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1.
J Asian Nat Prod Res ; 24(5): 403-431, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35282731

RESUMO

Quercetin is a plant-derived polyphenol flavonoid that has been proven to be effective for many diseases. However, the mechanism and in vivo metabolism of quercetin remains to be clarified. It achieves a wide range of biological effects through various metabolites, gut microbiota and its metabolites, systemic mediators produced by inflammation and oxidation, as well as by multiple mechanisms. The all-round disease treatment of quercetin is achieved through the organic combination of multiple channels. Therefore, this article clarifies the metabolic process of quercetin in the body, and explores the new pattern of action of quercetin in the treatment of diseases.


Assuntos
Microbioma Gastrointestinal , Quercetina , Flavonoides/farmacologia , Estrutura Molecular , Quercetina/farmacologia
2.
Front Pharmacol ; 13: 843872, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250593

RESUMO

Nonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), is a liver disease worldwide without approved therapeutic drugs. Anti-inflammatory and hepatoprotective drug bicyclol and multi-pharmacological active drug berberine, respectively, have shown beneficial effects on NAFLD in murine nutritional models and patients, though the therapeutic mechanisms remain to be illustrated. Here, we investigated the combined effects of bicyclol and berberine on mouse steatosis induced by Western diet (WD), and NASH induced by WD/CCl4. The combined use of these was rather safe and better reduced the levels of transaminase in serum and triglycerides and cholesterol in the liver than their respective monotherapy, accompanied with more significantly attenuating hepatic inflammation, steatosis, and ballooning in mice with steatosis and NASH. The combined therapy also significantly inhibited fibrogenesis, characterized by the decreased hepatic collagen deposition and fibrotic surface. As per mechanism, bicyclol enhanced lipolysis and ß-oxidation through restoring the p62-Nrf2-CES2 signaling axis and p62-Nrf2-PPARα signaling axis, respectively, while berberine suppressed de novo lipogenesis through downregulating the expression of acetyl-CoA carboxylase and fatty acid synthetase, along with enrichment of lipid metabolism-related Bacteroidaceae (family) and Bacteroides (genus). Of note, the combined use of bicyclol and berberine did not influence each other but enhanced the overall therapeutic role in the amelioration of NAFLD. Conclusion: Combined use of bicyclol and berberine might be a new available strategy to treat NAFLD.

4.
Small ; 18(9): e2105021, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35088527

RESUMO

Atherosclerosis (AS) is associated with high morbidity and mortality, thus imposing a growing burden on modern society. Herb-derived bicyclol (BIC) is a versatile bioactive compound that can be used to treat AS. However, its efficacy in AS is not yet described. Here, it is shown that BIC normalizes gut microflora dysbiosis induced by a high fat diet in Apoe(-/-) mice. Metagenome-wide association study analysis verifies that the modulation on carbohydrate-active enzymes and short-chain fatty acid generating genes in gut flora is among the mechanisms. The gut healthiness, especially the gut immunity and integrity, is restored by BIC intervention, leading to improved systemic immune cell dynamic and liver functions. Accordingly, the endothelial activation, macrophage infiltration, and cholesterol ester accumulation in the aortic arch are alleviated by BIC to lessen the plaque onset. Moreover, it is proved that the therapeutic effect of BIC on AS is transmissible by fecal microbiota transplantation. The current study, for the first time, demonstrates the antiatherosclerotic effects of BIC and shows that its therapeutic value can at least partially be attributed to its manipulation of gut microbiota.


Assuntos
Aterosclerose , Microbioma Gastrointestinal , Animais , Aterosclerose/tratamento farmacológico , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Disbiose , Camundongos , Camundongos Endogâmicos C57BL
5.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873151

RESUMO

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.


