Table 4.
Mechanism involved and pharmacological outcomes from miscellaneous investigations on alkannin/shikonin containing plant extracts, alkannin/shikonin and its derivatives.
| Test compounds | Cell lines/In vitro/In vivo assay | Mechanism involved | Disease targeted | References |
|---|---|---|---|---|
| Lithospermum erythrorhizon and Angelica sinensis extract | Human Bronchial Epithelial cell line (BEAS-2B) | Anti-inflammatory effect in Der-p2-stimulated BEAS-2 β cells; Inhibition of TSLP production and suppression of IKKα, caspase-1 and NLRP3 |
Allergic diseases such as asthma, atopic dermatitis and allergic rhinitis | Yen et al., 2017 |
| Onosma tauricum extract | Anti-oxidant assays (DPPH, CUPRAC, ferrous ion chelating, FRAP, polumolybednum, ABTS) and Enzyme inhibitory assays (AChE, α-amylase, BChE, tyrosinase, α-glucosidase) | Anti-oxidant and enzyme inhibitory activity | Evaluation of antioxidant and enzyme inhibitory potential | Kirkan et al., 2018 |
| Onosma sieheana and Onosma stenoloba extracts | Total phenolic assay, total flavonoid assay, anti-oxidant assay, tyrosinase assay, α-amaylase assay. | Anti-tyrosinase activity. Increased expression of p-Erk1/2 and reduced extression of tyrosinase related protein 1 and 2 |
Diabetes | Sarikurkcu, Sahinler, Ceylan, & Tepe, 2020 |
| Lithospermum radix aqueous extract | Sub-acute oral toxicity | Suppression of spinal inflammation | Chemotherapy induced neuropathy. | Kim et al., 2019 |
| Shikonin | PAI-1 activity assay, Clot lysis assay, mouse arterial thrombosis model, Mouse liver fibrosis model. | Inhibition of plasminogen activator inhibitor-1 activity; Anti-thrombotic and anti-fibrotic effect |
Fibrinolysis | Han et al., 2016 |
| Human endothelial cell line derived from human lung carcinoma cells and human umbilical vein endothelial cells | Induction of expression of PI3K/ Akt/Nrf 2- dependent antioxidant genes such as SOD-1, HO-1, Catalase, GPx-1, GCLM and GSR; Inhibition of oxLDL-induced intracellular ROS accumulation via NF-ƙβ adhesion |
Atherosclerosis | Huang et al., 2015 | |
| Human umbilical vein endothelial cells (HUVEC), human fibroblast-like synoviocyte (HFLS).Collagen-induced arthritis model. In vivo chick chorioallantoic membrane (CAM) assay. Ex vivo rat aortic ring assay |
Inhibition of pro-angiogenic mediators such as TNF-α, IL-12, TGF-β, IL-6, IL-8, VEGF, PDGF,IL-17A and MMPs; Increase expression of Treg/Th17 by deactivation of TLR4/MyD88 pathway |
Rheumatoid arthritis | Liu et al., 2020 | |
| Isovaleryl shikonin and isobutyryl shikonin | Acute toxicity, chronic toxicity, growth inhibition, antifeedant activity, AChE inhibitory activity and antioxidant assay. | Inhibition of AChE enzymes; Inhibition of mitochondrial respiration thereby inhibiting larval growth |
Inhibition of larval growth of Tobacco cutworm Spodoptera littoralis. | Sut et al., 2017 |
| Acetylshikonin | Behavioral testing (Morris Water Maze test) |
Inhibition of activation of p53/p21 signaling pathway; Upregulation of SIRTI in hippocampus; Anti-apoptotic activity in neuronal cells and attenuated H2O2 induced oxidative stress |
Alzheimer’s disease | Li, Zeng, Su, He, & Zhu, 2018 |
| L6 rat skeletal muscle cells. Alloxan-induced type I diabetic models. | Activation of p2C-β3/PKCδ cascades via activation of inositol lipid signaling and increase in DAG release | Diabetes. | Huang et al., 2019 | |
| Acetylshikonin and isobutyryl shikonin | Anti-genotoxic properties (Umu-test) and cytotoxicity assay (Lung fibroblast cell line (V79) | Inhibition of p450 enzymes, Free radical scavenging activity and anti-genotoxic activity | Carcinogenesis | Skrzypczak et al., 2015 |