Pharmacological Potential of Betulin as a Multitarget Compound

Abstract

Betulin is a natural triterpene, usually from birch bark, known for its potential wound-healing properties. Despite having a wide range of pharmacological targets, no studies have proposed betulin as a multitarget compound. Betulin has protective effects against cardiovascular and liver diseases, cancer, diabetes, oxidative stress, and inflammation. It reduces postprandial hyperglycemia by inhibiting α-amylase and α-glucosidase activity, combats tumor cells by inducing apoptosis and inhibiting metastatic proteins, and modulates chronic inflammation by blocking the expression of proinflammatory cytokines via modulation of the NFκB and MAPKs pathways. Given its potential to influence diverse biological networks with high target specificity, it can be hypothesized that betulin may eventually become a new lead for drug development because it can modify a variety of pharmacological targets. The summarized research revealed that the diverse beneficial effects of betulin in various diseases can be attributed, at least in part, to its multitarget anti-inflammatory activity. This review focuses on the natural sources, pharmacokinetics, pharmacological activity of betulin, and the multi-target effects of betulin on signaling pathways such as MAPK, NF-κB, and Nrf2, which are important regulators of the response to oxidative stress and inflammation in the body.

Synthesis, Pharmacological Properties, and Potential Molecular Mechanisms of Antitumor Activity of Betulin and Its Derivatives in Gastrointestinal Cancers

“…Due to the fact that betulin exhibits anti-inflammatory effects, research was performed to evaluate its effects on the production of pro-inflammatory cytokines [ 32 , 35 , 36 ]. Zhao et al [ 36 ] conducted the investigation on a mouse model of induced sepsis.…”

“…Nrf2 can be regulated both at the transcriptional level by NF- k B, aryl hydrocarbon receptor (AhR), or activating transcription factor 4 (ATF4), as well as post-transcriptionally or post-translationally [ 42 , 43 ]. The process of Nrf2 factor phosphorylation is triggered by keap1, MAPK, and PI3K/Akt, resulting in Nrf2 translocation [ 35 , 43 ].…”

“…The mechanism of action of BE is suggested to be via increased expression of HO-1 and Nrf2 and simultaneous inhibition of AhR receptor and keap1 protein expression [ 35 , 43 , 44 ]. It has also been suggested that BE enhances the expression of enzymes involved in glutathione metabolism, i.e., glutathione S-transferase (GST) [ 35 , 44 , 45 ]. The concomitant action of antioxidant enzymes also reduces the production of ROS, which further protects normal cells from damage.…”

“…The concomitant action of antioxidant enzymes also reduces the production of ROS, which further protects normal cells from damage. Decreased HO-1 levels result in the biochemical conversion of heme, producing an anti-inflammatory effect and releasing cytokines essential to the proper functioning of the immune system in the defense against cancer [ 35 , 46 , 47 , 48 ].…”

Innovative Approach to Enhance Bioavailability of Birch Bark Extracts: Novel Method of Oleogel Development Contrasted with Other Dispersed Systems

“…Betulin has been reported to be effective against inflammation and oxidative stress [ 8 , 9 , 10 ]. Additionally, it has demonstrated antidiabetic [ 11 ], hepatoprotective [ 12 ], cardioprotective [ 13 ], and neuroprotective effects [ 14 ]. Lupeol may help to manage osteoporosis and possesses potential cardioprotective and skin-protective properties [ 15 ].…”