Rutin ameliorated lipid metabolism dysfunction of diabetic NAFLD via AMPK/SREBP1 pathway.

BACKGROUND: In diabetic liver injury, nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Rutin is a bioflavonoid produced by the hydrolysis of glucosidases to quercetin. Its biological activities include lowering blood glucose, regulating insulin secretion, regulating dyslipidemia, and exerting anti-inflammatory effects have been demonstrated. However, its effect on diabetic NAFLD is rarely reported. PURPOSE: Our study aimed to investigate the protective effects of Rutin on diabetic NAFLD and potential pharmacological mechanism. METHODS: We used db/db mice as the animal model to investigate diabetic NAFLD. Oleic acid-treated (OA) HeLa cells were examined whether Rutin had the ability to ameliorate lipid accumulation. HepG2 cells treated with 30 mM/l d-glucose and palmitic acid (PA) were used as diabetic NAFLD in vitro models. Total cholesterol (TC) and Triglycerides (TG) levels were determined. Oil red O staining and BODIPY 493/503 were used to detect lipid deposition within cells. The indicators of inflammation and oxidative stress were detected. The mechanism of Rutin in diabetic liver injury with NAFLD was analyzed using RNA-sequence and 16S rRNA, and the expression of fat-synthesizing proteins in the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway was investigated. Compound C inhibitors were used to further verify the relationship between AMPK and Rutin in diabetic NAFLD. RESULTS: Rutin ameliorated lipid accumulation in OA-treated HeLa. In in vitro and in vivo models of diabetic NAFLD, Rutin alleviated lipid accumulation, inflammation, and oxidative stress. 16S analysis showed that Rutin could reduce gut microbiota dysregulation, such as the ratio of Firmicutes to Bacteroidetes. RNA-seq showed that the significantly differentially genes were mainly related to liver lipid metabolism. And the ameliorating effect of Rutin on diabetic NAFLD was through AMPK/SREBP1 pathway and the related lipid synthesis proteins was involved in this process. CONCLUSION: Rutin ameliorated diabetic NAFLD by activating the AMPK pathway and Rutin might be a potential new drug ingredient for diabetic NAFLD.

The Efficacy and Safety of Astragalus as an Adjuvant Treatment for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis evaluated the beneficial and potential adverse effects of Astragalus in the treatment of patients with type 2 diabetes mellitus (T2DM). Methods: The authors searched for randomized controlled trials of Astragalus treatment for patients with T2DM in the following databases: PubMed, Embase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI), Wanfang Data, China Science and Technology Journal Database (CQVIP), and SinoMed. Two reviewers conducted independent selection of studies, data extraction, and coding, as well as the assessment of risk of bias in the studies included. Standard meta-analysis and, if appropriate, meta-regression were performed using the STATA, v.15.1, software. Results: This meta-analysis encompasses 20 studies and a total of 953 participants. Compared to the control group (CG), the observation group (OG) decreased fasting plasma glucose (FPG) (WMD = -0.67, 95% CI: -1.13∼-0.20, P = 0.005), 2 hours postprandial plasma glucose (2hPG) (WMD = -0.67 (95% CI: -1.13∼-0.20, P=0.005), glycated hemoglobin A1C (HbA1c) (WMD = -0.93, 95% CI: -1.22∼-0.64, P = 0.000), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD = -0.45, 95% CI: -0.99∼0.99, P = 0.104), insulin sensitive index (WMD = 0.42, 95% CI: 0.13-0.72, P = 0.004). The total effective ratio of the OG is more effective than CG (RR = 1.33, 95% CI: 1.26-1.40, P = 0.000), the significant effective ratio (RR = 1.69, 95% CI: 1.48-1.93, P = 0.000). Conclusions: Astragalus may provide specific benefits for T2DM patients as an adjuvant treatment. Nonetheless, the certainty of the evidence and risk of bias fell short of optimal performance, indicating the need for additional clinical research to ascertain potential effects. PROSPERO REGISTRATION NUMBER CRD42022338491.

Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis.

