Spectrum-effect relationships between UPLC fingerprints and bioactivities of crude secondary roots of Aconitum carmichaelii Debeaux (Fuzi) and its three processed products on mitochondrial growth coupled with canonical correlation analysis

Ethnopharmacological relevance: The crude secondary roots of Aconitum carmichaelii Debeaux (Fuzi), together with its processed products, including Yanfuzi, Heishunpian and Paofupian, are commonly applied in clinic using for thousands of years, such as collapse, syncope, rheumatic fever, painful joints and various tumors.Aim of the study: To explore the different effects of Fuzi and its processed products on energy metabolism, with mitochondria as the model with the aim of guiding the clinical use of Fuzi and its products. fingerprints of Fuzi, Yanfuzi, Heishunpian and Paofupian were established by Ultra-high Performance Liquid Chromatography (UPLC) and effects of Fuzi and its processed products on rat’s liver׳s mitochondrial metabolism were studied by microcalorimetry. Spectrum-effect relationships between UPLC fingerprints and energy metabolism of mitochondria were investigated using canonical correlation analysis (CCA).Results: Because of their inherent differences in chemical compositions, the main activities of energy metabolism of mitochondria were different among Fuzi and its processed products. The potential bioactivity sequence of the tested products was Fuzi>Heishunpian>Paofupian>Yanfuzi. Results of CCA showed that compounds mesaconitine, benzoylaconitine, and benzoylhypacoitine might be the principal active components.Conclusion: Altogether, this work provides a general model of combination of UPLC and microcalorimetry to study the spectrum-effect relationships of Fuzi and its processed products which can offer some references for detecting principal components of traditional Chinese medicine on bioactivity to mitochondrial growth.     

An important mechanism of herb-induced hepatotoxicity: To produce RMs based on active functional groups-containing ingredients from phytomedicine by binding CYP450s

Reactive metabolites (RMs) generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury (DILI). Like many synthetic drugs undergoing metabolic activation to form RMs which are often associated with drug toxicity, it is recognized that some herbal components may be also converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450s (CYP450s). This review focuses on the metabolic activation of herbal components and its liver toxicological implications. By summarizing references, we found that hepatotoxic herbal components via producing RMs have some certain structural dependence. There is a correlation between the generation of RMs and the structures, which provides a good chance for the early discovery of toxic ingredients in Traditional Chinese medicines (TCMs): i) A potential hepatotoxic component information database based on active functional groups can be built, which might provide an early information for the basic research of hepatotoxic substances in TCMs; ii) RMs can combine with CYP450s to form a complete antigen, which eventually leads to an antigen-specific immune response. RMs-CYP450 protein complete antigen can be set up, and the potential idiosyncratic liver toxicity might be predicted by testing RMs-CYP450 protein antibody in plasma.     

不同炮制方法对民族药铁棒锤中生物碱含量的影响

目的:探讨不同民族医的炮制方法对铁棒锤药材中毒性成分和有效成分含量的影响,为研究其炮制机制和提高饮片质量提供依据。方法:采用藏医、羌医和回医的特色方法对铁棒锤进行炮制,结合超声波和酸溶碱沉方法从不同炮制品中提取出乌头生物碱,利用紫外光谱对经过酸性染料络合的生物碱进行分析,检测其中总生物碱、酯型生物碱和非酯型生物碱的含量。结果:铁棒锤生品经过不同方法炮制后,其总生物碱、酯型生物碱和非酯型生物碱的含量均有所降低;煮制使酯型生物碱含量从0.23mg/g降至0.03mg/g,非酯型生物碱含量从0.63mg/g降至0.11mg/g,而青稞酒炒制能较好地保存铁棒锤活性。结论:用辅料青稞酒对铁棒锤进行炮制能较大程度地降低毒性并保存活性,起到"减毒存效"的作用,可见藏医的炮制技术更趋科学和合理。     

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??OBJECTIVE To establish the fingerprint of Aconitum Flarum Hand. Mazz Busch. METHODS UPLC analysis was performed on ACQUITY UPLC BEH C₁₈ column(2.1 mm??50 mm,1.7 ??m). Gradient elution was conducted. Mobile A was 0.2% formic acid and 0.005% TFA in water; mobile B was methanol; and mobile C was acetonitrile. The flow rate was 0.3 mL??min^-1. The detection was carried out at 275 nm. The column temperature was maitained at 35 ??. The injection volume was 1.0 ??L. RESULTS The UPLC fingerprint of Aconitum Flarum Hand. Mazz was established, and 14 common peaks were found including the peaks of two major constituents. The similarity factors ranged from 0.850 to 0.980. In addition, there was significant difference between wild and cultivated samples. CONCLUSION This UPLC method has satisfactory precision, stability, repeatability and specificity. It provides a scientific method for identifying wild and cultivated Aconitum Flarum Hand. Mazz using fingerprint.     

