Jingui Shenqi Pills Regulate Bone‐Fat Balance in Murine Ovariectomy‐Induced Osteoporosis with Kidney Yang Deficiency

Abstract

Jingui Shenqi Pills (JGSQP) have been a staple of traditional Chinese medicine for thousands of years, used primarily as a treatment for kidney yang deficiency (KYD). In vitro analyses of JGSQP revealed strong induction of osteogenic differentiation and inhibition of adipogenic differentiation in bone-marrow-derived mesenchymal stem/stromal cells. However, the mechanisms by which JGSQP regulate the bone-fat balance in murine ovariectomy-induced osteoporosis with KYD have not been reported. Materials and Methods. Two-month-old female C57BL/6 mice were divided randomly into three groups: those receiving a sham operation (Sham); those undergoing bilateral ovariectomy and selection of KYD syndrome (Model); and those subjected to both bilateral ovariectomy and KYD syndrome selection for 8 weeks, followed by JGSQP treatment for 4 weeks (JGSQP). In the Sham and Model groups, mice were given the same dose of distilled water orally for 4 weeks. Animals from all three groups were euthanised at the 12th week. Vertebral microarchitecture and histomorphology were examined by micro-CT and H&E staining, respectively. In addition, we examined the mRNA expression of Akt, Wnt10b, Osterix (Osx), Fndc5, PPARγ, and Fabp4, as well as the protein of AKT, phosphorylation-AKT (p-AKT), BMP2, COL1A1, and FNDC5. Results. JGSQP treatment improved bone microarchitecture and mitigated histomorphological damage relative to the Model group. The osteoblast number (Ob.N/BS) and area (Ob.S/BS) were increased, whereas adipocyte number (adipocyte/tissue area) and area (adipocyte area/tissue area) were decreased in the JGSQP group. JGSQP treatment reduced the mRNA expression of Akt and adipogenesis-related genes (Fndc5, PPARγ, and Fabp4) while promoting osteogenesis-related genes (Wnt10b and Osx) mRNA expression. Additionally, the expression of p-AKT, BMP2, and COL1A1 proteins was increased and FNDC5 protein expression was decreased after JGSQP treatment. Conclusions. JGSQP treatment reversed murine ovariectomy-induced osteoporosis with KYD by controlling bone-fat balance via AKT pathway.

Early effects of ovariectomy on bone microstructure, bone turnover markers and mechanical properties in rats

“…With the prolongation of life span, the incidence rate of PMOP and fragility fracture is increasing year by year. According to the recent report showed that fragility fractures are related to up 50% of the disability rate and 20% of the mortality rate [ 9 ]. The medical expenses related to fragility fractures in China are expected to reach 163 billion RMB in 2050.…”

Early effects of ovariectomy on bone microstructure, bone turnover markers and mechanical properties in rats

“…With the prolongation of life span, the incidence rate of PMOP and fragility fracture is increasing year by year. According to Shang Q et al [9] showed that fragility fractures are related to up 50% of the disability rate and 20% of the mortality rate. The medical expenses related to fragility fractures in China are expected to reach 163 billion RMB in 2050.…”

Guifu Dihuang Pills Ameliorated Mucus Hypersecretion by Suppressing Muc5ac Expression and Inactivating the ERK-SP1 Pathway in Lipopolysaccharide/Cigarette Smoke-Induced Mice

“…The Guifu Dihuang pill (GFDHP, Chinese name 桂附地黄丸), composed of eight herbs, is a classical Chinese medicine for the treatment of kidney yang deficiency (KYD) syndrome [ 5 ]. It is also called the Jinkui Shenqi pill because it was first recorded in the Synopsis of Golden Chamber written by Zhang Zhongjing approximately 2000 years ago [ 6 ].…”

“…It had been used as an immunomodulator for preventing renal and immune hypofunction, particularly chronic nephritis, diabetes, hypothyroidism, adrenocortical hypofunction, sexual hypofunction, chronic bronchitis, asthma, and COPD [ 7 ]. According to the theory of Traditional Chinese Medicine (TCM), the long-term KYD can induce gradually deteriorating “lung inflation” and “phlegm retention,” which in turn accelerate the development of the KYD disease and eventually lead to the emergence of a malignant phenotype [ 5 ]. Thus, the eight herbs in GFDHP, most of which treat lung-distension and phlegm retention, would be helpful in recovering pulmonary ventilation function in patients with COPD [ 8 ].…”