Background: Acute gouty arthritis (AGA) significantly impairs patients' quality of life. Currently, existing therapeutic agents exhibit definite efficacy but also lead to serious adverse reactions. Therefore, it is essential to develop highly efficient therapeutic agents with minimal adverse reactions, especially within traditional Chinese medicine (TCM). Additionally, food polyphenols have shown potential in treating various inflammatory diseases. The Qingre-Huazhuo-Jiangsuan-Recipe (QHJR), a modification of Si-Miao-San (SMS), has emerged as a TCM remedy for AGA with no reported side effects. Recent research has also highlighted a strong genetic link to gout. Methods: The TCM System Pharmacology (TCMSP) database was used to collect the main chemical components of QHJR and AGA-related targets for predicting the metabolites in QHJR. HPLC-Q-Orbitrap-MS was employed to identify the ingredients of QHJR. The collected metabolites were then used to construct a Drugs-Targets Network in Cytoscape software, ranked based on their "Degree" of significance. Differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database using GEO2R online analysis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The DEGs were utilized to construct a Protein-Protein Interaction (PPI) Network via the STRING database. In vivo experimental validation was conducted using colchicine, QHJR, rapamycin (RAPA), and 3-methyladenine (3-MA) as controls to observe QHJR's efficacy in AGA. Synovial tissues from rats were collected, and qRT-PCR and Western blot assays were employed to investigate Ampk-related factors (Ampk, mTOR, ULK1), autophagy-related factors (Atg5, Atg7, LC3, p62), and inflammatory-related factors (NLRP3). ELISA assays were performed to measure inflammatory-related factor levels (IL-6, IL-1ß, TNF-α), and H&E staining was used to examine tissue histology. Results: Network analysis screened out a total of 94 metabolites in QHJR for AGA. HPLC-Q-Orbitrap-MS analysis identified 27 of these metabolites. Notably, five metabolites (Neochlorogenic acid, Caffeic acid, Berberine, Isoliquiritigenin, Formononetin) were not associated with any individual herbal component of QHJR in TCMSP database, while six metabolites (quercetin, luteolin, formononetin, naringenin, taxifolin, diosgenin) overlapped with the predicted results from the previous network analysis. Further network analysis highlighted key components, such as Caffeic acid, cis-resveratrol, Apigenin, and Isoliquiritigenin. Other studies have found that their treatment of AGA is achieved through reducing inflammation, consistent with this study, laying the foundation for the mechanism study of QHJR against AGA. PPI analysis identified TNF, IL-6, and IL-1ß as hub genes. GO and KEGG analyses indicated that anti-inflammation was a key mechanism in AGA treatment. All methods demonstrated that inflammatory expression increased in the Model group but was reversed by QHJR. Additionally, autophagy-related expression increased following QHJR treatment. The study suggested that AMPKα and p-AMPKα1 proteins were insensitive to 3 MA and RAPA, implying that AMPK may not activate autophagy directly but through ULK1 and mTOR. Conclusion: In conclusion, this study confirms the effectiveness of QHJR, a modified formulation of SMS (a classic traditional Chinese medicine prescription for treating gout), against AGA. QHJR, as a TCM formula, offers advantages such as minimal safety concerns and potential long-term use. The study suggests that the mechanism by which QHJR treats AGA may involve the activation of the AMPK/mTOR/ULK1 pathway, thereby regulating autophagy levels, reducing inflammation, and alleviating AGA. These findings provide new therapeutic approaches and ideas for the clinical treatment of AGA.

Rutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via PI3K/AKT/mTOR pathway in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a primary microvascular complication of diabetes. However, a complete cure for DKD has not yet been found. Although there is evidence that Rutin can delay the onset of DKD, the underlying mechanism remains unclear. PURPOSE: To investigate the renoprotective effect of Rutin in the process of DKD and to explore its potential molecular mechanisms. METHODS: Db/db mice and high glucose (HG)-induced human renal glomerular endothelial cells (GEnCs) were used as in vivo and in vitro models, respectively. Western blot (WB), Immunohistochemistry (IHC)and Immunofluorescence (IF) staining were used to identify the expression level of proteins associated with endothelial-to-mesenchymal transition (EndMT) and autophagy. Tandem Mass Tag (TMT)-based proteomics analysis was utilized to reveal the mechanism of Rutin in DKD. Transfection with small interfering RNA (siRNA) to reveal the role of histone deacetylase 1 (HDAC1) in HG-induced GEnCs. RESULTS: Following 8 weeks of Rutin administration, db/db mice's kidney function and structure significantly improved. In HG-induced GEnCs, activation of autophagy attenuates cellular EndMT. Rutin could alleviate EndMT and restore autophagy in vivo and in vitro models. Proteomics analysis results showed that HDAC1 significantly downregulated in the 200 mg/kg/d Rutin group compared with the db/db group. Transfection with si-HDAC1 in GEnCs partially blocked HG-induced EndMT and restored autophagy. Furthermore, Rutin inhibits the phosphorylation of the PI3K / AKT/ mTOR pathway. HDAC1 overexpression was suppressed in HG-induced GEnCs after using Rapamycin, a specific mTOR inhibitor, verifying the correlation between mTOR and HDAC1. CONCLUSION: Rutin alleviates EndMT by restoring autophagy through inhibiting HDAC1 via the PI3K/AKT/mTOR pathway in DKD.