A survey of herbal medicines as tumor microenvironment‐modulating agents

The tumor microenvironment (TME) is extremely complex, involving extensive interactions among stromal cells, immune cells, and signaling molecules. Therefore, an approach targeting the TME has emerged as a promising therapeutic strategy. Herbal medicines consist of multiple active compounds, which have multi‐target effects. Therefore, they have been regarded as potential anticancer agents; multiple studies have explored their effects on the TME. In this review, we report the effects of 29 single herb medicines or herbal formulas on the TME, based on the findings of 64 published studies. Specifically, we describe the effects of these herbal medicines on cancer‐associated fibroblasts/tumor‐associated fibroblasts, tumor‐associated endothelial cells, myeloid‐derived suppressor cells, and tumor‐associated macrophages. Among the reviewed herbal medicines, the most promising TME‐modulating effects were exhibited by curcumin, DHA, EGCG, resveratrol, and silibinin; these medicines showed the ability to regulate two or more components of the TME. The findings of this review support the notion that the combination of herbal medicines with conventional anticancer therapies are likely to exhibit a clinical benefit, which should be further explored in clinical trials.     

Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines

Ethnopharmacological relevance

While there is an increasing number of toxicity report cases and toxicological studies on Chinese herbal medicines, the guidelines for toxicity evaluation and scheduling of Chinese herbal medicines are lacking.

Aim

The aim of this study was to review the current literature on potentially toxic Chinese herbal medicines, and to develop a scheduling platform which will inform an evidence-based regulatory framework for these medicines in the community.

Materials and methods

The Australian and Chinese regulations were used as a starting point to compile a list of potentially toxic herbs. Systematic literature searches of botanical and pharmaceutical Latin name, English and Chinese names and suspected toxic chemicals were conducted on Medline, PubMed and Chinese CNKI databases.

Results

Seventy-four Chinese herbal medicines were identified and five of them were selected for detailed study. Preclinical and clinical data were summarised at six levels. Based on the evaluation criteria, which included risk–benefit analysis, severity of toxic effects and clinical and preclinical data, four regulatory classes were proposed: Prohibited for medicinal usage, which are those with high toxicity and can lead to injury or death, e.g., aristolochia; Restricted for medicinal usage, e.g., aconite, asarum, and ephedra; Required warning label, e.g., coltsfoot; and Over-the-counter herbs for those herbs with a safe toxicity profile.

Conclusion

Chinese herbal medicines should be scheduled based on a set of evaluation criteria, to ensure their safe use and to satisfy the need for access to the herbs. The current Chinese and Australian regulation of Chinese herbal medicines should be updated to restrict the access of some potentially toxic herbs to Chinese medicine practitioners who are qualified through registration.     

Multiple Chromatographic and Chemometric Methods for Quality Standardisation of Chinese Herbal Medicines

Quality standardization of complementary medicine is fundamental for industry and practice as it underpins the quality,safety and efficacy of Chinese herbal medicines.Current herbal standardizations are often based on the quantitative analysis of a single compound,which may not reflect the total characteristic,bioactive and toxic nature of the herbs or products.Therefore,there is a need to establish an internationally recognized methodology for quality standardization of Chinese herbal medicines.The analytical methods reviewed in this article are pharmacognosy,TLC,HPLC,LCMS,CE and chemo-metrics.This article also covers the developments and applications of these methods in quality standardization.Recent advances show that a combination of these methods creates an overall chemical profile of each herb.This iS supported by results reviewed in this article and obtained in our laboratory tests on medicinal herbs including Hypericum perforatum,Morinda officinalis and Centella asiatica.Significant variations in active components have been observed between herbal samples and products.It is proposed that the identification of active components,pharmacological activities and eventual clinical applications are required for a comprehensive quality standardization system.Our findings indicate that the combination of various chromatographic and chemometric methods will advance the methodology of quality standardization and enhance the overall confidence in herbal medicine for the health practitioner and the public.     