Assuntos
Antivirais/administração & dosagem , Azidas/administração & dosagem , COVID-19/tratamento farmacológico , Desoxicitidina/análogos & derivados , SARS-CoV-2/metabolismo , Timo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Coronavirus Humano OC43/metabolismo , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Timo/metabolismo , Timo/virologia
6.
J Pharm Anal ; 11(5): 628-637, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34765276

RESUMO

Berberine (BBR) is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes, hyperlipidemia and inflammation. Due to the low oral bioavailability of BBR, its mechanism of action is closely related to the gut microbiota. This study focused on the CYP51 enzyme of intestinal bacteria to elucidate a new mechanism of BBR transformation by demethylation in the gut microbiota through multiple analytical techniques. First, the docking of BBR and CYP51 was performed; then, the pharmacokinetics of BBR was determined in ICR mice in vivo, and the metabolism of BBR in the liver, kidney, gut microbiota and single bacterial strains was examined in vitro. Moreover, 16S rRNA analysis of ICR mouse feces indicated the relationship between BBR and the gut microbiota. Finally, recombinant E. coli containing cyp51 gene was constructed and the CYP51 enzyme lysate was induced to express. The metabolic characteristics of BBR were analyzed in the CYP51 enzyme lysate system. The results showed that CYP51 in the gut microbiota could bind stably with BBR, and the addition of voriconazole (a specific inhibitor of CYP51) slowed down the metabolism of BBR, which prevented the production of the demethylated metabolites thalifendine and berberrubine. This study demonstrated that CYP51 promoted the demethylation of BBR and enhanced its intestinal absorption, providing a new method for studying the metabolic transformation mechanism of isoquinoline alkaloids in vivo.

7.
Front Microbiol ; 12: 757914, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707597

RESUMO

Tuberculosis (TB) is still a threat to humans worldwide. The rise of drug-resistant TB strains has escalated the need for developing effective anti-TB agents. Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is essential for thymidylate biosynthesis to maintain the DNA integrity. In Mycobacterium tuberculosis, dUTPase provides the sole source for thymidylate biosynthesis, which also has the specific five-residue loop and the binding pockets absent in human dUTPase. Therefore, dUTPase has been regarded as a promising anti-TB drug target. Herein, we used a luminescence-based dUTPase assay to search for the inhibitors target M. tuberculosis dUTPase (Mt-dUTPase) and identified compound F0414 as a potent Mt-dUTPase inhibitor with an IC50 of 0.80 ± 0.09 µM. F0414 exhibited anti-TB activity with low cytotoxicity. Molecular docking model and site-directed mutation experiments revealed that P79 was the key residue in the interaction of Mt-dUTPase and F0414. Moreover, F0414 was shown to have stronger binding with Mt-dUTPase than with Mt-P79A-dUTPase by surface plasmon resonance (SPR) detection. Interestingly, F0414 exhibited insensitivity and weak directly binding on human dUTPase compared with that on Mt-dUTPase. All the results highlight that F0414 is the first compound reported to have anti-TB activity by inhibiting Mt-dUTPase, which indicates the potential application in anti-TB therapy.

8.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202717

RESUMO

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Saponinas/farmacocinética , Esteroides/farmacocinética , Animais , Biotransformação , Masculino , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia , Esteroides/farmacologia
9.
10.
Nat Prod Res ; : 1-7, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34121549

RESUMO

Two new prenylaromadendrane-type diterpenoids, and three known analogues, were isolated from the ethanol extract of the gum resin of B. sacra Flueck. The structures of the new compounds were elucidated using 1 D and 2 D NMR spectroscopic analyses, mass spectrometric data, circular dichroism spectra, and comparison with the other compounds in the literature. One diterpenoid represents the first example of an acetoxyl-substituted prenylaromadendranoid in frankincense. All compounds exhibited notable cytotoxicity against human malignant glioma (U87-MG) cell line, with inhibitory rates exceeding that of the positive control 5-fluorouracil. However, nitric oxide inhibition induced by lipopolysaccarides was not observed in primary mouse peritoneal macrophages.

