Shikonin, a naphthalene ingredient: Therapeutic actions, pharmacokinetics, toxicology, clinical trials and pharmaceutical researches

Sun, Qiang; Gong, Ting; Liu, Maolun; Ren, Shan; Yang, Han; Zeng, Shengkui; Zhao, Hui; Chen, Li; Ming, Tianqi; Meng, Xianli; Xu, Haibo

doi:10.1016/j.phymed.2021.153805

Cited by 62 publications

(36 citation statements)

References 208 publications

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“…As chemotherapeutics usually cause undesirable adverse events and multidrug resistance in patients with CRC, phytotherapy with natural products derived from medicinal plants is playing a progressively pivotal role in the management of CRC. Serving as an alternative treatment avenue, phytotherapy improving the clinical outcome of patients with CRC is broadly acknowledged at present (Sun et al, 2021; Zeng et al, 2021; Zhao, He, et al, 2021; Zhao, Zeng, et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Ursolic acid inhibits the activation of smoothened‐independent non‐canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade

Chen

Liu

Ren

et al. 2022

Phytotherapy Research

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It is being brought to light that smoothened (SMO)‐independent non‐canonical Hedgehog signaling is associated with the pathogenesis of various cancers. Ursolic acid (UA), a pentacyclic triterpenoid present in many medicinal herbs, manifests potent effectiveness against multiple malignancies including colorectal cancer (CRC). In our previous study, UA was found to protect against CRC in vitro by suppression of canonical Hedgehog signaling cascade. Here, the influence of UA on SMO‐independent non‐canonical Hedgehog signaling in CRC was investigated in the present study, which demonstrated that UA hampered the proliferation and migration, induced the apoptosis of HCT‐116hSMO− cells with SMO gene knockdown, accompanied by the augmented expression of the suppressor of fused (SUFU), and lessened levels of MYC (c‐Myc), glioma‐associated oncogene (GLI1) and Sonic Hedgehog (SHH), and lowered phosphorylation of protein kinase B (PKB, AKT), suggesting that UA diminished non‐canonical Hedgehog signal transduction in CRC. In HCT‐116hSMO− xenograft tumor, UA ameliorated the symptoms, impeded the growth and caused the apoptosis of CRC, with heightened SUFU expression, and abated levels of MYC, GLI1, and SHH, and mitigated phosphorylation of AKT, indicating that UA down‐regulated non‐canonical Hedgehog signaling cascade in CRC. Taken together, UA may alleviate CRC by suppressing AKT signaling‐dependent activation of SMO‐independent non‐canonical Hedgehog pathway.

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Section: Discussionmentioning

confidence: 99%

Ursolic acid inhibits the activation of smoothened‐independent non‐canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade

Chen

Liu

Ren

et al. 2022

Phytotherapy Research

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“…Shikonin, a naphthoquinone isolated from Lithospermum erythrorhizon, is well-known for its strong anti-tumor effects (Sun et al, 2022). It has been used to treat various cancers, such as colon, renal, and lung cancer (Pan et al, 2021;Shi G. et al, 2021;Tsai et al, 2021) Frontiers in Pharmacology frontiersin.org 7 cells with Shikonin treatment (Wei et al, 2016).…”

Section: Shikoninmentioning

confidence: 99%

Exosomes: A novel insight into traditional Chinese medicine

Zhao

Liang

et al. 2022

Front. Pharmacol.

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Exosomes are small extracellular vesicles and play an essential role in the mediation of intercellular communication both in health and disease. Traditional Chinese medicine (TCM) has historically been used to maintain human health and treat various diseases up till today. The interplay between exosomes and TCM has attracted researchers’ growing attention. By integrating the available evidence, TCM formulas and compounds isolated from TCM as exosome modulators have beneficial effects on multiple disorders, such as tumors, kidney diseases, and hepatic disease, which may associate with inhibiting cells proliferation, anti-inflammation, anti-oxidation, and attenuating fibrosis. Exosomes, a natural delivery system, are essential in delivering compounds isolated from TCM to target cells or tissues. Moreover, exosomes may be the potential biomarkers for TCM syndromes, providing strategies for TCM treatment. These findings may provide a novel insight into TCM from exosomes and serve as evidence for better understanding and development of TCM.

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“…These reviews also presented the biosynthesis and chemical synthesis of shikonin. The most recent review on shikonin was related to its pharmacology, pharmacokinetics, toxicology, clinical trials, and pharmaceutical applications, presenting all the aspects of shikonin in detail as mentioned above (Sun et al, 2022). In comparison to these articles, the present review includes all the possible aspects of shikonin and its derivatives, including various natural sources, distribution, isolation, biosynthesis, chemical synthesis, stability, pharmacology, patent, and toxicity.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical trials registered on clinicaltrials.gov related to shikonin and shikonin producing species (source-https://clinicaltrials.gov/andSun et al, 2022).…”

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confidence: 99%

Review of Shikonin and Derivatives: Isolation, Chemistry, Biosynthesis, Pharmacology and Toxicology

et al. 2022

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Shikonin and its derivatives, isolated from traditional medicinal plant species of the genus Lithospermum, Alkanna, Arnebia, Anchusa, Onosma, and Echium belonging to the Boraginaceae family, have numerous applications in foods, cosmetics, and textiles. Shikonin, a potent bioactive red pigment, has been used in traditional medicinal systems to cure various ailments and is well known for its diverse pharmacological potential such as anticancer, antithrombotic, neuroprotective, antidiabetic, antiviral, anti-inflammatory, anti-gonadotropic, antioxidants, antimicrobial and insecticidal. Herein, updated research on the natural sources, pharmacology, toxicity studies, and various patents filed worldwide related to shikonin and approaches to shikonin’s biogenic and chemical synthesis are reviewed. Furthermore, recent studies to establish reliable production systems to meet market demand, functional identification, and future clinical development of shikonin and its derivatives against various diseases are presented.

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Shikonin, a naphthalene ingredient: Therapeutic actions, pharmacokinetics, toxicology, clinical trials and pharmaceutical researches

Cited by 62 publications

References 208 publications

Ursolic acid inhibits the activation of smoothened‐independent non‐canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade

Ursolic acid inhibits the activation of smoothened‐independent non‐canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade

Exosomes: A novel insight into traditional Chinese medicine

Review of Shikonin and Derivatives: Isolation, Chemistry, Biosynthesis, Pharmacology and Toxicology

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