Osteogenic Potential of Cissus Quadrangularis: A Systematic Review

Download Article

DOI: 10.21522/TIJPH.2013.13.01.Art036

Authors : Dhanraj Ganapathy, Rajeshkumar Shanmugham, Saravanan Sekaran, Suganthi Ranganathan, Karthikeyan Murthykumar

Abstract:

Research shows that Cissus quadrangularis extracts can promote osteoblast proliferation, enhance collagen synthesis, and influence key signalling pathways like the Wnt/β-catenin pathway, which is vital for bone growth and remodelling. These findings suggest that Cissus quadrangularis could be an effective natural treatment for osteoporosis, bone fractures, and other skeletal disorders. A comprehensive search strategy was developed to systematically review the osteogenic potential of Cissus quadrangularis. Relevant studies were identified through searches of PubMed/MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science, and Google Scholar, using key terms such as "Cissus quadrangularis," "osteogenesis," "bone healing," and "bone regeneration." Boolean operators were employed to refine the search. Inclusion criteria focused on in vitro, in vivo, and clinical studies exploring the plant's role in bone health, while studies unrelated to osteogenesis or without original data were excluded. Titles, abstracts, and full texts were screened for relevance, followed by data extraction and quality assessment using appropriate tools. The strategy aimed to ensure comprehensive coverage of the available literature, minimizing bias and including diverse sources. A comprehensive search identified 975 articles. After excluding studies involving other plant extracts or review articles, the final selection included 8 cell line studies, 2 animal studies, and 5 clinical studies. The selected studies were analysed thoroughly. The systematic review underscores the osteogenic potential of Cissus quadrangularis, highlighting its ability to enhance bone formation and osseointegration based on cell line, animal, and clinical studies. While promising, the review also points out limitations, including a lack of high-quality clinical trials and challenges in conducting meta-analyses due to varied study designs and methodologies.


References:

[1].   Rajeshkumar, S., Menon, S., Kumar, S. V., Tambuwala, M. M., Bakshi, H. A., Mehta, M., Satija, S., Gupta, G., Chellappan, D. K., Thangavelu, L., & Dua, K., 2019, Antibacterial and antioxidant potential of biosynthesized copper nanoparticles mediated through Cissus arnotiana plant extract, Journal of Photochemistry and Photobiology B: Biology, 197, 111531.

[2].   Sharma, A., Sharma, C., Shah, O. P., Chigurupati, S., Ashokan, B., Meerasa, S. S., Rashid, S., Behl, T., & Bungau, S. G., 2023, Understanding the mechanistic potential of plant-based phytochemicals in management of postmenopausal osteoporosis, Biomedicine & Pharmacotherapy, 163, 114850.

[3].   Velmurugan, Y., Natarajan, S. R., Chakkarapani, N., Jayaraman, S., Madhukar, H., & Venkatachalam, R., 2024, In silico and in vitro studies for the identification of small molecular inhibitors from Euphorbia hirta Linn for rheumatoid arthritis: targeting TNF-α-mediated inflammation, Molecular Diversity, 17, 1-8.

[4].   Rajasekar, R., Shanmugam, R., & Anandan, J., 2024, Biosynthesis of Cissus rotundifolia stem-mediated titanium dioxide nanoparticles and their anticariogenic activity against Streptococcus mutans and Lactobacillus sp, Journal of Pharmacy and Bioallied Sciences, 16(Suppl 2), S1350-S1353.

[5].   Parameswaran, J., Krishnan, A., Manigandan, P., Shanmugam, R., & Thangavelu, L., 2024, Synthesis of silver nanoparticles using Ocimum gratissimum and Cissus quadrangularis: assessment of the antibacterial and cytotoxic effect of nanoparticles, Nanotechnology Perceptions, 6, 265-275.

[6].   Panda, A. K., & Rout, S., 2011, Puttur kattu (bandage)—A traditional bone setting practice in South India, J Ayurveda Integr Med, 2(4), 174-178.

[7].   Mahar, H. D., Agrawal, A. M., Mahar, D., & Mahar, D., 2016, Cultivation and biomedical application of Cissus quadrangularis L. in bone fracture, AMSE Journals-Series: Modelling C, 77, 1-4.

[8].   Mishra, G., Srivastava, S., & Nagori, B. P., 2010, Pharmacological and therapeutic activity of Cissus quadrangularis: an overview, International Journal of Pharmtech Research, 2(2), 1298-1310.

[9].   Sawangjit, R., Puttarak, P., Saokaew, S., & Chaiyakunapruk, N., 2017, Efficacy and safety of Cissus quadrangularis L. in clinical use: a systematic review and meta-analysis of randomized controlled trials, Phytotherapy Research, 31(4), 555-567.

[10].  Kumar, P., Dev, K., Sharma, K., Sahai, M., & Maurya, R., 2019, New lignan glycosides from Cissus quadrangularis stems, Natural Product Research, 33(2), 233-238.

[11].  Xue, W., Yu, J., & Chen, W., 2018, Plants and their bioactive constituents in mesenchymal stem cell-based periodontal regeneration: a novel perspective, BioMed Research International, 2018(1), 7571363.

[12].  Parisuthiman, D., Singhatanadgit, W., Dechatiwongse, T., & Koontongkaew, S., 2009, Cissus quadrangularis extract enhances biomineralization through up-regulation of MAPK-dependent alkaline phosphatase activity in osteoblasts, In Vitro Cellular & Developmental Biology-Animal, 45, 194-200.

[13].  Potu, B. K., Rao, M. S., Kutty, N. G., Bhat, K. M., Chamallamudi, M. R., & Nayak, S. R., 2008, Petroleum ether extract of Cissus quadrangularis (Linn) stimulates the growth of fetal bone during the intrauterine developmental period: a morphometric analysis, Clinics, 63, 815-820.

