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ObjectiveTo study the effect of Xihuangwan extract on mitochondrial energy metabolism in ovarian cancer SKOV3 and HEY cells and to explore the underlying mechanism. MethodSKOV3 and HEY cells were cultured in vitro and treated with different concentrations （0， 5， 10， 15， 20 g·L-1） of Xihuangwan extract. Methyl thiazolyl tetrazolium （MTT） was used to examine the viability of SKOV3 and HEY cells treated with Xihuangwan extract. The adenosine-triphosphate （ATP） levels in SKOV3 and HEY cells were measured by kit. Flow cytometry was employed to measure the content of reactive oxygen species （ROS） in cells. Western blot was employed to determine the protein levels of peroxisome proliferator-activated receptor-γ co-activator 1α （PGC1α）， transcription factor A， mitochondrial （TFAM）， translocase of outer mitochondrial membrane 20 （TOMM20）， and aplasia Ras homologue member Ⅰ （ARHⅠ） in SKOV3 and HEY cells. Mito-Tracker Green staining was used to observe the morphological changes of mitochondria in SKOV3 and HEY cells. ResultCompared with blank group， Xihuangwan extract treatment for 24， 48 h inhibited the viability of SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）. Compared with blank group， Xihuangwan extract （10， 15， 20 g·L-1） groups presented lowered ATP levels （P<0.05， P<0.01）， and the 20 g·L-1 Xihuangwan extract group had lower ATP level than the 10 and 15 g·L-1 Xihuangwan extract groups （P<0.05）. Compared with blank group， Xihuangwan extract increased the content of ROS in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the 20 g·L-1 Xihuangwan extract group had higher ROS content than the 10 g·L-1 Xihuangwan extract group （P<0.05）. Compared with blank group， Xihuangwan extract up-regulated the expression level of ARHⅠ protein in SKOV3 and HEY cells in a concentration-dependent manner （P<0.01）， and the expression levels of ARHⅠ protein was higher in the 20 g·L-1 Xihuangwan extract group than in the 10 and 15 g·L-1 Xihuangwan extract groups （P<0.05）. Compared with the blank group， Xihuangwan extract down-regulated the protein levels of PGC1α， TFAM， and TOMM20 in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the protein levels of TFAM and TOMM20 in the HEY cells treated with 20 g·L-1 Xihuangwan extract were lower than those in the HEY cells treated with 10， 15 g·L-1 Xihuangwan extract （P<0.05）. Compared with the blank group， 20 g·L-1 Xihuangwan extract decreased the Mito-Tracker fluorescence intensity of SKOV3 and HEY cells （P<0.05）. ConclusionXihuangwan can compromise the mitochondrial function of ovarian cancer SKOV3 and HEY cells and reduce cell energy metabolism to inhibit the proliferation of SKOV3 and HEY cells by up-regulating ARHⅠ and inhibiting PGC1α/TFAM signaling axis.
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Malignant tumors are currently seriously endangering human health and life， which has become one of the main causes of death in China. In modern Western medicine， they are mainly tackled by surgery， chemotherapy， and radiotherapy， but the death toll continues to rise year by year. At present， most of the anti-tumor chemotherapeutics used in clinical practice have toxic and side effects， affecting the anti-tumor efficacy and the conditions after treatment. Long-term medication will also induce drug resistance， making the good anti-tumor effect difficult to be achieved. With the vigorous development of traditional Chinese medicine （TCM）， it has played a crucial role in the fight against tumors. It is believed in TCM that "heat toxin" is one of the important causes of tumors. Therefore， the methods of clearing away heat and removing toxin are often emphasized in the treatment of tumors， and the resulting outcomes are satisfactory. There are many Chinese herbs and Chinese herbal compounds classified into the heat-clearing and toxin-removing type. Xihuangwan， a classic heat-clearing prescription， is composed of Calculus Bovis， Moschus， Olibanum， and Myrrh and has the effects of clearing away heat， removing toxin， eliminating edema， and dissipating mass， which is mainly used to treat carbuncle， pustule， scrofula， multiple abscess， and cancer caused by heat-toxin obstruction. In modern clinical practice， it has been employed in patients with lung cancer， breast cancer， gastric cancer， liver cancer， colorectal cancer， and other malignant tumors， especially during the advanced stage， as a routine or adjuvant treatment for alleviating their clinical symptoms and improving their quality of life. The main active components of Xihuangwan are pentacyclic triterpenoids （such as masticinic acids）， volatile oils， steroids （like porcine deoxycholic acid）， and bilirubin， which have been proved effective in anti-tumor. This paper reviewed the prescription source， pharmaceutical research， clinical anti-tumor research， and pharmacological mechanisms of Xihuangwan， which has provided reference for further expanding the anti-tumor applications of Xihuangwan and enhancing its secondary development.
