of mice [15], suggesting that administration of isoflavone may also increase the IGF-I production through increasing the CGRP levels in the skin of mice. Consistent with this hypothesis are observations in the present study demonstrating that administration of
isoflavone increased the dermal levels of IGF-I and IGF-I mRNA levels in WT mice but not CGRP-/- mice. Since estrogen has been shown to increase the CGRP levels in sensory neurons by enhancing NGF-mediated production of CGRP [20,34,35], isoflavone is referred to as phytoestrogen. In the present study, although isoflavone did not increase the release of CGRP from sensory neurons in vitro, it increased the dermal levels of CGRP and IGF-I in WT mice. Since numerous endogenous agonists are known to be capable of increasing the release of CGRP from sensory neurons [36], it is possible that the increase of the dermal levels of IGF-I in WT mice following isoflavone administration was induced via enhancement of CGRP release by these endogenous agonists such as anandamide.
IGF-I is synthesized in the hair follicle dermal papilla cells and plays a critical role in the promotion of hair growth by regulating cellular proliferation and migration during the development of hair follicles [8,14]. Consistent with this notion are our previous observations demonstrating that capsaicin promoted the hair growth in mice by increasing the expression of IGF-I in the dermal papilla cells through stimulation of sensory neurons [16]. Since isoflavone increased the dermal levels of IGF-I production by increasing its transcription via enhancing CGRP synthesis in WT mice, it is possible that isoflavone promotes the hair growth by increasing the expression of IGF-I in the hair follicle dermal papilla cells in mice. The results of our present study demonstrating that administration of isoflavone increased the expression of IGF-I in the outer root sheath and in the dermal papilla and increased the number of hair follicles in WT mice, but not in CGRP-/- mice are consistent with this notion. Furthermore, hair regrowth was apparently more promoted to a pronounced degree following administration of isoflavone in WT mice, but scarce effect was noted in CGRP-/- mice in the present study. These observations strongly suggest that isoflavone might promote hair growth by increasing IGF-I production in the dermal papilla through enhancing CGRP synthesis in WT mice.
Hair growth is associated with hair melanogenesis [37,38]. IGF-I has been shown to be expressed at high levels in hair follicles during the growth phase of the hair cycle (anagen) [39], and plays a critical role in regulation of the growth and function of melanocytes [40]. Melanogenesis was significantly increased in dorsal hairs of WT mice administered isoflavone, but not in those of CGRP-/-
mice administered isoflavone. These observations strongly suggest that administration of isoflavone may increase melanogenesis in dorsal hairs of WT mice by increasing IGF-I production in hair follicles through enhancing CGRP synthesis in sensory neurons.
We previously reported that administration of isoflavone enhanced capsaicin- induced increase in the expression of IGF-I production in the dermal papilla, thereby enhancing the capsaicin induced promotion of hair regrowth in WT mice [16]. These observations suggest that simultaneous administration of capsaicin and isoflavone might additively promote the hair growth by increasing the release and production, respectively, of CGRP in sensory neurons, thereby promoting hair growth. Promotion of hair growth was observed in 48 patients with alopecia administered capsaicin and isofalvone for 5 months and this therapeutic effect might be explained, at least in part, by the additive effects of capsaicin and isoflavone on dermal IGF-I production.
Expression of IGF-I in the dermal papilla has been shown to strongly correlate with the therapeutic efficacy of finasteride in patients with androgenetic alopecia (AGA) [41]. These observations strongly suggest that combined use of capsaicin/isoflavone and finasteride may exert enhanced therapeutic efficacy in AGA patients. We are currently investigating this possibility.
Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis,
Latha Devareddy, Journal of Nutritional Biochemistry 19 (2008) 694–699
Postmenopausal osteoporosis is by far the most common cause of age-related bone loss. It is well known that ovarian hormone deficiency is a major risk factor for osteoporosis. Aside from existing drug therapies, certain lifestyle and nutritional factors are known to reduce the risk of osteoporosis. A number of population-based studies have demonstrated the beneficial effects of fruits and vegetables intakes on indices of bone health in humans [1,2]. Some phytochemicals such as polyphenols present in these fruits and vegetables are responsible for their bone-protective effects [3]. However, the effectiveness of these polyphenols may vary depending on their chemical compositions. For instance, a study by Muhlbauer et al. [3] examined the effects of numerous fruits and vegetables on bone and concluded that consumption of select fruits and vegetables is beneficial to bone, albeit with varying intensity. They have also [3] demonstrated that these bone protective effects are likely due to their phytochemical contents.
