Overview of cannabidiol (CBD) and its analogues: Structures, biological activities, and neuroprotective mechanisms in epilepsy and Alzheimer's disease.

Herein, 11 general types of natural cannabinoids from Cannabis sativa as well as 50 (-)-CBD analogues with therapeutic potential were described. The underlying molecular mechanisms of CBD as a therapeutic candidate for epilepsy and neurodegenerative diseases were comprehensively clarified. CBD indirectly acts as an endogenous cannabinoid receptor agonist to exert its neuroprotective effects. CBD also promotes neuroprotection through different signal transduction pathways mediated indirectly by cannabinoid receptors. Furthermore, CBD prevents the glycogen synthase kinase 3ß (GSK-3ß) hyperphosphorylation caused by Aß and may be developed as a new therapeutic candidate for Alzheimer's disease.

Review of the molecular mechanisms of Ganoderma lucidum triterpenoids: Ganoderic acids A, C2, D, F, DM, X and Y.

Ganoderma lucidum is a multi-purpose plant medicine that is homologous to functional food. The most attractive properties of G. lucidum are its immunomodulatory and antitumour activities, which are mainly attributed to the following two major active components: G. lucidum polysaccharides and G. lucidum triterpenoids (GLTs). GLTs are effective as supplemental therapies and improve health when combined with other medications to treat hepatitis, fatigue syndrome, and prostate cancer. However, research investigating the mechanism and application of G. lucidum or GLTs in the treatment of diseases remains preliminary in terms of both the utilization efficacy and product type. This review offers comprehensive insight into the pharmacological activities of GLTs and their potential applications in the development of functional foods and nutraceuticals. Specifically, 83 GLTs were selected, and their molecular structures and chemical formulas were described. We also describe 7 ganoderic acids that are currently at different stages of clinical trials (ganoderic acids A, C2, D, F, DM, X and Y). The related pharmacodynamic mechanisms and targeted signalling proteins were further analysed. Notably, the specific relationship between autophagy and apoptosis induced by ganoderic acid DM is summarized here for the first time.

The development of Bruton's tyrosine kinase (BTK) inhibitors from 2012 to 2017: A mini-review.

Bruton's tyrosine kinase (BTK) has emerged as a promising drug target for multiple diseases, particularly haematopoietic malignancies and autoimmune diseases related to B lymphocytes. This review focuses on the diverse, small-molecule inhibitors of BTK kinase that have shown good prospects for clinical application. Individual examples of these inhibitors, including both reversible and irreversible inhibitors and a recently developed reversible covalent inhibitor of BTK, are discussed. Considerable progress has been made in the development of irreversible inhibitors, most of which target the SH3 pocket and the cysteine 481 residue of BTK. The present review also surveys the pharmacological advantages and deficiencies of both reversible and irreversible BTK drugs, with a focus on the structure-activity relationship (SARs) and binding modes of representative drugs, which could inspire critical thinking and new ideas for developing potent BTK inhibitors with less unwanted off-target effects.

Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids.

Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo. The most potent compound, 5c, arrested HepG2 cells (IC50 = 4.23 ± 0.79 µM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies.