Acetylshikonin stimulates glucose uptake in L6 myotubes via a PLC-β3/PKCδ-dependent pathway

Huang, Wendong; Zeng, Jiacheng; Liu, Zhaochun; Su, Meiling; Li, Qisen; Zhu, Bin

doi:10.1016/j.biopha.2019.01.049

Cited by 13 publications

(6 citation statements)

References 34 publications

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“…Similar to the above, various A/S derivatives have exhibited anti-obesity and anti-diabetic activities, such as a commercial sample of ACS ( Huang et al, 2019 ) isolated from Lithospermum erythrorhizon Siebold and Zucc. root extracts ( Gwon et al, 2012 ; Su M. L. et al, 2016 ; Su M et al, 2016 ), DMAS from Arnebia euchroma (Royle) I. M. Johnst.…”

Section: Introductionmentioning

confidence: 78%

Expanding the Biological Properties of Alkannins and Shikonins: Their Impact on Adipogenesis and Life Expectancy in Nematodes

et al. 2022

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Alkannin, shikonin (A/S) and their derivatives are naturally occurring hydroxynaphthoquinones biosynthesized in some species of the Boraginaceae family. These natural compounds have been extensively investigated for their biological properties over the last 40 years, demonstrating a plethora of activities, such as wound healing, regenerative, anti-inflammatory, antitumor, antimicrobial and antioxidant. This study aims to extend the current knowledge by investigating the effects of various A/S compounds on two model systems, namely on 3T3-L1 pre-adipocytes and the nematode Caenorhabditis elegans. The former constitutes an established in vitro model for investigating anti-obesity and insulin-mimetic properties, while the latter has been widely used as a model organism for studying fat accumulation, lifespan and the anthelmintic potential. A set of chemically well-defined A/S derivatives were screened for their effect on pre-adipocytes to assess cell toxicity, cell morphology, and cell differentiation. The differentiation of pre-adipocytes into mature adipocytes was examined upon treatment with A/S compounds in the presence/absence of insulin, aiming to establish a structure-activity relationship. The majority of A/S compounds induced cell proliferation at sub-micromolar concentrations. The ester derivatives exhibited higher IC50 values, and thus, proved to be less toxic to 3T3-L1 cells. The parent molecules, A and S tested at 1 μM resulted in a truncated differentiation with a reduced number of forming lipids, whereas compounds lacking the side chain hydroxyl group projected higher populations of mature adipocytes. In C. elegans mutant strain SS104, A/S enriched extracts were not able to inhibit the fat accumulation but resulted in a drastic shortage of survival. Thus, the set of A/S compounds were tested at 15 and 60 μg/ml in the wild-type strain N2 for their nematocidal activity, which is of relevance for the discovery of anthelmintic drugs. The most pronounced nematocidal activity was observed for naphthazarin and β,β-dimethyl-acryl-shikonin, followed by isovaleryl-shikonin. The latter 2 A/S esters were identified as the most abundant constituents in the mixture of A/S derivatives isolated from Alkanna tinctoria (L.) Tausch. Taken together, the findings show that the structural variations in the moiety of A/S compounds significantly impact the modulation of their biological activities in both model systems investigated in this study.

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Section: Introductionmentioning

confidence: 78%

Expanding the Biological Properties of Alkannins and Shikonins: Their Impact on Adipogenesis and Life Expectancy in Nematodes

et al. 2022

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“…However, the contraction-induced release of reactive oxygen species (ROS) and activation of AMP activated protein kinase (AMPK) may also lead to increased glucose uptake in skeletal muscle cells ( Mao, Yu, Li, & Li, 2008 , Su et al, 2016 ). Subsequently, acetylshikonin-induced glucose uptake was significantly inhibited by reduction of PLC-β3 in L6 myotubes, which makes it evident that acetylshikonin-induced glucose uptake may be triggered by activation of inositol lipid signaling and increased DAG release ( Huang et al, 2019 ). On the other hand, ageing is also considered as biggest cause of Alzheimer’s disease.…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Pharmacological and analytical aspects of alkannin/shikonin and their derivatives: An update from 2008 to 2022