Blueberry contains a group of phytochemicals that have been implicated as a mediator of cardiovascular protection. The phytochemicals present in blueberry include phenolic acids (e.g., gallic acid, p-hydroxybenzoic acid, chlorogenic, p- coumaric, caffeic, ferulic and ellagic acids) and flavonoids (anthocyanins, catechin, epichatechin, quercetin, kaempferol and myrecetin) [4–6].
Our recent findings suggest that dried plum, which shares some of the same phenolic and flavonoid compounds with blueberry, exhibits strong bone protective properties in both female [7,8] and male [9] rat models of osteoporosis.
There are also a number of animal [10,11] and human studies [12,13] that suggest isoflavones, a subclass of flavonoids, prevent bone loss due to ovarian hormone deficiency and aging per se [14]. Hence, it is expected that blueberry with its phenolic compounds can prevent bone loss in ovarian hormone deficiency.
Based on the findings of the present study, we can hypothesize that blueberry prevents bone loss in a manner similar to soy isoflavones, which have been shown to effectively lower the number of mature osteoclasts by inducing osteoclast apoptosis [26] and suppressing osteoclastogenesis [27], thereby reducing bone resorption. Furthermore, the mechanism by which blueberry prevents bone loss is different than that of other fruits examined by our group such as dried plum. Our earlier findings suggest that dried plum protects against bone loss by increasing bone formation, serum bonespecific ALP and IGF-I in postmenopausal women [28] and Ovx rats [29]. However, further studies are needed to elucidate the mechanisms by which blueberry prevents bone loss over time.
In summary, our findings indicate that blueberry can prevent bone loss as seen by the increases in (bone mineral density) BMD and favorable changes in biomarkers of bone metabolism.
Abstract
Sensory neurons release calcitonin gene-related peptide (CGRP) upon activation. We previously demonstrated that CGRP increases insulin-like growth
factor-I (IGF-I) production in various tissues of mice including the skin. We demonstrated that isoflavone increases the CGRP synthesis in the dorsal root ganglion (DRG) neurons in rats. Since IGF-I plays a critical role in hair growth, we hypothesized that isoflavones may promote hair growth by increasing the IGF-I production in hair follicles. We examined this hypothesis using wild-type
(WT) and CGRP-knockout (CGRP-/-) mice. Isoflavone significantly increased the CGRP mRNA levels in DRG neurons isolated from WT mice (Pb.01). Administration of isoflavone for 3 weeks increased the dermal levels of CGRP, IGF-I and
IGF-I mRNA in WT mice, but not in CGRP-/- mice. Isoflavone administration
increased the immunohistochemical expression of IGF-I in hair follicle dermal papilla cells in WT mice.
Significant enhancements of hair follicle morphogenesis, hair regrowth, and hair pigmentation were also observed in WT mice administered isoflavone. However,none of these effects in WT mice were observed in CGRP-/- mice. These observations strongly suggest that isoflavone might increase IGF-I production in the hair follicle dermal papilla cells in mice through increasing CGRP production in the sensory neurons, thereby promoting hair growth associated with melanogenesis in mice.
Introduction
The cyclical process of hair growth through three major stages (anagen, the growth phase; catagen, the involution phase; and telogen, the restingphase) is complex and regulated by several factors, including sensory neurons [1]. Sensory neurons contain neuropeptides such as calcitonine gene-related peptide (CGRP) and this CGRP is synthesized in the cell body and transported in vesicles to the peripheral nerve endings [2,3]. Previous reports have demonstrated that sensory neurons play important roles in the promotion of hair growth [4–6].