Transdermal Behavior of Geniposide in Shangyi Aerosol in vivo and in vitro

目的：观察伤益气雾剂中栀子苷透皮吸收的特点,探讨伤益气雾剂外用时栀子苷的透皮吸收的动力学。方法：利用体内外实验对栀子苷透皮量及其血药浓度进行测试观察。结果：无论体内体外试验均表明,给药后半小时栀子苷即可透过皮肤,在皮下组织中分布,同时血中也能明显测到栀子苷。其透出量具有累积增多的线性关系。结论：伤益气雾剂中栀子苷可明显透过皮肤,并在皮下组织及血液中分布。本实验为该药外用治疗相关病症的应用提供了实验依据。     

Herbal medicines for the prevention of alcoholic liver disease: A review

Ethnopharmacological relevance

Long-term excess alcohol exposure leads to alcoholic liver disease (ALD)—a global health problem without effective therapeutic approach. ALD is increasingly considered as a complex and multifaceted pathological process, involving oxidative stress, inflammation and excessive fatty acid synthesis. Over the past decade, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of ALD, due to their multiple targets and less toxic side effects. Several herbs, such as Cnidium monnieri (L.) Cusson (Apiaceae), Curcuma longa L. (Zingiberaceae) and Pueraria lobata (Willd.) Ohwi (Leguminosae), etc., have been shown to be quite effective and are being widely used in China today for the treatment of ALD when used alone or in combination.

Aim of the review

To review current available knowledge on herbal medicines used to prevent or treat ALD and their underlying mechanisms.

Materials and methods

We used the pre-set searching syntax and inclusion criteria to retrieve available published literature from PUBMED and Web of Science databases, all herbal medicines and their active compounds tested on ALD induced by both acute and chronic alcohol ingestion were included.

Results

A total of 40 experimental studies involving 34 herbal medicines and (or) active compounds were retrieved and reviewed. We found that all reported extracts and individual compounds from herbal medicines/natural plants could be beneficial to ALD, which might be attributed to regulate multiple critical targets involved in the pathways of oxidation, inflammation and lipid metabolism.

Conclusions

Screening chemical candidate from herbal medicine might be a promising approach to drug discovery for the prevention or treatment of ALD. However, further studies remain to be done on the systematic assessment of herbal medicines against ALD and the underlying mechanisms, as well as their quality control studies.     

中药对Hela细胞周期的影响

本文主要综述中药或其有效成分对宫颈癌HeLa细胞周期的影响,从而为筛选、开发更安全有效的抗宫颈癌药物提供新的思路。     

Antibacterial properties of Chinese herbal medicines against nosocomial antibiotic resistant strains of Pseudomonas aeruginosa in Taiwan

Pseudomonas aeruginosa is well-recognized as a nosocomial pathogen, which exhibits inherent drug resistance. In this study, the antibacterial activity of ethanol extracts of 58 Chinese herbal medicines used in Taiwan were tested against 89 nosocomial antibiotic resistant strains of Pseudomonas aeruginosa. The results gathered by the disc diffusion method showed that 26 out of the 58 herbal extracts exhibited antibacterial activity. Among the 26 herbal extracts, 10 extracts showed broad-spectrum antibacterial activities and were selected for further antibacterial property assay. The minimum inhibitory concentrations (MIC) of the active partition fractions ranged from 0.25 to 11.0 mg/L. The presence of flavonoid compounds in the active fractions of test herbal extracts was observed by the TLC-bioautography. The results from the time-kill assay revealed that most of the herbal extracts completely killed the test organisms within 4 hours. Exposure of the test strains to a sub-MIC level of the herbal extracts for 10 consecutive subcultures did not induce resistance to the active components. A combination of the active herbal fractions with antibiotics showed that one of the herbal medicines, the hexane fraction of Ramulus Cinnamomi, possessed a synergistic effect with tetracycline, gentamycin, and streptomycin. In conclusion, the tested Chinese medical herbs have the potential to be developed into natural antibiotics. This is the first evaluation for screening large amounts of medical plants against nosocomial antibiotic resistant bacteria in Taiwan.     

