elucidation-material-basis-yiqi-qingjie-formula-against-iga

Elucidation of the Material Basis of Yiqi Qingjie Formula Against IgA Nephropathy Using UHPLC-Q-Orbitrap HRMS Integrated with Network Pharmacology

This study employs UHPLC-Q-Orbitrap HRMS to characterize the water-extractable and blood-absorbed constituents of YQQJ. Network pharmacology and molecular ...

China Academy of Chinese Medical Sciences.

Berberine (BER) and BER-original herbal medicines have a variety of pharmacological functions and have been widely used in clinical. However, its effect of enzyme induction on cytochrome P450 (CYP) in human hepatocytes is unknown.

In vitro studies of berberine metabolism and its effect of enzyme induction on HepG2 cells.

Coptidis rhizoma (Coptis) and its alkaloids exert various pharmacological functions in cells and tissues; however, the oral absorption of these alkaloids requires further elucidation. The present study aimed to examine the mechanism underlying the poor absorption of alkaloids, including berberine (BER), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT). An ultra‑performance liquid chromatography (UPLC) method was validated for the determination of BER, COP, PAL and JAT in the above experimental medium. In addition, the apparent oil‑water partition coefficient (Po/w); apparent permeability coefficient (Papp), determined using a parallel artificial membrane permeability assay (PAMPA) plate; membrane retention coefficient (R %); and effect of P‑glycoprotein (P‑gp) inhibitor on the Papp of the four alkaloids were investigated. The intestinal absorption rate constant (Ka) and absorption percentage (A %) of the four alkaloids were also determined. The results of the present study demonstrated that the Po/w of the four alkaloids in 0.1 mol·l‑1 HCl medium was significantly higher (P<0.01), compared with those of the alkaloids in phosphate buffer (pH 7.4). The Papp of BER was 1.0‑1.2x10‑6 cm·s‑1, determined using a PAMPA plate, and the Papp of BER, COP, PAL and JAT decreased sequentially. The concentrations of the four alkaloids on the apical‑to‑basolateral (AP‑BL) surface and the basolateral‑to‑apical (BL‑AP) surface increased in a linear manner, with increasing concentrations between 10 and 100 µmol. In addition, the transportation of BER on the BL‑AP surface was significantly faster (P<0.01), compared with that on the AP‑BL surface and, following the addition of verpamil (a P‑gp inhibitor), the Papp (AP‑BL) of the four alkaloids increased, whereas the Papp (BL‑AP) was significantly decreased (P<0.01). The rat intestinal perfusion experiment demonstrated that the four alkaloids were poorly absorbed; however, the Ka of BER was significantly higher, compared with the three other alkaloids. Furthermore, the A % and Ka provided evidence that the absorption of BER was increased in the jejunum, compared with in the ileum. In conclusion, the four alkaloids from Coptis appeared to be poorly absorbed, determined using a shake flask, pre‑coated PAMPA plates, a Caco‑2 cell monolayer model and intestinal perfusion; however, absorption was higher in the jejunum than in the ileum. Among the four alkaloids, the permeability of BER was markedly higher than the others, and P‑gp efflux had a significant effect on the absorption of those alkaloids.

Poor permeability and absorption affect the activity of four alkaloids from Coptis.

We assumed that the pharmacokinetics of lovastatin could be changed by the induction effect of berberine.

In Vivo and in Vitro Study on Drug-Drug Interaction of Lovastatin and Berberine from Pharmacokinetic and HepG2 Cell Metabolism Studies.

The aim of the present study was to compare the different effects of berberine (Ber) and Coptischinensis extract (CCE) on a rat model of type 2 diabetes mellitus (T2DM), and the islet Rin‑5f cell line was used to examine the differences between Ber and CCE and the underlying mechanisms. CCE was extracted and purified prior to analysis. Male Sprague‑Dawley rats were provided with a high‑fat diet to induce insulin resistance prior to injecting with streptozotocinto establish the T2DM model, the T2DM rats were treated with Ber and CCE, and blood samples and pancreatic tissues were obtained and compared to examine T2DM metabolic syndromes among the groups of rats, which included healthy rats, model rats, and model rats treated with Ber and CCE at different doses between 0 and 8 weeks. The protective effects of Ber and CCE on the Rin‑5f islet cell line were also evaluated. The effects on Rin‑5f cell proliferation and cell cycle, glucose‑stimulated insulin release test (GSIS), the anti‑apoptotic effects caused by fat induction, and protein expression levels of poly ADP‑ribose polymerase (PARP‑1) were evaluated. The results showed that the content of the prepared CCE was 96.07% for five alkaloids. When it was used for treatment of the T2DM rats, compared with Ber, metformin and rosiglitazone, the fasting blood glucose, glucosylated serum protein (GSP) and glucose infusion rate indicesin the fasting rats were ameliorated, compared with those in the T2MD rats, with no significant differences between treatment with Ber or CCE and metformin or rosiglitazone. The indices of mean optical density and fasting β‑cell function index (FBCI) were different following treatment with Ber and CCE, compared with those in the model rats, which may have stimulated the pancreatic secretion of insulin. When Ber and CCE were used to examine the protective effects on Rin‑5F cells, it was found that the Rin‑5f cell GSIS, cell cycle, lipotoxic islet cell proliferation and protein expression of PARP‑1 were altered and improved, which may have protected pancreatic islet β‑cells by improving islet β‑cell proliferation and the protein expression of PARP‑1. CCE and Ber exerted similar effects when used for the treatment of T2MD rats, and may have stimulated the pancreatic secretion of insulin through the protective effect on islet β‑cells via improving islet β‑cell proliferation and the protein expression of PARP‑1.