Insulin-like growth factor-I (IGF-I) is a basic peptide composed of 70 amino acids that is rather ubiquitously distributed in various organs and tissues, including the skin, and promotes growth, survival and differentiation of cells [7]. IGF-I is critically involved in promoting hair growth by regulating cellular proliferation and migration during the development of hair follicles [8,9]. IGF-I receptor null (Igf- 1r./.) mice exhibited hypotrophic skin with a reduced number and size of the hair
follicles [10]. Patients with Laron syndrome (primary IGF-I deficiency) show sparse hair growth and decreased epidermal thickness [11,12]. Also overexpression of IGF-I in proliferating and in differentiating keratinocytes resulted in hyperplasia and tumor formation [13,14]. These observations indicate that
IGF-I may be a critical component in the promotion of hair growth.
We previously demonstrated that stimulation of sensory neurons with capsaicin increased the IGF-I production by increasing CGRP release in mice [15]. Furthermore, we showed that administration of capsaicin increased the expression of IGF-I in the hair follicle dermal papilla cells, thereby promoting hair growth in mice [16]. Isoflavones have biological activities similar to those of estrogens in vitro and in vivo, and are thus referred as phytoestrogens [17–19]. Estradiol-17â has been shown to increase CGRP synthesis in the DRG neurons through NGF- mediated mechanisms [20]. In this context, we reported that isoflavones, as well as estrogen, increases the transcription of CGRP in the sensory neurons in rats [21]. Taken together, these observations strongly suggest that administration of isoflavones might increase the dermal levels of CGRP and IGF-I in mice, thereby promoting hair growth. In the present study, we examined this hypothesis using wild-type (WT) mice and CGRP-knockout (CGRP./.) mice.
Materials
Fujiflavone P40, contains 43.5% isoflavones which consist of 23.5% daidzin, 13.6% glycitin and 6.3% genistin
...
...
Discussion
In the present study, we demonstrated that while isoflavone increased CGRP production, it did not increase the release of CGRP, in DRG neurons isolated from WT mice. These observations are consistent with our previous report demonstrating that isoflavone increased CGRP production, but did not increase CGRP release, in DRG neurons isolated from rats [21].
We previously reported that capsaicin administration increased IGF-I production by increasing CGRP release in the skin of mice [15], suggesting that administration of isoflavone may also increase the IGF-I production through increasing the CGRP levels in the skin of mice. Consistent with this hypothesis are observations in the present study demonstrating that administration of
isoflavone increased the dermal levels of IGF-I and IGF-I mRNA levels in WT mice but not CGRP-/- mice. Since estrogen has been shown to increase the CGRP levels in sensory neurons by enhancing NGF-mediated production of CGRP [20,34,35], isoflavone is referred to as phytoestrogen. In the present study, although isoflavone did not increase the release of CGRP from sensory neurons in vitro, it increased the dermal levels of CGRP and IGF-I in WT mice. Since numerous endogenous agonists are known to be capable of increasing the release of CGRP from sensory neurons [36], it is possible that the increase of the dermal levels of IGF-I in WT mice following isoflavone administration was induced via enhancement of CGRP release by these endogenous agonists such as anandamide.
IGF-I is synthesized in the hair follicle dermal papilla cells and plays a critical role in the promotion of hair growth by regulating cellular proliferation and migration during the development of hair follicles [8,14]. Consistent with this notion are our previous observations demonstrating that capsaicin promoted the hair growth in mice by increasing the expression of IGF-I in the dermal papilla cells through stimulation of sensory neurons [16]. Since isoflavone increased the dermal levels of IGF-I production by increasing its transcription via enhancing CGRP synthesis in WT mice, it is possible that isoflavone promotes the hair growth by increasing the expression of IGF-I in the hair follicle dermal papilla cells in mice. The results of our present study demonstrating that administration of isoflavone increased the expression of IGF-I in the outer root sheath and in the dermal papilla and increased the number of hair follicles in WT mice, but not in CGRP-/- mice are consistent with this notion. Furthermore, hair regrowth was apparently more promoted to a pronounced degree following administration of isoflavone in WT mice, but scarce effect was noted in CGRP-/- mice in the present study. These observations strongly suggest that isoflavone might promote hair growth by increasing IGF-I production in the dermal papilla through enhancing CGRP synthesis in WT mice.
