[Research progress on Rhododendron molle in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.

Oridonin synergistically enhances JQ1-triggered apoptosis in hepatocellular cancer cells through mitochondrial pathway.

Bromodomain and Extra-Terminal Domain (BET) inhibitors, such as JQ1 have emerged as novel drug candidates and are being enthusiastically pursued in clinical trials for the treatment of cancer. However, many solid cancers are resistance to BET inhibitors. To explore methods for improving the therapeutic potential of BET inhibitors, we investigated the combinational activity of JQ1 with Oridonin, a bioactive molecules derived from Traditional Chinese Medicine in hepatocellular carcinoma (HCC) cells. Our results showed that Oridonin synergistically enhanced the abilities of JQ1 to inhibit cell viability in HCC cells and, significantly augmented JQ1-triggered apoptosis in HCC cells and in HCC cancer stem-like cells. Moreover, Oridonin dose-dependently inhibited the expression of several anti-apoptotic proteins, such as Bcl-2, Mcl-1, and x-linked inhibitor of apoptosis (xIAP) in HCC cells. Cell fractionation and western blotting analysis showed that the enhancement of apoptosis by Oridonin was associated with cytochrome c release, activation of caspase-9, -3 and cleavage of PARP, indicating the activation of mitochondrial apoptosis pathway. Altogether, our findings demonstrate that Oridonin may be used to effectively enhance the sensitivity of BET inhibitors in HCC therapy via downregulation of the expression of multiple anti-apoptotic proteins.

Discovery, design and synthesis of 6H-anthra[1,9-cd]isoxazol-6-one scaffold as G9a inhibitor through a combination of shape-based virtual screening and structure-based molecular modification.

Protein lysine methyltransferase G9a is widely considered as an appealing antineoplastic target. Herein we present an integrated workflow combining shape-based virtual screening and structure-based molecular modification for the identification of novel G9a inhibitors. The shape-based similarity screening through ROCS overlay on the basis of the structure of UNC0638 was performed to identify CPUY074001 contained a 6H-anthra[1,9-cd]isoxazol-6-one scaffold as a hit. Analysis of the binding mode of CPUY074001 with G9a and 3D-QSAR results, two series compounds were designed and synthesized. The derivatives were confirmed to be active by in vitro assay and the SAR was explored by docking stimulations. Besides, several analogues showed acceptable anti-proliferative effects against several cancer cell lines. Among them, CPUY074020 displayed potent dual G9a inhibitory activity and anti-proliferative activity. Furthermore, CPUY074020 induced cell apoptosis in a dose-dependent manner and displayed a significant decrease in dimethylation of H3K9. Simultaneously, CPUY074020 showed reasonable in vivo PK properties. Altogether, our workflow supplied a high efficient strategy in the identification of novel G9a inhibitors. Compounds reported here can serve as promising leads for further study.

[Analysis of Volatile Oils from Different Processed Products of Zingiber officinale Rhizome by GC-MS].

OBJECTIVE: To analyze the volatile components in different processed products of Zingiber officinale rhizome, and to make clear the effect of different heating degree on them. METHODS: The volatile components were extracted from four kinds of processed products by applying steam distillation, and then were analyzed by GC-MS. RESULTS: There were totally 43 components of volatile oil identified from four kinds of processed products of Zingiber officinale rhizome. Fresh product, dried product, and charcoal product of Zingiber officinale rhizome each had 27 components of volatile oil, while sand fried product contained 24 components. Fresh Zingiber officinale rhizome contained 22. 59% of zingiberene, 20. 87% of a-citral and 11. 01% of ß-phellandrene, respectively. After processing in different heating degree, the volatile components changed greatly in both of their quantity and quality, For instance, dried Zingiber officinale rhizome contained 40. 48% of α-citral and 8-phellandrene content was slightly lower at 10. 38%. 32.73% of 3,7,11-trimethyl-l, 6, 10-dodecatriene,16. 38% of murolan-3, 9 (11)-diene-10-peroxy and 3. 36% of cubebene newly emerged in the sand fried Zingiber officinale rhizome, and eudesm-4 (14) and ß-bisabolol, etc. However, ß-phellandrene content was only 1. 95%. The zingiberene and ß-sesquiphellandrene were the highest in charcoal product, besides, new components such as α-cedrene, decanal and γ-elemene appeared. CONCLUSION: Volatile components in different processed products of Zingiber officinale rhizome were different in both of their kinds and contents. This method is suitable for the analysis of volatile components in Zingiber officinale rhizome, and this study can provide the experimental evidence for quality evaluation and clinical application for ginger processed products.