Protective role of berberine and Coptischinensis extract on T2MD rats and associated islet Rin‑5f cells.

 Decoction (SXD) is commonly used to treat type 2 diabetes mellitus (T2DM) in clinical practice of traditional Chinese medicine (TCM). In order to elucidate the specific analysis mechanisms of SXD for T2DM, the method of network pharmacology was applied to this article. First, the effective ingredients of SXD were obtained and their targets were identified based on the TCMSP database. The T2DM-related targets screened from the GEO database were also collected by comparing the differential expressed genes between T2DM patients and healthy individuals. Then, the common targets in SXD-treated T2DM were obtained by intersecting the putative targets of SXD and the differential expressed genes of T2DM. And the protein-protein interaction (PPI) network was established using the above common targets to screen key genes through protein interactions. Meanwhile, these common targets were used for GO and KEGG analyses to further elucidate how they exert antidiabetic effects. Finally, a gene pathway network was established to capture the core one in common targets enriched in the major pathways to further illustrate the role of specific genes. Based on the data obtained, a total of 67 active compounds and 906 targets of SXD were identified. Four thousand one hundred and seventy-six differentially expressed genes with a  value < 0.005 and ∣log2(fold change) | >0.5 were determined between T2DM patients and control groups. After further screening, thirty-seven common targets related to T2DM in SXD were finally identified. Through protein interactions, the top 5 genes (YWHAZ, HNRNPA1, HSPA8, HSP90AA1, and HSPA5) were identified. It was found that the functional annotations of target genes were associated with oxygen levels, protein kinase regulator, mitochondria, and so on. The top 20 pathways including the PI3K-Akt signaling pathway, cancers, HIF-1 signaling pathway, and JAK-STAT signaling pathway were significantly enriched. CDKN1A was shown to be the core gene in the gene-pathway network, and other several genes such as CCND1, ERBB2, RAF1, EGF, and VEGFA were the key genes for SXD against T2DM. Based on the network pharmacology approach, we identified key genes and pathways related to the prognosis and pathogenesis of T2DM and also provided a feasible method for further studying the chemical basis and pharmacology of SXD.

Elucidation of the Mechanisms and Molecular Targets of  Decoction for Type 2 Diabetes Mellitus Based on Network Pharmacology.

This work was carried out to establish and validate the specific characteristic chromatography of Scutellaria Extract and evaluate the quality of commercial Scutellaria Extract and optimize production process parameters. Scutellaria Extract and formulation samples collected from different manufacturers were analyzed using HPLC-characteristic chromatogram. The HPLC characteristic peaks were considered to be the index for the parameters optimization in preparations of Scutellaria Extract. The chemical pattern recognization was applied for the analysis of characteristic peak data. The established characteristic fingerprint method possessed a good precision, repeatability, and stability. Ten common characteristic peaks were determined and identified in the specific chromatogram of 31 batches of Scutellaria Extract and 4 batches of formulation. The process parameters influenced the characteristic peaks area significantly. The similarity analysis results showed that after removing baicalin peak, the similarity of the characteristic chromatography of 9 samples were less than 0.90, indicating that the quality of commercial Scutellaria Extract was inconsistent. Non-parametric test result showed that the relative peaks area of the number 4, 6, 7 characteristic peaks had significant differences(P&lt;0.05), indicating the differences of the Scutellaria Extract quality were mainly reflected in the characteristic peaks 4, 6 and 7(norwogonin-7-O-glucuronide, oroxylin A-7-O-glucuronide, wogonoside, respectively). The cluster analysis accurately classified 31 extract samples and 4 formulation samples into five categories based on 10 characteristic peaks. The quality of Scutellaria Extracts was comprehensively evaluated and ranked by PCA. The result showed that the higher content of baicalin, the score value of quality(F value) was lower, and the quality of the Scutellaria Extract should be evaluated by multi-components instead of a single baicalin component. The optimized characteristic peaks method is stable and reliable. It is advantageous for the extract and formulations integrative quality control by combining the chemical pattern recognization.

[Study on HPLC-characteristic chromatogram for evaluation of quality of Scutellaria Extract and influencing factors of preparations].

