Anti-Inflammatory and Anticancer Properties of Birch Bark-Derived Betulin: Recent Developments

Tuli, Hardeep Singh; Sak, Katrin; Gupta, Dhruv Sanjay; Kaur, Ginpreet; Aggarwal, Diwakar; Parashar, Nidarshana Chaturvedi; Choudhary, Renuka; Yerer, Mükerrem Betül; Kaur, Jagjit; Kumar, Manoj; Garg, Vivek Kumar; Sethi, Gautam

doi:10.3390/plants10122663

Cited by 42 publications

(33 citation statements)

References 177 publications

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“…Currently, we are describing anti-inflammatory properties of amino acid esters of BE in relation to BE, BA, and a classic corticosteroid-dexamethasone. The structural resemblance of BE to dexamethasone indicates a similar mode of action of both compounds-as described and confirmed in 2021 [28]. Several other studies considered the application of the natural compounds to hematological malignancies, including lymphomas and leukemias [29][30][31].…”

Section: Introductionsupporting

confidence: 58%

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

et al. 2022

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Betulin is a heavily studied natural compound for its use as an anticancer or pro-regenerative agent. The structural similarity between betulin to steroids gives rise to the idea that the substance may as well act as an anti-inflammatory drug. This study is the first to describe the anti-inflammatory properties of betulinic acid, betulin, and its derivatives with amino acids 1,4-diaminebutane (Dab), 1,3-diaminepropane (Dap), Ornithine (Orn), and lysine (Lys) on murine macrophages from lymphoma site. The compounds were compared to dexamethasone. To establish the response of the macrophages to the natural compounds, we tested the viability as well as sensitivity to the inflammatory signaling (IFNγR). IL-6 secretory properties and HSP-70 content in the cells were examined. Furthermore, we characterized the effects of compounds on the inhibition of cyclooxygenase-2 (COX-2) activity both in the enzymatic assays and molecular docking studies. Then, the changes in COX-2 expression after betulin treatment were assessed. Betulin and betulinic acid are the low-cytotoxicity compounds with the highest potential to decrease inflammation via reduced IL-6 secretion. To some extent, they induce the reorganization of IFNγR with nearly no effect on COX-2 activity. Conversely, Bet-Orn and Bet-Lys are highly cytotoxic and induce the aggregation of IFNγR. Besides, Bet-Lys reduces the activity of COX-2 to a higher degree than dexamethasone. Bet-Orn is the only one to increase the HSP-70 content in the macrophages. In case of IL-6 reduction, all compounds were more potent than dexamethasone.

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Section: Introductionsupporting

confidence: 58%

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

et al. 2022

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“…The used birch bark extract is approved for contact with food, is safe for humans, and has a neutral taste and smell. The literature sources describe in detail the betulin properties, its antibacterial, anti-inflammatory, and other functional properties [ 57 , 58 , 59 ].…”

Section: Methodsmentioning

confidence: 99%

Microscopic and Structural Studies of an Antimicrobial Polymer Film Modified with a Natural Filler Based on Triterpenoids

et al. 2022

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The aspects of component visualization of the antimicrobial triterpenoids (betulin) additive, both on the surface and in the bulk of the polymer, constituting food film packaging, are considered. This paper presents new knowledge about the morphology and surface structure of modified films using three independent methodological approaches: optical microscopy; a histological method adapted to packaging materials; and a method of attenuated total internal reflection (ATR) spectroscopy in the infrared region with Fourier transform. The use of these methods shows the betulin granules, individual or forming chains. To visualize the antimicrobial additive in the polymer bulk, a modified histological method adapted for film materials and attenuated total internal reflection (ATR) spectroscopy in the infrared region were used with Fourier transform using a Lumos Bruker microscope (Germany) (ATR crystal based on germanium). Sample sections were analyzed using Leica 818 blades at an angle of 45 degrees. The histological method consists of the study of a biological object thin section, in the transmitted light of a microscope, stained with contrast dyes to reveal its structures, and placed on a glass slide. In the method modified for the present study, instead of a biological one, a synthetic object was used, namely the developed film materials with the addition of natural organic origin. Individual granules are about 2 µm long; chains can be up to 10 µm long. The thickness of the granules ranged from 1 to 1.5 microns. It can be seen that the depth distribution of granules in the film from the inner surface to the outer one is rather uniform. Spectroscopic studies using the method of automatic ATR mapping in the region of 880 cm−1 made it possible to evaluate the distribution of an antimicrobial additive based on triterpenoids on the surface and in the polymer bulk.

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“…It can also be extracted from various parts of plants belonging to the Platanaceae, Dilleniaceae, Rhamnaceae, Rosaceae, and Fagaceae families [194]. Betulin has been shown to have antiinflammatory and anticancer effects such as the induction of mitochondrial oxidative stress, regulation of specific protein transcription factors, and the inhibition of signal transducers [194][195][196]. Cheng et al [84] evaluated betulin's effect on RCC 786-O and Caki-2 cell lines, where it was found to inhibit cell proliferation and decrease cell viability.…”

Section: Betulinmentioning

confidence: 99%

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

Bajalia

Azzouz

Chism

et al. 2022

Cancers

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Renal cell carcinoma (RCC) is associated with about 90% of renal malignancies, and its incidence is increasing globally. Plant-derived compounds have gained significant attention in the scientific community for their preventative and therapeutic effects on cancer. To evaluate the anticancer potential of phytocompounds for RCC, we compiled a comprehensive and systematic review of the available literature. Our work was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The literature search was performed using scholarly databases such as PubMed, Scopus, and ScienceDirect and keywords such as renal cell carcinoma, phytochemicals, cancer, tumor, proliferation, apoptosis, prevention, treatment, in vitro, in vivo, and clinical studies. Based on in vitro results, various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, suppressed cell viability, proliferation and growth, showed cytotoxic activity, inhibited invasion and migration, and enhanced the efficacy of chemotherapeutic drugs in RCC. In various animal tumor models, phytochemicals suppressed renal tumor growth, reduced tumor size, and hindered angiogenesis and metastasis. The relevant antineoplastic mechanisms involved upregulation of caspases, reduction in cyclin activity, induction of cell cycle arrest and apoptosis via modulation of a plethora of cell signaling pathways. Clinical studies demonstrated a reduced risk for the development of kidney cancer and enhancement of the efficacy of chemotherapeutic drugs. Both preclinical and clinical studies displayed significant promise of utilizing phytochemicals for the prevention and treatment of RCC. Further research, confirming the mechanisms and regulatory pathways, along with randomized controlled trials, are needed to establish the use of phytochemicals in clinical practice.

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Anti-Inflammatory and Anticancer Properties of Birch Bark-Derived Betulin: Recent Developments

Cited by 42 publications

References 177 publications

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

Microscopic and Structural Studies of an Antimicrobial Polymer Film Modified with a Natural Filler Based on Triterpenoids

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

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