Geraniol is an acyclic isoprenoid monoterpene isolated from the essential oils of aromatic plants including Cinnamomum tenuipilum, Valeriana officinalis, and several other plants. The limited source of geraniol from plant isolation cannot fulfill the great demand from the flavor and fragrance industries, which require maximizing geraniol production through biotechnology processes. The diverse activities of geraniol suggested that geraniol could treat various diseases as a promising drug candidate. In order to evaluate the potential of geraniol applied in a clinical trial, this review aims at providing a comprehensive summary of the pharmacological effects of geraniol. The publications retrieved from PubMed, ScienceDirect, Springer, and Wiley databases were collected and summarized for the last 6 years. Then, the potential application of geraniol as a drug is discussed based on its pharmacological properties, including antitumor, anti-inflammatory, antioxidative, and antimicrobial activities, and hepatoprotective, cardioprotective, and neuroprotective effects. Hence, this review aims at providing evidence of the pharmacological activities of geraniol in the context of further development as a drug candidate in clinical application.

The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5−80 μmol/L) for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π–π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2.

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Inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction using small-molecule inhibitors is an emerging immunotherapeutic approach. A novel series of [1,2,4]­triazolo­[4,3-a]­pyridines were designed and found to be potent inhibitors of the PD-1/PD-L1 interaction. Among them, compound A22 exhibited the most potent activity, as assessed by homogenous time-resolved fluorescence assay, with an IC50 of 92.3 nM. Furthermore, A22 dose-dependent elevated interferon-γ production in a co-culture model of Hep3B/OS-8/hPD-L1 and CD3 T cells. We concluded that A22 is a promising lead compound for the development of inhibitors of the PD-1/PD-L1 interaction. In addition, we explored the structure–activity relationships of the newly synthesized [1,2,4]­triazolo­[4,3-a]­pyridines and demonstrated that a ring fusion strategy can be employed for designing analogues of the Bristol-Myers Squibb chemical series. These studies pave the way for future drug design.

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