The Chemical Changes And Hypoglycemic Preliminary Study Of Different Herbal Pairs Of Rhizoma Coptidis Fermented By Eurotium Cristatum

Microorganisms have a strong biotransformation effect in the fermentation process of traditional Chinese medicine,which can improve the active ingredients and enhance the efficacy.Eurotium Cristatum,a main fungus isolated from post-fermented black tea,which can also improve the biological activities of the substrates.In addition,the secondary metabolites secreted by Eurotium Cristatum have biological activities such as reducing weight,regulating glucose metabolism and antioxidation,and have high medical application value.China has the largest number of patients with type diabetes(T2DM)in the world.Chinese medicinal materials have certain advantages in the treatment of T2 DM with complex factors,and can be processed by microbial fermentation for treating various diseases and discovering new clinical drugs.Rhizoma coptidis is a highly valued traditional Chinese medicine,which has been widely applied in complementary and alternative medicines in China.Rhizoma Coptidis,one of the most commonly used traditional Chinese medicines for the treatment T2 DM,which is often used together with other traditional Chinese medicinal materials.Coptidis rhizoma-Scutellariae radix(RS),Coptidis rhizoma-Panax notoginseng(RP)and Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma(RG)are classic medicine herbal pairs in the traditional Chinese medicine treatment of diabetes.At present,there has been no report on the fermentation of Coptidis rhizoma with the different herbal pairs.The purpose of this study was to investigate the effects of fermentation of Rhizome coptis-Scutellaria baicalensis(FRS),fermentation of Rhizome coptis-Glycyrrhizae Radix et Rhizoma(FRG)and fermentation of Rhizome coptis-Panax notoginseng(FRP)on the biological activities,chemical composition changes and hypoglycemic effects.The main results are as follows:1.Compared with the different herbal pairs of unfermented Rhizoma Coptidis,the total flavonoids contents of FRS,FRP and FRG groups were increased by 3.87,14.25 and 3.46 times,and the total phenol contents were increased by 1.22,1.23 and 1.10 times,respectively.The FRAP total reducing power,ABTS radical scavenging ability and DPPH radical scavenging ability of FRP,FRS and FRG groups were better than the unfermented,and FRAP total reducing power of FRS group was stronger than FRG and FRP groups.The ABTS free radical scavenging ability of FRS and FRG groups were comparable,which were better than FRP group.The DPPH radical scavenging ability of FRS and FRG groups were stronger than FRP group.The α-amylase inhibition of fermented Coptidis rhizoma-Scutellariae radix and Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma were stronger than that unfermented,but the improvement was not significant.The α-glucosidase inhibition of fermented Coptidis rhizoma-Scutellariae radix and Coptidis rhizoma-Panax notoginseng were stronger than the control.2.Using VIP > 1 as a screening condition,we found that 151 classes of differential metabolites between RG and FRG groups,35 in RS and FRS groups,and 120 in RP and FRP groups,including Organooxygen compounds,Carboxylic acids and derivatives,Fatty Acyls,Benzene and substituted derivatives,Flavonoids,Isoflavonoids,Steroids and steroid derivatives,Coumarins and derivatives,Cinnamic acids and derivatives,Quinolines and derivatives,Keto acids and derivatives,Phenols,etc.3.In terms of body weight,body weight gain were increased in FRS and FRG groups.MET and FRP groups significantly reduced the body weight of T2 DM rats,which was slightly lower than MG group.In terms of FBG level,MET group significantly reduced the FBG level of T2 DM rats at the second week of administration,which were higher than CK group.FRP group showed an upward trend of FBG level at the first,second,and third weeks of administration,which was significantly higher than MG group,and FBG level was lower than MG group at the fourth weeks.FRS and FRG groups decreased FBG level at the second week of administration,which was better than the FRP group,but FBG level was higher than MET Group.In terms of OGTT level,the blood glucose level of rats in the MET group increased significantly within 30 minutes,which was higher than FRP,FRS and FRG groups.After 30 minutes,the blood glucose of all T2 DM rats showed a downward trend,and MET group was higher than that in the FRP,FRS and FRG groups.In terms of serum biochemical parameters,the TG,TC and LDL-C levels in MG group was significantly higher than CK group,and HDL-C level was significantly lower than CK group.TG level was significantly reduced in MET and FRS groups,TC level were significantly reduced in FRS,FRG and FRP groups,but not MET group.MET and FRP groups significantly increased HDL-C level,while the MET,FRS,and FRG groups significantly reduced LDL-C level.In terms of pancreatic tissue,MG group showed atrophy,degeneration and necrosis,and MET,FRS,FRG and FRP groups repaired the pancreatic tissue of T2 DM rats in different degrees.The effects of MET and FRS groups in repairing pancreatic tissue of T2 DM rats were better than FRG and FRP groups.In terms of intestinal flora,compared with CK group,species OTUs of T2 DM rats in MG group was decreased,while significantly increased in FRG group.The significant differences were observed in the structure of the intestinal flora at the phylum,class,order and family species levels between CK,MG and different formula groups of fermented Rhizoma Coptidis groups.The proliferation of pathogenic bacteria,including Proteobacteria,Sutterellaceae and Enterobacteriaceae,were significantly inhibited in MET,FRP and FRS groups.FRS,FRP and FRG groups increased the abundance of beneficial bacteria Verrucomicrobiota and Oscillospiraceae.The FRP and FRG groups have the ability to promote proliferation of Leuconostocaceae and Lachnospirales,the FRP and FRS groups increased the abundance of beneficial bacteria Monoglobaceae and Clostridia.FRS and FRP treatment led to significant increases in the abundances of Spirochaetota and Akkermansiaceae,respectively.