Hair growth is associated with hair melanogenesis [37,38]. IGF-I has been shown to be expressed at high levels in hair follicles during the growth phase of the hair cycle (anagen) [39], and plays a critical role in regulation of the growth and function of melanocytes [40]. Melanogenesis was significantly increased in dorsal hairs of WT mice administered isoflavone, but not in those of CGRP-/-
mice administered isoflavone. These observations strongly suggest that administration of isoflavone may increase melanogenesis in dorsal hairs of WT mice by increasing IGF-I production in hair follicles through enhancing CGRP synthesis in sensory neurons.
We previously reported that administration of isoflavone enhanced capsaicin- induced increase in the expression of IGF-I production in the dermal papilla, thereby enhancing the capsaicin induced promotion of hair regrowth in WT mice [16]. These observations suggest that simultaneous administration of capsaicin and isoflavone might additively promote the hair growth by increasing the release and production, respectively, of CGRP in sensory neurons, thereby promoting hair growth. Promotion of hair growth was observed in 48 patients with alopecia administered capsaicin and isofalvone for 5 months and this therapeutic effect might be explained, at least in part, by the additive effects of capsaicin and isoflavone on dermal IGF-I production.
Expression of IGF-I in the dermal papilla has been shown to strongly correlate with the therapeutic efficacy of finasteride in patients with androgenetic alopecia (AGA) [41]. These observations strongly suggest that combined use of capsaicin/isoflavone and finasteride may exert enhanced therapeutic efficacy in AGA patients. We are currently investigating this possibility.
Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis,
Latha Devareddy, Journal of Nutritional Biochemistry 19 (2008) 694–699
Postmenopausal osteoporosis is by far the most common cause of age-related bone loss. It is well known that ovarian hormone deficiency is a major risk factor for osteoporosis. Aside from existing drug therapies, certain lifestyle and nutritional factors are known to reduce the risk of osteoporosis. A number of population-based studies have demonstrated the beneficial effects of fruits and vegetables intakes on indices of bone health in humans [1,2]. Some phytochemicals such as polyphenols present in these fruits and vegetables are responsible for their bone-protective effects [3]. However, the effectiveness of these polyphenols may vary depending on their chemical compositions. For instance, a study by Muhlbauer et al. [3] examined the effects of numerous fruits and vegetables on bone and concluded that consumption of select fruits and vegetables is beneficial to bone, albeit with varying intensity. They have also [3] demonstrated that these bone protective effects are likely due to their phytochemical contents.
Blueberry contains a group of phytochemicals that have been implicated as a mediator of cardiovascular protection. The phytochemicals present in blueberry include phenolic acids (e.g., gallic acid, p-hydroxybenzoic acid, chlorogenic, p- coumaric, caffeic, ferulic and ellagic acids) and flavonoids (anthocyanins, catechin, epichatechin, quercetin, kaempferol and myrecetin) [4–6].
Our recent findings suggest that dried plum, which shares some of the same phenolic and flavonoid compounds with blueberry, exhibits strong bone protective properties in both female [7,8] and male [9] rat models of osteoporosis.
There are also a number of animal [10,11] and human studies [12,13] that suggest isoflavones, a subclass of flavonoids, prevent bone loss due to ovarian hormone deficiency and aging per se [14]. Hence, it is expected that blueberry with its phenolic compounds can prevent bone loss in ovarian hormone deficiency.
Based on the findings of the present study, we can hypothesize that blueberry prevents bone loss in a manner similar to soy isoflavones, which have been shown to effectively lower the number of mature osteoclasts by inducing osteoclast apoptosis [26] and suppressing osteoclastogenesis [27], thereby reducing bone resorption. Furthermore, the mechanism by which blueberry prevents bone loss is different than that of other fruits examined by our group such as dried plum. Our earlier findings suggest that dried plum protects against bone loss by increasing bone formation, serum bonespecific ALP and IGF-I in postmenopausal women [28] and Ovx rats [29]. However, further studies are needed to elucidate the mechanisms by which blueberry prevents bone loss over time.
In summary, our findings indicate that blueberry can prevent bone loss as seen by the increases in (bone mineral density) BMD and favorable changes in biomarkers of bone metabolism.