Gushukang exerts osteopreserve effects by regulating vitamin D and calcium metabolism in ovariectomized mice

J Bone Miner Metab. 2019 Mar;37(2):224-234. doi: 10.1007/s00774-018-0924-1. Epub 2018 May 2.

Abstract

Calcium homeostasis plays vital roles in the management of bone health. Traditional herbal formula Gushukang (GSK) was clinically applied to treat primary osteoporosis. This study aimed to explore the osteoprotective effects of GSK and its roles in maintaining calcium homeostasis in ovariectomized (OVX) mice. The OVX mice were orally treated with low (0.38 g/kg), middle (0.76 g/kg) and high (1.52 g/kg) dose of GSK for 8 weeks. GSK treatment dramatically increased serum calcium level and decreased urinary calcium excretion as well as enhanced calcium content in bone of OVX mice. Serum level of 25-hydroxyvitamin D was significantly increased in OVX mice with exposure to GSK. Treatment with GSK improved bone mass and micro-structure of trabecular bone at distal metaphysis of femur and proximal metaphysis of tibia in OVX mice shown by safranin O staining and micro-CT measurement. GSK treatment at all doses up-regulated mRNA expression of calcium-binding protein-28k and vitamin D receptor in kidney of OVX mice, and dose-dependently decreased mRNA expression of claudin-14 and elevated mRNA expression of claudin-16 in duodenum of OVX mice. Taken together, GSK exerted beneficial effects on trabecular bone of OVX mice by improving calcium homeostasis via regulating paracellular calcium absorption in duodenum and transcellular calcium reabsorption in kidney.

Keywords: Calcium transport; Duodenum; Gushukang; Kidney; Osteoporosis.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Bone Density Conservation Agents / pharmacology*
  • Calcium / blood
  • Calcium / metabolism*
  • Calcium / urine
  • Claudins / genetics
  • Claudins / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Femur / metabolism
  • Femur / pathology
  • Gene Expression Regulation / drug effects
  • Intestinal Absorption / drug effects
  • Mice, Inbred C57BL
  • Ovariectomy*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tibia / diagnostic imaging
  • Tibia / drug effects
  • Tibia / metabolism
  • Tibia / pathology
  • Uterus / drug effects
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D / metabolism*
  • X-Ray Microtomography

Substances

  • Bone Density Conservation Agents
  • Claudins
  • Drugs, Chinese Herbal
  • RNA, Messenger
  • gushukang
  • Vitamin D
  • 25-hydroxyvitamin D
  • Calcium