Andrographis paniculata (Burm.f.) Nees is a medicinal plant that has been traditionally used as an anti-inflammatory and antibacterial remedy for several conditions. Andrographolide (AG), the active constituent of A. paniculata (Burm.f.) Nees, has anti-lipidic and anti-inflammatory properties as well as cardiovascular protective effects. The present study aimed to explore the effects of AG on the progression of atherosclerosis and to investigate related mechanisms via network pharmacology.

Andrographolide in atherosclerosis: integrating network pharmacology and in vitro pharmacological evaluation.

Sanhuang Xiexin Decoction (SHXD), consisting of Coptis chinensis Franch., Scutellaria baicalensis Georgi and Rheum palmatum L., is traditionally used for relieving fever, purging fire for removing toxins, eliminating phlegm and haemostasis, eliminating the wetness-evil from the upper warmer, clearing away the heat-evil and expelling superficial evils. Each of the three herbs contained in SHXD has been indicated to have anti-inflammatory effects in vivo, but its effects on rat NK-cell phenotypes remain unexplored, and the comprehensive mechanism of this compound SHXD in curing the inflammation induced by lipopolysaccharides (LPS) remains to be revealed.

Vitro UPLC analysis and mass method identification, and in vivo or cellular immune anti-inflammatory function of Sanhuang Xiexin Decoction (SHXD).

Sleep disorder is widespread and involves a variety of intricate factors in its development. Sleep deprivation is a manifestation of sleep disorder, can lead to energy metabolism disturbances, weakened immune system, and compromised body functions. In extreme situations, sleep deprivation can cause organ failure, presenting significant risks to human health.

Astragali radix vesicle-like nanoparticles improve energy metabolism disorders by repairing the intestinal mucosal barrier and regulating amino acid metabolism in sleep-deprived mice.

Melanoma, a highly aggressive malignancy with increasing global incidence, faces significant therapeutic challenges due to drug resistance, systemic toxicity, and immunosuppressive tumor microenvironment. Despite advances in targeted therapies and immunotherapies, the need for safer and more effective treatment options remains urgent. Chinese herbal medicine-derived polysaccharides (CHMPs), characterized by their natural origin, biocompatibility, and multifaceted bioactivities, have garnered increasing attention as promising candidates for melanoma therapy due to their low toxicity and multi-targeting capabilities. In this review, the dual roles of CHMPs with varied origins in anti-melanoma treatment will be systematically elucidated. As carrier-free anti-tumor agents, CHMPs exert anti-melanoma effects through multiple mechanisms, including immune modulation, apoptosis induction, cell cycle arrest, inhibiting tumor angiogenesis, and regulating signaling pathways. Moreover, as intelligent carriers, CHMPs can be chemically modified or physically assembled into targeted delivery systems, enhancing drug stability and bioavailability while minimizing off-target toxicity. Finally, current challenges for CHMPs in anti-melanoma treatments, such as structural heterogeneity, unclear structure-activity relationships, and limited clinical translation, will be outlined, and future efforts are also discussed. By bridging traditional herbal medicine and modern biomaterials science, we expect this review not only to provide a roadmap for developing CHMP-based multifunctional biomaterials platforms but also to inspire novel strategies to overcome current therapeutic bottlenecks in melanoma management, paving the way for safer and more effective treatments.

Article	Year
In vitro studies of berberine metabolism and its effect of enzyme induction on HepG2 cells. Journal of ethnopharmacology\| PubMed ID: 25456436	2014
Poor permeability and absorption affect the activity of four alkaloids from Coptis. Molecular medicine reports\| PubMed ID: 26352530	2015
In Vivo and in Vitro Study on Drug-Drug Interaction of Lovastatin and Berberine from Pharmacokinetic and HepG2 Cell Metabolism Studies. Molecules (Basel, Switzerland)\| PubMed ID: 27070564	2016
Protective role of berberine and Coptischinensis extract on T2MD rats and associated islet Rin‑5f cells. Molecular medicine reports\| PubMed ID: 28901416	2017
Elucidation of the Mechanisms and Molecular Targets of Decoction for Type 2 Diabetes Mellitus Based on Network Pharmacology. BioMed research international\| PubMed ID: 32851081	2020
[Study on HPLC-characteristic chromatogram for evaluation of quality of Scutellaria Extract and influencing factors of preparations]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 33350267	2020
Andrographolide in atherosclerosis: integrating network pharmacology and in vitro pharmacological evaluation. Bioscience reports\| PubMed ID: 35543243	2022
Vitro UPLC analysis and mass method identification, and in vivo or cellular immune anti-inflammatory function of Sanhuang Xiexin Decoction (SHXD). Journal of ethnopharmacology\| PubMed ID: 37544343	2024
Astragali radix vesicle-like nanoparticles improve energy metabolism disorders by repairing the intestinal mucosal barrier and regulating amino acid metabolism in sleep-deprived mice. Journal of nanobiotechnology\| PubMed ID: 39696385	2024
Advances of Chinese herbal medicine-derived polysaccharides as carrier-free and carrier agents in anti-melanoma therapy. Journal of materials chemistry. B\| PubMed ID: 40879676	2025

QiuYan Zhang

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