Total flavonoids of Taraxacum mongolicum inhibit non-small cell lung cancer by regulating immune function.

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum mongolicum Hand.-Mazz. has been used in lung cancer treatment in Chinese medicine. However, its specific mechanism of action has not yet been reported, and developing pharmaceutical anti-cancer resources is important. Here, we aimed to elucidate the anti-tumor effects of dandelion in vitro and in vivo and assess its effects on immune function in lung cancer patients. AIM OF THE STUDY: In the present study, we mainly observed the therapeutic effects of total flavonoids from Taraxacum mongolicum Hand.-Mazz. (TFTM) on non-small cell lung cancer and its influence on the body's immune function. MATERIALS AND METHODS: In vitro experiments on A549 and H1299 cells were performed using the CCK8 method; the proliferation and migration of cells were observed to investigate the wound healing effects of TFTM, and flow cytometry was used to detect the apoptotic rate of TFTM on lung cancer cells. In vivo experiments were preformed to establish a non-small cell lung cancer mouse model using subcutaneously transplanted Lewis cells, and the body weight and tumor growth of the mice were recorded. Hematoxylin and eosin staining was performed for tumor tissue to assess pathological changes. The thymus, spleen, and lungs were isolated for to calculate organ index. The CD4+, CD8+, and CD4+/CD8+ levels were detected in mouse spleen using flow cytometry, and IL-2, IL-3, IFN-γ, and TNF-α levels were determined in serum using enzyme-linked immunosorbent assay. Expressions of IL-2, IL-3, IFN-γ, and TNF-α were detected using quantitative real-time PCR in tumor tissues, and Ki67 expression was observed by immunofluorescence. RESULTS: At 24 h, TFTM (100 and 200 µg/mL) had the best inhibitory effect on the proliferation of A549 and H1299 cells. The cell migration rate significantly reduced (P < 0.01), and the tumor inhibition rate increased (P < 0.01) and promoted apoptosis (P < 0.01). The mouse thymus index significantly increased (P < 0.05) and mouse spleen index reduced (P < 0.05). The CD4+, CD8+, and CD4+/CD8+ levels in Lewis lung cancer mouse model increased, as did the levels of IL-2, IL-3, IFN-γ, and TNF-α in the serum and tumor of mice; Ki67 expression in tumor tissues significantly reduced (P < 0.01). CONCLUSION: TFTM has an inhibitory effect on lung cancer. The mechanism may be that it improves the host's protective immune response by having a milder tumor growth inhibitory effect than cyclophosphamide.

[Animal model analysis of diabetic lower extremity arterial disease based on clinical symptoms of traditional Chinese and Western medicine].

The evaluation standard of LEAD animal model was established according to the understanding of the etiology and pathogenesis of diabetic lower extremity vascular disease based on Chinese and Western medicine. The consistency between the existing LEAD animal model and the clinical characteristics of traditional Chinese and Western medicine was analyzed and evaluated. The advantages and disadvantages of the existing model were compared,the application scope of different models was considered,and the possible improvement methods of the existing model were proposed,so as to provide impetus for the improvement of LEAD animal model.We should reflect more characteristics of traditional Chinese medicine syndromes in the process of model improvement and development,making the LEAD animal model to get closer to clinical features of traditional Chinese and Western medicine.

[Analysis of animal models of chronic atrophic gastritis based on characteristics of clinical symptoms of traditional Chinese and Western medicine].

Based on the clinical characteristics of chronic atrophic gastritis in traditional Chinese and Western medicine, the domestic and foreign relevant literature reports and animal models of chronic atrophic as well as the clinical diagnostic indicators of traditional Chinese and western medicine, chronic atrophic gastritis evaluation standard was summarized to evaluate and analyze the coincidence degree of clinical symptoms of the existing chronic atrophic gastritis animal models. The statistical results found that modeling methods with a higher coincidence degree with the existing chronic atrophic gastritis animal models are disease and syndrome combination mode-ling, surgical modeling, multifactor comprehensive modeling and MNNG modeling. Although the animal models were reproduced by such methods as etiology, pathogenesis and disease and syndrome combination similar to those of human beings, there is still a big gap with the natural disease state. Further in-depth studies and improvement shall be made in clinical practice in the hope to provide refe-rence for clinical practice and experimental studies of chronic atrophic gastritis.

Study on the anti-hepatocarcinoma effect and molecular mechanism of Prunella vulgaris total flavonoids.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of Prunella vulgaris is for the treatment of liver cancer in a few areas of China. At present, it is used primarily for the treatment of thyroid cancer, throat cancer, and lymphosarcoma among others. However, there are few current scientific reports regarding its use for the treatment of liver cancer. In this paper, the effective treatment for liver cancer is studied to provide an experimental basis for the application of Prunella vulgaris, which is related to preparations in the treatment of liver cancer. AIM OF THE STUDY: To study the anti-hepatocarcinoma effect of Prunella vulgaris total flavonoids and explores the possible molecular mechanism. METHODS: The effects of Prunella vulgaris total flavonoids on the proliferation of SMMC-7721 cells were respected by RTCA analysis system. The tumor volume and weight were found in H22 tumor bearing mice. ELISA was used to observe the apoptosis and autophagy protein expressions in tumor tissue homogenate, along with the immune serum factor. Tumor tissue apoptosis was respected by the TUNEL method. And Bax, Bcl2, PI3K, Akt, mTOR, Beclin-1 and LC3-I/LC3-II expression were observed through Western blot. We also observed the expression of Beclin-1 and LC3-I/LC3-II through immunohistochemistry. RESULTS: The total flavonoids of Prunella vulgaris inhibited the activity of SMMC-7721 cells, and reduced the tumor volume and weight in H22 tumor bearing mice. HE staining showed that the Prunella vulgaris total flavonoids inhibited liver metastasis of H22 tumor. The Prunella vulgaris total flavonoids significantly made the expressions of IL-6, TNF-α and IFN-γ immune factors increasing in the serum of tumor bearing mice, and the contents of caspase-3 and caspase-9 increase as well in tumor tissue homogenate. TUNEL showed that the mean density in the intervention group was significantly higher than that in the control group. P62 content in tumor tissue homogenate increased and ATG5 decreased after intervention. Immunohistochemistry showed Beclin-1 expression decreased and LC3-I/LC3-II increased in the tumor tissue. Western blot showed Bcl2, Beclin-1 expression decreased and Bax, PI3K, Akt, mTOR, LC3-I/LC3-II increased in the tumor tissue. CONCLUSION: Prunella vulgaris total flavonoids have an obvious anti-hepatocarcinoma effect, and the mechanism may be linked to the inhibition of autophagy and promotion of apoptosis in liver cancer cells. The inhibition of autophagy may be related to activation of the PI3K/Akt/mTOR pathway.