Kaur

Sharma

Singh

et al. 2022

Chinese Herbal Medicines

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“…Acetylshikonin treatment could ameliorate diabetic nephropathy (DN) in mice through attenuation of renal inflammation, decrease in kidney fibrosis, and inhibition of the activation of TGF-b1/Smad pathway . In another study, acetylshikonin enhanced glucose transporter 4 translocation and induced glucose uptake in L6 myotubes via the PLC-b3/PKCd pathway to reduce blood glucose (Huang et al 2019). Free fatty acid receptor (FFA) 4 is a member of the G-protein coupled receptors, which may play a role in diabetes treatment and other diseases (Milligan et al 2017).…”

Section: Antidiabetic Effect Of Acetylshikoninmentioning

confidence: 99%

“…In another study, acetylshikonin enhanced glucose transporter 4 translocation and induced glucose uptake in L6 myotubes via the PLC-β3/PKCδ pathway to reduce blood glucose (Huang et al. 2019 ). Free fatty acid receptor (FFA) 4 is a member of the G-protein coupled receptors, which may play a role in diabetes treatment and other diseases (Milligan et al.…”

Section: Pharmacologymentioning

confidence: 99%

“…Currently, acetylshikonin has attracted much attention for its broad pharmacological effects such as anticancer, anti-inflammatory, antioxidative, antibacterial, antifungal, lipid-regulatory, antidiabetic, neuroprotective, and antiviral properties (Sasaki et al 2000;Cheng et al 2008;Kim et al 2009;Gwon et al 2012;Li et al 2012;Wang et al 2013;Xue and Li 2017;Huang et al 2019;Liao et al 2019). However, previous studies have reported the toxicity of acetylshikonin with respect to genotoxicity and reproductive toxicity (Li et al 2015;He et al 2016).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review

Zhang

Bai

Zeng

et al. 2020

Pharmaceutical Biology

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Context: Acetylshikonin, a naphthoquinone derivative, is mainly extracted from some species of the family Boraginaceae, such as Lithospermum erythrorhizon Sieb. et Zucc., Arnebia euchroma (Royle) Johnst., and Arnebia guttata Bunge. As a bioactive compound, acetylshikonin has attracted much attention because of its broad pharmacological properties. Objective: This review provides a comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of acetylshikonin focussing on its mechanisms on the basis of currently available literature. Methods: The information of acetylshikonin from 1977 to 2020 was collected using major databases including Elsevier, Scholar, PubMed, Springer, Web of Science, and CNKI. Acetylshikonin, pharmacology, toxicity, pharmacokinetics, and naphthoquinone derivative were used as key words. Results: According to emerging evidence, acetylshikonin exerts a wide spectrum of pharmacological effects such as anticancer, anti-inflammatory, lipid-regulatory, antidiabetic, antibacterial, antifungal, antioxidative, neuroprotective, and antiviral properties. However, only a few studies have reported the adverse effects of acetylshikonin, with respect to reproductive toxicity and genotoxicity. Pharmacokinetic studies demonstrate that acetylshikonin is associated with a wide distribution and poor absorption. Conclusions: Although experimental data supports the beneficial effects of this compound, acetylshikonin cannot be considered as a therapy drug without further investigations, especially, on the toxicity and pharmacokinetics.

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Acetylshikonin stimulates glucose uptake in L6 myotubes via a PLC-β3/PKCδ-dependent pathway

Cited by 13 publications

References 34 publications

Expanding the Biological Properties of Alkannins and Shikonins: Their Impact on Adipogenesis and Life Expectancy in Nematodes

Expanding the Biological Properties of Alkannins and Shikonins: Their Impact on Adipogenesis and Life Expectancy in Nematodes

Pharmacological and analytical aspects of alkannin/shikonin and their derivatives: An update from 2008 to 2022

Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review

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