A standardized extract of Coleus forskohlii root protects rats from ovariectomy-induced loss of bone mass and strength, and impaired bone material by osteogenic and anti-resorptive mechanisms

Frontiers in Endocrinology

Endocrinology

Koneni V. Sashidhara¹  Alka Raj Pandey¹  Navin Kumar²  Saroj Kumar²  Vaishnavi Singh³  Akanksha Singh³  Sanjana Baranwal³  Konica Porwal³  Shivani Sharma⁴  Chirag Kulkarni⁴  Swati Rajput⁴  Sreyanko Sadhukhan⁴  Naibedya Chattopadhyay⁴  Suriya Pratap Singh⁵  Aboli Girme⁶  Lal Hingorani⁶ 

[1] Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India;Medicinal and Process Chemistry Division, Council of Scientific & Industrial Research (CSIR)-Central Drug Research Institute, Lucknow, India;Sophisticated Analytical Instrument Facility & Research, Council of Scientific & Industrial Research-Central Drug Research Institute, Lucknow, India;Department of Mechanical Engineering, Indian Institute of Technology Ropar, Rupnagar, Punjab, India;Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), Council of Scientific & Industrial Research-Central Drug Research Institute, Lucknow, India;Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), Council of Scientific & Industrial Research-Central Drug Research Institute, Lucknow, India;Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India;Medicinal and Process Chemistry Division, Council of Scientific & Industrial Research (CSIR)-Central Drug Research Institute, Lucknow, India;Sophisticated Analytical Instrument Facility & Research, Council of Scientific & Industrial Research-Central Drug Research Institute, Lucknow, India;Pharmanza Herbal Pvt. Ltd., Anand, Gujarat, India;

关键词: Coleus forskohlii;    osteotomy;    new bone formation;    post-menopausal osteoporosis;    micro-computed tomography;    bone material and quality;    histomorphometry;   

DOI  :  10.3389/fendo.2023.1130003

 received in 2022-12-22, accepted in 2023-01-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionIn obese humans, Coleus forskohlii root extract (CF) protects against weight gain owing to the presence of forskolin, an adenylate cyclase (AC) activator. As AC increases intracellular cyclic adenosine monophosphate (cAMP) levels in osteoblasts that has an osteogenic effect, we thus tested the skeletal effects of a standardized CF (CFE) in rats.MethodsConcentrations of forskolin and isoforskolin were measured in CFE by HPLC. CFE and forskolin (the most abundant compound present in CFE) were studied for their osteogenic efficacy in vitro by alkaline phosphatase (ALP), cAMP and cyclic guanosine monophosphate (cGMP) assays. Femur osteotomy model was used to determine the osteogenic dose of CFE. In growing rats, CFE was tested for its osteogenic effect in intact bone. In adult ovariectomized (OVX) rats, we assessed the effect of CFE on bone mass, strength and material. The effect of forskolin was assessed in vivo by measuring the expression of osteogenic genes in the calvarium of rat pups.ResultsForskolin content in CFE was 20.969%. CFE increased osteoblast differentiation and intracellular cAMP and cGMP levels in rat calvarial osteoblasts. At 25 mg/kg (half of human equivalent dose), CFE significantly enhanced calcein deposition at the osteotomy site. In growing rats, CFE promoted modeling-directed bone formation. In OVX rats, CFE maintained bone mass and microarchitecture to the level of sham-operated rats. Moreover, surface-referent bone formation in CFE treated rats was significantly increased over the OVX group and was comparable with the sham group. CFE also increased the pro-collagen type-I N-terminal propeptide: cross-linked C-telopeptide of type-I collagen (PINP : CTX-1) ratio over the OVX rats, and maintained it to the sham level. CFE treatment decreased the OVX-induced increases in the carbonate-to-phosphate, and carbonate-to-amide-I ratios. CFE also prevented the OVX-mediated decrease in mineral crystallinity. Nanoindentation parameters, including modulus and hardness, were decreased by OVX but CFE maintained these to the sham levels. Forskolin stimulated ALP, cAMP and cGMP in vitro and upregulated osteogenic genes in vivo.ConclusionCFE, likely due to the presence of forskolin displayed a bone-conserving effect via osteogenic and anti-resorptive mechanisms resulting in the maintenance of bone mass, microarchitecture, material, and strength.

【 授权许可】

Unknown   
Copyright © 2023 Kulkarni, Sharma, Porwal, Rajput, Sadhukhan, Singh, Singh, Baranwal, Kumar, Girme, Pandey, Singh, Sashidhara, Kumar, Hingorani and Chattopadhyay