Exploration of material basis: Chemical composition profile, metabolic profile and pharmacokinetic characteristics in Xingbei Zhike granule.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Xingbei Zhike granule (XBZK), a widely prescribed Chinese patent medicine, is known for its efficacy in clearing lung qi, relieving cough and reducing phlegm, as well as fever, dry and bitter taste, and irritability. Despite its clinical popularity, comprehensive investigations into its chemical composition, in vivo metabolism, and pharmacokinetic characteristics are limited. AIM OF THE STUDY: This study investigates the chemical composition, in vivo metabolism, and in vivo dynamics of XBZK to clarify its material basis and pharmacokinetic characteristics. MATERIALS AND METHODS: Ultra-high performance liquid chromatography with Orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS) was used to determine the chemical composition and in vivo metabolic profile of XBZK. Additionally, UPLC with triple quadrupole mass spectrometry (UPLC-TQ-MS/MS) was performed to quantify its main components and evaluate its in vivo dynamics in rat plasma. RESULTS: In total, 57 components were identified in XBZK. Furthermore, 40 prototype components and 31 metabolites were detected in various biological matrices of rats, including plasma, tissues, bile, feces, and urine. After administration, the area under the curve (AUC) for ephedrine (Eph), pseudoephedrine (Peph), neotuberostemonine (Neo), amygdalin (Amy), and enoxolone (Eno) exhibited a strong linear relationship with the administered dose (r > 0.9) in all rats. And gender-related differences in the absorption of peiminine (Pmn), peimisine (Pms), and chrysin-7-O-glucuronide (Cog) were notable among rats, with male rats showing a dose-dependent pattern of absorption, while female rats exhibited minimal absorption. CONCLUSIONS: XBZK contains 57 components, primarily composed of flavonoids, alkaloids, and coumarins. The eight main components were rapidly absorbed and eliminated, with some, such as Eph, Peph, Neo, Amy and Eno, following a linear pharmacokinetic pattern. Furthermore, Pmn, Pms and Cog were well absorbed in male rats, showing a dose-dependent behavior.

Quercitrin alleviates lipid metabolism disorder in polycystic ovary syndrome-insulin resistance by upregulating PM20D1 in the PI3K/Akt pathway.

BACKGROUND: Abnormal endocrine metabolism caused by polycystic ovary syndrome combined with insulin resistance (PCOS-IR) poses a serious risk to reproductive health in females. Quercitrin is a flavonoid that can efficiently improve both endocrine and metabolic abnormalities. However, it remains unclear if this agent can exert therapeutic effect on PCOS-IR. METHODS: The present study used a combination of metabolomic and bioinformatic methods to screen key molecules and pathways involved in PCOS-IR. A rat model of PCOS-IR and an adipocyte IR model were generated to investigate the role of quercitrin in regulating reproductive endocrine and lipid metabolism processes in PCOS-IR. RESULTS: Peptidase M20 domain containing 1 (PM20D1) was screened using bioinformatics to evaluate its participation in PCOS-IR. PCOS-IR regulation via the PI3K/Akt signaling pathway was also investigated. Experimental analysis showed that PM20D1 levels were reduced in insulin-resistant 3T3-L1 cells and a letrozole PCOS-IR rat model. Reproductive function was inhibited, and endocrine metabolism was abnormal. The loss of adipocyte PM20D1 aggravated IR. In addition, PM20D1 and PI3K interacted with each other in the PCOS-IR model. Furthermore, the PI3K/Akt signaling pathway was shown to participate in lipid metabolism disorders and PCOS-IR regulation. Quercitrin reversed these reproductive and metabolic disorders. CONCLUSION: PM20D1 and PI3K/Akt were required for lipolysis and endocrine regulation in PCOS-IR to restore ovarian function and maintain normal endocrine metabolism. By upregulating the expression of PM20D1, quercitrin activated the PI3K/Akt signaling pathway, improved adipocyte catabolism, corrected reproductive and metabolic abnormalities, and had a therapeutic effect on PCOS-IR.

Baicalein Inhibits the Proliferation of Cervical Cancer Cells Through the GSK3ß-Dependent Pathway.

Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to possess multiple pharmacological activities, such as anticancer and anti-inflammatory properties. This study investigated the effect of baicalein in cervical cancer cells. Cell growth curve and MTT assay were performed and revealed that baicalein inhibited the proliferation of SiHa and HeLa cells in a dose-dependent manner. We further found that baicalein arrested the cell cycle of SiHa and HeLa cells at the G0/G1 phase by suppressing the expression of cyclin D1 through the downregulation of phosphorylated protein kinase B (p-AKT) and phosphorylated glycogen synthase kinase 3ß (p-GSK3ß) according to FACS assays and Western blotting. Moreover, when CHIR-99021, a GSK3ß inhibitor, was added to baicalein-treated SiHa cells, the expression of cyclin D1 was recovered, and cell proliferation was promoted. In conclusion, these data indicated that baicalein suspended the cell cycle at the G0/G1 phase via the downregulation of cyclin D1 through the AKT-GSK3ß signaling pathway and further inhibited the proliferation of SiHa and HeLa cervical cancer cells.

Artemisinin ameliorated proteinuria in rats with adriamycin-induced nephropathy through regulating nephrin and podocin expressions.

OBJECTIVE: To investigate the effects of artemisinin against proteinuria and glomerular filtration barrier damage in rats with adriamycin-induced nephropathy, and the potential mechanism underpinned the action. METHODS: Forty adriamycin rats were randomly divided into two groups with the ratio of 1 : 3; the small-number group served as control group (n = 10), and the rats in the large-number group were treated with adriamycin to induce nephropathy; then they were further randomly assigned into 3 subgroups: benazepril group (n = 10), artemisinin group (n = 10), and adriamycin group (n = 10). The benazepril group and artemisinin group were treated with benazepril suspl (5.0 mg/kg daily) and artemisinin suspl (150 mg/kg daily) respectively after being modeled; those in the control group and adriamycin group were intragastrically administered an equivalent volume of distilled water every day. The treatment after model establishment lasted for a total of 4 weeks. The 24 h uric protein, blood biochemicals, renal pathological changes, renal ultrastrutural changes, Nephrin and Podocin proteins and gene expressions were measured by Coomassie brilliant blue assay, completely automatic biochemical analyzer, light microscope, electron microscopy, Western blot and reverse transcription polymerase chain reaction, respectively. RESULTS: The rats in adriamycin group showed a significant increase in 24 h uric protein excretion, serum total cholesterol (TC), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (Scr) and decrease in albumin (Alb) (P < 0.05 or P < 0.01). Compared with adriamycin group, artemisinin could reduce uric protein excretion, decrease the serum TC, TG elevation, increase the serum Alb level, up-regulate the expressions of Nephrin and Podocin (P < 0.05 or P < 0.01), but no statistical significance effects on the levels of BUN, Scr in artemisinin group (P > 0.05). The renal pathological and ultrastrutural observation indicate that artemisinin could attenuate the severity of foot process effacement and fusion in the nephropathic rats. CONCLUSION: Artemisinin might have an effect on the nephropathy in rats caused by adriamycin, which may be at least partly correlated with attenu- ation of the severity of foot process effacement and fusion, up-regulation of the expressions of Nephrin and Podocin in the glomeruli in the rats.

"Qufeng Tongluo" acupuncture prevents the progression of glomerulonephritis by decreasing renal sympathetic nerve activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Although the exact mechanism(s) underlying acupuncture remain unknown, acupuncture and acupuncture-like somatic nerve stimulation have been used to treat different kidney diseases and several complications related to them.The aim of this preliminary study was to assess the effectiveness of acupuncture on glomerulonephritis (GN) according to the theory of "Wind-hided renal collaterals" previously proposed. MATERIAL AND METHODS: We used a New Zealand white rabbit model of cationized bovine serum albumin (cBSA)-induced glomerulonephritis and then administered them metoprolol, irbesartan or acupuncture to evaluate the effectiveness of acupuncture treatment and preliminarily explore its potential mechanism. RESULTS: After immunization, our results showed that compared to the cBSA+MET and cBSA+IRB medication groups, "Qufeng Tongluo" significantly lowered parameters of renal function and improved podocyte injury in the 3rd, 6th and 8th weeks of treatment. Moreover, acupuncture increased the protein expression of phosphorylated ERK1/2. CONCLUSIONS: Our study suggests that a potential mechanism by which acupuncture has an antihypertensive effect and can significantly halt deteriorating renal function due to cBSA GN might be mediated by inhibiting the Erk1/2 MAPK pathway to reduce renal sympathetic nerve activity (RSNA).