HPLC测定中药材玄参中有效成分的含量分析

[目的]建立高效液相色谱法(HLPC)测定中药材玄参中5种有效成分的含量,为玄参药材的质量控制提供依据。[方法]采用高效液相色谱法(HLPC)法,测定玄参中哈巴苷、哈巴俄苷、肉桂酸、麦角甾苷、安格洛苷C的含量。[结果]不同产地小儿中药材玄参中有效成分的含量不同,以浙江产玄参药材中5种成分的含量较高,而河南、山东产玄参药材有效成分的含量较低。[结论]应用HLPC测定不同产地中药材玄参中有效成分的含量,其方法准确可靠,重现性、专属性均较好,可用于中药材玄参的质量控制。     

Potential Genotoxicity of Traditional Chinese Medicinal Plants and Phytochemicals: An Overview

In the last decades, cases of poisoning due to herbal medicines have occurred in many countries; Chinese herbal medicines (CHMs) are occasionally involved. The experience gained from traditional use is efficient to detect immediate or near‐immediate relationship between administration and toxic effects but is quite unlikely to detect medium‐ to long‐term toxicities; thorough investigations of herbal medicines (toxicity assessments, active pharmacovigilance) appear then essential for their safe use. Genotoxicity is an especially insidious toxicity that may result in carcinoma development years after exposure; it can arise from multiple compounds, with or without metabolic activation. The present work reviews traditional CHMs and phytochemicals that have been shown to present a genotoxic hazard. Copyright © 2013 John Wiley & Sons, Ltd.     

《普济方》乌头类中药儿童应用探讨

目的:乌头类中药药理活性广泛,但其临床中毒剂量与治疗剂量接近,《普济方》是我国最大的方书,分析与研究《普济方》婴孩篇乌头类中药方剂,总结乌头类中药儿童的用药规律和特点,为指导乌头类中药在儿童临床运用提供参考。方法:收集和整理《普济方》婴孩篇乌头类中药方剂,建立乌头类中药处方数据表,统计与分析方剂中的乌头类中药、剂量、剂型、适应症及炮制品等。结果:共收集《普济方》婴孩篇中含附子、川乌、草乌、乌头、天雄5种乌头类中药方剂总计300首,64. 45%的处方以附子入药。治疗疾病种类涉及13种,主要是诸风、惊风(包括急慢惊风、慢脾风等)、吐泻、下痢、大小便淋秘等。乌头类中药用药剂量在3 g以下的方剂占有记载剂量的95. 10%,儿童乌头类中药方剂以内服剂型为主,且48. 33%为丸剂,同时丸剂用药剂量高于散剂、汤剂。使用炮制品的方剂有169首,占54. 17%,采用特殊服法的方剂有170首,"米饮服"所占比例最高。结论:儿童乌头类中药方剂占《普济方》比例较少,用药剂量较轻,且不同方剂剂型用药剂量存在差异。通过研究乌头类有毒中药在儿童方剂中的应用,临床应从辨证遣药、严格控制用药剂量和疗程、注重配伍、服药禁忌,加强临床用药监护等方面建立乌头类中药临床用药警戒,为儿童安全、有效地合理使用乌头类有毒中药提供参考。     

枳实薤白桂枝汤抗心肌细胞损伤活性成分的发现研究

用H2O2损伤乳鼠心肌细胞,并用二乙酸荧光素(fluorescein diacetate,FDA)标记活细胞,建立心肌细胞损伤模型用于心肌细胞保护物质的筛选;以抗坏血酸(Vc)为阳性对照,对枳实薤白桂枝汤的43个组分进行快速筛选,发现了7个心肌细胞保护作用较明显的组分;采用液相色谱-质谱联用法(LC-MS)对C18,D14,D15,D16和E09进行定性分析,推测出11个化学成分;对其中6个成分进行快速筛选,发现橙皮苷、新橙皮苷和圣草酚具有心肌细胞保护作用,而圣草酚的活性最强,且呈良好的量效关系.     

