Pharmacological properties and derivatives of shikonin—A review in recent years

Guo, Chuanjie; He, Junlin; Song, Xiaominting; Tan, Lu; Wang, Miao; Jiang, Peidu; Li, Yuzhi; Cao, Zhixing; Peng, Cheng

doi:10.1016/j.phrs.2019.104463

Cited by 197 publications

(132 citation statements)

References 84 publications

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“…Shikonin is the major bioactive component extracted from the roots of Lithospermum erythrorhizon [ 91 ] and has various pharmacological activities, such as anti‐inflammatory, [ 92 ] antioxidant [ 93 ] and neuroprotection activities. [ 94 ] Shikonin inhibited LPS‐induced NO release and reduced the release of various proinflammatory molecules from activated microglia.…”

Section: Quinones and Its Role In Admentioning

confidence: 99%

Quinones as preventive agents in Alzheimer’s diseases: focus on NLRP3 inflammasomes

Chen

Gao

Peng

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives Alzheimer's disease (AD) is a hidden neurological degenerative disease, which main clinical manifestations are cognitive dysfunction, memory impairment and mental disorders. Neuroinflammation is considered as a basic response of the central nervous system. NLRP3 (Nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3) inflammasome is closely related to the occurrence of neuroinflammation. Activation of the NLRP3 inflammasome results in the release of cytokines, pore formation and ultimately pyroptosis, which has demonstrated one of the critical roles in AD pathogenesis. Inhibition of the activity of NLRP3 is one of the focuses of the research. Therefore, NLRP3 represents an attractive pharmacological target, and discovery compounds with good NLRP3 inhibitory activity are particularly important. Key findings Quinones have good neuroprotective effects and prevent AD, which may be related to their regulation of inflammatory response. The molecular docking was used to explore 12 quinones with AD prevention and treatment and NLRP3. Docking results showed that the combination of anthraquinones and NLRP3 were the best, and the top two chemical compounds were Purpurin and Rhein, which are the most promising NLRP3 inhibitors. Summary These quinones may provide the theoretical basis for finding lead compounds for novel neuroprotective agents. Quinones as NLRP3 inflammasomes inhibitors Da-bao Chen et al.

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Section: Quinones and Its Role In Admentioning

confidence: 99%

Quinones as preventive agents in Alzheimer’s diseases: focus on NLRP3 inflammasomes

Chen

Gao

Peng

et al. 2020

Journal of Pharmacy and Pharmacology

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“…primarily constructed through multiple additions and substitutions with shikonin as the primary substrate to obtain a variety of derivatives with different structures (12). The 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) compound is commonly used to synthesize naphthoquinone derivatives.…”

Section: The Compound 2-benzylthio-58-dimethoxynaphthalene-14-dionementioning

confidence: 99%

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

Shen

Sun

et al. 2020

Exp Ther Med

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The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-Ras G12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-Ras G12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and β-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.

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“…Zicao is a commonly used herbal medicine in China (32). Zicao is believed to possess detoxification properties and has been used for the treatment of macular eruptions, measles, sore-throat, carbuncles and burns (33).…”

Section: Non-cytotoxic Doses Of Shikonin Inhibit Lipopolysaccharide-imentioning

confidence: 99%

Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑α expression via activation of the AMP‑activated protein kinase signaling pathway

Zhang

Gao

et al. 2020

Exp Ther Med

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Shikonin has been reported to exhibit a wide variety of medical functions. However, the strong non-selective cytotoxicity of shikonin can restrict its clinical application. The aim of the present study was to investigate the effects of shikonin at non-cytotoxic doses on the pro-inflammation functions of monocytes and macrophages. The present results suggested that the non-cytotoxic doses of shikonin effectively inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production, NF-κB activation and TNF-α expression in RAW 264.7 mouse macrophages via AMP-activated protein kinase (AMPK) signaling pathway. In addition, the non-cytotoxic doses of shikonin downregulated LPS-induced TNF-α expression via AMPK signaling activation in primary murine bone marrow-derived macrophages, and also in monocytes cultured ex vivo from patients with chronic obstructive pulmonary disease (COPD). The present in vivo results indicated that the low-toxic dose of shikonin suppressed LPS-induced endotoxin shock and TNF-α expression in mice. Collectively, the present results may provide clinical and translational relevance for treating COPD and other TNF-α-related inflammatory disorders.

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Pharmacological properties and derivatives of shikonin—A review in recent years

Cited by 197 publications

References 84 publications

Quinones as preventive agents in Alzheimer’s diseases: focus on NLRP3 inflammasomes

Quinones as preventive agents in Alzheimer’s diseases: focus on NLRP3 inflammasomes

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑α expression via activation of the AMP‑activated protein kinase signaling pathway

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Pharmacological properties and derivatives of shikonin—A review in recent years

Cited by 197 publications

References 84 publications

Quinones as preventive agents in Alzheimer’s diseases: focus on NLRP3 inflammasomes

Quinones as preventive agents in Alzheimer’s diseases: focus on NLRP3 inflammasomes

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑&alpha; expression via activation of the AMP‑activated protein kinase signaling pathway

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Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑α expression via activation of the AMP‑activated protein kinase signaling pathway