Figure - available from: Natural Product Communications
This content is subject to copyright.
Source publication
Reports on β-secretase inhibitors of natural origin are listed in order to reveal their chemical diversity. Various types of compounds were found to inhibit β-secretase, and natural resources included a wide spectrum of biological species. Among them, some triterpenes and moracin derivatives, which are nonpeptidic compounds, were determined to be c...
Citations
... At present, whether the function of γ-secretase in Aβ production can be specifically inhibited without interfering with other important functions of this protease remains unclear [38]. Thus, β-secretase inhibitor candidates are of particular interest to develop, and the majority of AD treatment studies targeting secretase inhibition have focused on this enzyme [39][40][41]. ...
... In total, 87 ChE inhibitors from microorganisms were presented in this review (Figures 2 and 3). Of these, there were fifteen territrem derivatives (13-23, 84-87), fifteen butenolide derivatives (64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78), thirteen terpenoids (10, 30, 49, 50, 53, 56, 57, 59, 79-82), seven alkaloids (1, 5, 7-9, 26, 55), five ether derivatives (29,(36)(37)(38)(39), four chromene derivatives (45)(46)(47)(48), three diketopiperazines (31)(32)(33), three polyketides (54,61,83), three hydroxyanthraquinones (40)(41)(42), two dimeric indole derivatives (3, 4), two terphenyls (51, 52), two lipopeptide epimers (34,35), one phenazine (2), one bicyclic enolphosphates (6), one benzopyran derivatives (11), one flavin (12), one ketal (24), one fatty alcohol (25), one oxaphenalenone dimer (27), one isopentenyl xanthenone (28), one benzophenone (43), one prenyl asteltoxin derivatives (44), one cyclohexanoid (58), one naphthoquinone (60), one steroid (62), and one trimeric cyclodepsipeptide (63). Based on the anti-ChE activity results, almost all territrem derivatives showed a more efficient inhibitory effect than other families, with IC50 values in the range of 0.001-26,000 nM [71,72,95]. ...
... Based on the amyloid hypothesis, inhibitors of β-secretase (BACE1)-an amyloid precursor proteolytic enzyme at position 1 beta (BACE)-are also potential candidates for the treatment of AD. Natural sources of BACE1 inhibitors are mainly obtained from plants [40,96], large fungi, marine organisms, and algae [41]. A few studies have investigated secondary compounds from some fungal strains [93,[97][98][99][100]. ...
Alzheimer’s disease (AD) is the most common form of dementia. It increases the risk of other serious diseases and causes a huge impact on individuals, families, and socioeconomics. AD is a complex multifactorial disease, and current pharmacological therapies are largely based on the inhibition of enzymes involved in the pathogenesis of AD. Natural enzyme inhibitors are the potential sources for targeting AD treatment and are mainly collected from plants, marine organisms, or microorganisms. In particular, microbial sources have many advantages compared to other sources. While several reviews on AD have been reported, most of these previous reviews focused on presenting and discussing the general theory of AD or overviewing enzyme inhibitors from various sources, such as chemical synthesis, plants, and marine organisms, while only a few reviews regarding microbial sources of enzyme inhibitors against AD are available. Currently, multi-targeted drug investigation is a new trend for the potential treatment of AD. However, there is no review that has comprehensively discussed the various kinds of enzyme inhibitors from the microbial source. This review extensively addresses the above-mentioned aspect and simultaneously updates and provides a more comprehensive view of the enzyme targets involved in the pathogenesis of AD. The emerging trend of using in silico studies to discover drugs concerning AD inhibitors from microorganisms and perspectives for further experimental studies are also covered here.
Keywords: Alzheimer’s disease; enzyme inhibitors; microbial source; virtual study; ChE; secretase; GSK-3β; MAO; PKC; PDE
... A previous study showed that corilagin was analyzed in silico, is considered an inhibitor of pancreatic lipase enzymes, and could be used to treat obese patients (Hairulazam et al. 2021). Furthermore, Moracin is reported to inhibit the activity of the secretase enzyme; therefore, it can inhibit the synthesis of amyloid in Alzheimer's and dementia conditions (Murata 2019). However, further studies are needed to identify other compounds in broader metabolomics studies. ...
