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

Alkannin/shikonin (A/S) and their derivatives are naturally occurring naphthoquinones majorly found in Boraginaceae family plants. They are integral constituents of traditional Chinese medicine Zicao (roots of Lithospermum erythrorhizon). In last two decades significant increase in pharmacological investigations on alkannin/shikonin and their derivatives has been reported that resulted in discovery of their novel mechanisms in various diseases and disorders. This review throws light on recently conducted pharmacological investigations on alkannin/shikonin and their derivatives and their outputs. Various analytical aspects are also discussed and brief summary of patent applications on inventions containing alkannin/shikonin and its derivatives is also provided.     

Naphthoquinones from the root barks of Juglans cathayensis Dode

Phytochemical investigation of Juglans cathayensis Dode root barks led to the isolation of two novel nitrogen-containing naphthoquinones named juglonbutine (1) and binaphthine (2). Their structures were elucidated by the extensive analysis of the spectroscopic data. In addition, six known naphthoquinones (3–8) were also isolated from the same material for the first time.     

茜草属植物化学成分研究进展

目的: 对茜草属植物化学成分的研究进行整理分析,为合理开发利用茜草属植物资源提供科学依据和理论基础。 方法: 检索 CNKI,Wiley Online和ScienceDirec等数据库对该属植物化学成分研究的文献,并进行分析、归纳。 结果: 茜草属植物是世界上开发应用较早的天然植物资源之一,具有抗菌、抗肿瘤和抗氧化等生物活性。迄今为止从该属植物中已分离得到175个化合物,其中蒽醌类化合物近70个,此外还包括萘醌类、环己肽类和萜类成分等。 结论: 通过对该属植物化学成分系统总结,为从茜草属植物中开发利用有价值的天然产物提供科学依据。     

Dimeric naphthoquinones, a novel class of compounds with prostate cancer cytotoxicity

What’s known on the subject? and What does the study add? Sexual function is often impaired after radical prostatectomy (RP) resulting in reduced sexual activity and sexual bother. The main focus in the literature concerning sexual adverse effects has been on erectile dysfunction and impairment of sexual function rather than the actual sexual bother it causes, although the sexual bother is most important to the individual patient’s quality of life. The relation between these measures, and in particular pre‐operative prediction of post‐operative sexual bother, has only been studied limitedly and with varying results. Some studies have found good mental health, low levels of pre‐operative sexual bother, and higher education to be associated with absence of post‐operative sexual bother, but another study could not identify any pre‐operative predictors of a post‐operative sexual bother. Severe sexual bother after RP were reported by 64% to 95% of the patients three years after operation, and the prevalence was associated with the level of pre‐treatment sexual bother and pre‐operative nerve‐preservation. On the other hand, others have reported that only 43% of men have sexual bother 2 years after RP. However, none of these studies stratified patients according to their pre‐operative sexual activity and most of them were American. It has been shown that American findings concerning sexual bother may not always be valid for non‐American patients due to differing sex role expectations thus warranting the need for more non‐American studies. This study has shown that two thirds of patients experienced sexual bother one year after RP. We have identified patients with increased risk of experiencing overall sexual bother post‐operatively: those who report pre‐operative sexual bother, those who are sexually active before RP, and those who display neurotic personality‐traits. Another important finding was that the proportion of patients who experienced bother relevant to having impaired post‐operative SF was significantly higher among pre‐operatively sexually active patients than those who had been inactive. This study adds knowledge that patients’ pre‐operative sexual activity, sexual bother and personality should be taken into account to be able to give individualized information about the risk of getting sexual bother after RP.

OBJECTIVES

• ? To evaluate the cytotoxicity of dimeric naphthoquinones (BiQs) in prostate cancer cells.
• ? To assess the interaction of dimeric naphthoquinones with common therapies including radiation and docetaxel.

MATERIALS AND METHODS

• ? The cytotoxicity of 12 different dimeric naphthoquinones was assessed in androgen‐independent (PC‐3, DU‐145) and androgen‐responsive (LNCaP, 22RV1) prostate cancer cell lines and in prostate epithelial cells (PrECs).
• ? BiQ2 and BiQ11 were selected for determination of dose response, effects on colony formation and initial exploration into mechanism of action.
• ? Synergistic effects with radiation and docetaxel were explored using colony‐forming and MTT assays.