11.
Curr Microbiol ; 78(5): 2165-2172, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33839887

RESUMO

A Gram-negative, facultative anaerobic, non-lagellated and rod-shaped bacterium FML-4T was isolated from a chlorothalonil-contaminated soil in Nanjing, China. Phylogenetic analyses of 16S rRNA genes revealed that the strain FML-4T shared the highest sequence similarity of 97.1% with Ciceribacter thiooxidans KCTC 52231T, followed by Rhizobium rosettiformans CCM 7583T (97.0%) and R. daejeonense KCTC 12121T (96.8%). Although the sequence similarities of the housekeeping genes thrC, rceA, glnII, and atpD between strain FML-4T and C. thiooxidans KCTC 52231T were 83.8%, 88.7%, 86.2%, and 92.0%, respectively, strain FML-4T formed a monophyletic clade in the cluster of Rhizobium species. Importantly, the feature gene of the genus Rhizobium, nifH gene (encoding the dinitrogenase reductase), was detected in strain FML-4T but not in C. thiooxidans KCTC 52231T. In addition, strain FML-4T contained the summed feature 8 (C18:1ω7c and/or C18:1ω6c), C19:0 cyclo ω8c and C16:0 as the major fatty acids. Genome sequencing of strain FML-4T revealed a genome size of 7.3 Mbp and a G+C content of 63.0 mol%. Based on the results obtained by phylogenetic and chemotaxonomic analyses, phenotypic characterization, average nucleotide identity (ANI, similarity 77.3-75.4%), and digital DNA-DNA hybridization (dDDH, similarity 24.5-22.3%), it was concluded that strain FML-4T represented a novel species of the genus Rhizobium, for which the name Rhizobium flavescens sp. nov. was proposed (type strain FML-4T = CCTCC AB 2019354T = KCTC 62839T).


Assuntos
Rhizobium , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos , Nitrilas , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S/genética , Rhizobiaceae , Rhizobium/genética , Análise de Sequência de DNA , Solo
12.
J Asian Nat Prod Res ; 23(6): 536-544, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33779421

RESUMO

Three previously unidentified polycyclic polyprenylated acylphloroglucinols (PPAPs) derivatives, hypseudohenrins I-K (1-3), along with a known analogue hyphenrone X (4), were isolated from the aerial part of Hypericum pseudohenryi. The structures of the new compounds were elucidated by NMR spectroscopy and ECD calculation. The anti-inflammatory activity of the compounds was evaluated. Compounds 1-3 showed mild anti-inflammatory activity while hyphenrone X showed prominent anti-inflammatory activity.[Formula: see text].


Assuntos
Hypericum , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Floroglucinol/farmacologia
13.
Signal Transduct Target Ther ; 6(1): 77, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33623004

RESUMO

The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (L-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H• through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of L-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The L-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut-brain dialog activated by BBR's effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson's disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal L-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of L-dopa in the gut microbiota through a vitamin-like effect.


Assuntos
Berberina/farmacologia , Di-Hidroxifenilalanina/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Animais , Berberina/análogos & derivados , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/microbiologia , Dopamina/metabolismo , Enterococcus faecalis/metabolismo , Enterococcus faecium/metabolismo , Humanos , Levodopa/metabolismo , Camundongos , Doença de Parkinson/metabolismo , Doença de Parkinson/microbiologia , Tirosina 3-Mono-Oxigenase/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-35309096

