Tissue Distribution and Anti-Lung Cancer Effect of 10-Hydroxycamptothecin Combined with Platycodonis Radix and Glycyrrhizae Radix ET Rhizoma.

10-Hydroxycamptothecin (HCPT) is a broad-spectrum chemotherapeutic drug, although its side effects and multidrug resistance (MDR) limit its clinical application. A range of drug delivery systems have been utilized to overcome its shortcomings and maintain its therapeutic efficacy, however the use of the transport effect of traditional Chinese medicines (TCMs) to improve the distribution of chemotherapeutic drugs has not been widely reported. Platycodonis Radix (JG) and Glycyrrhizae Radix ET Rhizoma (GC) are common TCMs in clinics and are often combined as drug pairs to act as "transport agents". In the present study, the effect of JG and GC (JGGC) on the distribution of HCPT in tissues and its antitumor efficacy after being combined as a therapy were investigated, for which ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used. Furthermore, the effect on the protein expression of multidrug resistance proteins (P-gp and LRP), and the immunomodulatory and synergistic antiapoptotic effect on Lewis lung cancer-bearing C57BL/6J mice were also evaluated. The results demonstrate that JGGC significantly increased the area under the concentration time curve (AUC) and mean residence time (MRT) and reduced the clearance rate (CL) of HCPT. In addition, the combined use of JGGC decreased the levels of LRP, P-gp and Bcl-2/Bax when treated with HCPT. JGGC also significantly elevated the levels of RBCs, PLTs, HGB, IL-2, and IFN-γ, and decreased IL-10 levels. In summary, an increased concentration of HCPT in tissues was observed when it was combined with JGGC through inhibition of efflux protein, with a synergistic enhancement of the anticancer effect observed through promotion of apoptosis and immunity due to a reversion of the Th1/Th2 shift. Our findings provide a reference for the feasibility of combining JGGC with chemotherapy drugs in clinical applications.

Study on anti-hyperuricemia effects and active ingredients of traditional Tibetan medicine TongFengTangSan (TFTS) by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

TongFengTangSan (TFTS), a traditional Tibetan medicine comprising of Tinospora sinensis (TS), Terminalia chebula Retz (TC) and Trogopterori faeces (TF), is used to treat joint diseases like gout, gout arthritis, swelling, pain etc. Despite the significant therapeutic effects of TFTS, its pharmacological components have not been analyzed so far. Therefore, the chemical composition of the effective part of TFTS was analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). The results show that the ethanol extract (EE) of TFTS was more effective in reducing the serum uric acid (SUA) and XOD (Serum and Liver) levels in a hyperuricemic rats model compared to the TFTS raw powder (RP). UHPLC-Q-TOF-MS/MS identified a total of 106 compounds in the positive and negative ion mode, of which 87 were from TC, 13 from TS and 6 from TF. In addition, 106 compounds contained 57 tannins, 6 triterpenoids, 10 alkaloids, 7 flavonoids, 22 organic acids and 4 phenylpropanoids. The preliminary results indicate that the EE of TFTS includes the active anti hyperuricemic substances. The present study first investigated the efficacy and the active components of TFTS in hyperuricemic treatment, and further summarized the diagnostic ion and neutral loss patterns of MS/MS cracking of tannic compounds. These findings lay the foundation for the further study and clinical application of TFTS.

Effect of sulfated polysaccharides from Laminaria japonica on vascular endothelial cells in psychological stress rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Laminaria japonica is a popular seafood and medicinal plant in China. Laminaria japonica is used in traditional Chinese medicine to treat and prevent hypertension and edema. MATERIALS AND METHODS: The vascular protective activity and mechanism of sulfated polysaccharides were studied in adrenalin-induced vascular endothelial damage in rats after psychological stress (PS). Vehicle (sham and PS groups), sulfated polysaccharide from Laminaria japonica (LP; 1mg/kg and 5mg/kg) and enoxaparin sodium (1IU/kg, reference drug) were all administered for 10 days. Behavioral changes were recorded. Plasma levels of adrenalin, cortisol, monoamine oxidase (MAO), semicarbazide-sensitive amine oxidase (SSAO), formaldehyde, H2O2, nitric oxide (NO), endothelin-1 (ET-1), 6-keto-prostaglandin F1a (6-keto-PGF1a), and thromboxane B2 (TXB2) were measured. Endothelium-dependent relaxation of the thoracic aorta was measured and transmission electron microscopy of aortic vessels was performed. RESULTS: Adrenalin metabolites in plasma were significantly lower (P<0.01) in rats after LP administration compared with those in the PS groups. The normalized ratios of plasma NO/ET-1 and 6-keto-PGF1a/TXB2 were maintained and endothelium-dependent relaxation of the aorta was greatly enhanced after LP treatment (P<0.05). Morphological alterations were observed in vascular endothelial cells (VECs) in PS rats, with a higher number of lysosomes and vague mitochondrial cristae compared with those in the sham group. However, these histopathological changes were markedly alleviated after LP treatment. CONCLUSIONS: This study shows a protective effect of LP on VECs in PS rats. LP can regulate plasma levels of NO, ET-1, and 6-keto-PGF1a, enhance endothelium-dependent relaxation, and alleviate histopathological changes of lysosomes and mitochondria in VECs. The potential mechanism of LP on VECs in PS rats is related to its function of reducing metabolites of adrenalin.