附子炮制历史沿革研究

为了理清历代中药附子炮制加工方法,以《历代中药炮制资料辑要》一书为线索,回溯核查西汉至清朝时间本草原著59部,并查阅建国后各版《中国药典》8部、《全国中药炮制规范》1988年版和地方炮制规范14部,对古今文献中所收载的与附子炮制有关的内容加以归纳、整理和文献循证。附子传统的炮制方法较多、历史悠久,始见于汉代,其方法多为炮、煨、炒、烧等;唐代以后,增加了黑豆制、蜜制、姜制、醋制、甘草制、童便制及多种辅料浸制、煮制、蒸制的炮制方法,其主要目的均在于解毒。古人认为附子不宜用黄连、童便炮制,现早已废除。自明代起,附子用胆巴腌制防腐,再采用水火共制的加工方法来实现减毒增效,经历了"火制-单一辅料炮制-多种辅料水火共制"的变迁。通过系统概况中药附子炮制历史沿革,可为附子炮制、商品规格的研究提供文献依据。     

铁棒锤毒性研究及炮制方法

铁棒锤是我国一种传统中草药,具有多种生理活性,临床有广泛应用,但同时也是毒性药材之一.目前对铁棒锤的毒性及炮制方法研究尚不完善,难以对其质量及安全性进行控制.对铁棒锤的炮制、毒性、化学成分、药理活性、临床应用方面进行详细论述,以进一步完善对铁棒锤毒性及炮制方法的研究.     

Phytochemicals from traditional medicinal plants used in the treatment of diarrhoea: modes of action and effects on intestinal function

Medicinal plants have been used as traditional treatments for numerous human diseases for thousands of years. Diarrhoeal diseases continue to be a major cause of morbidity and mortality throughout the world and there is renewed interest in the discovery of novel compounds that can be used to fight these diseases. Numerous studies have validated the traditional use of antidiarrhoeal medicinal plants by investigating the biological activity of extracts of such plants, which have antispasmodic effects, delay intestinal transit, suppress gut motility, stimulate water adsorption or reduce electrolyte secretion. Of the numerous phytochemicals (such as alkaloids, tannins, flavonoids and terpenes) present in active extracts, tannins and flavonoids are thought to be responsible for antidiarrhoeal activity by increasing colonic water and electrolyte reabsorption. Others act by inhibiting intestinal motility. As some of the active ingredients are potentially toxic, there is a need to evaluate the safety of plant preparations. A few clinical trials have evaluated the safety and tolerability of traditional and herbal medicine preparations used to treat diarrhoea and generally indicate that minimal side effects are observed. However, with the increased popularity of plant-derived and herbal medicines in Western society, the benefits and potential dangers of these medicines must be considered.     

丹参破壁饮片与传统饮片水溶性成分指纹图谱及丹酚酸B含量对比研究

目的建立10批丹参传统饮片、冷冻破壁饮片、普通破壁饮片的水溶性成分UPLC指纹图谱,同时测定水溶性指标成分丹酚酸B的含量,为丹参破壁饮片质量与安全性提供参考依据。方法采用UPLC法以Waters ACQUITY BEH C₁₈(2.1 mm×150 mm,1.7μm)为色谱柱,乙腈-0.02%的磷酸为流动相,梯度洗脱;检测波长270 nm;流速0.15 mL/min;柱温30℃;进样量2μL;采用HPLC法按照2015版《中华人民共和国药典》测定丹酚酸B含量,并利用相似度评价软件与SPSS 22.0软件对指纹图谱与丹酚酸B含量进行分析。结果通过相似度软件分析冷冻破壁饮片、普通破壁饮片、传统饮片分别为12、13、14个共有峰,并通过对照品指认得到丹参素钠(3号峰)、原儿茶醛(4号峰)、咖啡酸(6号峰)、迷迭香酸(13号峰)、丹酚酸B(14号峰)等5种成分,丹酚酸B含量范围为2.354%~7.606%,利用SPSS 22.0的多个相关样本的非参数检验对10批3种粉碎方式指纹图谱与丹酚酸B含量分析得到3种粉碎方式的水溶性指纹图谱与丹酚酸B含量均无明显差异性。结论从定性与定量两个方面对丹参破壁前后水溶性化学成分进行研究,可为丹参破壁饮片的临床应用与开发提供依据。     

靶向表皮生长因子受体治疗结直肠癌的耐药机制及中药研究进展

综述靶向表皮生长因子受体(EGFR)治疗结直肠癌的耐药机制和中药研究进展。EGFR信号通路的分子改变和代偿性信号通路的异常激活是抗-EGFR治疗耐药发生的主要机制。中药多靶点的作用特点,使其在逆转肿瘤耐药方面具有明显优势。多种中药及其有效成分不仅具有直接抗肿瘤作用,与靶向药物联合使用还可以增强抗肿瘤西药敏感性,并克服肿瘤耐药,值得进一步深入研究。