New paeonol derivative C302 reduces hypertension in spontaneously hypertensive rats through endothelium-dependent and endothelium-independent vasodilation.

Hypertension is a major risk factor for cardiovascular disease and Chinese herb monomers could provide new structural skeletons for anti-hypertension new drug development. Paeonol is a Chinese herbal monomer extracted from Cortex moutan, exhibited some anti-hypertensive activity. The study focused on the structural optimization of paeonol to provide promising lead compounds for anti-hypertension new drug development. Herein, twelve new paeonol derivatives (PD) were designed and synthesized and their vasodilation activity was evaluated by in vitro vasodilation drug screening platform based on Myograph. Its anti-hypertension activity, PD-C302 (2-hydroxy-4-methoxyvalerophenone) as a representative with the optimal vasodilation activity, was determined by its response to blood pressure in spontaneously hypertensive rats (SHR) in vivo. Moreover, its molecular mechanism was probed by the vasodilation activity of rat superior mesenteric artery rings with or without endothelium pre-contracted by potassium chloride (KCl) or phenylephrine hydrochloride (PE). It was indicated that PD-C302 significantly reduced the blood pressure in SHR, which would involve in PD-C302-induced vasodilation. Furthermore, endothelium-dependent pathways and endothelium-independent pathways both contributed importantly to PD-C302-induced vasodilation at low concentration of PD-C302. Endothelium-independent pathways (vascular smooth muscle cell-mediated vasodilation), were mainly responsible for the PD-C302-induced vasodilation at high concentration of PD-C302, which involved in opening multiple K+ channels to restrain Ca2+ channels, and then triggered vasodilation to reduce blood pressure. PD-C302 has a simple structure and favorable anti-hypertensive activity in vivo, which could be a promising lead compound for anti-hypertension new drug development.

Liuwei Dihuang Decoction for primary osteoporosis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Primary osteoporosis (POP) is one kind of global disease, as a serious threat to human health. Liuwei Dihuang Decoction (LWDHD) has been recommended to treat osteoporosis alone or combined with medicine in China; however, its efficacy is unclear. The object of this systematic review and meta-analysis is to evaluate the efficacy and safety of LWDHD in the management of POP. METHODS: We will search The Cochrane Library, Medline, PubMed, Elsevier, Springer, Web of Science, Ovid, WHO ICTRP, CNKI, CBM, VIP, and WanFang Database from their inception to February 2019. All randomized controlled trials (RCTs) of LWDHD for the treatment of POP will be included. The language is limited to Chinese and English. The fracture incidence will be accepted as the primary outcomes. Data synthesis, subgroup analysis, sensitivity analysis will be performed by using RevMan V.5.3.5 software. RESULTS: A high-quality synthesis of current evidence for the treatment of POP with LWDHD will be provided from efficacy and safety. CONCLUSION: This systematic review will generate evidence for judging whether LWDHD is an effective and safe intervention for POP or not. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 4201926066.

Ginsenoside 20(S)-Rg3 induced autophagy to inhibit migration and invasion of ovarian cancer.

BACKGROUND: Autophagy maintains cellular homeostasis through engulfing cytoplasmic proteins and organelles, and plays an important role in cancer initiation and progression. Ginsenoside 20(S)-Rg3, an active ingredient of Panax ginseng, exerts anti-cancer functions in various cancers. However, its molecular mechanisms, including its effect on autophagy, are not fully elucidated in tumor models. METHODS: Ovarian cancer cell line SKOV3 was treated by various concentrations of 20(S)-Rg3. Markers of autophagy were detected by real-time PCR, western blot, immunofluorescence and immunohistochemistry. Cell viability was observed by CCK8 assays and cell migration and invasion were examined with Transwell. RESULTS: 20(S)-Rg3 induced autophagy in SKOV3 ovarian cancer cells in a dose-dependent manner as indicated by the upregulation of autophagy-associated molecules including LC3 II, ATG5 and ATG7. The autophagy inhibitor chloroquine antagonized the inhibition of 20(S)-Rg3 on migration and invasion of SKOV3 cells, but slightly enhanced the impairment of 20(S)-Rg3 on cell viability. Immunohistochemistry staining of LC3, ATG5 and ATG7 on subcutaneous xenograft tissue sections from previously established nude mice models showed that 20(S)-Rg3 upregulated LC3, ATG5 and ATG7 as observed in cell models. CONCLUSION: Autophagy induction was one mechanism mediating inhibition of 20(S)-Rg3 on ovarian cancer invasive progression.