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Xihuangwan is composed of four Chinese medicines： Bovis Calculus， Olibanum， Myrrha， and Moschus. Modern pharmacology studies have shown that Xihuangwan has anti-inflammatory， antibacterial， anti-tumor， anti-mammary gland hyperplasia effect， and can enhance the body's immune function. Cancer seriously endangers public health and safety-of-life， and is a major cause of mortality of Chinese citizens. It is a disease with intricate etiopathogenesis caused by the joint action of circumstances and hereditary factors. At present， anti-tumor chemotherapy drugs in clinical application not only have toxic and side effect， but also affect clinical efficacy and prognosis of patients. Long-term use will also lead to drug resistance of tumors. As a traditional classic anti-cancer prescription， Xihuangwan has been used more and more in tumor research with the rise of Chinese medicine culture. It is provided with remarkable inhibitory effect on liver cancer， gastric cancer， carcinoma of the lungs， mammary gland， colorectal carcinoma and other malignant tumors. In clinical practice， Xihuangwan ， mostly used as adjuvant drugs in combined use with chemotherapy drugs for anti-tumor effect， can reduce the side effect of chemotherapy drugs and the untoward reaction of sufferers， improve the survivability of patients to chemotherapy， reduce or delay postoperative tumor recurrence， enhance the body's immune function， and reverse the tolerance of tumor cells. Based on the anti-tumor research of Xihuangwan， we summarized its mechanisms in inducing cell apoptosis， regulating amino acid metabolism， reversing drug resistance， interfering with cell cycle， resisting tumor metastasis and invasion， regulating immune function， improving tumor microenvironment， and regulating signal pathways， as well as its clinical combination with chemotherapeutic anti-tumor drugs， analyzed the current anti-tumor research status of Xihuangwan's research， and put forward the shortcomings and unresolved problems in order to provide theoretical basis for further research and clinical application of Xihuangwan.
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Objective:To study the antitumor effect of Xihuangwan on A549 lung cancer nude mice in inflammatory microenvironment, and explore the effect of Xihuangwan on the expressions of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory bodies and their products in serum and tumor tissue of A549 lung cancer nude mice. Method:The lung cancer A549 cell model was established in nude mice with lung cancer, and the lung cancer A549 cell model was established in inflammatory microenvironment by adding lipopolysaccharide (LPS) + adenosine triphosphate (ATP) to the culture medium. After modeling, the rats were randomly divided into blank group (equal volume of normal saline), positive drug control group (MCC950 solution, 0.79 g·kg-1), and low, medium, high-dose Xihuangwan groups (0.39, 0.78, 1.95 g·kg-1). The rats were administered orally once a day for 21 days, and then sacrificed. The tumor tissues were stripped to measure the tumor body. The expressions of NLRP3, malondialdehyde（MDA）, interleukin (IL)-1β, IL-18 and NLRP3 were detected by Western blot, and the levels of IL-1β, IL-18 and MDA were detected by enzyme linked immunosorbent assay（ELISA）. Result:Compared with the blank group, the tumor inhibition rates in the positive drug control group and the low, medium and high dose Xihuangwan group were 39.21%, 31.72%, 42.24% and 55.68%. ELISA showed that the high-dose Xihuangwan group could significantly reduce the expressions of MDA, IL-1β and IL-18 in the serum of nude mice (P<0.05). Western blot showed that the high-dose Xihuangwan group could effectively reduce the protein expressions of MDA, IL-1β, IL-18 and NLRP3 in tumor of nude mice (P<0.05), the results of immunohistochemistry showed that the expression rate of NLRP3 in the tumor tissues of nude mice was reduced in the positive drug group and each dose of Xihuangwan group (P<0.05). Conclusion:Xihuangwan can inhibit the growth of tumor tissue of A549 cells bearing lung cancer in nude mice. The mechanism may be that it can inhibit the growth of tumor cells by inhibiting the expression of NLRP3 inflammatory bodies, IL-1β, IL-18, MDA tables, and then inhibiting the inflammatory microenvironment of tumor cells.
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Objective To investigate effect of Bailing Capsule combined with Xihuangwan in stage III breast cancer patients of ER, MMP-9, tumor markers and estrogen.Methods 76 Patients with stage III breast cancer were selected and divided into control group anf experiment group.Control group were treated by clinical routine method.Experiment group were treated on the base of the control group with Bailing Capsule combined with Xihuangwan.The ER, MMP-9, tumor markers, estrogen, survival time and quality of life were observed and compared.ResuIts Compared with control group, the survival period of the experiment group were longer(P<0.05),the quality of life score were higher(P<0.05),the ER, MMP-9, E2, E1 level and the serum levels of CA15-3, CA125 and CEA were lower(P<0.05).ConcIusion Bailing capsule combined with Xihuang Pill can effectively reduce stage III breast cancer tumor marker levels, decrease the ER, the expression of MMP-9 and estrogen level and prolong survival time, improve the quality of life, has the vital significance to the clinical therapy for stage III breast cancer.
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On basis of syndrome differentiation of TCM, 1 case of brain stem glioma was treated with decoction and Xihuangwan produced by Tongrentang. She has lived past 3 years with good life quality. More attention should be paid to the function of liver, spleen and stomach. The method of checking liver-yang and smoothing liver-qi, strengthening spleen-qi and harmonizing stomach-qi were used. Smoothing liver-qi can keep good blood and liquid circulation, and can reduce phlegm and blood stasis in the body; Checking liver-yang can prevent brain being disturbed by internal wind. Strengthening spleen-qi and harmonizing stomach-qi was the source of qi-blood. Xihuangwan can directly arrive at brain tumor because of its specific fragrant, it can smooth the qi and remove the blood stasis, can clear heat and detoxify. Only with the combination of disease and syndrome differentiation, whole body and local tumor, dispelling xie and strengthening zheng, can this case be treated successfully.