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

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

Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology 2021;94():153805

PMID: 34749177

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Shikonin is one of the major phytochemical components of Lithospermum erythrorhizon (Purple Cromwell), which is a type of medicinal herb broadly utilized in traditional Chinese medicine. It is well established that shikonin possesses remarkable therapeutic actions on various diseases, with the underlying mechanisms, pharmacokinetics and toxicological effects elusive. Also, the clinical trial and pharmaceutical study of shikonin remain to be comprehensively delineated.

PURPOSE

The present review aimed to systematically summarize the updated knowledge regarding the therapeutic actions, pharmacokinetics, toxicological effects, clinical trial and pharmaceutical study of shikonin.

METHODS

The information contained in this review article were retrieved from some authoritative databases including Web of Science, PubMed, Google scholar, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database and so on, till August 2021.

RESULTS

Shikonin exerts multiple therapeutic efficacies, such as anti-inflammation, anti-cancer, cardiovascular protection, anti-microbiomes, analgesia, anti-obesity, brain protection, and so on, mainly by regulating the NF-κB, PI3K/Akt/MAPKs, Akt/mTOR, TGF-β, GSK3β, TLR4/Akt signaling pathways, NLRP3 inflammasome, reactive oxygen stress, Bax/Bcl-2, etc. In terms of pharmacokinetics, shikonin has an unfavorable oral bioavailability, 64.6% of the binding rate of plasma protein, and enhances some metabolic enzymes, particularly including cytochrome P450. In regard to the toxicological effects, shikonin may potentially cause nephrotoxicity and skin allergy. The above pharmacodynamics and pharmacokinetics of shikonin have been validated by few clinical trials. In addition, pharmaceutical innovation of shikonin with novel drug delivery system such as nanoparticles, liposomes, microemulsions, nanogel, cyclodextrin complexes, micelles and polymers are beneficial to the development of shikonin-based drugs.

CONCLUSIONS

Shikonin is a promising phytochemical for drug candidates. Extensive and intensive explorations on shikonin are warranted to expedite the utilization of shikonin-based drugs in the clinical setting.

Address: State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.; Department of Ultrasound, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, Sichuan, China.; State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

DOI: 10.1016/j.phymed.2021.153805