RESULTS

• ? At concentrations of 15µM, BiQ2, BiQ3, BiQ11, BiQ12, and BiQ15 demonstrated cytotoxicity in all prostate cancer cell lines.
• ? Treatment with BiQs limited the ability of prostate cancer cells to form colonies in clonogenic assays.
• ? Exposure of prostate cancer to BiQs increased cellular reactive oxygen species (ROS), decreased ATP production, and promoted apoptosis.
• ? BiQ cytotoxicity was independent of NADP(H):quinone oxidoreductase 1 (NQO1) activity in PrECs, PC‐3 and 22RV1, but not DU‐145 cells.
• ? Exposure of prostate cancer cells to radiation before treatment with BiQs increased their activity allowing for inhibitory effects well below the IC₅₀s of these compounds in PrECs.
• ? Co‐administration of BiQs with docetaxel had minimal additive effects.

CONCLUSIONS

• ? Dimeric naphthoquinones represent a new class of compounds with prostate cancer cytotoxicity and synergistic effects with radiation. The cytotoxic effect of these agents is probably contributed to by the accumulation of ROS and mitochondrial dysfunction.
• ? Further studies are warranted to better characterize this class of potential chemo‐therapeutics.

     

DNA条形码鉴定与功效组分测定在紫草质量评价中的应用

目的:利用DNA条形码技术对中药紫草进行基源鉴定,并建立紫草的功效多组分含量测定方法,为全面评价紫草药材质量提供依据。方法:对不同产地紫草进行DNA条形码基原鉴定;采用高效液相色谱法测定紫草中萘醌类成分与含量,Thermo BDS Hypersil C_(18)色谱柱(4.6 mm×250 mm,5μm),流动相0.2%冰乙酸-乙腈梯度洗脱,流速0.8 m L·min~(-1),检测波长275 nm,柱温35℃。结果:经DNA条形码鉴定了11批药材,均为紫草科植物新疆紫草Arnebia euchroma的干燥根;测定了11批新疆紫草的8种萘醌类功效组分含量,各组分均显示良好分离;不同成分在线性范围内线性关系良好,平均回收率在95.26%~101.40%,RSD均在0.7%~1.8%(n=6)。结论:DNA条形码鉴定确保了新疆紫草药材基源的准确性,组分含量测定方法准确可靠、重复性好,二者结合可作为紫草的质量控制方法。     

紫草素及其衍生物抗肿瘤作用研究进展

紫草素是从草本植物紫草Arnebiae Radix中提取的一种具有抗炎、抗病毒、抗肿瘤、促伤口愈合等生物活性的萘醌类化合物。近年来,紫草素及其衍生物的抗肿瘤作用被广泛研究。从构效关系、抗肿瘤作用机制等方面综述近5年紫草素及其衍生物的抗肿瘤作用的研究进展,以期为紫草素类化合物的研究及利用提供参考。     

Activity of Some Plant and Fungal Metabolites towards Aedes albopictus (Diptera,Culicidae)

Aedes albopictus (Skuse) is a widespread mosquito, a vector of important human arboviruses, including Chikungunya, Dengue and Zika. It is an extremely difficult species to control even for the onset of resistances to chemicals insecticides, therefore ecofriendly products are urgently needed. In this study, the activity of Amaryllidaceae alkaloids and some of their semisynthetic derivatives, of 2-methoxy-1,4-naphthoquinone and two analogues, of cyclopaldic acid and epi-epoformin on the survival and development of Ae. albopictus larvae was evaluated. First-instar larval exposure for 24 and 48 h to cyclopaldic acid, resulted in mortality mean per-centage of 82.4 and 96.9 respectively; 1,2-O,O-diacetyllycorine 48h post-treatment caused 84.7% mortality. Larval and pupal duration were proved to decrease significantly when larvae were exposed to cyclopaldic acid, 1,2-O,O-diacetyllycorine and N-methyllycorine iodide. The mean number of third-instar larvae surviving to 2-methyl-1,4-naphthoquinone, 2-hydroxy-1,4-naphthoquinone and 2-methoxy-1,4-naphthoquinone was significantly lower than the number of correspondent control larvae over the time. This study indicated that 1,2-O,O’-diacetyllycorine, N-methyllycorine iodide, cyclopaldic acid and 1,4-naphthoquinone structural derivatives have good potential for developing bioinsecticides for mosquito control programs. The obtained results are of general interest due to the global importance of the seri-ous human diseases such a vector is able to spread.     