Effects of total flavonoids from Eucommia ulmoides Oliv. leaves on polycystic ovary syndrome with insulin resistance model rats induced by letrozole combined with a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. leaves are the dry leaves of Eucommia ulmoides Oliv. Modern studies have shown that Eucommia ulmoides Oliv. leaves and its extracts have many pharmacological effects, such as regulating hypothalamus pituitary ovary (HPO) axis function, estrogen like effects, correcting insulin resistance (IR), regulating lipids, and reducing weight, which are consistent with the clinical manifestations in polycystic ovary syndrome (PCOS) patients. PCOS patients often have HPO axis disorder, low estrogen, high androgen, high IR complication rate, and obesity. Previous preclinical studies have shown that total flavonoids from Eucommia ulmoides Oliv. leaves (TFEL) can improve the imbalance in sex hormone secretion in perimenopausal animal models by regulating the function of the HPO axis. Thus, it is important to understand if flavonoids are the active parts of Eucommia ulmoides Oliv. leaves that interfere with polycystic ovary syndrome with insulin resistance (PCOS-IR), and determine the regulatory role they play in sex hormones and IR? AIM OF THE STUDY: Investigate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the ovary and kisspeptin/insulin like growth factor/leptin receptor1/androgen receptor (Kiss1/IGF-1/LEPR/AR) in the HPO axis to determine the mechanism of TFEL intervention in a rat model of PCOS-IR model rats. MATERIALS AND METHODS: A rat model of PCOS-IR was established using a high-fat diet (49 d) combined with letrozole (1 mg/kg·d, for 28 d). Then, metformin (300 mg/kg·d) and TFEL (220 mg/kg·d, 110 mg/kg·d, and 55 mg/kg·d) were administered continuously for 21 days. At the end of the experiment, samples were taken and the related indexes were measured. RESULTS: TFEL reduced the body weight, Lee's index, ovarian index, ovarian area and ovarian volume, increased serum E2, SHBG levels and ISI, decreased serum levels of T, LEP, INS, and FBG (whole blood), and reduced the HOMA-IR in rats with PCOS-IR. TFEL downregulate Kiss1, IGF-1, and AR in the arcuate nucleus of hypothalamus, and upregulate Kiss1, downregulate IGF-1 and AR in the pituitary gland, and upregulate Kiss1, downregulate IGF-1, LEPR, and AR in the ovary of rats with PCOS-IR. TFEL could downregulate p-IRS-1Ser307, upregulate IRS-1, p-IRS-1Tyr895, PI3Kp85α, p-PI3Kp85α, AKT, p-AKT, and GLUT4 in the ovary, and ameliorated histopathological changes in the ovary and pancreas of rats with PCOS-IR. CONCLUSION: TFEL can inhibit ovarian hyperplasia, regulate disorders of glucose and lipid metabolism and improve the secretion of sex hormones, by regulating the expression of PI3K/AKT signaling pathway-related proteins in the ovary and Kiss1/IGF-1/LEPR/AR in the HPO axis.

Total glucosides of herbaceous peony (Paeonia lactiflora Pall.) flower attenuate adenine- and ethambutol-induced hyperuricaemia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbaceous peony (Paeonia lactiflora Pall.) flower has been used widely in dietotherapy in China and other countries. It has good ethnopharmacological value in the treatment of various metabolic diseases. However, the molecular mechanisms by which it lowers serum uric acid are unknown. The development of pharmaceutical resources is very important. Here, we sought to elucidate the mode of action of herbaceous peony in terms of reducing uric acid levels. AIM OF THE STUDY: In the present research, the effects of the total glucosides of herbaceous peony flower were investigated in a rat hyperuricaemia model. Another aim of the study was to clarify the mechanism by which herbaceous peony flower (TGPF) lowers serum uric acid levels. MATERIALS AND METHODS: A hyperuricaemic rat model was induced via intragastric administration of 100 mg/kg adenine and 250 mg/kg ethambutol hydrochloride (EH) for 23 d. Then TongFengShu 600 mg/kg, allopurinol 42 mg/kg, or TGPF (50 mg/kg, 100 mg/kg, or 200 mg/kg) was administered 1 h after the adenine and EH treatments. RESULTS: TGPF improved weight loss and decreased serum UA, XOD, MCP-1, TNF-α, Cr, and BUN in the rats with hyperuricaemic nephropathy. TGPF downregulated renal URAT1 and GLUT9, upregulated renal OAT1, and ameliorated histopathological changes in the thymus, spleen, and kidney. CONCLUSION: TGPF is promising as a therapeutic agent against hyperuricaemia. It regulates the uric acid transporters and diminished serum uric acid levels, and alleviates renal pathology associated with hyperuricaemia.