Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

BACKGROUND Since the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) to be a pandemic infection, important severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (nsp) have been analysed as promising targets in virtual screening approaches. Among these proteins, 3-chymotrypsin-like cysteine protease (3CLpro), also named main protease, and the RNA-dependent RNA polymerase (RdRp), have been identified as fundamental targets due to its importance in the viral replication stages. OBJECTIVES To investigate, in silico, two of the most abundant flavonoid glycosides from Dysphania ambrosioides; a medicinal plant found in many regions of the world, along with some of the putative derivatives of these flavonoid glycosides in the human organism as potential inhibitors of the SARS-CoV-2 3CLpro and RdRp. METHODS Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives. FINDINGS Docking analysis, based on the crystal structure of 3CLpro and RdRp, indicated rutin, nicotiflorin, and their glucuronide and sulfate derivatives as potential inhibitors for both proteins. Also, the importance of the hydrogen bond and π-based interactions was evidenced for the presumed active sites. MAIN CONCLUSIONS Overall, these results suggest that both flavonoid glycosides and their putative human metabolites can play a key role as inhibitors of the SARS-CoV-2 3CLpro and RdRp. Obviously, further researches, mainly in vitro and in vivo experiments, are necessary to certify the docking results reported here, as well as the adequate application of these substances. Furthermore, it is necessary to investigate the risks of D. ambrosioides as a phytomedicine for use against COVID-19.

Flavonoid chemical composition and antidiabetic potential of Brachychiton acerifolius leaves extract

Objective:To evaluate Brachychiton acerifolius leaf extracts as antidiabetic potential agent and to identify the main active constituents using bioactivity guided fractionation.Methods:In vitro antioxidant activity was evaluated for B.acerifolius different extracts using DPPH assay and vitamin C as control.Antidiabetic activity was then determined using STZ-induced rats treated daily with ethyl acetate and 70％ ethanol leaf extracts for 4 weeks at a dose of 200 g/kg body weight against gliclazide reference drug.Blood glucose,α-amylase,lipid profile,liver function enzymes and oxidative stress markers were assessed along with histopathological study for liver and pancreatic tissues.Isolation and structural elucidation of active compounds were made using Diaion and Sephadex followed by spectral analyses.Results:The results indicated that ethyl acetate and ethanol leaf extracts exhibited the strongest antioxidant activity compared to that of vitamin C (IC50 0.05,0.03 and 12 mg/mL,respectively).Both extracts showed potent anti-hyperglycemic activity evidenced by a significant decrease in serum glucose levels by 82.5％ and 80.9％ and α-amylase by 45.2％ and 53.6％,as compared with gliclazide 68％ and 59.4％,respectively.Fractionation of ethanol extract resulted in the isolation of 9 flavonoids including apigenin-7-O-α-rhamnosyl(1 → 2)-β-D-glucuronidc,apigenin-7-O-β-D-glucuronide,apigcnin-7-O-β-D-glucoside and luteolin-7-O-β-D-glucuronide.Conclusions:This study highlights the potential use of B.acerifolius leaf extract enriched in flavones for the treatment of diabetes that would warrant further clinical trials investigation.

Flavonoid chemical composition and antidiabetic potential of Brachychiton acerifolius leaves extract

Objective To evaluate Brachychiton acerifolius leaf extracts as antidiabetic potential agent and to identify the main active constituents using bioactivity guided fractionation. Methods In vitro antioxidant activity was evaluated for B. acerifolius different extracts using DPPH assay and vitamin C as control. Antidiabetic activity was then determined using STZ-induced rats treated daily with ethyl acetate and 70% ethanol leaf extracts for 4 weeks at a dose of 200 g/kg body weight against gliclazide reference drug. Blood glucose, α-amylase, lipid profile, liver function enzymes and oxidative stress markers were assessed along with histopathological study for liver and pancreatic tissues. Isolation and structural elucidation of active compounds were made using Diaion and Sephadex followed by spectral analyses. Results The results indicated that ethyl acetate and ethanol leaf extracts exhibited the strongest antioxidant activity compared to that of vitamin C (IC

Advances in study on biosynthsis of O-glucuronides / 中草药

Glucuronidation is one of the most important metabolic reactions in vivo, while O-glucuronidation is the major reaction type. The synthesis of O-glucuronides is very helpful for the further studies on the evaluation of biological activity and safety of O-glucuronids, as well as drug metabolism and pharmacokinetic studies. The enzymatic catalysis process using UDP-glucuronosyltransferases (UGTs) is the major method for O-glucuronides biosynthesis. This review summarized the recent progress in enzymatic preparation of O-glucuronides by using different enzyme sources including plants, microorganisms, animals, and recombinant human UGTs. Furthermore, this review also summarized several new techniques to improve the efficacy for biosynthesis of O-glucuronides.