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Phenanthrenoid Coelogin Isolated from Coelogyne cristata Exerts Osteoprotective Effect Through MAPK-Mitogen-Activated Protein Kinase Signaling Pathway

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Abstract

Osteoporosis is a major health problem in postmenopausal women globally. This study determined the mechanism through which coelogin stimulates osteoblastogenesis and its osteoprotective and bone regenerating potential. Coelogin effect on primary calvarial osteoblast cells was determined by measuring alkaline phosphatase activity, mineralization, osteoblast survival, and apoptosis and protein expression studies. The osteoprotective effect of coelogin was also evaluated on osteopenic adult female Swiss mice. At autopsy, bones were collected for dynamic and histomorphometry studies. Serum samples were also collected for assessment of serum parameters. Coelogin treatment led to increased osteoblast proliferation, survival, differentiation, and mineralization in osteoblast cells. Coelogin supplementation to Ovx mice promoted new bone formation, prevented Ovx-induced deterioration of bone microarchitecture, and enhanced bone regeneration. In addition, signaling studies revealed that coelogin treatment activates the ER-Erk and Akt-dependent signaling pathways which stimulate the osteoblastogenesis in osteoblast cells.

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Funding

Supporting Grants: Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), Council of Scientific and Industrial Research (CSIR), National Medicinal Plants Board (NMPB) project number R&D/UP-01/2015, Ministry of AYUSH, Government of India.

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Author notes

  1. Ravi Prakash, Tripti Mishra and Kapil Dev have contributed equally.

Authors and Affiliations

  1. Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Ravi Prakash, Kriti Sharma, Aijaz Ahmad John, Alok Tripathi & Divya Singh

  2. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Tripti Mishra & Narender Tadigoppula

  3. Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Jitendra Kuldeep & Mohd Imran Siddiqi

  4. Sophisticated Analytical Instrument Facility, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Brijesh Kumar

  5. Ethnobotany Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Kapil Dev, Chetan Sharma & Kamal Ram Arya

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  1. Ravi Prakash
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Correspondence to Narender Tadigoppula or Divya Singh.

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Conflict of interest

Ravi Prakash, Tripti Mishra, Kapil Dev, Kriti Sharma, Jitendra Kuldeep, Aijaz Ahmad John, Alok Tripathi, Chetan Sharma, Kamal Ram Arya, Brijesh Kumar, Mohd Imran Siddiqi, Narender Tadigoppula, and Divya Singh have no conflicts of interest.

Human and Animal Rights and Informed Consent

The experimental procedure was performed according to the regulations and guidelines approved by the Institutional Animal Ethics Committee (IAEC), Council of Scientific and Industrial Research-Central Drug Research Institute (CPCSEA Registration number: 34/GO/REBI/S/99 dated 12.3.15; Approval reference number: IAEC/2012/70N/Renew 05 (214/16) dated 4.11.2016) and Council for the Purpose of Control and Supervision of Experiments on Animals, Ministry of Social Justice and Empowerment, Government of India.

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Prakash, R., Mishra, T., Dev, K. et al. Phenanthrenoid Coelogin Isolated from Coelogyne cristata Exerts Osteoprotective Effect Through MAPK-Mitogen-Activated Protein Kinase Signaling Pathway. Calcif Tissue Int 109, 32–43 (2021). https://doi.org/10.1007/s00223-021-00818-3

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