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Oral Administration of Isovitexin, a Naturally Occurring Apigenin Derivative Showed Osteoanabolic Effect in Ovariectomized Mice: A Comparative Study with Teriparatide.
Pal, Subhashis; Sharma, Shivani; Porwal, Konica; Riyazuddin, Mohammed; Kulkarni, Chirag; Chattopadhyay, Sourav; Sanyal, Sabyasachi; Gayen, Jiaur R; Chattopadhyay, Naibedya.
Affiliation
  • Pal S; Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.
  • Sharma S; Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.
  • Porwal K; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
  • Riyazuddin M; Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.
  • Kulkarni C; Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India.
  • Chattopadhyay S; Division of Endocrinology and Center for Research in Anabolic Skeletal Target in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.
  • Sanyal S; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
  • Gayen JR; Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India.
  • Chattopadhyay N; Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India.
Calcif Tissue Int ; 111(2): 196-210, 2022 08.
Article in En | MEDLINE | ID: mdl-35451627
Isovitexin (apigenin-6C-glucopyranose) is found in several food items and medicinal plants. Recently, we showed that isovitexin stimulated osteoblast differentiation through mitochondrial biogenesis and respiration that required adiponectin receptors (AdipoRs). Here, we studied whether oral isovitexin has a bone anabolic effect in vivo. At first, using a femur osteotomy model in adult mice, we compared the bone regenerative effect of isovitexin and apigenin. Whereas isovitexin-stimulated bone formation at the osteotomy site at 2.5 mg/kg and 5 mg/kg dose, apigenin had no effect. Subsequently, we tested the effect of isovitexin (5 mg/kg) in ovariectomized (OVX) osteopenic mice and observed that it restored bone mass and architecture of trabecular bones (femur metaphysis and fifth lumbar vertebra/L5) and cortical bones (femur diaphysis). Isovitexin completely restored bone strength at L5 (compressive strength) and femur (bending strength) in OVX mice. The bone anabolic effect of isovitexin was demonstrated by the increased surface referent bone formation parameters, increased expression of osteogenic genes (Runx2, bone morphogenetic protein-2 and type 1 collagen) in bones, and increased serum procollagen type 1N-terminal propeptide in OVX mice and these were on a par with teriparatide. Isovitexin inhibited bone and serum sclerostin as well as the serum type I collagen cross-linked C-telopeptide in OVX mice. Isovitexin has an oral bioavailability of 14.58%. Taken together, our data show that isovitexin had a significant oral bioavailability that translated to osteoanabolic effect equivalent to teriparatide and inhibited bone resorption, which implied a durable effect over teriparatide.
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Full text: 1 Database: MEDLINE Main subject: Teriparatide / Anabolic Agents Language: En Journal: Calcif Tissue Int Year: 2022 Type: Article Affiliation country: India

Full text: 1 Database: MEDLINE Main subject: Teriparatide / Anabolic Agents Language: En Journal: Calcif Tissue Int Year: 2022 Type: Article Affiliation country: India