Kaempferol has osteogenic effect in ovariectomized adult Sprague-Dawley rats.
Kaempferol (K), a flavonol, is known to have anti-osteoclastogenic effect. We here show that K, from 0.2 to 5.0 microM, increased mineralized nodules in rat primary osteoblasts. K also significantly attenuated adipocyte formation from bone marrow cells (BMCs). A single oral dose of 1 mg/kg body weight of K in Sprague-Dawley (180-200 g) rats resulted in a peak serum level of 2.04+/-0.8 nM in 30 min (Tmax), suggesting its rapid absorption. The Cmax of K in bone marrow was 0.684 nM after 90 min. Rats were ovariectomized (OVx) along with sham-operated rats and left for 4 weeks. Daily oral administration of K (5 mg/kg body weight) was then started to one group of OVx rats, and continued for 10 weeks. K levels were found to be 0.311 and 0.838 nM at the end of 4 and 10 weeks, respectively. K exhibited no estrogenicity at the uterine level. The K-treated group exhibited significantly higher bone mineral density (BMD) in the trabecular regions (femur neck, proximal tibia and vertebrae) and lower serum ALP (bone turnover marker) compared with the OVx rats. The compressive energy of the vertebrae was significantly higher in the OVx+K-treated group compared with the OVx group. K treatment of OVx rats resulted in the increase in osteoprogenitor cells as well as inhibition of adipocyte differentiation from BMCs compared with the OVx group. Together we show that K is non-estrogenic in vivo and exerts bone anabolic activity with attendant inhibition of bone marrow adipogenesis.
Trivedi
Ritu
R
Division of Endocrinology, Central Drug Research Institute, Chattar Manzil, Lucknow, India. ritu_pgi@yahoo.com
Kumar
Sudhir
S
Kumar
Avinash
A
Siddiqui
Jawed A
JA
Swarnkar
Gaurav
G
Gupta
Varsha
V
Kendurker
Amruta
A
Dwivedi
Anil Kumar
AK
Romero
Jose R
JR
Chattopadhyay
Naibedya
N
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000284:Administration, Oral; D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D005272:Femur Neck / Q000502:physiology; D044949:Kaempferols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008159:Lumbar Vertebrae / Q000502:physiology; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000502:physiology
D044949:Kaempferols; C006552:kaempferol