ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

ObjectiveThe study aims to investigate the intervention effect of modified Xiangsha Liujunzitang （M-XSLJZ） on intestinal-derived lipopolysaccharide （LPS）-activated Kupffer cell inflammation in rats with hyperlipidemia spleen deficiency syndrome. MethodsSeventy male SD rats were randomly divided into seven groups （n=10）： blank control （CON）， high-fat diet without spleen deficiency （HFD）， high-fat diet with spleen deficiency （SD-HFD）， M-XSLJZ low-， medium-， and high-dose groups （XS-L， XS-M， XS-H）， and western medicine control （R）. Spleen deficiency was induced in SD-HFD， XS-L， XS-M， XS-H， and R groups via irregular diet combined with exhaustive swimming for 15 days. The CON group received a standard diet， while other groups were fed a high-fat diet for 10 weeks to establish the hyperlipidemia model. After successful modeling， rats were treated for 8 weeks： M-XSLJZ was administered at 3.51， 7.02， 14.04 g·kg^-1 in XS-L， XS-M， and XS-H groups， respectively. The R group received 9×10^-4 g·kg^-1 of a reference drug. D-xylose excretion rate was measured by the phloroglucinol method. Blood lipids were assessed using an automated biochemical analyzer. Hematoxylin-eosin （HE） staining was used to evaluate the pathological conditions of the liver， and oil red O staining was used to observe the lipid deposition in the liver. The levels of LPS， portal vein serum LPS， LPS-binding protein （LBP）， serum interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to evaluate CD86 expression and CD68/TLR4 co-localization in the liver. Protein levels of TLR4， MyD88， NF-κB p65， and p-NF-κB p65 in Kupffer cells were analyzed via Western blot automated protein analysis. Hepatic IL-6， TNF-α， and IL-1β mRNA and protein levels were measured using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the CON group， the SD-HFD group showed a decrease in D-xylose excretion （P<0.01）. TC， TG， HDL-C， and LDL-C increased （P<0.05， P<0.01）. A large number of hepatic lipid vacuoles and orange-red lipid droplet deposition appeared in the liver. Ileal LPS， portal LPS， and LBP increased （P<0.05， P<0.01）. The levels of serum IL-6， TNF-α， and IL-1β increased （P<0.01）. The expression of CD86 was upregulated （P<0.01）， and the co-expression of CD68 and TLR4 was enhanced. The protein levels of TLR4， MyD88， and p-p65 in Kupffer cells increased （P<0.01）. The mRNA and protein levels of IL-6， TNF-α， and IL-1β increased （P<0.05， P<0.01）. Compared with the HFD group， the SD-HFD group exhibited decreased D-xylose excretion （P<0.01）， higher HDL-C， LDL-C （P<0.05）， increased portal LBP and LPS （P<0.05）， increased serum IL-6 and TNF-α （P<0.01）， upregulated CD86 （P<0.01）， enhanced CD68/TLR4 co-expression， and higher TNF-α mRNA/protein （P<0.05）. Compared with the SD-HFD group， all M-XSLJZ treatment groups showed reduced TC， TG， and LDL-C （P<0.05， P<0.01）. XS-H and R groups displayed improved hepatic lipid deposition. XS-H and R groups had lower ileal LPS， portal LPS， and LBP levels （P<0.05， P<0.01）. All M-XSLJZ treatment groups exhibited reduced serum IL-6， IL-1β， and TNF-α （P<0.01）. The XS-H group showed downregulated CD86 （P<0.01） and weakened CD68/TLR4 co-expression. The XS-H group had reduced TLR4， MyD88， and p-NF-κB p65 in Kupffer cells （P<0.01）. XS-H and R groups showed lower IL-6， TNF-α， and IL-1β mRNA/protein （P<0.05， P<0.01）. ConclusionM-XSLJZ may exert its lipid-lowering effects by inhibiting intestinal-derived LPS and alleviating Kupffer cell inflammation in the liver.