RESUMO

Many microorganisms have mechanisms that protect cells against attack from viruses. The fermentation components of Streptomyces sp. 1647 exhibit potent anti-influenza A virus (IAV) activity. This strain was isolated from soil in southern China in the 1970s, but the chemical nature of its antiviral substance(s) has remained unknown until now. We used an integrated multi-omics strategy to identify the antiviral agents from this streptomycete. The antibiotics and Secondary Metabolite Analysis Shell (antiSMASH) analysis of its genome sequence revealed 38 biosynthetic gene clusters (BGCs) for secondary metabolites, and the target BGCs possibly responsible for the production of antiviral components were narrowed down to three BGCs by bioactivity-guided comparative transcriptomics analysis. Through bioinformatics analysis and genetic manipulation of the regulators and a biosynthetic gene, cluster 36 was identified as the BGC responsible for the biosynthesis of the antiviral compounds. Bioactivity-based molecular networking analysis of mass spectrometric data from different recombinant strains illustrated that the antiviral compounds were a class of structural analogues. Finally, 18 pseudo-tetrapeptides with an internal ureido linkage, omicsynins A1-A6, B1-B6, and C1-C6, were identified and/or isolated from fermentation broth. Among them, 11 compounds (omicsynins A1, A2, A6, B1-B3, B5, B6, C1, C2, and C6) are new compounds. Omicsynins B1-B4 exhibited potent antiviral activity against IAV with the 50% inhibitory concentration (IC50) of approximately 1 µmol∙L-1 and a selectivity index (SI) ranging from 100 to 300. Omicsynins B1-B4 also showed significant antiviral activity against human coronavirus HCoV-229E. By integrating multi-omics data, we discovered a number of novel antiviral pseudo-tetrapeptides produced by Streptomyces sp. 1647, indicating that the secondary metabolites of microorganisms are a valuable source of novel antivirals.

15.
J Agric Food Chem ; 68(26): 6967-6976, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32530641

RESUMO

Dichlorprop [(RS)-2-(2,4-dichlorophenoxy)propanoic acid; DCPP], an important phenoxyalkanoic acid herbicide (PAAH), is extensively used in the form of racemic mixtures (Rac-DCPP), and the environmental fates of both DCPP enantiomers [(R)-DCPP and (S)-DCPP] mediated by microorganisms are of great concern. In this study, a bacterial strain Sphingopyxis sp. DBS4 was isolated from contaminated soil and was capable of utilizing both (R)-DCPP and (S)-DCPP as the sole carbon source for growth. Strain DBS4 preferentially catabolized (S)-DCPP as compared to (R)-DCPP. The optimal conditions for Rac-DCPP degradation by strain DBS4 were 30 °C and pH 7.0. In addition to Rac-DCPP, other PAAHs such as (RS)-2-(4-chloro-2-methylphenoxy)propanoic acid, 2,4-dichlorophenoxyacetic acid, 4-chloro-2-methylphenoxyacetic acid, and 2,4-dichlorophenoxyacetic acid butyl ester could also be catabolized by strain DBS4. Bioremediation of Rac-DCPP-contaminated soil by inoculation of strain DBS4 exhibited an effective removal of both (R)-DCPP and (S)-DCPP from the soil. Due to its broad substrate spectrum, strain DBS4 showed great potential in the bioremediation of PAAH-contaminated sites.


Assuntos
Ácido 2,4-Diclorofenoxiacético/análogos & derivados , Herbicidas/metabolismo , Sphingomonadaceae/metabolismo , Ácido 2,4-Diclorofenoxiacético/química , Ácido 2,4-Diclorofenoxiacético/metabolismo , Biodegradação Ambiental , Herbicidas/química , Estereoisomerismo
16.
Phytochemistry ; 177: 112425, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32535347

RESUMO

Ten undescribed cembrane-type diterpenes boscartins AL-AU, as well as five known analogues were isolated from Boswellia sacra Flueck. The relative configurations of these boscartins were established by extensive spectroscopic analysis of NMR spectra, IR and MS. The absolute configurations of boscartin AL, boscartin AN and isoincensole oxide were unequivocally assigned by single crystal X-ray diffraction. Meanwhile, the absolute configurations of boscartin AM, boscartin AP and boscartin AQ were determined by an empirical in situ formed Rh-complex ECD method. Biological evaluations showed that four compounds exhibited obvious hepatoprotective activities against paracetamol-induced HepG2 cell damage at 10 µM. Regarding neuroprotective activity, some isolates displayed moderate to evident protective effects against glutamate-induced toxicity in primary cultured fetal rat cortical neurons or oxygen-glucose deprivation toxicity in SK-N-SH Cells at 10 µM.


