**4. Reinforcing kidney drugs and diseases**

There are many successful medical records of diseases treatment through kidney‐nourish‐ ing therapy. For a good illustration of the fundamental role of tonifying kidney, as shown in **Table 1**, we summarize 10 common Chinese medical herbs for tonifying kidney and sum up their pharmacological activities.

2,3,5,4′‐Tetrahydroxystilbene‐2‐*O*‐β‐D‐glucoside (THSG) is the main composition of Polygonum Multiflorum (Thunb.) Harald., a traditional kidney‐yin reinforcing herb. Our research has showed that THSG inhibited vascular aging [50] and regulated the expression of klotho, espe‐ cially in the brain, testis, and kidney [47]. It also has the therapeutic benefits in bone diseases. For instance, THSG enhances the bone strength *in vivo* [47]. It has been reported that kidney‐ nourishing herbs improve the metabolism of calcium and phosphorus [51], regulate the levels of estrogen and 1,25‐dihydroxyvitamin D3 [52], and increase the activity of 1‐α hydroxylase in renal disorder diseases [53]. Another kidney‐yang nourishing herb, Epimedium brevicornu Maxim., and its active ingredient icariin can increase the klotho expression *in vitro* and *in vivo* [54]. The extract of polysaccharides of Cornus officinalis Sieb. et Zucc. [55] has a similar effect.

Bavachalcone, one of the effective components of Psoralea corylifolia L., is also a kidney‐yang reinforcing herb. Our results demonstrated that bavachalcone not only prevents endothelial cells senescence [56, 57], but also promotes differentiation of bone marrow stem cells and endothelial progenitor cell via EPO/AMPK pathway (our unpublished data). Effects of kidney‐nourishing herbs on differentiation of bone marrow mesenchymal stem cells also have been reported recently. For example, Epimedium brevicornu Maxim. enhances proliferation and osteogenic differen‐ tiation [58]; Davallia mariesii Moore ex Bak. stimulates differentiation into chondrocytes [59]; icariin facilitates differentiation into cardiomyocytes [60]; Rehmannia glutinosa polysaccharides


Modern medical research has elucidated that α‐klotho deficiency causes bone matrix protein distribution changes and calcification defect [40]; and participates in calcium and phosphorus metabolism [41]. α‐Klotho also regulates the expression of vitamin D receptor [42]. It is clear

that the introduction of variant KL‐VS of the human KLOTHO gene in mice enhances cogni‐

It has also been observed that there is a relationship between klotho and reproductive func‐ tion [39]. The Nabeshima group also found that klotho‐deficient mice have abnormal regula‐ tion of gonadotropins [45]. Recent studies have shown that maternal serum α‐klotho exhibits positive association with fetal birth weight [46]. Our research shows that klotho expression in testis in 30‐week‐old SHR is significantly lower than that of normal controls Wistar‐Kyoto (WKY) rats [47]. At present, although there is no direct evidence to prove the relationship between angiotensin II and klotho in testes, a lot of circumstantial evidence appears that klotho protect the organs and antagonistic effects of angiotensin II [48, 49]. Overall, we find that klotho function and the "kidney stores essence" theory have many overlapping and cov‐

There are many successful medical records of diseases treatment through kidney‐nourish‐ ing therapy. For a good illustration of the fundamental role of tonifying kidney, as shown in **Table 1**, we summarize 10 common Chinese medical herbs for tonifying kidney and sum up

2,3,5,4′‐Tetrahydroxystilbene‐2‐*O*‐β‐D‐glucoside (THSG) is the main composition of Polygonum Multiflorum (Thunb.) Harald., a traditional kidney‐yin reinforcing herb. Our research has showed that THSG inhibited vascular aging [50] and regulated the expression of klotho, espe‐ cially in the brain, testis, and kidney [47]. It also has the therapeutic benefits in bone diseases. For instance, THSG enhances the bone strength *in vivo* [47]. It has been reported that kidney‐ nourishing herbs improve the metabolism of calcium and phosphorus [51], regulate the levels

in renal disorder diseases [53]. Another kidney‐yang nourishing herb, Epimedium brevicornu Maxim., and its active ingredient icariin can increase the klotho expression *in vitro* and *in vivo* [54]. The extract of polysaccharides of Cornus officinalis Sieb. et Zucc. [55] has a similar effect. Bavachalcone, one of the effective components of Psoralea corylifolia L., is also a kidney‐yang reinforcing herb. Our results demonstrated that bavachalcone not only prevents endothelial cells senescence [56, 57], but also promotes differentiation of bone marrow stem cells and endothelial progenitor cell via EPO/AMPK pathway (our unpublished data). Effects of kidney‐nourishing herbs on differentiation of bone marrow mesenchymal stem cells also have been reported recently. For example, Epimedium brevicornu Maxim. enhances proliferation and osteogenic differen‐ tiation [58]; Davallia mariesii Moore ex Bak. stimulates differentiation into chondrocytes [59]; icariin facilitates differentiation into cardiomyocytes [60]; Rehmannia glutinosa polysaccharides

can lead to osteoporosis [43]. Studies have shown

[52], and increase the activity of 1‐α hydroxylase

that the lack of 1,25‐dihydroxyvitamin D3

tive function and increases serum α‐klotho levels [44].

18 Chinese Medical Therapies for Diabetes, Infertility, Silicosis and the Theoretical Basis

ering, reflecting the similarities between the two.

**4. Reinforcing kidney drugs and diseases**

their pharmacological activities.

of estrogen and 1,25‐dihydroxyvitamin D3


**Table 1.** Ten kinds of kidney‐nourishing herbs used in clinical treatments.

induces the formation of neuron‐like cells or endothelial‐like cells [61]; Curculigo orchioides Gaertn promotes differentiation into neurons [62]; and polysaccharides from Morinda officinalis How. and THSG promotes the proliferation and differentiation of bone marrow stem cells, and increases the number of peripheral blood cells in cancer chemotherapy [63].

Kidney‐nourishing herbs also display effects of promoting cognitive function in type 1 dia‐ betes and vascular cognitive impairment [64, 65]. Moreover, they successfully support the luteal insufficiency infertility [66]. Animal experiments further confirmed that the nourishing kidney treatment can promote ovulation and ovarian luteinizing hormone receptor expres‐ sion in infertile rats [67].

## **5. Conclusion**

Kidney essence declines with aging and leads to a variety of diseases, such as infertility, osteoporosis, senile dementia, aplastic anemia, and senility. Given the importance of kidney essence to life, researchers seek to understand the connotation of the "kidney stores essence" theory. Although "stem cells are congenital essence" is prevailing now, the plausible models and nonspecific indexes still need improvement. The kidney endocrine substances are similar with the kidney essence in their source and functions. It may have some help for the com‐ prehension of the Zang‐Fu theory and point to new targets for antiaging drugs. However, whether the kidney‐nourishing medicine has implications on the kidney endocrine substance, still need further researching and discussing.
