Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable.Notably,the infiltration of Treg cells is the main trigger.Dahuang Zhechong pill(DHZCP)is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma.DHZCP can heal and nourish while slowing the onset of the disease,thereby strengthening the body’s immune function.It can localize tumors and ultimately achieve the goal of eliminating tumors.In this study,an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity,which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment,while more IFN-γwas secreted to activate CD8^(+)T cells and Treg cell production was inhibited,thereby suppressing the growth of HCC.Finally,we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.

Clinical Study of Dahuang Zhechong Pill (大黄■虫丸) in Treating Posthepatitis B Hepatic Fibrosis

Hepatic fibrosis is the only way for all kinds of chronic hepatic diseases to develop into liver cirrhosis. How to block and reverse hepatic fibrosis is the key issue for treatment of all kinds of chronic hepatic disease. After many years’ arduous effort in treating hepatic fibrosis, no satisfactory results in western medical treatment have been obtained. Though hepatic fibrosis could be definitely re-

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill

Cancer still has elevated morbidity and mortality,which undoubtedly impacts the life quality of affected individuals.Remarkable advances have been made in cancer therapy,although the toxicities of traditional therapies remain an obvious challenge.Dahuang Zhechong Pill(DHZCP),developed by Zhongjing Zhang in the Synopsis of the Golden Chamber,represents an effective anticancer traditional Chinese medicine(TCM).In this review,it was found that DHZCP is therapeutically utilized in liver,lung,gastric,pancreatic and other cancers in clinic.Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest,apoptosis and autophagy,as well as suppressed tumor cell proliferation,obstructed angiogenesis and metastasis,enhanced immunity,and reversal of multidrug resistance.The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

Effects and Mechanisms of the Functional Parts of Dahuang Zhechong Pill(大黄虫丸) Containing Serum on Platelet-Derived Growth Factor-Stimulated Proliferation of Vascular Smooth Muscle Cells

Objective： To investigate and compare the effects and mechanisms of three functional parts of Dahuang Zhechong Pill （大黄〈庶虫〉虫丸, DHZCP）, including drugs with the function of removing blood stasis and promoting blood circulation （FP- I ）, drugs with the function of expelling heat and moistening dryness （FP-II）, and drugs with the function of nourishing yin and replenishing blood （FP-m） of DHZCP, on platelet-derived growth factor （PDGF）-stimulated vascular smooth muscle cells （VSMCs） proliferation with the method of serum pharmacology. Methods： VSMCs proliferation of rat was assayed by measuring the cell viability with the 3-（4, 5-dimethylthiazol-2yl）-2, 5-diphenyltetrazolium bromide （Ml-I＇） method. DNA synthesis in VSMCs was examined by detecting 5＇-bromo-2＇-deoxyuridine incorporation with the immunocytochemical method. Cycle of VSMCs was evaluated with flow cytometry. Expression of cyclin D1, p27, PKC a, and phosphorylated extracollular signal regulated kinase 1/2 （ERK1/2） was quantified by the Western blotting method. Results： The FP- I and FP-m containing serum was capable of inhibiting PDGF-stimulated proliferation and DNA synthesis of VSMCs, arrested VSMCs in G1 phase, downregulated cycUn D1, and upregulated p27 expression （P〈0.01 or P〈0.05）. The FP- I and FP-11I containing serum also inhibited the PDGF-induced phosphorylation of tyrosine of ERK1/2 and PKCo~ expression （P〈0.01 or P〈0.05）. Conclusions： FP- I and FP-$ of DHZCP are able to inhibit VSMCs proliferation via interrupting PKC a-ERK1/2 signaling, modulating the expression of cell cycle proteins to result in arresting the cells in G1 phase. The inhibitory effect is mainly related to the function of removing blood stasis and promoting blood circulation, slightly to the function of nourishing yin and replenishing blood, but not to the function of expelling heat and moistening dryness.

Dahuang Zhechong Pill(大黄虫丸) Containing Serum Inhibited Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells Proliferation by Inducing G_1 Arrest Partly via Suppressing Protein Kinase C α-Extracellular Regulated Kinase 1/2 Signaling

Objective： To investigate effects of Dahuang Zhechong Pill （大黄庶虫丸, DHZCP） on the cell cycle and the related signal pathways in vascular smooth muscle cells （VSMCs） stimulated by platelet-derived growth factor （PDGF） with the method of serum pharmacology. Methods： DNA synthesis in VSMCs was examined by detecting 5＇-bromo-2＇-deoxyuridine incorporation with the immunocytochemical method. The cycle of VSMCs was evaluated with flow cytometry. Expressions of cyclin D1, p27, protein kinase C α （PKC α）, and phosphorylated extracellular signal regulated kinase 1/2 （ERK1/2） were quantified by Western blot method. Results： DHZCP containing serum significantly inhibited DNA synthesis of PDGF-stimulated VSMCs, arrested the cells in G1 phase, modulated the protein expressions of cyclin D1 and p27, and suppressed the activation of PKC α and ERK1/2. Conclusion： DHZCP containing serum inhibits VSMCs proliferation via modulating the expressions of cell cycle proteins to arrest the cell in G1 phase, which is attributed to, at least in part, suppressing PKC α -ERK1/2 signaling in VSMCs.

Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics

Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.