Naphthoquinones: A continuing source for discovery of therapeutic antineoplastic agents

Naturally occurring naphthoquinones, usually in forms of botanical extracts, have been implicated with human life since ancient time, far earlier than their isolation and identification in modern era. The long use history of naphthoquinones has witnessed their functional shift from the original purposes as dyes and ornaments toward medicinal benefits. Hitherto, numerous studies have been carried out to elucidate the pharmacological profile of both natural and artificial naphthoquinones. A number of entities have been identified with promising therapeutic potential. Apart from the traditional effects of wound healing, anti‐inflammatory, hemostatic, antifertility, insecticidal and antimicrobial, etc., the anticancer potential of naphthoquinones either in combination with other treatment approaches or on their own is being more and more realized. The molecular mechanisms of naphthoquinones in cells mainly fall into two categories as inducing oxidant stress by ROS (reactive oxygen species) generation and directly interacting with traditional therapeutic targets in a non‐oxidant mechanism. Based on this knowledge, optimized agents with naphthoquinones scaffold have been acquired and further tested. Hereby, we summarize the explored biological mechanisms of naphthoquinones in cells and review the application perspective of promising naphthoquinones in cancer therapies.     

均匀设计优选玉红膏中紫草油炸提取工艺研究

摘要 目的: 以羟基萘醌总色素得率为指标,优化玉红膏中紫草的油炸提取工艺。方法: 通过单因素试验考察闷润溶剂的种类、闷润溶剂的浓度对羟基萘醌总色素的影响;采用均匀设计法安排试验,紫外分光光度法测定羟基萘醌总色素含量,考察闷润溶剂的浓度、闷润溶剂的用量、油炸温度和油炸时间对提取提取工艺的影响,优选紫草的油炸提取工艺。结果: 最佳油炸提取工艺：采用68.87 %乙醇闷润,用量为紫草的3.20倍,油炸温度为160.15 ℃,提取1.96 min。结论: 采用均匀设计优化紫草的油炸提取工艺可行、稳定,可以为紫草的传统油炸提取工艺提供试验依据。 关键词：玉红膏;紫草;均匀设计;提取工艺;羟基萘醌总色素     

In vitro activity and mutagenicity of bisbenzylisoquinolines and quinones against Trypanosoma cruzi trypomastigotes

The accidental transmission of Chagas' disease by donor blood is recognized as a serious problem in the Latin America. This paper describes the screening of natural products as possible new chemoprophylactic additives in blood banks. Ten plant-derived alkaloids, three terpenes, three quinones and 14 crude plant extracts were tested against bloodstream forms of Trypanosoma cruzi Y strain in vitro at 4°C at a concentration of 250 μg/mL, using gentian violet as the baseline drug. The bisbenzylisoquinoline alkaloids, cocsuline, daphnandrine, daphnoline, isochondodendrine, gyrocarpine, limacine and pheanthine and the naphthoquinone, plumbagin completely lysed the trypomastigote forms of T. cruzi at a concentration of 250 μg/mL, this activity was verified by the subculture of the treated medium during 4 months. The active alkaloids, pheanthine, daphnoline and limacine were evaluated for mutagenicity by the sister chromatid exchange assay (SCE) in peripheral lymphocytes. Daphnoline and pheanthine elicited no significant increase of the SCE up to 50 μg/mL, while limacine significantly increased the SCE values at a concentration of 25 μg/mL, and 50 μg/mL.