Yunita E, Kurniati T, Rosa FL, Melati P, LestariN. 2022. Short Communication: Analysis of detected metabolites compounds from the crude extract of Rimau Gerga Lebong orangesfruit (Citrus reticulata ‘RGL’) using LC-QTOF-MS/MS. Biodiversitas 23: 3778-3783. Rimau Gerga Lebong (RGL) oranges are the leading commodity in Bengkulu Province. However, the content of bioactive compounds in RGL oranges has not been widely reported. This study aims to identify the flavonoid, alkaloids, and tannins from the ethanol extract of RGL oranges. The results of further identification will be used as a reference in further research on molecular docking in various biological activities. Chemical compounds were identified using qualitative tandem liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS). The measurement of vitamin C levels was carried out using High-Performance Liquid Chromatography (HPLC). The results showed 25 identified compounds, consisting of 6 compounds belonging to the alkaloid group, 17 from the flavonoid group, and 2 from the tannin group. The alkaloid group compounds were 2?, 3?, 6exo-trihydroxy nortopane, 2?, 3?-dihydroxy nortopane, isosalsolin,3?-dihydrocadambine, chelidimerine, and oleracein D. The compounds from identified flavonoid group were chebuloside, neokurarinol, rutinoside, flavonone, glucoside, licochalcone, viscumneoside, and pinnatifinoside. The identified tannins are corilagin and moracin. These compounds that have been identified have biological activity potential as antioxidants, anti-asthma, anti-dementia, and anticancer. The vitamin C content of the ethanol extract of RGL oranges was 0.02±0.0001%. This vitamin C supports the antioxidant activity of RGL orange.
Alzheimer's Disease (AD) is the most common form of dementia, affecting almost 50 million of people around the world, characterized by a complex and age-related progressive pathology with projections to duplicate its incidence by the end of 2050. AD pathology has two major hallmarks, the amyloid beta (Aβ) peptides accumulation and tau hyperphosphorylation, alongside with several sub pathologies including neuroinflammation, oxidative stress, loss of neurogenesis and synaptic dysfunction. In recent years, extensive research pointed out several therapeutic targets which have shown promising effects on modifying the course of the disease in preclinical models of AD but with substantial failure when transposed to clinic trials, suggesting that modulating just an isolated feature of the pathology might not be sufficient to improve brain function and enhance cognition. In line with this, there is a growing consensus that an ideal disease modifying drug should address more than one feature of the pathology. Considering these evidence, β-secretase (BACE1), Glycogen synthase kinase 3β (GSK-3β) and acetylcholinesterase (AChE) has emerged as interesting therapeutic targets. BACE1 is the rate-limiting step in the Aβ production, GSK-3β is considered the main kinase responsible for Tau hyperphosphorylation, and AChE play an important role in modulating memory formation and learning. However, the effects underlying the modulation of these enzymes are not limited by its primarily functions, showing interesting effects in a wide range of impaired events secondary to AD pathology. In this sense, this review will summarize the involvement of BACE1, GSK-3β and AChE on synaptic function, neuroplasticity, neuroinflammation and oxidative stress. Additionally, we will present and discuss new perspectives on the modulation of these pathways on AD pathology and future directions on the development of drugs that concomitantly target these enzymes.
Background
Psoralea corylifolia L. is an important herbal medicine mainly used for the treatment of coronary artery disease, osteoporosis, bacterial infections, vitiligo, and psoriasis. P. corylifolia contains numerous active phytochemicals including bavachalcone. Polyphenolic compounds, including flavonoidal class phytochemicals are secondary plant metabolites found to be present in numerous plant species and reported to have multiple functions to counteract free radicals.
Methods
The aim of the present study is to review the medicinal importance and pharmacological activities of bavachalcone. To know the therapeutic benefit of bavachalcone in medicine, here in the present work we have attempted to provide scientific information of bavachalcone. The present paper has been divided into the overview of flavonoids and P. corylifolia, pharmacological activities of bavachalcone, and analytical aspects of bavachalcone. Detailed pharmacological activities of bavachalcones have been discussed in the present paper. Further Bioanalytical aspects have been also discussed for development of analytical techniques for separation, isolation, and identification of bavachalcone. In the present work, numerous scientific databases such as PubMed, Science Direct, Scopus, Google Scholar, and Google have been searched.
Results
Scientific data analysis revealed that bavachalcone is an important phytochemicals, found to be present in P. corylifolia. Scientific data analysis revealed the biological importance and therapeutic benefit of bavachalcone in medicine. Pharmacological data analysis revealed their effectiveness against cancer, oxidative stress, Alzheimer's disease, angiogenesis, tissue repair, osteoclastogenesis and various enzymes. Further pharmacokinetic and analytical data of bavachalcone have been also collected and analyzed in the present work.
Conclusion
Scientific data analysis revealed that several molecular mechanisms are responsible for pharmacological activities of bavachalcone.