Qingre Huazhuo Jiangsuan Decoction promotes autophagy by inhibiting PI3K/AKT/mTOR signaling pathway to relieve acute gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Gout belongs to the category of "arthralgia syndrome" in traditional Chinese medicine. It is believed that gout is caused by stagnation of blood stasis, heat, and turbid toxin. Qingre Huazhuo Jiangsuan Decoction (QHJD) is a traditional Chinese medicine prescription developed from the classic Chinese medicine prescription Simiao powder to clear heat, remove turbidity, reduce acid, and reduce inflammation. Now Traditional Chinese Medicine (TCM) physicians often apply it to treat acute gouty arthritis (AGA). However, the mechanism of QHJD in relieving acute gouty arthritis is still unclear, and further research is needed. AIM OF THE STUDY: Here, we aim to explore the potential mechanism of QHJD in relieving acute gouty arthritis. MATERIALS AND METHODS: Acute gouty arthritis model was established by injecting monosodium urate (MSU) suspension into knee joint. The pathological state of synovial tissue in each group was evaluated by hematoxylin-eosin (HE) staining. The level of TNF-α, IL-6, and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). qRT-PCR was used to detect the mRNA expression of NLRP3, ATG5, ATG7, PI3K, AKT, and mTOR. The protein expression of LC3II/I, p62, ULK1, P-ULK1, Beclin-1, PI3K, AKT, mTOR, P-PI3K, P-AKT, and P-mTOR were detected by Western blot. RESULTS: (1) The level of autophagy protein (mRNA) was significantly up-regulated in QHJD group and rapamycin, while the expression of autophagy protein (mRNA) was significantly downregulated in the 3-methyladenoenoic acid (3 MA) group; (2) QHJD and rapamycin significantly inhibited PI3K/AKT/mTOR pathway, while 3 MA group activated this pathway. (3) It was worth noting that after treatment with QHJD and rapamycin, the inflammatory pathological state of AGA synovial tissue was significantly reduced with the activation of the autophagy gene in knee synovial tissue, and the inhibition of PI3K/AKT/mTOR pathway. CONCLUSIONS: This research revealed that QHJD activates autophagy by inhibiting PI3K/AKT/mTOR pathway, thereby relieving acute gouty arthritis.

Current situation and progress of drugs for reducing intraocular pressure.

Glaucoma, the most common cause of irreversible blindness worldwide, usually causes characteristic optic nerve damage. Pathological intraocular pressure (IOP) elevation is a major risk factor. Drug reduction of IOP is the preferred treatment for clinicians because it can delay the progression of disease. However, the traditional IOP-lowering drugs currently used by patients may be poorly tolerated. Therefore, in recent years, some new drugs have been put into clinical application or in clinical phase I-III studies. They have a better IOP-lowering effect and fewer adverse reactions. Because glaucoma is a chronic disease, drugs need to be administered continuously for a long time. For patients, good compliance and high drug bioavailability have a positive effect on the prognosis of the disease. Therefore, clinicians and scientists have developed drug delivery systems to solve this complex problem. In addition, natural compounds and dietary supplements have a good effect of reducing IOP, and they can also protect the optic nerve through antioxidant action. We summarize the current traditional drugs, new drugs, sustained-release drug delivery systems, and complementary drugs and outline the mechanism of action and clinical effects of these drugs on glaucoma and their recent advances.

A Chinese classical prescription Qianjinweijing Decoction in treatment of lung cancer: An overview.

Lung cancer is one of the most common malignant tumors in the world, and its incidence and mortality rate rank among the top malignant tumors worldwide, which has become an important killer threatening human survival rate and well-being. Modern medical treatment for lung cancer is mainly based on surgery and radiotherapy, with gene, targeted drugs and immunotherapy as auxiliary treatments, which are effective, but there are problems such as postoperative recurrence, resistance to radiotherapy, toxic side effects and poor compliance. In recent years, with the continuous development of TCM, TCM is popular among physicians and patients for its high efficiency, low toxicity, low side effects and economic benefits, etc. As a classical TCM formula, Qianjin Weijin Decoction(QJWJ) has certain value in the treatment of lung cancer. This paper summarizes and analyzes the clinical research, molecular mechanism, pharmacological effects and chemical composition of QJWJ in the treatment of lung cancer, in order to provide more ideas and theoretical basis for the treatment of lung cancer with QJWJ.

Crocetin attenuates DHT-induced polycystic ovary syndrome in mice via revising kisspeptin neurons.

Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of women in reproductive age, is typical with hyperandrogenism and disturbance of the hypothalamus-pituitary-ovary (HPO) axis, i.e. abnormal expression of hypothalamic gonadotropin-releasing hormone (GnRH) followed by the elevated ratio of serum luteinizing hormone (LH) level to follicle-stimulating hormone (FSH) level. This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of GnRH. Crocetin, one of the main components of Saffron clinically used as traditional medicine in gynecology diseases, was evaluated for its therapeutic effects on PCOS induced by prenatally exposure to dihydrotestosterone (DHT) in mice. Herein, we found that DHT-treated mice showed a similar phenotype to human PCOS such as heavier ovary, prolonged diestrus, multiple enlarged follicles with fewer corpus luteum, and higher LH and testosterone levels. Kisspeptin expression was lower in anteroventral periventricular nucleus (AVPV) but higher in arcuate nucleus (ARC). Treatment of crocetin prevented the prolongation of diestrus and reduction in corpora luteum, recover the levels of GnRH, FSH, LH, progesterone (P4), estradiol (E2) and testosterone (T), and increase the kisspeptin level in AVPV but reduce that in ARC. The present study provides in vivo evidence that crocetin improved the PCOS in mice via increasing AVPV-kisspeptin and reducing ARC-kisspeptin expression.

Chemical Constituents of Plants from the Genus Eupatorium (1904-2014).

Eupatorium (family: Compositae), which comprises nearly 1200 species, is distributed throughout tropical America, Europe, Africa, and Asia. Up to now, the reported constituents from the genus Eupatorium involve flavonoids, terpenoids, pyrrolizidine alkaloids, phenylpropanoids, quinonoids, essential oils, and some others, altogether more than 300 compounds. Studies have shown that Eupatorium and its active principles possess a wide range of pharmacological activities, such as cytotoxic, antifungal, insecticidal, antibacterial, anti-inflammatory, and antinociceptive activities. Currently, effective monomeric compounds or active parts have been screened for pharmacological activities from Eupatorium in vivo and in vitro. Increasing amount of data supports application and exploitation for new drug development.

Mediated protective effect of electroacupuncture pretreatment by miR-214 on myocardial ischemia/reperfusion injury.

BACKGROUND: Electroacupuncture pretreatment plays a protective role in myocardial ischemia/reperfusion (I/R) injury and microRNAs (miRNAs) could act on various facets of cardiac function. However, the role of miRNAs in the cardioprotection by electroacupuncture pretreatment on myocardial I/R injury remains unknown. The purpose of the study was to examine whether miR-214 was involved in cardioprotection by electroacupuncture. METHODS: Using rat myocardial I/R model, we examined the role of electroacupuncture pretreatment in myocardial I/R injury and analyzed the changes in the expression of miR-214. In addition, I/R was simulated in vitro by performing oxygen-glucose deprivation (OGD) on H9c2 cell cultures, and the effect of electroacupuncture pretreatment on I/R injury as well as expressional level of miR-214 were examined in vitro. Furthermore, the miR-214 mimic was transfected into OGD-treated H9c2 cells, we analyzed the cell apoptosis, lactate dehydrogenase (LDH) and creatine kinase (CK) activities, intracellular free Ca(2+) concentration ([Ca(2+)]i) as well as the relative protein levels of sodium/calcium exchanger 1(NCX1), BCL2-like 11 (BIM), calmodulin-dependent protein kinase IIδ (CaMKIIδ) and Cyclophilin D (CypD). RESULTS: The in vivo results revealed that compared with the I/R group, the electroacupuncture pretreatment group showed significant decreased myocardial infarct size, as well as the increased indices of the cardiac function, including heart rate, mean arterial pressure, left ventricular systolic pressure and maximal rate for left ventricular pressure rising and declining (±dp/dt max). In addition, electroacupuncture pretreatment could inhibit the elevation of LDH and CK activities induced by I/R injury. The quantitative PCR (qPCR) results demonstrated electroacupuncture pretreatment could provide cardioprotection against myocardial I/R injury in rats with miR-214 up-regulation. In the meanwhile, in vitro, electroacupuncture pretreatment protected H9c2 cells from OGD-induced injury. Transfection of miR-214 mimic showed protective effects on OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK activities, rescuing the OGD-induced Ca(2+) and down-regulating elevated protein levels of NCX1, BIM, CaMKIIδ and CypD. CONCLUSIONS: Our findings firstly demonstrated that electroacupuncture pretreatment promotes the expression of miR-214 in myocardial I/R injury and miR-214 contributes to the protective effect of electroacupuncture on myocardial I/R injury.