Sini Decoction (SND) is the main prescription for treating Shaoyin disease in Zhang Zhongjing's Treatise on Typhoid Diseases in Han Dynasty. It is composed of Aconitum carmichaeli Debeaux, Glycyrrhiza uralensis Fisch ex DC and Zingiber officinale Roscoe. It has the effects of warming middle-jiao to dispel cold and revive the yang for resuscitation. Nowadays, it is mainly used in diseases in cardiovascular system, nervous system, digestive system and so on. In this paper, the effect and mechanism of the compatibility of Aconitum carmichaelii, Glycyrrhiza uralensis Fisch ex DC and Zingiber officinale Roscoe in SND were described. The results showed that SND performed remarkbly on strengthening heart, promoting blood circulation as well as inhibiting cardiomyocyte apoptosis, anti-inflammatory and anti-hypothyroidism. The toxic effect of Aconitum carmichaelii was relieved by the combination of Glycyrrhiza uralensis Fisch ex DC and Zingiber officinale Roscoe. The mechanism of increasing efficiency and reducing toxicity after the compatibility of medicines in SND was discussed from the perspective of changes in biological effects and chemical compositions. In terms of biological effects, the mechanism of SND in treating heart failure, myocardial ischemia, myocardial hypertrophy and hypothyroidism and protecting cell injury were discussed. As to chemical composition changes, most studies have compared the changes of main components in Aconitum carmichaelii, Glycyrrhiza uralensis Fisch ex DC and Zingiber officinale Roscoe with the whole prescription, drug pair and single Decoction, which further confirmed the effect of Glycyrrhiza uralensis Fisch ex DC on the detoxification of Aconitum carmichaelii and the significance of compatibility efficiency of SND. For the application of differently processed varieties of Aconitum carmichaelii in SND, the treatment of different diseases has siginificant tendencies and differences in the selections of Aconitum carmichaelii processed varieties. This paper will lay a foundation on clarifying the mechanism of drug compatibility of SND and in the future, provide a reference for the proper selection of differently processed products of Aconitum carmichaelii in SND in order to exert better effects in clinical pratices.
The protective effect of phloridzin (PHL) and its potential mechanism were examined in mice with liver injury induced by isoniazid (INH) and rifampicin (RFP). The mice were randomly divided into normal control group, model group, low (80 mg/kg), medium (160 mg/kg) and high (320 mg/kg) phloridzin-treated groups. After 28 days treatment, blood and liver tissue were collected and analysed. The results revealed that PHL regulated liver function related indicators and reduced the pathological tissue damage, indicating that PHL significantly alleviated the liver injury. Furthermore, the level of cytochrome P450 (CYP450) enzyme, the expression of cytochrome P450 3A4 (CYP3A4), cytochrome P450 2E1 (CYP2E1), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and protein were inhibited by PHL. These results indicated that PHL exerts a protecting effect against liver injury induced by combination of RFP and INH. The potential mechanisms may be concerned with the activation of Nrf2/HO-1 signaling pathway containing its key antioxidant enzymes and regulation of CYP3A4 and CYP2E1.
A C10CO-NalLeuVal (C10NLV) tripeptide was synthesized and explored as a carrier for paclitaxel (TAX) delivery. Five types of TAX-loaded micelles were produced by loading TAX with different doses of C10NLV. MTT assay showed that TAX-loaded micelles dramatically reduced TAX IC50 values of TAX-resistant A549 (A549/TAX) and LLC cells in a C10NLV-dose-dependent manner, with micelles 4 and 5 exhibited comparable inhibitory effects on A549/TAX proliferation. Flow cytometry analysis showed that TAX-loaded micelles 4 promoted lung cancer cell apoptosis in a TAX-dose-dependent manner. Immunofluorescent staining and Western blotting revealed that TAX-loaded micelles 4 dramatically reduced the protein levels of F-actin, p53, Bcl-2, and LC3A/B in A549/TAX cells. Wound healing, cell adhesion, migration, and invasion assays demonstrated that TAX-loaded micelles 4 suppressed the metastatic abilities of lung cancer cells. Furthermore, compared with the same dose of free TAX, TAX-loaded micelles 4 significantly reduced the volumes and weights of A549/TAX-generated tumors as well as the numbers of LLC-generated pulmonary metastatic foci in mice, without affecting the organ/body weight ratios, body weights, and blood cell counts. Histological analysis demonstrated that TAX-loaded micelles 4 administration resulted in tubulin and CD206 downregulation as well as cytoplasm disappearance and nuclear shrinkage in xenograft tumors. These data suggest that TAX-loaded micelles 4 inhibits the proliferative and metastatic capacity of lung cancer cells, despite TAX resistance. TAX-loaded micelles 4 suppresses lung tumor growth and metastasis in vivo without inducing systemic toxicity. Thus, the C10NLV-based TAX delivery is effective and safe to combat TAX resistance and metastasis in lung cancer.