Anti-Inflammatory and Anticancer Properties of Birch Bark-Derived Betulin: Recent Developments
Hardeep Singh Tuli,
Katrin Sak,
Dhruv Sanjay Gupta,
Ginpreet Kaur,
Diwakar Aggarwal,
Nidarshana Chaturvedi Parashar,
Renuka Choudhary,
Mukerrem Betul Yerer,
Jagjit Kaur,
Manoj Kumar,
Vivek Kumar Garg,
Gautam Sethi
Affiliations
Hardeep Singh Tuli
Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, Haryana, India
Katrin Sak
NGO Praeventio, 50407 Tartu, Estonia
Dhruv Sanjay Gupta
Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’s NMIMS, Mumbai 40056, Maharashtra, India
Ginpreet Kaur
Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’s NMIMS, Mumbai 40056, Maharashtra, India
Diwakar Aggarwal
Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, Haryana, India
Nidarshana Chaturvedi Parashar
Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, Haryana, India
Renuka Choudhary
Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, Haryana, India
Mukerrem Betul Yerer
Department of Pharmacology, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey
Jagjit Kaur
ARC Centre of Excellence in Nanoscale Biophotonics (CNBP), Graduate School of Biomedical Engineering, Faculty of Engineering, The University of New South Wales, Sydney 2052, Australia
Manoj Kumar
Department of Chemistry, Maharishi Markandeshwar University, Sadopur 134007, Haryana, India
Vivek Kumar Garg
Department of Medical Laboratory Technology, University Institute of Applied Health Sciences, Chandigarh University, Gharuan, Mohali 140413, Punjab, India
Gautam Sethi
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
Birch tree bark-derived betulin has attracted scientific interest already for several centuries, being one of the first natural products identified from plants. However, the cellular events regulated by betulin and precise molecular mechanisms under these processes have been begun to be understood only recently. Today, we know that betulin can exert important anticancer activities through modulation of diverse cellular pathways. In this review article, betulin-regulated molecular signaling is unraveled and presented with a special focus on its participation in anti-inflammatory processes, especially by modulating nuclear factor-κB (NF-κB), prostaglandin/COX, and nuclear factor erythroid2-related factor 2 (Nrf2)-mediated cascades. By regulating these diverse pathways, betulin can not only affect the development and progression of different cancers, but also enhance the antitumor action of traditional therapeutic modalities. It is expected that by overcoming the low bioavailability of betulin by encapsulating it into nanocarriers, this promising natural compound may provide novel possibilities for targeting inflammation-related cancers.