[14].  Muthusami, S., Senthilkumar, K., Vignesh, C., Ilangovan, R., Stanley, J., Selvamurugan, N., & Srinivasan, N., 2011, Effects of Cissus quadrangularis on the proliferation, differentiation, and matrix mineralization of human osteoblast-like SaOS-2 cells, Journal of Cellular Biochemistry, 112(4), 1035-1045.

[15].  Siddiqui, S., Ahmad, E., Gupta, M., Rawat, V., Shivnath, N., Banerjee, M., Khan, M. S., & Arshad, M., 2015, Cissus quadrangularis Linn exerts dose-dependent biphasic effects: osteogenic and anti-proliferative, through modulating ROS, cell cycle, and Runx2 gene expression in primary rat osteoblasts, Cell Proliferation, 48(4), 443-454.

[16].  Parvathi, K., Krishnan, A. G., Anitha, A., Jayakumar, R., & Nair, M. B., 2018, Poly (L-lactic acid) nanofibers containing Cissus quadrangularis induced osteogenic differentiation in vitro, International Journal of Biological Macromolecules, 110, 514-521.

[17].  Tasadduq, R., Gordon, J., Al-Ghanim, K. A., Lian, J. B., Van Wijnen, A. J., Stein, J. L., Stein, G. S., & Shakoori, A. R., 2017, Ethanol extract of Cissus quadrangularis enhances osteoblast differentiation and mineralization of murine pre-osteoblastic MC3T3-E1 cells, Journal of Cellular Physiology, 232(3), 540-547.

[18].  Toor, R. H., Malik, S., Qamar, H., Batool, F., Tariq, M., Nasir, Z., & Tassaduq, R., 2019, Osteogenic potential of hexane and dichloromethane fraction of Cissus quadrangularis on murine preosteoblast cell line MC3T3-E1 (subclone 4), Journal of Cellular Physiology, 234(12), 23082-23096.

[19].  Toor, R. H., Tasadduq, R., Adhikari, A., Chaudhary, M. I., Lian, J. B., Stein, J. L., Stein, G. S., & Shakoori, A. R., 2019, Ethyl acetate and n-butanol fraction of Cissus quadrangularis promotes the mineralization potential of murine pre-osteoblast cell line MC3T3-E1 (sub-clone 4), Journal of Cellular Physiology, 234(7), 10300-10314.

[20].  Ruangsuriya, J., Charumanee, S., Jiranusornkul, S., Sirisa-Ard, P., Sirithunyalug, B., Sirithunyalug, J., Pattananandecha, T., & Saenjum, C., 2020, Depletion of β-sitosterol and enrichment of quercetin and rutin in Cissus quadrangularis Linn fraction enhanced osteogenic but reduced osteoclastogenic marker expression, BMC Complementary Medicine and Therapies, 20, 1-2.

[21].  Nair, P. R., Sreeja, S., & Sailaja, G. S., 2021, In vitro biomineralization and osteogenesis of Cissus quadrangularis stem extracts: an osteogenic regulator for bone tissue engineering, Journal of Biosciences, 46, 1-4.

[22].  Liao, L., Zhu, W., Tao, C., Li, D., & Mao, M., 2023, Cissus quadrangularis L extract-loaded tricalcium phosphate reinforced natural polymer composite for guided bone regeneration, Journal of Materials Science: Materials in Medicine, 34(7), 33.

[23].  Robertson, S. F., & Bose, S., 2020, Enhanced osteogenesis of 3D printed β-TCP scaffolds with Cissus quadrangularis extract-loaded polydopamine coatings, Journal of the Mechanical Behavior of Biomedical Materials, 111, 103945.

[24].  Azam, Z., Sapra, L., Baghel, K., Sinha, N., Gupta, R. K., Soni, V., Saini, C., Mishra, P. K., & Srivastava, R. K., 2023, Cissus quadrangularis (Hadjod) inhibits RANKL-induced osteoclastogenesis and augments bone health in an estrogen-deficient preclinical model of osteoporosis via modulating the host osteoimmune system, Cells, 12(2), 216.

[25].  Singh, N., Singh, V., Singh, R. K., Pant, A. B., Pal, U. S., Malkunje, L. R., & Mehta, G., 2013, Osteogenic potential of Cissus quadrangularis assessed with osteopontin expression, National Journal of Maxillofacial Surgery, 4(1), 52-56.

[26].  Brahmkshatriya, H. R., Shah, K. A., Ananthkumar, G. B., & Brahmkshatriya, M. H., 2015, Clinical evaluation of Cissus quadrangularis as osteogenic agent in maxillofacial fracture: a pilot study, AYU (An International Quarterly Journal of Research in Ayurveda), 36(2), 169-173.

[27].  Managutti, A., Shah, D., Patel, J., Puttanikar, N., Shah, D., & Managutti, S., 2015, Evaluation of clinical efficacy of Cissus quadrangularis in pain management and bone healing after implant placement—a pilot study, Medico Research Chronicles, 2(5), 618-625.

[28].  Nayak, T., 2020, An assessment of the osteogenic potential of Cissus quadrangularis in mandibular fractures: a pilot study, Journal of Maxillofacial and Oral Surgery, 19, 106-112.

[29].  Altaweel, A. A., Baiomy, A. A., Shoshan, H. S., Abbas, H., Abdel-Hafiz, A. A., Gaber, A. E., Zewail, A. A., & Elshiekh, M. A., 2021, Evaluation of osteogenic potential of Cissus quadrangularis on mandibular alveolar ridge distraction, BMC Oral Health, 21, 1-8