ABSTRACT
Gout is a metabolic disorder characterized by elevated uric acid levels， often caused by purine metabolism disturbances or abnormalities in uric acid （UA） excretion. Currently， western medicine is the primary treatment approach for gout， but it often comes with significant side effects. Traditional Chinese medicine （TCM） has gained significant development in the field of gout treatment due to its safety and effectiveness. This article aimed to explore TCM strategies in the management of gout， providing insights for the development and application of TCM in the field of gout treatment. Relevant literature retrieved from PubMed， Web of Science， China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP databases was systematically analyzed with such keywords as "Chinese herbal medicine"， "traditional Chinese medicine"， "TCM"， and "gout". The findings suggest that TCM can treat gout through a syndrome differentiation approach that encompasses four pathological mechanisms： phlegm， blood stasis， dampness， and deficiency， simultaneously addressing both excess and deficiency syndromes in gout. Based on the pathological characteristics of four syndromes， namely dampness-heat retention， blood stasis-heat obstruction， phlegm-turbidity obstruction， and liver and kidney Yin deficiency， TCM adopts specific treatment approaches including clearing heat and promoting diuresis， activating blood and resolving stasis， resolving phlegm and reducing turbidity， and nourishing the liver and kidneys. These targeted approaches have proven to be effective in gout management. The main mechanisms of TCM in gout management include inflammation resistance ［regulating inflammatory pathways such as tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， interleukin-8 （IL-8）， and other chemokines， as well as inflammatory signaling pathways like nuclear factor-kappa B （NF-κB） and NOD-like receptor protein 3 （NLRP3）］， uric acid reduction （modulating uric acid transporters and inhibiting xanthine oxidase （XOD） activation）， antioxidant stress mitigation （suppressing reactive oxygen species and regulating nitric oxide， malondialdehyde， and other oxidative markers）， and immune system regulation.
ABSTRACT
OBJECTIVE:To study the mechanism of Aurantii fructus immaturus(AFI)and its main active ingredients in pro-moting gastrointestinal motility of model rats with spleen deficiency. METHODS:170 rats were randomly divided into blank group (10 rats) and modeling group (160 rats),rats in modeling group was induced models with spleen deficiency by bitter cold diar-rhea+irregular diet. After modeling, rats were randomly divided into model group, naringin (NA) low-dose, medium-lose, high-dose groups(3.267,6.535,13.070 mg/mL),neohesperidin(NE)low-dose,medium-lose,high-dose groups(3.865,7.730, 15.460 mg/mL),synephrine(SY)low-dose,medium-lose,high-dose groups(0.252,0.504,1.008 mg/mL),compatibility groups with 3 monomer ingredients (NA-NE-SY) low-dose,medium-lose,high-dose and AFI water decoction low-dose,medium-lose, high-dose groups(0.104,0.208,0.416 g/mL,calculated by crude drug),ig,once a day,10 mL/kg,for 7 d. After the last admin-istration,gastrin (GAS) in serum,and acetylcholine (ACh),motilin (MTL),substance P (SP),vasoactive intestinal peptide (VIP)levels in plasma were detected. RESULTS:Compared with blank group,GAS level in serum and ACh,MTL,SP levels in plasma in model group were reduced(P<0.01),VIP level in plasma was increased(P<0.05). Compared with model group,ex-cept for the GAS level in serum showed no obvious change in NA high-dose group and SY doses groups,other medicine groups were obviously increased (P<0.05 or P<0.01);the ACh levels in serum were obviouly increased in NE high-dose group,SY high-dose group and AFI water decoction low-dose group(P<0.01). MTL levels in plasma were obviously increased in NE medi-um-dose,high-dose groups,SY high-dose group,compatibility low-dose,medium-dose groups and AFI water decoction medi-um-dose,high-lose groups (P<0.05);SP levels in plasma were obviously increased in NA low-dose,medium-dose groups and NE doses groups(P<0.05 or P<0.01);VIP levels were reduced in NA low-dose group,SY high-dose group and AFI water decoc-tion low-dose,medium-lose groups(P<0.05). CONCLUSIONS:AFI may promote the gastrointestinal motility of model rats with spleen deficiency by promoting the secretion of GAS,ACh,MTL,and inhibiting the secretion of VIP;there are differences be-tween AFI and the 3 monomer ingredients in regulation of gastrointestinal hormones.
ABSTRACT
Bromodomain and extra-terminal domain(BET)Bromodomain has become a new target for the treatment of cancers and other human disorders. Nowadays,several classes of its potent and selective small-molecule inhibitors have been identified,many of which are in clinical trials. Preclinical and clinical data have shown that BET Bromodomain inhibitors have good prospects. Howev-er,there are potential therapeutic deficiencies,such as drug resistance. At present,attempts are being made to develop BET Bromodo-main inhibitors and degraders based on polypharmacology,combining BET Bromodomain with other targets of different mechanisms. In this paper,small-molecule kinase/BET inhibitors,small-molecule histone deacetylases(HDAC)/BET inhibitors and BET protein degraders are reviewed,which may provide guidance for further research on BET protein.