The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry* ; Tannins/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Plant Extracts

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

This study explored the mechanism of Xiangsha Liujunzi Decoction(XSLJZD) in the treatment of functional dyspepsia(FD) based on inositol-requiring enzyme 1(IRE1)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway-mediated autophagy in interstitial cells of Cajal(ICC). Forty-eight SPF-grade male SD suckling rats were randomly divided into a blank group and a modeling group, and the integrated modeling method(iodoacetamide gavage + disturbance of hunger and satiety + swimming exhaustion) was used to replicate the FD rat model. After the model replications were successfully completed, the rats were divided into a model group, high-dose, medium-dose, and low-dose groups of XSLJZD(12, 6, and 3 g·kg~(-1)·d~(-1)), and a positive drug group(mosapride of 1.35 mg·kg~(-1)·d~(-1)), and the intervention lasted for 14 days. The gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The histopathological changes in the gastric sinus tissue of rats in each group were observed by hematoxylin-eosin(HE) staining. The ultrastructure of ICC was observed by transmission electron microscopy. The immunofluorescence double staining technique was used to detect the protein expression of phospho-IRE1(p-IRE1), TNF receptor associated factors 2(TRAF2), phospho-ASK1(p-ASK1), phospho-JNK(p-JNK), p62, and Beclin1 in ICC of gastric sinus tissue of rats in each group. Western blot was used to detect the related protein expression of gastric sinus tissue of rats in each group. Compared with those in the blank group, the rats in the model group showed decreased body weight, gastric emptying rate, and intestinal propulsion rate, and transmission electron microscopy revealed damage to the endoplasmic reticulum structure and increased autophagosomes in ICC. Immunofluorescence staining revealed that the ICC of gastric sinus tissue showed a significant elevation of p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins and a significant reduction of p62 protein. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. Compared with the model group, the body weight of rats in the high-dose and medium-dose groups of XSLJZD was increased, and the gastric emptying rate and intestinal propulsion rate were increased. Transmission electron microscopy observed amelioration of structural damage to the endoplasmic reticulum of ICC and reduction of autophagosomes, and the p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins in the ICC of gastric sinus tissue were significantly decreased. The p62 protein was significantly increased. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. XSLJZD can effectively treat FD, and its specific mechanism may be related to the inhibition of the expression of molecules related to the endoplasmic reticulum stress IRE1/ASK1/JNK pathway in ICC and the improvement of autophagy to promote gastric motility in ICC.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Autophagy/drug effects* ; Rats ; Rats, Sprague-Dawley ; Interstitial Cells of Cajal/metabolism* ; Dyspepsia/physiopathology* ; Protein Serine-Threonine Kinases/genetics* ; MAP Kinase Kinase Kinase 5/genetics* ; MAP Kinase Signaling System/drug effects* ; Humans ; Endoribonucleases/genetics* ; Multienzyme Complexes

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

This study aims to explore whether Guzheng playing training has a positive impact on the brain functional state of children with Autism Spectrum Disorder (ASD) based on power spectral and sample entropy analyses. Eight ASD participants were selected to undergo four months of Guzheng playing training, with one month as a training cycle. Electroencephalogram (EEG) signals and behavioral data were collected for comparative analysis. The results showed that after Guzheng playing training, the relative power of the alpha band in the occipital lobe of ASD children increased, and the relative power of the theta band in the parietal lobe decreased. The differences compared with typically developing (TD) children were narrowed. Moreover, some channels exhibited a gradual increase or decrease in power with the extended training period. Meanwhile, the sample entropy parameter also showed a similar upward trend, which was consistent with the behavioral data representation. The study shows that Guzheng training can enhance the brain function of ASD patients, with better effects from longer training. Guzheng playing training could be used as a daily intervention for autism.
Humans ; Electroencephalography ; Entropy ; Music Therapy ; Child ; Brain/physiopathology* ; Autism Spectrum Disorder/therapy* ; Male ; Female ; Autistic Disorder/therapy*