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

• Published in: Frontiers in endocrinology (Lausanne) Vol. 14; p. 1130003
• Main Authors: Kulkarni, Chirag, Sharma, Shivani, Porwal, Konica, Rajput, Swati, Sadhukhan, Sreyanko, Singh, Vaishnavi, Singh, Akanksha, Baranwal, Sanjana, Kumar, Saroj, Girme, Aboli, Pandey, Alka Raj, Singh, Suriya Pratap, Sashidhara, Koneni V, Kumar, Navin, Hingorani, Lal, Chattopadhyay, Naibedya
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.02.2023
• Subjects: Alkaline Phosphatase; Animals; bone material and quality; Coleus forskohlii; Colforsin - pharmacology; Collagen; Endocrinology; Female; Humans; micro-computed tomography; new bone formation; Osteogenesis; osteotomy; Ovariectomy - adverse effects; Plectranthus; post-menopausal osteoporosis; Rats; histomorphometry; micro-computed tomography; osteotomy; post-menopausal osteoporosis; bone material and quality; new bone formation; Coleus forskohlii
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2023.1130003

In obese humans, 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. Concentrations 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 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 by measuring the expression of osteogenic genes in the calvarium of rat pups. Forskolin 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 and upregulated osteogenic genes . CFE, likely due to the presence of forskolin displayed a bone-conserving effect osteogenic and anti-resorptive mechanisms resulting in the maintenance of bone mass, microarchitecture, material, and strength.