Assuntos
Boswellia , Diterpenos , Acetaminofen , Animais , Cristalografia por Raios X , Células Hep G2 , Estrutura Molecular , Ratos
17.
Pain Res Manag ; 2020: 1876862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454918

RESUMO

Purified from the roots of the plant Sinomenium acutum, sinomenine is traditionally used in China and Japan for treating rheumatism and arthritis. Previously, we have demonstrated that sinomenine possessed a broad analgesic spectrum in various chronic pain animal models and repeated administration of sinomenine did not generate tolerance. In this review article, we discussed sinomenine's analgesic mechanism with focus on its role on immune regulation and neuroimmune interaction. Sinomenine has distinct immunoregulative properties, in which glutamate, adenosine triphosphate, nitric oxide, and proinflammatory cytokines are thought to be involved. Sinomenine may alter the unbalanced neuroimmune interaction and inhibit neuroinflammation, oxidative stress, and central sensitization in chronic pain states. In conclusion, sinomenine has promising potential for chronic pain management in different clinical settings.


Assuntos
Analgésicos/farmacologia , Dor Crônica , Morfinanos/farmacologia , Neuroimunomodulação/efeitos dos fármacos , Animais , Dor Crônica/tratamento farmacológico , Dor Crônica/fisiopatologia , Humanos
18.
ACS Sens ; 5(6): 1650-1656, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32466642

RESUMO

The specific detection of pathogens has long been recognized as a vital strategy for controlling bacterial infections. Herein, a novel hydrophilic aromatic-imide-based thermally activated delayed fluorescence (TADF) probe, AI-Cz-Neo, is designed and synthesized by the conjugation of a TADF emitter with a bacterial 16S ribosomal RNA-targeted moiety, neomycin. Biological data showed for the first time that AI-Cz-Neo could be successfully applied for the dual-mode detection of bacterial 16S rRNA using confocal fluorescence imaging and time-resolved fluorescence imaging (TRFI) in both cells and tissues. These findings greatly expand the application of TADF fluorophores in time-resolved biological imaging and provide a promising strategy for the precise and reliable diagnosis of bacterial infections based on the dual-mode imaging of bacterial 16S rRNA by fluorescence intensity and fluorescence lifetime.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Interações Hidrofóbicas e Hidrofílicas , Neomicina , RNA Ribossômico 16S/genética
19.
Front Pharmacol ; 11: 647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457629

RESUMO

AIM: This study is designed to investigate whether or not AMP-activated protein kinase α1 (AMPKα1) is required for natural product berberine (BBR) to improve glucose and lipid metabolism in HepG2 cells. METHODS: AMPKα1 knocked-out (KO, AMPKα1-/- ) cells were obtained by co-transfection of the CRISPR/Cas9 KO and HDR (homology-directed repair) plasmid into HepG2 cells, as well as subsequent screen with puromycin. The expression levels of target proteins or mRNAs were determined by western blot or real-time RT-PCR, respectively. Cellular AMPK activity, glucose consumption, lactate release, glucose production, and lipid accumulation were determined by kits. RESULTS: The results showed that the AMPKα1 gene was successfully KO in HepG2 cells. In AMPKα1-/- cells, the protein expression of AMPKα1 and phosphorylated-AMPKα1 (p-AMPKα1) disappeared, the level of total AMPKα declined to about 45-50% of wild type (p < 0.01), while p-AMPKα level and AMPK activity were reduced to less than 10% of wild type (p < 0.001). BBR increased p-AMPKα1, p-AMPKα, AMPK activity, and stimulated glucose consumption, lactate release, inhibited glucose production in wild type HepG2 cells (p < 0.05 or p < 0.01). BBR also reduced intracellular lipid accumulation and suppressed the expression of lipogenic genes in oleic acid (OA) treated wild type HepG2 cells (p < 0.05 or p < 0.01). In AMPKα1-/- HepG2 cells, the stimulating effects of BBR on p-AMPKα1, p-AMPKα, AMPK activity, and its improving effects on glucose and lipid metabolism were completely abolished. CONCLUSION: Our study proves that AMPKα1 plays a critical role for BBR to improve glucose and lipid metabolism in HepG2 cells. Our results will provide new information to further understand the molecular mechanisms of BBR.

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